Stereoselective synthesis of l,2-CIS-2-aminoglycosides

Abstract

Described herein is a general solution to 1,2-cis-amino-glycoside synthesis through an iron-catalyzed, exclusively 1,2-cis-selective glycal aminoglycosylation via cooperative atom transfer catalysis. Further described is a 1,2-cis-selective glycal aminoacyloxylation method for 2-amino saccharide synthesis. The methods are effective for a wide variety of glycosyl donors with consistently high stereoselectivity and excellent functional-group compatibility, which facilitates late-stage amino group incorporation for complex-carbohydrate and other biologially-related molecule synthesis.

Description

STEREOSELECTIVE SYNTHESIS OF l,2-CIS-2-AMINOGLYCOSIDESCROSS-REFERENCE TO RELATED APPLICATION

[0001] This application claims priority to U. S. Application Serial Number 63 / 720,861, filed November 15, 2024, which is incorporated herein by reference in its entirety.STATEMENT REGARDING FEDERALLY SPONSORED RESEARCH OR DEVELOPMENT

[0002] This invention was made with government support under GM 134926, and GM128442 awarded by the National Institutes of Health. The government has certain rights in the invention.BACKGROUND

[0003] This application relates to methods for the stereoselective synthesis of 1,2-cis-2-aminoglycosides. In particular, this application relates to exclusively 1,2-cis-selective glycosylation by cooperative atom transfer catalysis.

[0004] Complex carbohydrates are directly involved in numerous physiological and disease processes. However, their structural complexity and limited availability in homogeneous forms represent a major roadblock that hampers study of their important biological functions. While standard synthetic approaches for nucleic acids and proteins have been established and widely adopted, assembly of complex carbohydrates has been challenging. A significant challenge is the need to precisely control anomeric stereoselectivity in the glycosylation reaction. Despite progress, robust and easily adaptable glycosylation approaches are still urgently needed in order to rapidly and stereoselectively assemble glycosidic linkages that prove challenging using existing glycosylation methods.

[0005] Most established glycosylation reactions proceed through nucleophilic substitution reactions on an sp3-hybrized anomeric center, which represents a mechanistic continuum between two classical limiting mechanisms (SNi-type and SNi-type), as shown in FIG. 1. In these mechanisms, stereoselectivity of glycosylation is dictated by a variety of non-covalent interactions that orchestrate the transition state. Since both glycosyl donors and acceptors are stereochemically complex and conformationally flexible, subtle structure variations in either of them can disrupt these interactions and thereby compromise stereoselectivity, such that the reactions often afford a mixture of diastereomers. This is a particularly challenging issue for solid-phase and automated carbohydrate synthesis, because stereoisomeric products cannot be separated on solid supports.

[0006] The stereoselectivity of glycosylation can also be influenced by existing stereogeniccenters, most notably the one vicinal to the anomeric center. Glycosylation methods based upon anchimeric assistance from neighboring participating groups have been successful in the assembly of 1,2-trans glycosidic bonds (FIG. 2 A). However, the stereoselective formation of 1,2-cis glycosidic linkages is still challenging (FIG. 2B). Although many creative 1,2-cis-selective glycosylation methods have been invented, they are most effective for certain sets of substrates. The stereoselectivity often varies with other substrates and a general solution is yet to be discovered.

[0007] In particular, the l,2-cis-2-amino glycosidic moiety is present in numerous complex glycans and glycoconjugates of biological importance, for example anticoagulant heparin / heparan sulfate and Fondaparinux, pathogenic microbial glycans, aminoglycoside antibiotics, and N- and O-linked glycoproteins. Although synthetic approaches for l,2-trans-2-aminoglycosides are well established, l,2-cis-2-amino glycosidic linkages are known to be difficult to form reliably in high stereoselectivity using conventional glycosylation methods. An array of specialized glycosyl donors that minimize anchimeric assistance were developed to enhance the 1,2-cis-selectivity (FIG. lb). These valuable methods can indeed achieve high cis-selectivity with a range of substrates, but substrate structural variations can often compromise the selectivity.

[0008] For example, synthetic methods involving nitrogen atom transfer to glycals represent an important strategy for synthesis of 2-amino monosaccharides and l,2-trans-2-aminoglycosides. A two-step 1,2- trans-sulfonaminoglycosylation of glycals that involves a glycal iodosulfonamidation-aziridination-ring opening sequence has been reported (FIG. 3). A one-step glycal aziridination using manganese nitrido complex in the presence of trifluoroacetic anhydride has also been reported. Subsequent aziridine ring opening with water provides 2-amino monosaccharides.

[0009] There remains a need in the art for highly stereoselective methods of synthesizing l,2-cis-2-amino-glycosidic linkages that are applicable to a wide variety of glycosyl donors and acceptors.BRIEF SUMMARY

[0010] The inventive method described herein provides a general solution to 1,2-cis-amino-glycoside synthesis through an ir on-catalyzed, exclusively 1,2-cis-selective glycal aminoglycosylation via cooperative atom transfer catalysis.

[0011] Based on the foregoing, a method for stereoselective synthesis of l,2-cis-2-aminoglycoside is shown in Scheme A, which includes reacting a glycal of formula (I) with an amination agent of formula (II) and a glycosyl acceptor of formula (III) in the presence of aniron(II) catalyst, a solvent, and molecular sieves to provide the l,2-cis-2-aminoglycoside of formula (IV):Scheme A.Iron(II) catalyst Molecular seives Solvent+R8— OH(HD (IV) wherein the variables in formulas (I), (II), (III), and (IV) are as described herein.

[0012] Another method for stereoselective synthesis of a l,2-cis-2-aminoglycoside is shown in Scheme B, and includes reacting a glycal of formula (I) reacting a glycal of formula (I) with an amination agent of formula (II) and a glycosyl acceptor of formula (V) in the presence of an iron(II) catalyst, a solvent, and molecular sieves to provide the 1.2-cis-2-aminoglycoside of formula (VI): Scheme B.wherein the variables in formulas (I), (II), (V), and (VI) are as described herein.

[0013] In another method, as shown in Scheme C, a glycal of formula (I) is reacted with an amination agent of formula (II) in the presence of an iron(II) catalyst, a solvent, and molecular sieves to provide the l,2-cis-2-aminoglycoside of formula (VI):Scheme C(I) (ID (VI)wherein in formulas (I), (II), and (VI), the variables are as described herein.

[0014] In an aspect, the method further includes cleaving R6from the R6HN- moiety of formula (IV) and (VI) to provide the corresponding poly(l,2-cis-2-aminoglycoside).

[0015] Iterative methods for the synthesis of complex carbohydrates are further disclosed.

[0016] Certain poly(l,2-amino-2-aminoglycoside)s) and poly(l,2-cis-2 aminoglycosides are further disclosed.BRIEF DESCRIPTION OF THE DRAWINGS

[0017] The invention is illustrated by the following drawings, which are not intended to limit the claims. The patent or application file contains at least one drawing executed in color. Copies of this patent or patent application publication with color drawing(s) will be provided by the Office upon request and payment of the necessary fee.

[0018] FIG. 1A illustrates prior art processes for glycosylation via StH-and SN2-type pathways.

[0019] FIG. 2A illustrates prior art processes for 1,2-trans-aminoglycoside bond formation.

[0020] FIG. 2B illustrates prior art processes for 1,2-cis-aminoglycoside bond formation.

[0021] FIG. 3 illustrates a prior art process for glycal trans-aminoglycosylation via selective nitrogen atom transfer.

[0022] FIG. 4 shows a proposed mechanistic pathway to TEMPO-oxygenation product.

[0023] FIG. 5 shows a proposed mechanistic pathway to 1,2-cis-aminofluoride formation.

[0024] FIG. 6 shows a proposed mechanistic pathway to the Brpnsted base-promoted glycal cis-aminoacyloxylation.

[0025] FIG. 7 shows a mechanistic working hypothesis for the iron-catalyzed cisaminoglycosylation of glycal 2 with primary glycosyl acceptor 4.

[0026] FIG. 8 shows a mechanistic working hypothesis for the iron-catalyzed cisaminoglycosylation of glycal S10 with a primary glycosyl acceptor 4.

[0027] FIG. 9 shows a mechanistic working hypothesis for the iron-catalyzed cisaminoglycosylation of glycal 2 with a secondary glycosyl acceptor 4.

[0028] FIG. 10 shows a mechanistic working hypothesis of the iron-catalyzed glycal cisaminoglycosylation. Lex, exchangeable ligand.

[0029] FIG. 11 shows an X-ray crystallographic analysis of 1.

[0030] FIG. 12 shows un-decoupled HSQC analysis to determine stereochemistry of 5 at the Cl position.

[0031] FIG. 13A shows an NOE analysis to determine stereochemistry of 5 at the C2 position, and FIG. 13B shows the assignments.

[0032] FIG. 14 shows an X-ray crystallographic analysis of 5.

[0033] FIG. 15 shows un-decoupled HSQC analysis to determine stereochemistry of 41 at the Cl positions.

[0034] FIG. 16 is an X-ray crystallographic analysis of TEMPO-oxygenated Product 53.

[0035] FIG. 17 shows a mechanistic working hypothesis for iron-catalyzed glycal cis-aminoacyloxylation in the absence of a glycosyl acceptor.

[0036] FIG. 18 shows COSY Analysis forNMR Assignment of compound 4d in Scheme 90.DETAILED DESCRIPTION

[0037] As described above, stereoselectivity in glycosylation often varies with substrates. making it difficult to develop a highly selective glycosylation method that is also broadly effective. The inventors hereof have discovered that an atom transfer catalyst (M) can cooperatively activate both a glycosyl acceptor and an oxidant, such that it can subsequently transfer these two moieties to a glycal that is otherwise unreactive in the absence of the catalyst. In particular, because both the atom-transfer step and the glycosyl-acceptor transfer step would be directed by the iron catalyst, the amino (or the hydroxy) group and the catalyst-activated glycosyl acceptor could be cooperatively delivered to a glycal in an exclusively cis-selective manner. A general mechanism for the synthesis of a l,2-cis-2-functionalized glycoside using iron as the catalyst and an oxidant OX is shown in Scheme 1, where SET is single electron transfer.Scheme 1.glycosyl acceptorX: O or NCO2R3X: O or NCO2R3exclusive formation of1,2-c / s-glycosidic bond

[0038] As shown in Scheme 1, cooperative atom transfer catalysis can be used to provide an exclusively 1,2-cis-glycosidic bond wherein the functional group at the 2-position can be an amino group. Distinct from most existing glycosylation methods, the uncoordinated glycosyl acceptor in solution is unlikely to compete for the same glycosylation intermediate, which minimizes or eliminates stereochemical erosion resulting from competing, non- stereo selective glycosylation pathways. Unlike prior art methods that can achieve high cis- selectivity with a range of substrates, structural variations within either glycosylation partner can often compromise high cis- selectivity. The methods described herein, an iron-catalyzed, exclusively 1,2-cis- selective glycal aminoglycosylation method by cooperative atom transfer catalysis can provide a general solution to this synthetic challenge.

[0039] To develop this method, the inventors made a careful selection of both the metal catalyst and the amination reagent, so that they could be compatible with highly functionalized carbohydrate substrates. Secondly, both the metal catalyst and the amination reagent were selectively modulated such that the exclusively cis-selective glycosylation could be achieved across a wide variety of substrates. Finally, the new cooperative catalysis strategy was developed to favor the glycosyl acceptor transfer over the previously investigated carboxylate transfer in olefin aminohydroxylation. With respect to this last feature, because the atom-transfer step and the catalyst-directed glycosyl-acceptor transfer step cooperatively occurs from the catalyst center, both the amino group and the catalyst-activated glycosyl acceptor can be delivered to a glycal in nearly exclusive cis-selective fashion. This is distinct from most existing glycosylation approaches, in that a non-activated glycosyl acceptor in solution is unlikely to compete for the same reactive intermediate, which minimizes or even eliminates stereochemical erosion resulting from the competing, non- stereoselective glycosylation pathways.

[0040] Stereoselective assembly of l,2-cis-2-amino glycosidic linkages were selected to determine the validity of this approach. As stated above, the 2-amino glycosidic moiety is present innumerous complex glycans and glycoconjugates of biological importance, including heparin, heparan sulfate, and a variety of O-linked glycoproteins. In an aspect, an iron-catalyzed single-step glycal cis-aminoglycosylation method is described that achieves exclusive 1.2-cis selectivity for a broad range of substrates by cooperative atom transfer catalysis.1. As shown in Scheme 2, a prototypical glycal 2 and a primary glycosyl acceptor 4 were used as the model substrates, both of which are readily derived from D-(+)-glucose. Initial glycosylation attempts (shown generally in Scheme 2) using a variety of iron catalysts and the amination reagents developed for olefin aminohydroxylation resulted in either very low reactivity or undesired glycal aminoacyloxylation products in modest yields.Scheme 2.iron catalyst (10 mol%) -40 °C, c = 03 M 5 A MS, solvent, 1 h 3a 4 8a 1 5 equiv 1 2 equiv dr >20:1 dr >20:1at the C1 and C2Reactions were performed on a 0.3 mmol scale with iron catalyst (10 mol %), glycal 2 (1.0 equiv), glycosyl acceptor 4 (1.2 equiv), and amination reagents 3a (1.5 equiv) in CH2CI2 with 5 Angstrom (A) molecular sieves at -40 °C for 1 h. Ligands LI, L2, and L3 in Table 1 are as follows, and results are shown in Table 1.All yields in Table 1 are isolated yields.Table 1.entry iron catalyst solvent conversion (%) yield of 5 (%)ayield of 8a (%) 1 Fe(OTf)₂— L1 (1:1) CH2CI2 / MeCN (10:1) <5 NA NA 2 Fe(NTf2)2— L1 (1:1) CH2CI2 / MeCN (10:1) 35 <5 22 3 FeCI2— L1 (1:1) CH2CI2 / MeCN (10:1) <5 NA NA 4 Fe(NTf2)2— L2 (1:1) CH2CI2 / MeCN (10:1) <5 NA NA 5 Fe(NTf2)2— L3 (1:1) CH2CI2 / MeCN (10:1) <5 NA NA 6 Fe(CIO4)2-xH2O— L1 (1:1) CH2CI2 / MeCN (10:1) 42 <5 25 7 Fe(BF4)2«6H2O— L1 (1:1) CH2CI2 / MeCN (10:1) 58 21 30 8 Fe(L1)(BF4)2(MeCN)(H2O)2CH2CI2 / MeCN (10:1 ) 65 25 35 9 Fe(L1)(BF4)2(MeCN)(H2O)2CH2CI2>95 65 <5Certain amination reagents provided poor yields under the conditions shown in Scheme 3.Scheme 3.Fe(L1)(BF4)2(MeCN)(H2O)2(1) (10 mol%) CH2CI2, 5 A MS -40 °C, 1 h22. Amination reagents and yields are shown in Scheme 4.o zx Y „OTs 1. OMe CI3C O N CI3C O N H H3p 3qBoCx ✓’OTs Boc^,,x°x^ NMeBoc^ BoCx.. / O'SY Ad N Y N T N T H H O H O H O3s 3t 3u 3vAmination reagents were further explored as shown generally in Scheme 5 (Eq. 1 and Eq. 2), using reagents 3a-3g. Again, reactions were performed on a 0.3 mmol scale with iron catalyst 1 (10 mol %), glycal 2 (1.0 equiv), glycosyl acceptor 4 (1.2 equiv), and amination reagents 3 (1.5 equiv) in CH₂Cl₂ with 5 Angstrom molecular sieves at -40 °C for 1 hour.Scheme 5.CH2CI2The reagents and yields of product are shown in Scheme 6.Scheme 6.H Me3a 3b 3c 3d7: 47% yield 7: 50% yield 7: 20% yield 7: 50% yield8: 27% yeld 8: 29% yield 8: 61% yield 8: 31% yieldCH2OBZ Me Me BoCx..^°'sz' \ Me Me y J CH2OBz H °R: 2,4-CI2-benzoyl 3e 3f 3g3w7: 65% yield 7: 67% yield 7: 71% yield8: 10% yield 8: 10% yield 8: <5% yield 5: 87% yield

[0041] Thus, further structural modulation of the O-acyl activating group on carbamate 3 revealed that an array of readily available, aliphatic O-acyl activating groups appear to induce more effective glycal cis-aminoglycosylation with acyloxy carbamates, cleanly affording disaccharide 5 in excellent yield (over 60% with 3a, and 3c, and over 80% yield with 3b and 3w, and 87% with 3d).

[0042] Extensive exploration of catalysts, amination reagents, as well as other reaction parameters revealed that an Fe(BF4)2-tridentate ligand LI catalyst complex, Fe(Ll)(BF4)2(MeCN)(H2O)2. is uniquely effective to promote the glycal cis-aminoglycosylation.(LI)This iron catalyst facilitates facile cleavage of the N-0 bond of acyloxy carbamate 3 and subsequently transfers both the carbamate fragment of, e.g., carbamate 3a and the primary glycosyl acceptor 4 to glycal 2 in an exclusively cis-selective manner from the a-face, affording a 2-amino-a-1,6-glycoside 5 as a single diastereomer (dr >20:1 both at the C-l and C-2 positions). Selective N-Boc deprotection almost quantitatively afforded 2-aminoglycoside SI.Me(SI)

[0043] Glycosylation with secondary glycosyl acceptors, such as 6, proved challenging because a rapid glycal cis-aminoacyloxylation with formation of 8 became a major pathway (Scheme 5, Eq. 2). Glycosylation of 2 with 6 in the presence of 3a-3d afforded the desired a-1,3-linked disaccharide 7 (dr >20:1), but only in moderate yields. Without being bound by theory, it is believed that the secondary hydroxyl group of 6 is less sterically accessible and therefore could be more difficult to activate by coordination with the iron catalyst, so that the competing carboxylate transfer leading to 8 prevailed. To modulate these two competing pathways, the reactivity of 3 with a large number of O-acyl activating groups was explored (Schemes 7 and 8).Scheme 7.Fe(L1)(BF4)2(MeCN)(H2O)2(1) (15 mol%) CH2CI2, 5 A MS -40 °C, 2 h dr >20:1 at the C1 and C2Scheme 8.OF.,Ph Me Me3a 3x 3y 3z 3d 3w 7: 47% yield 7: 31% yield 7: 15% yield 7: 35% yield 7: 51% yield 7: 45% yieldCH2OBZ H Ph k / v-MeBocy(IT CH2OBZ H(±)3e 3aa 3c 3ab 3b 3ac 7: 65% yield 7: 23% yield 7: 20% yield 7: 47% yield 7: 52% yield 7: 55% yieldMe Me Me Me Me Me BOCXMXOX\" H J NHBoc y J OR H O H OR: 2,4-CI2-benzoyl31 3ad 3ae 3af 3ag 3g 7: 67% yield 7: 31% yield 7: 42% yield 7: 65% yield 7: 33% yield 7: 71% yieldIt was discovered that use of reactant 3g with a hindered 2-benzoyloxyisobutanoyl group almost completely suppressed the competing reaction and provided the desired disaccharide 7 (71% yield).In addition, 3e with a hindered dibenzoyloxypivaloyl O-activating group provides evidently improved selectivity (65% of 7 and only 10% of 8). The more readily available 2-acetoxyisobutanoyl O-activating group of 3f is equally effective.

[0044] Other synthetically valuable N-acyl activating groups, including N-CCFMe, N-Troc, N-Cbz, and N-Fmoc were explored (Scheme 9 and Scheme 10). All yields are isolated yields.Reactions were performed on a 0.3 mmol scale with iron catalyst 1 (15 mol %), glycal 2 (1.0 equiv), glycosyl acceptor 6 (1.2 equiv), and amination reagents 3 (1.5 equiv) in CH2CI2 with 5 A molecular sieves at -40 °C for 2 h.Scheme 9.Fe(L1)(BF4)2(MeCN)(H2O)2 (1) (15 mol%) CH2CI2, 5 A MS -40 °C dr >20:1 2 3 at the C1 and C2Scheme 10.Me Me Me3j 3k 3ah7i: 26% yield 7j: 37% yield 7k: 32% yield 71: 29% yield 7ah: <5% yieldThe results show that all lead to diminished chemoselectivity (3h-3k, 26-37% yield for 7).Electronic tuning eventually led to 3g (Scheme 8) which almost completely suppresses the competing glycal cis-aminoacyloxylation and provides the desired product 7 in 71% yield.

[0045] The effect of different secondary glycosyl acceptors was explored (Scheme 11). Reactions were performed on a 0.3 mmol scale with iron catalyst 1 (10 mol %), glycal 2 (1.0 equiv), glycosyl acceptor (1.2 equiv), and amination reagents 3 (1.5 equiv) in CH₂Cl₂ with 5 Angstrom molecular sieves at -40 °C for 1 hour.Scheme 11.dr >20:1at the C1 and C2 nThe products and yields are shown in Scheme 8. All yields shown in Scheme 12 are isolated yields.Scheme 12.5 7 987% yield (3d) 71% yield (3g) 85% yield (3a)Me Me Me13 14 1567% yield (3h) 76% yield (3d) 70% yield (3g)

[0046] A variety of glycals and glycosyl acceptors were explored to establish the generality of this method (Scheme 13). Reactions were performed on a 0.3 mmol scale with iron catalyst 1 (10-15 mol %), glycal (1.0 equiv), glycosyl acceptor (1.2-1.4 equiv), and amination reagents 3 (1.5-2.5 equiv) in CH2CI2 with 5 A molecular sieves at -40 °C for 1-3 h. Products and yields are shown in Scheme 14.Scheme 13.Scheme 14.5 787% yield (3d) 71% yield (3g) 85% yield (3a) 82% yield (3a)11 12 13 14 2% yield (3a) 74% yield (3g) 67% yield (3h) 76% yield (3d)15 16 17 18 % yield (3g) 73% yield (3e) 72% yield (3b) 70% yield (3b)19 20 21 22 % yield (3g) 74% yield (3d) 72% yield (3d) 72% yield (3d)23 24 25 26 % yield (3d) 71% yield (3g) 70% yield (3g) 76% yield (3b)27 28 29 30 % yield (3d) 73% yield (3d) 67% yield (3g) 71 % yield (3d)31 32 33 34 63% yield (3g) 72% yield (3d) 72% yield (3d) 70% yield (3d)35 S29 84% yield (3d) 73% yield (3f) 76% yield (3b) 74% yield (3b)S3068% yield (3g)

[0047] First, it was found that glycals with three electron-donating substituents are the most reactive substrates and form the aminoglycosides in high yield with a variety of primary acceptors and amination reagents (Fig. 2b, products 5, 9-11, 14, 16-18). Notably, sterically more hindered amination reagents (3e-3g) must be used for the glycosylation of these donors with secondary acceptors to minimize the competing aminoacyloxylation (with formation of 7, 12-13, 15, and 19).Tri-O-acyl glycals are not suitable glycosyl donors; however, changing the 3-O-acyl group to a 3-0-silyl group is sufficient to achieve reactivity. With these substrates, glycosylation with 3d is effective for both primary and secondary acceptors in the formation of 20-22, and 33-34 in Fig. 2b, while reaction with (3e-3g) provides lower conversion.

[0048] Several synthetically valuable 6-azido-glucals and 6-deoxy-glucals, were explored since the corresponding glycosylation products are often present in complex microbial glycans. Allof them can be swiftly assembled with a variety of primary and secondary glycosyl acceptors with exclusive cis-selectivity, leading to products 23-29. 3-Deoxy glycals could only provide modest a-selectivity in previously reported nitrogen atom transfer reactions, but the absence of the C3-substituent does not lead to erosion of the a-selectivity in the formation of products 30 and 31. In addition, a xylal-based glycal without a C5 substituent is a suitable substrate for this highly cis-a-selective glycosylation, leading to 32. l,2-cis-2- Amino galactosidic linkages are prevalent in biologically important O-linked glycoproteins, in particular mucin-type O-linked glycoconjugates. However, the cis-selectivity frequently varies with substrates using the existing methods. It was observed that 3-O-TBS-4,6-di-O-acetyl galactal is an excellent substrate in this iron-catalyzed glycosylation, leading to products 33 and 34. This method is also compatible with amino acid-based glycosyl acceptors, including challenging serine substrates. Most notably, gram-scale (7 g, 20 mmol) aminoglycosylation of a galactal with N-Cbz-protected serine and threonine methyl esters, afforded more than 11 g of biologically valuable, fully- protected Tn-antigens 35 and 36 in excellent yield (dr >20:1).

[0049] These studies gave rise to the possibility of selective 1,2-cis- selective glycalamino acyloxylation in the absence of a glycosyl acceptor. Initial studies for this reaction were directed to amination reagent discovery for iron-catalyzed glycal czs-aminoacyloxylation, as shown in Scheme AA.

[0050] In Scheme AA, glucal 2 was selected as the model substrate and extensive explorations revealed that the electrophilic iron(II)-tridentate ligand LI complexes are crucial to catalyze the intermolecular nitrogen atom transfer reaction. Utilizing a highly electrophilic iron catalyst, Fe(Ll)(BF4)2(MeCN)(H2O)2 the N-0 bond in a range of functionalized acyloxyl carbamates with different A-acti vating groups (3a-3e) was readily cleaved (Scheme 89).Concurrently, both the A-carbamoyl and the carboxylate fragments of 3 were transferred to glucal 2 with exclusive cA-selectivity from the alpha face. While commonly used A-activating groups such as A-Troc, A-Fmoc, and A-Cbz were all well-tolerated under the reaction condition (products 4a-4d in 40-73% yield, dr >20:1). amination reagent 3e with an A-Boc group is most effective, with which the desired l,2-cA-2-amino glycosyl ester 4e was obtained in high yield (80% yield, dr >20:1). Further structural modulation of 3e revealed that amination reagent 3f, bearing a more electron-withdrawing 2-bromoisobutyrate moiety, promotes an even more efficient glycosylation to afford 4f (85% yield, dr >20:1). The glycosyl esters can be readily deprotected using standard deacetylation procedures and an external carboxylic acid can be incorporated into the glycosyl esteras well (detailed discussions in the SI). Notably, iron catalyst 1 as well as the amination reagents 3 and glycal 2 are all bench- stable.Scheme AA.N'Fe(L1)(BF4)2(MeCN)(H2O)2Me^VO- (1) (15 mol%)TBSO- CH2CI215 A MS -40 °C, 2 h dr >20:1 n 4 O at the C1 and C2FmoCx Me N'NH O 3a 3b 3c4a: 75% yield 4b: 40% yield 4c: 65% yield3d 3e 3f4d: 73% yield 4e: 80% yield 4f: 85% yield

[0051] A variety of glycals was next used to assess the generality of the method (Scheme BB). Reactions were performed on a 0.3 mmol scale in CH2CI2 with 5 A molecular sieves at -40 °C for 2 h.Scheme BB.Me iron catalyst (1) (15 mol%) CH2CI2, 5 A MS -40 °C, 2 h 1.0 equiv 1.5 equiv dr >20:14f 85% yield10 11 69% yield 75% yield16 17 18 1973% yield 70% yield 84% yield 66% yield

[0052] Referring to Scheme BB, it was first found that glucals with three electron-donating substituents readily underwent glycosylation to afford the corresponding l,2-czw2-amino glycosyl esters in good to excellent yields as single diastereomers (products 4f, 5, 6, 70-85% yield). It wasfurther found that lectron-deficient and less electron-rich glucals containing one or two electronwithdrawing substituents are also excellent substrates, delivering single diastereomeric glycosylation products 7-9 in good yields. Notably, tri-O-acetyl-D-glucal, a commercially available substrate previously found unreactive in the iron-catalyzed glycal 1,2-cN-ami noglycosylation, underwent smooth 1,2-cN-ami noacyloxy lation with amination reagent 3f to afford product 10 in 69% yield (dr >20:1). Further exploration of galactals proved that they are suitable substrates, which were converted to corresponding 2-amino glycosyl esters 11-13 in excellent yields (dr >20:1).

[0053] Moreover, the reactivity of deoxygenated glycals was explored. Notably, 3-deoxy glycals, a type of previously challenging substrates with diminished oc- selectivity in nitrogen atom transfer reactions, underwent swift glycosylation to afford product 14 as a single diastereomer, presumably due to the steric bulk of the iron catalyst. Additionally, a 6-deoxy glucal was readily converted to l,2-cM-2-amino glycosyl ester 15 (dr >20:1), a structural motif often present in complex microbial glycans.1It is also noteworthy that a xylal-based glycal, despite the absence of a C5 substituent, participated smoothly in the m-selective glycosylation, affording 16 (dr >20:1).

[0054] To explore functional group compatibility of this method with complex carbohydrates, several disaccharide-based glycals with an array of glycosidic linkages was investigated. First, both a glucosamine (GlcN)-a-l,6-glucose (Glu) and a GlcN-a-l,3-Glu-dervied glycals, easily prepared via the iron-catalyzed glycal L2-cA-aminoglycosylation, (see, Li, H.; et al., Stereoselective Glycosylation for 1,2-cis- Aminoglycoside Assembly by Cooperative Atom Transfer Catalysis. J. Am. Chem. Soc. 2024, Vol. 146, 33316-33323) are excellent substrates (corresponding products 17-18, dr >20:1). Next, a synthetically valuable glycal derived from D-lactose, most relevant in AM inked glycoprotein synthesis, can be smoothly converted to 2-amino glycosyl ester 19 (dr >20:1).

[0055] Based on the previous mechanistic studies of the iron-catalyzed olefin aminoacyloxylation and glycal m-aminoglycosylation. both implying highly electrophilic iron species possessing significant radical character in the nitrogen atom transfer reactions, and without being bound by theory, a mechanistic working hypothesis for the iron-catalyzed glycal cis-aminoacyloxylation is shown in FIG. 17. First, an iron(II) catalyst could readily coordinate with an acyloxyl carbamate 3 in the presence of molecular sieves to form complex I, in which the iron catalyst gets oxidized to generate a highly reactive iron nitrenoid II or an iron iminyl radical intermediate II'. II / II' could undergo radical amination with a glycal to afford a 2-amidoglycosylradical intermediate III. The exclusive oc-stereoselectivity, observed even with 3-deoxy glycals, may be determined by the transition state geometry that leads to the 2-amidoglycosyl radical species III in its most stable 62,5 conformation. Reversible deprotonation of the carboxylic acid ligand in III could generate intermediate IV, which could further undergo direct carboxylate ligand transfer to the 2-amidoglycosyl radical intermediate to afford the aminoacyloxylation product VII.Alternatively, the electrophilic iron(III) in III could oxidize the 2-amidoglycosyl radical, presumably via single electron transfer (SET), to generate a 2-amidoglycosyl oxocarbenium ion V, from which product VII can be generated via either direct carboxylic acid ligand transfer or carboxylate ligand transfer through the intermediacy of VI.

[0056] Based on the foregoing, a method for stereoselective synthesis of l,2-cis-2-, which aminoglycoside is shown in Scheme A includes reacting a glycal of formula (1) with an amination agent of formula (II) and a glycosyl acceptor of formula (III) in the presence of an iron(II) catalyst, a solvent, and molecular sieves to provide the l,2-cis-2-aminoglycoside of formula (IV):Scheme A.R>2 „R4 47-R' — R r n(l ) ca aly t r4I o l t s -R5— R5Molecular selves 0 Solvent5+R8— OH(II) (HI) wherein in each of formulas (I), (II), (III), and (IV)R1, R2, R3, R4, and R5are each independently hydrogen, alkyl, cycloalkyl, heteroalkyl, or heterocycloalkyl, optionally substituted with one or more of oxo, halo, cyano, azido, nitro, Ra, -CH2OR3, --OR3, — -N(Ra)(R3). — (C=O)Ra, — (C=O)ORa, — -(C==O)N(Ra)(Ra), — O(C=O)Ra. — N( Ra)(O0 )R — O(C-O)N(Ra)(Ra), or — -N(Ra)(C==O)ORa,:R6and R7are each independently hydrogen, -S(=O)2Ra, -S(==O)2Oa, (--- (C=O)Ra, --- (C=O)ORa, — (C=O)N(Ra)(Ra), — -O(C==O)Ra, — N(Ra)(O0)R\ — 0(C=0)N(Ra)(Ra), or — N(Ra)(C O)OR3.R8is alkyl, alkyl-C(=O)-, cycloalkyl, cycloalkyl— C(=O)-, heteroalkyl, heteroalkyl-C(=0)-, heterocycloalkyl, or heterocycloalkyl-C(=0)-, optionally substituted with one or more of oxo. halo, cyano, azido, nitro, Ra, —OR3, — N(Ra)(Ra), — (C==O)Ra, — (C=O)ORa, — (OO)N(Ra)(Ra), -O(C=O)Ra, -N(Ra)(C=O)Rs, — O(C-O)N(Ra)(R3), or — N(Ra)(C=O)ORa, andeach Rais independently at each occurrence hydrogen, alkyl, aryl, heteroalkyl, heteroaryl, cycloalkyl, heterocycloalkyl, or trialkylsilyl, each of which Raother than hydrogen is optionally substituted with one or more of alkyl, heteroalkyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, alkoxy, aryloxy, amino, alkylamino, dialkylamino, hydroxyl, halo, acylamino, aminoacyl, cyano, nitro, azido, acyl, acyloxy, carboxyl, carboxyl ester, alkanoyl, carboxamide, haloalkyl, or haloalkoxy; ortwo Ragroups together with the atoms to which they are attached form a cycloalkyl, heterocycloalkylaryl, or heteroaryl ring, each of which ring is optionally substituted with one or more of alkyl, heteroalky], cycloalkyl, heterocycloalkyl, aryl, heteroaryl, alkoxy, aryloxy, amino, alkylamino, dialkylamino, hydroxyl, halo, acylamino, aminoacyl, cyano, nitro, azido, acyl, acyloxy, carboxyl, carboxyl ester, alkanoyl, carboxamide, haloalkyl, haloalkoxy,

[0057] In an aspect, the l,2-cis-2-aminoglycoside (III) is produced at a diastereomeric ratio of cisitrans of greater than 5:1, or greater than 10:1. or greater 20:1, or greater than 40:1, or greater than 50:1.

[0058] In another aspect, the method further includes cleaving R6from the R6HN- moiety to provide the corresponding a l,2-cis-2-aminoglycoside. The l,2-cis-2-aminoglycoside can have a diastereomeric ratio of cis:trans of greater than 5:1, or greater than 10:1, or greater 20:1, or greater than 40:1, or greater than 50:1.

[0059] Another method for stereoselective synthesis of a l,2-cis-2-aminoglycoside is shown in Scheme B, and includes reacting a glycal of formula (I) reacting a glycal of formula (I) with an amination agent of formula (II) and a glycosyl acceptor of formula (V) in the presence of an iron(II) catalyst, a solvent, and molecular sieves to provide the l,2-cis-2-aminoglycoside of formula (VI): Scheme B.(I) (II) (V) (VI) wherein in formula (I), (II), (V), and (VI),r is 0 or 1,each R1, R2, R\ R4, and R3are independently hydrogen, azido, cyano, halo, hydroxy, nitro, — ORa, — SR alkyl, cycloalkyl, heteroalkyl, heterocycloalkyl, aryl, or heteroaryl, wherein each of R1, R2, R3. R4. and R5that is not hydrogen, azido, cyano, halo, hydroxy, or nitro is optionally substituted with one or more of azido, cyano, halo, hydroxy, oxo, nitro, Ra, — ORa, — SRa, — N(Ra)(Ra), — (C=O)Ra. — (C=O)ORa, — (C=O)N(R’)(R’), -O(C=O)R’, — N(Ra)(O0)Ra, ------O(C— O)N(Ra)(Ra), or ------N(Ra)(C-=O)ORa. or two R4or two R5together are oxo;R6and R7are each independently hydrogen, -S(=O)2Ra, -S(=O)2ORa, - -(C==O)Ra, ------ (C=C)ORa, — (C==O)N(Ra)(Ra), — O(C=O)Ra, —N(Ra)(C=O)Ra, — 0(C=O)N(Ra)(Ra), or --NT(Ra)(CX))OR3, ora residue of an amino acid, peptide, diagnostic agent, lipid, metabolite, nucleoside, polynucleoside, nucleotide, polynucleotide, monosaccharide, polysaccharide, steroid, or therapeutic agent; andeach Rais independently at each occurrence hydrogen, azido, cyano, halo, hydroxyl, nitro, alkyl, cycloalkyl, heteroalkyl, heterocycloalkyl, aryl, heteroaryl, or trialkylsilyl, each of which Raother than hydrogen azido, cyano, halo, hydroxyl, or nitro is optionally substituted with one or more of hydrogen, azido, cyano, halo, alkyl, aryl, cycloalkyl, heterocycloalkyl, heteroaryl, heterocycloalkyl, alkoxy, aryloxy, amino, alkylamino, dialkylamino, acylamino, aminoacyl, acyl, acyloxy, carboxyl, carboxyl ester, alkanoyl, carboxamide, haloalkyl, or haloalkoxy: ortwo Ragroups together with the atoms to which they are attached form a cycloalkyl, heterocycloalkylaryl, or heteroaryl ring, each of which ring is optionally substituted with one or more of alkyl, heteroalkyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, alkoxy, aryloxy, amino, alkylamino, dialkylamino, hydroxyl, halo, acylamino, aminoacyl, cyano, nitro, azido, acyl, acyloxy. carboxyl, carboxy] ester, alkanoyl. carboxamide, haloalkyl. or haloalkoxy.

[0060] In an aspect, the l,2-cis-2-aminoglycoside (VI) in Scheme B is produced at a diastereomeric ratio of cis:trans of greater than 5:1, or greater than 10:1, or greater 20:1, or greater than 40:1, or greater than 50:1.

[0061] In another aspect, the method further includes cleaving R6from the R6HN- moiety of l,2-cis-2-aminoglycoside (VI) of Scheme B to provide the corresponding a l,2-cis-2-aminoglycoside. The l,2-cis-2-aminoglycoside can have a diastereomeric ratio of cis:trans ofgreater than 5:1, or greater than 10:1, or greater 20:1, or greater than 40:1, or greater than 50:1.

[0062] Another method for stereoselective synthesis of a 1,2-cis-aminoglycoside omits the glycosyl acceptor. Thus, further described is a 1.2-m-selective glycal aminoacyloxylation method for 2-amino saccharide synthesis that is effective for a wide variety of glycosyl donors with consistently high stereoselectivity and excellent functional-group compatibility, which facilitates late-stage amino group incorporation for complex-carbohydrate synthesis. In this method, as shown in Scheme C, a glycal of formula (I) is reacted with an amination agent of formula (II) in the presence of an iron(II) catalyst, a solvent, and molecular sieves to provide the l,2-cis-2-aminoglycoside of formula (VT)Iron(ll) catalyst Molecular selvesSolventwherein in formulas (I), (II), and (VI)r is 0 or 1,each R1, R2, R3, R4, and R5are independently hydrogen, azido, cyano, halo, hydroxy, nitro, — ORa, — SRa, alkyl, cycloalkyl, heteroalkyl, heterocycloalkyl, aryl, or heteroaryl, wherein each of R1, R2, R3, R4, and R5that is not hydrogen, azido, cyano, halo, hydroxy, or nitro is optionally substituted with one or more of azido, cyano, halo, hydroxy, oxo, nitro, Ra, — ORa, — SRa, — N(Ra)(Ra), — (C=O)Ra, — (C=O)ORa, — (C=O)N(Ra)(Ra), — O(C=O)Ra, — N(Ra)(C=O)Ra, — O(C=O)N(Ra)(Ra), or — N(Ra)(C=O)ORa, or two R4or two R5together are oxo;R6and R'' are each independently hydrogen, -S(=O)2Ra, -S(=O>2ORa, — (C=O)Ra, — (C=O)ORa, — (C=O)N(Ra)(Ra), — O(C=O)Ra, — N(Ra)(C=O)Ra, — O(C=O)N(Ra)(Ra), or — N(Ra)(C=O)ORa; andeach Rais independently at each occurrence hydrogen, azido, cyano, halo, hydroxyl, nitro, alkyl, cycloalkyl, heteroalkyl, heterocycloalkyl, aryl, heteroaryl, or trialkylsilyl, each of which Raother than hydrogen is optionally substituted with one or more of hydrogen, azido, cyano, halo, alkyl, aryl, cycloalkyl, heterocyclo alkyl, heteroaryl, heterocycloalkyl, alkoxy, aryloxy, amino, alkylamino, dialkylamino, acylamino, aminoacyl, acyl, acyloxy, carboxyl, carboxyl ester, alkanoyl, carboxamide, haloalkyl, or haloalkoxy; ortwo Ragroups together with the atoms to which they are attached form a cycloalkyl, heterocycloalkylaryl, or heteroaryl ring, each of which ring is optionally substituted with one or more of alkyl, heteroalkyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, alkoxy, aryloxy, amino, alkylamino, dialkylamino, hydroxyl, halo, acylamino, aminoacyl, cyano, nitro, azido, acyl, acyloxy, carboxyl, carboxyl ester, alkanoyl, carboxamide, haloalkyl, or haloalkoxy.

[0063] The glycal (I) in Scheme C can be a 3-deoxy glucal or a 6-deoxy glucal. In some aspects, the glycal (I) in Scheme C is of the formulaAcO^\ AcO— r-A^o AcO—Me TBSOAcO TBSO— r~ — -O TBSO—

[0064] In an aspect, the l,2-cis-2-aminoglycoside (VI) in Scheme C is produced at a diastereomeric ratio of cisitrans of greater than 5:1. or greater than 10:1, or greater 20:1. or greater than 40: 1, or greater than 50: 1.

[0065] In another aspect, the method further includes cleaving R6from the R6HN- moiety of l,2-cis-2-aminoglycoside (VI) in Scheme C to provide the corresponding a l,2-cis-2-aminoglycoside. The l,2-cis-2-aminoglycoside can have a diastereomeric ratio of cis:trans of greater than 5:1, or greater than 10:1. or greater 20:1. or greater than 40:1, or greater than 50:1.

[0066] The various reactants in Schemes A, B, and C will now be described in further detail.

[0067] In Schemes A, B, and C, the glycal (I) can be of the formula(la) H (ib) or H (ic)wherein R3, R4, and R3are each independently hydrogen, azide, alkyl, cycloalky!, heteroalkyl, or heterocycloalkyl, optionally substituted with one or more of oxo, halo, cyano, azido, nitro, Ra, — OR8, — N(R8)(Ra), — (C=O)R’, — (C=O)0R’, — (C=O)N(Ra)(Ra), — O(C=O)Ra, — N(Ra)(C O)Ra, --O(C— O)N(Ra)(Ra), or --N(Ra)(C=O)ORa.

[0068] In formulas (la), (Ib), and (Ic), R3, R4, and R3can each independently be hydrogen, azide, alkyl optionally substituted with one or more of oxo, halo, cyano, azido, Ra, — ORa, — (O0)Ra, --(OO)ORa, --(C— O)N1(R3)(R3), — O( C=O )Ra, — N(Ra)(C=O )Ra, — O(C=O)N(R3)(Ra), or — N(R3)(C=O)ORawherein Rais defined as above.

[0069] Still further in the glycal (II), R3, R4. and R5are each independently hydrogen, azide, or alkyl optionally substituted with one or more of oxo, halo, cyano, azido, nitro, Ra, — ORa, — N(Ra)(Ra), (C=O)R -- (C=O)ORa, -- (C=O)N(Ra)(Ra), — O(C=O)Ra, -- N(Ra)(C=O)Ra, O(C==O)N(Ra)(Ra), or — N(Ra)(C=O)ORawherein Rais defined as above.

[0070] In another aspect, the glycal can be of formula (Id)(Id).

[0071] In formula (Id), R3and R4are each independently hydrogen, azide, alkyl, cycloalkyl, heteroalkyl, or heterocycloalkyl, optionally substituted with one or more of oxo, halo, cyano, azido, nitro, R3, --OR3, — N(R3)(Ra), — -(OO)R3, (( O)ORa, --(C-O)N(Ra)(Ra), ()i( 1=0 )Ri!, — N(Ra)(C==O)Ra, — O(C==O)N(Ra)(Ra), or — N(Ra)(C==O)ORawherein Rais defined as above.

[0072] Further in formula (Ic), R5is heterocycloalkyl or — Cl-fcheterocycloalkyl. optionally substituted with one or more of oxo, halo, cyano, azido, nitro, R3, — OR3, — N(R3)(R8), — (C=O)R3,.....,(C=O)ORa. — (C=O)N(Ra)(Ra), — -O(C=O)Ra, ~~ (RaXC ))Ra. — O(C= O)N(Ra.)(Ra), or -N(Ra)(C= O)ORa. heterocycloalkyl, or — CHzheterocycloalkyl, optionally substituted with one or more of oxo, halo, cyano, azido, nitro, Ra, — ORa, — N(Ra)(Ra), — (C=O)R — ■(C=O)ORa, ----(C=-O)N(Ra)(Ra), — O(C=O)Ra, -- N(R3)(O-0)Ra, — O(C^O)N(Ra)(Ra), or — N(Ra)(C=O)0Rawherein Rais defined as above.

[0073] Specifically, the glycal (I) can be of the formulaOptionally each of the foregoing glycal formulas, each acetal, acetyl, benzyl, benzoyl, tert¬ butyldimethylsilyl, benzyl, or benzoyl protecting group can be independently replaced with a different hydroxy-protecting group.

[0074] In Schemes A, B, and C the amination agent (II) can be of the formulaooooOS(O)2Ra / S(O)2ORaH2N Ra, orwherein each Rais as defined above in Schemes A, B, and C, and each Ra2is the same as Ra, with the proviso that Ra2is not hydrogen.

[0075] In another aspect, the amination agent (II) can of the formula

[0076] In Schemes A and B, the glycosyl acceptor (III) can be of formula (Illa) or (Illb)OR9X^OHR8-OH (Illa) or(Illb)wherein R8is as described above in Scheme A, and R9is alkyl, cycloalkyl, heteroalkyl, heterocycloalkyl, optionally substituted with one or more of oxo, halo, cyano, azido, nitro, Ra, ------()Ra, -~-~-N(Ra)(Ra), 4 <-O: OK:. ^(CX))N(Ra)(R3), — O(C> O)Ra, — N(Ra)(C==O)Ra, -~-O(C==O)N(Ra)(Ra), or --N(Ra)(C==O)ORa.

[0077] In an aspect, the glycosyl acceptor (Illa) or (Illb) is a cyclic sugar or sugar derivativehaving a primary or secondary hydroxyl group, for example a pyranose or hexose of formula (IIIc) or (Hid)o(IIIc) or (Hid)whereinX is O, N, or S,, preferably O;G1is a bond or a linking group that can be an alkylene, alkyh cycloalkylene, heteroalkylene, heterocycloalkylene optionally substituted with one or more of oxo, halo, cyano, azido, nitro. Ra, —OR8, — N(R8)(R8.), — (C=O)R‘, — (C=O)ORa, — (C=O)N(R‘)(R’), — - O(C=O)Ra, — N(Ra)(C=O)Ra, — O(C==O)N(Ra)(Ra). or — N(Ra)(C==O)ORa: andand each R6is independently hydrogen, alkyl, cycloalkyl, heteroalkyl, heterocycloalkyl, optionally substituted with one or more of oxo, halo, cyano, azido, nitro, Ra, — OR3, — N(Ra)(Ra). ((:=O)Ra. — (C-O)ORa. — (C=-O)N(Ra)(Ra), — 0(C-0 )R \ -N(Rs)(C=O)Ra. — -O(C=O)N(Ra)(Ra), or Nsa)(C=O)ORa;each Rais as defined above in Schemes A and B; andn is 1 or 2 and m is the number of valences on the carbon atoms available for substitution.

[0078] For example, glycosyl acceptor (III) can be a hexose or pentose of the formula (Ille)wherein X is O, N, or S, preferably O;G1is a bond or a linking group that can be an alkylene, alkyl, cycloalkylene, heteroalkylene, or heterocycloalkydene optionally substituted with one or more of oxo, halo, cyano, azido, nitro, R3, --OR3. — N(Ra)(Ra), --(C 0)R3, — (O-O)OR3, — (C=O)N(Ra)(Ra), — 0(C=O)Ra. — N(Ra)(C=O)Ra, -0(00)N(Ra)(Ra). or — N(Ra)(C=O)ORa: andand each R11is independently hydrogen, alkyl, cycloalkyl, heteroalkyl, heterocycloalkyl, optionally substituted with one or more of oxo, halo, cyano, azido, nitro, Ra, — OR’1, —N(Ra)(R3), (C==O)Ra, — (C=O)OR — (C=O)N(Ra)(Ra). — O(C==O)R\ — N(Ra)(C=O)R3, --O(C-O)N(Ra)(R3). or --N(R3)(C==O)ORa;each Rais as defined above in Schemes 1, 2, and 3: andn is 1 or 2.

[0079] It is to be further understood that the glycosyl acceptor (Illa), (IIIc), or (Ille) can be any one of the glycals described above (e.g., Formulas (I), (la), (lb), (Ic) or (Id)), provided that the glycal has a primary or secondary hydroxyl group.

[0080] Exemplary glycosyl acceptors (III) can be cyclohexanol, t-butyl alcohol, n-pentanol, 2,2,2-triflouroethanol, 2-phenylethanol, allyl alcohol, t-butyl 2-hydroxylacetate, or of the formulaHO OH, or

[0081] A wide variety of iron(II) catalysts can be used effectively. The method can proceed with a catalyst of the formulaFe(II)XY- nH2Owherein X and Y are each independently the same or different organic or inorganic counter anion, provided that at least one of X and Y is a noncoordinating anion.

[0082] The noncoordinating anion can be of the formula (RfSCDN-, Al(OCRf)4-, B(RAi -, B(Rf)4-, or RiSCh, wherein R is an aryl group or a substituted aryl group, of which the one or more substituents are the same or different and are alkyl, or aryl. Rf is a monovalent alkyl, cycloalkyl, aryl, or aryl, each of which is substituted fluorine, fluorinated or perfluorinated alkyl, or fluorinated or perfluorinated aryl, CF3SO3, (CF3SO2)N, CB11H12, C104, A1(OC(CF3)3)4. AsFe, SbFe, BF4, PF6-, B(C6F5)4’, B(C6H4)4, or B(3,5-(CF3)2C6H3)4-.

[0083] In an aspect, the iron(II) catalyst includes a tridentate nitrogen-containing ligand, the tridentate nitrogen-containing ligand is of the formulas Ligl, Lig2, Lig3, or Lig4:R6R5R3Lig4wherein in formulas Ligl, Lig2, Lig3, or Lig4, each R1, R2. R3, R‘:, R5, R'', and Rzare independently hydrogen, azido, cyano, hah), hydroxy, nitro, alkyl, cycloalkyl, heteroalkyl, heterocycloalkyl, aryl, or heteroaryl, wherein each of R1, R2, R’, R4, R5, Rb, and R7that is not hydrogen, azido, cyano, halo, hydroxy, or nitro is optionally substituted with one or more of azido, cyano, halo, hydroxy, oxo, nitro, - 0Ra, - SRa, --N(Ra)(Ra), - (O0)Ra, - (C=O)ORa, --(O0)N( R3)( R3), --- O(C===O)Ra, — •N(Ra)(C=O)Ra, 010=0 )N( Ra)( Ra), or -N(R2)(C=0)0R wherein each Rais as defined in formula (I). In some aspects, the iron(II) catalyst includes a ligand of formula LI, L2, or L3.L3Preferably ligand LI is used. The catalyst iron catalyst the formula Fe(Ll)(BF4)2< MeCN)(H2O)2 is preferred.

[0084] The glycosciences have been significantly advanced by robust glycosylation methods that can be used in solid-phase and automated carbohydrate synthesis. While the feasibility of automated carbohydrate synthesis has been established for complex-glycan synthesis, stereoselective assembly of 1,2-cis-aminoglycosides through solid-phase synthesis has been difficult because these linkages are challenging to form reliably with high stereoselectivity. In another aspect, the iron-catalyzed glycosylation can be used for reiterative glycosylation, which can allow solid-state synthesis. Such methods are valuable from a research and manufacturing standpoint. Stereoselective assembly of 1,2-cis-aminoglycosides through solid-phase synthesis has been challenging because this type of linkage was previously difficult to form reliably in high stereoselectivity.

[0085] A reiterative glycal cis-aminoglycosylation approach that can be operated in a continuous way, for example for applications in automated carbohydrate synthesis has been developed as shown in Scheme 15.Scheme 15.a) 1 (15 mol%) a) 1 (15 mol%), 40 and 3d 71 % yield^ 69% yield cfr >20:1 dr >20:1 282% yield

[0086] As shown in Scheme 15, it was discovered that a glycal 37 with an electron-deficient 3-O-acyl group will not function as a donor, but can be used as an acceptor with electron-rich glycosyl donor 2 delivering a single diastereomeric disaccharide 38. Subsequently, the glycal moiety in 38 can be activated by selective enzymatic hydrolysis of the allylic acetate followed by silylation (see Examples), and that 39 now reacts as a donor in a second iron-catalyzedglycosylation with disaccharide acceptor 40■OHBnO^ -QBnO- BOCHNQAcO-T-^OOAc —40generating tetra- saccharide 41, again as a single diastereomer. If desired, the glycal moiety of tetrasaccharide 41 can be activated for further reiterative glycosylation. The reiterative glycosylation provides a convenient approach that readily couples complex oligosaccharide fragments.

[0087] To explore other coupling strategies, the reactivity of complex carbohydrates, including disaccharide-based donors and acceptors 42, 44, and 46 were explored. They are all compatible with this method and the corresponding trisaccharides (43, 45, and 47) were all obtained as single diastereomers (Scheme 15).Me424371 % yield (3d), dr >20:14572% yield (3d), dr >20:14767% yield (3g), cfr>20:1If desired, the glycal moiety of the tri- saccharides can be activated for further reiterative glycosylation to provide tetra- and higher polysaccharides.

[0088] The reiterative glycal cis-aminoglycosylation provides a convenient approach for rapid oligosaccharide assembly that readily couples complex oligosaccharide fragments. Uronic acids are critical components in heparin / heparan sulfate and other glycosaminoglycans (GAGs), but it is challenging to directly incorporate uronic acid building blocks into GAGs via highly 1,2-cis-selective glycosylation. Here, uronic esters (48 and 50) with an electron-deficient glycal moiety can be effectively coupled with an electron-rich glycal 2, delivering both an a-l,3-linked and an a- 1,4-linked 1,2-cis-aminoglycoside (49 and 51 in Scheme 16). This discovery paves the way for ongoing efforts of rapid synthesis of heparin and heparan sulfate.Scheme 16.CO2Me CO2Me HO— AHO— 4^-^ 48 50 a) 1 (15 mol%), 3f a) 1 (15 mol%), 3h 78% yield 57% yield dr>20:1 dr >20:1

[0089] Accordingly, a reiterative method for stereoselective synthesis of a poly(l,2-cis-2-aminoglycoside) includesa first reacting of a glycal of formula (I),R3RA ^-U^^R4R1'X^'O'X^'R6(I)R k N RI7H(IDand a glycal of the formulaR3R4R5'(la)in the presence of an iron catalyst, to provide a first 1,2-cis disaccharide comprising an enol ether group derived from the cyclic enol ether;a second reacting offirst disaccharide comprising an enol ether group,a second amination agent of the formulaR6^N R77IH(II), anda cyclic saccharide having a primary or secondary hydroxyl group,in the presence of an iron catalyst, to provide a 1,2-cis polysaccharide; andoptionally repeating the second reacting.whereinR’, R2, R-’, R4, and R5are independently hydrogen, alkyl, cycloalkyl, heteroalkyl, or heterocycloalkyi, wherein each of RJand R2that is not hydrogen is optionally substituted with one or more of oxo, halo, cyano, azido, nitro, Ra, — ORa, — N(Ra)(Ra), — (C=O)Ra, — (C=O)OR8, ---(C-O)N(Ra)(Ra), ■— O(C=O)Ra, --- N(Ra)(C=O)Ra, —O(C=O)N(Ra)(Ra), orR:::•{('—R‘, R2, R’, R4, and R5are independently hydrogen, hydroxy, alkyl, cycloalkyl, heteroalkyl, or heterocycloalkyi, wherein each of R1and R2that is not hydrogen is optionally substituted with one or more of hydroxy, oxo, halo, cyano, azido, nitro, Ra, — ()Ra. — N(Ra)(Ra), — (C-O)Ra, --( C-O)OR:\ (C~() )N( Ra)( Ra), O(C-O iR '. --N( R1)(C=O )Ra, --- O(C=O)N(Ra)(Ra), or — N(Ra)(C=O)ORa, with the proviso that at least one of R1, R2, R3, R4, and R5include a primary or secondary hydroxy group;R6and R7are each independently hydrogen, -S(~ O);: Ra, -S(==O)2ORa, ( — (C==O)Ra, —(C==O)ORa, ---(O0)N(Ra)(Ra). -O(C=O)Ra, -N(Rs)(C=O)Ra, — -O(C=O)N(Ra)(Ra), or --N(Ra)(C-O)ORa,R8is alkyl, alkyl -C (=0)-. cycloalkyl, cycloalkyl — C(=0)-, heteroalkyl, heteroalkyl-C(==0)-, heterocycloalkyl, or he4erocycloaIkyl-C(==<))-, optionally substituted with one or more of oxo, halo, cyano, azido, nitro, Ra, — 0Ra, — N(Ra)(Ra). — (C=0)Ra, — (C=O)ORa, — (C=O)N(Ra)(Ra), -0(C=O)Rs, --- N(Ra)(C=0)Ra, ----- -O(C==O)N(Ra)(Ra). or -- N(Ra)(C~O)C)Ra, andeach Rais independently at each occurrence hydrogen, alkyl, aryl, heteroalkyl, heteroaryl, cycloalkyl, heterocycloalkyl, or trialkylsilyl, each of which Raother than hydrogen is optionally substituted with one or more of alkyl, heteroalkyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, alkoxy, aryloxy, amino, alkylamino, dialkylamino, hydroxyl, halo, acylamino, aminoacyl, cyano, nitro, azido, acyl, acyloxy, carboxyl, carboxyl ester, alkanoyl, carboxamide, haloalkyl, or haloalkoxy; ortwo Ragroups together with the atoms to which they are attached form a cycloalkyl, heterocycloalkylaryl, or heteroaryl ring, each of which ring is optionally substituted with one or more of alkyl, heteroalkyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, alkoxy, aryloxy, amino, alkylamino, dialk iarnino, hydroxyl, halo, acylamino, aminoacyl, cyano, nitro, azido, acyl, acyloxy, carboxyl, carboxyl ester, alkanoyl, carboxamide, haloalkyl, haloalkoxy.

[0090] It is surprising that the relatively simple, achiral iron catalyst described herein promotes a challenging stereoselective cascade process. Not only does the catalyst tolerate a variety of functional groups, but it also induces the exclusive 1,2-cis- selectivity for a broad range of substrates. To better understand this new type of reactivity and develop more efficient catalysts and amination reagents, the inventors have comprehensively probed for mechanistic insight into this reaction, including the activation of the amination reagent, the nature of the C-N and C-0 bond forming processes during glycal cis-aminoglycosylation, and the origin of 1,2-cis-aastereoselectivity.

[0091] Previous mechanistic studies of the iron-catalyzed olefin aminohydroxylation suggested that a highly electrophilic iron species may be generated upon catalyst oxidation and that it possesses significant radical character on nitrogen. In collaboration with Neidig, we tried to directly detect this reactive species using an array of spectroscopic techniques, especially freezetrapped57Fe Mossbauer spectroscopy. It was observed that a variety of iron(II)-Ll catalystcomplexes are rapidly decomposed to stable iron(III) species upon being oxidized by amination reagent 3, while the putative reactive iron species, either an iron-nitrenoid or an iron iminyl radical, may have unusually high reactivity and thus is too short-lived to be observed. Notably, multiple high-spin iron(II) species were observed in the pre-catalytic mixture, which adds to the difficulty in studying this reaction computationally. Therefore, the reactivity of designed mechanistic probes was investigated to better understand this reaction (Scheme 15).Scheme 15.a) 1 (15 mol%) 3d (1 5 equiv) <20% conversion2 52 53 541 0 equiv 04 equiv 4% yield 15% yieldFirst, a radical trap TEMPO (52) was introduced to the iron-catalyzed glycosylation of 2 with 4 (Scheme 15). The desired product 5 (8%) was observed together with TEMPO-containing product 53 (4%) and N-BocNFE 54 (15%) in a reaction that has <20% conversion. These data suggested that the iron catalyst is largely deactivated by TEMPO; however, the highly reactive species (55a or 55b)'BuOFeLnHR355acan still be generated, which could react with TEMPO to afford 53, presumably via a 1,5-hydrogen atom transfer from the initial TEMPO addition product (see FIG. 4).

[0092] Next. 1,2-cis-aminofluoride 57 was identified as a byproduct in glycosylation between 2 and 56 (Scheme 17).Scheme 17.a) 1 (15 mol%) or c) 1 (15 mol%) K2CO3(20 equiv) 2 3f 8f 57 a: 74% yield <5% yield 20% yieldc;30% yield 47% yield 10% yieldThis observation suggested that the glycosyl oxocarbenium ion is formed from the initially generated 2-aminoglycosyl radical species and that it may exist as a contact ion pair with tetrafluoroborate before the subsequent C-0 or C-F bond forming step (FIG. 5). Addition of 20 equivalents of solid K2CO3 significantly decreased the yield of disaccharide 12 but increased the yield of glycosyl carboxylate 8f (Scheme 17). This result suggested that an iron-bound carboxylate should be transferred more effectively than an iron-bound glycosyl acceptor (FIG. 6).

[0093] Preliminary kinetic studies of this iron-catalyzed glycosylation of electron-rich glycal 2 with primary acceptor 4 and amination reagent 3d (Scheme 5, Eq. 1) suggested that its initial rate has a first-order dependence on the iron catalyst, an inverse first-order dependence on acceptor 4, and a zero-order dependence on both glycal 2 and amination reagent 3d. This implies that an iron catalyst-4 complex probably contains at least two molecules of 4 and that it may be the resting state of the catalyst (in the presence of molecular sieves which can remove the water or acetonitrile ligand). Its dissociation with release of a primary acceptor 4 to form a coordinatively unsaturated iron catalyst may occur prior to the rate-determining, reactive species generation step (FIG. 7). Similar kinetic studies with an electron-deficient glycal S10 leading to aminoglycoside 20 from 4 and 3d suggested that its initial rate has a first-order dependence on the glycal. This result indicates that the rate-determining step (RDS) is no longer the reactive species generation, but instead the radical amination with the electron-deficient glycal S10 (FIG. 8).

[0094] Kinetic studies further revealed that the initial rate of glycosylation of 2 with secondary acceptor 6 and 3f (Scheme 5, Eq. 2) has a first-order dependence on the iron catalyst but a zero-order dependence on each of acceptor 6, glycal 2, and amination reagent 3f (Fig. S 19-S22). This differs from the glycosylation with a primary acceptor, which suggested that resting state of the iron catalyst may contain just one molecule of 6 and its dissociation of another exchangeable ligand (most likely acetonitrile) may occur prior to the RDS (FIG. 9).

[0095] Without being bound by theory these data allow formulation of a general mechanistic working hypothesis for the cis-selective glycosylation (FIG. 10). First, an electrophilic iron(II) catalyst could readily coordinate with a glycosyl acceptor in the presence of molecularsieves to generate an iron catalyst-glycosyl acceptor complex la or lb, which could reversibly dissociate an exchangeable ligand or a glycosyl acceptor to afford a coordinatively unsaturated complex II. Complex II could thereby rapidly coordinate with amination reagent 3 to generate complex III, in which the iron catalyst gets oxidized, affording a highly reactive yet short-lived intermediate (either an iron-nitrenoid IV or an iron iminyl radical IV).L0096J Reactive intermediates IV / IV could decompose in the absence of a suitable glycosyl donor, affording N-B0CNH265. However, in the presence of a reactive glycal, it could participate in an irreversible and exclusively a-selective radical amination to afford a putative 2-aminoglycosyl radical species V that is associated with the bulky and electrophilic iron catalyst. Intermediate IV / IV reacts rapidly with an electron-rich glycal but its addition to an electron-deficient glycal becomes rate-determining. It is worth noting that the exclusive a- stereo selectivity may be influenced by the stereogenic centers of the glycal and determined by the transition state geometry that leads to the 2-aminoglycosyl radical species V in its most stable B25 conformation.

[0097] The electrophilic iron(III) in intermediate V could oxidize the 2-aminoglycosyl radical, presumably via single electron transfer (SET), to the corresponding 2-aminoglycosyl oxocarbenium ion VI that exists as a contact ion pair with tetrafluoroborate. With a less-sterically demanding glycosyl acceptor, the catalyst-directed glycosyl acceptor transfer occurs rapidly, reminiscent of intramolecular aglycon delivery and the proposed reactivity of alkoxy palladium species in deoxyglycoside synthesis, furnishing the glycal cis-aminoglycosylation product VII. However, with a more hindered glycosyl acceptor, the rate of transfer could decrease such that the competing glycal cis-aminoacyloxylation (leading to byproduct IX) could become the major pathway. Presumably, deprotonation of the carboxylic acid ligand of intermediate VI could afford intermediate VIII, which could undergo carboxylate transfer to the 2-aminoglycosyl oxocarbenium ion, affording byproduct IX. It is also likely that deprotonation occurs with V, leading to intermediate X which might directly undergo iron(III)-bound carboxylate ligand transfer to the 2-aminoglycosyl radical species to afford IX as well.

[0098] This mechanistic insight is particularly valuable for engaging challenging acceptors in the glycosylation. Structural modulation of the amination reagent can favor glycal cis-aminoglycosylation over cis-aminoacyloxylation: when a less acidic, yet sterically bulky carboxylic acid, is generated upon reductive cleavage of the N-0 bond in an amination reagent, the corresponding carboxylate ligand cannot get transferred effectively by the iron catalyst; therefore, high chemoselectivity will be achieved.

[0099] It is to be understood that any one or more of the products described herein is within the scope of the invention.

[0100] The invention is further illustrated by the following Examples, which are nonlimiting.EXAMPLESA. General Information

[0101] General Procedures. All reactions were performed in oven-dried or flame-dried round-bottom flasks and vials. Stainless steel syringes and cannula were used to transfer air- and moisture-sensitive liquids. Flash chromatography was performed using silica gel 60 (230-400 mesh) from Sigma-Aldrich.

[0102] Materials. Commercial reagents were purchased from Sigma- Aldrich, TCI, Oakwood Chemicals, Combi-Blocks, Chem-Impex, Thermo Fischer Scientific and used as received. All solvents were used after being freshly distilled unless otherwise noted.

[0103] Instrumentation. Proton nuclear magnetic resonanceNMR) spectra, carbon nuclear magnetic resonance (13C NMR) spectra, and fluorine nuclear magnetic resonance (19F NMR) spectra were recorded on Advance NEO 400 (400 MHz) and Varian 400-MR (400 MHz). Chemical shifts for protons are reported in parts per million downfield from tetramethylsilane and are referenced to the NMR solvent residual peak (CHCh 67.26). Chemical shifts for carbons are reported in parts per million downfield from tetramethylsilane and are referenced to the carbon resonances of the NMR solvent (CDCh 577.0). Chemical shifts for fluorines are reported in parts per million upfield from and referenced to the fluorine resonances of CFCh (50.00). Data are represented as follows: chemical shift, multiplicity (br = broad, s = singlet, d = doublet, t = triplet, q = quartet, quint = quintet, m = multiplet), coupling constants in Hertz (Hz), and integration. The mass spectroscopic data were obtained at Brandeis Mass Spectrometry Facility using a Bruker timsTOF Pro instrument by electrospray ionization (ESI). Infrared (IR) spectra were obtained using a Nicolet IR200 spectrometer with a diamond ATR. Data are represented as follows: frequency of absorption (cm1) and absorption strength (s = strong, m = medium, w = weak). Optical rotations were measured on a Jasco P-2000 Polarimeter. The cuvette dimension is 10 cm and holds 1.5 mL.

[0104] Abbreviations used are shown in the Table below.THF -tetrahydrofuran EtOAc - ethyl acetateEtOH-ethanol Et; O - diethyl etherCEECF-dichloromethane MeCN - acetonitrileTEA-triethylamine TFA - trifluoroacetic acidTLC - thin layer chromatography B0C2O - di-tert-butyl dicarbonateDMAP - 4-dimethylaminopyridine TEMPO - 2, 2, 6, 6- tetramethyl-l-piperidinyloxyTsOH HiO - p-toluenesulfonic acid monohydrate Bn - benzylBz-benzoyl Cbz - benzyloxycarbonylTBS - tert-butyldimethylsilyl TMS - trimethylsilylmg-milligram mmol-millimoleh-hour min-minequiv-equivalents TLC-thin layer chromatographymL-milliliter A - AngstromMe-methyl Et-ethylPh - phenyl TBSCl-tert-butyldimethylsilyl chlorideB. Reaction Discovery for the Iron-Catalyzed Glycal cis-AminoglycosylationScheme 18.Me Me Me O^\ O'V'Lo TBSO—8 dr >20:1at the C1 and C2 a. General Procedure for the Reaction Discovery

[0105] To a flame-dried sealable 2-dram vial (vial A) equipped with a stir bar were added glycal 2 (90 mg, 0.3 mmol, 1.0 equiv), glycosyl acceptor 4 (125 mg, 0.36 mmol, 1.2 equiv), iron catalyst (0.03 mmol, 10 mol %) and freshly activated 5 A molecular sieves, powder (ca. 150 mg). After the vial was evacuated and backfilled with N2 three times, anhydrous CH2CI2 (0.5 mL) was added and the solution was cooled to -40 °C. To a second flame-dried sealable 2-dram vial (vial B) was added amination reagent 3 (0.45 mmol, 1.5 equiv). Vial B was evacuated and backfilled with N2 three times and then anhydrous CH₂Cl₂ (0.5 mL) was added. Amination reagent 3 was added to vial A using a syringe pump within 10 min. The reaction was kept at -40 °C for an additional 1 h and quenched by precipitating the iron catalyst with Et20 (4 mL) at the same temperature. The mixture was stirred for two minutes and subsequently warmed up to room temperature. The solution was then filtered through a piece of cotton and washed with saturated aq. NaHCO3 solution (2 mL). The organic phase was separated from the aqueous one, which was further extracted with CH2CI2 (3 mL x 3). The combined organic phase was dried over anhydrous Na₂SO₄h and concentrated in vacuo.The residue was purified through a silica gel flash column to afford the desired glycal cisaminoglycosylation product.b. Synthesis of New Amination Reagents for the Glycal cis- Aminoglycosylation Scheme 19.o DCC (1.1 equiv)HO^R2DMAP (0.1 equiv) oR2R1O N - R1O‘1 0 CH2CI2, 22 °C,1, oH C = 0.5 M, 2-4 hH1.0 equiv 1.0 equiv 3

[0106] To a 250 mL flame-dried round bottom flask equipped with a stir bar, an N-hydroxyl carbamate (20 mmol, 1.0 equiv), carboxylic acid (20 mmol, 1.0 equiv), DMAP (244 mg, 2 mmol, 0.1 equiv), and anhydrous CH2CI2 (40 mL) were added. The flask was cooled to 0 °C. DCC (4.53 g, 22 mmol, 1.1 equiv) was added portion wise. The reaction mixture was stirred for 2-4 h at 22 °C until the N-hydroxyl carbamate was fully consumed (monitored by TLC). The white precipitate (V, V'-dicyclohexylurea) was removed by filtration and the filtrate was concentrated in vacuo and dissolved again in Et20 (30 mL). The solution was cooled to -20 °C for 2 h and filtered again to remove additional precipitate. The organic laver was then concentrated in vacuo and the residue was purified through column chromatography (hexanes / Et2O) to afford the corresponding acyloxyl carbamate 3 (yield 72-82%).

[0107] tert-Butyl ((2,2-diphenylpropanoyl)oxy)carbamate (3b): compound 3b was prepared according to the general procedure and isolated as a white solid (5.26 g, 77% yield, m.p.7779 °C). IR vma\ (neat)Zcm’1: 3292 (w), 2981 (w), 1744 (m), 1444 (m), 1267 (m), 1154 (m), 1095 (m), 850 (w); ‘H NMR (400 MHz, CDCh) 87.84 (s, 1H), 7.37 - 7.27 (m, 10H), 2.05 (s, 3H), 1. 49 (s, 9H);13C NMR (100 MHz, CDCh) 8 174.8, 155.5, 143.1 (2C), 128.2 (4C), 128.0 (4C), 127.2 (2C). 83.2, 55.7, 28.0 (3C), 26.9; LRMS: m / z (APCI) calcd for C20H27N2O4+, [M + NH4]+, 359.2, found 359.2.

[0108] 2-(((tert-Butoxycarbonyl)amino)oxy)-2-oxoethyl acetate (3c): compound 3b was prepared according to the general procedure and isolated as a white solid (5.26 g, 77% yield, m.p.77-79 °C). IRvmax (neat)Zcm’1: 3292 (w), 2981 (w), 1744 (m), 1444 (m), 1267 (m), 1154 (m), 1095 (m), 850 (w); NMR (400 MHz, CDCh) 87.84 (s, 1H), 7.37-7.27 (m, 10H), 2.05 (s. 3H), 1.49 (s, 9H);13C NMR (100 MHz, CDCh) 8 174.8, 155.5, 143.1 (2C), 128.2 (4C), 128.0 (4C), 127.2 (2C),83.2, 55.7, 28.0 (3C), 26.9: m / z (ESI) calcd for C20H24NO [M + H]+, 342.1700, found 342.1697.

[0109] tert-Butyl ((2-bromo-2-methylpropanoyl)oxy)carbamate (3d): compound 3c was prepared according to the general procedure and isolated as colorless oil (3.64 g, 78% yield). IR vmax (neat)Zcm1: 3264 (w), 2982 (w), 1737 (s), 1370 (m), 1229 (m), 1131 (s), 843 (m); ’H NMR (400 MHz, CDCh) 57.89 (brs, 1H), 4.76 (s, 2H), 2.17 (s, 3H), 1.49 (s, 9H);13C NMR (100 MHz, CDCh) 8 170.1, 167.4, 155.1, 83.8, 59.2, 27.9, 20.3; HRMS: m / z (ESI) calcd for C9HI6NO6+, [M + H]+, 234.0972, found 234.0977.

[0110] 2-((((tert-Butoxycarbonyl)amino)oxy)carbonyl)-2-methylpropane-l,3-diyl dibenzoate (3e): compound 3e was prepared according to the general procedure and isolated as a white solid (7.50 g, 82% yield). IR Vmax (neat)Zcm1: 3299 (w), 2981 (w), 1733 (m), 1478 (m), 1369 (s), 1245 (m), 1047 (m). 867 (m);JH NMR (400 MHz, CDCh) 68.06-7.98 (m. 4H), 7.95 (s, 1H).7.59-7.51 (m, 2H), 7.46-7.38 (m, 4H), 4.66 (d, J = 11.2 Hz, 2H), 4.63 (d, J = 11.2 Hz, 2H), 1.54 (s, 3H), 1.44 (s, 9H);13C NMR (100 MHz, CDCh) 8 172.5, 165.9 (2C), 155.1. 133.3 (2C), 129.7 (4C), 129.4 (2C). 128.4 (4C), 83.5, 65.6 (2C), 46.4. 27.9 (3C), 17.7; HRMS: m / z (ESI) calcd for C24H28NOS+, [M + H]+, 458.1809, found 458.1801.

[0111] l-(((tert-Butoxy carbon yl)amino)oxy)-2-methyl-l-oxopropan-2-yl acetate (3f): compound 3f was prepared according to the general procedure and isolated as a white solid (4.18 g, 80% yield, m.p. 74-76°C). IRvmax (neat)Zcm’1: 3261 (w), 2984 (w), 1732 (m), 1370 (m), 1250 (m), 1161 (m). 1101 (m), 839 (w);1H NMR (400 MHz, CDCh) 87.96 (s, 1H), 2.05 (s, 3H), 1.61 (s, 6H), 1.46 (s, 9H);13C NMR (100 MHz, CDCh) 8 171.9, 170.1, 155.4, 83.1, 77.2, 29.4 (3C), 24.4 (2C), 20.9; HRMS: m / z (ESI) calcd for CnH20NO6+, [M + H]+, 262.1285, found 262.1277.

[0112] l-(((tert-Butoxycarbonyl)amino)oxy)-2-methyl-l-oxopropan-2-yl 2,4-dichlorobenzoate (3g): compound 3f was prepared according to the general procedure and isolated as a white solid (4.18 g, 80% yield, m.p. 74-76°C). IR Vmax (neat) / cm-1: 3261 (w), 2984 (w), 1732 (m), 1370 (m), 1250 (m), 1161 (m), 1101 (m), 839 (w); ’H NMR (400 MHz, CDCh) 87.96 (s, 1H), 2.05 (s, 3H), 1.61 (s, 6H), 1.46 (s, 9H);13C NMR (100 MHz, CDCh) 8 171.9, 170.1, 155.4, 83.1, 77.2, 29.4 (3C), 24.4 (2C), 20.9; HRMS: m / z (ESI) calcd for CnH2oN06+, [M + H]+. 262.1285, found 262.1277.

[0113] l-(((tert-Butoxycarbonyl)amino)oxy)-2-methyl-l-oxopropan-2-yl pivalate (3h): compound 3f was prepared according to the general procedure and isolated as a white solid (4.18 g, 80% yield, m.p. 74-76°C). IR vmax(neat) / cm-1: 3261 (w), 2984 (w), 1732 (m), 1370 (m), 1250 (m), 1161 (m), 1101 (m), 839 (w); ’ll NMR (400 MHz, CDCh) 87.96 (s, 1H), 2.05 (s, 3H), 1.61 (s, 6H),1.46 (s, 9H);13C NMR (100 MHz, CDCh) 5 171.9, 170.1, 155.4, 83.1, 77.2, 29.4 (3C), 24.4 (2C), 20.9; HRMS: m / z (ESI) calcd for CnH20NO6+, [M + H]+, 262.1285, found 262.1277.0114] l-(((Methoxycarbonyl)amino)oxy)-2-methyl-l-oxopropan-2-yl acetate (3i):compound 3i was prepared according to the general procedure and isolated as a white solid (473 mg, 72% yield). IR vmax(neat^cm’1: 3259 (w), 2951 (w), 1793 (m), 1742 (s), 1456 (m), 1370 (m), 1250 (s), 1109 (s), 872 (m); ‘H NMR (400 MHz, CDCh) 88.44 (brs, 1H), 3.76 (s, 3H), 2.05 (s, 3H), 1.60 (s, 6H);13C NMR (100 MHz, CDCh) 8 171.6, 170.3, 156.9, 77.2, 53.3, 24.3, 20.8; HRMS: m / z (ESI) calcd for C8HI4NO6+, [M + H]+, 220.0816, found 220.0818.

[0115] 2-Methyl-l-oxo-l-((((2,2,2-trichloroethoxy)carbonyl)amino)oxy)propan-2-yl acetate (3j): compound 3j was prepared according to the general procedure and isolated as a white solid (1.58 g. 78% yield). IR vmax (neat) / cm h 3175 (w), 2970 (w). 1802 (m), 1760 (s). 1707 (s), 1456 (m), 1373 (m), 1252 (s), 1126 (s), 1093 (s), 850 (m), 750 (m), 723 (s);XH NMR (400 MHz, CDCh) 84.79 (s, 2H), 2.09 (s, 3H), 1.64 (s, 6H);13C NMR (100 MHz, CDCh) 8 171.3, 170.6, 154.5, 94.4, 77.3, 75.1, 24.4 (2C), 20.9; HRMS: m / z (ESI) calcd for C9Hi3ChNO6+, [M + H]+, 335.9803, found 335.9800.

[0116] l-((((Benzyloxy)carbonyl)amino)oxy)-2-methyl-l-oxopropan-2-yl acetate (3k): compound 3k was prepared according to the general procedure and isolated as a colorless syrup (1.31 g, 74% yield). IR vmax(nea^ / cm’1: 2951 (w), 1737 (s), 1455 (m), 1368 (m), 1251 (s), 1170 (m). 1129 (s), 1018 (m). 697 (m); ’HNMR (400 MHz, CDCh) 88.45 (s, 1H), 7.53-7.30 (m, 5H). 5.19 (s, 2H), 2.03 (s, 3H), 1.60 (s, 6H);13C NMR (100 MHz, CDCh) 8 171.6, 170.3, 156.3, 134.9, 128.50 (2C), 128.47, 128.3 (2C), 77.2, 68.2, 24.3 (2C), 20.8; HRMS: m / z (ESI) calcd for Ci4Hi8NO6+, [M + H]+, 296.1129, found 296.1129.

[0117] 3-l-(((((9H-Fluoren-9-yl)methoxy)carbonyl)amino)oxy)-2-methyl-l-oxopropan-2-yl acetate (31): compound 31 was prepared according to the general procedure and isolated as a colorless syrup (1.70 g, 74% yield). IR vmax(neaQ / cm1: 3245 (w), 2970 (w), 1792 (m), 1737 (s), 1450 (m), 1369 (m), 1245 (s), 1158 (m), 1100 (s), 1020 (m), 758 (s), 738 (s); ‘H NMR (400 MHz, CDCh) 88.43 (d, J = 1.3 Hz, 1H), 7.76 (dd, J = 7.6, 1.0 Hz, 2H), 7.65-7.53 (m, 2H), 7.46-7.37 (m, 2H). 7.32 (td, J = 7.5, 1.2 Hz, 2H), 4.49 (d, J = 7.1 Hz, 2H), 4.27 (t, J = 7.2 Hz, 1H), 2.09 (s, 3H), 1.64 (s, 6H);13C NMR (100 MHz, CDCh) 8 171.7, 170.3, 156.2, 143.2 (2C), 141.2 (2C), 127.8 (2C), 127.1 (2C), 125.0 (2C), 120.0 (2C), 77.3. 68.4, 46.7, 24.4 (2C), 20.9; HRMS: m / z (ESI) calcd for C2IH22NO6+.[M + H]+, 384.1442, found 384.1437.c. Synthesis of the Iron Catalyst 1

[0118] The iron catalyst 1 was synthesized according to the following procedure.Scheme 20.Fe(BF4)2• 6H2O Fe(L1)(BF4)2(MeCN)(H2O)21

[0119] To a 250 mL oven-dried round-bottom flask under N2 atmosphere equipped with a magnetic stirring bar, Fe(BF4)2-6HiO (6.6 g, 1.1 equiv), freshly activated powered 5 A molecular sieves (16 g), and ligand LI (4.86 g, 1.0 equiv) were added. Anhydrous CH2CI2 (108 mL) and acetonitrile (36 mL) was added, and the reaction mixture was stirred for 3 hours. The molecular sieves were removed by centrifugation and the liquid layer was transferred to a 500 mL oven- dried round-bottom flask and then concentrated in vacuo. Anhydrous CH2CI2 (60 mL) was added to redissolve the orange foam and anhydrous Et2O (180 mL) was added drop wise to the solution to precipitate the iron catalyst. The ether layer was removed via a syringe and the catalyst was washed with additional anhydrous Et2O (120 mL) and further dried in vacuo to afford yellow to orange powder.

[0120] The structure of 1 was elucidated by X-ray crystallographic analysis, and is shown in FIG. 11.

[0121] The desired glycal cis-aminoglycosylation product 5 was purified through a silica gel flash column (hexanes / ethyl acetate: from 20:1 to 3:1) as a white solid (232 mg, 87% yield, m.p. 155-157 °C).

[0122] (2R,3R,4S,5R,6S)-2-((((4aR,6S,7R,8R,8aR)-7-((tert-Butoxycarbonyl)amino)-8-((tert- butyldimethylsilyl)oxy)-2,2-dimethylhexahydropyrano[3,2-d][l,3]dioxin-6-yl)oxy)methyl)-6-methoxytetrahydro-2H-pyran-3,4,5-triyl tribenzoate (5): [a]^2+94.8 (acetone, c = 1.0); IR Vmax (neatycm1: 2927 (w), 1723 (s), 1382 (m), 1250 (s), 1138 (s), 1070 (m), 1023 (m), 837 (m), 708 (m); 'H NMR (400 MHz, CDCI3) 87.98 (t, J = 7.7 Hz, 4H), 7.86 (d, J = 7.6 Hz, 2H), 7.51 (dd, J = 12.8, 7.1 Hz, 2H), 7.44-7.31 (m, 5H), 7.27 (t, J = 8.0 Hz, 2H), 6.14 (t, J = 9.9 Hz, 1H), 5.59 (t, J = 10.0 Hz, 1H), 5.24-5.23 (m, 2H), 5.14 (d, J = 10.1 Hz, 1H), 4.91 (d, J = 3.4 Hz, 1H), 4.24 (dd, J = 10.1, 4.5 Hz, 1H), 3.91-3.78 (m, 2H), 3.78-3.70 (m, 2H), 3.70-3.58 (m, 3H), 3.54-3.41 (m, 4H), 1.46 (s, 9H), 1.45 (s, 3H), 1.36 (s, 3H), 0.89 (s, 9H). 0.09 (s, 3H), 0.07 (s, 3H);13C NMR (100 MHz, CDCI3) 8 165.8, 165.6, 165.2, 155.4, 133.4, 133.3, 133.0, 129.9 (2C), 129.8 (2C),129.6 (2C), 129.2, 129.0, 128.8, 128.43 (2C), 128.35 (2C), 128.2 (2C), 99.2, 98.8, 97.0, 79.4, 74.8, 72.2, 71.0, 70.5, 69.1, 68.8, 64.8, 63.9, 62.4, 55.5 (two peaks overlapped, 2C), 29.0, 28.5 (3C), 25.8 (3C), 18.9, 18.3, -4.3, -5.1; HRMS: m / z (ESI) calcd for C48H64NOi5Si+. [M + H]+, 922.4040, found 922.4023. ’ I-HI = 173.6 Hz, 172.8 Hz.

[0123] The Cl stereochemistry was determined by measuring ^CI-HI through undecoupled HSQC experiments (FIG. 12).

[0124] The C2 stereochemistry was determined by NOE analysis. As shown in FIG. 13A and FIG. 13B, strong NOE was observed between H2 and H4, as well as between H3 and N-H; however, there was no NOE observed between Hl and H3. The structure of 5 was further corroborated by X-ray crystallographic analysis (FIG. 14).

[0125] N-Boc deprotection of 5 was earned out according to the following procedure. Scheme 21.2,6-lutidine (3 equiv)TMSOTf (2 equiv)CH2CI20 °C to rt, 0.2 M, 1.5 h 95% yield

[0126] To a 2-dram vial equipped with a stir bar were added 5 (100 mg, 0.108 mmol, 1.0 equiv) and anhydrous CH₂Cl₂ (0.54 mL). The mixture was cooled to 0 °C before 2,6-lutidine (38 pL, 0.325 mmol, 3.0 equiv), TMSOTf (39 pL, 0.217 mmol, 2.0 equiv) were added sequentially. The mixture was brought back to room temperature and was stirred for 1.5 h until the starting material was fully consumed (monitored by TLC). The mixture was then diluted with CH2CI2 (1 mL) and washed with saturated aq. NH4CI solution (1 mL). The organic phase was separated from the aqueous one, which was further extracted with CH2CI2 (1 mL x 3). The combined organic phase was dried over anhydrous Na2SO4 and concentrated in vacuo. The residue was purified through a silica gel flash column (hexanes / ethyl acetate: from 20:1 to 2:1) to afford the desired product SI as white foam (85 mg, 95% yield).

[0127] Methyl 2-amino-3-O-tert-butyldimethylsilyl-4,6-O-isopropylidene-2-deoxy-a-D-glucopyranosyl-(l— >6)-2,3,4-tri-O-benzoyl-a-D-glucopyranoside (SI): [a]^5+91.7 (acetone, c = 1.0); IRvmax (neatyem1: 2928 (w), 1727 (s), 1452 (w), 1371 (w), 1259 (m), 1173 (w), 1092 (s),1067 (s), 1025 (s), 856 (m), 707 (s); 'H NMR (400 MHz, CDCh) 88.01-7.93 (m, 4H), 7.90-7.81 (m, 2H), 7.57-7.47 (m, 2H), 7.45-7.34 (m, 5H), 7.33-7.25 (m, 2H), 6.14 (t, J = 9.9 Hz, 1H), 5.57 (t, J = 9.9 Hz, 1H), 5.32 (dd, J = 10.2. 3.6 Hz, 1H). 5.25 (d, J = 3.7 Hz. 1H), 4.96 (d, J = 3.5 Hz, 1H), 4.26 (ddd, J = 10.3, 6.1, 2.0 Hz, 1H), 3.85 (dd, J = 11.5, 6.1 Hz, 1H), 3.77-3.63 (m, 4H), 3.57 (t, J = 9.0 Hz, 1H), 3.48 (s, 3H), 3.40 (t, J = 8.8 Hz, 1H), 2.75 (dd, J = 9.4, 3.5 Hz. 1H), 2.04 (brs, 2H), 1.45 (s, 3H), 1.38 (s, 3H), 0.91 (s, 9H), 0.11 (s, 3H), 0.09 (s, 3H);13C NMR (100 MHz, CDCh) 8 165.8, 165.8, 165.3, 133.4, 133.3, 133.0, 129.9 (2C), 129.8 (2C), 129.7 (2C), 129.2, 129.1, 128.9, 128.43 (2C), 128.37 (2C), 128.2 (2C), 99.8, 99.2, 96.9, 77.21, 74.4, 72.2, 70.6, 69.3, 68.8. 65.7, 64.2, 62.4, 57.6, 55.5, 29.1, 26.0 (3C), 19.0, 18.3, -3.9, -4.8.; HRMS: m / z (ESI) calcd for C43H56NO13SE, [M + H]+, 822.3515, found 822.3508.

[0128] With respect to Scheme 3, the desired glycal cis-aminoglycosylation product 7 was purified through column chromatography (hexane s / ethyl acetate: from 20:1 to 4:1) as white foam (147 mg, 71% yield).

[0129] Methyl 2-tert-butoxycarbonylamino-3-O-tert-butyldimethylsilyl-4,6-O-isopropylidene-2-deoxy-a-D-glucopyranosyl-( 1— >3)-2-O-acetyl-4,6-O-isopropylidene-a-D-glucopyranoside (7): [a] □3+83.4 (acetone, c = 1.0); IR vmax (neat) / cm-1: 2930 (w), 1745 (m), 1719 (s), 1505 (m), 1367 (s), 1234 (m), 1270 (s), 1130 (s), 1043 (s), 875 (m), 778 (m);JH NMR (400 MHz. CDCh) 85.02-4.89 (m, 2H). 4.86-4.74 (m, 2H), 3.96 (t. J = 8.9 Hz, 1H). 3.87 (dd, J = 10.4, 4.6 Hz, 1H), 3.84-3.60 (m, 7H), 3.56-3.38 (m, 2H), 3.32 (s, 3H), 2.10 (s, 3H), 1.49 (s, 3H), 1.43-1.33 (m, 15H), 1.31 (s, 3H). 0.82 (s, 9H), 0.03 (s, 6H);13C NMR (100 MHz, CDCh) 8 170.5, 155.2, 100.3, 99.7, 99.3, 97.8, 79.4, 74.8, 74.31, 74.29, 72.1, 71.1, 64.4, 62.8, 62.4, 62.3, 55.8, 55.2, 29.14, 29.07, 28.5 (3C), 25.8 (3C), 20.9, 19.05, 18.96, 18.3, -4.3, -5.0; HRMS: m / z (ESI) calcd for C32H58NO13SE, [M + H]+, 692.3672. found 692.3675. ^’CI-HI = 174.0 Hz, 171.2 Hz.

[0130] Methyl 2-inethoxycarbonylamino-3-O-tert-butyldimethylsilyl-4,6-O-isopropylidene-2-deoxy-a-D-glucopyranosyl-( 1— >3)-2-O-acetyl-4,6-O-isopropylidene-a-D-glucopyranoside (7i): [a]p8+67.9 (acetone, c = 1.0); IR vmax (neat) / cm-1: 2993 (w), 2929 (w), 2856 (w), 1730 (m), 1714 (m), 1530 (w), 1463 (w), 1371 (m), 1234 (s), 1198 (m), 1170 (m), 1129 (m), 1082 (s), 1028 (s), 942 (m), 866 (s), 852 (s). 837 (s), 799 (s). 777 (m);JH NMR (400 MHz, CDCh) 85.30 (d, J = 10.2 Hz, 1H), 4.95 (d, J = 3.5 Hz, 1H), 4.86 (dd, J = 9.5, 3.8 Hz, 1H), 4.80 (d, J = 3.8 Hz, 1H), 3.97 (t, J = 9.0 Hz, 1H), 3.87 (dd, J = 10.3, 4.5 Hz, 1H), 3.81 (m, 2H), 3.76-3.43 (m, 10H), 3.35 (s. 3H), 2.12 (s. 3H). 1.49 (s, 3H), 1.44 (s, 3H), 1.40 (s, 3H), 1.35 (s. 3H). 0.84 (s, 9H). 0.03 (s,3H), 0.01 (s, 3H);13C NMR (100 MHz, CDCh) 5 170.4, 156.5, 100.6, 99.9, 99.3, 97.8, 75.6, 74.5, 74.1, 72.0, 71.4, 64.7, 62.9, 62.3, 62.3, 56.6, 55.2, 51.9, 29.0, 28.9, 25.6 (3C), 21.0, 19.00, 18.96, 18.2, -4.3, -5.2; HRMS: m / z (ESI) calcd for Ci^NOisSF, [M + H]+, 650.3202, found 650.3204.! J13C1-HI = 171.6 Hz, 171.8 Hz.

[0131] Methyl 2-(2,2,2-trichloroethoxycarbonylamino)-3-O-tert-butyldimethylsilyl-4,6-O-isopropylidene-2-deoxy-a-D-glucopyranosyl-( 1— ►3)-2-O-acetyl-4,6-O-isopropylidene-a-D-glucopyranoside (7j): [CC]Q7+102.8 (acetone, c = 1.0); IR vmax (neat) / cm-1: 2994 (w), 2929 (w), 2856 (w), 1737 (s), 1526 (w), 1371 (m), 1230 (s), 1200 (m), 1130 (m), 1031 (s), 943 (m), 866 (s), 852 (s), 837 (s), 779 (m), 720 (m); ‘H NMR (400 MHz, CDCh) 85.55 (d, J = 10.1 Hz, 1H), 5.02 (d, J = 3.4 Hz, 1H), 4.89 (dd, J = 9.6, 3.8 Hz, 1H), 4.81 (d, J = 3.8 Hz, 1H), 4.75 (d, J = 12.7 Hz, 1H), 4.62 (d, J = 12.0 Hz, 1 H), 4.01 (t, J = 9.2 Hz, 1 H), 3.93-3.81 (m, 3H), 3.81 -3.59 (m, 6H), 3.51 (t, J = 8.8 Hz, 1H), 3.37 (s, 3H), 2.13 (s, 3H), 1.51 (s, 3H), 1.46 (s, 3H), 1.44 (s, 3H), 1.36 (s, 3H), 0.85 (s, 9H), 0.05 (s, 3H), 0.04 (s, 3H);13C NMR (100 MHz, CDCh) 8 170.4. 154.4, 100.1, 99.9, 99.4, 97.9, 95.2, 75.2, 75.0, 74.6, 74.1, 72.1, 71.0, 64.7, 62.9, 62.3, 62.2, 57.1, 55.3, 29.2, 29.1, 25.7 (3C), 21.0, 19.2, 19.0, 18.2, -4.2, -5.0; HRMS: m / z (ESI) calcd for C30H5iCl3NOi3Si+, [M + H]+, 766.2190, found 766.2185. ^’CI-HI = 172.2 Hz, 171.1 Hz.

[0132] Methyl 2-benzyloxycarbonylamino-3-O-tert-butyldimethylsilyl-4,6-O-isopropylidene-2-deoxy-a-D-glucopyranosyl-( 1— >3)-2-O-acetyl-4,6-O-isopropylidene-a-D-glucopyranoside (7k): [CC]Q8+101.3 (acetone, c = 1.0); IRvmax(neat) / cm-1: 2993 (w), 2929 (w), 2856 (w). 1725 (s), 1524 (w), 1371 (m), 1231 (s), 1200 (m), 1129 (m), 1080 (s), 1024 (s), 1002 (m), 943 (m), 866 (s), 852 (s), 837 (s), 778 (m);1H NMR (400 MHz, CDCh) 87.33 (m, 5H), 5.32 (d, J = 10.2 Hz, 1H), 5.05 (s, 2H), 4.98 (d, J = 3.5 Hz, 1H), 4.84 (dd, J = 9.5, 3.8 Hz, 1H), 4.80 (d, J = 3.8 Hz, 1H), 3.97 (t, J = 9.0 Hz, 1H), 3.90-3.78 (m, 3H), 3.78-3.60 (m, 5H), 3.53 (m, 2H), 3.35 (s, 3H), 2.13 (s, 3H), 1.45 (s, 3H), 1.38 (s, 3H), 1.35 (s, 3H), 1.25 (s, 3H), 0.84 (s, 9H), 0.03 (s, 3H), -0.00 (s, 3H);13C NMR (100 MHz, CDCh) 8 170.5, 156.0, 136.3, 128.9 (2C), 128.6 (2C), 128.3, 100.6, 100.0, 99.5, 98.0, 75.5, 74.7, 74.3, 72.2, 71.5, 67.1. 64.8. 63.0. 62.5. 62.4, 56.7, 55.4, 29.2, 29.0, 25.8 (3C), 21.1, 19.2, 19.1, 18.4, -4.1, -5.0; 8 170.4, 155.9, 136.2, 128.7 (2C), 128.4 (2C), 128.2, 100.5, 99.8, 99.3, 97.8, 75.3, 74.6, 74.1, 72.0, 71.3, 66.9, 64.6, 62.9, 62.3, 62.3, 56.5, 55.2, 29.1, 28.9, 25.7 (3C), 21.0, 19.0, 18.9, 18.2, -4.3, -5.1. HRMS: m / z (ESI) calcd for C35H56NOi3Si+, [M + H]+, 726.3515, found 726.3514. ^’CI-HI = 172.8 Hz, 174.4 Hz

[0133] Methyl 2-(fluoren-9-ylmethoxycarbonylamino)-3-O-tert-butyldimethylsilyl-4,6-O-isopropylidene-2-deoxy-a-D-glucopyranosyl-( 1— >3)-2-O-acetyl-4,6-O-isopropylidene-a-D-glucopyranoside (71): [a] □8+58.6 (acetone, c = 0.33); IR vmax (neat) / cm-1: 2994 (w), 2928 (w), 2855 (w), 1736 (s), 1726 (s), 1636 (m), 1522 (w), 1450 (w), 1371 (m), 1231 (s), 1217 (s), 1200 (m), 1129 (m), 1080 (s), 1045 (s), 1027 (m), 1004 (m), 942 (m), 866 (s), 851 (s), 837 (s), 777 (m); ‘H NMR (400 MHz, C6D6, 338 K) 87.68-7.53 (m, 4H), 7.36-7.21 (m, 4H), 5.40 (d, J = 9.7 Hz, 1H), 5.11 (d, J = 3.4 Hz, 1H). 4.98 (dd, J = 9.6, 3.8 Hz. 1H), 4.78 (dd, J = 7.9, 3.7 Hz, 1H), 4.55 (d, J = 6.6 Hz, 2H), 4.29-4.04 (m, 3H), 4.00-3.68 (m, 5H), 3.67-3.40 (m, 4H), 3.04 (s, 3H), 1.98 (s, 3H), 1.42 (s, 6H), 1.31 (s, 6H), 1.07 (s, 9H), 0.24 (s, 3H), 0.23 (s, 3H);13C NMR (100 MHz, C6D6, 338 K) 6 170.3. 145.3 (2C), 145.0 (2C), 142.3. 128.3 (2C), 127.7 (2C), 125.8 (2C). 120.7 (2C), 101.3, 100.6, 100.0, 99.0, 76.3, 75.9, 75.1, 73.1, 72.4, 67.5, 65.6, 64.1, 63.1, 63.1, 58.2, 55.3, 48.5, 29.8, 29.7, 26.5 (3C), 21.0, 19.9, 19.6, 19.0, -3.5, -4.1; HRMS: m / z (ESI) calcd for C42H6oNOi3Si+, [M + H]+, 814.3828, found 814.3835. ^ci-m = 172.2 Hz, 171.2 Hz

[0134] 2-tert-Butoxycarbonylamino-3-O-tert-butyldimethylsilyl-4,6-O-isopropylidene-2-deoxy-a-D-glucopyranosyl 2,4-dichlorobenzoate (8a): IR vmax(neat) / cm: 2970 (w), 1737 (s), 1502 (m), 1367 (s), 1229 (m), 1131 (m), 1079 (m), 988 (m), 837 (m), 779 (m); ’H NMR (400 MHz, CDCh) 87.91 (d, J = 8.5 Hz, 1H), 7.53 (d. J = 2.0 Hz, 1H), 7.39 (dd, J = 8.5, 2.0 Hz, 1H). 6.34 (d, J = 3.7 Hz. 1H), 4.53 (d, J = 9.7 Hz, 1H), 4.08 (td, J = 9.4, 5.8 Hz, 1H). 3.89-3.81 (m, 1H), 3.80-3.66 (m, 3H), 3.63 (t, J - 8.9 Hz, 1H), 1.49 (s, 3H), 1.42 (s, 9H), 1.40 (s, 3H), 0.88 (s, 9H), 0.08 (s, 6H);13C NMR (100 MHz, CDCh) 8 163.5, 155.0, 139.3, 134.4, 133.6, 131.3, 127.7, 127.5. 99.6. 94.3, 80.1, 74.3, 71.3, 66.5, 62.1, 54.7, 28.9, 28.3 (3C), 25.7 (3C), 19.0, 18.3, -4.2, -5.0; HRMS: m / z (ESI) calcd for C27H42CI2NO8SE, [M + H]+, 606.2051, found 606.2047. ^CI-HI = 178.8 Hz

[0135] 2-tert-Butoxycarbonylamino-3-O-tert-butyldimethylsilyl-4,6-O-isopropylidene-2-deoxy-a-D-glucopyranosyl 2,2-diphenylpropanoate (8b): IR vmax(neat)Zcm1: 2970 (w), 1747 (s), 1503 (m), 1367 (s), 1229 (m), 1172 (m), 1076 (m), 989 (m), 836 (m), 779 (m); ’HNMR (400 MHz, CDCh) 87.41-7.25 (m, 10H), 6.10 (d, J = 3.7 Hz, 1H), 3.81 (td, J = 9.9, 3.8 Hz, 1H), 3.74 (dd, J = 10.7, 5.4 Hz, 1H), 3.64 (t, J = 10.5 Hz, 1H), 3.49 (d, J = 9.9 Hz, 1H), 3.43 (t, J = 9.4 Hz, 1H), 3.17 (dd, J = 10.1, 5.3 Hz, 1H), 3.10 (t, J = 9.4 Hz, 1H). 1.96 (s, 3H), 1.42 (s, 12H), 1.34 (s, 3H), 0.80 (s, 9H), -0.04 (s, 3H), -0.07 (s, 3H);13C NMR (100 MHz, CDCh) 8 172.9, 154.7, 144.0, 143.7, 128.5 (2C), 128.3 (2C), 128.2 (2C), 127.7 (2C), 127.3, 127.2, 99.3, 92.8, 79.6, 74.0, 71.0, 66.0, 62.0, 57.0, 54.6, 28.9. 28.4 (3C), 27.0. 25.7 (3C), 18.9. 18.1. -4.3. -5.1; HRMS: m / z (ESI) calcd for C35H52NO8SE, [M + H]+, 642.3457, found 642.3459. ^CI-HI - 177.9 Hz.

[0136] 2-tert-Butoxycarbonylamino-3-O-tert-butyldimethylsilyl-4,6-O-isopropylidene-2-deoxy-a-D-glucopyranosyl 2-acetoxyacetate (8c): IR vmax(neat) / cm-1: 2970 (w), 1739 (s), 1716(s), 1520 (m), 1365 (s), 1217 (m), 1128 (m), 1074 (m), 994 (m), 836 (m), 779 (m); ’H NMR (400 MHz, CDCh) 86.15 (d, J = 3.7 Hz, 1H), 4.69 (d, J = 16.1 Hz, 1H), 4.65 (d, J = 16.1 Hz, 1H), 4.48 (d, J = 9.7 Hz, 1H), 4.05-3.92 (m, 1H). 3.84 (dd, J = 10.4, 4.3 Hz, 1H), 3.74-3.65 (m, 1H). 3.63-3.50 (m, 3H), 2.17 (s, 3H), 1.46 (s, 3H), 1.42 (s, 9H), 1.39 (s, 3H), 0.86 (s, 9H), 0.07 (s, 3H), 0.06 (s, 3H);13C NMR (100 MHz, CDCh) 8 170.4, 166.2, 155.0, 99.5, 93.7, 80.0, 74.3, 71.0, 66.1, 62.0, 60.7, 54.6, 28.9, 28.3 (3C), 25.7 (3C), 20.4, 18.9, 18.2, -4.2, -5.1; HRMS: m / z (ESI) calcd for C24H44NO10SE, [M + H]+, 534.2729, found 534.2723. ^’CI-HI = 181.6 HZ.

[0137] 2-tert-Butoxycarbonylamino-3-O-tert-butyldimethylsilyl-4,6-O-isopropylidene-2-deoxy-a-D-glucopyranosyl 3-(benzoyloxy)-2-((benzoyloxy)methyl)-2-methylpropanate (8e):IR Vmax (neat) / cnr1: 2929 (w), 1718 (s), 1503 (m), 1367 (s), 1262 (s), 1108 (s), 995 (m), 837 (m), 780 (m); ‘H NMR (400 MHz, CDCh) 88.02-8.00 (m, 4H), 7.61-7.50 (m, 2H), 7.43 (td, J = 7.8, 2.6 Hz, 4H), 6.23 (d, J = 3.7 Hz, 1H), 4.75 (t, J = 12.4 Hz, 2H), 4.65-4.56 (m, 2H), 4.51 (d, J = 11.2 Hz, 1H), 4.00 (td, J = 9.7, 3.7 Hz, 1H), 3.68-3.55 (m, 5H), 1.50 (s, 3H), 1.44 (s. 3H), 1.36 (s, 3H). 1.30 (s, 9H), 0.86 (s, 9H), 0.07 (s, 6H);13C NMR (100 MHz, CDCh) 8 171.1, 166.0 (2C), 155.3, 133.42, 133.38, 129.71 (2C), 129.67 (2C), 129.4, 129.2, 128.6 (4C), 99.5, 93.4, 79.8, 74.4, 70.8, 66.3, 66.0, 65.6, 62.0, 54.9, 47.4, 28.9, 28.2 (3C), 25.7 (3C), 18.9, 18.4. 18.2. -4.2, -5.2; HRMS; m / z (ESI) calcd for C39H56NO12SF, [M + H]+, 758.3566, found 758.3574.1J13ci-m - 180.8 Hz.

[0138] 2-tert-Butoxycarbonylamino-3-O-tert-butyldimethylsilyl-4,6-O-isopropylidene-2-deoxy-a-D-glucopyranosyl 2-acetoxy-2-methylpropanoate (8f): IR vmax(neat) / cm h 2970 (w), 1737 (s), 1715 (s), 1514 (m), 1368 (s), 1229 (m), 1128 (m), 1079 (m), 994 (m), 836 (m), 780 (m);JH NMR (400 MHz. CDCh) 86.18 (d. J = 3.6 Hz, 1H), 4.83 (d, J = 10.0 Hz, 1H), 3.97 (td, I = 9.9.3.6 Hz, 1H), 3.85 (dd, J = 10.4, 4.5 Hz, 1H), 3.70 (t, J = 10.0 Hz, 1H), 3.65-3.41 (m, 3H), 2.09 (s, 3H), 1.61 (s, 3H), 1.56 (s, 3H), 1.47 (s, 3H), 1.42 (s, 9H), 1.39 (s, 3H), 0.86 (s, 9H), 0.06 (s, 6H);13C NMR (100 MHz, CDCh) 8 170.6, 170.5, 155.4, 99.5, 93.6, 79.4, 78.4, 74.3, 71.1, 66.4. 62.1. 54.9, 28.9, 28.3 (3C), 25.7 (3C), 25.2, 23.9, 21.1, 18.9, 18.2, -4.4, -5.1; HRMS: m / z (ESI) calcd for C26H48NOioSi+, [M + H]+, 562.3042. found 562.3039. ^’CI-HI = 181.1 HzC. General Procedures for the Iron-Catalyzed Glycal ds-Aminoglycosylation

[0139] General Procedure A. To a flame-dried sealable 2-dram vial (vial A) equipped with a stir bar were added a glycal (0.3 mmol, 1.0 equiv), a glycosyl acceptor (0.32 mmol, 1.2 equiv), iron catalyst 1 Fe(Ll)(BF4)2(MeCN)(H2O)2 (26.5 mg, 0.045 mmol, 15 mol %) and freshly activated 5 A molecular sieves, powder (ca. 150 mg). After the vial was evacuated and backfilled with N2three times, anhydrous CH2CI2 (0.5 mL) was added and the solution was cooled to -40 °C. To a second flame-dried sealable 2-dram vial (vial B) was added amination reagent 3 (0.45 mmol, 1.5 equiv). Vial B was evacuated and backfilled with N2 three times and then anhydrous CH2CI2 (0.5 mL) was added. Amination reagent 3 was added to vial A using a syringe pump within 10 min. The reaction was kept at -40 °C for an additional 2 h and quenched by precipitating the iron catalyst with Et2O (4 mL) at the same temperature. The mixture was stirred for two minutes and subsequently warmed up to room temperature. The solution was then filtered through a piece of cotton and washed with saturated aq. NaHCO3 solution (2 mL). The organic phase was separated from the aqueous one, which was further extracted with CH2CI2 (3 mL x 3). The combined organic phase was dried over anhydrous Na2SC>4 and concentrated in vacuo. The residue was purified through a silica gel flash column to afford the desired glycal cis-aminoglycosylation product.

[0140] General Procedure B. To a flame-dried sealable 2-dram vial (vial A) equipped with a stir bar were added a glycal (0.3 mmol, 1.0 equiv), amination reagent 3 (0.45 mmol, 1.5 equiv), and freshly activated 5 A powdered molecular sieves (ca. 150 mg). After the vial was evacuated and backfilled with N2 three times, anhydrous CH2O2 (0.5 mL) was added and the solution was cooled to -40 °C. To a second flame-dried sealable 2-dram vial (vial B) were added a glycosyl acceptor (0.36 mmol, 1.2 equiv), iron catalyst 1 Fe(Ll)(BF4)2(MeCN)(H2O)2 (26.5 mg, 0.045 mmol, 15 mol %) and freshly activated 5 A powdered molecular sieves (ca. 150 mg). Vial B was evacuated and backfilled with N2 three times and then anhydrous CH2CI2 (0.5 mL) was added and stirred for 5 min, then vial B solution was added to vial A drop wise in 2 min. The reaction was kept at -40 °C for an additional 2 h and quenched by precipitating the iron catalyst with Et2O (4 mL) at the same temperature. The mixture was stirred for two minutes and subsequently warmed up to room temperature. The solution was then filtered through a piece of cotton and washed with saturated aq. NaHCCL solution (2 mL). The organic layer was separated from the aqueous one, which was further extracted with CH2CI2 (3 mL x 3). The combined organic layers were dried over anhydrous NazSC and concentrated in vacuo. The residue was purified through a silica gel flash column to afford the desired glycal cis-aminoglycosylation product.

[0141] General Procedure C. To a flame-dried sealable 2-dram vial (vial A) equipped with a stir bar were added the preformed iron catalyst 1 Fe(Ll)(BF4)2(MeCN)(H2O)2 (26.5 mg, 0.045 mmol, 15 mol %) and freshly activated 5 A powdered molecular sieves (ca. 150 mg). After the vial was evacuated and backfilled with N2 three times, the vial was cooled to -40 °C. To a second flame-dried sealable 2-dram vial (vial B) was added a glycal (0.3 mmol, 1.0 equiv) and a glycosylacceptor (0.36 mmol, 1.2 equiv). Vial B was evacuated and backfilled with N2 three times and then anhydrous CH2CI2 (0.5 mL) was added and cooled to -78 °C, then vial B solution was quickly transferred into vial A via a syringe. To a third flame-dried sealable 2-dram vial (vial C) was added amination reagent 2 (0.45 mmol, 1.5 equiv). Vial C was evacuated and backfilled with N2 three times and then anhydrous CH2CI2 (0.5 mL) was added. 2 was added to vial A using a syringe pump within 10 min. The reaction was kept at -40 °C for an additional 2 h and quenched by precipitating the iron catalyst with Et2O (4 mL) at the same temperature. The mixture was stirred for two minutes and subsequently warmed up to room temperature. The solution was then filtered through a piece of cotton and washed with saturated aq. NaHCO₃ solution (2 mL). The organic layer was separated from the aqueous one, which was further extracted with CH₂Cl₂ (3 mL x 3). The combined organic layers were dried over anhydrous Na2SC>4 and concentrated in vacuo. The residue was purified through a silica gel flash column to afford the desired glycal cis-aminoglycosylation product.Scheme 22.Fe(L1)(BF4)2(MeCN)(H2O)2(1) (10 mol%) CH2CI2, 5 A MS -40 °C, c = 0.3 M, 1 h 87% yield4 3d 1 2 equiv 1.5 equiv

[0142] In Scheme 22, 2 was synthesized according to the procedure of M. H. D. Postema et al., Total Synthesis of Ipomoeassin F. Org. Lett. 11, 1417-1420 (2009), and 4 was synthesized according to the procedure of E. I. Balmond et al., a-Selective Organocatalytic Synthesis of 2-Deoxygalactosides. Angew. Chem. Int. Ed. 51, 9152-9155 (2012).

[0143] The glycal cis-aminoglycosylation was carried out on a 0.3 mmol scale by following the General Procedure A with the modifications: 1 (10 mol %) was used. The desired product 5 was purified through a silica gel flash column (hexanes / ethyl acetate: from 20:1 to 3:1) as a white solid (232 mg, 87% yield, m.p. 155-157 °C).

[0144] Methyl 2-tert-butoxycarbonylamino-3-O-tert-butyldimethylsilyl-4,6-O-isopropylidene-2-deoxy-a-D-glucopyranosyl-(l— >6)-2,3,4-tri-O-benzoyl-a-D-glucopyranoside (5): [a]p2+94.8 (acetone, c = 1.0); IR vmax (neat) / cm-1: 2927 (w), 1723 (s), 1382 (m), 1250 (s), 1138 (s), 1070 (m), 1023 (m), 837 (m), 708 (m);1H NMR (400 MHz, CDCh) 57.98 (t, J = 7.7 Hz, 4H),7.86 (d, J = 7.6 Hz, 2H), 7.51 (dd, J = 12.8, 7.1 Hz, 2H), 7.44-7.31 (m, 5H), 7.27 (t, J = 8.0 Hz, 2H), 6.14 (t, J = 9.9 Hz, 1H), 5.59 (t, J = 10.0 Hz, 1H), 5.24-5.23 (m, 2H), 5.14 (d. J = 10.1 Hz. 1H), 4.91 (d, J = 3.4 Hz, 1H), 4.24 (dd, J = 10.1, 4.5 Hz. 1H). 3.91-3.78 (m, 2H), 3.78-3.70 (m, 2H). 3.70-3.58 (m, 3H), 3.54-3.41 (m, 4H), 1.46 (s, 9H), 1.45 (s, 3H), 1.36 (s, 3H), 0.89 (s, 9H), 0.09 (s, 3H), 0.07 (s. 3H);13C NMR (100 MHz, CDC13) 8 165.8, 165.6, 165.2, 155.4, 133.4, 133.3, 133.0, 129.9 (2C), 129.8 (2C), 129.6 (2C), 129.2, 129.0, 128.8, 128.43 (2C), 128.35 (2C), 128.2 (2C), 99.2, 98.8, 97.0, 79.4, 74.8, 72.2, 71.0, 70.5, 69.1, 68.8, 64.8, 63.9, 62.4, 55.5 (two peaks overlapped, 2C), 29.0, 28.5 (3C), 25.8 (3C), 18.9, 18.3, -4.3, -5.1; HRMS: m / z (ESI) calcd for C₄₈H₆₄NO₁₅Si⁺, [M + H]+, 922.4040, found 922.4023.1J13CI-HI = 173.6 Hz, 172.8 Hz.Scheme 23.Me Fe(L1)(BF4)2(MeCN)(H2O)2(1) (15 mol%) CH2CI2, 5 A MS R: 2,4-CI2-benzoyl -40 °C, c = 0.3 M, 2 h 6 71% yield3g1.2 equiv 1.5 equivIn Scheme 23, 6 was synthesized according to a modified procedure of Allen, C. L. & Miller, S. J. Chiral Copper(II) Complex-Catalyzed Reactions of Partially Protected Carbohydrates. Org. Lett. 15, 6178-6181 (2013).To a 100 mL flame-dried round bottom flask equipped with a stir bar, compound S2 (2.34 g, 10 mmol, 1.0 equiv), Cu(OAc)2 (182 mg, 1.0 mmol, 0.1 equiv), 1,10-phenanthroline (180 mg, 1.0 mmol, 0.1 equiv), DIPEA (2.48 mL, 15.0 mmol, 1.5 equiv) and anhydrous CH2CI2 (50 mL) were added. The flask was cooled to 0 °C. AcCl (0.75 mL, 10.5 mmol, 1.05 equiv) was then added. Thereaction mixture was stirred for 6 h at 22 °C until the starting material S2 was fully consumed (monitored by TLC). The reaction mixture was quenched with sat. NaHCO₃ solution (15 mL). The organic phase was separated from the aqueous phase, and the aqueous phase was extracted with CH2CI2 (15 mL x 2). The combined organic phase was washed with brine (20 mL) and dried over Na₂SO₄ After concentration in vacuo, the residue was purified through column chromatography (hexanes / EtOAc: from 100:1 to 2:1) to afford the desired product 6 (2.16 g, 78% yield, m.p. 132— 134 °C) as a white solid.

[0145] Methyl 2-O-acetyl-4,6-O-isopropylidene-a-D-glucopyranoside (6): IRvmax (neat)Zcm’1: 2938 (w), 1741 (s), 1371 (s), 1267 (s), 1236 (m), 1031 (s), 1025 (s), 850 (m); ’H NMR (400 MHz, CDCh) 84.88 (d, J = 3.7 Hz, 1H), 4.72 (dd, J = 9.7, 3.8 Hz, 1H), 3.98 (td, J = 9.3, 3.2 Hz, 1H), 3.85 (dd, J = 10.5, 5.0 Hz, 1H). 3.73 (t, J = 10.3 Hz, 1H). 3.63 (td. J = 9.8, 5.0 Hz, 1H), 3.56 (t, J = 9.2 Hz, 1H), 3.34 (s, 3H), 2.77 (d, J = 3.2 Hz, 1H), 2.12 (s, 3H), 1.50 (s, 3H), 1.42 (s, 3H);13C NMR (100 MHz, CDCh) 8 170.6, 99.9, 97.5, 74.1, 73.7, 68.8, 62.8, 62.2, 55.2, 29.0, 20.9, 19.1; HRMS: m / z (ESI) calcd for C₁₂H₂₁O₇⁺, [M + H]+, 277.1282. found 277.1281.

[0146] The glycal cis-aminoglycosylation was carried out on a 0.3 mmol scale by following the General Procedure C. The desired product 7 was purified through column chromatography (hexanes / ethyl acetate: from 20:1 to 4:1) as white foam (147 mg, 71% yield).

[0147] Methyl 2-tert-butoxycarbonyIamino-3-O-tert-butyldimethylsilyl-4,6-O-isopropylidene-2-deoxy-a-D-glucopyranosyl-( 1— >3)-2-O-acetyl-4,6-O-isopropylidene-a-D-glucopyranoside (7): [a] D3+83.4 (acetone, c = 1.0); IRvmax (neat) / cm-1: 2930 (w), 1745 (m), 1719 (s), 1505 (m), 1367 (s), 1234 (m), 1270 (s), 1130 (s), 1043 (s), 875 (m), 778 (m);1H NMR (400 MHz, CDCh) 85.02-4.89 (m, 2H), 4.86-4.74 (m, 2H), 3.96 (t, J = 8.9 Hz, 1H), 3.87 (dd, J = 10.4, 4.6 Hz, 1H), 3.84-3.60 (m, 7H), 3.56-3.38 (m, 2H), 3.32 (s, 3H), 2.10 (s, 3H), 1.49 (s, 3H), 1.43-1.33 (m, 15H), 1.31 (s, 3H). 0.82 (s, 9H), 0.03 (s, 6H);13C NMR (100 MHz, CDCh) 8 170.5, 155.2, 100.3, 99.7, 99.3, 97.8, 79.4, 74.8, 74.31, 74.29, 72.1, 71.1, 64.4, 62.8, 62.4, 62.3, 55.8, 55.2, 29.14, 29.07, 28.5 (3C), 25.8 (3C), 20.9, 19.05, 18.96, 18.3, -4.3, -5.0; HRMS: m / z (ESI) calcd for C₃₂H₅₈NO₁₃Si⁺, [M + H]+, 692.3672. found 692.3675. 'j' i-Hi = 174.0 Hz, 171.2 Hz.Scheme 24.Me

[0148] S3 was synthesized according to Wang, M. et al. Non-Classical C-Saccharide Linkage of Dehydroalanine: Synthesis of C-Glycoamino Acids and C-Glycopeptides. Chem.Commun. 59, 3305-3308 (2023).

[0149] The glycal cis-aminoglycosylation was carried out on a 0.3 mmol scale by following the General Procedure A with the modifications: 1 (10 mol %) was used. The desired product 9 was purified through column chromatography (hexanes / ethyl acetate: from 20:1 to 3:1) as white foam (235 mg, 85% yield).

[0150] Methyl 2-tert-butoxycarbonylamino-3-O-tert-butyldimethylsilyl-4,6-O-isopropylidene-2-deoxy-a-D-glucopyranosyl-( 1 — >6)-2,3,4-tri-O-benzoyl-a-D-galactopyranoside (9): [a]o° +157.4 (acetone, c = 1.0); IRvmax (neat) / cm-1: 2925 (w), 1722 (m), 1381 (m), 1261 (m), 1137 (s), 1070 (m), 710 (m); ‘H NMR (400 MHz, CDCh) 58.10 (d, J = 7.5 Hz, 2H), 7.99 (d, J = 7.4 Hz, 2H), 7.78 (d, J = 7.4 Hz, 2H), 7.61 (t, J = 7.4 Hz, 1H), 7.49 (q, J = 7.3 Hz, 3H), 7.45-7.31 (m, 3H). 7.22 (t, J = 7.6 Hz, 2H), 6.00 (dd, J = 10.6, 3.3 Hz, 1H). 5.96 (brs, 1H), 5.67 (dd, J= 10.6, 3.5 Hz, 1H), 5.31 (d, J = 3.5 Hz, 1H), 4.86 (d, J = 10.1 Hz, 1H), 4.69 (d, J = 3.4 Hz, 1H), 4.42 (t, J = 6.4 Hz, 1H), 3.92-3.78 (m, 3H), 3.78-3.61 (m, 3H), 3.57 (dd, J=10.0 Hz, 6.2 Hz 1H), 3.54-3.48 (m. 4H), 1.47 (s, 3H), 1.40 (s, 12H). 0.87 (s, 9H), 0.072 (s, 3H), 0.067 (s, 3H);nC NMR (100 MHz, CDCh) 5 166.0, 165.5, 165.4, 155.3, 133.5, 133.3, 133.0, 129.9 (2 C), 129.8 (2 C), 129.6 (2 C), 129.1 (3 peaks overlapped, 3 C), 128.5 (2C), 128.3 (2C), 128.1 (2C), 99.3, 98.7, 97.6, 79.3, 74.9, 71.1, 69.5. 69.3. 68.2. 67.1. 65.0, 64.0, 62.4, 55.8, 55.3, 29.0, 28.3 (3C), 25.8 (3C), 18.9, 18.2, -4.3, -5.1; HRMS: m / z (ESI) calcd for C₄₈H₆₄NO₁₅Si⁺, [M + H]+, 922.4040, found 922.4029. ^’CI-HI = 175.2 Hz. 168.7 Hz.Scheme 25.S41 2 equiv

[0151] In Scheme 25, S4 was synthesized according to Wang, M. et al. Non-Classical C-Saccharide Linkage of Dehydroalanine: Synthesis of C-Glycoamino Acids and C-Glycopeptides. Chem. Commun. 59, 3305-3308 (2023).

[0152] The glycal cis-aminoglycosylation was carried out on a 0.3 mmol scale by following the General Procedure A with the modifications: 1 (10 mol %) was used. The desired product 10 was purified through column chromatography (hexanes / ethyl acetate: from 20: 1 to 3:1) as white foam (227 mg, 82% yield).

[0153] Methyl 2-tert-butoxycarbonylamino-3-O-tert-butyldimethylsilyl-4,6-O-isopropylidene-2-deoxy-a-D-glucopyranosyl-(l— >6)-2,3,4-tri-O-benzoyl-a-D-mannopyranoside (10): [a]^1-31.7 (acetone, c = 1.0); IR vmax (neat) / cm-1: 2930 (w), 1727 (m), 1451 (m), 1382 (m), 1278 (m), 1135 (s), 1070 (m), 837 (m),709 (m); ‘H NMR (400 MHz, CDCh) 58.08 (d, J = 7.4 Hz, 2H), 7.98 (d, J = 7.5 Hz, 2H), 7.81 (d, J = 7.5 Hz, 2H), 7.60 (t, J = 7.4 Hz, 1H), 7.54-7.47 (m, 3H), 7.45-7.34 (m, 3H). 7.24 (t, J = 7.9 Hz, 2H), 5.88 (dd, J = 10.0, 3.4 Hz, 1H), 5.76 (t, J = 10.1 Hz, 1H), 5.69 (dd, J = 3.2, 1.5 Hz, 1H), 4.99 (s, 1H), 4.84 (d, J = 3.3 Hz, 1H), 4.80 (d, J = 10.1 Hz, 1H), 4.28 (t, J = 8.2 Hz, 1H), 3.95-3.79 (m, 2H), 3.78-3.59 (m, 5H), 3.45 (s, 3H), 3.53-3.46 (m, 1H), 1.44 (s. 3H). 1.39 (s, 9H), 1.36 (s, 3H), 0.86 (s, 9H), 0.04 (s. 3H). 0.02 (s, 3H);13C NMR (100 MHz, CDCh) 8 165.49, 165.46, 165.3, 155.2, 133.5 (2 C), 133.1, 129.8 (2 C), 129.7 (2 C), 129.6 (2 C), 129.2, 129.0, 128.8, 128.6 (2 C), 128.4 (2 C), 128.2 (2 C), 99.2, 98.6, 98.4, 79.4, 74.7, 71.2, 70.4, 69.9, 69.2, 67.3, 66.0, 63.9, 62.3, 55.41, 55.35, 29.0, 28.4 (3C), 25.7 (3C), 18.9, 18.2, -4.3, -5.1; HRMS: m / z (ESI) calcd for C₄₈H₆₄NO₁₅Si⁺, [M + H]+, 922.4040, found 922.4033. ^CI-HI = 172.1 Hz, 172.1 Hz.Scheme 26.

[0154] In Scheme 26, S5 was synthesized according to Balmond, E. I., Coe, D. M., Galan, M. C. & McGarrigle, E. M. a-Selective Organocatalytic Synthesis of 2-Deoxygalactosides. Angew. Chem. Int. Ed. 51, 9152-9155 (2012).

[0155] The glycal cis-aminoglycosylation was carried out on a 0.3 mmol scale by following the General Procedure A with the modifications: 1 (10 mol %) was used. The desired product 11 was purified through column chromatography (hexanes / ethyl acetate: from 20:1 to 3:1) as a white solid (190 mg, 72% yield, m.p. 142-144 °C).

[0156] Methyl 2-tert-butoxycarbonylamino-3-O-tert-butyldimethylsilyl-4,6-O-isopropylidene-2-deoxy-a-D-glucopyranosyl-(l— >6)-2,3,4-tri-O-benzyl-a-D-glucopyranoside (11): [a] ° +107.0 (acetone, c = 1.0); IR vmax(neat)Zcm1: 2931 (w), 1719 (m), 1499 (m), 1382 (m).1141 (m), 1073 (m), 873 (m), 735 (m); ’H NMR (400 MHz, CDC13) 87.42-7.26 (m, 15H), 5.02 (d, J = 10.7 Hz, 1H), 4.93 (d, J= 11.1 Hz. 1H), 4.86-4.78 (m, 3H), 4.75-4.67 (m, 2H), 4.66 (d, J = 3.4 Hz, 1H), 4.62 (d, J = 11.1 Hz, 1H), 4.03 (t, J = 9.2 Hz, 1H), 3.81-3.77 (m, 3H), 3.74-3.69 (m, 3H), 3.64-3.60 (m, 2H), 3.58-3.46 (m, 2H), 3.41-3.39 (m, 4H), 1.46 (s, 3H), 1.42 (s, 9H), 1.40 (s, 3H), 0.88 (s, 9H), 0.05 (s. 6H);13C NMR (100 MHz, CDCI3) 8 155.0, 138.4, 137.9, 137.8, 128.4 (two peaks overlapped, 4 C), 128.3 (2 C), 128.0 (2 C), 127.9 (2 C), 127.84, 127.83, 127.8 (2 C), 127.6, 99.2, 98.7, 97.7, 82.0, 80.1, 79.3, 77.7, 75.8, 74.9, 74.7, 73.2, 71.3, 69.5, 66.1, 63.8, 62.3, 55.4, 55.0, 29.0, 28.4 (3 C), 25.7 (3 C). 18.9, 18.2, -4.3, -5.1: HRMS: m / z (ESI) calcd for C₄₈H₇₀NO₁₂Si⁺, [M + H]+, 880.4662, found 880.4675.1J13ci-m - 172.0 Hz, 168.5 Hz.Scheme 27.

[0157] In Scheme 27, 56 was synthesized according to Yoshida, K. et al. Amine-Free Silylation of Alcohols under 4-Methylpyridine N-Oxide-Catalyzed Conditions. Tetrahedron Lett.57, 627-631 (2016).

[0158] The glycal cis-aminoglycosylation was carried out on a 0.3 mmol scale by following the General Procedure A with the modifications: 3g (1.6 equiv) was used. The desired product 12 was purified through column chromatography (hexanes / ethyl acetate: from 20:1 to 5:1) as a white solid (170 mg, 74% yield, m.p. 153-155 °C).

[0159] Methyl 2-tert-butoxycarbonyIamino-3-O-tert-butyldimethylsilyl-4,6-O-isopropylidene-2-deoxy-a-D-glucopyranosyl-( 1— >2)-6-O-tert-butyldimethylsilyl-3,4-O-isopropylidene-a-D-galactopyranoside (12): [a]^1+101.4 (acetone, c = 1.0); IR Vmax (neat) / cm-1: 2931 (w), 1722 (m), 1505 (m), 1381 (m), 1250 (m), 1134 (s), 1073 (s), 836 (s), 777 (m); 'HNMR (400 MHz, CDCh) 54.93 (d. J = 9.9 Hz, 1H). 4.74 (d, J = 3.7 Hz. 1H), 4.67 (d, J = 3.4 Hz, 1H), 4.20 (dd, J - 5.27 Hz, 2.12 Hz, 1H), 4.14-4.18 (m, 1H), 3.96 (td, J - 6.3, 1.7 Hz, 1H), 3.89-3.82 (m, 2H), 3.81-3.73 (m, 3H), 3.73-3.65 (m, 2H), 3.65-3.60 (d, J = 9.0 Hz, 1H). 3.46 (t, J = 9.3 Hz, 1H), 3.40 (s, 3H), 1.45 (s, 3H), 1.44 (s, 3H), 1.40 (s, 9H), 1.37 (s, 3H), 1.32 (s, 3H), 0.88 (s, 9H), 0.84 (s, 9H), 0.06 (s, 6H), 0.03 (s, 3H), 0.02 (s, 3H);13C NMR (100 MHz, CDCh) 5 155.2, 109.2, 99.2, 97.2, 96.9, 79.1, 74.7, 74.5, 74.2, 73.1. 71.4, 68.1, 63.5, 62.4, 62.3, 55.5, 55.4, 28.9, 28.5 (3C), 28.2, 26.4, 25.8 (3C), 25.7 (3C), 18.9, 18.2 (two peaks overlapped, 2C), -4.2, -5.1, -5.4, -5.5; HRMS: m / z (ESI) calcd for C₃₆H₇₀NO₁₂Si₂⁺, [M + H]+, 764.4431, found 764.4476.1J13CI-HI = 168.9 Hz. 169.0 Hz.Scheme 28.

[0160] In Scheme 28, S6 was synthesized according to Lu, D.-F., Zhu, C.-L., Jia, Z.-X. & Xu, H. Iron(II)-Catalyzed Intermolecular Amino-Oxygenation of Olefins through the N-0 Bond Cleavage of Functionalized Hydroxylamines. J. Am. Chem. Soc. 136, 13186-13189 (2014). S7 was synthesized according to Ellis, D., Norman, S. E. & Osborn, H. M. I. Synthesis of S-Linked Carbohydrate Analogues via a Ferrier Reaction. Tetrahedron 64, 2832-2854 (2008).

[0161] The glycal cis-aminoglycosylation was earned out on a 0.3 mmol scale by following the General Procedure A with the modifications: 3h (2.0 equiv) was used. The desired product 13 was purified through column chromatography (hexanes / ethyl acetate: from 20:1 to 2:1) as white foam (149 mg, 67% yield).

[0162] Methyl 2-tert-butoxycarbonylamino-3-O-trimethylsilyl-4,6-O-isopropylidene-2-deoxy-a-D-glucopyranosyl-( l^-4)-2,3-di-0-acetyl-6-0-benzyl-a-D-glucopyranoside (13): [CC]Q2+74.8 (acetone, c = 0.69); IRvmax (neat) / cm-1: 2931 (w), 1751 (s), 1718 (s), 1500 (m), 1367 (m), 1237 (s), 1214 (s), 1163 (s), 1077 (s), 1050 (s), 1026 (s), 985 (s), 881 (s), 841 (s), 735 (m); 'll NMR (400 MHz, CDCh) 87.38-7.26 (m. 5H). 5.52 (t, J = 9.6 Hz, 1H), 5.02 (d. J = 3.8 Hz, 1H). 4.87 (d, J - 3.6 Hz, 1H), 4.79 (dd, J = 10.2, 3.6 Hz, 1H), 4.62 (d, J - 12.0 Hz, 1H), 4.57 (d, J - 12.0 Hz, 1H), 4.47 (d, J = 10.4 Hz, 1H), 3.97 (t, J = 9.2 Hz, 1H), 3.85-3.76 (m, 3H), 3.75-3.68 (m, 2H), 3.68-3.54 (m, 2H), 3.54-3.45 (m, 2H), 3.40 (s, 3H), 2.04 (s, 3H), 2.03 (s, 3H), 1.46 (s, 9H), 1.43 (s, 3H), 1.37 (s, 3H), 0.09 (s, 9H);13C NMR (100 MHz, CDCh) 8 170.3, 169.7, 155.6, 137.9, 128.4 (2C), 127.62, 127.57 (2C), 100.4, 99.4, 96.6, 79.7, 74.5, 74.4, 73.6. 72.4, 71.4, 71.3, 69.8, 68.7, 65.0, 62.2, 55.6, 55.3, 29.0, 28.4 (3C), 21.0, 20.8, 19.0, 0.4 (3C); HRMS: m / z (ESI) calcd for C₃₅H₅₆NO₁₄Si⁺, [M + H]+, 742.3465, found 742.3445. ^’CI-HI = 173.6 Hz, 170.2 Hz.Scheme 29.

[0163] In Scheme 29, S8 was synthesized according to a modified procedure of Blackbume, L. Fredericks, P. & Guthrie, R. Studies on Unsaturated Sugars with Particular Reference to the Synthesis of 6-Deoxy-6-Fluoro Derivatives. Aust. J. Chem. 29, 381-391 (1976).

[0164] The glycal cis-aminoglycosylation was carried out on a 0.3 mmol scale by following the General Procedure A with the modifications: 1 (10 mol %) was used. The desired product 14 was purified through column chromatography (hexanes / ethyl acetate: from 20:1 to 3:1) as white foam (205 mg, 76% yield).

[0165] Methyl 3-O-benzyl-2-tert-butoxycarbonylamino-4,6-O-isopropylidene-2-deoxy-«-D-glucopyranosyl-(l— >6)-2,3,4-tri-O-benzoyl-a-D-glucopyranoside (14): [a]p3+114.6 (acetone, c = 1.0); IR vmax (neat) / cm-1: 2927 (w), 1724 (s), 1504 (m), 1314 (m), 1250 (s), 1067 (m), 1024 (m), 994 (s), 941 (m), 707 (s); 'H NMR (400 MHz, CDCh) 88.01-7.93 (m, 4H), 7.89-7.82 (m, 2H), 7.52-7.45 (m, 2H), 7.42-7.22 (m, 12H), 6.13 (t, J = 9.5 Hz, 1H), 5.56 (t, J = 9.9 Hz, 1H), 5.28-5.18 (m, 2H), 4.95 (d, J = 10.0 Hz, 1H), 4.88 (d, J = 3.7 Hz, 1H), 4.84 (d, J = 12.1 Hz, 1H), 4.61 (d, J = 12.1 Hz, 1H), 4.20 (ddd, J = 10.3, 5.6, 2.1 Hz, 1H), 3.95 (td, J = 10.1, 3.6 Hz, 1H), 3.82 (dd, J = 11.8, 5.6 Hz, 1H), 3.78-3.62 (m, 5H), 3.54-3.44 (t, J = 9.4 Hz, 1H), 3.41 (s. 3H), 1.50-1.47 (s. 12H), 1.41 (s, 3H);13C NMR (100 MHz, CDCh) 5 165.7, 165.6, 165.2, 155.6, 138.9, 133.4, 133.3, 133.0, 129.9 (2C), 129.8 (2C), 129.6 (2C), 129.1, 129.0, 128.8, 128.4 (2C), 128.3 (2C), 128.2 (2C), 128.0 (2C), 127.6 (2C), 127.2. 99.2, 98.8, 96.9, 79.5, 76.8, 75.2, 73.8, 72.1, 70.4, 69.2. 68.5. 65.6. 63.8. 62.4, 55.6, 53.9, 29.2, 28.4 (3C), 19.1; HRMS: m / z (ESI) calcd for C₄₉H₅₆NO₁₅⁺, [M + H]+, 898.3644, found 898.3647. ^’CI-HI = 176.4 Hz, 176.4 Hz.Scheme 30.

[0166] In Scheme 30, S8 and 56 were obtained as described above. The glycal cisaminoglycosylation was carried out on a 0.3 mmol scale by following the General Procedure A with the modifications: 3g (1.8 equiv) was used. The desired product 15 was purified through column chromatography (hexanes / ethyl acetate: from 20:1 to 5:1) as white foam (155 mg, 70% yield).

[0167] Methyl 3-O-benzyl-2-tert-butoxycarbonylamino-4,6-O-isopropylidene-2-deoxy-a-D-glucopyranosyl-( 1— >2)-6-O-tert-butyldimethylsilyl-3,4-O-isopropylidene-a-D-galactopyranoside (15): [a]p2+96.5 (acetone, c = 1.0); IRvmax(neat) / cm-1: 2927 (w), 1721 (m), 1505 (m). 1455 (m), 1362 (s), 1247 (s), 1150 (s), 1073 (s), 839 (s), 778 (m);NMR (400 MHz. CDCh) 87.35-7.20 (m, 5H), 5.02 (d, J = 9.8 Hz, 1H), 4.86 (d, J = 12.1 Hz, 1H), 4.80 (d, J = 3.8 Hz, 1H), 4.69 (d, J = 3.5 Hz, 1H), 4.63 (d, J = 12.1 Hz, 1H), 4.21 (dd, J = 5.1, 2.3 Hz, 1H), 4.17 (dd, J = 7.7, 5.4 Hz. 1H), 4.02-3.89 (m, 3H), 3.88-3.78 (m, 3H), 3.78-3.67 (m. 3H), 3.57 (dd. J = 10.0, 9.0 Hz, 1H), 3.41 (s, 3H), 1.49 (s, 3H), 1.47 (s, 3H), 1.45 (s, 9H), 1.43 (s, 3H), 1.34 (s, 3H), 0.90 (s, 9H), 0.08 (s, 6H);13C NMR (100 MHz, CDCh) 8 155.5, 139.1, 128.1 (2C), 127.3 (2C), 127.1, 109.2. 99.3, 97.2, 96.9, 79.3, 77.7, 75.2, 74.7, 74.2. 74.0. 73.1. 68.2. 63.7, 62.5, 62.3, 55.5, 53.9, 29.2, 28.4 (3C), 28.2, 26.4, 25.8 (3C), 19.2, 18.2, -5.4, -5.5; HRMS: m / z (ESI) calcd for C₃₇H₆₂NO₁₂Si⁺, [M + H]+, 740.4036. found 740.4063. ^’CI-HI = 175.4 Hz. 169.1 Hz.Scheme 31.

[0168] In Scheme 31, S9 was synthesized according to Aurrecoechea, J. M., Gil, J. H. & L pez, B. Substituent Effects on the Sml2 / Pd(0)-Promoted Carbohydrate Ring-Contraction of 5-Alkynylpyranosides. Tetrahedron 59, 7111-7121 (2003).

[0169] The glycal cis-aminoglycosylation was carried out on a 0.3 mmol scale by following the General Procedure A with the modifications: 1 (10 mol %) was used. The desired product 16 was purified through column chromatography (hexanes / ethyl acetate: from 20:1 to 3:1) as white foam (233 mg, 73% yield).

[0170] Methyl 3,4-di-O-benzyl-2-tert-butoxycarbonylamino-6-O-tert-butyldimethylsilyl-2-deoxy-a-D-gIucopyranosyl-(l— >6)-2,3,4-tri-O-benzoyl-a-D-glucopyranoside (16): [a]^,3+98.9 (acetone, c = 1.0); IR vmax(neat) / cm-1: 2929 (w), 1725 (m), 1382 (m), 1251 (m), 1141 (s), 1025 (m), 708 (m); ’H NMR (400 MHz, CDC13) 58.00 (dd, J = 6.9, 1.3 Hz, 2H), 7.96 (d, J = 6.9, 1.3 Hz, 2H), 7.88 (dd, J = 7.3, 1.0 Hz, 2H), 7.56-7.46 (m, 2H), 7.41 (m, 3H), 7.38-7.23 (m, 14H), 6.15 (t. J = 9.8 Hz, 1H), 5.60 (t, J = 9.9 Hz, 1H), 5.35-5.18 (m, 2H), 4.95 (d, J = 10.1 Hz, 1H), 4.89-4.77 (m, 3H), 4.68 (t, J = 11.0 Hz, 2H), 4.22 (ddd, J = 10.2, 5.5, 2.4 Hz, 1H), 3.94 (dt, J = 9.4, 3.7 Hz, 1H), 3.84 (dd, J = 11.7, 5.4 Hz, 1H), 3.76 (dd, J = 11.5, 3.6 Hz, 1H), 3.71-3.61 (m, 4H), 3.59-3.54 (m, 1H), 3.45 (s, 3H), 1.49 (s, 9H), 0.87 (s, 9H), 0.00 (s, 3H), -0.01 (s, 3H);13C NMR (100 MHz, CDCI3) 5 165.8, 165.7, 165.2, 155.5, 138.61, 138.55, 133.4, 133.3, 133.0, 129.9 (two peaks overlapped, 4C), 129.6 (2C), 129.2, 129.0, 128.9, 128.39 (2C), 128.36 (2C), 128.3 (2C), 128.2 (two peaks overlapped, 4C), 128.1 (2C), 127.8 (2C), 127.54, 127.48, 98.2, 96.9, 80.5, 79.5, 78.1, 75.1, 74.7, 72.2, 72.1, 70.5, 69.3, 68.4, 65.2, 61.7, 55.6, 54.3, 28.4 (3C), 25.8 (3C), 18.2, -5.2, -5.5; HRMS: m / z (ESI) calcd for C59H72NO15SP, [M + H]+, 1062.4666,found 1062.4680. ^ I-HI - 172.0 Hz, 172.4 Hz.Scheme 32.Fe(L1)(BF4)2(MeCN)(H2O)2TBSO'A (1) (10 mol%)BnO~-K -s> CH2CI2, 5 A MS-40 °C, c = 0.3 M, 2 h72% yieldS9 S3 3b1 2 equiv 1.5 equiv

[0171] The glycal cis-aminoglycosylation was carried out on a 0.3 mmol scale by following the General Procedure A with the modifications: 1 (10 mol %) was used. The desired product 17 was purified through column chromatography (hexanes / ethyl acetate: from 20:1 to 3:1) as white foam (229 mg, 72% yield).

[0172] Methyl 3,4-di-O-benzyl-2-tert-butoxycarbonylamino-6-O-tert-butyldimethylsilyl-2-deoxy-a-D-gIucopyranosyl-(l— >6)-2,3,4-tri-O-benzoyl-a-D-galactopyranoside (17): [a]^3+128.0 (acetone, c = 1.0); IRvmax (neat) / cm-1: 2927 (w), 1721 (m), 1505 (m), 1391 (m), 1261 (m), 1141 (m), 1068 (m), 834 (m), 708 (m); 'H NMR (400 MHz, CDC13) 58.14 (d, J = 7.8 Hz, 2H), 7.89 (d, J = 7.8 Hz, 2H), 7.78 (d, J = 7.8 Hz, 2H), 7.65-7.55 (m, 1H), 7.53-7.45 (m, 3H). 7.43-7.25 (m, 12H), 7.25-7.17 (m, 3H). 6.06-5.94 (m, 2H), 5.66 (dd, J = 9.9, 3.7 Hz, 1H), 5.28 (d, J = 3.6 Hz, 1H), 5.04 (d, J = 10.1 Hz, 1H), 4.92-4.69 (m, 3H), 4.69-4.54 (m, 2H), 4.37 (t, J = 6.7 Hz, 1H), 4.02-3.76 (m, 4H), 3.73-3.60 (m, 3H), 3.56-3.40 (m, 4H), 1.44 (s. 9H), 0.88 (s. 9H). 0.04 (s, 6H):13C NMR (100 MHz, CDCh) 5 166.0, 165.7, 165.3. 155.6, 138.4, 138.3, 133.5, 133.3, 133.0, 129.9 (2C), 129.8 (2C), 129.6 (2C), 129.2, 129.12, 129.11, 128.5 (2C), 128.3 (two peaks overlapped, 4C), 128.15 (2C), 128.13 (2C), 128.0 (2C), 127.8 (2C). 127.6, 127.4, 98.0, 97.6, 80.8, 79.3, 78.0, 75.3, 74.9, 72.5, 69.5, 69.2, 68.0, 66.8, 64.2, 62.0, 55.8, 54.2, 28.3 (3C), 25.8 (3C), 18.2, -5.2, -5.4; HRMS: m / z (ESI) calcd for C59H72NO15SE, [M + H]+, 1062.4666, found 1062.4689. ^ I-HI = 176.0 Hz, 174.4 Hz.Scheme 33.Fe(L1)(BF4)2(MeCN)(H2O)2(1) (10 mol%) CH2CI2, 5 A MS-40 °C, c = 0.3 M, 2 h70% yieldS4 3b1.2 equiv 1.5 equiv

[0173] The glycal cis-aminoglycosylation was carried out on a 0.3 mmol scale by following the General Procedure A with the modifications: 1 (10 mol %) was used. The desired product 18 was purified through column chromatography (hexanes / ethyl acetate: from 20:1 to 3:1) as white foam (223 mg, 70% yield).

[0174] Methyl 3,4-di-O-benzyl-2-tert-butoxycarbonylamino-6-O-tert-butyldimethylsilyl-2-deoxy-a-D-glucopyranosyl-(l— >6)-2,3,4-tri-O-benzoyl-a-D-mannopyranoside (18): [a]o3-10.1 (acetone, c = 1.0); IR vmax (neat) / cm b 2927 (w). 1727 (m), 1451 (m), 1391 (m), 1277 (m), 1138 (s), 1069 (m), 834 (m), 710 (m); ’H NMR (400 MHz, CDCh) 8 8.09 (d, J = 7.6 Hz, 2H), 7.99 (d, J = 7.7 Hz, 2H), 7.83 (d, J = 7.8 Hz, 2H), 7.51-7.41 (m, 5H), 7.39-7.13 (m, 14H), 6.01-5.80 (m, 2H), 5.68 (s, 1H), 4.98 (s, 1H), 4.91 (d, J = 10.0 Hz, 1H), 4.87-4.75 (m, 2H), 4.70 (d, J= 11.1 Hz, 1H), 4.67 (d, J - 11.1 Hz, 1H), 4.55 (d, J = 11.2 Hz, 1H), 4.26 (brs, 1H), 4.00-3.89 (m. 2H), 3.78 (d, J = 11.4 Hz, 1H), 3.73-3.60 (m. 5H), 3.51 (s, 3H). 1.42 (s, 9H), 0.85 (s, 9H), -0.03 (s, 6H);13C NMR (100 MHz, CDCh) 8 165.5, 165.44, 165.39, 155.4, 138.59, 138.55, 133.5, 133.4, 133.1, 129.8 (2C), 129.74 (2C), 129.68 (2C), 129.3, 129.1, 128.9, 128.7 (2C), 128.4 (2C). 128.3 (2C), 128.22 (2C). 128.16 (2C), 127.9 (2C). 127.8 (2C), 127.6, 127.4, 98.5, 98.2, 81.1, 79.4, 78.0, 75.0, 74.7, 72.4, 70.5, 70.0, 69.1, 67.4, 66.3, 61.8, 55.5, 54.3, 28.4 (3C), 25.8 (3C), 18.2, -5.2, -5.5; HRMS: m / z (ESI) calcd for Cs^NOisSE, [M + H]+, 1062.4666, found 1062.4679. ^’CI-HI = 175.7 Hz, 169.8 Hz.Scheme 34.TBSO-A BnO^rA-OBnO—S9 56 3g1.2 equiv 1.5 equiv

[0175] The glycal cis-aminoglycosylation was earned out on a 0.3 mmol scale by following the General Procedure A. The desired product 19 was purified through column chromatography (hexanes / ethyl acetate: from 20:1 to 5:1) as white foam (190 mg, 68% yield).

[0176] Methyl 3,4-di-O-benzyl-2-tert-butoxycarbonylamino-6-O-tert-butyldimethylsilyl-2-deoxy-a-D-gIucopyranosyl-(l—>2)-6-O-tert-butyldimethylsilyl-3,4-O-isopropylidene-a-D- galactopyranoside (19): [a]p3+82.7 (acetone, c = 1.0); IRvmax (neat) / cm-1: 2929 (w), 1723 (s), 1505 (m), 1364 (m), 1249 (m), 1071 (m), 1040 (m), 835 (s), 777 (m); ’H NMR (400 MHz, CDCh) 87.41-7.25 (m, 10H), 5.09 (d, J = 9.7 Hz, 1H), 4.87-4.68 (m, 6H), 4.19 (dd. J = 5.5, 2.3 Hz. 1H). 4.16-4.10 (m, 1H), 4.02-3.94 (m, 2H), 3.94-3.66 (m. 8H). 3.42 (s, 3H). 1.46 (s, 3H), 1.45 (s, 9H), 1.30 (s, 3H), 0.90 (s, 9H), 0.89 (s, 9H), 0.09 (s, 6H), 0.03 (s, 6H);13C NMR (100 MHz, CDCh) 8 155.5, 138.7 (two peaks overlapped, 2C), 128.4 (2C), 128.2 (2C), 127.91 (2C), 127.87 (2C), 127.6, 127.4, 109.1, 97.0, 96.9, 81.4, 79.2, 77.7, 77.2, 75.4, 74.9, 74.3, 73.0, 71.9, 68.3, 62.3, 61.5, 55.5, 54.4, 28.5 (3C), 28.1, 26.3, 25.9 (3C), 25.8 (3C), 18.29, 18.25, -5.0, -5.3, -5.5 (2C); HRMS: m / z (ESI) calcd for C47H78NOi2Si2+, [M + H]+, 904.5057, found 904.5024. h^ci-m = 168.8 Hz, 166.5 Hz.Scheme 35.S10 41.4 equiv 1.8 equiv

[0177] In Scheme 35, S10 was synthesized according to Pal, K. B., Lee, J., Das, M. & Liu, X.-W. Palladium(II)-Catalyzed Stereoselective Synthesis of C-Glycosides from Glycals with Diaryliodonium Salts. Org. Biomol. Chem. 18, 2242-2251 (2020).

[0178] The glycal cis-aminoglycosylation was carried out on a 0.3 mmol scale by following the General Procedure B with the modifications: 1 (10 mol %), 4 (1.4 equiv), and 3d (1.8 equiv) were used. The desired product 20 was purified through column chromatography (hexanes / ethyl acetate: from 20:1 to 3:1) as white foam (214 mg, 74% yield).

[0179] Methyl 4,6-di-O-acetyl-2-tert-butoxycarbonyIamino-3-O-tert-butyldimethylsilyl-2-deoxy-a-D-glucopyranosyI-(l— >6)-2,3,4-tri-O-benzoyl-a-D-glucopyranoside (20): [a]^1+96.0 (acetone, c = 1.0); IRv™ (neat) / cm-1: 2935 (w), 1740 (m), 1513 (m), 1379 (m), 1140 (m), 1035 (m), 831 (m);NMR (400 MHz, CDCh) 58.03-7.90 (m, 4H), 7.85 (d, J = 7.5 Hz, 2H), 7.55-7.45 (m, 2H), 7.45-7.33 (m, 5H), 7.26 (t, 7.7 Hz, 2H), 6.21-6.08 (m, 1H), 5.64 (t, J = 10.0 Hz, 1H), 5.35-5.18 (m, 2H), 5.12 (d, J = 10.0 Hz, 1H), 5.03-4.81 (m, 2H), 4.26 (ddd, J = 10.3, 5.2, 1.7 Hz, 1H), 4.00 (dd, J = 4.9, 12.3 Hz, 1H), 3.97-3.86 (m, 2H), 3.88-3.68 (m, 4H), 3.46 (s, 3H), 2.05 (s, 3H). 2.02 (s, 3H). 1.47 (s, 9H), 0.86 (s, 9H), 0.16 (s. 3H). 0.06 (s, 3H);13C NMR (100 MHz, CDCh) 8 170.6, 169.3, 165.7, 165.6, 165.0, 155.1, 133.5, 133.3, 133.0, 129.8 (2C), 129.7 (2C), 129.5 (2C), 129.0, 128.9, 128.7, 128.4 (2C), 128.3 (2C), 128.1 (2C), 98.1, 96.9, 79.6, 72.1, 71.4. 70.5. 70.4. 68.8. 68.7, 68.3, 64.7, 62.3, 55.4, 55.1, 28.4 (3C), 25.6 (3C), 21.1, 20.6, 17.8, -4.4, -4.6; HRMS: m / z (ESI) calcd for C49H64NO17SP, [M + H]+, 966.3938, found 966.3931. ^’CI-HI = 176.0 Hz. 172.8 Hz.Scheme 36.Fe(L1)(BF4)2(MeCN)(H2O)2AcO-A (1) (15 mol%) Ac0^r~+-0 TBSO-A^-S- CH2CI2, 5 A MS -40 °C, c = 0.3 M, 3 h 72% yieldS10 56 3d 1.4 equiv 2.0 equivThe glycal cis-aminoglycosylation was carried out on a 0.3 mmol scale by following the General Procedure B with the modifications: 56 (1.4 equiv) and 3d (2.0 equiv) were used. The desired product 21 was purified through column chromatography (hexanes / ethyl acetate: from 20:1 to 5:1) as white foam (175 mg, 72% yield).

[0180] Methyl 4,6-di-O-acetyl-2-tert-butoxycarbonylamino-3-O-tert-butyldimethylsilyl-2-deoxy-a-D-glucopyranosyl-(l— >2)-6-O-tert-butyldimethylsilyl-3,4-O-isopropylidene-a-D-galactopyranoside (21): [a]p3+78.8 (acetone, c = 1.0); IRvmaX(neat) / cm-1: 2930 (w), 1742 (s), 1723 (s), 1505 (m), 1366 (s), 1235 (s), 1219 (s), 1035 (s), 836 (s), 776 (s); 'H NMR (400 MHz, CDCh) 55.02 (dd. J = 10.2. 8.5 Hz, 1H), 4.86-4.77 (m. 2H), 4.70 (d, J = 3.5 Hz, 1H), 4.28-4.16 (m, 3H), 4.13-4.07 (m, 1H), 4.00-3.90 (m, 2H), 3.89-3.76 (m, 4H), 3.74 (dd, J = 7.3, 3.3 Hz, 1H), 3.42 (s, 3H), 2.07 (s, 3H), 2.04 (s, 3H), 1.47 (s, 3H), 1.42 (s, 9H), 1.33 (s, 3H), 0.90 (s, 9H), 0.83 (s, 9H), 0.08 (s, 6H), 0.05 (s, 3H), -0.00 (s, 3H);13C NMR (100 MHz, CDCh) 8 171.0, 169.3, 155.0, 109.3, 96.7, 96.5, 79.6, 79.4, 74.6, 74.4, 73.1, 71.1, 68.1, 67.9, 62.2, 62.0, 55.5, 54.9, 28.5 (3C), 28.3, 26.3, 25.8 (3C), 25.6 (3C), 21.2, 20.8, 18.2, 17.8, -4.3, -4.5, -5.3, -5.5; HRMS: m / z (ESI) calcd for C37H7oNOi4Si2+, [M + H]+, 808.4329, found 808.4283. ^ I-HI = 168.6 Hz, 170.2 Hz.Scheme 37.

[0181] The glycal cis-aminoglycosylation was carried out on a 0.3 mmol scale by following the General Procedure A with the modifications: 6 (1.4 equiv) and 3d (2.0 equiv) were used. The desired product 22 was purified through column chromatography (hexanes / ethyl acetate: from 20:1 to 3:1) as white foam (159 mg, 72% yield).

[0182] Methyl 4,6-di-O-acetyl-2-tert-butoxycarbonylamino-3-O-tert-butyldimethylsilyl-2-deoxy-a-D-glucopyranosyl-(l— >3)-2-O-acetyl-4,6-O-isopropylidene-a-D-glucopyranoside (22): [a] D3+96.4 (acetone, c = 1.0); IR vmax(neat) / cm-1: 2926 (w), 1743 (s), 1513 (m), 1367 (m), 1232 (s), 1036 (s), 776 (m);]H NMR (400 MHz, CDC13) 85.08 (d, J = 10.3 Hz, 1H), 5.00 (d, J = 3.2 Hz, 1H), 4.92 (t, J = 9.6 Hz, 1H), 4.84 (dd, J = 9.6, 3.8 Hz, 1H), 4.78 (d, J = 3.9 Hz, 1H), 4.17-4.10 (m, 1H), 4.02-3.93 (m, 2H), 3.91-3.79 (m, 3H), 3.78-3.62 (m, 4H), 3.35 (s, 3H), 2.10 (s. 3H), 2.08 (s, 3H). 2.04 (s, 3H), 1.52 (s, 3H), 1.43 (s. 3H), 1.41 (s, 9H). 0.82 (s, 9H), 0.04 (s, 3H), 0.00 (s, 3H);13C NMR (100 MHz, CDCI3) 8 171.0, 170.4, 169.3, 155.1, 100.1, 99.8, 97.8, 79.5, 75.6, 73.9, 72.3, 71.4, 70.6, 69.4, 62.9, 62.3 (two peaks overlapped, 2C), 55.6, 55.3, 29.2, 28.5 (3C), 25.6 (3C), 21.2, 20.9, 20.7, 19.2, 17.8, -4.3, -4.5; HRMS: m / z (ESI) calcd for C33H58NO15SE. [M + H]+, 736.3570, found 736.3569. ^’CI-HI - 172.0 Hz, 175.2 Hz.Scheme 38.1 2 equiv 1.5 equivIn Scheme 38, S12 was synthesized according to the following procedure.TMSCI (3.0 equiv)imidazole (4.5 equiv)DMF, 45 °Cc = 0.2 M, 5 hS12

[0183] To a 100 mL flame-dried round bottom flask equipped with a stir bar, 6-azido-6-deoxy-D-glucal (Sil) Kugelman, M„ Mallams, A. K. & Vernay, H. F. Semisynthetic Aminoglycoside Antibacterials. Part IV. Synthesis of Antibiotic JI-20A, Gentamicin B, and Related Compounds. J. Chem. Soc., Perkin Trans. 1, 1126-1134 (1976)) (1.71 g, 10 mmol, 1.0 equiv), imidazole (3.06 g, 45 mmol, 4.5 equiv) and anhydrous DMF (50 mL) were added. The flask was cooled to 0 °C and TMSC1 (3.8 mL, 30 mmol, 3.0 equiv) was then added. The reaction mixture was stirred for 5 h at 45 °C until Sil was fully consumed (monitored by TLC). The reaction mixture was quenched with saturated NH4CI solution (20 mL) and diluted with Et2O (20 mL). The organic phase was separated from the aqueous phase, and the aqueous phase was extracted with Et2O (15 mL x 2). The combined organic phase was washed with brine (20 mL) and dried over Na2SO4. After concentration in vacuo, the residue was purified through column chromatography (hexanes / EtOAc: from 100:1 to 10:1) to afford the desired product S12 (2.78 g, 88% yield) as colorless oil.

[0184] 6-Azido-3,4-di-O-trimethylsilyl-6-deoxy-l,5-anhydro-2-deoxy-D-arabino-hex-l-enitol (S12): IRvmax(neat) / cm: 2958 (w), 2099 (s), 1649 (s), 1248 (s), 1115 (m), 1091 (m), 882 (m). 831 (s); NMR (400 MHz, CDCh) 86.30 (dd. J = 6.1, 1.5 Hz, 1H), 4.66 (dd, J = 6.1, 2.3 Hz, 1H), 4.20 (dt, J - 6.6, 1.9 Hz, 1H), 3.88 (ddd, J - 8.7, 5.6, 2.9 Hz, 1H), 3.76 (dd, J = 9.2, 6.5 Hz,1H), 3.57 (dd, J = 13.1, 2.8 Hz, 1H), 3.43 (dd, J = 13.1, 5.6 Hz, 1H), 0.17 (s, 18H);13C NMR (100 MHz, CDCh) 8 143.1. 103.9, 77.8, 71.3, 70.5, 51.0, 0.6, 0.5; LRMS: m / z (APCI) calcd for Ci2H26N3O3Si2+. [M + H]+, 316.2, found 316.2.

[0185] The glycal cis-aminoglycosylation was carried out on a 0.3 mmol scale by following the General Procedure A with the modifications: 1 (10 mol %) was used. The desired product 23 was purified through column chromatography (hexanes / ethyl acetate: from 20:1 to 4:1) as white foam (214 mg, 76% yield). Methyl 6-azido-2-tert-butoxycarbonylamino-3,4-di-O-trimethylsilyl-2,6-dideoxy-a-D-glucopyranosyl-(l— >6)-2,3,4-tri-O-benzoyl-a-D-glucopyranoside (23): [a]p3+108.1 (acetone, c = 1.0); IR vmax (neat) / cm-1: 2936 (w), 2099 (m), 1724 (s), 1451 (m), 1381 (w), 1249 (m). 1141 (s), 880 (m), 708 (m);NMR (400 MHz, CDCh) 88.02-7.93 (m, 4H), 7.91-7.81 (m, 2H), 7.54-7.46 (m, 2H). 7.43-7.33 (m. 5H), 7.30-7.23 (m, 2H), 6.19-6.10 (m, 1H). 5.66 (t, J = 10.0 Hz, 1H), 5.31-5.15 (m, 3H), 4.95 (d, J - 3.2 Hz, 1H), 4.31-4.21 (m, 1H), 3.90-3.75 (m, 3H), 3.70-3.59 (m, 2H), 3.53-3.43 (m, 4H), 3.33 (dd, J = 13.1, 2.4 Hz, 1H). 3.20 (dd, J = 13.0, 5.5 Hz, 1H), 1.50 (s, 9H), 0.20 (s, 9H), 0.15 (s, 9H);13C NMR (100 MHz, CDCh) 8 165.7, 165.6, 165.0, 155.5, 133.4, 133.3, 133.0, 129.84 (2C), 129.79 (2C), 129.6 (2C), 129.1, 129.0, 128.8, 128.4 (2C), 128.3 (2C). 128.1 (2C), 98.0, 97.0, 79.6, 73.4. 73.0, 72.2, 71.8, 70.5, 68.8 (two peaks overlapped, 2C), 64.4, 55.5, 55.0, 51.2, 28.5 (3C), 0.9 (3C), 0.8 (3C); HRMS: m / z (ESI) calcd for C45H6iN4Oi4Si2+, [M + H]+, 937.3717, found 937.3729.1J13CI-HI = 175.4 Hz, 174.4 Hz.Scheme 39.1.2 equiv 2.0 equiv

[0186] The glycal cis-aminoglycosylation was carried out on a 0.3 mmol scale by following the General Procedure A with the modifications: 3g (2.0 equiv) was used. The desired product 24was purified through column chromatography (hexanes / ethyl acetate: from 20:1 to 5:1) as white foam (166 mg, 71% yield).

[0187] Methyl 6-azido-2-tert-butoxycarbonylainino-3,4-di-O-trimethylsilyl-2,6-dideoxy-a-D-glucopyranosyl-(1^2)-6-O-tert-butyldimethylsilyl-3,4-O-isopropylidene-a-D-galactopyranoside (24): [a]^3+131.8 (acetone, c = 1.0); IRvmax(neat)Zcm’1: 2936 (w), 2102 (m), 1722 (s), 1502 (m), 1381 (m), 1249 (m), 1142 (s), 882 (m), 838 (s); ’H NMR (400 MHz, CDCh) 8 4.93 (d, J = 10.0 Hz, 1H), 4.78 (d, J = 3.6 Hz, 1H), 4.70 (d, J = 3.6 Hz, 1H), 4.20 (dd, J=5.5 Hz, 2.1 Hz, 1H), 4.18-4.14 (m, 1H), 4.00-3.92 (m. 2H), 3.85 (dd. J = 6.4, 10 Hz, 1H), 3.82-3.67 (m. 3H), 3.61 (t, J = 9.0 Hz, 1H), 3.54 (t, J = 8.8 Hz, 1H), 3.47-3.39 (m, 4H), 3.29 (dd, J = 13.1, 4.1 Hz, 1H), 1.50 (s, 3H), 1.43 (s, 9H), 1.32 (s, 3H), 0.89 (s, 9H), 0.15 (s, 9H), 0.12 (s, 9H), 0.08 (s, 6H);13C NMR (100 MHz, CDCh) 8 155.4, 109.2, 96.8, 96.7, 79.4, 74.5, 74.3, 73.9, 73.0. 72.6. 71.7. 68.3, 62.3, 55.5, 54.9, 51.2, 28.5 (3C), 28.1, 26.2, 25.8 (3C), 18.2, 1.0 (3C), 0.8 (3C), -5.4, -5.5; HRMS: m / z (ESI) calcd for C33H67N40iiS+, [M + H]+. 779.4109, found 779.4110. ^’CI-HI = 168.8 Hz.172.7 Hz.Scheme 40.S12 6 3g 251.2 equiv 1.8 equiv

[0188] The glycal cis-aminoglycosylation was carried out on a 0.3 mmol scale by following the General Procedure A with the modifications: 3g (1.8 equiv) was used. The desired product 25 was purified through column chromatography (hexanes / ethyl acetate: from 20:1 to 3:1) as white foam (148 mg, 70% yield).

[0189] Methyl 6-azido-2-tert-butoxycarbonylamino-3,4-di-O-trimethylsilyI-2,6-dideoxy-a-D-glucopyranosyl-( 1— >3)-2-O-acetyl-4,6-O-isopropylidene-a-D- lucopyranoside (25): [ct]p3+141.5 (acetone, c = 1.0); IRvmax(neat) / cm-1: 2959 (w), 2102 (m), 1719 (s), 1511 (m), 1446 (m). 1248 (m), 1198 (m), 1107 (m), 1041 (m). 881 (m), 845 (m), 752 (w); 'H NMR (400MHz, CDCh) 85.13 (d, J = 10.3 Hz, 1H), 4.92 (d, J = 3.2 Hz, 1H), 4.85 (dd, J = 9.4, 3.9 Hz, 1H), 4.77 (d, J = 3.9 Hz, 1H), 3.94 (t, J = 8.9 Hz, 1H), 3.87 (dd, J = 9.9, 3.5 Hz, 1H), 3.79-3.64 (m, 5H), 3.60-3.50 (m, 2H). 3.45 (dd, J = 13.3, 2.6 Hz, 1H), 3.35 (s. 3H), 3.23 (dd. J = 13.3, 3.3 Hz, 1H), 2.12 (s, 3H), 1.51 (s, 3H), 1.44 (s, 3H), 1.42 (s, 9H), 0.13 (s, 9H), 0.11 (s, 9H);13C NMR (100 MHz, CDCh) 8 170.3, 155.5, 100.4, 99.8, 97.8, 79.5, 76.3, 73.64, 73.58, 72.6, 72.4, 72.2, 62.8, 62.3, 55.7, 55.3, 50.7, 29.2, 28.5 (3C), 21.1, 19.1, 1.0 (3C), 0.8 (3C); HRMS: m / z (ESI) calcd for C29H55N4Oi2Si2+, [M + H]+, 707.3350, found 707.3356. ^’CI-HI = 176.4 Hz, 175.9 Hz.Scheme 41.

[0190] In Scheme 41, S13 was synthesized from D-rhamnal (Pihko, A. J., Nicolaou, K. C. & Koskinen, A. M. P. An Expedient Synthesis of D-Callipeltose. Tetrahedron: Asymmetry 12, 937-942 (2001) according to Paquette, L. A. & Oplinger, J. A. Limitations in the Application of Anionic Oxy-Cope Sigmatropy to Elaboration of the Forskolin Nucleus. Tetrahedron 45, 107-124 (1989).

[0191] The glycal cis-aminoglycosylation was carried out on a 0.3 mmol scale by following the General Procedure A with the modifications: 1 (10 mol %) was used. The desired product 26 was purified through column chromatography (hexanes / ethyl acetate: from 20:1 to 4:1) as white foam (234 mg, 76% yield).

[0192] Methyl 2-tert-butoxycarbonylamino-3,4-di-O-tert-butyldimethylsilyl-2,6-dideoxy-a-D- glucopyranosyl-(l— >6)-2,3,4-tri-O-benzoyl-a-D-glucopyranoside (26): [a]p3+83.1 (acetone, c = 1.0); IRvmax (neat) / cm-1: 2926 (w), 1727 (s), 1506 (w), 1250 (s), 1095 (s), 1026 (m). 837 (m), 773 (m), 707 (m);JH NMR (400 MHz. CDCh) 88.01-7.93 (m, 4H). 7.91-7.83 (m, 2H), 7.54-7.47 (m, 2H), 7.44-7.34 (m, 5H), 7.27 (t, J = 7.7 Hz, 2H), 6.21-6.06 (m, 1H), 5.59 (t, J =9.9 Hz, 1H), 5.27-5.11 (m, 3H), 4.87 (d, J= 1.4 Hz, 1H), 4.25 (ddd, J = 10.2, 5.4, 1.4 Hz, 1H), 3.86 (dd, J = 11.8, 5.6 Hz, 1H), 3.81-3.64 (m, 4H), 3.47 (s, 3H), 3.32-3.24 (m, 1H), 1.46 (s, 9H), 1.19 (d, J = 6.6 Hz, 3H), 0.91 (s. 9H), 0.90 (s, 9H). 0.18 (s, 3H), 0.11 (s, 6H), 0.08 (s. 3H);13C NMR (100 MHz, CDC13) 6 165.8, 165.7, 165.1, 155.5, 133.3 (two peaks overlapped, 2C), 133.0, 129.9 (2C), 129.8 (2C), 129.7 (2C), 129.3, 129.16, 129.13, 128.40 (2C), 128.37 (2C), 128.2 (2C), 96.9, 96.3, 79.1, 76.1, 72.8, 72.3, 71.3, 70.7, 69.2, 68.9, 65.2, 55.5, 54.5, 28.5 (3C), 26.22 (3C), 26.20 (3C), 18.1 (two peaks overlapped, 2C), 18.0, -2.8, -3.1, -3.65, -3.69; HRMS: m / z (ESI) calcd for C5iH74N2Oi4Si2+, [M + H]+. 980.4642. found 980.4597. ^’ci-ni = 175.8 Hz. 169.1 Hz.Scheme 42.Me AcO- TBSO—S141.2 equiv 1.8 equiv

[0193] In Scheme 43, S14 was synthesized from D-rhamnal (see above) according to Balmond, E. I. et al. A 3,4-trans-Fused Cyclic Protecting Group Facilitates a-Selective Catalytic Synthesis of 2-Deoxyglycosides. Angew. Chem. Int. Ed. 53, 8190-8194 (2014).

[0194] The glycal cis-aminoglycosylation was earned out on a 0.3 mmol scale by following the General Procedure A with the modifications: 3d (1.8 equiv) was used. The desired product 27 was purified through column chromatography (hexanes / ethyl acetate: from 20:1 to 5:1) as white foam (167 mg, 74% yield).

[0195] Methyl 4-O-acetyl-2-tert-butoxycarbonylamino-3-O-tert-butyldimethylsilyl-2,6-dideoxy-a-D- glucopyranosyl-(l— >2)-6-O-tert-butyldimethylsilyl-3,4-O-isopropylidene-a-D-galactopyranoside (27): [a]p3+109.9 (acetone, c = 1.0); IRvmax(neat) / cm-1: 2927 (w), 1715 (s), 1508 (m), 1366 (m), 1068 (m), 1228 (s), 1034 (m), 907 (m), 836 (m), 775 (m), 732 (m);1H NMR (400 MHz, CDCI3) 84.83 (d, J = 9.3 Hz, 1H). 4.74-4,64 (m, 3H), 4.23-4.12 (m, 2H), 4.05-3.91 (m.2H), 3.88-3.66 (m, 5H), 3.40 (s, 3H), 2.04 (s, 3H), 1.46 (s, 3H), 1.40 (s, 9H), 1.32 (s, 3H), 1.07 (d, I= 6.3 Hz, 3H), 0.88 (s, 9H), 0.80 (s, 9H), 0.06 (s, 6H), 0.03 (s, 3H), -0.02 (s, 3H);13C NMR (100 MHz, CDCh) 8 169.8. 155.1, 109.1, 96.8, 96.1, 79.2, 76.5, 74.4, 74.0, 73.1, 71.0, 68.0, 65.8, 62.2, 55.5, 55.2, 28.5 (3C), 28.2, 26.4, 25.8 (3C), 25.6 (3C), 21.3, 18.2, 17.8. 17.4. -4.4, -4.5, -5.4, -5.5; HRMS: m / z (ESI) calcd for CasHesNOnSii*, [M + H]+, 750.4275, found 750.4287. ^CI-HI = 170.0 Hz, 170.0 Hz.Scheme 43.

[0196] The glycal cis-aminoglycosylation was carried out on a 0.3 mmol scale by following the General Procedure C with the modifications: 3d (2.5 equiv) was used. The desired product 28 was purified through column chromatography (hexanes / ethyl acetate: from 20:1 to 5:1) as white foam (149 mg, 73% yield).

[0197] Methyl 4-O-acetyl-2-tert-butoxycarbonylainino-3-O-tert-butyldimethylsilyl-2,6-dideoxy-a-D- glucopyranosyl-(l— >3)-2-O-acetyl-4,6-O-isopropylidene-a-D-glucopyranoside (28): [a]p3+96.5 (acetone, c = 1.0); IRvmax (neat) / cm-1: 2927 (w), 1742 (m), 1719 (m), 1449 (w), 1392 (m), 1362 (m), 1138 (s), 1069 (m), 840 (m); ’H NMR (400 MHz, CDCh) 85.11 (d, J - 10.2 Hz, 1H), 4.95-4.81 (m, 2H), 4.77 (d, J = 3.7 Hz. 1H), 4.67 (t, J = 9.4 Hz, 1H), 3.98-3.83 (m, 2H), 3.83-3.60 (m, 6H), 3.36 (s, 3H), 2.11 (s, 3H), 2.04 (s, 3H), 1.53 (s, 3H), 1.44 (s, 3H), 1.41 (s, 9H), 1.06 (d, J = 6.2 Hz, 3H), 0.82 (s, 9H), 0.03 (s, 3H), -0.00 (s, 3H);13C NMR (100 MHz, CDCh) 8 170.4, 169.6. 155.2, 100.5, 99.8, 97.9, 79.4, 76.6, 76.5, 73.7. 72.3, 70.6, 67.0, 62.9, 62.3, 56.1, 55.3, 29.3, 28.5 (3C), 25.6 (3C), 21.3, 21.1, 19.2, 17.8, 17.5, -4.3, -4.5; HRMS: m / z (ESI) calcd for C31H56NO13SE, [M + H]+, 678.3515, found 678.3534.1J13CI-HI = 169.2 Hz. 170.0 Hz.Scheme 44.S15 S16 3h1.3 equiv 1.8 equiv

[0198] S15 was synthesized from D-Rhamnal as described above according to a modified literature procedure as in Scheme 42.

[0199] The glycal cis-aminoglycosylation was earned out on a 0.3 mmol scale by following the General Procedure A with the modifications: 3d (1.8 equiv) was used. The desired product 27 was purified through column chromatography (hexanes / ethyl acetate: from 20:1 to 5:1) as white foam (167 mg, 74% yield).

[0200] Methyl 4-O-acetyl-2-tert-butoxycarbonylamino-3-O-trimethylsilyl-2,6-dideoxy-a-D-glucopyranosyl-( 1— >4)-2,3,6-tri-O-acetyl-a-D-glucopyranoside (29): [a]p3+47.0 (acetone, c = 1.0); IRvmax (neat)Zcm-1: 2969 (w), 1741 (s), 1501 (m), 1366 (s), 1163 (m), 1030 (s), 1005 (s), 880 (m), 842 (m); NMR (400 MHz, CDCh) 55.52 (dd, J = 10.2, 8.3 Hz, 1H), 5.00 (d, J = 3.8 Hz, 1H), 4.86 (d. J = 3.6 Hz, 1H). 4.79 (dd, J = 10.2, 3.6 Hz, 1H), 4.69 (t. J = 9.4 Hz, 1H). 4.47 (dd, J = 12.0, 1.9 Hz, 1H), 4.42 (d, J = 10.2 Hz, 1H), 4.17 (dd, J = 12.1, 4.0 Hz, 1H), 3.98-3.77 (m, 3H), 3.70-3.63 (m, 1H), 3.60 (dd, J = 10.3, 8.9 Hz. 1H), 3.40 (s, 3H), 2.12 (s, 3H), 2.07 (s, 3H), 2.05 (s, 3H), 2.04 (s, 3H), 1.45 (s, 9H), 1.10 (d, J = 6.2 Hz, 3H), 0.07 (s, 9H);13C NMR (100 MHz, CDCh) 5 170.6, 170.3, 169.6, 169.5, 155.2, 99.6, 96.6, 79.9, 76.2, 74.0, 72.2, 71.2, 70.9, 68.0, 67.3, 62.9, 55.4, 55.2, 28.4 (3C), 21.2, 21.0, 20.8, 20.7, 17.5, 0.4 (3C); HRMS: m / z (ESI) calcd for C29H50NO15SC, [M + H]+, 680.2944, found 680.2944. ^’CI-HI = 175.6 Hz, 175.5 Hz.Scheme 45.S17 561.2 equiv

[0201] In Scheme 45, S17 was synthesized according to Yin, B.-L. et al. SodiumB or ohydride- Nickel Chloride-Methanol Catalytic System for Regioselective Reduction of Electron-Rich Conjugated Dienes and Reductive Cleavage of Allyl Esters Involving 7t- Allylnickel Intermediates. Adv. Synth. Catal. 353, 3319-3324 (2011).

[0202] The glycal cis-aminoglycosylation was carried out on a 0.3 mmol scale by following the General Procedure A with the modifications: 3d (1.8 equiv) was used. The desired product 30 was purified through column chromatography (hexanes / ethyl acetate: from 20:1 to 5:1) as white foam (160 mg, 71% yield).

[0203] Methyl 4-O-acetyl-2-tert-butoxycarbonylamino-6-O-tert-butyldimethylsilyl-2,3-dideoxy-a-D-ribo-hexopyranosyl-(l— >6)-2,3,4-tri-O-benzoyl-a-D-glucopyranoside (30): [a]^,3+108.5 (acetone, c = 0.73); IR vmax (neatj / cm1: 2925 (w), 1732 (s), 1382 (m), 1260 (m), 1142 (s), 1026 (s), 834 (w), 708 (m);!H NMR (400 MHz, CDCh) 85.12 (d, J = 9.2 Hz, 1H), 4.87 (td, J = 10.9, 4.8 Hz, 1H), 4.75 (d, J = 3.3 Hz, 1H), 4.73 (d, J = 3.4 Hz, 1H), 4.28-4.18 (m, 2H), 3.97 (td, J = 6.2, 1.4 Hz, 1H), 3.94-3.76 (m, 5H), 3.73 (dd, J= 11.4, 3.4 Hz, 1H), 3.65 (dd, J= 11.4, 1.4 Hz, 1H), 3.41 (s, 3H), 2.31 (dt, J = 10.6, 5.0 Hz. 1H), 2.00 (s, 3H). 1.71-1.59 (m, 1H), 1.48 (s. 3H), 1.42 (s, 9H), 1.32 (s, 3H), 0.90 (s, 9H), 0.86 (s, 9H), 0.08 (s, 6H), 0.00 (s, 6H);13C NMR (100 MHz, CDCh) 8 169.4, 154.9, 109.3, 97.0, 95.5, 79.2, 74.4, 74.2, 73.1, 70.4, 68.5, 66.1, 62.3, 61.8, 55.3, 48.1, 30.5, 28.4 (3C), 28.0, 26.3, 25.9 (3C), 25.8 (3C), 21.1, 18.4, 18.3, -5.38, -5.43. -5.5, -5.6; HRMS: m / z (ESI) calcd for CasHesNOnSii*, [M + H]+, 750.4275, found 750.4235.1J13ci-m - 169.6 Hz, 170.0 Hz.Scheme 46.MeS18In Scheme 46, S18 was synthesized according to Popadynec, M„ Gibbard, H. & Clark, J. S.Bidirectional Synthesis of the UK Fragment of Ciguatoxin CTX3C by Sequential Double Ring-Closing Metathesis and Tsuji-Trost Allylation. Org. Lett. 22, 3734-3738 (2020).

[0204] The glycal cis-aminoglycosylation was carried out on a 0.3 mmol scale by following the General Procedure C. The desired product 31 was purified through column chromatography (hexanes / ethyl acetate: from 20:1 to 3:1) as white foam (106 mg, 63% yield).

[0205] Methyl 2-tert-butoxycarbonylamino-4,6-O-isopropylidene-2,3-dideoxy-a-D-ribo-hexopyranosyl-(l— >3)-2-O-acetyl-4,6-O-isopropylidene-a-D-glucopyranoside (31): [a]^,2+99.1 (acetone, c = 1.0); IRvmax (neat) / cm-1: 2937 (w). 1743 (m), 1710 (s). 1501 (s). 1367 (s), 1234 (s), 1198 (s), 1089 (s), 1034 (s), 983 (s), 851 (m), 734 (m); ’H NMR (400 MHz, CDC13) 85.09 (d, J = 9.1 Hz, 1H), 4.88 (d, J = 3.1 Hz, 1H), 4.86-4.77 (m, 2H), 4.01 (t, J = 8.7 Hz, 1H), 3.91-3.69 (m, 4H), 3.68-3.54 (m, 5H), 3.34 (s, 3H), 2.13 (s, 3H), 2.05-1.96 (m, 1H), 1.60-1.49 (m, 4H), 1.43 (s, 3H), 1.41 (s, 9H), 1.40 (s, 3H), 1.34 (s, 3H);13C NMR (100 MHz, CDCI3) 8 170.4, 154.9, 99.7, 99.2, 98.4, 97.7, 79.6, 74.6, 74.3, 72.1. 68.7, 65.6, 62.8, 62.6, 62.3, 55.2, 49.5, 31.2, 29.2, 29.0, 28.4 (3C), 20.9, 19.0, 18.9; HRMS: m / z (EST) calcd for C26H44NO12L [M + H]+, 562.2858, found 562.2843. ^’CI-HI = 172.0 Hz, 171.6 Hz.Scheme 47.Fe(L1)(BF4)2(MeCN)(H2O)2(1) (15 mol%) CH2CI2, 5 A MS " -40 °C, c = 0.3 M, 2 h69 % yield S17 6 3f1.2 equiv 2.0 equiv

[0206] The glycal cis-aminoglycosylation was carried out on a 0.3 mmol scale by following the General Procedure C with the modifications: 3f (2.0 equiv) was used. The desired product S32 was purified through column chromatography (hexanes / ethyl acetate: from 20:1 to 3:1) as white foam (140 mg, 69% yield).

[0207] Methyl 4-O-acetyl-2-tert-butoxycarbonylamino-6-O-tert-butyldimethylsilyl-2,3-dideoxy-a-D-ribo-hexopyranosyl-(l— >3)-2-O-acetyl-4,6-O-isopropylidene-a-D-glucopyranoside (S32): [a] o1+108.9 (acetone, c = 1.0); IR vmax (neat) / cm-1: 2925 (w), 1732 (s), 1382 (m). 1260 (m), 1142 (s), 1026 (s), 834 (w), 708 (m);!H NMR (400 MHz, CDCh) 55.05 (d, J = 9.1 Hz, 1H), 4.97 (s, 1H), 4.84-4.82 (m, 3H), 4.07 (brs, 1H), 3.93-3.80 (m, 2H), 3.80-3.62 (m, 6H), 3.35 (s, 3H), 2.26 (dt, J = 10.9, 4.9 Hz, 1H), 2.12 (s, 3H), 1.99 (s, 3H), 1.58-1.50 (m, 4H), 1.42 (s. 12H), 0.87 (s. 9H), 0.02 (s, 6H);13C NMR (100 MHz. CDCh) 8 170.5, 169.2. 154.8, 99.8, 98.0. 97.8, 79.5, 74.5, 74.4, 72.3, 70.7, 66.3, 62.9, 62.3, 62.0, 55.2, 48.7, 30.4, 29.1, 28.4 (3C), 25.8 (3C), 21.0 (two peaks overlapped, 2C), 19.0, 18.3, -5.48, -5.54; HRMS: m / z (ESI) calcd for C3iH%NOi3Si+, [M + H]+, 678.3515, found 678.3515. 'j' i-Hi = 174.3 Hz, 172.3 Hz.Scheme 48A.Fe(L1)(BF4)2(MeCN)(H2O)2(1) (10 mol%)AcO— T^°,+CH2CI2, 5 A MS-40 °C, c = 0.3 M, 2 h73% yieldS20 4 3d1.2 equiv 1.8 equivThe glycal cis-aminoglycosylation was carried out on a 0.3 mmol scale by following the General Procedure A with the modifications: 1 (10 mol %) and 3d (1.8 equiv) were used. The desired product S33 was purified through column chromatography (hexanes / ethyl acetate: from 20:1 to 3:1) as white foam (196 mg, 73% yield).

[0208] Methyl 4-O-acetyl-2-tert-butoxycarbonylamino-3-O-tert-butyldimethyIsilyl-2-deoxy-a-D-xylopyranosyl-( 1— >6)-2,3,4-tri-O-benzoyl-a-D-glucopyranoside (S33): [a]p3+91.1 (acetone, c = 1.0); IR vmax (neat) / cm-1: 2931 (w), 1732 (w), 1450 (w), 1391 (m), 1281 (w), 1141 (s), 1073 (m), 851 (w);JH NMR (400 MHz, CDC13) 88.03-7.92 (m, 4H), 7.86 (d, J = 7.7 Hz, 2H), 7.55-7.46 (m, 2H), 7.44-7.32 (m. 5H), 7.26 (t. J = 7.7 Hz, 2H), 6.24-6.05 (m. 1H), 5.65 (t. J = 10.0 Hz.1H), 5.31-5.16 (m, 3H), 4.93-4.84 (s, 1H), 4.79-4.62 (m, 1H), 4.26 (ddd, J = 10.4, 5.3, 1.7 Hz, 1H), 3.89-3.80 (m, 3H), 3.80-3.66 (m, 2H), 3.46 (s, 3H), 3.43 (t, J = 10.4 Hz. 1H), 2.04 (s, 3H), 1.48 (s, 9H), 0.88 (s, 9H), 0.17 (s. 3H), 0.10 (s. 3H);13C NMR (100 MHz. CDCI3) 8 169.8, 165.7. 165.6, 165.0, 155.3, 133.3, 133.2, 133.0, 129.8 (2C), 129.7 (2C), 129.5 (2C), 129.1, 128.93, 128.88, 128.34 (2C), 128.29 (2C), 128.1 (2C), 98.2, 96.9, 79.4, 72.5, 72.2. 70.5, 70.0, 68.9, 68.8, 64.7, 59.3, 55.4, 54.9, 28.4 (3C), 25.6 (3C), 21.0, 17.9, -4.6 (two peaks overlapped, 2C); HRMS: m / z (ESI) calcd for C46H6oNOi5Si+, [M + H]+, 894.3727, found 894.3741. ^’CI-HI = 170.8 Hz, 174.4 Hz.Scheme 48B.

[0209] S21 was synthesized according to the following procedure.TBSCI (1.2 equiv)imidazole (1.5 equiv)DMF, 45 °Cc = 0.2 M, 2 hS20 S21To a 100 mL flame-dried round bottom flask equipped with a stir bar, 4,6-di-(9-acetyl galactal (S20) (2.3 g, 10 mmol, 1.0 equiv), imidazole (1.02 g, 15 mmol, 1.5 equiv), and anhydrous DMF (50 mL) were added. The flask was cooled to 0 °C and TBSC1 (1.81 g, 12 mmol, 1.2 equiv) was then added. The reaction mixture was stirred for 2 h at 45 °C until S20 was fully consumed (monitored by TLC). The reaction mixture was quenched with saturated NH4CI solution (20 mL) and diluted with EtOAc (20 mL). The organic phase was separated from the aqueous phase, and the aqueous phase was extracted with EtOAc (15 mL x 2). The combined organic phase was washed with brine (20 mL) and dried over Na2SO4. After concentration in vacuo, the residue was purified through column chromatography (hexanes / EtOAc: from 100:1 to 5:1) to afford the desired product S21 (3.1 g, 90% yield) as colorless oil.OAcTBSOS21

[0210] 4,6-Di-O-acetyl-3-O-ferf-butyldimethylsilyl-2,6-anhydro-5-deoxy-D-ara&frao-hex- 5-enitol (S21): IRvmax (neat) / cm-1: 2953(w), 2857 (w), 1743 (s), 1646 (s), 1370 (m), 1221 (s), 1102(m), 1043 (m), 835 (s), 777 (m);NMR (400 MHz, CDCh) 56.32 (dd, J = 6.2, 1.3 Hz, 1H), 5.22 (dt, J = 3.5, 1.2 Hz, 1H), 4.70 (ddd, J= 6.3, 3.2, 1.1 Hz, 1H), 4.50-4.43 (m, 1H), 4.38-4.21 (m, 3H), 2.11 (s, 3H), 2.08 (s. 3H). 0.88 (s, 9H), 0.08 (s, 3H), 0.04 (s, 3H);13C NMR (100 MHz, CDCh) 5 170.7, 170.2, 143.2, 103.3, 73.0, 67.1, 62.7, 62.4, 25.6 (3C), 20.9, 20.8, 18.0, -4.9, -5.1; LRMS: m / z (APCI) calcd for Ci6H29O6Si+, [M + H]+, 345.2, found 345.2.[0211J The glycal ds-aminoglycosylation was carried out on a 0.3 mmol scale by following the General Procedure A with the modifications: 1 (10 mol %), 4 (1.4 equiv), and 3d (2.0 equiv) were used. The desired product 33 was purified through column chromatography (hexanes / ethyl acetate: from 20: 1 to 2:1) as white foam (209 mg, 72% yield).

[0212] Methyl 4,6-di-O-aceyl-2-tert- bu toxycarbonylami no-3-D- / e / 7-hu ty Idi methy Isily 1-2-deoxy-a-D-galactopyranosyl-(l— >6)-2,3,4-tri-O-benzoyl-a-D-glucopyranoside (33): [a]!,3+112.0 (acetone, c = 1.0); IR vmax (neat) / cm-1: 2933 (w), 1744 (m), 1509 (m), 1380 (m), 1226 (m), 1142 (m). 1038 (m), 839 (m); ’H NMR (400 MHz, CDCh) 57.99-7.93 (m, 4H), 7.85 (d, J= 7.7 Hz, 2H), 7.56-7.46 (m, 2H), 7.45-7.35 (m, 5H), 7.27 (t, J = 7.7 Hz, 2H), 6.14 (t, J = 9.9 Hz, 1H), 5.63 (t, J= 9.9 Hz, 1H), 5.24-5.19 (m, 3H), 5.03-4.94 (m, 2H), 4.26 (dd. 7= 10.1, 3.9 Hz, 1H), 4.14 (td, J = 10.4, 3.5 Hz. 1H), 4.07-3.99 (m, 2H), 3.94-3.79 (m. 3H). 3.74 (d, J= 11.7 Hz, lH),f 3.47 (s, 3H). 2.10 (s, 3H), 1.92 (s, 3H), 1.46 (s, 9H), 0.87 (s, 9H), 0.14 (s, 3H), 0.11 (s, 3H);13C NMR (100 MHz, CDCh) 5 170.4, 170.3, 165.73, 165.70, 165.2, 155.3, 133.6, 133.3, 133.1, 129.9 (2C), 129.7 (2C), 129.6 (2C), 129.1, 129.0, 128.8, 128.5 (2C), 128.4 (2C), 128.2 (2C), 98.6, 97.0, 79.4, 72.1, 70.5, 70.3, 68.9, 68.6, 68.2, 67.5, 64.9, 63.0, 55.5, 51.3, 28.5 (3C), 25.6 (3C), 20.8, 20.6, 17.7, -4.9, -5.0; HRMS: m / z (ESI) calcd for C49H64NO17SP. [M + H]+, 966.3938, found 966.3942. J13CI-HI = 175.2 Hz, 172.8 Hz.Scheme 48C.Fe(L1)(BF4)2(MeCN)(H2O)2(1) (15 mol%) CH2CI2, 5 A MS -40 °C, c = 0.3 M, 2 h70 S21 6 3d % yield1.4 equiv 1.8 equiv

[0213] The glycal m-aminoglycosylatiori was carried out on a 0.3 mmol scale by following the General Procedure A with the modifications: 6 (1.4 equiv) and 3d (1.8 equiv) were used. The desired product 34 was purified through column chromatography (hexanes / ethyl acetate: from 20:1 to 2:1) as white foam (155 mg, 70% yield).

[0214] Methyl 4,6-di-O-aceyl-2-tert-butoxycarbonylamino-3-O-te7t-butyldimethylsilyl-2-deoxy-a-D-galactopyranosyl-(l— >3)-2-O-acetyl-4,6-O-isopropylidene-a-D-glucopyranoside (34): [a]^1+112.1 (acetone, c = 0.72); IR vmax (neat) / cm-1: 2933 (w), 1744 (m), 1509 (m), 1380 (m), 1226 (m). 1142 (m). 1038 (m), 839 (m); ’H NMR (400 MHz, CDCh) 55.20 (d, J= 3.2 Hz, 1H), 5.12 (d, J = 10.4 Hz, 1H), 5.01 (d, J = 3.4 Hz, 1H), 4.83-4.72 (m, 2H), 4.21-4.10 (m, 2H), 4.06 (td, J = 10.4, 3.2 Hz, 1H), 4.00-3.93 (m, 1H), 3.91-3.80 (m, 2H), 3.79-3.63 (m, 4H), 3.34 (s, 3H), 2.08 (s, 3H), 2.07 (s, 3H), 2.05 (s. 3H), 1.51 (s, 3H). 1.43 (s, 3H), 1.39 (s, 9H), 0.81 (s. 9H),0.04 (s, 3H), 0.02 (s, 3H);13C NMR (100 MHz, CDCh) 8 170.7, 170.4, 170.3, 155.3, 100.8, 99.8, 97.7, 79.3, 76.3, 73.6, 72.7, 70.1, 68.4, 68.1, 62.9. 62.6, 62.3, 55.3, 52.0, 29.2 (3C), 28.5 (3C), 25.5, 20.8, 20.7, 20.6, 19.1, 17.7, -4.9, -5.0; HRMS: m / z (ESI) calcd for CaaHssNOisSC, [M + H]+, 736.3570, found 736.3569. = 175.2 Hz, 169.2 Hz.Scheme 48D.

[0215] S22 was synthesized according to a literature procedure. The glycal cisaminoglycosylation was carried out on a 20 mmol scale by the following procedure.

[0216] To a flame-dried 250 mL round bottom flask (flask A) equipped with a stir bar were added S21 (6.89 g, 20 mmol, 1 equiv), S22 (7.09 g, 28 mmol, 1.4 equiv) the pre-formed iron catalyst 1 Fe(Ll)(BF4)2(MeCN)(H2O)2 (1.16 g, 2 mmol, 10 mol %), and freshly activated 5 A powdered molecular sieves (ca. 8 g). After the flask was evacuated and backfilled with N2 twice, anhydrous CH2CI2 (20 mL) was added and the flask was cooled to -78 °C. To a flame-dried 50 mL round bottom flask (flask B) was added acyloxyl carbamate 3d (8.46 g, 30 mmol, 1.5 equiv). Flask B was evacuated and backfilled with N2 twice and then anhydrous CH2O2 (20 mL) was added, then solution in flask B was added to flask A via a syringe in 10 min. The reaction was kept at -78 °C for an additional 3 min before switched to -40 °C. The reaction was kept at -40 °C for 4 h and quenched by precipitating the iron catalyst with Et20 (80 mL) at the same temperature. The mixture was stirred for two minutes and subsequently warmed up to room temperature. The solution was then filtered through a short pad of Celite® and washed with saturated aq. NaHCO3 solution (30 mL). The organic phase was separated from the aqueous one, which was further extracted with CH2CI2 (30 mL x 3). The combined organic phase was dried over anhydrous Na2SO4 and concentrated in vacuo. The residue was purified through a silica gel flash column (hexanes / ethyl acetate: from 20:1 to 2:1) to afford the desired product 35 as white foam (11.98 g, 84% yield).

[0217] V-benzylo\ycaibonyl- -(4,6-di-6>-ace)l-2- / e / 7-butoxycarbonylainino-3-6>- / e / 7-butyldimethylsilyl-2-deoxy-(x-D-galactopyranosyl)-L-serine methyl ester (35): [CC]Q3+78.5 (acetone, c = 1.0); IRvmax (neatycm1: 2927 (w), 1747 (m), 1381 (m), 1137 (s), 1071 (m); ’H NMR (400 MHz, CDCh) 87.40-7.28 (m, 5H), 5.76 (d, 7= 8.2 Hz, 1H), 5.20 (d, 7 = 3.3 Hz, 1H), 5.18-5.06 (m, 2H), 4.77 (d, J= 3.7 Hz, 1H). 4.57 (dt. J = 7.9, 3.4 Hz, 1H), 4.36 (d. J= 10.2 Hz, 1H). 4.17-4.09 (m, 1H), 4.09-3.98 (m, 2H), 3.98-3.84 (m, 3H), 3.78 (s, 3H), 3.69 (dd, J = 10.4, 3.4 Hz, 1H), 2.08 (s, 3H), 2.01 (s, 3H), 1.40 (s. 9H), 0.81 (s, 9H),0.03 (s, 3H), 0.06 (s, 3H);13C NMR (100 MHz, CDCh) 6 170.5, 170.3, 170.2, 155.7, 154.9, 135.9, 128.5 (2C), 128.3, 128.2 (2C), 99.8, 79.6, 69.8, 69.5, 68.1, 67.8, 67.2, 62.7, 54.3, 52.6, 51.2, 28.4 (3C), 25.5 (3C), 20.7, 20.6, 17.6, -4.9, -5.1; HRMS: m / z (ESI) calcd for C33H53N2O13SE, [M + H]+, 713.3311. found 713.3327. 'J!CI-HI = 169.6 Hz.Scheme 48E.

[0218] S23 was synthesized according to a literature procedure. The glycal cis-aminoglycosylation was carried out on a 20 mmol scale by the following procedure.

[0219] To a flame-dried 250 mL round bottom flask (flask A) equipped with a stir bar wereadded S21 (6.89 g, 20 mmol, 1 equiv), S23 (7.48 g, 28 mmol, 1.4 equiv) the pre-formed iron catalyst 1 Fe(Ll)(BF4)2(MeCN)(H2O)2 (1.16 g, 2 mmol, 10 mol %), and freshly activated 5 A powdered molecular sieves (ca. 8 g). After the flask was evacuated and backfilled with N2 twice, anhydrous CH2CI2 (20 mL) was added and the flask was cooled to -78 °C. To a flame-dried 50 mL round bottom flask (flask B) was added acyloxyl carbamate 3d (8.46 g, 30 mmol, 1.5 equiv). Flask B was evacuated and backfilled with N2 twice and then anhydrous CH2CI2 (20 mL) was added, then solution in flask B was added to flask A via a syringe in 10 min. The reaction was kept at -78 °C for an additional 3 min before switched to -40 °C. The reaction was kept at -40 °C for 4 h and quenched by precipitating the iron catalyst with Et2O (80 mL) at the same temperature. The mixture was stirred for two minutes and subsequently warmed up to room temperature. The solution was then filtered through a short pad of Celite® and washed with saturated aq. NaHCO3 solution (30 mL). The organic phase was separated from the aqueous one, which was further extracted with CH2O2 (30 mL x 3). The combined organic phase was dried over anhydrous Na2SC>4 and concentrated in vacuo. The residue was purified through a silica gel flash column (hexanes / ethyl acetate: from 20:1 to 2:1) to afford the desired product 36 as white foam (10.61 g, 73% yield).

[0220] A-benzyloxycarbonyl-O-(4,6-di-O-aceyl-2-tert-butoxycarbonylamino-3-O-tert-butyldimethylsilyl-2-deoxy-a-D-galactopyranosyl)-L-threonine methyl ester (36): [cc] p3+69.6 (acetone, c = 1.0); IR vmax (neat)Zcm1: 2930 (w), 1718 (m), 1505 (m), 1366 (m), 1223 (m), 1167 (m), 947 (m), 697 (m); NMR (400 MHz, CDCh) 57.45-7.12 (m, 5H), 5.49 (d, J= 9.5 Hz, 1H), 5.17 (d, J= 3.4 Hz, 1H), 5.09 (s, 2H), 4.79 (d. J= 3.7 Hz, 1H), 4.48-4.38 (m. 2H), 4.18-4.17 (m, 1H), 4.07-3.87 (m, 4H), 3.75 (s, 3H), 3.65 (dd, J = 10.5, 3.4 Hz, 1H), 2.04 (s, 3H), 1.95 (s, 3H), 1.37 (s, 9H), 1.27 (d, J = 6.4 Hz, 3H), 0.77 (s, 9H), 0.03 (s, 3H), 0.01 (s, 3H);13C NMR (100 MHz, CDCh) 5 171.1, 170.4, 170.3, 156.4. 155.1, 135.9, 128.6 (2C). 128.4, 128.3 (2C), 100.8, 79.6, 77.5, 70.0, 68.1, 67.9, 67.5, 62.9, 58.4, 52.6, 51.5, 28.5 (3C), 25.6 (3C), 20.8, 20.6, 17.7, 17.6, -4.5, -5.0; HRMS: m / z (ESI) calcd for C34H55N2O13SE, [M+H]+, 727.3468, found 727.3488. J13CI-HI = 175.6Hz.D. Reiterative Glycal cis-Aminoglycosylation and Glycal cis-Aminoglycosylation for Complex SubstratesScheme 49.1.4 equiv 1.65 equiv

[0221] In Scheme 49, 37 was synthesized according to Filice, M., et al., Regioselective Monodeprotection of Peracetylated Carbohydrates. Nat. Protoc.7, 1783-1796 (2012).

[0222] To a 100 mL flame-dried round bottom flask (flask A) equipped with a stir bar were added glycal 2 (1.5 g, 5.0 mmol, 1.0 equiv), glycosyl acceptor 37 (1.61 g, 7.0 mmol, 1.4 equiv), iron catalyst 1 Fe(Ll)(BF4)2(MeCN)(H2O)2 (436 mg, 0.75 mmol, 15 mol %) and freshly activated 5 A molecular sieves, powder (ca. 1.5 g). After the flask was evacuated and backfilled with N2 twice, anhydrous CH2CI2 (10 mL) was added and the solution was cooled to -40 °C. To a second flame-dried round bottom flask (flask B) was added acyloxyl carbamate 3c (1.92 g, 8.25 mmol, 1.65 equiv). Flask B was evacuated and backfilled with N2 twice and then anhydrous CH2O2 (7 mL) was added. 3c was added to flask A using a syringe pump within 1.5 h. The reaction was kept at -40 °C for an additional 2 h and diluted with additional CH2CI2 (20 mL).

[0223] EhN (1.4 mL) and aqueous NaH2PO4 / Na2HPC>4 buffer (20 mL, pH = 7.0) were added sequentially at the same temperature. The mixture was subsequently warmed up to room temperature and stirred for another 5 min until organic phase became colorless. The organic phase was separated from the aqueous one, which was further extracted with CH2CI2 (20 mL x 3). The combined organic phase was dried over anhydrous Na2SO4 and concentrated in vacuo. The residue was purified through a silica gel flash column (hexanes / ethyl acetate: from 10:1 to 3:1) to afford thedesired product 38 as white foam (2.29 g, 71% yield).

[0224] 3,4-Di-O-acetyl-l,5-anhydro-6-O-(2-tert-butoxycarbonylamino-3-O-tert-butyldimethylsilyl-4,6-0-isopropylidene-2-deoxy-a-D-glucopyranosyl)-2-deoxy-D-arabino-hex-l-enitol (38): [a]p3+63.1 (acetone, c = 0.47); IR Vmax (neat) / cm-1: 2930 (w), 1718 (s), 1506 (m), 1367 (s), 1219 (s), 1169 (m), 1130 (m). 1017 (m), 911 (m), 778 (m);1H NMR (400 MHz, CDCh) 86.44 (d, J = 6.0 Hz, 1H), 5.42-5.32 (m, 1H), 5.33-5.26 (m, 1H), 5.03 (d, J = 10.1 Hz, 1H), 4.88-4.77 (m, 2H), 4.18 (brs, 1H), 3.86-3.75 (m, 3H), 3.75-3.62 (m, 2H), 3.62-3.42 (m, 3H), 2.10 (s, 3H), 2.03 (s, 3H), 1.46 (s, 3H), 1.42 (s, 9H). 1.37 (s, 3H), 0.86 (s, 9H), 0.07 (s, 3H), 0.05 (s, 3H);13C NMR (100 MHz, CDCh) 8 170.4, 169.5, 155.4, 145.9, 99.34, 99.27, 99.1, 79.3, 75.5, 74.8, 70.9, 68.0, 67.5, 64.7, 63.8, 62.4, 55.5, 29.0, 28.4 (3C), 25.8 (3C), 21.0, 20.9, 18.9, 18.2, -4.3, -5.0; HRMS: m / z (ESI) calcd for C3oH52NOi2Si+. [M + H]+, 646.3253, found 646.3258.Scheme 50.TBSO-A HO-"\BnO-rA-°v AcO-rA-'°xBnO— AcO— 1^-sJ371.2 equiv

[0225] The glycal cis-aminoglycosylation was carried out on a 0.3 mmol scale by following the General Procedure A with the modifications: 3b (1.8 equiv) were used. The desired product S34 was purified through column chromatography (hexane s / ethyl acetate: from 20:1 to 3:1) as white foam (167 mg, 71% yield).

[0226] 3,4-Di-O-acetyl-l,5-anhydro-6-O-(3,4-di-O-benzyl-2-tert-butoxycarbonylamino-6-O-tert-butyldimethylsilyl-2-deoxy-a-D-glucopyranosyl)-2-deoxy-D-arabino-hex-l-enitol (S34): [a]p2+50.3 (acetone, c = 1.0); IRvmax(neat) / cm-1: 2930 (w), 1740 (m), 1499 (m), 1363 (m), 1219 (m), 1142 (m), 1071 (m), 777 (m), 697 (m); ’H NMR (400 MHz, CDCh) 87.46-7.17 (m, 10H), 6.44 (d, J = 6.2 Hz, 1H), 5.37 (dd, J = 6.0, 3.2 Hz, 1H), 5.28 (t, J = 6.8 Hz, 1H), 5.01 (d, J = 10.1 Hz, 1H), 4.90-4.79 (m, 4H), 4.76 (d, J = 11.0 Hz, 1H), 4.66 (d, J = 10.9 Hz, 1H), 4.24-4.17 (m,1H), 3.92 (dt, J = 3.3, 9.9 Hz, 1H), 3.88-3.74 (m, 3H), 3.73-3.53 (m, 4H), 2.09 (s, 3H), 2.05 (s, 3H), 1.45 (s, 9H), 0.90 (s, 9H), 0.06 (s, 3H), 0.05 (s, 3H);13C NMR (100 MHz, CDCh) 8 170.3, 169.5, 155.4, 145.8. 138.4, 138.3, 128.3 (2C), 128.2 (2C), 127.9 (two peaks overlapped, 4C). 127.6, 127.4, 98.8, 98.3, 80.8, 79.3, 77.9, 75.3, 75.2, 74.9, 72.3, 67.7, 67.6, 64.4, 61.9, 54.4, 28.3 (3C), 25.8 (3C), 20.9, 20.8, 18.2, -5.2, -5.5; HRMS: m / z (ESI) calcd for C41H60NO12SP, [M + H]+, 786.3879, found 786.3870. ^CI-HI = 170.4 Hz.Scheme 51.In Scheme 51, 39 was synthesized according to the following procedure.Amano Lipase (15 wt%) O' ■QTBSO- TMSOTf (1.2 equiv) phosphate buffer (pH=7) / actone BocHN^ Et3N (24 equiv)c = 0.16M, rt, 20 h THF, rt, 2 h 9 AcO- Q0% yield 91% yieldHO-S35Glycal Activation through a Chemo-Enzymatic Procedure. To a 100 mL round bottom flask were added Amano Lipase from Pseudomonas fluorescens (0.3 g, 15 wt %), disaccharide 38 (2.0 g, 3.1 mmol, 1.0 equiv), aqueous NaFLPCL / NaiHPCh buffer (16.5 mL, pH = 7.0) and acetone (4.2 mL). The mixture was stirred at room temperature for 20 h. EtOAc (20 mL) was added to dilute the reaction. The organic phase was separated from the aqueous phase and the aqueous phase was further extracted with EtOAc (20 mLx4). The combined organic phase was washed with brine (20 mL) and dried over Na2SO4. After concentration in vacuo, the residue was purified through column chromatography (hexanes / EtOAc: from 50:1 to 1:1) to afford the hydrolyzed product S35 ascolorless oil (1.68 g, 90% yield).

[0227] To a 100 mL round bottom flask were added hydrolyzed product S35 (1.68 g, 2.79 mmol, 1.0 equiv), THF (20 mL) and EhN (0.93 mL, 6.7 mmol, 2.4 equiv). The flask was cooled to 0 °C, TMSOTf (0.61 mL, 3.35 mmol, 1.2 equiv) was then added. The reaction mixture was stirred for 2 h at 22 °C until the starting material was fully consumed (monitored by TLC). The reaction mixture was quenched with sat. NaHCO3 solution (10 mL) and diluted with EtOAc (20 mL). The organic phase was separated from the aqueous phase, and the aqueous phase was extracted with EtOAc (20 mL x 2). The combined organic phase was washed with brine (15 mL) and dried over Na2SO4. After concentration in vacuo, the residue was purified through column chromatography (hexanes / EtOAc: from 50:1 to 3:1) to afford product 39 as white foam (1.72 g, 91% yield).

[0228] 4-O-Acetyl-l,5-anhydro-6-O-(2-tert-butoxycarbonylamino-3-O-tert-butyldimethylsilyl-4,6-O-isopropylidene-2-deoxy-a-D-glucopyranosyl)-2-deoxy-D-arabino-hex-l-enitol (S35): 'll NMR (400 MHz, CDCh) 56.40 (d, J = 6.1 Hz, 1H), 5.10 (dd, J = 8.6, 6.4 Hz, 1H), 4.99 (d. J = 10.0 Hz, 1H). 4.90-4.79 (m, 2H), 4.36-4.20 (m, 1H), 4.12-4.05 (m. 1H). 3.87-3.76 (m, 3H), 3.75-3.66 (m, 2H), 3.62-3.43 (m, 3H), 2.42 (brs, 1H), 2.17 (s, 3H), 1.46 (s, 3H), 1.43 (s. 9H), 1.38 (s, 3H), 0.87 (s, 9H), 0.07 (s, 3H), 0.06 (s. 3H); HRMS: m / z (ESI) calcd for C28H5oNOiiSi+, [M + H]+, 604.3148, found 604.3143.

[0229] 4-O-Acetyl-l,5-anhydro-6-O-(2-tert-butoxycarbonylamino-3-O-tert-butyldimethylsilyl-4,6-0-isopropylidene-2-deoxy-a-D-glucopyranosyl)-2-deoxy-3-0-trimethylsilyl-D-arabino-hex-l-enitol (39): [ct]^,3+60.4 (acetone, c = 1.0); IR vmax(neat) / cm-1: 2969 (w), 1740 (s), 1719 (s), 1504 (m), 1367 (s), 1228 (s), 1170 (m), 1080 (s), 838 (s), 779 (m);]H NMR (400 MHz, CDCh) 86.34 (d, J = 6.1 Hz, 1H), 5.09 (dd, J = 5.9, 7.0 Hz, 1H), 4.99 (d, J = 10.2 Hz, 1H), 4.81 (d, J = 3.6 Hz, 1H), 4.70 (dd, J = 6.1, 3.1 Hz, 1H), 4.25-4.19 (m, 1H), 4.15-4.07 (m, 1H), 3.86-3.75 (m, 3H), 3.71 (t, J = 10.4 Hz, 1H), 3.65 (dd, J = 12.1, 2.5 Hz. 1H), 3.62-3.52 (m, 2H), 3.52-3.41 (m, 1H), 2.11 (s, 3H), 1.46 (s, 3H), 1.43 (s, 9H), 1.38 (s, 3H), 0.86 (s, 9H), 0.12 (s, 9H), 0.07 (s, 3H), 0.05 (s, 3H);13C NMR (100 MHz, CDCh) 8 169.4, 155.4, 143.5, 103.3, 99.3, 99.1, 79.3, 75.4, 74.8, 71.0, 70.5, 65.9, 65.2, 63.7, 62.5. 55.5. 29.1, 28.4 (3C). 25.8 (3C). 21.1. 19.0, 18.3, 0.1 (3C), -4.2, -5.0; HRMS: m / z (ESI) calcd for C3iH58NOiiSi2+, [M + H]+, 676.3543, found 676.3555.

[0230] In Scheme 51, 40 was synthesized according to the following procedure:TBSO'BnO" oBnO- TBAF (1.5 equiv)BocHN^ AcOH (1 equiv)■O THF, rt, 2 hAcO- AcO- 89% yieldS34 40[0231 J To a 100 mL round bottom flask were added disaccharide S34 (1.22 g, 1.55 mmol, 1.0 equiv), THF (2.4 mL). The flask was cooled to 0 °C, a premixed solution of TBAF (2.3 mL of 1 M THF solution, 2.3 mmol, 1.5 equiv) and AcOH (2.3 mL, 40 mmol, 25.8 equiv) was then added. The reaction mixture was stirred for 2 h at 22 °C until the starting material was fully consumed (monitored by TLC). The reaction mixture was diluted with EtOAc (5 mL) quenched with saturated aq. NaHCO3 solution (10 mL). The organic phase was separated from the aqueous phase, and the aqueous phase was extracted with EtOAc (10 mL x 2). The combined organic phase was washed with brine (15 mL) and dried over NaqSOq. After concentration in vacuo, the residue was purified through column chromatography (hexanes / EtOAc: from 50:1 to 3:1) to afford the hydrolyzed product 40 as white foam (930 mg, 89% yield).

[0232] The glycal cis-aminoglycosylation was carried out on a 0.2 mmol scale by following this procedure.

[0233] To a flame-dried sealable 2-dram vial (vial A) equipped with a stir bar were added the pre-formed iron catalyst 1 Fe(Ll)(BF4)2(MeCN)(H2O)2 (17.5 mg, 0.03 mmol, 15 mol %) and freshly activated 5 A powdered molecular sieves (ca. 100 mg). After the vial was evacuated and backfilled with N2 twice, the vial was cooled to -40 °C. To a second flame-dried sealable 2-dram vial (vial B) was added glycal 39 (135 mg, 0.2 mmol, 1.0 equiv) and disaccharide 40 (188 mg, 0.28 mmol, 1.4 equiv). Vial B was evacuated and backfilled with N2 twice and then anhydrous CH2CI2 (0.4 mL) was added and cooled to -78 °C, then solution in vial B was quickly transferred into vial A via a syringe. To a third flame-dried sealable 2-dram vial (vial C) was added acyloxyl carbamate 3d (113 mg, 0.4 mmol, 2.0 equiv). Vial C was evacuated and backfilled with N2 twice and then anhydrous CH2CI2 (0.4 mL) was added. 3d was added to vial A using a syringe pump within 10 min. The reaction was kept at -40 °C for an additional 2 h and quenched by precipitating the iron catalyst with Et2O (4 mL) at the same temperature. The mixture was stirred for two minutes and subsequently warmed up to room temperature. The solution was then filtered through a piece of cotton and washed with saturated aq. NaHCO3 solution (2 mL). The organic phase was separated from the aqueous one, which was further extracted with CH₂Cl₂ (3 mL x 3). The combined organicphase was dried over anhydrous NasSOi and concentrated in vacuo. The residue was purified through a silica gel flash column (hexanes / ethyl acetate: from 20:1 to 1:1) to afford the desired product 41 as white foam (202 mg, 69% yield).

[0234] 3,4-Di-O-acetyl-l,5-anhydro-6-O-[(2-tert-butoxycarbonylamino-3-O-tert-butyldimethylsilyl-4,6-O-isopropylidene-2-deoxy-a-D-glucopyranosyl)-( 1— >6)-(4-O-acetyl-2-tert-butoxycarbonylamino-3-O-triinethylsilyl-2-deoxy-a-D-glucopyranosyl)-(l— >6)-(3,4-di-O-benzyl-2-tert-butoxycarbonylamino-2-deoxy-a-D-glucopyranosyl)]-2-deoxy-D-arabino-hex-l-enitol (41): [a]p2+91.1 (acetone, c = 1.0): IRvmax (neat) / cm-1: 2929 (w), 1718 (s). 1501 (s), 1367 (m), 1227 (s), 1155 (s), 1030 (s), 838 (m), 779 (m); ’H NMR (400 MHz, C6D6) 57.47-7.34 (m, 2H), 7.29-7.18 (m, 6H), 7.14-7.07 (m, 2H), 6.17 (d, J = 6.0 Hz, 1H), 5.82 (d, J = 9.3 Hz, 1H), 5.61-5.50 (m, 2H), 5.37 (t, J = 9.2 Hz. 1H). 5.24-5.13 (m, 2H), 4.95-4.82 (m, 3H), 4.79-4.66 (m. 3H), 4.59-4.49 (m, 2H), 4.40-4.28 (m, 2), 4.17-4.07 (m, 1H), 4.03-3.97 (m, 1H), 3.58-3.46 (m, 6H), 1.78 (s, 3H), 2.06 (s, 3H), 2.05 (s, 3H), 1.45 (brs, 30H), 1.36 (s, 3H), 0.86 (s, 9H), 0.09 (s, 9H), 0.06 (s, 3H), 0.05 (s, 3H); ‘H NMR (400 MHz, CDCh) 57.43-7.21 (m, 10H), 6.44 (d, J = 5.5 Hz, 1H), 5.45-5.39 (m, 1H), 5.38-5.28 (m, 1H), 5.09 (d, J = 9.7 Hz, 1H), 4.95-4.93 (m, 3H), 4.90-4.71 (m, 6H), 4.59-4.56 (m, 2H), 4.25-4.08 (m. 1H), 4.01-3.95 (m, 1H), 3.96-3.69 (m, 8H). 3.67-3.34 (m, 8H), 1.78 (s, 3H), 1.74 (s, 6H), 1.69 (s, 9H), 1.51 (s, 9H), 1.45 (s, 12H), 1.27 (s, 3H), 1.13 (s, 9H), 0.35 (s, 3H), 0.29 (s, 3H), 0.18 (s, 9H);13C NMR (100 MHz, CDC13) 8 170.5, 169.6, 168.8, 155.4, 155.3, 155.0, 145.8, 138.1. 138.0, 128.5 (2C), 128.3 (2C). 128.1 (2C), 127.9, 127.7, 127.5 (2C), 99.3. 99.2. 98.9.98.5, 81.1, 79.6, 79.5, 79.4, 78.0, 77.2, 75.6, 75.5, 74.9, 74.8, 72.2, 71.3, 71.1, 70.5, 69.3, 68.2, 67.6, 66.7, 65.0, 64.6, 63.7, 62.4, 55.5, 55.2, 54.4, 29.1, 28.5 (3C), 28.4 (3C). 28.3 (3C). 25.8 (3C), 21.1, 21.0, 20.9, 18.9, 18.2, 0.4 (3C), -4.3, -4.9; HRMS: m / z (ESI) calcd for C7iHii2N3O25Si2+, [M + H]+, 1462.7118, found 1462.7165. ^’CI-HI = 175.7 Hz, 175.0 Hz, 175.3 Hz.

[0235] FIG. 15 shows an un-decoupled HSQC analysis to determine the stereochemistry of 41 at the Cl positions.Scheme 52.

[0236] In Scheme 52, 42 was synthesized according to the following procedure.2,4,6-collidine (1 1 equiv) AgOTf (1 1 equiv) _ Lipase c c (20 wt%) CH2CI2 / PhMe 3:1 AcOH / AcONa buffer (pH=5) / actone 5 A MS, c- 0 18 M 3:1 1 2 equiv -40 °C, 3 h c = 0 11 M, 35 °C, 12 hS36 S37 81% yield S38 90% yield

[0237] To a 100 mL round bottom flask were added glycosyl bromide S36 (2.4 g, 3.6 mmol, 1.2 equiv), glycal S37 (690 mg, 3 mmol, 1.0 equiv), CH₂Cl₂ (15 mL), and freshly activated 5 A powdered molecular sieves (ca. 500 mg). The mixture was stirred for 3 minutes before 2,4,6-collidine (0.44 mL, 3.3 mmol, 1.1 equiv) was added. The flask was cooled to -40 °C, AgOTf (848 mg, 3.3 mmol, 1.1 equiv) in toluene (5 mL) was then added. The reaction mixture was stirred for 3 h at the same temperature until S37 was fully consumed (monitored by TLC). The reaction mixture was diluted with CH2O2 (20 mL) and quenched with saturated aq. NaHCO3 solution (10 mL). The organic phase was separated from the aqueous phase, and the aqueous phase was extracted with CH2CI2 (10 mL x 2). The combined organic phase was washed with brine (15 mL) and dried over Na2SC>4. After concentration in vacuo, the residue was purified through column chromatography (hexanes / EtOAc: from 50:1 to 4:1) to afford the product S38 as white foam (1.96 g, 81% yield). To a 100 mL round bottom flask were added Lipase from Candida rugosa ( 150 mg, 20 wt%), disaccharide S38 (730 mg, 0.9 mmol, 1.0 equiv), aqueous AcOH / AcONa buffer (6 mL, pH = 5.0) and 1.4-dioxane (2 mL). The mixture was stirred at 35 °C for 12 h. EtOAc (15 mL) was added to dilute the reaction. The organic phase was separated from the aqueous phase and the aqueous phase was further extracted with EtOAc (15 mLx4). The combined organic phase was washed with brine (20 mL) and dried over Na2SO4. After concentration in vacuo, the residue was purified through column chromatography (hexanes / EtOAc: from 50:1 to 3:2) to afford the hydrolyzed product 42 aswhite foam (621 mg, 90% yield).

[0238] 4-O-Acetyl-l,5-anhydro-3-O-(2,3,4,6-tetra-O-benzoyl-a-D-glucopyranosyl)-2-deoxy-D-arabino-hex-l-enitol (42): IRvmax(neat) / cm-1: 3509 (w), 2927 (w), 1720 (s), 1450 (w), 1247 (s), 1177 (w), 1093 (w), 1024 (s), 960 (s), 706 (s);NMR (400 MHz, CDCh) 68.17-8.03 (m, 2H), 7.92 (ddd, J = 9.8, 8.2, 1.4 Hz, 4H), 7.82-7.71 (m. 2H), 7.68-7.54 (m, 2H), 7.52-7.38 (m, 8H), 7.33-7.24 (m, 2H), 6.36 (dd, J = 6.2, 1.4 Hz, 1H), 6.04 (d, J = 5.3 Hz, 1H), 5.72 (dd, J = 3.2, 1.6 Hz, 1H), 5.46 (dt, J = 8.9, 1.4 Hz, 1H), 5.10 (dd, J = 8.2, 5.7 Hz, 1H), 4.81 (ddd, J = 5.3, 3.2, 1.2 Hz, 1H), 4.68 (dd, J = 6.2, 3.1 Hz, 1H), 4.50 (dd, J = 12.1, 3.0 Hz. 1H), 4.36 (dd, J = 12.1, 5.2 Hz, 1H), 4.12 (ddd, J = 5.4, 3.3, 1.3 Hz, 1H), 4.04 (ddd, J = 8.5, 5.2, 3.0 Hz, 1H), 3.85 (ddd, J = 8.3, 4.9, 3.4 Hz, 1H), 3.77-3.63 (m, 2H), 2.41 (dd, J = 8.3, 5.5 Hz, 1H), 2.05 (s, 3H); 13C NMR (100 MHz, CDCh) 5 170.4, 165.9, 165.1 (two peaks overlapped. 2C), 164.6, 144.9, 135.3. 133.7, 133.5, 133.0, 130.0 (2C), 129.8 (two peaks overlapped, 3C), 129.6 (2C), 129.0, 128.9, 128.5 (2C), 128.4 (2C), 128.3 (2C), 128.2 (2C), 126.3 (2C), 121.7, 100.4, 97.7, 76.4, 72.3, 69.2, 68.9, 68.4, 67.9, 67.6, 63.9, 60.7, 20.9; HRMS: m / z (ESI) calcd for C42H39O1 [M + H]+, 767.2334, found 767.2356. ^CI-HI = 183.4 Hz.

[0239] The glycal cis-aminoglycosylation was earned out on a 0.3 mmol scale by following the General Procedure C. The desired product 43 was purified through column chromatography (hexanes / ethyl acetate: from 20:1 to 2:1) as a white solid (252 mg, 71% yield, m.p. 113-115 °C).

[0240] 4-O-Acetyl-l,5-anhydro-[2,3,4-tri-O-benzoyl-a-D-glucopyranosyl-( 1— >3)]-[2-tert-butoxycarbonyIamino-3-O-tert-butyldimethylsilyI-4,6-O-isopropylidene-2-deoxy-a-D-glucopyranosyl-( 1— >6)]-2-deoxy-D-arabino-hex-l-enitol (43): [a]p3+45.4 (acetone, c = 1.0); IR vmax (neat) / cm-1: 2930 (w), 1722 (s), 1506 (m), 1368 (m), 1246 (s), 1171 (m), 1084 (m), 1024 (m), 874 (m), 708 (s);JH NMR (400 MHz, CDCh) 88.08 (d, J = 7.5 Hz, 2H), 7.92 (t, J = 7.0 Hz, 4H), 7.77 (dd, J=7.8Hz, 1.4Hz. 2H) 7.65-7.55 (m, 2H). 7.52-7.37 (m. 8H), 7.27 (t. J = 7.8 Hz, 2H), 6.32 (d, J = 6.1 Hz, 1H), 6.01 (d, J = 5.2 Hz, 1H), 5.73-5.68 (m, 1H), 5.45 (d, J = 8.8 Hz, 1H), 5.18 (dd, J=7.2 Hz, 6.1 Hz, 1H), 4.99 (d, J = 10.1 Hz, 1H), 4.82-4.74 (m, 2H), 4.69 (dd, J=6.12 Hz, 3.0 Hz, 1H), 4.48 (dd, J = 12.1, 2.7 Hz, 1H), 4.34 (dd, J = 12.1, 5.0 Hz, 1H), 4.09-4.05 (m, 1H), 4.05-3.94 (m, 2H), 3.83-3.71 (m, 3H), 3.70-3.40 (m, 5H), 2.06 (s, 3H), 1.44 (s, 3H), 1.39 (s, 9H), 1.36 (s, 3H), 0.85 (s, 9H), 0.05 (s. 3H), 0.04 (s, 3H);13C NMR (100 MHz. CDCh) 8 169.2, 165.9. 165.0, 164.5, 155.3, 144.7, 135.5, 133.7, 133.5, 133.0, 130.0 (2C), 129.82 (2C), 129.78, 129.6 (2C), 129.5, 129.0, 128.9, 128.5 (2C), 128.4 (2C), 128.3 (2C), 128.2 (2C), 126.3 (2C), 121.7, 100.8, 99.2, 99.0, 97.6, 79.2, 75.6, 74.8, 72.3, 70.9, 69.1. 68.5. 68.3. 68.1, 67.5, 65.0, 63.8, 63.7, 62.4, 55.4, 29.0, 28.3 (3C),25.7 (3C), 21.0, 18.9, 18.2, -4.3, -5.1; HRMS: m / z (ESI) calcd for C62H76NO20SP, [M + H]+, 1182.4724, found 1182.4741.1J13CI-HI = 171.2 Hz, 169.2 Hz.Scheme 53.•o•O pA— 0BnO—BnOT-^0. CH2CI2, 5 A MSBnO— -40 °C, c = 03 M, 2 h72% yield4 3d BzO—1.2 equiv 1 5 equiv

[0241] In Scheme 53, 44 was synthesized according to the following procedure.AgOTf (1 2 equiv) ■Ocollidine (1 3 equiv) PVOCH2CI2. 5 A MSezu Br BnO -78 °C, 12 h BnO- 1.2 equiv 1.0 equivTo a 100 mL flame-dried round bottom flask equipped with a stir bar, glycosyl bromide S36 (3.96 g, 6.0 mmol, 1.2 equiv), 3,4-dibenzyl glucal S39 (1.63 g, 5.0 mmol, 1.0 equiv), freshly activated 5 A molecular sieves, powder (ca. 2 g), and anhydrous CH₂Cl₂ (40 mL) were added. The mixture was stirred for 3 minutes before 2,4,6-collidine (0.86 mL, 6.5 mmol, 1.3 equiv) was added. The flask was cooled to -78 °C. AgOTf (1.54 g, 6.0 mmol, 1.2 equiv) in toluene (10 mL) was added using a syringe pump within 20 min. The reaction mixture was stirred for 12 h at -78 °C until the glucal S39 was fully consumed (monitored by TLC). The reaction mixture was quenched with sat. NaHCO₃ solution (15 mL). The organic phase was separated from the aqueous phase, and the aqueous phase was extracted with CH2CI2 (15 mL x 2). The combined organic phase was washed with brine (20 mL) and dried over Na2SO4. After concentration in vacuo, the residue was purified through column chromatography (hexanes / EtOAc: from 100:1 to 6:1) to afford the desired product 44 (3.08 g, 68% yield) as white foam.

[0242] The glycal cis-aminoglycosylation was carried out on a 0.3 mmol scale by following the General Procedure C. The desired product 45 was purified through column chromatography (hexanes / ethyl acetate: from 20:1 to 2:1) as white foam (330 mg, 72% yield).

[0243] Methyl 2,3,4,6-tetra-O-benzoyl- > -D-glucopyranosyl-(l—>6)-3,4-di-O-benzyl-2-tert-butoxycarbonylamino-2-deoxy-a-D-gIucopyranosyl-(l— >6)-2,3,4-tri-O-benzoyl-a-D-glucopyranoside (45): [a]^,3+60.5 (acetone, c = 1.0); IRmax (neat) / cm-1: 2927 (w), 1727 (s), 1451 (m), 1391 (s), 1261 (s), 1150 (s), 1027 (m), 708 (m); ‘H NMR (400 MHz, CDCh) 88.02-7.96 (m, 4H), 7.96-7.92 (m. 2H), 7.89-7.82 (m, 6H), 7.85-7.80 (m, 2H), 7.57-7.45 (m, 4H), 7.45-7.21 (m, 26H), 7.07 (d, J = 5.7 Hz, 1H), 6.09 (t, J = 9.9 Hz, 1H), 5.90-5.79 (m, 1H), 5.71-5.55 (m, 2H), 5.45 (t, J = 8.6 Hz, 1H), 5.22 (dd, J = 9.9, 3.6 Hz, 1H), 5.18-5.11 (m, 1H), 4.91 (d, J = 10.0 Hz, 1H), 4.77 (d, J = 7.8 Hz, 1H), 4.74 (d. J = 2.9 Hz, 1H), 4.64-4.63 (m. 2H), 4.59 (dd. J = 12.2, 3.5 Hz, 1H), 4.54-4.42 (m, 2H), 4.26 (d, J = 11.1 Hz, 1H), 4.14-3.95 (m, 3H), 3.92-3.82 (m, 1H), 3.65 3.49 (m, 4H), 3.49-3.31 (m, 5H), 1.47 (s, 9H);13C NMR (100 MHz. CDCh) 8 166.1, 165.81, 165.79, 165.7, 165.2, 165.1. 164.8, 155.3, 138.4, 138.1. 133.4 (two peaks overlapped, 2C), 133.3, 133.2. 133.11, 133.08, 133.0, 130.0 (2C), 129.9 (2C), 129.8 (2C), 129.71 (two peaks overlapped, 4C), 129.67 (two peaks overlapped, 4C), 129.5, 129.2 (two peaks overlapped, 2C), 129.1, 128.9, 128.8, 128.7, 128.4 (four peaks overlapped, 8C), 128.31 (2C), 128.27 (2C), 128.2 (two peaks overlapped, 4C), 128.1 (2C), 128.0 (2C), 127.6 (2C), 127.5, 127.4, 101.2, 98.2, 97.0, 80.6, 79.5, 78.0, 74.8, 74.5, 72.8, 72.2, 72.1, 71.8, 70.6, 70.2, 69.8, 68.8. 68.4, 68.2, 64.9, 63.2, 55.7, 54.0, 28.4 (3C); HRMS: m / z (ESI) calcd for C87H84NO2 [M + H]+, 1526.5378, found 1526.5406. ^’CI-HI - 173.2 Hz, 172.8 Hz, 160.8 Hz.Scheme 54.

[0244] In Scheme 54, 46 was synthesized according to the following procedure.TBAF (1 1 equiv)AcOH (1.1 equiv)THF, rt, c = 1 M3 h97% yield38 46To a 2-dram vial equipped with a stir bar were added glycal 38 (423 mg, 0.7 mmol, 1 equiv), TBAF (0.77 mL of 1 M THF solution, 0.77 mmol, 1.1 equiv), AcOH (44 pL, 0.77 mmol, 1.1 equiv). The mixture was stirred for 3 h until the starting material was fully consumed (monitored by TLC). The mixture was then diluted with EtOAc (2 mL) and washed with saturated aq. NaHCO₃ solution (1 mL). The organic phase was separated from the aqueous one, which was further extracted with EtOAc (2 mL x 3). The combined organic phase was dried over anhydrous Na2SO4 and concentrated in vacuo. The residue was purified through a silica gel flash column (hexanes / ethyl acetate: from 20:1 to 1:1) to afford the desired product 46 as white foam (361 mg, 91% yield).

[0245] The glycal cis-aminoglycosylation was carried out on a 0.2 mmol scale according to the following procedure. To a flame-dried sealable 2-dram vial (vial A) equipped with a stir bar were added the pre-formed iron catalyst 1 Fe(Ll)(BF4)2(MeCN)(H2O)2 (17.5 mg, 0.03 mmol, 15 mol %) and freshly activated 5 A powdered molecular sieves (ca. 100 mg). After the vial was evacuated and backfilled with N2 twice, the vial was cooled to -40 °C. To a second flame-dried sealable 2-dram vial (vial B) was added glycal S6 (52 mg, 0.2 mmol, 1.0 equiv) and disaccharide 46 (149 mg, 0.28 mmol, 1.4 equiv). Vial B was evacuated and backfilled with N2 twice and then anhydrous CH2CI2 (0.4 mL) was added and cooled to -78 °C, then vial B solution was quickly transferred into vial A via a syringe. To a third flame-dried sealable 2-dram vial (vial C) was added acyloxyl carbamate 3g (157 mg, 0.4 mmol, 2.0 equiv). Vial C was evacuated and backfilled with N2 twice and then anhydrous CH₂Cl₂ (0.4 mL) was added. 3g was added to vial A using a syringe pump within 10 min. The reaction was kept at -40 °C for an additional 2 h and quenched by precipitating the iron catalyst with Et2O (4 mL) at the same temperature. The mixture was stirred for two minutes and subsequently warmed up to room temperature. The solution was then filtered through a piece of cotton and washed with saturated aq. NaHCCL solution (2 mL). The organic phase was separated from the aqueous one, which was further extracted with CH2CI2 (3 mL x 3). The combined organic phase was dried over anhydrous Na2SC>4 and concentrated in vacuo. The residue was purified through a silica gel flash column (hexanes / ethyl acetate: from 20:1 to 1:1) to afford the desired product 47 as white foam (121 mg, 67% yield).

[0246] 3,4-Di-O-acetyl-l,5-anhydro-6-O-[(2-tert-butoxycarbonylamino-3-O-trimethylsilyl-4,6-O-isopropylidene-2-deoxy-a-D-glucopyranosyl)-(l— >3)-(2-tert-butoxycarbonylamino-4,6-O-isopropylidene-2-deoxy-a-D-glucopyranosyl)]-2-deoxy-D-arabino-hex-l-enitol (47): IR Vmax (neat) / cm-1: 2930 (w), 1721 (s), 1503 (s), 1247 (m), 1228 (m), 1172 (m), 1082 (m), 886 (m), 758 (m);1H NMR (400 MHz, CDCh) 86.44 (d, J = 6.0 Hz, 1H), 5.38-5.33 (m, 1H), 5.32-5.22 (m, 2H), 4.96 (dd, J = 12.1, 3.7 Hz, 2H), 4.83-4.80 (m, 2H), 4.18-4.17 (m, 1H), 4.03-3.98 (m, 1H), 3.88-3.75 (m, 4H), 3.73-3.62 (m, 7H), 3.57-3.47 (m, 2H), 2.09 (s, 3H), 2.04 (s, 3H), 1.48 (s. 9H), 1.44 (s, 15H), 1.38 (s, 3H). 1.36 (s, 3H), 0.08 (s, 9H);13C NMR (100 MHz, CDCh) 8 170.4, 169.4, 155.5, 155.2, 145.9, 100.7, 99.6, 99.2, 99.1, 98.8, 80.1, 79.3, 75.62, 75.57, 75.0, 74.3, 71.7, 68.0, 67.5, 64.7, 64.3, 63.8, 62.4, 62.0, 55.4, 53.6, 29.1, 28.9, 28.5 (3C), 28.1 (3C), 21.0, 20.9, 19.1, 18.9, 0.4 (3C); HRMS: m / z (ESI) calcd for C41H69N2O18SP. [M + H]+, 905.4309, found 905.4321.1J13ci in - 175.6 Hz, 175.6 Hz.Scheme 55.1.4 equiv 1 6 equiv

[0247] In Scheme 55, 48 was synthesized according to a modified procedure described by Schell, P., et al., Synthesis and Transformations of D-Glucuronic and L-Iduronic Acid Glycals. Tetrahedron Lett. 42, 3811-3814 (2001).

[0248] The glycal cis-aminoglycosylation was earned out on a 0.5 mmol scale by following the General Procedure A with the modifications: the reaction was performed at 0.5 M with 1.4 equiv of 48 and 1.6 equiv of 3f. The desired product 49 was purified through column chromatography (hexanes / ethyl acetate: from 20:1 to 3:1) as white solid (246 mg, 78% yield, m.p.121.4-123.8 °C).

[0249] Methyl 4-O-acetyl-3-O-(2-tert-butoxycarbonylamino-3-O-tert-butyldimethylsilyl-4,6-O-isopropylidene-2-deoxy-a-D-glucopyranosyl)-D-glucuronal (49):[a]p5+27.8 (acetone, c = 1.0); IRvmax (neat) / cm-1: 2930 (w). 1760 (m), 1707 (m), 1655 (m), 1520 (m), 1370 (m), 1242 (s), 1165 (m), 1131 (s), 1032 (m), 1012 (s), 914 (s), 795 (m); ^ NMR (400 MHz, CDCh) 56.54 (d, J = 6.3 Hz, 1H), 5.36 (td, J = 3.1, 1.4 Hz, 1H), 4.95-4.81 (m, 2H), 4.79-4.74 (m, 1H), 4.70 (d. J = 10.1 Hz. 1H), 3.86 (ddd, J = 5.1, 2.6, 1.3 Hz, 1H), 3.80-3.70 (m, 5H), 3.65 (t, J = 10.3 Hz, 1H), 3.56 (td, J = 9.6, 5.0 Hz, 1H), 3.51-3.39 (m, 2H), 2.06 (s, 3H), 1.41 (s, 12H), 1.34 (s, 3H), 0.81 (s, 9H), 0.01 (s, 3H), 0.00 (s, 3H);13C NMR (100 MHz, CDCh) 8 169.5, 167.8, 155.3, 144.8, 100.1. 99.9. 99.3. 79.39. 74.8. 72.7. 71.1. 68.6, 68.0, 64.2, 62.2, 55.2, 52.6, 28.9, 28.4 (3C), 25.6 (3C), 20.8, 18.8, 18.1, -4.3, -5.1; HRMS: m / z (ESI) calcd for C29H50NO12SP, [M + H]+, 632.3097, found 632.3088. ^’CI-HI = 172.2 Hz.Scheme 56.50 3h 511 4 equiv 1.8 equiv

[0250] In Scheme 56, 50 was synthesized according to a modified procedure described by Schell, P., et al., Synthesis and Transformations of D-Glucuronic and L-Iduronic Acid Glycals. Tetrahedron Lett. 42, 3811-3814 (2001).

[0251] The glycal cis-aminoglycosylation was carried out on a 0.5 mmol scale by following the General Procedure A with the modifications; the reaction was performed at 0.5 M with 1.4 equiv of 50 and 1.8 equiv of 3h. The desired product 51 was purified through column chromatography (hexane s / acetone: from 20:1 to 8:1) as white solid (180 mg, 57% yield).

[0252] Methyl 3-O-allyl-4-O-(2-tert-butoxycarbonylamino-3-O-tert-butyldimethylsilyl-4,6-O-isopropylidene-2-deoxy-a-D-glucopyranosyl)-D-glucuronal (51): [a]p5+27.8 (acetone, c = 1.0); IRvmax (neatycm1: 2929 (w), 1720 (m), 1503 (m), 1367 (m), 1248(s), 1171 (s), 1128 (s), 1075 (s), 1033 (s), 995 (s), 875 (s), 778 (s); 'H NMR (400 MHz, CDCh) 86.62 (d, J - 6.3 Hz, 1H), 5.89-5.74 (m, 1H), 5.22 (dd, J = 17.2, 1.7 Hz, 1H), 5.18-5.09 (m, 1H). 4.99 (d, J = 3.9 Hz. 1H),4.97-4.89 (m, 1H), 4.77 (dd, J = 3.2, 1.3 Hz, 1H), 4.53 (d, J = 9.9 Hz, 1H), 4.28 (d, J = 1.8 Hz, 1H), 4.02-3.91 (m, 1H), 3.94-3.85 (m, 1H), 3.86-3.63 (m, 7H), 3.59 (td, J = 9.6, 4.9 Hz, 1H), 3.50 (p, J = 8.7 Hz, 2H), 1.44 (s. 3H), 1.41 (s, 9H). 1.36 (s, 3H), 0.83 (s, 9H), 0.03 (s. 3H), 0.02 (s, 3H);13C NMR (100 MHz, CDCh) 8 168.0, 155.1, 145.3, 134.2, 117.5, 99.3, 99.0, 98.0, 79.5, 74.6, 73.9, 72.1, 71.0, 68.5, 67.0, 64.4, 62.2, 55.4, 52.2, 29.0, 28.4 (3C), 25.7 (3C), 18.9, 18.2, -4.2, -5.1; HRMS: m / z (ESI) calcd for C3oH52NOiiSi+, [M + H]+, 630.3304, found 630.3326.1J13ci-m = 170.6 Hz.[02531 Additional glycosyl acceptors were explored as shown in Scheme 57.Scheme 57.Fe(L1 )(BF4)2(MeCN)(H2O)2(1) (10 - 15 mol%) CH2CI2 / 1,4-dioxane = 9:1 or CH2CI25 A MS, -40 °C FT O c = 05 M, 2-4 h72% yield 68% yield 67% yield 76% yieldO 'PrR= n-C5Hi R= n-C5Hi i 73% yield 58% yield 54% yieldR= n-CsHu R= n-CsHu57% yield 45% yield

[0254] Still more additional glycosyl acceptors were explored as shown in Scheme 58. Scheme 58.Fe(L1)(BF4)2(MeCN)(H2O)2v— o (1) (10 - 15 mol%) (R1o)nr<l^ + R2— OH CH2CI23 A / 5 A molecular sieves -20 - 40 °C 1 - 4 h5d 74% 68% 82% conversionMe81% 76% 88% 81%87% conversion62% (1:3 rr) 30%72% conversion

[0255] The compounds in Schemes 57 and 58 were prepared according to General Procedure D.

[0256] General Procedure D. To a flame-dried sealable 2-dram vial (vial A) equipped with a stir bar were added a glycal (0.5 mmol, 1.0 equiv), a glycosyl acceptor (0.7 mmol, 1.4 equiv), iron catalyst 1 Fe(Ll)(BF4)2(MeCN)(H2O)2 (44 mg, 0.075 mmol, 15 mol %) and freshly activated 5 A molecular sieves, powder (ca. 150 mg). After the vial was evacuated and backfilled with N2 three times, anhydrous CH2CI2 (0.5 mL) was added and the solution was cooled to -40 °C. To a second flame-dried sealable 2-dram vial (vial B) was added amination reagent 3 (0.8 mmol, 1.6 equiv). Vial B was evacuated and backfilled with N2 three times and then anhydrous CH2CI2 (0.5 mL) wasadded. Amination reagent 3 was added to vial A using a syringe pump within 10 min. The reaction was kept at -40 °C for an additional 2 h and quenched by precipitating the iron catalyst with Et2<3 (4 mL) at the same temperature. The mixture was stirred for two minutes and subsequently warmed up to room temperature. The solution was then filtered through a piece of cotton and washed with saturated aq. NaHCO3 solution (2 mL). The organic phase was separated from the aqueous one, which was further extracted with CH2CI2 (3 mL x 3). The combined organic phase was dried over anhydrous Na2SC>4 and concentrated in vacuo. The residue was purified through a silica gel flash column to afford the desired glycal cA-aminoglycosylation product.Scheme 59.

[0257] The glycal cA-aminoglycosylation was earned out on a 0.5 mmol scale by following the General Procedure D. The desired product was purified through a silica gel flash column (hexanes / diethyl ether: from 20:1 to 6:1) as white foam (191 mg, 74% yield).Me OH1.4 equiv

[0258] ’H NMR (400 MHz, CDCI3) 84.87 (d, J= 3.9 Hz, 1H), 4.60 (d, J = 10.0 Hz, 1H), 3.85-3.72 (m, 2H), 3.75-3.63 (m, 2H), 3.59 (t,. / = 9.2 Hz, 1H). 3.49 (td,. / = 9.1, 3.4 Hz, 2H), 1.89- 1.80 (m, 2H), 1.72 (h. J = 4.4 Hz, 2H). 1.58-1.46 (m. 5H), 1.43 (s. 9H). 1.39 (s, 3H). 1.34-1.19 (m.4H), 0.86 (s, 9H), 0.06 (s, 3H), 0.05 (s, 3H);13C NMR (100 MHz, CDCI3) 6 155.2, 99.2, 97.1, 79.1, 75.9, 74.9, 71.3, 63.6, 62.4, 55.5, 33.4, 31.4, 29.0, 28.3 (3C). 25.7 (3C). 25.5, 24.1, 23.8, 18.9, 18.2, -4.2, -5.1; HRMS: m / z (ESI) calcd for C26H50NO7Si+, [M+H]+, 516.3351, found 516.3366. J13CI-HI = 170.2 Hz.Scheme 60.Fe(L1)(BF4)2(MeCN)(H2O)2(1) (15 mol%)TBSO^\TBSO^V^-O CH2CI2, 5 A MSTBSO^U -^ -24 °C, c = 0.5 M, 4 h1.4 equiv 1.6 equiv 69% yield77% conversion

[0259] The glycal ds-aminoglycosylation was carried out on a 0.5 mmol scale by following the General Procedure D with the modifications: reaction was performed at -24 °C. The desired product was purified through a silica gel flash column (hexanes / diethyl ether: from 100:1 to 19:1) as a colorless syrup (262 mg, 69% yield, 77% conversion).

[0260] XH NMR (400 MHz, CDCh)85.01 (d,. / = 10.0 Hz, 1H), 4.86 (d,.7 = 2.8 Hz, 1H), 3.94-3.74 (m, 4H), 3.66 (t, J= 8.8 Hz, 1H), 3.58 (t, J= 5.5 Hz, 1H), 3.28 (td, J = 10.5, 4.3 Hz, 1H), 2.29-2.11 (m, 2H). 1.71-1.57 (m, 2H), 1.46-1.34 (m, 11H). 1.31-1.18 (m, 2H), 1.10-0.95 (m, 2H), 0.95-0.78 (m, 32H), 0.75 (d, J= 7.0 Hz, 3H), 0.13 (s, 3H), 0.11 (s, 3H), 0.10 (s, 6H), 0.06 (s, 6H);13C NMR (100 MHz, CDCh) 8 155.3, 96.9, 80.8, 78.7, 77.2, 73.0, 71.0. 62.1, 54.1, 48.5, 42.7, 34.3, 31.6, 28.3 (3C), 26.1 (3C), 26.0 (3C), 25.9 (3C), 25.2, 22.9, 22.3, 21.1, 18.3, 18.1, 18.0. 15.8. -3.3. -3.5, -3.9, -4.1, -5.2, -5.4; HRMS: m / z (ESI) calcd for C39H82NO7Si3+, [M+H]+, 760.5394, found 760.5379. J13CI-HI = 170.4 Hz.Scheme 63.1.4 equiv

[0261] The glycal cA-aminoglycosylation was carried out on a 0.5 mmol scale by following the General Procedure D. The desired product was purified through a silica gel flash column (hexanes / diethyl ether: from 100:1 to 7:1) as a white solid (179 mg, 76% yield).

[0262] ‘H NMR (400 MHz, CDCh) 85.84 (ddt, J= 16.3, 10.5, 5.8 Hz, 1H), 5.23 (dq, J = 17.2, 1.6 Hz, 1H), 5.16 (dq, J = 10.4. 1.4 Hz, 1H), 4.74 (d, J = 3.7 Hz, 1H). 4.61 (d, J = 10.0 Hz, 1H), 4.13-4.03 (m, 1H), 3.91 (dd, J= 13.0, 6.2 Hz, 1H), 3.81-3.71 (m, 2H), 3.67 (t, J = 10.4 Hz, 1H), 3.62-3.50 (m, 2H), 3.45 (t, J= 9.1 Hz, 1H), 1.42 (s, 3H), 1.38 (s, 9H), 1.34 (s, 3H), 0.81 (s, 9H), 0.00 (s, 3H), -0.01 (s, 3H);13C NMR (100 MHz, CDCh) 8 155.2, 133.8, 118.2. 100.4, 98.3, 79.5, 75.0, 71.3, 68.4, 63.8, 62.5, 55.5, 29.1, 28.5 (3C), 25.8 (3C), 25.8, 19.0, 18.3, -4.1, -5. O.; HRMS: m / z (ESI) calcd for C23H44NO7Si+, [M+H]+, 474.2882, found 474.2854. J13CI-HI = 170.4 Hz.Scheme 63A.Fe(L1)(BF4)2(MeCN)(H2O)2(1) (15 mol%) CH2CI2, 3 A MS * -40 °C, c = 0.5 M, 3 h1.4 equiv 1.6 equiv

[0263] The glycal ch-aminoglycosylation was carried out on a 0.5 mmol scale by following the General Procedure D. The desired product was purified through a silica gel flash column (hexanes / ethyl acetate: from 100:1 to 8:1) as a white solid (175 mg, 68% yield, m.p. 82.4-84.6 °C).

[0264] 1H NMR (400 MHz, CDCh) 84.85 (d, J = 3.7 Hz, 1H), 4.62 (d, J = 10.0 Hz, 1H), 4.01-3.77 (m, 4H), 3.71 (t, J = 10.0 Hz, 1H). 3.65-3.47 (m, 3H), 1.46 (s, 3H), 1.42 (s, 9H), 1.39 (s, 3H), 0.87 (s, 9H), 0.06 (s, 3H), 0.05 (s, 3H);13C NMR (100 MHz, CDCh) 6 155.2, 123.6 (d, J = 278.5 Hz), 99.9, 99.4, 79.7, 74.6, 70.8, 64.9 (q, J = 35.0 Hz), 64.3, 62.2, 55.3, 29.0, 28.3 (3C), 25.7 (3C), 18.9, 18.2, -4.2, -5.1.;19F NMR (376 MHz, CDCh) 8 -74.07 (t, J = 8.7 Hz); HRMS: m / z (ESI) calcd for C22H41F3NO7+, [M+H]+, 516.2599, found 516.2589.= 177.0 Hz.Scheme 64.

[0265] The glycal d -aminoglycosylation was carried out on a 0.5 mmol scale by following the General Procedure D. The desired product was purified through a silica gel flash column (hexanes / ethyl acetate: from 100:1 to 8:1) as a colorless syrup (188 mg, 81% yield).

[0266] ‘H NMR (400 MHz, CDCh) 87.36-7.28 (m, 2H), 7.26-7.16 (m, 3H), 5.85 (ddt, J = 16.3, 10.6, 5.4 Hz, 1H), 5.25 (dq,.7= 17.2, 1.8 Hz, 1H), 5.12 (d, J = 10.5 Hz, 1H), 4.73 (d, 7= 3.7 Hz, 1H), 4.55 (d, 7= 10.1 Hz, 1H), 4.30 (dd, 7= 13.3, 5.0 Hz, 1H), 4.03 (dd, 7= 13.2, 5.9 Hz, 1H), 3.96-3.77 (m, 2H). 3.77-3.57 (m, 4H), 3.55-3.32 (m, 2H), 2.89 (td, 7= 6.9, 1.8 Hz. 2H), 1.47 (s, 3H), 1.44 (s, 9H), 1.39 (s, 3H);13C NMR (100 MHz, CDCh) 8 155.4, 138.5, 135.3, 128.8, 128.4, 126.4, 116.1, 99.2, 98.5. 79.4, 77.5, 77.0, 76.7, 74.9, 72.8, 68.4, 63.8, 62.4, 53.8, 35.9, 29.1, 28.3 (3C), 19.1; HRMS: m / z (ESI) calcd for C25H38NO7Si+. [M+H]+. 464.2643, found 464.2640.^J13CI-HI = 170.5 Hz.Scheme 65.2.0 equiv 1.6 equiv 76% yield87% conversion

[0267] The glycal cz -aminoglycosylation was carried out on a 0.5 mmol scale by following the General Procedure D. The desired product was purified through a silica gel flash column (hexanes / diethyl ether: from 1:0 to 19:1) as a colorless syrup (191 mg, 76% yield).

[0268] NMR (400 MHz, CDCh) 54.71 (d, J= 3.8 Hz, 1H), 4.63 (d. J= 10.1 Hz, 1H).3.85-3.74 (m, 2H), 3.70 (t, J= 10.4 Hz, 1H), 3.65-3.52 (m, 3H), 3.51-3.44 (m, 1H), 3.36 (dt, J = 9.9, 6.7 Hz. 1H), 1.58 (p, J= 6.9 Hz, 2H), 1.46 (s, 3H), 1.42 (s, 9H), 1.38 (s, 3H), 1.35-1.28 (m, 4H), 0.92 (t, J= 6.8 Hz, 3H), 0.85 (s, 9H), 0.05 (s, 3H), 0.04 (s, 3H);13C NMR (100 MHz, CDCh) 6 155.2, 99.3, 98.8, 79.3, 74.9, 71.4, 68.1, 63.6, 62.5, 55.6, 29.03, 28.97, 28.4 (3C), 28.2, 25.8 (3C), 22.4, 18.9, 18.2, 14.0, -4.2, -5.1; HRMS: m / z (ESI) calcd for C25H50NO7Si+, [M+H]+, 504.3351, found 504.3341. J13CI-HI = 170.3 Hz.Scheme 66.Fe(L1)(BF4)2(MeCN)(H2O)2(1) (15 mol%) CH2CI2, 5 A MS1.4 equiv 1.5 equiv

[0269] The glycal d -aminoglycosylation was carried out on a 0.5 mmol scale by following the General Procedure D. The desired product was purified through a silica gel flash column (hexanes / diethyl ether: from 100:1 to 8:1) as a colorless syrup (253 mg, 88% yield).

[0270] ’H NMR (400 MHz, CDCh) 55.01 (d, J= 4.0 Hz, 1H), 4.49 (d. J= 10.0 Hz, 1H), 4.16-4.07 (m, 1H), 3.81-3.63 (m, 3H), 3.57 (t, 7= 9.2 Hz, 1H), 3.47 (t, 7= 8.7 Hz, 1H), 1.47 (s, 3H), 1.42 (s, 9H), 1.39 (s, 9H), 1.22 (s, 9H), 0.86 (s, 9H), 0.053 (s, 3H), 0.046 (s, 3H);13C NMR (100 MHz, CDCh) 8 155.2. 99.2. 93.4. 79.2, 75.3, 75.1, 71.2, 63.2, 62.5, 55.7, 29.1, 28.44 (3C), 28.39 (3C), 25.7 (3C), 18.9, 17.7, -4.2, -5.1; HRMS: m / z (ESI) calcd for C24H48NO7Si+, [M+H]+, 490.3195, found 490.3201.XJ13CI-HI = 168.0 Hz.Scheme 68.Me1.4 equiv 1.5 equiv 81 % yield

[0271] The glycal cd-aminoglycosylation was carried out on a 0.5 mmol scale by followingthe General Procedure D. The desired product was purified through a silica gel flash column (hexanes / diethyl ether: from 100:1 to 9:1) as white foam (229 mg, 81% yield).10272] NMR (400 MHz, CDCh) 55.08 (d, J= 4.0 Hz, 1H), 4.47 (d. J= 10.0 Hz, 1H). 3.77-3.58 (m, 4H), 3.53 (t, J= 9.2 Hz, 1H), 3.42 (t, J= 8.9 Hz, 1H), 2.14-2.04 (m, 3H), 1.79-1.63 (m, 7H), 1.62-1.49 (m, 7H), 1.41 (s, 3H), 1.37 (s, 8H), 1.34 (s, 3H), 0.81 (s, 10H), 0.00 (s. 3H), -0.01 (s, 3H);13C NMR (100 MHz, CDCh) 5 154.8, 98.3, 91.9, 79.2, 75.1, 74.5, 71.3, 63.3, 62.6, 55.7, 40.9 (3C), 36.2 (3C), 30.6 (3C), 29.1, 28.5 (3C), 25.8 (3C), 19.0, 18.3, -4.1, -5.0; HRMS: m / z (ESI) calcd for C30H54NO7Si+, [M+H]+, 568.3664, found 568.3682. J13CI-HI = 170.4 Hz.Scheme 69.MeTBSO1.6 equiv

[0273] The glycal ds-aminoglycosylation was carried out on a 0.5 mmol scale by following the General Procedure D. The desired product was purified through a silica gel flash column (hexanes / diethyl ether: from 20:1 to 7:1) as white foam (219 mg, 81% yield).

[0274] JH NMR (400 MHz, CDCh) 54.96 (d, J = 10.8 Hz, 1H), 4.79 (d, J = 3.6 Hz, 1H), 3.93-3.76 (m, 3H), 3.75-3.63 (m, 4H), 3.54-3.48 (m, 1H), 1.48 (s, 9H), 1.47 (s, 3H), 1.44 (s, 9H), 1.39 (s, 3H), 0.86 (s, 9H), 0.06 (s, 3H), 0.05 (s, 3H);13C NMR (100 MHz, CDCh) 8 168.6, 155.3, 99.3, 99.2, 81.9, 79.2, 74.7, 71.0, 64.8. 64.1, 62.3, 55.3, 28.9, 28.3 (3C), 28.0 (3C), 25.7 (3C), 18.8, 18.2, -4.3, -5.1; HRMS: m / z (ESI) calcd for C26H50NO9Si+, [M+H]+, 548.3249, found 548.3257.= 170.0 Hz.Scheme 70.62% yield1:3 rr

[0275] The glycal c / .v-aminoglycosylation was carried out on a 0.3 mmol scale by following the General Procedure D. The desired product was purified through a silica gel flash column (hexanes / ethyl acetate: from 100:1 to 7:1) as white foam (129 mg, 1:3 r.r., 62% yield).

[0276] ’H NMR (400 MHz, CDCh) 84.99 (d, J = 3.8 Hz, 1H), 4.84 (d, J= 1.8 Hz, 1H), 4.59 (d, J = 9.5 Hz, 1H), 4.22 (q, J = 5.9 Hz, 1H), 4.04 (dd, 7 = 4.9, 1.8 Hz, 1H), 3.98 (q, J= 5.1 Hz, 1H), 3.92-3.77 (m. 2H), 3.76-3.62 (m, 4H), 3.63-3.50 (m, 2H), 3.35 (s, 3H), 2.37 (d. J = 7.2 Hz, 1H), 1.47 (s, 3H), 1.44 (s, 9H), 1.39 (s, 3H), 0.91 (s, 9H), 0.87 (s, 9H), 0.087 (s, 3H), 0.084 (s, 3H), 0.064 (s, 3H), 0.055 (s, 3H);13C NMR (100 MHz, CDCh) 8 155.3, 106.2, 99.5, 98.8, 84.1, 80.9, 79.8, 74.7, 71.7, 70.9, 64.5, 64.3, 62.2, 55.5, 55.3, 29.0, 28.4 (3C), 25.9 (3C), 25.7 (3C), 18.9, 18.4, 18.2, -4.1, -5.0, -5.4, -5.5; HRMS: m / z (ESI) calcd for C32H64NO11Si2+, [M+H]+, 694.4012, found 694.4020. J13CI-HI = 171.3 Hz.

[0277] 1H NMR (400 MHz, CDCh) 4.94 (s, 1H), 4.84 (s, 1H), 4.80-4.74 (m, 1H), 4.30 (dd,.7= 6.6, 4.5 Hz, 1H), 4.09 (d, J= 2.5 Hz, 1H), 3.84-3.66 (m, 5H), 3.63 (m, 3H), 3.51 (d, J= 9.0 Hz, 1H), 3.33 (s, 3H), 2.60 (brs. 1H) 1.46 (s. 3H), 1.42 (s, 9H). 1.38 (s, 3H), 0.91 (s, 9H), 0.86 (s. 9H), 0.10 (s, 3H), 0.09 (s, 3H), 0.07 (s, 3H), 0.06 (s, 3H);13C NMR (100 MHz, CDCh) 8 155.6, 108.2, 99.4, 98.1, 81.6, 80.1, 74.7, 73.1, 71.2, 70.7, 64.6, 64.2, 62.2, 56.1, 55.1, 28.9, 28.3 (3C), 26.0 (3C), 25.8 (3C), 18.9, 18.5, 18.2, -4.0, -5.1, -5.3 (2C); HRMS: m / z (ESI) calcd for C32H64NO11Si2+, [M+H]+, 694.4012, found 694.4026. J13CI-HI = 171.1 Hz.Scheme 71.

[0278] The glycal ch-aminoglycosylation was carried out on a 0.3 mmol scale by following the General Procedure D. The desired product was purified through a silica gel flash column (hexanes / ethyl acetate: from 100:1 to 1:1) as white foam (67 mg, 30% yield).

[0279] ’H NMR (400 MHz, CDCh) 85.05 (dd, J = 10.3, 8.8 Hz, 1H), 4.97 (d, J= 3.3 Hz, 1H), 4.84 (d, J= 3.7 Hz, 1H). 4.60 (d, J = 10.0 Hz, 1H), 4.40-4.31 (m, 2H), 4.25-4.16 (m, 1H), 4.10 (d,.7= 2.7 Hz, 1H), 4.05 (dd,.7= 11.1, 7.0 Hz, 1H), 4.01-3.90 (m, 1H), 3.93-3.84 (m, 2H), 3.76 (dd, J = 10.4, 8.8 Hz, 1H), 3.62-3.48 (m, 6H), 3.46 (s, 3H), 3.43 (s, 3H), 2.08 (s, 3H), 2.06 (s, 4H), 2.05 (s. 2H), 1.42 (s, 9H). 0.84 (s, 9H), 0.07 (s, 3H), 0.01 (s. 3H);13C NMR (100 MHz. CDCh)13CNMR (100 MHz, CDCh) 8 171.0, 170.1, 169.3, 154.7, 99.5, 97.6, 80.4, 78.8, 77.1, 73.2, 71.0, 70.6, 68.3, 68.0, 61.9, 61.4, 58.5, 58.2, 55.4, 55.4, 28.3 (3C), 25.6 (3C), 21.2, 20.8, 20.7, 17.9, -4.4 (2C); HRMS: m / z (ESI) calcd for C32H58NO15Si+, [M+HJ+, 724.3570, found 724.3535.= 170.4 Hz.Scheme 72.NHCbz 1.4 equiv 1.5 equiv 72% yieldL0280J The glycal ds-aminoglycosylation was carried out on a 0.5 mmol scale by following the General Procedure D. The desired product was purified through a silica gel flash column (hexanes / ethyl acetate: from 100:1 to 4:1) as white foam (260 mg, 72% yield).

[0281] ’H NMR (400 MHz, CDCh) d 7.43-7.29 (m, 5H), 5.47 (d, J = 9.5 Hz, 1H), 5.43-5.37 (m, 1H), 5.14 (s, 2H), 4.97 (dd, J= 11.3, 3.2 Hz, 1H), 4.89 (d, J= 3.8 Hz, 1H), 4.62 (d, J = 10.3 Hz, 1H), 4.45 (dd, J = 9.5. 2.5 Hz, 1H), 4.30-4.21 (m. 1H), 4.17 (td, J= 10.7, 3.7 Hz, 1H). 4.01 (t, J = 6.6 Hz, 1H), 3.78 (s, 3H), 3.63-3.50 (m, 2H), 2.12 (s, 3H), 1.97 (s, 3H), 1.42 (s, 9H), 1.33 (d, J = 6.4 Hz, 3H), 0.85 (s, 9H), 0.01 (s, 3H), 0.00 (s, 3H);13C NMR (100 MHz, CDCh) d 171.2, 170.7, 170.2, 156.5. 155.4, 136.1, 128.7 (2C), 128.4. 128.3 (2C), 100.4, 79.8, 77.4, 70.2, 69.6, 67.7. 67.5.61.4, 58.5, 52.8, 49.2, 28.4 (3C), 25.9 (3C), 20.9, 20.8, 18.3, 18.1, -5.5, -5.6; HRMS: m / z (ESI) calcd for C34H55N2O13Si+. [M+H]+. 727.3468. found 724.3445. J13CI-HI =171.7 Hz.Scheme 73.TBSOAcO- AcO-+HO OMe+ BocNHCbz1.4 equiv 1.5 equiv 68% yield[0282J The glycal ds-aminoglycosylation was carried out on a 0.5 mmol scale by following the General Procedure D. The desired product was purified through a silica gel flash column (hexanes / ethyl acetate: from 100:1 to 4:1) as white foam (244 mg, 68% yield).

[0283] 1H NMR (400 MHz, CDCh) d1H NMR (400 MHz, CDCh) d 7.45-7.28 (m, 5H), 5.73 (d, J= 8.7 Hz, 1H), 5.14 (s, 2H), 5.1 -4.99 (m, 2H), 4.78 (d, J = 3.7 Hz, 1H), 4.63 (d, J = 10.1 Hz, 1H), 4.60-4.53 (m, 1H), 3.97-3.88 (m. 3H), 3.78 (s, 3H). 3.75-3.69 (m, 1H), 3.68-3.58 (m, 2H), 2.00 (s, 3H), 1.99 (s, 3H), 1.40 (s, 9H), 0.86 (s, 9H), 0.01 (s, 3H), 0.00 (s, 3H);13C NMR (100 MHz, CDCh) d 171.4, 170.8, 169.6, 156.3, 155.5, 136.5, 129.0 (2C). 128.7, 128.6 (2C), 99.4, 80.4, 72.3, 71.4, 70.0, 69.0, 67.7, 62.4. 54.7. 53.4. 53.2, 28.7 (3C). 26.3 (3C). 21.7. 21.2, 18.7, -5.0, -5.1; HRMS: m / z (ESI) calcd for C33H53N2O13SE, [M+H]+, 713.3311, found 713.3298.1J13CI-HI =173.8 Hz.Scheme 74.1.4 equiv 1.5 equiv 67% yield

[0284] The glycal cN-aminoglycosylation was carried out on a 0.5 mmol scale by following the General Procedure D. The desired product was purified through a silica gel flash column (hexanes / ethyl acetate: from 100:1 to 5:1) as white foam (195 mg, 67% yield).

[0285] ’H NMR (400 MHz, CDCh) 37A2-1.28 (m, 5H), 5.73 (d, J = 8.4 Hz, 1H), 5.14 (s, 2H), 4.75 (td, J = 11.0, 4.6 Hz, 1H), 4.67 (s, 1H), 4.64-4.48 (m, 2H), 4.23-4.04 (m, 2H), 3.98 (d, J = 10.4 Hz, 1H), 3.93-3.83 (m, 2H), 3.82-3.72 (m, 4H), 2.27-2.16 (m, 1H), 2.05 (s, 3H), 2.02 (s, 3H), 1.58 (q, J = 11.9 Hz, 1H), 1.41 (s, 9H);;13C NMR (100 MHz, CDCh) 3 170.9, 170.6, 169.6, 155.9, 154.7, 136.1, 128.7 (2C), 128.5, 128.3 (2C), 97.8. 80.0, 69.3, 68.7, 67.4, 66.1, 62.5, 54.4, 52.9, 48.0, 31.0, 28.4 (3C), 21.0, 20.8; HRMS: m / z (ESI) calcd for C27H39N2Oi2+, [M+H]+, 583.2498, found 583.2476. J13ci-m =170.7 Hz.Scheme 75.Fe(L1)(BF4)2(MeCN)(H2O)2N3- ^ (15 mol%) TMSO-T-^O + + Bo<x TMSO— - CH2CI2:dioxane = 9:15 A MS, -40 °C c = 0.5 M, 3 h1.4 equiv 1.6 equiv 76% yield

[0286] The glycal m-aminoglycosylatiori was carried out on a 0.5 mmol scale by following the General Procedure D. The desired product was purified through a silica gel flash column (hexanes / ethyl acetate: from 100:1 to 5:1) as white foam (260 mg, 76% yield).

[0287] ’H NMR (400 MHz, CDCh) 87.44-7.28 (m, 5H), 5.68 (d, J = 8.4 Hz, 1H), 5.14 (s, 2H), 4.70 (d, 7= 3.7 Hz, 1H), 4.58 (dt, J = 8.1, 3.3 Hz, 1H), 4.44 (d, 7 = 10.4 Hz, 1H), 3.95 (dd, 7 = 10.3, 3.1 Hz, 1H), 3.87 (dd, J= 10.4, 3.6 Hz, 1H), 3.83-3.68 (m, 4H), 3.67-3.58 (m, 1H), 3.55-3.44 (m, 2H), 3.41 (dd, J = 13.0, 2.5 Hz, 1H), 3.25 (dd, 7= 13.1, 5.5 Hz, 1H), 1.43 (s, 9H), 0.15 (s, 9H), 0.13 (s, 9H);13C NMR (100 MHz, CDCh) 8 170.5, 155.8, 155.0, 136.0, 128.6 (2C), 128.3, 128.2 (2C), 99.3, 79.8, 73.6, 72.8, 72.3, 69.3, 67.3, 54.9, 54.2, 52.6, 51.1, 28.4 (3C), 0.9 (3C), 0.8 (3C); HRMS: m / z (ESI) calcd for C29H5oN5OioSi2+, [M+H]+, 684.3091, found 684.3105. J13CI-HI =170.1 Hz.Scheme 76.AcO / OAc Fe(L1 )(BF4)2(MeCN)(H2O)2 (1) (15 mol%) o TBSO CH2CI2, 5 A MS ” -40 °C, c = 0.3 M, 3 h1.4 equiv

[0288] The glycal m-aminoglycosylation was earned out on a 0.3 mmol scale by following the General Procedure D. The desired product was purified through a silica gel flash column (hexanes / ethyl acetate: from 100:1 to 3:1) as white foam (180 mg, 73% yield).

[0289] NMR (400 MHz, CDCh) 57.39-7.26 (m, 5H), 6.87 (d. J = 7.8 Hz, 1H). 5.28 (d, J = 8.2 Hz, 1H), 5.24 (d, J = 3.3 Hz, 1H), 5.16 (d, J = 12.1 Hz, 1H), 5.04 (d, J = 12.5 Hz, 1H), 4.79-4.70 (m, 2H), 4.41 (d, J = 10.2 Hz, 1H), 4.26-4.16 (m, 1H), 4.16-3.86 (m, 5H), 3.81-3.73 (m, 5H), 2.09 (s. 3H), 2.02 (s. 3H). 1.73-1.62 (m, 2H), 1.59-1.48 (m, 1H), 1.41 (s, 9H), 0.94 (d. J = 4.8 Hz, 6H), 0.82 (s, 9H), 0.08 (s, 3H), 0.06 (s, 3H);13C NMR (100 MHz, CDC13) 5 171.9, 170.7, 170.3, 170.2, 156.3, 154.9, 136.0, 128.5 (2C), 128.2, 128.0 (2C), 99.5, 79.7, 69.9, 68.8, 68.1, 67.7. 67.1, 62.7, 60.3, 53.7, 52.7, 52.5, 51.2, 40.9, 28.4 (3C), 25.5 (3C), 24.6 (2C), 22.8, 20.8, 20.7, 17.2, -4.9, -5.0; HRMS: m / z (ESI) calcd for C39H64N3O14SE, [M+H]+, 826.4152, found 826.4116. J13CI-HI = 171.4 Hz.Scheme 77.AcO / OAc Fe(L1)(BF4)2(MeCN)(H2O)2(1 ) (15 mol%) o TBSO CH2CI2, 5 A MS -40 °C, c = 0.3 M, 3 hR= n-C5H| 11.4 equiv 65% yield

[0290] The glycal m-aniinoglycosylalioii was carried out on a 0.3 mmol scale by following the General Procedure D. The desired product was purified through a silica gel flash column (hexanes / ethyl acetate: from 100:1 to 3:1) as white foam (164 mg, 65% yield).

[0291] NMR (400 MHz, CDCh) 57.45-7.27 (m, 5H), 6.97 (d, J= 7.9 Hz, 1H), 5.45 (d, J = 7.8 Hz, 1H), 5.24 (d, 7= 3.3 Hz, 1H), 5.16 (d, 7= 12.1 Hz, 1H), 5.11-5.00 (m, 1H), 4.79-4.68 (m, 2H), 4.43 (d, 7= 10.3 Hz, 1H), 4.36-4.02 (m, 6H), 4.00-3.85 (m, 2H), 3.83-3.73 (m, 2H), 2.09 (s, 3H), 2.01 (s, 3H), 1.71-1.60 (m, 2H), 1.41 (s, 9H), 1.37-1.29 (m. 4H). 0.93-0.88 (m, 3H), 0.82 (s.9H), 0.08 (s, 3H), 0.05 (s, 3H);13C NMR (100 MHz, CDCh) 8 172.9, 170.7, 170.3, 169.7, 156.0, 154.9, 128.5 (2C), 128.2, 128.0 (2C), 99.5, 79.7, 69.9, 68.9, 68.1, 67.7, 67.0, 66.1, 62.7, 52.7, 51.2, 50.5, 28.4 (3C), 28.1, 27.9, 25.5 (3C), 22.2, 20.7, 20.7, 18.0, 17.6, 13.9, -4.9, -5.0; HRMS: m / z (ESI) calcdfor C40H66N3O14SE, [M+H]+, 840.4309, found 840.4288. J13CI-HI = 170.1 Hz.Scheme 78.o ■OX / CF2BuO' N fl H OOR CH2CI2 / 1,4 dioxane = 20:1 OR TBSO NHCbz 5 A MS, -40 °C c = 03 M, 3 h NHCbzR= C5H11R= C5Hn 1.4 equiv 58% yield

[0292] The glycal m-aminoglycosylation was carried out on a 0.3 mmol scale by following the General Procedure D. The desired product was purified through a silica gel flash column (hexanes / ethyl acetate: from 10-0:1 to 3:1) as white foam (147 mg, 58% yield).

[0293] 1H NMR (400 MHz, CDCh) 8 1H NMR (400 MHz, CDC13) 87.41-7.27 (m, 5H), 6.83 (d, J = 7.2 Hz, 1H). 5.74 (d, J = 4.8 Hz, 1H), 5.22 (d, J = 3.1 Hz, 1H), 5.18-5.06 (m, 2H), 4.96-4.88 (m, 2H), 4.62 (p, J = 7.2 Hz, 1H), 4.38 (brs, 1H), 4.23-3.87 (m, 7H), 3.82 (dd, J = 10.2, 4.3 Hz, 1H), 3.70 (t, J = 9.3 Hz, 1H), 2.11 (s, 3H), 2.01 (s, 3H), 1.72-1.61 (m, 3H), 1.50-1.41 (m, 12H), 1.38-1.27 (m, 4H). 0.95-0.86 (m, 3H), 0.83 (s. 9H), 0.09 (s, 3H), 0.08 (s, 3H);13C NMR (100 MHz, CDCh) 8 173.2, 170.8, 170.6, 168.9, 155.45, 155.53, 136.1, 128.7 (3C), 128.5, 128.3 (3C), 99.4, 79.8, 70.3, 68.8, 67.8, 67.8, 67.4, 66.2, 63.1, 53.6, 51.6, 48.4, 28.6 (3C), 28.3, 28.0, 25.8 (3C), 22.4, 21.0, 20.9, 18.8, 17.8, 14.1, -4.8, -4.9; HRMS: m / z (ESI) calcd for C40H66N3O14SR, [M+H]+, 840.4309, found 826.4335.= 170.4 Hz.Scheme 79.CF3BuOFe(L1)(BF4)2(MeCN)(H2O)2 AcO / OAc (1) (25 mol%) o CH2CI2 / 1,4 dioxane = 20:1 TBSO 5 A MS, -40 °C c = 0.3 M, 3 h n-C5Hii R= n-C5H| |1.4 equiv 54% yield

[0294] The glycal c / -aminoglycosylation was carried out on a 0.3 mmol scale by following the General Procedure D. The desired product was purified through a silica gel flash column (hexanes / ethyl acetate: from 100:1 to 3:1) as white foam (140 mg, 54% yield).

[0295] NMR (400 MHz, CDCh)1H NMR (400 MHz, CDCh) 57.40-7.27 (m, 5H), 6.69 (d, J= 8.6 Hz, 1H), 5.74 (d, J= 7.0 Hz, 1H), 5.23 (d, J= 3.3 Hz, 1H), 5.18-5.08 (m, 2H), 4.93-4.83 (m, 2H), 4.64-4.56 (m, 1H), 4.44-4.37 (m, 1H), 4.24-3.88 (m, 7H), 3.85-3.77 (m, 1H), 3.70 (t, J = 9.2 Hz, 1H), 2.20 (dq, J = 12.0. 7.1 Hz, 1H). 2.11 (s, 3H), 2.01 (s, 3H), 1.64 (q, J = 6.9 Hz, 2H), 1.43 (s, 9H), 1.38-1.29 (m, 4H), 1.00-0.88 (m, 9H), 0.83 (s, 9H), 0.08 (s, 3H), 0.06 (s, 3H);13C NMR (100 MHz, CDCh) 5 172.1, 170.7, 170.5, 168.7, 155.8, 155.4, 136.1, 129.1 (2C), 128.3, 128.1 (2C). 99.5, 79.6, 70.2, 69.5, 69.4, 68.2, 67.7, 67.6. 67.3. 65.9. 63.0. 57.9, 55.6, 51.2, 28.5 (3C), 28.2, 28.0, 25.6 (3C), 22.2, 20.9, 20.7, 19.0, 17.7, 13.9, -4.9, -5.0; HRMS: m / z (ESI) calcd for C42H7oN3Oi4Si+, [M+H]+, 868.4622, found 868.4654. J13CI-HI = 172.0 Hz.Scheme 80.u BuO'Fe(L1)(BF4)2(MeCN)(H2O)2 (1) (25 mol%) CH2CI2 / 1,4 dioxane = 20:1 5 A MS. -40 °C c = 0.3 M, 3 hR= n-CgH^ R= n-CgHn 1.4 equiv 57% yield

[0296] The glycal d -aminoglycosylation was carried out on a 0.3 mmol scale by following the General Procedure D. The desired product was purified through a silica gel flash column (hexanes / ethyl acetate: from 100:1 to 3:1) as white foam (140 mg, 57% yield).

[0297] ‘H NMR (400 MHz, CDCh) 57.39-7.27 (m, 5H), 5.57 (d, J= 8.6 Hz, 1H), 5.25 (d, J = 3.2 Hz, 1H), 5.15-5.03 (m, 2H), 4.97 (d, J = 10.1 Hz, 1H), 4.82 (d, J = 3.4 Hz, 1H), 4.77 (t, J = 7.2 Hz, 1H), 4.56-4.46 (m, 1H), 4.22-4.04 (m, 5H), 4.03-3.90 (m, 2H), 3.89-3.76 (m, 2H), 3.75-3.60 (m, 2H), 2.29-2.14 (m, 1H). 2.13-1.92 (m, 9H), 1.69-1.59 (m, 2H), 1.43 (s, 9H), 1.36-1.28 (m, 4H), 0.94-0.86 (m, 3H), 0.82 (s, 9H), 0.06 (s, 3H), 0.04 (s, 3H);13C NMR (100 MHz, CDCh) 5 171.7, 170.5, 170.4, 168.6, 155.7, 155.4, 136.0, 128.5 (2C), 128.2, 128.1 (2C), 98.8, 79.3, 69.7, 67.6, 67.1, 65.5, 62.8, 58.4, 51.4, 51.3. 47.3. 29.1. 28.5 (3C). 28.2. 27.9. 24.8 (3C). 22.3. 17.6, 13.9, -5.0, -5.1; HRMS: m / z (ESI) calcd for C42H68N3O14SE, [M+H]+, 866.4465, found 866.4438. 'j''a-m = 170.4 Hz.Scheme 81.OBuOf^1.4 equiv 45% yield

[0298] The glycal m-aminoglycosylation was earned out on a 0.3 mmol scale by following the General Procedure D. The desired product was purified through a silica gel flash column (hexanes / acetone: from 100:1 to 4:1) as white foam (123 mg, 45% yield).

[0299] NMR (400 MHz, CDCh) 57.39-7.27 (m, 5H), 6.99 (d. J= 6.8 Hz, 1H), 6.92 (d, 1H), 5.48 (d, 5.2 Hz, 1H), 5.23 (d, J= 2.9 Hz, 1H), 5.10 (d, J= 8.4 Hz, 2H), 4.98 (d, J= 9.6 Hz, 1H), 4.85 (s, 1H), 4.59 (h, J = 5.3, 4.1 Hz, 2H), 4.33-4.24 (m, 1H), 4.21-3.99 (m, 7H), 3.98-3.88 (m, 1H), 3.73-3.68 (m, 1H), 2.10 (s, 3H), 2.01 (s, 3H), 1.71-1.58 (m, 2H), 1.47-1.37 (s, 15H), 1.37-1.29 (m, 4H), 0.93-0.85 (m, 3H), 0.83 (s, 9H), 0.09 (s, 3H), 0.08 (s, 3H);13C NMR (100 MHz, CDCh) 813C NMR (100 MHz, CDCh) 8 173.0, 172.3, 170.7, 170.4, 168.6, 156.1, 155.3, 136.1. 128.6 (2C), 128.3, 128.1 (2C), 99.1, 79.7, 70.2, 67.8, 67.5, 67.2, 67.1, 66.1, 62.9, 52.1, 51.4, 50.7, 48.4, 28.6, 28.5 (3C), 28.2, 28.2, 27.9, 25.6 (3C), 25.3, 22.3, 20.9, 20.8, 18.4, 17.7, 13.9, -4.9 (2C); HRMS: m / z (ESI) calcd for C43H7iN40i5Si+, [M+H]+, 911.4680, found 911.4677. J13CI-HI = 171.6 Hz.E. Mechanistic Studies for the Iron-Catalyzed Glycal cis-Aminoglycosylationa. Ligand Exchange and Its Influence on ChemoselectivityScheme 82.To a flame-dried sealable 2-dram vial (vial A) equipped with a stir bar were added glycal 2 (90 mg, 0.3 mmol, 1.0 equiv), iron catalyst 1 Fe(Ll)(BF4)2(MeCN)(H2O)2 (26.1 mg, 0.03 mmol, 15 mol %), secondary glycosyl acceptor 6 (99.5 mg, 0.36 mmol, 1.2 equiv), primary glycosyl acceptor 4 (182.2 mg, 0.36 mmol, 1.2 equiv), and freshly activated 5 A molecular sieves, powder (ca. 150 mg). After the vial was evacuated and backfilled with N2 three times, anhydrous CH2CI2 (0.5 mL) was added. The mixture was stirred for 3 minutes at room temperature before cooling to -40 °C. To a second flame-dried sealable 2-dram vial (vial B) was added acyloxyl carbamate 3f (118 mg, 0.45 mmol, 1.5 equiv). Vial B was evacuated and backfilled with N2 three times and then anhydrous CH2CI2 (0.5 mL) was added. 3f was added to vial A using a syringe pump within 15 min. The reaction was kept at -40 °C for an additional 3 h and quenched by precipitating the iron catalyst with Et20 (4 mL) at the same temperature. The mixture was stirred for two minutes and subsequently warmed up to room temperature. The solution was then filtered through a piece of cotton and washed with saturated aq. NaHCCb solution (2 mL). The organic phase was separated from the aqueous one, which was further extracted with CH2CI2 (3 mL x 3). The combined organic phase was dried over anhydrous Na2SC>4 and concentrated in vacuo. The residue was purified through a silica gel flash column (hexanes / ethyl acetate: from 20:1 to 3:1) to afford only the aminoglycosylation product 5 (235 mg, 85%).

[0300] The strong preference observed in this reaction for the primary acceptor is likely due to the preferred coordination of the less-hindered primary glycosyl acceptor 4 to the iron catalyst.Scheme 83.Fe(L1)(BF4)2(MeCN)(H2O)2(1) (15 mol%) CH2CI2, 5 A MS -40 °C, c = 03 M, 3 h dr >20:1 2 5 3f at the C1 and C2>95% conversion 1 equiv 1 2 equiv 1 5 equiv 10% yieldFe(L1)(BF4)2(MeCN)(H20)2(1) (15 mol%) CH2CI2, 5 A MS -40 °C, c = 03 M, 3 h dr >20:1 at the C1 and C2 2 6 S40 3f >95% conversion 1 equiv 47% yield 40% yield

[0301] The first reaction in Scheme 83 was performed by following the General Procedure D.

[0302] The second and the third reactions were performed by the following procedure. To a tlame-dried sealable 2-dram vial (vial A) equipped with a stir bar were added glycal 1 (90 mg, 0.3 mmol, 1.0 equiv), iron catalyst 1 Fe(Ll)(BF4)2(MeCN)(H2O)2 (26.1 mg, 0.045 mmol, 15 mol %), glycosyl acceptor 5 (99.5 mg, 0.36 mmol, 1.2 equiv), carboxylic acid S40 or S41 (21.9 mg or 25 mg, 0.15 mmol, 0.5 equiv), and freshly activated 5 A molecular sieves, powder (ca. 150 mg). After the vial was evacuated and backfilled with N2 three times, anhydrous CH2CI2 (0.5 mL) was added. The mixture was stirred for 3 minutes at room temperature before cooling to -40 °C. To a second flame-dried sealable 2-dram vial (vial B) was added acyloxyl carbamate 3f (118 mg, 0.45 mmol, 1.5 equiv). Vial B was evacuated and backfilled with N2 three times and then anhydrous CH2CI2 (0.5 mL) was added. 3f was added to vial A using a syringe pump within 15 min. The reaction was kept at -40 °C for an additional 3 h and quenched by precipitating the iron catalyst with Et2O (4 mL) at the same temperature. The mixture was stirred for two minutes and subsequently wanned up to room temperature. The solution was then filtered through a piece of cotton and washed with saturated aq. NaHCCL solution (2 mL). The organic phase was separated from the aqueous one,which was further extracted with CH2CI2 (3 mL x 3). The residue was purified through a silica gel flash column (hexanes / ethyl acetate: from 20:1 to 3:1) to afford aminoglycosylation product 7 (98 mg, 47% yield) and aminoacyloxylation product 8f (68 mg, 40% yield) in the case of reaction with external carboxylic acid S40, and aminoglycosylation product 7 (87 mg, 42% yield), aminoacyloxylation product 8f (39 mg, 23% yield), and aminoacyloxylation product 8d (51 mg, 29% yield) in the case of reaction with external carboxylic acid S41.

[0303] The results suggest that rapid ligand exchange did occur in the presence of a glycosyl acceptor, and it could lead to multiple competing pathways that compromise chemoselectivity.b. Iron Catalyst Deactivation and Reactive Intermediate Trapping by TEMPO RadicalScheme 84.52 0 4 equiv Fe(L1)(BF4)2(MeCN)(H2O)2 (1) (15 mol%) CH2CI2, 5 A MS -40 °C, c = 03 M, 2 h <20% conversion 2 4 3d1 2 equiv 1 5 equiv

[0304] To a flame-dried sealable 2-dram vial (vial A) equipped with a stir bar were added glycal 2 (90 mg, 0.3 mmol, 1.0 equiv), glycosyl acceptor 4 (182 mg, 0.36 mmol, 1.2 equiv), iron catalyst 1 Fe(Ll)(BF4)2(MeCN)(H2O)2 (26.1 mg, 0.045 mmol, 15 mol %) and freshly activated 5 A molecular sieves, powder (ca. 150 mg). After the vial was evacuated and backfilled with N2 three times, anhydrous CH2CI2 (0.4 mL) was added. The mixture was transferred to a -78 °C bath and started stirring. To a second flame-dried sealable 2-dram vial (vial B) was added acyloxyl carbamate 3d (127 mg, 0.45 mmol, 1.5 equiv). Vial B was evacuated and backfilled with N2 three times and then anhydrous CH2CI2 (0.3 mL) was added. 3d was added to vial A drop wise in 1 min. To a third flame-dried sealable 2-dram vial (vial C) was added TEMPO (52) (18.8 mg, 0.12 mmol, 0.4 equiv). Vial C was evacuated and backfilled with N2 three times and then anhydrous CH2CI2 (0.3 mL) was added. 52 was added to vial A dropwise in 1 min. The reaction was kept at -78 °C for an additional 3 min before transferring to -40 °C. The mixture was stirred for 2 h and then quenched by precipitating the iron catalyst with Et2O (4 mL) at the same temperature. The mixture was stirredfor 2 min and subsequently warmed up to room temperature. The solution was then filtered through a piece of cotton and washed with saturated aq. NaHCO3 solution (2 mL). The organic phase was separated from the aqueous one, which was further extracted with CH2CI2 (3 mL x 3). The combined organic phase was dried over anhydrous Na2SC>4and concentrated in vacuo. The residue was purified through a silica gel flash column (hexanes / ethyl acetate: from 20:1 to 3:1 to 1:1) to afford the recovered glycal 2 (72 mg, 80% recovery), product 5 as a white solid (22 mg, 8% yield), product 53 as a white solid (3.3 mg, 4% yield), and product 54 as a white solid (5.3 mg, 15% yield).

[0305] The observed low conversion may be due to deactivation of most of the iron catalyst by TEMPO radical (52). Nevertheless, the successful isolation of the aminoglycosylation product 5 suggested that the highly reactive iron-bound nitrogen species (resonance structures of 55a and 55b) were still being generated and they could react with glycal 2 to proceed along the desired glycosylation pathway. Alternatively, 55a / 55b could react with TEMPO to form intermediate 55c, which can then undergo hydrogen atom transfer (HAT) to produce carbo radical 55d. This radical could subsequently be trapped by TEMPO to yield product 53.

[0306] 2-Methyl-l-((2,2,6,6-tetramethylpiperidin-l-yl)oxy)propan-2-yl carbamate (53):IR Vmax (neat)Zcm-1: 2970 (w). 1738 (s), 1456 (m), 1366 (s), 1228 (m), 1216 (m), 1151 (m), 1078 (m), 912 (m), 741 (m); ’H NMR (400 MHz, CDCh) 84.41 (brs, 2H), 3.87 (s, 2H), 1.50 (s, 6H), 1.47-1.24 (m, 6H), 1.17 (s, 6H), 1.12 (s, 6H);13C NMR (100 MHz, CDCh) 8 155.9, 81.0, 80.7, 60.1, 39.8, 33.0, 24.0, 20.2, 17.1; HRMS: m / z (ESI) calcd for Ci4H29N2O3+, [M + H]+. 273.2173, found 273.2172.

[0307] The structure of compound 53 was corroborated by X-ray crystallographic analysis (FIG. 16).

[0308] Based upon kinetic studies, the RDS of the iron-catalyzed cis-aminoglycosylation of electron-rich glycal 2 is the reactive iron species generation while the RDS of the cis-aminoglycosylation with electron-deficient glycal S10 is the glycal amination. The TEMPO radical’s effect was further evaluated in the following reaction shown in Scheme 60.Scheme 85.52 04 equiv Fe(L1)(BF4)2(MeCN)(H2O)2OMe Me Me (1) (15 mol%) H2N'^O'^^°'N^> + BOCNH2CH2CI2, 5 A MS -40 °C. C - 03 M. 2 h Me"^\z <8% conversion Me S10 53 541 2 equiv 1 5 equiv 2% yield 4% yield 15% yield

[0309] This reaction was performed following the aforementioned procedure. The residue was purified through a silica gel flash column (hexanes / ethyl acetate: from 20:1 to 3:1 to 1:1) to afford the recovered glycal 2 (95 mg, 92% recovery), product 20 as a white solid (5.8 mg, 2% yield), product 53 as a white solid (3.3 mg, 4% yield), and product 54 as a white solid (5.3 mg, 15% yield).

[0310] Additionally, TEMPO’S effect in the absence of a glycal was studied.Scheme 86.Fe(L1)(BF4)2(MeCN)(H2O)2OMe Me Me (1) (15 mol%)H2N^(T '~''°'N^> BOCNH2CH2CI2, 5 A MS-40 °C, c = 0.3 M, 2 hMe4 3d 52 53 541.2 equiv 1.5 equiv 0.4 equiv 4% yield 15% yield

[0311] This reaction was performed following the aforementioned procedure, except for the absence of a glycal. The residue was purified through a silica gel flash column (hexanes / ethyl acetate: from 20: 1 to 3: 1 to 1: 1 ) to afford product 53 as a white solid (3.3 mg, 4% yield) and product 54 as a white solid (5.3 mg, 15% yield).c. 1,2-cis- Aminofluoride Formation from a Glycosyl Oxocarbenium Ion Pair and Bronsted Base-Promoted Glycal cis-AminoacyloxylationScheme 87.This reaction was performed following the General Procedure D.

[0312] 2-tert-Butoxycarbonylamino-3-O-tert-butyldimethylsilyl-4,6-O-isopropylidene-2-deoxy-a-D-glucopyranosyl fluoride (57): [a]p3+24.5 (acetone, c = 1.0); IR vmax(neat) / cm-1: 2969 (w), 2855 (w), 1718 (s), 1520 (m), 1367 (s), 1251 (m), 1202 (m), 1171 (s), 1028 (m), 942 (m), 835 (m), 778 (m);NMR (400 MHz, CDCh) 55.53 (dd. J = 53.0. 2.9 Hz, 1H). 4.64 (d, J = 9.8 Hz, 1H), 3.95-3.79 (m, 2H), 3.78-3.69 (m, 2H), 3.64 (t, J - 9.2 Hz, 1H), 3.61-3.52 (m, 1H), 1.48 (s, 3H), 1.43 (s, 9H), 1.40 (s, 3H), 0.87 (s. 9H), 0.07 (s, 3H), 0.06 (s, 3H);13C NMR (100 MHz, CDCh) 8 155.1, 107.8 (d, J = 221.7 Hz), 99.5, 80.0, 73.9, 70.9, 65.8 (d, J = 3.1 Hz), 62.0, 55.7 (d, J = 23.9 Hz), 28.9, 28.4 (3C), 25.7 (3C), 18.9, 18.2, -4.2, -5.1;19F NMR (376 MHz, CDCh) 8 -145.26 (dd, J = 53.0, 29.2 Hz. IF); HRMS: m / z (ESI) calcd for C20H39FNO6SF, [M + H]+, 436.2525. found 436.2536. ^ I-HI = 185.0 Hz.

[0313] The structure of compound 57 was corroborated by X-ray crystallographic analysis (FIG. 17).

[0314] The isolation of l,2-cis-2-aminofluoride 57 suggested the intermediacy of a glycosyl oxocarbenium ion in the glycosylation. The glycosyl oxocarbenium ion can be directly captured by the tetrafluoroborate ion and it can also be trapped by fluoride ion which was released through interaction between tetrafluoroborate ion and glycosyl acceptor 56.Scheme 88.

[0315] To a flame-dried sealable 2-dram vial (vial A) equipped with a stir bar were added glycal 2 (90 mg, 0.3 mmol, 1.0 equiv), iron catalyst 1 Fe(Ll)(BF4)2(MeCN)(H2O)2 (26.1 mg, 0.045 mmol, 10 mol %), glycosyl acceptor 56 (125.5 mg, 0.36 mmol, 1.2 equiv), freshly oven-dried anhydrous K2CO3 powder (829 mg, 6 mmol, 20 equiv) and freshly activated 5 A molecular sieves, powder (ca. 150 mg). After the vial was evacuated and backfilled with N2 three times, anhydrous CH2CI2 (0.6 mL) was added. The mixture was stirred for 3 minutes at -20 °C before cooling to -40 °C. To a second flame-dried sealable 2-dram vial (vial B) was added acyloxyl carbamate 3f (118 mg, 0.45 mmol, 1.5 equiv). Vial B was evacuated and backfilled with N2 three times and then anhydrous CH2CI2 (0.4 mL) was added. 3f was added to vial A using a syringe pump within 15 min. The reaction was kept at -40 °C for an additional 3 h and quenched by precipitating the iron catalyst with Et2< D (4 mL) at the same temperature. The mixture was stirred for two minutes and subsequently warmed up to room temperature. The solution was then filtered through a piece of cotton and washed with saturated aq. NaHCCL solution (2 mL). The organic phase was separated from the aqueous one, which was further extracted with CH₂Cl₂ (3 mL x 3). The combined organic phase was dried over anhydrous Na SO4and concentrated in vacuo. The residue was purified through a silica gel flash column (hexanes / ethyl acetate: from 20:1 to 9:1) to afford cisaminoglycosylation product 12 (30% yield), cis-aminoacyloxylation product 8f (47% yield), and cis-aminofluorination product 57 (10% yield).

[0316] The observation of a decreased yield of 12 (glycal cis-aminoglycosylation product) and an increased yield of 8f (glycal cis-aminoacyloxylation product) suggested that solid K2CO3 can facilitate irreversible deprotonation of the carboxylic acid ligand in intermediate VI to form intermediate VIII, which possesses a more nucleophilic iron-bound carboxylate ligand that could compete more effectively with the glycosyl acceptor in the subsequent transfer step, affording 8fmore favorably.F. Kinetic Studies for the Iron-Catalyzed Glycal cis-Aminoglycosylation

[0317] To better understand the underlying mechanism of this iron-catalyzed glycosylation, particularly reaction rate order dependence over the iron catalyst and each substrate, we carried out kinetic studies by measuring the initial reaction rate. It is known from synthetic studies that the iron catalyst decomposes over the reaction course; at the same time, a stoichiometric amount of carboxylic acid is gradually generated, which can coordinate with the iron catalyst and induce the competing glycal cis-aminoacyloxylation. So, initial rate studies should provide more accurate kinetic information.

[0318] We selected three model reactions for initial rate studies.

[0319] Model Reaction A; the iron-catalyzed glycosylation between glycal 2, primary glycosyl acceptor 4, and amination reagent 3d.Me

[0320] Model Reaction B: the iron-catalyzed glycosylation between glycal S10, primary glycosyl acceptor 4, and amination reagent 3d.1 4 equiv 1 8 equiv

[0321] Model Reaction C; the iron-catalyzed glycosylation between glycal 2, secondary glycosyl acceptor 6, and amination reagent 3f.Me1 2 equiv 1 5 equiv

[0322] Since the reactive iron species is highly sensitive towards air and moisture, we implemented kinetics studies by quenching a series of reactions set up simultaneously at different time points rather than taking a conventional approach in which aliquots are taken during the course of a reaction. We selected using1H NMR for reaction conversion and product yield determination. It is known from synthetic studies that the iron-catalyzed glycal cis-aminoglycosylation is exceedingly slow below -40 °C and it is essentially halted at -78 °C. To facilitate ease of operation and ensure data reliability, we mixed all the substrates and the catalyst at -78 °C and kept it at that temperature for 3 min before moving the reaction to a -40 °C cold bath and initiating the kinetic measurement.

[0323] Compared to the synthetic experiment conditions, we decreased the concentration of Model Reaction A from 0.3 M to 0.1 M and decreased the iron catalyst loading from 10 mol % to 5 mol % to ensure enough data points can be accurately collected before the conversion reaches 20%.

[0324] For same considerations, we decreased the concentration of Model Reaction B from 0.3 M to 0.2 M. Additionally, we decreased the concentration of Model Reaction C from 0.3 M to 0.2 M and decreased the catalyst loading from 15 mol % to 5 mol %.E. Preliminary Kinetic Studies for Model Reaction AMe2 4 3d1 0-20 equiv 1 1-33 equiv 1 0-20 equiv

[0325] To a flame-dried sealable 2-dram vial (vial A) equipped with a stir bar were added glycal 2 (30-60 mg, 0.1-0.2 mmol. 1.0-2.0 equiv), iron catalyst 1 Fe(Ll)(BF4)2(MeCN)(H2O)2 (2.9-5.8 mg, 0.005-0.01 mmol, 5-10 mol %), glycosyl acceptor 4 (55.7-167.1 mg, 0.11-0.33 mmol, 1.1-3.3 equiv), and freshly activated 5 A molecular sieves, powder (ca. 150 mg). After the vial was evacuated and backfilled with N2 three times, anhydrous CH2CI2 (0.7 mL) was added. The mixture was stirred for 1 minute at room temperature before cooling to -78 °C. To a second flame-dried sealable 2-dram vial (vial B) was added acyloxyl carbamate 3d (28.2-56.4 mg, 0.10-0.20 mmol, 1.0-2.0 equiv). Vial B was evacuated and backfilled with N2 three times and then anhydrous CH2O2 (0.3 mL) was added. 3d was added to vial A dropwise within 1 min. The reaction was kept at -78 °C for an additional 3 min before transferring to -40 °C. After 3-16 min the reaction was quenched by adding 1 M imidazole in Et20 solution (2.5 mL) at the same temperature. The mixture was stirred for two minutes and subsequently warmed up to room temperature. The solution was then filtered through a piece of cotton and washed with saturated aq. NaHCCL solution (2 mL). The organic phase was separated from the aqueous one, which was further extracted with CH2CI2 (3 mL x 3). The combined organic phase was dried over anhydrous Na2SO4 and concentrated in vacuo. The product distribution in the residue was determined through quantitative NMR analysis with 1,3,5-trimethoxybenzene (8.4 mg, 0.05 mmol, 0.25-0.5 equiv) added as the internal standard.

[0326] We first aimed to determine the initial rate order dependence on iron catalyst 1. In these experiments, the initial concentration of glycal 2 is 0.1 M, the initial concentration of primary acceptor 4 is 0.22 M, and the initial concentration of amination reagent 3d is 0.15 M. We measured the initial rates with iron catalyst loadings ranging from 5 mol %, 7.5 mol %. to 10 mol %.

[0327] Based on concentration decrease of glycal 2, the corresponding initial rates are 1.82 mM-min’1, 2.69 mM-min’1, and 3.58 mM-min’1.

[0328] Based on concentration increase of glycosylation product 5, the corresponding initial rates are 1.46 mM-min’1, 2.40 mM-min’1, and 2.93 mM-min’1.

[0329] These data suggested that the initial rate has a first-order dependence on iron catalyst 1.

[0330] We next evaluated the initial rate order dependence on primary glycosyl acceptor 4. In these experiments, the initial concentration of glycal 2 is 0.1 M, the initial concentration of amination reagent 3d is 0.15 M, and the initial concentration of iron catalyst 1 is 0.005 M. We measured the initial rates when the concentration of glycosyl acceptor 4 varies from 0.22 M to 0.33 M.

[0331] Based on concentration decrease of glycal 2, the corresponding initial rates are 1.82 mM-min’1and 1.20 mM-min’1.

[0332] Based on concentration increase of glycosylation product 5, the corresponding initial rates are 1.46 mM-min’1and 1.14 mM-min’1.

[0333] These data suggested that the initial rate has an inverse first-order dependence on primary glycosyl acceptor 4.

[0334] We further evaluated the initial rate order dependence on amination reagent 3d. In these experiments, the initial concentration of glycal 2 is 0.1 M, the initial concentration of primary acceptor 4 is 0.22 M, and the initial concentration of iron catalyst 1 is 0.005 M. We measured the initial rates with the amination reagent ranging from 1.0 equiv, 1.5 equiv. to 2.0 equiv.

[0335] Based on concentration decrease of glycal 2, the corresponding initial rates are 1.77 mM-min’1, 1.82 mM-min’1, and 1.75 mM-min’1.

[0336] These data suggested that the initial rate should have zero order dependence on the amination reagent 3d.

[0337] Additionally, we evaluated the initial rate order dependence on glycal 2. In these experiments, the initial concentration of primary acceptor 4 is 0.22 M, the initial concentration of amination reagent 3d is 0.15 M, and the initial concentration of iron catalyst 1 is 0.005 M. We measured the initial rates with glycal’s amount ranging from 1.0 equiv, 2.0 equiv, to 3.0 equiv.

[0338] Based on concentration decrease of glycal 2, the corresponding initial rates are 1.82 mM-min’1, 1.83 mM-min’1, and 1.88 mM-min’1.These data suggested that the initial rate should have zero-order dependence on glycal 2.

[0339] These preliminary kinetic studies suggested that the initial rate has a first-order dependence on the iron catalyst yet an inverse first-order dependence on the primary acceptor 4. At the same time, the rate has a zero-order dependence on both glycal 2 and amination reagent 3d.

[0340] This implies that an iron catalyst-4 complex containing at least two molecules of 4 may be the resting state of the catalyst in the presence of molecular sieves and that its dissociation to release a primary acceptor may occur prior to the rate-determining, reactive iron species generation. (Figure. S16).

[0341] The initial rate’s zero-order dependence on amination reagent 3d suggested that coordination of 3d to the active iron catalyst is fast (Figure S20). The initial rate’s zero-order dependence on glycal 2 is particularly noteworthy, which suggested that the rate-determining step (RDS) in this catalytic glycal cis-aminoglycosylation with electron-rich glycal 2 may be the reactive species generation step instead of the glycal amination step. This insight corroborates the freezetrapped57Fe Mossbauer spectroscopic studies that the putative reactive iron species, either an iron-nitrenoid or an iron iminyl radical, may have unusually high reactivity; therefore, its radical amination with an electron-rich glycal may no longer be rate-limiting.a. Preliminary Kinetic Studies for Model Reaction B

[0342] To further investigate whether the reactive iron species generation step is always the RDS in this catalytic glycal cis-aminoglycosylation, we next evaluated the kinetics of cis-aminoglycosylation with electron-deficient glycal S10.OAc'A OAC^TA"C1 TBSO—S101.0-2.0 equiv

[0343] To a flame-dried sealable 2-dram vial (vial A) equipped with a stir bar were added glycal S10 (68.9-137.8 mg, 0.2-0.4 mmol, 1.0-2.0 equiv). iron catalyst 1Fe(Ll)(BF4)2(MeCN)(H2O)2 (11.6 mg, 0.01 mmol, 10 mol %), glycosyl acceptor 4 (223 mg, 0.44 mmol, 2.2 equiv), and freshly activated 5 A molecular sieves, powder (ca. 150 mg). After the vial was evacuated and backfilled with N2 three times, anhydrous CH₂Cl₂ (0.7 mL) was added. The mixture was stirred for 1 minute at room temperature before cooling to -78 °C. To a second flame-dried sealable 2-dram vial (vial B) was added acyloxyl carbamate 3d (84.6 mg, 0.3 mmol, 1.5 equiv). Vial B was evacuated and backfilled with N2 three times and then anhydrous CH2CI2 (0.3 mL) was added. 3d was added to vial A dropwise within 1 min. The reaction was kept at -78 °C for an additional 3 min before transferring to -40 °C. After 4-16 min the reaction was quenched by adding 1 M imidazole in Et2O solution (2.5 mL) at the same temperature. The mixture was stirred for two minutes and subsequently warmed up to room temperature. The solution was then filtered through a piece of cotton and washed with saturated aq. NaHCCL solution (2 mL). The organic phase was separated from the aqueous one, which was further extracted with CH2CI2 (3 mL x 3). The combined organic phase was dried over anhydrous Na2SC>4 and concentrated in vacuo. The product distribution in the residue was determined through quantitative NMR analysis with 1,3,5-trimethoxybenzene (16.8 mg, 0.1 mmol, 0.25-0.5 equiv) added as the internal standard.

[0344] We aimed to determine the initial rate order dependence on the electron-deficient glycal S10. In these experiments, the initial concentration of primary acceptor 4 is 0.44 M, the initial concentration of amination reagent 3d is 0.30 M, and the initial concentration of iron catalyst 1 is 0.02 M. We measured the initial rates with the amount of glycal S10 ranging from 1.0 equiv to 2.0 equiv.

[0345] Based on concentration decrease of glycal S10, the corresponding initial rates are 1.20 mM-min1and 2.44 mM-min1.

[0346] Based on concentration increase of glycosylation product 20, the corresponding initial rates are 1.20 mM-min1and 2.39 mM-min1.

[0347] These data suggested that the initial rate has a first-order dependence on glycal S10.

[0348] These data suggested that, in the catalytic cis-aminoglycosylation with electrondeficient glycal S10. the RDS is likely the glycal amination step instead of the reactive iron species generation step.b. Preliminary Kinetic Studies for Model Reaction C

[0349] Additionally, we further studied the kinetics of catalytic glycal cis-aminoglycosylation with secondary glycosyl acceptor 6.Me TBSO—21 0-2.0 equiv 2.2-3.3 equiv 1.0-2.5 equivTo a flame-dried sealable 2-dram vial (vial A) equipped with a stir bar were added glycal 2 (60-120 mg, 0.2-0.4 mmol, 1.0-2.0 equiv), iron catalyst 1 Fe(Ll)(BF4)2(MeCN)(H2O)2 (2.9-8.7 mg, 0.005-0.02 mmol, 2.5-7.5 mol%), glycosyl acceptor 6 (121.6-182.4 mg, 0.44-0.66 mmol, 2.2-3.3 equiv), and freshly activated 5 A molecular sieves, powder (ca. 150 mg). After the vial was evacuated and backfilled with N2 three times, anhydrous CH2CI2 (0.7 mb) was added. The mixture was stirred for 1 minute at room temperature before cooling to -78 °C. To a second flame-dried sealable 2-dram vial (vial B) was added acyloxyl carbamate 3f (52.3-130.6 mg, 0.2-0.5 mmol, 1.0-2.5 equiv). Vial B was evacuated and backfilled with N2 three times and then anhydrous CH2O2 (0.3 mL) was added.3f was added to vial A dropwise within 1 min. The reaction was kept at -78 °C for an additional 3 min before transferring to -40 °C. After 3-14 min the reaction was quenched by adding 1 M imidazole in Et20 solution (2.5 mL) at the same temperature. The mixture was stirred for two minutes and subsequently warmed up to room temperature. The solution was then filtered through a piece of cotton and washed with saturated aq. NaHCCL solution (2 mL). The organic phase was separated from the aqueous one, which was further extracted with CH2CI2 (3 mL x 3). The combined organic phase was dried over anhydrous Na SO4and concentrated in vacuo. The product distribution in the residue was determined through quantitative NMR analysis with 1,3,5-trimethoxybenzene (16.8 mg, 0.1 mmol, 0.5 equiv) added as the internal standard.

[0350] We first aimed to determine the initial rate order dependence on iron catalyst 1. In these experiments, the initial concentration of glycal 2 is 0.2 M, the initial concentration of secondary acceptor 6 is 0.44 M, and the initial concentration of amination reagent 3f is 0.3 M. We measured the initial rates with iron catalyst loadings ranging from 2.5 mol %, 5.0 mol %, to 7.5 mol %.

[0351] Based on concentration decrease of glycal 2, the corresponding initial rates are 1.14 mM-min1, 2.25 mM-min1, and 3.23 mM-min1.

[0352] Based on concentration increase of glycosylation product 5, the corresponding initial rates are 0.77 mM-min1, 1.54 mM-min1, and 2.20 mM-min1.

[0353] These data suggested that the initial rate has a first-order dependence on iron catalyst 1.

[0354] We next aimed to determine the initial rate order dependence on secondary alcohol acceptor 6. In these experiments, the initial concentration of glycal 2 is 0.2 M, the initial concentration of amination reagent 3f is 0.30 M, and the initial concentration of iron catalyst 1 is 0.01 M. We measured the initial rates with acceptor loadings at 2.2 equiv and 3.3 equiv.

[0355] Based on concentration decrease of glycal 2, the corresponding initial rates are 2.25 mM-min1and 2.18 mM-min1.

[0356] These data suggested that the initial rate may have zero-order dependence on the secondary glycosyl acceptor 6.

[0357] We further evaluated the initial rate order dependence on amination reagent 3f. In these experiments, the initial concentration of glycal 2 is 0.2 M, the initial concentration of secondary acceptor 6 is 0.44 M, and the initial concentration of iron catalyst 1 is 0.01 M. We measured the initial rates with the amination reagent ranging from 1.0 equiv, 1.5 equiv, to 2.5 equiv.

[0358] Based on concentration decrease of glycal 2, the corresponding initial rates are 2.21 mM-min1, 2.25 mM-min1, and 2.21 mM-min1.

[0359] These data suggested that the initial rate should have a zero order dependence on the amination reagent 3f.

[0360] Additionally, we evaluated the initial rate order dependence on glycal 2. In these experiments, the initial concentration of primary acceptor 4 is 0.44 M, the initial concentration of amination reagent 3d is 0.3 M, and the initial concentration of iron catalyst 1 is 0.01 M. We measured the initial rates with glycal’s amount ranging from 1.0 equiv, 1.5 equiv, to 2.0 equiv.

[0361] Based on concentration decrease of glycal 2, the corresponding initial rates are 2.25 mM-min1, 2.18 mM-min1, and 2.21 mM-min1.

[0362] These data suggested that the initial rate should have a zero-order dependence on glycal 2.

[0363] These preliminary kinetic studies suggested that the initial rate has a first-order dependence on the iron catalyst but a zero-order on each of acceptor 6, glycal 2, and amination reagent 3f. These results suggested that the resting state of the iron-6 complex may contain only one molecule of 6 and the dissociation of an exchangeable ligand may occur before the RDS.G. 1,2-czs-Selective Glycal Aminoacyloxylationa. Reaction Discovery for the Iron-Catalyzed Glycal cis-AminoacyloxylationScheme 89.Fe(L1)(BF4)2(MeCN)(H2O)2(1) (15 mol%)CH2CI2, 5 A MS-40 °C, 2 hdr >20:13 at the C1 and C21.5 equiv

[0364] General Procedure for the Reaction Discovery. To a flame-dried sealable 2-dram vial (vial A) equipped with a stir bar were added a glycal (0.3 mmol, 1.0 equiv), amination reagent 3 (0.45 mmol, 1.5 equiv), and freshly activated 5 A powdered molecular sieves (ca. 150 mg). After the vial was evacuated and backfilled with N2 three times, anhydrous CH2CI2 (0.5 mL) was added and the solution was cooled to -78 °C. To a second flame-dried sealable 2-dram vial (vial B) were added iron catalyst 1 Fe(Ll)(BF4)2(MeCN)(H2O)2 (26.5 mg, 0.045 mmol, 15 mol %) and freshly activated 5 A powdered molecular sieves ca. 150 mg). Vial B was evacuated and backfilled with N2 three times and then anhydrous CH2CI2 (0.5 mL) was added and stirred for 3 min, then vial B solution was added to vial A dropwise via a syringe within 1 min. The reaction was subsequently raised to -40 °C and kept at the same temperature for an additional 2 h. The reaction was then quenched by precipitating the iron catalyst with Et20 (4 mL) at the same temperature. The mixture was stirred for 2 min and subsequently warmed up to room temperature. The solution was then filtered through a piece of cotton and washed with saturated aq. NaHCO3 solution (2 mL). The organic layer was separated from the aqueous one, which was further extracted with CH2CI2 (3 mL x 3). The combined organic layers were dried over anhydrous Na2SO4 and concentrated in vacuo. The residue was purified through a silica gel flash column to afford the desired glycal cis-aminoacyloxylation product.

[0365] The reactions and products are shown in Scheme AA. All yields are isolated yields. Reactions were performed on a 0.3 mmol scale with iron catalyst 1 (15 mol %), glycal 2 (1.0 equiv), and amination reagents 3 (1.5 equiv) in CH2CI2 with 5 A molecular sieves at -40 °C for 2 h.

[0366] Amination reagents 3a-3f and the iron catalyst 1 were prepared according to literature procedures (Li, H. et al. Stereoselective Glycosylation for 1, 2-cis- Aminoglycoside Assembly by Cooperative Atom Transfer Catalysis. J. Am. Chem. Soc. 2024, 146, 33316.)

[0367] The stereochemistry of the aminoacyloxylation product at Cl and C2 positions was determined by NMR analysis of product 4d of Scheme 90.Scheme 90.MeFe(L1)(BF4)2(MeCN)(H2O)2(1) (15 mol%)CH2CI2, 5 A MS-40 °C, c = 0.3 M, 2 hO3d 4d1 5 equiv 73% yield

[0368] The glycal cA-aminoacyloxylation was carried out on a 0.3 mmol scale. The desired product 4d was purified through a silica gel flash column (hexanes / ethyl acetate: from 100:1 to 6:1) as white foam (130 mg, 73% yield).

[0369] 2-(Benzyloxycarbonylamino)-3-0-terf-butyldimethylsilyl-4,6-0-isopropylidene-2-deoxy-a-D-glucopyranosyl 2-bromo-2-methylpropanoate (4d): IR vmax (neat) / cm: 3385 (w), 2993 (w), 2951 (w), 2929 (w), 2886 (w), 2856 (w), 1758 (m), 1724 (s), 1524 (m), 1472 (w), 1370 (m). 1253 (s), 1227 (m). 1202 (m), 1153 (m), 1127 (s), 1076 (s). 1004 (s), 940 (m), 904 (m), 854 (s), 836 (s); ‘H NMR (400 MHz, CDC13) 87.36-7.27 (m, 5H), 6.26 (d, J = 3.6 Hz, 1H), 5.24 (d, J = 10.2 Hz, 1H), 5.11 (ABq, VAB = 10.1 Hz, JAB = 12.4 Hz, 2H), 4.09 (ddd, J = 10.2, 8.9, 3.6 Hz, 1H), 3.87 (dd, J = 10.1. 4.3 Hz, 1H). 3.73 (t, J = 9.8 Hz. 1H), 3.67 (dt, J = 9.6, 4.6 Hz, 1H), 3.61 (t, J = 8.2 Hz, 1H), 3.54 (t, J = 8.9 Hz, 1H), 2.08 (s, 3H), 1.61 (s, 3H), 1.57 (s, 3H), 1.49 (s, 3H), 1.41(s, 3H), 0.83 (s, 9H), 0.05 (s, 3H), 0.01 (s, 3H);13C NMR (100 MHz, CDC13) 5 171.0, 170.7, 156.4, 136.8, 128.4 (2C), 128.0 (2C), 127.9, 99.7, 93.6, 78.7, 74.4, 71.4, 66.9, 66.7, 62.3, 55.7, 29.1, 25.7 (3C), 25.4, 24.0, 21.3. 19.1. 18.3. -4.2. -5.0; HRMS: m / z (ESI) calcd for C29H46NOioSi+, [M + H]+.596.2885, found 596.2875. J13CI-HI = 178.0 Hz.

[0370] Based on COSY analysis (FIG. 18), Hl is assigned to the doublet at 6.26 ppm, N-H is assigned to the doublet at 5.24 ppm, H2 is assigned to the doublet of doublet of doublets at 4.09 ppm, and H3 is assigned to the triplet at 3.54 ppm. Sinceci-iu is 178.0 Hz which corresponds to an Hl in the equatorial position, a small JHI-H2 of 3.6 Hz and a large JH2-H3 of 8.9 HZ suggests an axial H2 and therefore a 1,2-cis relationship between the Cl and C2 substituents.Scheme 91.Fe(L1)(BF4)2(MeCN)(H2O)2(1) (15 mol%)CH2CI2, 5 A MS-40 °C, c = 0.3 M, 2 h3a1.5 equiv 75% yield

[0371] The glycal cz -aminoacyloxylation was carried out on a 0.3 mmol scale. The desired product 4a was purified through a silica gel flash column (hexanes / ethyl acetate: from 100:1 to 6:1) as white foam (121 mg, 75% yield).Me

[0372] 3-O-ferf-Butyldimethylsilyl-4,6-O-isopropylidene-2-methoxycarbonylamino-2-deoxy-a-D-glucopyranosyl 2-bromo-2-methylpropanoate (4a): IR vmax (neat) / cm4: 3390 (w), 2993 (w), 2951 (w), 1930 (w), 2886 (w), 2857 (w), 2362 (w), 1760 (m), 1723 (s), 1527 (m), 1472 (w), 1371 (m), 1254 (s), 1201 (m), 1170 (s), 1153 (s), 1128 (s), 1080 (s), 1012 (s), 932 (m), 904 (w),854 (s), 837 (s); ‘H NMR (400 MHz, CDC13) 56.24 (d, J = 3.5 Hz, 1H), 5.14 (d, J = 10.3 Hz, 1H), 4.07 (td, J = 10.1, 3.6 Hz, 1H), 3.86 (dd, J = 10.1, 4.2 Hz, 1H), 3.75-3.57 (m, 6H), 3.50 (dd, J = 9.9, 8.2 Hz. 1H). 2.12 (s, 3H), 1.62 (s, 3H), 1.56 (s. 3H), 1.48 (s, 3H). 1.40 (s, 3H), 0.85 (s, 9H), 0.05 (s, 3H), 0.04 (s, 3H);13C NMR (100 MHz, CDCI3) 6 171.2, 170.5, 156.8, 99.6, 93.4, 78.6, 74.2, 71.5, 66.6, 62.2, 55.5, 52.3, 28.9, 25.54 (3C), 25.50, 23.7, 21.3, 19.0, 18.2, -4.3, -5.2.; HRMS: m / z (EST) calcd for C23H42NO10SE, [M + H]+, 520.2572, found 520.2586. ^CI-HI = 178.0 Hz.Scheme 92.Fe(L1)(BF4)2(MeCN)(H2O)2(1) (15 mol%)Troc^CH2CI2, 5 A MS-40 °C, c = 03 M, 2 h3b1.5 equiv 40% yield

[0373] The glycal m-aminoacyloxylation was carried out on a 0.3 mmol scale. The desired product 4b was purified through a silica gel flash column (hexanes / ethyl acetate: from 100:1 to 6:1) as white foam (76 mg, 40% yield).4b

[0374] 3-O-te -Butyldimethylsilyl-4,6-O-isopropylidene-2-(2,2,2-trichloroethoxycarbonylamino)-2-deoxy-a-D-glucopyranosyl 2-bromo-2-methylpropanoate (4b): IRvmax (neat) / cm-1: 3364 (w), 3237 (w), 2995 (w), 2952 (w), 2887 (w), 2857 (w), 2360 (w), 1800 (w), 1739 (s), 1727 (s), 1532 (w). 1472 (w), 1370 (m), 1326 (w), 1252 (s), 1158 (s), 1118 (s),1093 (s), 1020 (s), 976 (m), 941 (m), 904 (m), 855 (s), 837 (s), 818 (m);NMR (400 MHz, CDCh) 86.28 (d, J = 3.5 Hz, 1H), 5.56 (d, J = 10.0 Hz, 1H), 4.69 (ABq, VAB = 31.8 Hz, JAB = 12.0 Hz, 2H), 4.04 (td, J = 9.8, 3.5 Hz, 1H). 3.88 (dd, J = 10.0, 4.2 Hz. 1H), 3.73 (t. J = 9.9 Hz, 1H), 3.70-3.55 (m, 3H), 2.12 (s, 3H), 1.62 (s, 3H), 1.58 (s, 3H), 1.49 (s, 3H), 1.41 (s, 3H), 0.86 (s, 9H), 0.07 (s, 6H);13C NMR (100 MHz, CDCh) 8 171.0, 170.5, 154.6, 99.7, 95.3, 93.2, 78.6, 74.9, 74.2, 70.9, 66.7, 62.1, 56.0, 28.9, 25.6 (3C), 25.1, 24.0, 21.3, 19.0, 18.2, -4.3, -5.0; HRMS: m / z (ESI) calcd for C24H41CI3NO10SE, [M + H]+, 636.1560, found 636.1557. J13CI-HI = 178.0 Hz.Scheme 93.Fe(L1)(BF4)2(MeCN)(H2O)2(1) (15 mol%)CH2CI2, 5 A MS-40 °C, c = 0.3 M, 2 h3c 4c1 5 equiv 65% yield

[0375] The glycal cz -aminoacyloxylation was carried out on a 0.3 mmol scale. The desired product 4c was purified through a silica gel flash column (hexanes / ethyl acetate: from 100:1 to 6:1) as white foam (133 mg, 65% yield).

[0376] 3-O-fcrf-Butyldimethylsilyl-2-(fluoren-9-ylmethoxycarbonylamino)-4,6-O-isopropylidene-2-deoxy-a-D-glucopyranosyl 2-bromo-2-methylpropanoate (4c): IRvmax (neat) / cm-1: 3384 (w), 2994 (w), 2930 (w), 2888 (w), 2856 (w), 1712 (s), 1529 (m), 1450 (w), 1366 (m), 1250 (s), 1221 (s), 1153 (m), 1128 (s), 1078 (s), 1053 (s), 941 (m), 904 (m), 854 (s), 837 (s);!H NMR (400 MHz. CDCh, 323 K) 87.75 (d, J = 7.5 Hz, 2H), 7.68 (t, J = 8.5 Hz, 2H), 7.38 (t, J =7.5 Hz, 2H), 7.30 (t, J = 7.5 Hz, 2H), 6.33 (d, J = 3.4 Hz, 1H), 5.42 (d, J = 10.2 Hz, 1H), 4.48 (dd, J = 10.2, 7.2 Hz, 1H), 4.25 (t. J = 7.5 Hz, 1H), 4.13 (ddd, J = 15.9, 11.3, 6.4 Hz, 2H), 3.92-3.86 (m, 1H), 3.78-3.57 (m. 4H), 2.16 (s, 3H). 1.68 (s, 3H), 1.62 (s, 3H), 1.51 (s. 3H), 1.44 (s, 3H). 0.87 (s, 9H), 0.10 (s, 3H), 0.08 (s, 3H);13C NMR (100 MHz, CDC13, 323 K) 8 171.2, 170.5, 156.2, 144.2, 143.9, 141.22, 141.20. 127.6, 127.5, 127.0, 126.9, 125.6, 125.4, 119.8, 119.78, 99.6, 93.5, 78.7, 74.2, 71.3, 67.2, 66.7, 62.2, 55.6, 47.1, 29.0, 25.6 (3C), 25.4, 23.8, 21.4, 19.0, 18.2, -4.3, -5.1;HRMS: m / z (ESI) calcd for C36H5oNOioSi+, [M + H]+, 684.3198, found 684.3179. J13CI-HI = 178.4 Hz.Scheme 94.Me3e1.5 equiv 80% yield

[0377] The glycal m-aminoacyloxylation was carried out on a 0.3 mmol scale. The desired product 4e was purified through a silica gel flash column (hexanes / ethyl acetate: from 100:1 to 12:1) as white foam (135 mg, 80% yield).

[0378] 2-terZ-Butoxycarbonylamino-3-O-fCT -butyldimethylsilyl-4,6-O-isopropylidene-2-deoxy-a-D-glucopyranosyl 2-acetoxy-2-methylpropanoate (4e): IR vmax(neat) / cm-1: 2970 (w), 1737 (s), 1715 (s), 1514 (m), 1368 (s), 1229 (m), 1128 (m), 1079 (m), 994 (m), 836 (m), 780 (m); H NMR (400 MHz. CDCI3) 86.18 (d. J = 3.6 Hz, 1H), 4.83 (d. J = 10.0 Hz, 1H). 3.97 (td. J = 9.9,3.6 Hz, 1H), 3.85 (dd, J = 10.4, 4.5 Hz, 1H), 3.70 (t, J = 10.0 Hz, 1H), 3.65-3.41 (m, 3H), 2.09 (s, 3H), 1.61 (s, 3H), 1.56 (s, 3H), 1.47 (s, 3H), 1.42 (s, 9H), 1.39 (s, 3H), 0.86 (s, 9H), 0.06 (s, 6H);13C NMR (100 MHz, CDCh) 5 170.6, 170.5, 155.4, 99.5, 93.6, 79.4, 78.4, 74.3, 71.1, 66.4, 62.1. 54.9, 28.9, 28.3 (3C), 25.7 (3C), 25.2, 23.9, 21.1, 18.9, 18.2, -4.4, -5.1; HRMS: m / z (ESI) calcd for C26H48NOioSi+, [M + H]+, 562.3042. found 562.3039. J13CI-HI = 181.1 HZ.Scheme 95.Me Fe(L1)(BF4)2(MeCN)(H2O)2(1) (15 mol%)CH2CI2, 5 A MS-40 °C, c = 0.3 M, 2 h3f1.5 equiv 85% yield

[0379] The glycal ch-aminoacyloxylation was carried out on a 0.3 mmol scale by following the general procedure. The desired product 4f was purified through a silica gel flash column (hexane s / ethyl acetate: from 100:1 to 12:1) as white foam (148 mg, 85% yield).4f

[0380] 2- / e / 7-lhit()xycarbonylaniin()-3-O- / e / 7-biityldiniethvlsilyl-4.6-O-isopropylidene-2-deoxy-a-D-glucopyranosyl 2-bromo-2-methylpropanoate (4f): IR vmax (neat) / cm-1: 2970 (w), 1739 (s), 1435 (m), 1366 (s), 1228 (m), 1216 (m), 989 (m), 836 (m), 779 (m); ‘H NMR (400 MHz. CDCh) 86.14 (d, J = 3.7 Hz, 1H), 4.51 (d, J = 9.7 Hz, 1H), 4.03 (td, J = 9.7, 3.1 Hz, 1H), 3.86 (dd, J = 9.8, 4.1 Hz, 1H), 3.76-3.53 (m, 4H), 2.00 (s, 3H), 1.98 (s, 3H), 1.49 (s, 3H), 1.41 (s, 12H), 0.88 (s. 9H). 0.08 (s, 6H);13C NMR (100 MHz, CDCh) 8 169.8, 155.0, 99.6, 93.9, 80.0, 74.2, 71.1, 66.4, 62.1, 55.9, 55.1, 30.6, 30.4, 28.9, 28.3 (3C), 25.7 (3C), 19.0, 18.2, -4.2, -5.0; HRMS: m / z (ESI)calcd for C24H45BrNO8Si+, [M + H]+, 582.2092, found 582.2093. J13CI-HI = 181.7 Hz.

[0381] General Procedure for the Iron-Catalyzed Glycal c / .s-Aniinoacyloxylation To a flame-dried sealable 2-dram vial (vial A) equipped with a stir bar were added a glycal (0.3 mmol, 1.0 equiv), amination reagent 3 (0.45 mmol. 1.5 equiv), and freshly activated 5 A powdered molecular sieves (ca. 150 mg). After the vial was evacuated and backfilled with N2 three times, anhydrous CH2CI2 (0.5 mL) was added and the solution was cooled to -78 °C. To a second flame-dried sealable 2-dram vial (vial B) were added iron catalyst 1 Fe(Ll)(BF4)2(MeCN)(H2O)2 (26.5 mg, 0.045 mmol, 15 mol %) and freshly activated 5 A powdered molecular sieves (ca. 150 mg). Vial B was evacuated and backfilled with N2 three times and then anhydrous CH2CI2 (0.5 mL) was added and stirred for 3 min, then vial B solution was added to vial A dropwise via a syringe within 1 min. The reaction was subsequently raised to -40 °C and kept at the same temperature for an additional 2 h. The reaction was then quenched by precipitating the iron catalyst with EtzO (4 mL) at the same temperature. The mixture was stirred for 2 min and subsequently wanned up to room temperature. The solution was then filtered through a piece of cotton and washed with saturated aq. NaHCCL solution (2 mL). The organic layer was separated from the aqueous one, which was further extracted with CH2CI2 (3 mL x 3). The combined organic layers were dried over anhydrous Na2SO4and concentrated in vacuo. The residue was purified through a silica gel flash column to afford the desired glycal m-aminoacyloxylation product.Scheme 96.Me Fe(L1)(BF4)2(MeCN)(H2O)2(1) (15 mol%)CH2CI2, 5 A MS-40 °C, c = 03 M, 2 h3f1.5 equiv

[0382] Compound 2 in Scheme 96 was synthesized according to a literature procedure (Postema, M. H. D. et al.. Total Synthesis of Ipomoeassin F. Org. Let. 2009. 11. 1417).

[0383] The glycal m-aminoacyloxylation was carried out on a 0.3 mmol scale by followingthe general procedure. The desired product 4f was purified through a silica gel flash column (hexanes / ethyl acetate: from 100:1 to 12:1) as white foam (148 mg, 85% yield).

[0384] 2-ZerZ-Butoxycarbonylamino-3-O-ferZ-butyldimethylsilyl-4,6-O-isopropylidene-2-deoxy-a-D-glucopyranosyl 2-bromo-2-methylpropanoate (4f): IR vmax (neal) / cni: 2970 (w), 1739 (s), 1435 (m), 1366 (s), 1228 (m), 1216 (m), 989 (m), 836 (m), 779 (m); 'H NMR (400 MHz, CDCh) 56.14 (d, J = 3.7 Hz. 1H), 4.51 (d, J = 9.7 Hz. 1H), 4.03 (td, J = 9.7, 3.1 Hz, 1H), 3.86 (dd, J = 9.8, 4.1 Hz, 1H), 3.76-3.53 (m, 4H), 2.00 (s, 3H), 1.98 (s, 3H), 1.49 (s, 3H), 1.41 (s, 12H), 0.88 (s, 9H), 0.08 (s, 6H);13C NMR (100 MHz, CDCh) 8 169.8, 155.0, 99.6, 93.9, 80.0, 74.2, 71.1, 66.4, 62.1, 55.9, 55.1, 30.6, 30.4, 28.9. 28.3 (3C). 25.7 (3C), 19.0. 18.2. -4.2. -5.0; HRMS: m / z (ESI) calcd for Ci^BrNOsSC, [M + H]+, 582.2092, found 582.2093. J13CI-HI = 181.7 Hz.Scheme 97.Fe(L1)(BF4)2(MeCN)(H2O)2(1) (15 mol%)CH2CI2, 5 A MS-40 °C, c = 03 M, 2 hS1 3f1.5 equiv

[0385] Compound SI in Scheme 97. was synthesized according to a literature procedure (Blackburne, I. et al., Studies on Unsaturated Sugars with Particular Reference to the Synthesis of 6-Deoxy-6-Fluoro Derivatives. Aust. J. Chem. 1976, 29, 381).

[0386] The glycal m-aminoacyloxylation was carried out on a 0.3 mmol scale by following the general procedure. The desired product 5 was purified through a silica gel flash column(hexanes / ethyl acetate: from 100:1 to 6:1) as white foam (117 mg, 70% yield).

[0387] 2-ZerCButoxycarbonylamino-3-O-benzyl-4,6-O-isopropylidene-2-deoxy-a-D-glucopyranosyl 2-bromo-2-methylpropanoate (5): IR vmax (neat) / cm-1: 3362 (w), 2979 (w). 2933 (w), 1749 (m), 1708 (m), 1505 (m), 1455 (w), 1366 (m), 1265 (m), 1153 (m), 1124 (s), 1076 (m), 1009 (m), 940 (m), 870 (m), 851 (m); 'H NMR (400 MHz, CDCh) 57.42-7.27 (m, 5H), 6.18 (d, J = 3.7 Hz, 1H), 4.77 (ABq. VAB = 104.9 Hz, JAB = 11.9 Hz, 2H), 4.37 (d, J = 9.1 Hz, 1H), 4.07 (td, J = 9.9, 3.4 Hz, 1H), 3.92-3.79 (m, 2H), 3.79-3.66 (m, 2H), 3.56 (t, J = 9.6 Hz, 1H), 1.94 (s, 3H), 1.91 (s, 3H), 1.51 (s, 3H), 1.46 (s, 3H). 1.43 (s, 9H);13C NMR (100 MHz, CDCh) 5 169.5, 155.2, 138.3, 128.3 (2C). 128.0 (2C), 127.7, 99.6, 93.5, 80.0, 75.9, 74.8, 73.9, 66.4. 62.1. 55.7. 53.4. 30.5, 30.3, 29.1, 28.3 (3C), 19.1; HRMS: m / z (ESI) calcd for C25H37BrNO8+, [M + H]+, 558.1697, found 558.1683. J13CI-HI = 178.4 Hz.Scheme 98.TBSO^XTBSO-VA-C)TBSO—S2

[0388] S2 was synthesized according to a literature procedure (Nicolaou. K. C, et al.Stereospecific synthesis of 1,1 -dialkylglycosides. J. Chem. Soc., Chem. Commun. 1986, 925.)

[0389] The glycal c / s-aminoacyloxylation was carried out on a 0.3 mmol scale by following the general procedure. The desired product 6 was purified through a silica gel Hash column(hexanes / diethyl ether: from 100:1 to 20:1) as colorless oil (169 mg, 73% yield).TBSO'TBSO' ■oTBSO- MeBocHN^

[0390] 2-ferZ-Butoxycarbonylamino-3,4,6-tri-O-terf-butyldimethylsilyl-2-deoxy-a-D-glucopyranosyl 2-bromo-2-methylpropanoate (6): IR vmax (neat) / cm-1: 3435 (w), 2954 (w), 2930 (w), 2886 (w), 2858 (w), 1747 (w), 1720 (m), 1507 (w), 1472 (w), 1463 (w), 1390 (w), 1365 (w), 1253 (m), 1158 (m), 1135 (m), 1082 (m), 1049 (m). 1022 (m), 1005 (m), 939 (w), 832 (s); ‘H NMR (400 MHz, CDCh) 56.09 (d,.1 = 1.6 Hz, 1H), 5.87 (d,.1 = 9.5 Hz, 1H), 4.06 (dd, J = 9.4, 8.2 Hz, 1H), 4.01-3.95 (m, 1H), 3.92-3.84 (m, 3H), 3.78 (dt, J = 3.1, 1.6 Hz, 1H), 1.94 (s, 3H), 1.94 (s, 3H), 1.40 (s, 9H), 0.93 (s. 9H), 0.91 (s, 9H). 0.88 (s, 9H), 0.15 (s, 3H), 0.12 (s. 3H), 0.11 (s, 3H). 0.10 (s, 3H), 0.05 (s, 3H), 0.04 (s, 3H);13C NMR (100 MHz, CDCh) 8 169.9, 155.1, 89.9, 82.0, 78.9, 72.6, 68.2, 61.6, 55.7, 51.0, 30.7, 30.5, 28.4 (3C), 25.8 (3C), 25.8 (3C), 25.7 (3C), 18.1, 17.9, 17.8, -4.7 (two peaks overlapped, 2C), -4.8, -4.9. -5.3 (two peaks overlapped, 2C); HRMS: m / z (ESI) calcd for C33H69BrNO8Si3+, [M + H]+, 770.3509, found 770.3527.{J13CI-HI = 170.4 Hz.Scheme 99.Fe(L1)(BF4)2(MeCN)(H2O)2AcO'X (1) (15 mol%)AcO-T~X-O +TBSO—U^sA CH2CI2, 5 A MS-40 °C, c = 0.3 M, 2 hS3 3f1.5 equiv

[0391] S3 was synthesized according to a literature procedure (Pal, K. B., et al., Palladium(II)-Catalyzed Stereoselective Synthesis of C-Glycosides from Glycals with Diaryliodonium Salts. Org. Biomol. Chem. 2020, 18, 2242).

[0392] The glycal cz -aminoacyloxylation was carried out on a 0.3 mmol scale by followingthe general procedure. The desired product 7 was purified through a silica gel flash column (hexanes / ethyl acetate: from 100:1 to 6:1) as white foam (134 mg, 71% yield).

[0393] 4,6-Di-O-acetyl-2-terf-butoxycarbonylamino-3-O-tezt-butyldimethylsilyl-2-deoxy-a-D-glucopyranosyl 2-bromo-2-methylpropanoate (7): IRvmas(neat) / cm-1: 3373 (w), 2956 (w), 2932 (w), 2895 (w), 2858 (w), 1749 (s), 1723 (m), 1505 (w), 1463 (w), 1367 (m), 1236 (s), 1220 (s), 1156 (s), 1130 (s), 1100 (m), 1037 (m), 923 (w), 839 (s); ‘H NMR (400 MHz, CDC13) 86.19 (d. 7 = 3.5 Hz, 1H), 5.06 (dd, J = 10.3.8.9 Hz, 1H). 4.45 (d, J = 9.8 Hz, 1H). 4.20-4.11 (m, 1H), 4.11-4.02 (m, 2H), 3.95 (d, J = 10.7 Hz, 1H), 3.86 (t, J = 9.5 Hz, 1H), 2.09 (s, 3H), 2.07 (s, 3H), 1.99 (s, 3H), 1.99 (s, 3H), 1.42 (s. 9H), 0.85 (s, 9H), 0.09 (s, 3H), 0.06 (s, 3H);13C NMR (100 MHz. CDCI3) 8 170.8, 169.4. 169.3, 154.7, 93.2, 80.2, 70.8, 70.73, 70.71, 62.0, 56.1, 54.7, 30.6, 30.4, 28.3 (3C), 25.5 (3C), 21.2, 20.7, 17.8, -4.4 (two peaks overlapped, 2C); HRMS: m / z (ESI) calcd for C25H45BrNOioSi+, [M + H]+, 626.1991, found 626.1998. J13CI-HI = 178.4 Hz.Scheme 100.Fe(L1)(BF4)2(MeCN)(H2O)2TBSO^\ (1) (15 mol%)AcO'T-V-OAcO—k^i CH2CI2, 5 A MS-40 °C, c = 0.3 M, 2 hS4 3f1.5 equiv

[0394] S4 was synthesized according to a literature procedure (Nicolaou, K. C., et al., Total Synthesis of Vancomycin. Angew. Chem. Int. Ed. 1999, 38, 240).

[0395] The glycal ds-aminoacyloxylation was carried out on a 0.3 mmol scale by followingthe general procedure. The desired product 8 was purified through a silica gel flash column (hexanes / ethyl acetate: from 100:1 to 6:1) as white foam (131 mg, 70% yield).TBSO" \AnO— <4AcO MeBOCHN OJL^ > Ir-. M.e8

[0396] 3,4-Di-O-acetyl-2-terf-butoxycarbonylamino-6-O-terf-butyldimethylsilyl-2-deoxy-a-D-glucopyranosyl 2-bromo-2-methylpropanoate (8): IR Vmax (neat) / cm: 3345 (w), 2930 (w). 2857 (w), 1750 (s), 1715 (m). 1505 (w), 1463 (w), 1366 (m). 1234 (s), 1219 (s), 1157 (m), 1126 (s), 1005 (s), 835 (s); ‘HNMR (400 MHz, CDC13) 86.25 (d, 7= 3.6 Hz, 1H), 5.25-5.15 (m, 2H), 4.63 (d, J = 9.5 Hz, 1H), 4.14 (td, J = 10.0, 3.4 Hz, 1H), 3.94-3.88 (m, 1H), 3.72-3.63 (m, 2H), 2.05 (s, 3H), 2.03 (s, 3H), 1.99 (s, 3H), 1.98 (s, 3H), 1.40 (s, 9H), 0.86 (s, 9H), 0.02 (s, 3H), 0.01 (s, 3H);13C NMR (100 MHz, CDCI3) 8 171.4, 169.7, 169.2, 155.2, 92.6, 80.5, 73.2, 71.3, 68.2, 62.0, 55.6, 53.0, 30.7, 30.6, 28.3 (3C), 25.9 (3C), 20.9, 20.8, 18.4, -5.26, -5.31: HRMS: m / z (ESI) calcd for C25H45BrNOioSi+, [M + H]+, 626.1991, found 626.1990.[J13CI-HI = 178.0 Hz.Scheme 101.Fe(L1)(BF4)2(MeCN)(H2O)2TBSO'A (1) (15 mol%)AcO'-r-A-'°\TBSO~V -5> CH2CI2, 5 A MS-40 °C, c = 03 M, 2 hS5 3f1 5 equiv

[0397] S5 was synthesized according to a literature procedure (Balmond, E. I., et al., A 3,4- / / r -Fused Cyclic Protecting Group Facilitates a-Selective Catalytic Synthesis of 2-Deoxyglycosides. Angew. Chem. Int. Ed. 2014, 53, 8190.7

[0398] The glycal m-aminoacyloxylation was carried out on a 0.3 mmol scale by following the general procedure. The desired product 9 was purified through a silica gel flash column(hexanes / ethyl acetate: from 100:1 to 20:1) as colorless oil (151 mg, 72% yield).TBSO'AcO- ■OTBSO- MeBocHNMeO9

[0399] 4-O-Acetyl-2-terf-butoxycarbonylamino-3,6-di-O-terf-butyldimethylsilyl-2-deoxy-a-D-glucopyranosyl 2-bromo-2-methylpropanoate (9): IR vmax(neat) / cm-1: 3435 (w), 2953 (w). 2930 (w), 2857 (w), 1753 (m), 1726 (m), 1504 (w), 1369 (w), 1252 (m), 1224 (m). 1158 (m), 1133 (s), 1061 (w), 1003 (m), 837 (s); 'H NMR (400 MHz, CDCh) 86.20 (d, J = 3.6 Hz, 1H), 4.95 (dd, J = 10.2, 8.8 Hz, 1H), 4.48 (d, J = 9.8 Hz, 1H), 4.07-3.96 (m, 1H), 3.91-3.71 (m, 2H), 3.68-3.56 (m, 2H). 2.08 (s, 3H), 1.99 (s, 3H), 1.97 (s, 3H), 1.42 (s, 9H). 0.85 (s, 18H), 0.09 (s, 3H), 0.05 (s, 3H), 0.02 (s, 3H), 0.01 (s, 3H);13C NMR (100 MHz, CDCh) 8 169.5, 169.2, 154.9, 93.2, 80.1, 73.9, 71.5, 70.9, 62.8, 56.2, 54.9, 30.7, 30.5, 28.3 (3C), 25.8 (3C), 25.6 (3C), 21.3, 18.3, 17.9, -4.39. -4.43, -5.3, -5.4; HRMS: m / z (ESI) calcd for C29H57BrNO9Si2+. [M + H]+. 698.2750, found 698.2740. J13CI-HI = 178.4 Hz.Scheme 102.Fe(L1)(BF4)2(MeCN)(H2O)2AcCTA (1) (15 mol%)AcO-T-^O.AcO— CH2CI2, 5 A MS-40 °C, c = 03 M, 2 hS6 3f 101.5 equiv 69% yield

[0400] The glycal m-aminoacyloxylation was carried out on a 0.3 mmol scale by following the general procedure. The desired product 10 was purified through a silica gel flash column (hexanes / diethyl ether: from 100:1 to 1:1) as white foam (115 mg, 69% yield).

[0401] 3,4,6-Tri-O-acetyl-2-te -butoxycarbonylammo-2-deoxy-a-D-glucopy ranosyl 2-bromo-2-methylpropanoate (10): lRvmax (neat) / cm-1: 3355 (w), 2978 (w), 2361 (w), 1750 (s), 1719 (m), 1508 (w), 1457 (w), 1368 (m), 1229 (s), 1156 (m), 1130 (m), 1012 (m); *H NMR (400 MHz, CDCh) 86.25 (d, 7= 3.6 Hz, 1H), 5.33-5.11 (m, 2H), 4.62 (d, 7 = 9.5 Hz, 1H), 4.32-4.16 (m, 2H), 4.12-4.06 (m, 2H), 2.07 (s, 3H), 2.06 (s, 3H), 2.05 (s, 3H), 2.00 (s, 6H), 1.41 (s, 9H);13C NMR (100 MHz, CDCh) 8 171.0, 170.5, 169.3, 169.2, 154.9, 92.2, 80.4, 70.7, 70.2, 67.5, 61.4, 55.4, 52.7, 30.4, 30.3, 28.1 (3C), 20.6 (two peaks overlapped, 2C), 20.5; HRMS: m / z (ESI) calcd for C2iH33BrNOn+, [M + H]+, 554.1232, found 554.1227. J13CI-HI = 179.8 Hz.Scheme 103.

[0402] S7 was synthesized according to a literature procedure (Kirschning, A. Oxidation of Fully Protected Glycals by Hypervalent Iodine Reagents. 7. Org. Chem. 1995, 60, 1228).

[0403] The glycal s-aminoacyloxylation was carried out on a 0.3 mmol scale by following the general procedure. The desired product 11 was purified through a silica gel flash column (hexanes / ethyl acetate: from 100:1 to 6:1) as white foam (141 mg, 75% yield).

[0404] 4,6-Di-O-acetyl-2-ZerCbutoxycarbonylamino-3-O-terf-butyldimethylsilyl-2-deoxy-a-D-galactopyranosyl 2-bromo-2-methylpropanoate (11): IR Vmax (neat) / cm: 3424 (w), 2958 (w), 2931 (w), 2858 (w), 1747 (s), 1723 (m), 1504 (w), 1367 (m), 1222 (s), 1160 (s), 1132 (s), 1119 (s), 1103 (s), 1050 (m), 1030 (m), 1006 (m), 944 (m), 837 (s);NMR (400 MHz, CDCh) 8 6.24 (d. J = 3.3 Hz, 1H), 5.33 (d, J = 3.3 Hz, 1H), 4.37 (d, J = 9.9 Hz, 1H), 4.33-4.20 (m. 2H), 4.16 (dd, J = 11.4, 5.4 Hz, 1H), 3.98 (dd, J = ]AA, 7 z, 1H), 3.88 (dd, J = 10.3, 3.3 Hz, 1H), 2.12 (s, 3H), 2.02 (s, 3H), 1.97 (s, 6H), 1.41 (s, 9H), 0.84 (s, 9H), 0.11 (s, 3H), 0.08 (s, 3H);13C NMR (100 MHz. CDCh) 8 170.5, 170.1. 169.5, 155.0, 93.9, 80.0, 69.8, 69.3. 68.1. 62.2. 56.1. 50.8. 30.6, 30.4, 28.3 (3C), 25.5 (3C), 20.7 (two peaks overlapped, 2C), 17.7, -4.8, -5. O.; HRMS: m / z (ESI) calcd for C25H45BrNOioSi+, [M + H]+, 626.1991, found 626.1982. J13CI-HI = 178.4 Hz.Scheme 104.Me'' | 1 MeMe Me Fe(L1)(BF4)2(MeCN)(H2O)2(1) (15 mol%) ■OfA MeCH2CI2, 5 A MS-40 °C, c = 0.3 M, 2 h3f 121.5 equiv 78% yield

[0405] S8 was synthesized according to a literature procedure (Kirschning, A. Oxidation of Fully Protected Glycals by Hypervalent Iodine Reagents. J. Org. Chem. 1995, 60, 1228).

[0406] The glycal cA-aminoacyloxylation was carried out on a 0.3 mmol scale by followingthe general procedure. The desired product 12 was purified through a silica gel flash column (hexanes / ethyl acetate: from 100:1 to 6:1) as white foam (147 mg, 78% yield).12(04071 3,4-Di-O-acetyl-2-ferf-butoxycarbonylamino-6-O-ferf-butyldimethylsilyl-2-deoxy-a-D-galactopyranosyl 2-bromo-2-methylpropanoate (12): IR vmax (neat) / cm4: 3354 (w), 2956 (w), 2930 (w), 2857 (w), 1748 (s), 1714 (s), 1523 (w), 1464 (w), 1367 (m), 1241 (s), 1167 (s), 1150 (s), 1115 (s), 1103 (s), 1064 (m), 1049 (m), 1033 (m), 941 (m), 836 (s); ‘H NMR (400 MHz, CDCh) 86.27 (d, J = 3.7 Hz, 1H), 5.54 (d, J = 3.2 Hz, 1H), 5.16 (dd, 7 = 11.3, 3.2 Hz, 1H), 4.58 (d, J = 9.8 Hz, 1H), 4.42 (td, J = 10.6, 3.7 Hz, 1H). 4.09 (t, J = 6.9 Hz, 1H), 3.64 (dd, J = 10.0, 5.9 Hz, 1H), 3.56 (dd, J = 10.0, 7.7 Hz, 1H), 2.15 (s, 3H), 2.02 (s, 3H), 1.99 (s, 3H), 1.98 (s, 3H), 1.41 (s, 9H), 0.84 (s, 9H), 0.001 (s, 3H), -0.004 (s, 3H);13C NMR (100 MHz, CDCh) 8 170.7, 169.9, 169.7, 155.2. 93.2. 79.8. 71.9, 68.7, 66.7, 60.6, 55.6, 48.7, 30.5, 30.4, 28.2 (3C), 25.7 (3C), 20.8 (two peaks overlapped, 2C), 18.1, -5.6, -5.7; HRMS: m / z (ESI) calcd for C25H45BrNOioSi+, [M + H]+. 626.1991, found 626.1997. J13CI-HI = 179.1 Hz.Scheme 105.

[0408] S9 was synthesized according to a literature procedure (Kirschning, A. Oxidation of Fully Protected Glycals by Hypervalent Iodine Reagents.. J. Org. Chem. 1995, 60, 1228).

[0409] The glycal czs-aminoacyloxylation was carried out on a 0.3 mmol scale by following the general procedure. The desired product 13 was purified through a silica gel flash column (hexanes / ethyl acetate: from 100:1 to 20:1) as colorless oil (172 mg, 82% yield).AcO zOTBSUVo

[0410] 4-0- Acety l-2- / e / 7-butoxycarbony laini no-3.6-di-D- / e / 7- bu ty Idi inethy lsilyl-2-deoxy-a-D-galactopyranosyl 2-bromo-2-methylpropanoate (13): IRvmax (neat) / cm4: 3433 (w), 2953 (w), 2930 (w), 2886 (w), 2857 (w), 1750 (m), 1726 (m), 1504 (w), 1463 (w), 1390 (w), 1252 (m), 1224 (m). 1124 (m), 1102 (m), 1055 (w), 1030 (m). 1006 (m), 940 (m), 836 (s);1H NMR (400 MHz, CDCh) 66.22 (d, J = 3.4 Hz, 1H), 5.41 (d, J = 3.2 Hz, 1H), 4.42 (d, J = 9.9 Hz, 1H), 4.26 (td, J = 10.2, 3.5 Hz, 1H), 3.99 (t, J = 6.6 Hz, 1H), 3.87 (dd, J = 10.5, 3.2 Hz, 1H), 3.58 (m, 2H), 2.11 (s, 3H), 1.98 (s. 3H), 1.96 (s, 3H), 1.41 (s, 9H), 0.85 (s, 18H), 0.11 (s, 3H), 0.08 (s, 3H), 0.002 (s, 3H), -0.001 (s, 3H).;13C NMR (100 MHz, CDCh) 8 169.8, 169.6, 155.1, 94.1, 79.8, 72.8, 69.3, 68.5, 61.2, 56.2, 51.0, 30.7, 30.5, 28.3 (3C), 25.7 (3C), 25.6 (3C), 20.8, 18.1, 17.8, -4.8, -5.1, -5.56, -5.61.; HRMS: m / z (ESI) calcd for C29H57BrNO9Si2+, [M + H]+. 698.2750, found 698.2762.1J13ci—m = 178.4 Hz.Scheme 106.N-Fe(L1)(BF4)2(MeCN)(H2O)2(1) (15 mol%) AcO •OBuO N [] tA MeH O -40 °C, o = 0.3 M, 2 h3f 141.5 equiv 76% yield

[0411] S10 was synthesized according to a literature procedure (Yin, B.-L., et al., SodiumBorohydride-Nickel Chloride-Methanol Catalytic System for Regioselective Reduction of Electron-Rich Conjugated Dienes and Reductive Cleavage of Allyl Esters Involving it- Allylnickel Intermediates. Adv. Synth. Catal. 2011, 353. 3319).

[0412] The glycal ch-aminoacyloxylation was carried out on a 0.3 mmol scale by following the general procedure. The desired product 14 was purified through a silica gel flash column (hexanes / ethyl acetate: from 100:1 to 8:1) as white foam (130 mg, 76% yield).AcO

[0413] 4-0- Acety l-2- / e / 7-bn toxycarbony knni no-6-D- / (r / -buty kliniethy Isily 1-2.3-di-deoxy-a-D-n£>o-hexopyranosyl 2-bromo-2-methylpropanoate (14): IR Vmax (neat) / cm-1: 3394 (w), 2954 (w), 2930 (w), 2857 (w), 2361 (w), 1742 (s), 1717 (s), 1506 (m), 1463 (w), 1391 (w), 1367 (m). 1233 (s), 1158 (s), 1130 (s), 1082 (m), 1022 (m), 838 (m); 'H NMR (400 MHz, CDCh) 5 6.16 (d. J = 2.1 Hz, 1H), 4.91 (tdd. J = 9.9, 4.7. 1.6 Hz, 1H), 4.53 (d, J = 9.4 Hz, 1H). 4.08 (t, J = 9.7 Hz, 1H), 3.81-3.60 (m, 3H), 2.42-2.32 (m, 1H), 2.05 (s, 3H), 1.99 (d, J = 1.7 Hz, 3H), 1.97 (s, 3H), 1.69 (q, J = 12.0 Hz, 1H), 1.41 (s, 9H). 0.86 (s, 9H), 0.02 (s, 3H), 0.01 (s, 3H);13C NMR (100 MHz, CDCh) 8 169.7, 169.4, 154.7, 91.9, 80.1, 73.2, 65.9, 61.9, 56.1, 47.6, 30.7, 30.6, 30.5, 28.3 (3C), 25.8 (3C), 21.0, 18.3, -5.36, -5.43; HRMS: m / z (ESI) calcd for C23H43BrNO8Si+, [M + H]+, 568.1936, found 568.1947.1J13CI-HI = 178.0 Hz.Scheme 107.Fe(L1)(BF4)2(MeCN)(H2O)2Me (1) (15 mol%)AcO-r^-0TBSO-k^S* CH2CI2, 5 A MS-40 °C, c = 0.3 M, 2 h S11 3f 151.5 equiv 74% yield

[0414] Sil was synthesized was synthesized from D-rhamnal (Pihko, A. J.; Nicolaou, K. C.; Koskinen, A. M. P. An Expedient Synthesis of D-Callipeltose. Tetrahedron: Asymmetry 2001, 12, 937) according to a literature procedure (Balmond, E. I., et al., A 3,4-fra / 75-Fused Cyclic Protecting Group Facilitates a-Selective Catalytic Synthesis of 2-Deoxyglycosides. Angew. Chem. Int. Ed.2014, 53, 8190).

[0415] The glycal m-aminoacyloxylation was carried out on a 0.3 mmol scale by following the general procedure. The desired product 15 was purified through a silica gel flash column (hexanes / ethyl acetate: from 100:1 to 12:1) as white foam (126 mg, 74% yield).

[0416] 4-O-Acetyl-2-terf-butoxycarbonylamino-3-O-ferf-butyldimethylsilyl-2,6-di-deoxy-a-D-glucopyranosyl 2-bromo-2-methylpropanoate (15): IR vmax (neat) / cm-1: 3420 (w), 2931(w), 2858 (w), 1750 (m), 1720 (m), 1504 (w), 1463 (w), 1391 (w), 1367 (m), 1249 (m), 1223 (s), 1156 (s), 1130 (s), 1104 (m), 1087 (m), 1062 (m), 1045 (m), 999 (s), 922 (m), 837 (s); ‘H NMR (400 MHz, CDC13) 86.13 (d, J = 3.5 Hz, 1H), 4.82 (t, J = 9.4 Hz, 1H), 4.48 (d, J = 9.8 Hz, 1H), 4.01 (td, J = 10.0, 3.4 Hz. 1H), 3.91-3.74 (m, 2H), 2.10 (s, 3H), 1.99 (s, 3H), 1.97 (s, 3H). 1.41 (s, 9H), 1.15 (d, J = 6.3 Hz, 3H), 0.85 (s, 9H), 0.08 (s, 3H), 0.05 (s, 3H);13C NMR (100 MHz, CDCI3) 8 169.6, 169.5, 154.8, 93.4, 80.0, 75.8, 70.6, 68.9, 56.2, 55.0, 30.6, 30.4, 28.3 (3C), 25.6 (3C), 21.3,17.8, 17.5, -4.4 (two peaks overlapped, 2C); HRMS: m / z (ESI) calcd for C23H43BrNOsSi+, [M + H]+, 568.1936, found 568.1952. Va-m = 178.4 Hz.Scheme 108.Fe(L1)(BF4)2(MeCN)(H2O)2(1) (15 mol%)TBSO-r - OTBSO— CH2CI2, 5 A MS-40 °C, c = 0.3 M, 2 hS12

[0417] S12 was synthesized according to a literature procedure (Li, H. et al. Stereoselective Glycosylation for 1,2- - Aminoglycoside Assembly by Cooperative Atom Transfer Catalysis. J. Am. Chem. Soc. 2024, 146, 33316).

[0418] The glycal m-aminoacyloxylation was carried out on a 0.3 mmol scale by following the general procedure. The desired product 16 was purified through a silica gel flash column (hexanes / diethyl ether: from 100:1 to 14:1) as white foam (137 mg, 73% yield).

[0419] 2-ter / -Butoxycarbonylamino-3,4-di-O-ter / -butyIdimethylsilyl-2-deoxy-a-D-xylopyranosyl 2-bromo-2-methylpropanoate (16): IR Vmax (neat)Zcm’1: 3433 (w), 2954 (w), 2930 (w), 2895 (w), 2858 (w), 1749 (m), 1718 (m), 1508 (m), 1463 (w), 1390 (w), 1366 (m), 1252 (m), 1158 (m), 1106 (m), 1052 (m), 1001 (m), 834 (s);1H NMR (400 MHz, CDCh) 85.94 (d, J = 1.9 Hz, 1H), 5.81 (d. J = 10.3 Hz, 1H). 4.04 (dd, J = 12.5, 2.0 Hz. 1H), 3.88 (ddd, J = 10.4, 3.9, 1.9 Hz, 1H), 3.83-3.71 (m, 2H), 3.47 (dd, J = 3.9, 2.3 Hz, 1H), 1.94 (s, 3H), 1.93 (s, 3H), 1.40 (s, 9H), 0.93 (s, 9H), 0.90 (s, 9H), 0.14 (s, 3H), 0.10 (s, 6H), 0.09 (s, 3H).;13C NMR (100 MHz, CDCh) 8 169.8, 155.2, 93.3, 78.9, 71.5, 69.9, 68.2, 55.6, 51.8, 30.6. 30.4. 28.4 (3C). 25.8 (3C). 25.7 (3C), 17.9. 17.8, -4.8, -4.9 (two peaks overlapped, 2C), -5.0; HRMS: m / z (ESI) calcd for C26H53BrNO? Si+, [M+ H]+, 626.2538, found 626.2554. J13CI-HI = 178.4 Hz.Scheme 109.3f1.5 equiv

[0420] S13 was synthesized according to a literature procedure (Li, H. et al. Stereoselective Glycosylation for 1,2-cis- Aminoglycoside Assembly by Cooperative Atom Transfer Catalysis. J. Am. Chem. Soc. 2024, 146, 33316).

[0421] The glycal cA-aminoacyloxylation was carried out on a 0.3 mmol scale by following the general procedure. The desired product 17 was purified through a silica gel flash column (hexanes / ethyl acetate: from 100:1 to 5:1) as white foam (210 mg, 70% yield).

[0422] 2-terZ-Butoxycarbonylamino-3-O-te7t-butyldimethylsilyl-4,6-O-isopropylidene-2-deoxy-a-D-glucopyranosyl-(l— >6)-4-O-acetyl-2-terr-butoxycarbonylamino-3-O-terf-butyldimethylsilyl-2-deoxy-a-D-glucopyranosyl 2-bromo-2-methylpropanoate (17): IR vmax (neat) / cm’1: 3384 (w), 2930 (w), 2857 (w), 1753 (m), 1715 (m), 1505 (m), 1367 (m), 1224 (m),1155 (s), 1129 (s), 1081 (m), 1037 (m), 999 (s), 944 (m), 922 (w), 863 (m), 836 (s); ‘H NMR (400 MHz, acetone-tfc) 56.12 (d, J = 3.8 Hz, 1H), 5.70 (d, J = 9.6 Hz, 1H), 5.61 (d, J = 8.2 Hz, 1H), 5.14 (t, J = 9.7 Hz, 1H). 4.79 (d, J = 2.6 Hz, 1H). 4.23-4.10 (m, 2H), 4.04 (td, J = 10.0. 3.7 Hz, 1H), 3.79-3.67 (m, 5H), 3.60-3.46 (m, 3H), 2.15 (s, 3H), 2.00 (s, 3H), 1.99 (s, 3H), 1.49 (s, 3H), 1.44 (s, 9H), 1.40 (s, 9H), 1.36 (s, 3H). 0.88 (s, 9H), 0.87 (s, 9H), 0.15 (s, 3H), 0.11 (s, 6H), 0.10 (s, 3H);13C NMR (100 MHz, acetone-^) 8 170.4, 169.9, 156.1, 156.0, 100.2, 99.9, 93.8, 79.6, 79.1, 75.9, 72.8, 72.2, 72.1, 71.9, 66.0, 64.6, 62.9, 58.0, 56.7, 56.0, 30.62, 30.56, 29.6, 28.8 (3C), 28.6 (3C), 26.4 (3C), 26.2 (3C), 21.6, 19.4, 18.9, 18.6, -3.8, -4.1, -4.2, -4.6; HRMS: m / z (ESI) calcd for C43H8oBrN2Oi5Si2+, [M + H]+, 999.4275, found 999.4289. JISCI-HI = 181.4 Hz, 171.6 Hz.Scheme 110.OU•'BuO^S14 3f1 5 equiv

[0423] S14 was synthesized according to a literature procedure ((Li, H. et al. Stereoselective Glycosylation for 1,2-cis- Aminoglycoside Assembly by Cooperative Atom Transfer Catalysis. J. Am. Chem. Soc. 2024, 146, 33316).

[0424] The glycal cA-aminoacyloxylation was carried out on a 0.3 mmol scale by following the general procedure. The desired product 18 was purified through a silica gel flash column (hexanes / diethyl ether: from 100:1 to 1:1) as white foam (223 mg, 84% yield).

[0425] 2-ter / -Butoxycarbonylamino-3-O-terf-butyldimethylsilyl-4,6-O-isopropylidene-2-deoxy-a-D-glucopyranosyl-(l— >3)-4,6-di-O-acetyl-2-terCbutoxycarbonylamino-2-deoxy-a-D-glucopyranosyl 2-bromo-2-methylpropanoate (18): IRvmax (neat) / cm-1: 3443 (w). 2976 (w), 2930 (w), 2856 (w), 1752 (m), 1718 (m), 1502 (m), 1462 (w), 1368 (m), 1235 (m), 1216 (m), 1158 (s), 1130 (s), 1081 (m), 1033 (m). 1014 (m), 944 (w), 875 (m), 838 (m); 'HNMR (400 MHz, CDCh) 5 6.32 (d, J = 3.6 Hz, 1H), 5.17 (t, J = 9.7 Hz, 1H), 4.92 (d, J = 4.1 Hz, 1H), 4.67 (d, J = 9.0 Hz, 1H), 4.55 (d, J = 10.2 Hz, 1H), 4.17-4.02 (m, 3H), 3.99-3.78 (m, 4H), 3.76-3.59 (m, 2H), 3.57-3.42 (m, 2H), 2.073 (s, 3H), 2.068 (s, 3H), 1.98 (s, 3H), 1.98 (s, 3H), 1.46 (s, 18H), 1.45 (s. 3H), 1.37 (s, 3H), 0.85 (s, 9H), 0.04 (s, 6H);13C NMR (100 MHz, CDCh) 5 170.6, 169.3, 169.3, 155.4, 154.7, 100.8, 99.3, 92.4, 80.9, 79.9, 75.3, 74.6, 71.0, 70.6, 70.2, 64.5, 62.2, 56.4, 55.4, 52.8, 30.5, 30.4, 28.8, 28.5 (3C), 28.0 (3C), 25.8 (3C), 20.9, 20.7 (two peaks overlapped, 2C). 18.9, 18.3, -4.2. -4.9: HRMS: m / z (ESI) calcd for C39H68BrN2Oi6Si+, [M + H]+, 927.3516, found 927.3513. J13ci-m = 186.0 Hz, 170.8 Hz.Scheme 111.Fe(L1)(BF4)2(MeCN)(H2O)2 (1) (15 mol%) CH2CI2, 5 A MS 40 °C, c = 0.3 M, 2 h 3f1.5 equiv

[0426] S15 was synthesized according to a literature procedure (Upreti, M.; Vishwakarma, R. A., Synthesis of the phosphodisaccharide repeat of antigenic lipophosphoglycan of Leishmania donovani parasite. Tetrahedron Lett. 1999, 40, 2619).

[0427] The glycal cA-aminoacyloxylation was carried out on a 0.3 mmol scale by following the general procedure. The desired product 19 was purified through a silica gel flash column (CH2Cl2 / MeOH: from 100:1 to 50:1) as white foam (167 mg, 66% yield).

[0428] 2,3,4,6-Tetra-O-acetyl-b-D-galactopyranosyl-( 1— >4)-3,6-di-O-acetyl-2-tert-butoxycarbonylamino-2-deoxy-a-D-glucopyranosyl 2-bromo-2-methylpropanoate (19): IR Vmax(neat)Zcm1: 3340 (w), 2980 (w), 1742 (s), 1712 (m), 1517 (w). 1434 (w), 1367 (m), 1214 (s), 1157 (m), 1132 (m), 1046 (m), 954 (w), 901 (w); ’H NMR (400 MHz, CDCh) 86.19 (d, J = 3.7 Hz, 1H), 5.36 (dd, J = 3.5, 1.2 Hz, 1H), 5.22 (dd, J = 10.9, 9.1 Hz, 1H), 5.14 (dd, J = 10.4, 7.9 Hz, 1H), 4.96 (dd. J = 10.4, 3.4 Hz, 1H), 4.65 (d. J = 9.6 Hz, 1H), 4.53 (d. J = 7.9 Hz, 1H), 4.44 (dd, J = 12.1, 2.1 Hz, 1H), 4.11 (tdd, J = 10.9, 9.4, 7.7, 4.8 Hz, 4H), 4.03-3.96 (m, 1H), 3.92-3.78 (m, 2H), 2.15 (s, 3H), 2.10 (s, 6H). 2.07 (s, 3H), 2.04 (s, 3H), 1.99 (s, 6H), 1.97 (s, 3H), 1.40 (s, 9H);13C NMR (100 MHz. CDCh) 6 170.6. 170.3. 170.2, 170.05. 170.01, 169.5, 169.1. 155.1. 101.3, 92.0, 80.4, 75.9, 71.0, 70.91, 70.87, 70.6, 69.1, 66.5, 61.5, 60.7, 55.3, 52.9, 30.4, 30.3, 28.1 (3C), 20.8, 20.7, 20.6 (three peaks overlapped, 3C), 20.5.: HRMS: m / z (ESI) calcd for Cs3H49BrNOi9+, [M + H]+, 842.2077, found 842.2090. '. J' 'CI-HI = 178.0 Hz, 162.4 Hz.H. Iron-Catalyzed Glycal cis-Aminoacyloxylation with External Carboxylic Acids Scheme 112Fe(L1)(BF4)2(MeCN)(H2O)2(1) (15 mol %) CH2CI2, 5 A MS -40 C, c = 0 3 M, 2 h 2 31 S16 4e 4f1 5 equiv 1 0 equiv 38% yield 44% yield

[0429] To a flame-dried sealable 2-dram vial (vial A) equipped with a stir bar were added glycal 2 (90 mg, 0.3 mmol, 1.0 equiv). amination reagent 3f (127 mg, 0.45 mmol, 1.5 equiv), carboxylic acid S16 (44 mg, 0.3 mmol, 1.0 equiv), and freshly activated 5 A powdered molecularsieves (ca. 150 mg). After the vial was evacuated and backfilled with N2 three times, anhydrous CH2O2 (0.5 mL) was added and the solution was cooled to -78 °C. To a second flame-dried sealable 2-dram vial (vial B) were added iron catalyst 1 Fe(Ll)(BF4)2(MeCN)(H2O)2 (26.5 mg, 0.045 mmol, 15 mol %) and freshly activated 5 A powdered molecular sieves ca. 150 mg). Vial B was evacuated and backfilled with N2 three times and then anhydrous CH2CI2 (0.5 mL) was added and stirred for 3 min, then vial B solution was added to vial A dropwise via a syringe within 1 min. The reaction was subsequently raised to -40 °C and kept at the same temperature for an additional 2 h. The reaction was then quenched by precipitating the iron catalyst with Et2O (4 mL) at the same temperature. The mixture was stirred for 2 min and subsequently warmed up to room temperature. The solution was then filtered through a piece of cotton and washed with saturated aq. NaHCO3 solution (2 mL). The organic layer was separated from the aqueous one, which was further extracted with CH2O2 (3 mL x 3). The combined organic layers were dried over anhydrous Na2SC>4 and concentrated in vacuo. The residue was purified through a silica gel flash column (hexanes / ethyl acetate: from 100:1 to 12:1) to afford glycal cA-aminoacyloxylation products 4e (64 mg, 38% yield) and 4f (77 mg, 44% yield) both as white foam.

[0430] In this experiment, the reaction was conducted in the presence of 1.0 equivalent of external carboxylic acid S16. In addition to the anticipated aminoacyloxylation product 4f, glycosyl ester 4e was also isolated in comparable yield. This result indicates that external carboxylic acids are capable of undergoing ligand exchange with the native carboxylic acid component and can be competitively incorporated into the glycosyl ester product under the reaction conditions.Terms and defintions

[0431] "‘Amine protecting groups” as used herein include carbonyloxy groups of the formula -C(=O)OR2) wherein R2is Ci-10 alkyl, C1-10 perhaloalkyl, C2-10 alkenyl, C2-10 alkynyl, C3-10 carbocyclyl, 3-14 membered heterocyclyl, CA-u aryl, and 5-14 membered heteroaryl, or two R2groups are joined to form a 3-14 membered heterocyclyl or 5-14 membered heteroaryl ring, wherein each alkyl, alkenyl, alkynyl, carbocyclyl, heterocyclyl, aryl, and heteroaryl is optionally substituted. Together with the nitrogen, these can be referred to as carbamate groups, and include, but are not limited to, methyl carbamate, ethyl carbamante, 9-fluorenylmethyl carbaminclude, but are not limited to, methyl carbamate, ethyl carbamante, 9-fluorenylmethyl carbamate (Fmoc). 9-(2- sulfo)fluorenyhnethyl carbamate. 9-(2,7-dibromo)fluoroenylmethyl carbamate, 2,7-di-t-butyl-[9- (10, 10-dioxo- 10,10, 10, 10-tetrahydrothioxanthyl)]methyl carbamate (DBD-Tmoc), 4-methoxyphenacyl carbamate (Phenoc), 2,2,2-trichloroethyl carbamate (Troc), 2-trimethylsilylethyl carbamate (Teoc), 2-phenylethyl carbamate (hZ), l-(l-adamantyl)-l-methylethyl (Adpoc), 1,1-dimethyl-2-haloethyl carbamate, 1,1 -dimethyl- 2,2 ■dibromoethyl carbamate (DB-t-BOC), 1.1- dimethyl-2,2,2-trichloroethyl carbamate (TCBOC), 1 -methyl- 1 -(4-biphenylyl)ethyl carbamate (Bpoc), l-(3,5-di-t-butylphenyl)-l -methylethyl carbamate (t-Bumeoc), 2-(2’- and 4'-pyridyl)ethyl carbamate (Pyoc), 2-(N, N-dicyclohexylcarboxamino)ethyl carbamate, t- butyl carbamate (BOC), 1 -adamantyl carbamate (Adoc), vinyl carbamate (Voc), allyl carbamate (Alloc), 1 -isopropylallyl carbamate (Ipaoc), cinnamyl carbamate (Coc), 4-nitrocinnamyl carbamate (Noc), 8-quinolyl carbamate, N-hydroxypiperidinyl carbamate, alky Idithio carbamate, benzyl carbamate (Cbz), p-methoxy benzyl carbamate (Moz), p-nitobenzyl carbamate, p-bromobenzyl carbamate, p-chlorobenzyl carbamate, 2,4-dichlorobenzyl carbamate. 4-methy I sulfinylbenzyl carbamate (Msz), 9-anthrylmethyl carbamate, diphenylmethyl carbamate, 2 -methylthioethyl carbamate, 2-methylsulfonylethyl carbamate, 2-(p-toluenesulfonyl)ethyl carbamate, [2-(l,3-dithianyl)]methyl carbamate (Dmoc), 4-methylthiophenyl carbamate (Mtpc). 2,4-dimethylthiophenyl carbamate (Bmpc), 2-phosphonioethyl carbamate (Peoc), 2-triphenylphosphonioisopropyl carbamate (Ppoc), 1, 1 -dimeth yl-2-cyanoethyl carbamate, m-chloro- p- -acy lox benz 1 carbamate, p- (dihydroxyboryl)benzyl carbamate, 5-benzisoxazolylmethyl carbamate, 2-(trifluoromethyl)-6- chromonylmethyl carbamate (Tcroc), m-nitrophenyl carbamate, 3,5-dimethoxybenzyl carbamate, o-nitrobenzyl carbamate, 3,4-dimethoxy-6-nitrobe-nzyl carbamate, phenyl(o-nitrophenyl)methyl carbamate, t-amyl carbamate, S-benzyl thiocarbamate, p-cyanobenzyl carbamate, cyclobutyl carbamate, cyclohexyl carbamate, cyclopentyl carbamate, cyclopropylmethyl carbamate, p- decyloxybenzyl carbamate, 2.2-dimethoxyacylvinyl carbamate, o-(N, N- dimet.hylcarboxamino)benzyl carbamate, l,l-dimethyl-3-(N, N-dimethylcai’boxamino)propyl carbamate, 1,1-dimethylpropyrtyl carbamate, di(2-pyridyl)methyl carbamate, 2-furanylmethyl carbamate. 2-iodoethyl carbamate, isoborynl carbamate, isobutyl carbamate, isonicotinyl carbamate, p- •(p’-methoxyphenylazo)benzyl carbamate, 1 -methylcyclobutyl carbamate, 1 -methylcyclohexyl carbamate, 1 -methyl- 1 -cyclopropylmethyl carbamate. l-methyl-l-(3,5-dimethoxyphenyl)ethyl carbamate, 1 -methyl- l-(p-phenylazophenyl)ethyl carbamate, 1 -methyl- 1 -phenylethyl carbamate, 1-mothyl-l-(4-pyridyl)ethyl carbamate, phenyl carbamate, p-(phenylazo)benzyl carbamate, 2,4.6-tri-t-butylphenyl carbamate, 4-(trimethylammonium)benzyl carbamate, and 2.4,6- trimethylbenzyl carbamate.

[0432] “Diagnostic agent” as used herein is a molecule used in the diagnosis of a conditionof an animal (in particular a human), fungi, insect, or plant. A diagnostic agent can be, for example, an amino acid, peptide, antibiotic, small molecule drug, prodrug, saccharide, inorganic atom, inorganic molecule, dye, imaging agent, lipid, nucleoside, radionuclide, oligonucleotide, or toxin.

[0433] “Glycal” is a cyclic enol ether derivative of a 5- or 6-carbon sugar having a double bond between carbon atoms 1 and 2 of the ring, endo to the ring.

[0434] “Hydroxy protecting group” is a labile chemical moiety that protects a hydroxyl group against undesired reactions during a synthetic procedure. After the synthetic procedure, the hydroxy protecting group may be selectively removed. Hydroxy protecting groups as known in the art are described generally in T. H. Greene and P. G. M. Wuts. Protective Groups in Organic Synthesis. 3rd edition, John Wiley & Sons, New York (1999). A protecting group reacts selectively in good yield to give a protected substrate that is stable to the projected reactions; the protecting group is preferably selectively removable by readily available, preferably nontoxic reagents that do not attack the other functional groups; the protecting group forms a separable derivative (more preferably without the generation of new stereogenic centers); and the protecting group will preferably have a minimum of additional functionality to avoid further sites of reaction. By way of non-limiting example, hydroxyl protecting groups include methyl (Me), methoxylmethyl (MOM), methylthiomethyl (MTM), t-butylthiomethyl, (phenyldimethylsilyl)methoxymethyl (SMOM), benzyloxymethyl (BOM), p-methoxybenzyloxymethyl (PMBM), (4-methoxyphenoxy)methyl (p-AOM), guaiacolmethyl (GUM), t-butoxymethyl, 4-pe-ntenyloxymethyl (POM), siloxymethyl, 2- methoxyethoxymethyl (MEM), 2, 2, 2-trichloroetb xymethyl. bis(2-chloroethoxy)methyl, 2- (triethylsilyl)ethoxymethyl (SEMOR), tetrahydropyranyl (THP), 3-bromotetrahydropyranyl, tetrahydrothiopyranyl, 1- methoxy cyclohexyl, 4-methoxytetrahydropyranyl (MTHP), 4- methoxytetrahydrothiopyranyl, 4-methoxytetrahydrothiopyranyl S,S-dioxide. l-[(2-chloro-4- methyl)phenyl]-4-methoxypiperidin-4-yl (CTMP), 1,4-dioxan-2-yl, tetrahydrofuranyl, tetrahydrothiofuranyl. 2,3,3a,4.5,6,7.7a-octahydro-7,8,8-trimethyl-4,7-methanobenzofuran-2-yl, 1-ethoxyethyl, l-(2-chloroethoxy)ethyl, 1 -methyl- 1 -methoxyethyl, 1 -methyl- 1 -benzyloxyethyl, 1- methyl-l-benzyloxy-2-fluoroethyl, 2,2,2-trichloroethyl, 2-trimethylsilylethyl, 2-(phenylselenyl)ethyl, t-butyl, allyl, p-chlorophenyl, p-methoxyphenyl, 2,4-dinitrophenyl, benzyl, p- methoxybenzyl, 3, 4- dimeth oxy benzyl, o-nitrobenzyl, p-nitrobenzyl, p-halobenzyl, 2,6- dichlorobenzyl, p-cyanobenzyl. p-phenylbenzyl, 2-picolyl. 4-picolyl, 3-methyl-2-picolyl N-oxido, diphenylmethyl, p,p’-dinitrobenzhydryl, 5-dibenzosuberyl, triphenylmethyl, a- naphthyldiphenylmethyl, p-methoxyphenyldiphenylmethyl, di(p-methoxyphenyl)phenylmethyl,tri(p-methoxyphenyl)methyl, 4-(4’-bromophenacyloxyphenyl)diphenylraethyl, 4,4',4"-tris(4.5-dichlorophthalimidophenyl)methyl, 4,4',4”-tris(levulinoyloxyphenyl)methyl, 4,4’,4"-tris(benzoyloxyphenyl)methyl, 3-(imidazol- l-yl)bis(4*,4"-dimethoxyphenyl)methyl, 1, l-bis(4- methoxyphenyl)-r-pyrenylmethyl, 9-anthryl, 9-(9-phenyl)xanthenyl, 9-(9-phenyl-10-oxo)anthryl, l,3-benzodithiolan-2-yl, benzisothiazolyl S, S-dioxido, trimethylsilyl (TMS), triethylsilyl (TES), triisopropylsilyl (TIPS), dimethylisopropylsilyl (IPDMS), diethylisopropylsilyl (DEIPS), dimethyl thexylsilyl, t-butyldimethylsilyl (TBDMS), t-butyldiphenylsilyl (TBDPS), tribenzylsilyl, tri-p-xylylsilyl, triphenylsilyl. diphenylmethylsilyl (DPMS), t-butylmethoxyphenylsilyl (TBMPS), formate, benzoylformate, acetate, chloroacetate, dichloroacetate, trichloroacetate, tri fluoroacetate, methoxyacetate, triphenylmethoxyacetate, phenoxyacetate, p-chlorophenoxyacetate, 3- phenylpropionate, 4-oxopentanoate (levulinate), 4,4-(ethyIenedithio)pentanoate (levuHnoyldithioacetal), pivaloate, adamantoate, crotonate, 4-methoxycrotonate, benzoate, p- phenylbenzoate, 2,4,6-trimethylbenzoate (mesitoate), alkyl methyl carbonate, 9-fluorenylmethyl carbonate (Fmoc). alkyl ethyl carbonate, alkyl 2.2,2-trichloroethyl carbonate (Troc). 2- (trimethylsilyl)ethyl carbonate (TMSEC), 2-(phenylsulfonyl)ethyl carbonate (Psec), 2- (triphenylphospbonio) ethyl carbonate (Peoc), alkyl isobutyl carbonate, alkyl vinyl carbonate alkyl allyl carbonate, alkyl p-nitrophenyl carbonate, alkyl benzyl carbonate, alkyl p-methoxybe-nzyl carbonate, alkyl 3,4-dimethoxybenzyl carbonate, alkyl o-nitrobenzyl carbonate, alkyl p-nitrobenzyl carbonate, alkyl S-benzyl thiocarbonate, 4-ethoxy- 1-napththyl carbonate, methyl dithiocarbonate, 2- iodobenzoate, 4-azidobutyrate, 4-nitro-4-methylpentanoate, o-(dibromomethyl)benzoate, 2- formylbenzenesulfonate, 2-(methylthiomethoxy)ethyl, 4-(methylthiomethoxy)butyrate, 2- (methylthiomethoxymethyl)benzoate, 2,6-dichloro-4-methylphenoxyacetate, 2,6-dichloro-4- (l,1.3,3-tetramethylbutyl)phenoxyacetate, 2,4-bis(l,l-dimethylpropyl)phenoxyacetate, chlorodiphenylacetate, isobutyrate, monosuccinoate, (E)-2-methyl-2-butenoate, o-(methoxycarbonyl)benzoate, a-naphthoate, nitrate, alkyl N, N, N', N'-tetramethylphosphorodiamidate, alkyl N-phenylcarbamate, borate, dimethylphosphinothioyl, alkyl 2,4-dinitrophenylsulfenate, sulfate, methanesulfonate (mesylate), benzylsulfonate, and tosylate (Ts).

[0435] For protecting 1,2- or 1,3-diols, the protecting groups include methylene acetal, ethylidene acetal, 1-t-butylethylidene ketal, 1-phenylethylidene ketal, (4-methoxyphenyl)ethylidene acetal. 2,2,2-trichloroethylidene acetal, acetonide, cyclopentylidene ketal, cyclohexylidene ketal, cycloheptylidene ketal, benzylidene acetal, p-methoxybenzylidene acetal, 2,4- dimethoxybenzylidene ketal, 3,4-dimethoxybenzylidene acetal, 2-nitrobenzylidene acetal,methoxymethylene acetal, ethoxymethylene acetal, dimethoxymethylene ortho ester, 1 - methoxyethylidene ortho ester, 1 -ethoxy ethylidine ortho ester, 1,2-dimethoxyethylidene ortho ester, a-methoxybenzylidene ortho ester, l-(N, N-dimethylamino)ethylidene derivative, a-(N, N'-dimethylamino)benzylidene derivative, 2-oxacyclopentylidene ortho ester, di-t-butylsilylene group (DTBS), l,3-(l,l,3,3-tetraisopropyldislloxanylidene) derivative (TIPDS), tetra-t-butoxydisiloxane-1,3-diylidene derivative (TBDS). cyclic carbonates, cyclic boronates, ethyl boronate. and phenyl boron ate,

[0436] Specific examples of hydroxy protecting groups include, but are not limited to, methyl (Me), benzyloxycarbonyl (Cbz), 4-nitrobenzyloxycarbonyl, 4-bromobenzyloxycarbonyl, 4-methoxy benzyloxy carbonyl, methoxycarbonyl, tert-butoxycarbonyl (Boc), isopropoxycarbonyl, diphenylmethoxycarbonyl, 2,2,2-trichloroethoxycarbonyl, 2-(trimethylsilyl)ethoxycarbonyl, 2-furfuryloxycarbonyl, allyloxycarbonyl, acetyl (Ac), formyl, chloroacetyl, trifluoroacetyl, methoxyacetyl, phenoxyacetyl, benzoyl (Bz), methyl, t-butyl, 2,2,2-trichloroethyl, 2 -trimethylsilyl ethyl, l,l-dimethyl-2-propenyl, 3-methyl-3-butenyl. allyl, benzyl, para-methoxybenzyldiphenylmethyl, triphenylmethyl (trityl), tetrahydrofuryl, methoxymethyl, methylthiomethyl, benzyloxymethyl, 2,2,2-trichloroethoxymethyl. 2-(trimethylsilyl)ethoxymethyl, methanesulfonyl, para-toluenesulfonyl. trimethylsilyl, triethylsilyl, and triisopropylsilyl.

[0437] A “non-coordinating counter anion” as used herein is an anion that does not form a coordination bond with the iron of the catalyst system, or that forms a weak coordination bond. Examples of non-coordinating anions include metal (e.g., aluminum, gold, or platinum) or metalloid (e.g., boron, aluminum, phosphorus, or silicon) complexes. Examples include (RfSO2)N‘, Al(OCRf)4, B(R / S)4-- B(Rf)4, or RfSO₃⁻, wherein R is an aryl group or a substituted aryl group, of which the one or more substituents are the same or different and are alkyl, or aryl, Rf is a monovalent alkyl, cycloalkyl, aryl, or aryl, each of which is substituted fluorine, fluorinated or perfluorinated alkyl, or fluorinated or perfluorinated aryl, CF3SO3, (CF3SO2)N_, CB₁₁H₁₂⁻, C1O4‘, A1(OC(CF3)3)4, ASF6’, SbF6", BF4", PF6⁻, B(C6F5)4’, B(C6H4)4", or B(3,5-(CF3)2C6H3)4-. a halogen atom, halogenated aryl, and haloalkylaryl groups

[0438] A nucleoside as used herein is a molecule including a nucleobase (e.g., adenine (A), aminoadeneine (Z), cytosine (C), guanine (G), thymine (T), or uracil (U)), where the N9 of a purine or the N1 of a pyrimidine is linked via a glycosidic bond to the anomeric carbon of a saccharide (e.g., ribose or deoxyribose). A polynucleoside can have, for example, 2-50, 2-40, 2-30, 2-20, 2-15, 2-10, 2-7, 2-5, 2-4. or 2-3 nucleoside units.

[0439] A nucleotide as used herein is a molecule including a nucleoside and a phosphate group linked to a primary hydroxy group of the nucleoside. A polynucleoside can have, for example, 2-50. 2-40, 2-30, 2-20, 2-15, 2-10. 2-7, or 2-5, or 2-4, or 2-3 nucleoside units.

[0440] “Peptides” as used herein is a chain of amino acids linked via peptide bonds, and can have from 2-50, 2-40, 2-30, 2-20, 2-15, 2-10, 2-8, or 2-5 amino acids.

[0441] A “saccharide” as used herein is a monosaccharide or a polysaccharide that can have, for example, 2-40, 2-30, 2-20, 2-15, 2-10, 2-8, or 2-5 monosaccharide units. Exemplary monosaccharides include, but are not limited to, natural sugars, such as allose, altrose. glucose, mannose, gulose, idose, galactose, talose, ribose, arabinose, xylose, and lyxose. Disaccharides are two joined monosaccharides. Exemplary disaccharides include, but are not limited to, sucrose, maltose, cellobiose, and lactose. Typically, an oligosaccharide includes between three and ten monosaccharide units (e.g., raffinose, stachyose). The saccharide can be a natural sugar or a modified sugar. Exemplary modified sugars include, but are not limited to, sugars where the hydroxyl group is replaced with an amino group and / or alkyl group (e.g., such as desosamine), 2'-deoxyribose wherein a hydroxyl group is removed, 2'-fluororibose wherein a hydroxyl group is replaced with a fluorine, or N-acetylglucosamine, or a nitrogen-containing form of glucose (e.g., 2'-fluororibose, deoxyribose, and hexose), and the like.

[0442] “Therapeutic agent” as used herein is a molecule intended for cure, mitigation, treatment, or prevention of disease in humans or other animals, or in plants, or to otherwise enhance physical or mental well-being of humans or animals or plants. A therapeutic agent can be in active or prodrug form. Examples of therapeutic agents include, for example, antibiotics, anti-viral agents, anti-inflammatory agents, anti-tumor agents, anti-anxiety agents, cardiovascular agents, fungicides, hormones, insecticides, growth factors, mitocides, steroidal agents, vitamin, vitamin cofactor, or the like.

[0443] A dash (“-”) that is not between two letters or symbols is used to indicate a point of attachment for a substituent. For example, -(C=O)NH2 is attached through the carbon of the keto (C=O) group.

[0444] “Alkyl” is a branched or straight chain saturated aliphatic hydrocarbon group. In an aspect, the alkyl group contains from about 1 to about 50 carbon atoms, more generally from 1 to about 36 carbon atoms, from 1 to about 12 carbon atoms, from 1 to about 8 carbon atoms, from 1 to about 6 carbon atoms, or from 1 to about 4 carbon atoms. In certain aspects, the alkyl is C1-C2, C1-C3, C1-C4, C1-C5, C1-C6, C1-C7, C1-C8, C1-C9, or C1-C10. For example, the term Ci-Cealkyl as usedherein indicates a straight chain or branched alkyl group having from 1, 2, 3, 4, 5, or 6 carbon atoms and is intended to mean that each of these are described as an independent species. In an aspect “alkyl” is a Ci-Cioalkyl. C1-C9alkyl, C1-C8alkyl, C1-C7alkyl, C1-C6alkyl, C1-C5alkyl, C1-C4alkyl, C1-C3alkyl, or C1-C2alkyl. In some aspects, the alkyl group is optionally substituted as defined herein

[0445] Examples of alkyl include, but are not limited to, methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, t-butyl, n-pentyl, isopentyl, tert-pentyl, neopentyl, n-hexyl, 2-methylpentane, 3-methylpentane. 2,2-dimethylbutane, and 2,3-dimethylbutane. In some aspects, the alkyl group is optionally substituted as defined herein.

[0446] “Alkenyl” is an alkyl group as described above having 2 to 50 carbon atoms where at least two carbon atoms are joined by a double bond. In certain aspects, the alkenyl is, C2-3, C2-4, C2-5. C2-6, C2-7, C2-8, C2-9, or C2-10. In some aspects, the alkenyl group is optionally substituted as defined herein.

[0447] “Alkynyl” is an alkyl group as described above having 2 to 50 carbon atoms where at least two carbon atoms are joined by a double bond. In certain aspects, the alkynyl is, C2-3, C2-4, C2-C5, C2-6. C2-7, C2-8, C2-9, or C2-10. In some aspects, the alkynyl group is optionally substituted as defined herein.

[0448] “Cycloalkyl” is a saturated group containing all carbon rings and from 3 to 50 carbon atoms (“C3-50cycloalkyl”) and zero heteroatoms in a monocyclic or polycyclic (e.g., bicyclic or tricyclic) non-aromatic ring system. In an aspect, a cycloalkyl group has 3 to 14 ring atoms (“C3-i4cycloalkyl”), or 3 to 10 ring atoms (“Cs-iocycloalkyl”), or 3 to 9 ring atoms (“C3-9cycloalkyl”). In an aspect, a cycloalkyl group has 3 to 8 ring atoms (“Cs-Cscycloalkyl”). In an aspect, a cycloalkyl group has 3 to 7 ring atoms (“Cs-vcycloalkyl”). In an aspect, a cycloalkyl group has 3 to 6 ring atoms (“Cs-Cecycloalkyl”). In an aspect, a cycloalkyl group has 4 to 6 ring atoms (“C4-ecycloalkyl”). In an aspect, a cycloalkyl group has 5 to 6 ring atoms (“Cs-ecycloalkyl”). In an aspect, a cycloalkyl group has 5 to 10 ring atoms (“Cs-iocycloalkyl”). In an aspect “cycloalkyl” is a C3-8cycloalkyl, C3-C7cycloalkyl, Cs-ecycloalkyl, C3-5cycloalkyl, C3-4cycloalkyl, C4-scycloalkyl, C5-Cscycloalkyl, or Ce-scycloalkyl. Exemplary C3-10cycloalkyl groups include, without limitation, cyclopropyl (C3), cyclobutyl (C4), cyclopentyl (C5), cyclohexyl (C6), cycloheptyl (C7), cyclooctyl (C8), cyclononyl (C9), cyclodecenyl (C10), and the like. In an aspect, a cycloalkyl group may be a bicyclic alkyl group, for example a spirocyclic alkyl group, a fused bicyclic alkyl group, or a bridged bicyclic alkyl group. In an aspect, “cycloalkyl” also includes ring systems wherein thecycloalkyl ring, as defined above, is fused with one heterocycloalkyl, aryl, or heteroaryl ring wherein the point of attachment is on the cycloalkyl ring, and in such instances, the number of carbon atoms continue to designate the number of carbons in the cycloalkyl ring system. Additional non-limiting examples of “cycloalkyl” include dihydro-indene and tetrahydronaphthalene wherein the point of attachment for each group is on the cycloalkyl ring. In an aspect, the cycloalkyl group is optionally substituted as defined herein.

[0449] “Heterocycloalkyl” is a cycloalkyl group as defined herein that contains at least one heteroatom, for example nitrogen, oxygen, sulfur, phosphorous, boron, or silicon, in place of a carbon atom. Heterocycloalkyl groups comprise monocyclic 3-8 membered rings, as well as 5-16 membered bicyclic ring systems (which can include bridged, fused, and spiro-fused bicyclic ring systems). It does not include rings containing -O-O, -0-S-, and -S-S- portions. In an aspect, “heterocycloalkyl” also includes groups that contain unsaturation between the heteroatom and a neighboring carbon in such a manner that results in the formation of a stable moiety, for example a -C=N- moiety. In an aspect, “heterocycloalkyl” also includes ring systems wherein the cycloalkyl ring, as defined above, is fused with one cycloalkyl, aryl, or heteroaryl ring wherein the point of attachment is on the heterocycloalkyl ring, and in such instances, the number of atoms continue to designate the number of atoms in the heterocycloalkyl ring system. In an aspect, the cycloalkyl group is optionally substituted as defined herein. In an aspect, the heterocycloalkyl group is optionally substituted as defined herein. Examples of heterocycloalkyl groups include saturated 3-to 6-membered heteromonocyclic groups containing 1 to 4 nitrogen atoms; saturated 3- to 6-membered heteromonocyclic groups containing 1 to 2 oxygen atoms and 1 to 3 nitrogen atoms; and saturated 3- to 6-membered heteromonocyclic groups containing 1 to 2 sulfur atoms and 1 to 3 nitrogen atoms. Additional examples of heterocycloalkyl groups include aziridinyl, oxiranyl, thiiranyl, azetidinyl, 1,3-diazetidinyl, oxetanyl, thietanyl, pyrrolidinyl, pyrazolidinyl, imidazolidinyl, 2-pyrazolinyl, 2-imidazolinyl, tetrahydrofuranyl, 1,3-dioxolanyl, tetrahydrothienyl, piperidinyl, piperazinyl, 1,2-oxathiolanyl, 1,3-oxathiolanyl, tetrahydropyranyl, 1,3-dioxanyl, thianyl, 1,3-dithianyl, 1,4-dithianyl, 1,3,5-trithianyl, morpholinyl, thiomorpholinyl, pyrrolizidinyl, indolinyl, isoindolinyl, decahydroisoquinolinyl, decahydroquinolinyl, 1,2,3,4-tetrahydroquinolinyl, quinuclidinyl, 1-azaadamantanyl, 2-azaadamantanyl, oxepanyl, azocanyl, thiocanyl, 1-oxaspiro[4.5]decanyl, l,6-dioxaspiro[3.4]octanyl, l-oxaspiro[4.4]nonanyl, 2-oxa-7-axaspiro[3.5]nonanyl, l,4-dioxa-7-axaspiro[4.4]nonanyl, oxazolidinyl, isoxazolidinyl, thiazolidinyl, isothiazolidinyl, dioxolanyl, dithiolanyl, dihydrobenzofuranyl, and dihydrobenzothienyl. Additionalnon-limiting examples of “heterocycloalkyl” include tetrahydrofuran, 1,3-dioxolane, tetrahydrothiophene, 1,2-oxathiolane, and l,3-oxathiolane;piperidine, piperazine, tetrahydropyran, 1.4-dioxane, thiane, 1.3-dithiane. 1,4-dithiane, morpholine, and thiomorpholine; indoline, tetrahydroquinoline, tetrahydroisoquinoline, and dihydrobenzofuran wherein the point of attachment for each group is on the heterocyclic ring. In an aspect, the cycloalkyl group is optionally substituted as defined herein.

[0450] “Aryl” is a group of a monocyclic or polycyclic (e.g., bicyclic or tricyclic) 4n+2 aromatic ring system (e.g., having 6, 10, or 14π electrons shared in a cyclic array) having 6-14 ring carbon atoms and zero heteroatoms provided in the aromatic system (“Ce-Cuaryl”). In an aspect, an aryl group has 6 ring carbon atoms (“Cearyl”; e.g., phenyl); or 10 ring carbon atoms (“Cioaryl”; e.g., naphthyl such as 1-naphthyl and 2-naphthyl); or 14 ring carbon atoms (“Cearyl”; e.g., anthracyl). “Aryl” also includes ring systems wherein the aryl ring, as defined above, is fused with one or more cycloalkyl or heterocycloalkyl groups wherein the point of attachment is on the aryl ring, and in such instances, the number of carbon atoms continue to designate the number of carbon atoms in the aryl ring system. The one or more fused cycloalkyl or heterocycloalkyl groups can be 4 to 7 or 5 to 7-membered cycloalkyl or heterocycloalkyl groups that optionally contain 1, 2, or 3 heteroatoms, including nitrogen, oxygen, phosphorous, sulfur, silicon, boron, or a combination thereof. In one non-limiting aspect, aryl groups are pendant. An example of a pendant ring is a phenyl group substituted with a phenyl group. In an aspect, the aryl group is optionally substituted as defined herein.

[0451] Non-limiting examples of “aryl” include phenyl, biphenyl, indoline, tetrahydroquinoline, tetrahydroisoquinoline, and dihydrobenzofuran wherein the point of attachment for each group is on the aromatic ring, dihydro-indene and tetrahydronaphthalene wherein the point of attachment for each group is on the aromatic ring.

[0452] “Heteroaryl” is an aryl ring system that contains one or more heteroatoms selected from O, N, and S, wherein the ring nitrogen and sulfur atom(s) are optionally oxidized, and nitrogen atom(s) are optionally quaternized. Examples include, but are not limited to: unsaturated 5- to 6-membered heteromonocyclyl groups containing 1 to 4 nitrogen atoms, such as pyrrolyl, imidazolyl, pyrazolyl, 2-pyridyl, 3-pyridyl, 4-pyridyl, pyrimidyl, pyrazinyl, pyridazinyl, and triazolyl [e.g., 4H- 1.2.4-triazolyl, lH-l,2,3-triazolyl, and 2H-l,2,3-triazolyl]; unsaturated 5- to 6-membered heteromonocyclic groups containing an oxygen group, for example, pyranyl, 2-furyl, 3-furyl, etc.; unsaturated 5- to 6-membered heteromonocyclic groups containing a sulfur atom, for example, 2-thienyl, 3-thienyl, etc.; unsaturated 5- to 6-membered heteromonocyclic groups containing 1 to 2 oxygen atoms and 1 to 3 nitrogen atoms, for example, oxazolyl, isoxazolyl, and oxadiazolyl [e.g., 1,2,4-oxadiazolyl, 1.3.4-oxadiazolyl. and 1,2,5-oxadiazolyl]: and unsaturated 5- to 6-membered heteromonocyclic groups containing 1 to 2 sulfur atoms and 1 to 3 nitrogen atoms, for example, thiazolyl and thiadiazolyl [e.g., 1,3,4-thiadiazolyl and 1,2,5-thiadiazolyl]. “Heteroaryl” also refers to polycyclic aromatic ring systems containing heteroatoms within the ring, for example, 1,4-dihydropyrollo[3,2-b]pyrrolyl, l,6-dihydropyrrolo[2,3-b]pyrrolyl, 6H-furo[2,3-b]pyrrolyl, 4H-furo[3,2-b]pyrrolyl, 4H-thieno[3,2-b]pyrrolyl, 6H-thieno[2,3-b]pyrrolyl, indolyl. isoindolyl, indolizinyl, indazolyl, benzimidazolyl, 7-azaindolyl, 6-azaindolyl, 5-azaindolyl, 4-azaindolyl, 7-azaindazolyl, pyrazole[l,5-a]pyrimidinyl, purinyl, benzofuryl, isobenzofuryl, benzo [c] thienyl, benzo[b]thienyl, 1,2-benzisoxazolyl, 2,1-benzisoxazolyl. 2,1-benzisothiazolyl, benzoxazolyl, benzothiazolyl, benzo[c][l,2,5]thiadiazolyl, quinolinyl, isoquinolinyl, 4H-quinolizinyl, quinoxalinyl, phthalazinyl, quinazolinyl, cinnolinyl, 1,8-naphthyridinyl, pyrido[3,2-d]pyrimidinyl, pyrido[4,3-d]pyrimidinyl, pyrido[3,4-b]pyrazinyl, pyrido[2,3-b]pyrazinyl, pteridinyl, carbazolyl, dibenzofuryl, acridinyl, phenazinyl, phenoxazinyl, phenothiazinyl, and phenoxathiinyl. Additional examples of heteroaryl groups include azepinyl, 1,2-diazepinyl, 1,3-diazepinyl, 1,4-diazepinyl, thiepinyl, 1,4-thiazepinyl, and azocinyl. Non-limiting examples of “heteroaryl” groups that are bicyclic include indole, benzofuran, isoindole, indazole, benzimidazole, azaindole, azaindazole, purine, isobenzofuran, benzothiophene, benzoisoxazole, benzoisothiazole, benzooxazole, and benzothiazole “Heteroaryl” also includes ring systems wherein the heteroaryl ring, as defined above, is fused with one or more cycloalkyl or heterocycloalkyl groups wherein the point of attachment is on the heteroaryl ring, and in such instances, the number of atoms continue to designate the number of atoms in the heteroaryl ring system. The one or more fused cycloalkyl or heterocycloalkyl groups can be 4 to 7 or 5 to 7-membered cycloalkyl or heterocycloalkyl groups that optionally contain 1, 2, or 3 heteroatoms independently selected from nitrogen, oxygen, phosphorous, sulfur, silicon, and boron. In one non-limiting aspect, aryl groups are pendant.

[0453] In an aspect “heteroaryl” is a 5-membered aromatic group containing 1, 2, 3, or 4 nitrogen atoms. Non-limiting examples of 5-membered heteroaryl groups include pyrrole, furan, thiophene, pyrazole, imidazole, triazole, tetrazole, isoxazole, oxazole, oxadiazole, oxatriazole, isothiazole, thiazole, thiadiazole, and thiatriazole.

[0454] “Substituted” denotes the substitution of a group herein by a moiety that forms a stable molecule and meets the desired purpose of the invention and includes, but is not limited toalkyl, heteroalkyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, alkoxy, cycloalkoxy, heterocycloalkoxy, aryloxy, heteroaryloxy, amino, alkylamino, dialkylamino, arylamino, diarylamino, heteroarylamino, alkylsufonamino, arylsufonamino, alkylimino, arylimino, alkylsulfonimino, arylsulfonimino, hydroxyl, halo, sulfhydryl, alkylthio, arylthio, alkylsulfonyl, arylsulfonyl, acylamino, aminoacyl, aminothioacyl, amidino, guanidine, ureido, cyano, nitro, azido, acyl, thioacyl, acyloxy, carboxyl, carboxyl ester, alkanoyl, carboxamide, alkylsufinyl, haloalkyl, B(OH)2, phosphate, phosphonate, and haloalkoxy. Such groups may be further substituted, for example with hydroxyl, alkyl, alkoxy, halogen, and amino, in such a manner that results in a stable moiety.

[0455] Unless specifically excluded by name (such as the “l,2-cis-2-aminoglycosides”), context or stereochemistry shown in a formula, the compounds in any of the other formulas may be in the form of a racemate, enantiomer, mixture of enantiomers, diastereomer, mixture of diastereomers, tautomer, N-oxide, or other isomer, such as a rotamer, as if each is specifically described unless specifically excluded by context.

[0456] The amino acids, peptides, hormones, nucleic acids, polynucleic acids, nucleosides, polynucleosides, polynucleotides, metabolites, steroids, vitamins, vitamin cofactors, and other biological materials as referred to herein can be the natural molecule, a non-natural molecule, a modified natural molecule, or a modified non-natural molecule

[0457] The compositions, methods, and articles can alternatively comprise, consist of, or consist essentially of, any appropriate materials, steps, or components herein disclosed. The compositions, methods, and articles can additionally, or alternatively, be formulated so as to be devoid, or substantially free, of any materials (or species), steps, or components, that are otherwise not necessary to the achievement of the function or objectives of the compositions, methods, and articles.

[0458] The terms “a” and “an” and “the” do not denote a limitation of quantity, but rather denote the presence of at least one of the referenced item. Thus, reference to “an” element in a claim followed by reference to “the” element is inclusive of one element and a plurality of the elements. The term “or” means “and / or” unless clearly indicated otherwise by context. Reference throughout the specification to “an aspect,” means that a particular element (e.g., feature, structure, step, or characteristic) described in connection with the aspect is included in at least one aspect described herein, and may or may not be present in other aspects. In addition, it is to be understood that the described elements may be combined in any suitable manner in the various aspects. Theterm “combination” is inclusive of blends, mixtures, alloys, reaction products, and the like. “At least one of’ preceding a list means that the list is inclusive of each element individually, as well as combinations of two or more elements of the list, and combinations of at least one element of the list with like elements not named.

[0459] When an element such as a layer, film, region, or substrate is referred to as being “on” another element, it can be directly on the other element or intervening elements may also be present. In contrast, when an element is referred to as being “directly on” another element, there are no intervening elements present.

[0460] In general, the compositions, methods, and articles can alternatively comprise, consist of, or consist essentially of, any ingredients, steps, or components herein disclosed. The compositions, methods, and articles can additionally, or alternatively, be formulated, conducted, or manufactured so as to be devoid, or substantially free, of any ingredients, steps, or components not necessary to the achievement of the function or objectives of the present claims.

[0461] The endpoints of all ranges directed to the same component or property are inclusive of the endpoints, are independently combinable, and include all intermediate points and ranges. For example, ranges of ...

Claims

CLAIMSWhat is claimed is:

1. A method for stereoselective synthesis of a l,2-cis-2-aminoglycoside, the method comprisingreacting a glycal of formula (I) with an amination agent of formula (II) and a glycosyl acceptor of formula (III) in the presence of an iron(II) catalyst, a solvent, and molecular sieves to provide the l,2-cis-2-aminoglycoside of formula (IV)(I) (ID (HD (IV) whereinr is 0 or 1,each R1, R2, R3, R4, and R5are independently hydrogen, azido, cyano, halo, hydroxy, nitro. — ()Ra, -~SRa, alkyl, cycloalkyl, heteroalkyl, heterocycloalkyd, aryl, or heteroaryl, wherein each of R!, RZ, R-\ R4. and R5that is not hydrogen, azido, cyano, halo, hydroxy, or nitro is optionally substituted with one or more of azido, cyano, halo, hydroxy, oxo, nitro, Ra, — ORa, —SR”, — N(Ra)(Ra), -- (C=O)Ra, — (C=O)ORa, - (C=O)N(Ra)(Ra), -■O(C=O)Ra, - N(Ra)(C— O)Ra, — O(C= O)N( Ra)( R?j, or — N( Ra)(C™O)ORa, or two R4or two R3together are oxo;R6and R7are each independently hydrogen, -S(~O)2Ra, -S(~O)2ORa, — (C=O)Ra, — (OO)OR3, ~(C=0)N(R3)(Ra), -O(C=O)Ra, — N(Ra)(O0)Ra, -O(C=O)N(R3)(R8), or —N(Ra)(C-=O)ORa,R8isan organic moiety having 1 to 60 carbon atoms and optionally 1 to 12 heteroatoms, wherein the heteroatoms are each independently N, O, P, S, Si, F, Br, I, As, or B, provided that the organic moiety includes no groups that would substantially adversely affect the reaction; oralkyl, cycloalkyl, heteroalkyl, heterocycloalkyl, aryl, or heteroaryl, or each of which R8is optionally substituted with one or more of azido, cyano, halo, hydroxy, nitro, oxo, Ra,OR-', SR". --N(Ra)(Ra), 4 )1G (( O)()Ra, --(O0)N(Ra)(Ra). -- O(C=O )Ra, - N(Ra)(C O)Ra, O(( O)N( Ra)(Ra), --N(Ra)(C=O)ORa, or a residue of an amino acid, peptide, diagnostic agent, lipid, metabolite, nucleoside, polynucleoside, nucleotide, polynucleotide, monosaccharide, polysaccharide, steroid, or therapeutic agent; andeach Rais independently at each occurrence hydrogen, azido, cyano, halo, hydroxyl, nitro, alkyl cycloalkyl, heteroalkyl, heterocycloalkyl, aryl, heteroaryl, or tri alkylsilyl, each of which Raother than hydrogen azido, cyano, halo, hydroxyl, or nitro is optionally substituted with one or more of hydrogen, azido, cyano, halo, alkyl, aryl, cycloalkyl, heterocycloalkyl, heteroaryl, heterocycloalkyl, alkoxy, aryloxy, amino, alkylamino, dialkylamino, acylamino, aminoacyl, acyl, acyloxy, carboxyl, carboxyl ester, alkanoyl, carboxamide, haloalkyl, or haloalkoxy; ortwo Ragroups together with the atoms to which they are attached form a cycloalkyl, heterocycloalkylaryl, or heteroaryl ring, each of which ring is optionally substituted with one or more of alkyl, heteroalkyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, alkoxy, aryloxy, amino, alkylamino, dialkylamino, hydroxyl, halo, acylamino, aminoacyl, cyano, nitro, azido, acyl, acyloxy, carboxyl, carboxyl ester, alkanoyl, carboxamide, haloalkyl. or haloalkoxy.

2. The method of claim 1, whereinthe glycosyl acceptor (III) is a monosaccharide or a polysaccharide having a primary or secondary hydroxyl group and optionally one or more protected hydroxy groups, protected amino groups, or a combination thereof; orthe glycosyl acceptor (III) is of the formulaorwhereinX is O, N, or S,. preferably O;G1is a bond or a linking group that can be an alkylene, cycloalkylene, heteroalkylene, orheterocycloalkylene. each optionally substituted with one or more of azido, cyano, halo, hydroxyl, nitro, Ra, OR3. --SR3, — N(Ra)(Ra),: C=O )R \ — (C==O)ORa, --- (C=O)N(Ra)(Ra), ()(( O)Ra, --N(Ra)(CX))Ra. --0(O0)N(Ra)(Ra). or — N(Ra)(C=O)ORa; andand each R11is independentlyhydrogen, azide, cyano, halo, hydroxy, nitro, alkyl, cycloalkyl, heteroalkyl.heterocycloalkyl, aryl, heteroaryl, — ORa, or — SRa, each of which R11is optionally substituted with one or more of oxo, halo, hydroxy, cyano, azido, nitro. Ra. OR:. --- SR\ ---N(Ra)(Ra). --(C-=O)Ra, --(C=-O)OR3, — (C=-0 )N( Ra)( Ra), OfC-dfiR — N(Ra)(C==O)R --()(O0)N(Ra)(Ra), -N(R’)(C=O)OR‘, wherein each Rais as defined in claim 1,or a residue of an amino acid, peptide, diagnostic agent, lipid, metabolite, nucleoside, polynucleoside, nucleotide, polynucleotide, monosaccharide, polysaccharide, steroid, or therapeutic agent: andn is 1 or 2 and m is the number of valences on the carbon atoms available for substitution; or the glycosyl acceptor (III) is a glycal of the formulawhereinr is 0 or 1, andR;i, R4, and R5are each independently hydrogen, azide, cyano, halo, hydroxy, nitro, - — ()Ra, — SRa, alkyl, cycloalkyl, heteroalkyl, heterocycloalkyl, aryl, or heteroaryl, each optionally substituted with one or more of hydrogen, azido, cyano, halo, hydroxy, nitro, — ORa, oxo, — SRa, Ra, OR '. --N(Ra)(Ra),;( > O)Ra, --(O0)0Ra, --(C=O)N(Ra)(R3), --- O(C=O)Ra, -N(Ra)(C=O)R -0(C=O)N(Rs)(R‘). or— N(Ra)(C==O)ORa, provided that at least one of R3, R4, or R5is a hydroxyl group or includes a hydroxyl group; orthe glycosyl acceptor (III) is cyclohexanol, t-butyl alcohol, n-pentanol, 2,2,2-triflouroethanol, 2- phenylethanol, allyl alcohol, t-butyl 2-hydroxylacetate, or of the formulaMe OOH,OACUA-OMeOMeOQMe, or3. A method for stereoselective synthesis of a l,2-cis-2-aminoglycoside, the method comprisingreacting a glycal of formula (I) with an amination agent of formula (II) and a glycosyl acceptor of formula (V) in the presence of an iron(II) catalyst, a solvent, and molecular sieves to provide the l,2-cis-2-aminoglycoside of formula (VI)whereinr is 0 or 1,each R1, R2, R3, R4, and R’ are independently hydrogen, azido, cyano, halo, hydroxy, nitro, — ORa, — SRa, alkyl, cycloalkyl, heteroalkyl, heterocycloalkyl, aryl, or heteroaryl, wherein each of R1, R2, R3, R4, and R5that is not hydrogen, azido, cyano, halo, hydroxy, or nitro is optionally substituted with one or more of azido, cyano, halo, hydroxy, oxo, nitro, Ra, - — ORa, -~SRa, --N(Ra)(Ra)> --(( O)Ra. --(C-O)ORa, —(C=O)N(Ra)(Ra), OtC-OiR'. -- N( Ra)(( O)Ra, -O(C=O)N(Ra)(Ra), or m( ) jGR or two R4or two R5together are oxo;R6and R7are each independently hydrogen, -S(=O)?. Ra, -S(=O)2ORa, — (C— 0? R. — (C=O)ORa, --(C-=O)N(Ra)(Ra), --0(00 )Ra, --N(Ra)(C^O)Ra, — O(( 1=O)N( Ra)( Ra), or — N(Ra)(C==O)ORa,ora residue of an amino acid, peptide, diagnostic agent, lipid, metabolite, nucleoside, polynucleoside, nucleotide, polynucleotide, monosaccharide, polysaccharide, steroid, or therapeutic agent; andeach Rais independently at each occurrence hydrogen, azido, cyano, halo, hydroxyl, nitro, alkyl, cycloalkyl, heteroalkyl, heterocycloalkyl, aryl, heteroaryl, or trialkylsilyl, each of which Raother than hydrogen azido, cyano, halo, hydroxyl, or nitro is optionally substituted with one or more of hydrogen, azido, cyano, halo, alkyl, aryl, cycloalkyl, heterocycloalkyl, heteroaryl, heterocycloalkyl, alkoxy, aryloxy, amino, alkylamino, dialkylamino, acylamino, aminoacyl, acyl, acyloxy, carboxyl, carboxyl ester, alkanoyl, carboxamide, haloalkyl, or haloalkoxy; ortwo Ragroups together with the atoms to which they are attached form a cycloalkyl, heterocycloalkylaryl, or heteroaryl ring, each of which ring is optionally substituted with one or more of alkyl, heteroalkyl, cycloalky 1, heterocycloalkyl, aryl, heteroaryl, alkoxy.aryloxy, amino, alkylamino, dialkylamino, hydroxyl, halo, acylamino, aminoacyl, cyano, nitro, azido, acyl, acyloxy, carboxyl, carboxyl ester, alkanoyl, carboxamide, haloalkyl, or haloalkoxy.

4. The method of claim 3, whereinthe glycosyl acceptor (V) is a monosaccharide or a polysaccharide having a primary or secondary -C(O)OH group and optionally one or more protected hydroxy groups, protected amino groups, or a combination thereof; orthe glycosyl acceptor (III) or (V) is of the formulax\HO - C - G1-! — (C),R11whereinX is O, N, or S, preferably O;G1is a bond or a linking group that can be an alkylene, cycloalkylene, heteroalkylene, or heterocycloalkylene, each optionally substituted with one or more of azido, cyano, halo, hydroxyl, nitro, Ra, — ORa, — SRa, — N(Ra)(Ra), — (C=O)R% —(O0)0Ra, — (C=O)N(Ra)(Ra), O(C=O)Ra, --N(Ra)(O0)Ra, -- O(C=O)N(Ra)(Ra), or -- N(Ra)(C™O)ORa;each R11is independentlyhydrogen, azide, cyano, halo, hydroxy, nitro, alkyl, cycloalkyl, heteroalkyl, heterocycloalkyl, aryl, heteroaryl, —OR3, or— SR3, each of which R11is optionally substituted with one or more of oxo, halo, hydroxy, cyano, azido, nitro. Ra. — OR3, — SRa, — N(Ra)(Ra), — (C=O)R% — (C==O)ORa, — (C==O)N(Ra)(Ra), -O(C=O)Ra, — N(Ra)(C==O)Ra, — 0(C==0)N(Ra)(R3), — N(Ra)(C==O)ORa, wherein each Rais as defined in claim 3,or a residue of an amino acid, peptide, diagnostic agent, lipid, metabolite, nucleoside, polynucleoside, nucleotide, polynucleotide, monosaccharide, polysaccharide, steroid, or therapeutic agent; andn is 1 or 2 and m is the number of valences on the carbon atoms available for substitution.

5. A method for stereoselective synthesis of a 1,2-cis-aminoglycoside, the method comprisingreacting a glycal of formula (I) with an amination agent of formula (II) in the presence of an iron(II) catalyst, a solvent, and molecular sieves to provide the l,2-cis-2-aminoglycoside of formula (VI)whereinr is 0 or 1,each R1, R2, R-\ R4, and R5are independently hydrogen, azido, cyano, halo, hydroxy, nitro, — ORa, — SRa, alkyl, cycloalkyl, heteroalkyl, heterocycloalkyl, aryl, or heteroaryl, wherein each of R1, R2. R3, R4. and R5that is not hydrogen, azido, cyano, halo, hydroxy, or nitro is optionally substituted with one or more of azido, cyano, halo, hydroxy, oxo, nitro, Ra, — OR3, SR'. ---N(R3)(R3). --(OO )R \ --(C-O)OR3, t(’=O )N( Ra)( Ra), OtC-OsR -- N(Ra)(C==O)Ra, — O(C==O)N(Ra)(Ra), or — N(Ra)(C==O)ORa, or two R4or two R3together are oxo;R6and R7are each independently hydrogen, -S(~O)2R”, -S(— OhOR3, — (C— O)Ra, — (C=O)ORa. --(C=-O)N(Ra)(Ray ---O(C-=O)Ra, -N(Ra)(C=O)Ra, --O(C™O)N(Ra)(Ra), or -~-N(Ra)(O0)()Ra; andeach Rais independently at each occurrence hydrogen, azido, cyano, halo, hydroxyl, nitro, alkyl, cycloalkyl, heteroalkyl, heterocycloalkyl, aryl, heteroaryl, or trialkylsilyl, each of which Raother than hydrogen is optionally substituted with one or more of hydrogen, azido, cyano, halo, alkyl, aryl, cycloalkyl, heterocycloalkyl, heteroaryl, heterocycloalkyl, alkoxy, aryloxy, amino, alkylamino, dialkylamino, acylamino, aminoacyl, acyl, acyloxy, carboxyl, carboxyl ester, alkanoyl, carboxamide, haloalkyl, or haloalkoxy; ortwo Ragroups together with the atoms to which they are attached form a cycloalkyl, heterocycloalkylaryl, or heteroaryl ring, each of which ring is optionally substituted with one or more of alkyl, heteroalkyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, alkoxy.aryloxy, amino, alkylamino, dialkylamino, hydroxyl, halo, acylamino, aminoacyl, cyano, nitro, azido, acyl, acyloxy, carboxyl, carboxyl ester, alkanoyl, carboxamide, haloalkyl, or haloalkoxy.

6. The method of claim 5, wherein the glycal (I) isa 3-deoxy glucal or a 6-deoxy glucal, ora glucal of the formulaAcO^X TBSO^\ AcO^r-^o Aco^r^o TBSO— AcO—TBSOAcO TBSO^r— o TBSO—, or7. The method of any one of the preceding claims, wherein the glycal (I) is of the formulaR3whereinr is 0 or 1, andR3, R4, and Rsare each independently hydrogen, azide, cyano, halo, hydroxy, nitro, — ORa, — SRa, alkyl, cycloalkyl, heteroalkyl, heterocycloalkyl, aryl, or heteroaryl, each optionally substituted with one or more of hydrogen, azido, cyano, halo, hydroxy, nitro, — OR6, oxo, — SRa, Ra, OR --N(Ra)(Ra), ---(C=-O)Ra, ---(C=O)0Ra, ----- (C==O)N(Ra)(R3), -- 0(C=0)R8, — N(R’)(C=O)Ra, — O(C=O)N(R8)(Ra), or — N(Ra)(C=O)ORa.

8. The method of any one of the preceding claims, wherein the glycal of the formulaR3and R4are each independently hydrogen, azide, alkyl, cycloalkyl, heteroalkyl, or heterocycloalkyl, optionally substituted with one or more of oxo. halo, cyano, azido, nitro, R6, --OR6, ---N(Ra)(R3), --(C-O)R6, --(C-O)OR6, --(OO)N(R3)(Ra), --0(00)R6, -- N(Ra)(O0)Ra, — O(CX))N(Ra)(Ra), or — N(Ra)(€ O)ORawherein Rais defined as in claim 1; andR5is heterocycloalkyl or — CH heterocycloalkyl, optionally substituted with one or more of oxo, halo, cyano, azido, nitro, Ra, — OR6, — N(Ra)(Ra), — (C==O)Ra, — (C=O)ORa, --- (C=0)N(Ra)(Ra), --0(C-0)Ra. -~N(Ra)(C==0)Ra, --0(C-0)N(Ra)(Ra), or -- N(Ra)(C=0)0Ra. heterocycloalkyl, or — Cl beterocycloalkyl, optionally substituted with one or more of oxo, halo, cyano, azido, nitro, Ra, — OR6, — N(Ra)(Ra), --- (C==O)Ra, — - (C-0)0Ra. — (O0)N(Ra)(R3), — O(C-O)Ra, - -N(Ra)(O0)Ra, -^0(C-0)N(Ra)(Ra), or ----- XR6)(C—O)ORawherein Rais defined as above.

9. The method of any one of the preceding claims, wherein the glycal is of the formulawhereinR and R4are each independently hydrogen, azide, cya.no, halo, hydroxy, nitro. — 0Ra, — SRa, alkyl, cycloalkyl, heteroalkyl, heterocycloalkyl, aryl, or heteroaryl, each optionallysubstituted with one or more of azide, cyano, halo, hydroxy, nitro, Ra, — ORa, oxo, - — SR3, — N( Ra)( R::), — (C-O)R3, — (( O)ORa, --(( 1=0 )N( R3)( R5), — 0(C-0 )Ra, — - N(Ra)(C==O)Ra, — O(C=O)N(Ra)(Ra), or — N(Ra)(C=O)ORa,R5is hydrogen, alkyl, — CH2ORa, Cl bSR'. -Cl hcycloalkyl. Ci heteroalky 1, or — CHiheterocycloalkyl, optionally substituted with one or more of azide, cyano, halo, hydroxy, nitro. Ra. —OR3. oxo, — SR — N Ra)(Ra). — (C==O)Ra. — (C=O)ORa, — (O0)N(R3)(Ra), — O(C~O)Ra, — N(R3)(O0)R3, — 0(O0)N(Ra)(R3), or — N(Ra)(C==O)ORa, each of the foregoing groups further being heterocycloalkyl or — CHzheterocycloalkyl, optionally substituted with one or more of oxo, halo, cyano, azido, nitro, Ra, —OR3, — N(R3)(Ra), — Si(R3)(Ra), — (C O)Ra. — (C-O)OR3, —(C=O )N( Rax Ra), — O(C===O)R\ — N(Rs)(C=O)Ra, — 0(C-0)N(Ra)(R3). — N(Ra)(C==O)ORa. heterocycloalkyl, or- — CH2heterocycloalkyl, each of the substituents being optionally substituted with one or more of oxo, halo, cyano, azido, nitro, R3, — OR3, — N(R3)(Ra). — (OO)R3, — (C O)ORa, — (O0)N(R3XR3), — 0(00)Ra, — N(R3)(C-=O)Ra, OiC-O )N( IC )( Ra), or — N(R3)(C-0)0Raor wherein the glycal is of the formula. orwherein optionally in each formula, each acetal, acetyl, benzyl, benzoyl, tert -butyldimethyl silyl, benzyl, or benzoyl group can be independently replaced with a different hydroxy- protecting group.

10. The method of any one of the preceding claims, wherein the amination agent is of the formula / O RS(O)2R1 C)H YO,, S(O)2R10NHwhereinR9is alkyl, cycloalkyl, heteroalkyl, heterocycloalkyl, aryl, or heteroaiyl, each of which R9is optionally substituted with one or more of azido, cyano, halo, hydroxy, nitro, oxo, Ra, — 0a, — -SRa, — N(Ra)(Ra). — (C==0)Ra, -(C=O)OR‘, —(C— 0)N(Ra)(Ra), 0(C-() )R — N( Ra)(C=0)Ra, ---0(C=0)N(Ra)(Rs), N(Ra)(C= 0 iOR or R9is a residue of an amino acid, peptide, diagnostic agent, lipid, metabolite, nucleoside, polynucleoside, nucleotide, polynucleotide, monosaccharide, polysaccharide, steroid, or therapeutic agent;R10is hydrogen, alkyl, cycloalkyl, heteroalkyl, heterocycloalkyl, aryl, or heteroaryl, each of which R10is optionally substituted with one or more of oxo, halo, hydroxy, cyano, azido, nitro, Ra, —OR3. —SR3, — N(R3)(Ra), — (OO)R3, — (OO)OR3. — (C=O)N(Ra)(Ra), — O(C==O)Ra, — N(Ra)(C=O)Ra, — 0(C ))N(Ra)(Ra), — N(Ra)(C— 0)0Ra, or R10is a residue of an amino acid, peptide, diagnostic agent, lipid, metabolite, nucleoside, polynucleoside, nucleotide, polynucleotide, monosaccharide, polysaccharide, steroid, or therapeutic agent; andeach Rais as in claim 1.

11. The method of any one of the preceding claims, wherein the amination agent (II) is of the formulaMe BoCx Boc^3ad 3ae 3at 3agMeR: 2,4-CI2-benzoyl3gwherein optionally in each formula, each acetal, acetyl, benzyl, benzoyl, te-rt-butyldimethylsilyl, benzyl benzoyl or 9-fluorenylmethyI carbamate group can be independently replaced with a different hydroxy-protecting group, or each t-butyl carbonyl or benzyl carbonyl can be independently replaced with a different amine-protecting group.

12. The method of any one of the preceding claims, wherein the iron(II) catalyst is of the formulaFe(II)XY nH2OwhereinX and Y are each independently the same or different organic or inorganic counter anion, provided that at least one of X and Y is a noncoordinating anion.

13. The method of claim 12, wherein the noncoordinating anion is of the formula (RfSC>2)N’, Al(OCRf)4, B(R4)4-, B(Rf)4-, or RfSOf, wherein R is an aryl group or a substituted aryl group, of which the one or more substituents are the same or different and are alkyl, or aryl, Rf is a monovalent alkyl, cycloalkyl, aryl, or aryl, each of which is substituted fluorine, fluorinated or perfluorinated alkyl, or fluorinated or perfluorinated aryl, CF3SO3, (CF3SO2)N_, CB11H12, 004', A1(OC(CF3)3)4', ASF6", SbFf, BF4", PF6’, B(C6F5)4’, B(C6H4)4’, or B(3,5-(CF3)2C6H3)4‘.

14. The method of any one of claims 12 or 13, wherein the iron(ll) catalyst includes a tridentate nitrogen-containing ligand.

15. The method of claim 14, wherein the tridentate nitrogen-containing ligand is of the formulas LI, L2, L3, or L4wherein in formulas LL L2, L3, or L4, each R1. R2. R3, R‘\ R5, R6, and R!are independently hydrogen, azido, cyano, halo, hydroxy, nitro, alkyl, cycloalkyl, heteroalkyl, heterocycloalkyl, aryl, or heteroaryl, wherein each of R1, R2, R R4, R3, R6, and R1that is not hydrogen, azido, cyano, halo, hydroxy, or nitro is optionally substituted with one or more of azido, cyano, halo, hydroxy, oxo, nitro, --0Ra, S '. -~-N(Ra)(Ra), tC-O ) \ --(C=-O)ORa, ---(C=-O)N( Ra)( Ra). -- 0(C= 0)R\ - — N(Ra)(C= 0)Ra, — 0(C= O)N(Ra)(Ra), or — N(R8)(C= 0)0R wherein each Rais as defined in claim 1.

16. The method of any one of claims 12 to 15, the preceding claims, wherein the iron catalyst includes a ligand of formula LI, L2, or L3L317. The method of claim 16, wherein the iron catalyst includes a ligand of formula LIMe Me18. The method of claim 17, wherein iron catalyst is of the formulaFe(L 1 )(BF4)2(MeCN)(H2O)2.

19. The method of any one of the preceding claims, wherein the solvent is an aprotic solvent, such as xylene, diethyl ether, chloroform, ethyl acetate, dichloromethane, tetrahydrofuran, 1,4-dioxane, acetone, acetonitrile, N, N-dimethyl formamide, dimethyl sulfoxide, benzene, toluene, trifluorotoluene, mesitylene, xylene, anisole, hexamethylphosphoric acid triamide, 1,2-dichloroethane, 1,1,2-trichloroethane, chlorobenzene, o-dichlorobenzene, dioxane, cyclohexane, n-pentane, n-hexane. n-heptane, n-octane, n-nonane, n-decane, methyl ethyl ketone, cyclohexanone, butyl acetate, ethyl cellosolve acetate, ethylene glycol, ethylene glycol monobutyl ether, ethylene glycol monoethyl ether, ethylene glycol monomethyl ether, dimethoxy ethane, propylene glycol, diethoxy methane, triethylene glycol monoethyl ether, N-methyl-2-pyrrolidone, or a combination thereof.

20. The method of claim 19, wherein the solvent is methylene chloride, dichloroethane, chloroform, or ethyl acetate, optionally in combination with toluene, trifluorotoluene, diethyl ether, or 1,4-dioxane.

21. The method of any one of the preceding claims, wherein the molecular sieves are freshly activated and are 3 A, 4 A, or 5 A molecular sieves.

22. The method of any of one of the preceding claims, wherein the l,2-cis-2-aminoglycoside is produced at a diastereomeric ratio of cis:trans of greater than 5:1, or greater than 10:1, or greater 20:1, or greater than 40:1, or greater than 50:1.

23. The method of any one of the preceding claims, further comprising cleaving R6from the R6HN- moiety in the l,2-cis-2-aminoglycoside (IV) or (VI) to provide the corresponding 1,2-cis-2-aminoglycoside having an -NH2 group.

24. A reiterative method for stereoselective synthesis of a poly(l,2-cis-2-aminoglycoside) the method comprisinga first reacting ofa glycal of the formulaan amination agent of the formula / Ox. vN RI7H(II)and a cyclic enol ether of the formula (VII)H R3(VII)in the presence of an iron catalyst, to provide a first 1,2-cis disaccharide comprising an enol ether group derived from the cyclic enol ether;a second reacting ofthe first disaccharide comprising an enol ether group,a second amination agent of the formulaR(kN R7I7H, anda cyclic saccharide having a primary or secondary hydroxyl group,in the presence of an iron catalyst, to provide a 1,2-cis polysaccharide; andoptionally repeating the second reacting.whereinR R2. R3, R \ and R' are independently hydrogen, alkyl, cycloalkyl, heteroalky 1. or heterocycloalkyl, wherein each of R1and R2that is not hydrogen is optionally substituted with one or more of oxo, halo, cyano, azido, nitro, R3, — ORa, — N(Ra)(Ra), — (C==O)Ra, — (C=O)ORa, --< C==O)N(Ra)(Ra), — O(C==O)Ra, -- N(Ra)(C=O)Ra. O(C==O)N(Ra)(Ra), orN( RR!, R2, R3, R4, and R5are independently hydrogen, hydroxy, alkyl, cycloalkyl, heteroalkyl, or heterocycloalkyl, wherein each of R1and R2that is not hydrogen is optionally substituted with one or more of hydroxy, oxo, halo, cyano, azido, nitro, Ra, — OR3, — -N(Ra)(Ra), — (C==O)Ra, -- (C=O)ORa, — (C==O)N(Ra)(Ra), -4)(O=O)R‘, - - -N(Ra)(C=O)Ra, -- O(C=O)N(Ra)(Ra), or — N(Ra)(C=O)ORa. with the proviso that at least one of R1, R2', R}’. R1. and R5include a primary or secondary hydroxy group;R6and R7are each independently hydrogen, -S(= O)? Ra, -S(==O)2OR ( — (C= O)Ra, — (C=O)ORa. ---(O0)N(R3)(R3), — O(C=O)Ra, — N(Ra)(C=O)Ra, O(C==O)N(Ra)(Ra), or --N(R3)(C-O)ORa.R8is alkyl, alkyl-C(==O)-. cycloalkyl, cycloalkyl — C(=O)-, heteroalkyl, heteroalkyl-C(=0)-, heterocycloalkyl, or heterocycloalkyl-C(=0)-, optionally substituted with one or more of oxo, halo, cyano, azido, nitro, R3, — 0Ra, — N(Ra)(Ra), — (C=0)Ra, — (C==O)0Ra, — (C==0)N(Ra)(Ra), 0(C==0)Ra, --N(Ra)(O0)Ra, --- 0(C=0)N(Ra)(Ra), or -- N(R3)(C™O)OR3, andeach Rais independently at each occurrence hydrogen, alkyl, aryl, heteroalkyl, heteroaryl, cycloalkyl, heterocycloalkyl, or trialkylsilyl, each of which Raother than hydrogen is optionally substituted with one or more of alkyl, heteroalkyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, alkoxy, aryloxy, amino, alkylamino, dialkylamino, hydroxyl, halo, acylamino, aminoacyl, cyano, nitro, azido, acyl, acyloxy. carboxyl, carboxy] ester, alkanoyl. carboxamide, haloalkyl, or haloalkoxy; ortwo Ragroups together with the atoms to which they are attached form a cycloalkyl, heterocycloalkylaryl, or heteroaryl ring, each of which ring is optionally substituted with one or more of alkyl, heteroalkyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, alkoxy,aryloxy, amino, alkylamino, dialkylamino, hydroxyl, halo, acylamino, aminoacyl, cyano, nitro, azido, acyl, acyloxy, carboxyl, carboxyl ester, alkanoyl, carboxamide, haloalkyl, haloalkoxy,25. The method of claim 24, further comprising cleaving R6from the R6HN- moiety to provide the corresponding poly(l,2-cis-2-aminoglycoside).

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