Iron complexes for enantioselective cis-dihydroxylation of olefins

Abstract

Disclosed is a process for asymmetric cis-dihydroxylation ("AD") of styrene and conjugated dienes to produce cis-glycols of styrene and conjugated dienes or tetrols of conjugated dienes in high yields (i.e. Yields > = 30%) and high enantioselectivity (i.e. Enantiomeric excess > = 60%). The process uses an iron-based catalyst, such as one or more Fe (II) complexes, etc., as a catalyst. The process generally includes: (i) maintaining the reaction mixture at a temperature sufficient to form a product for a period of time, where the reaction mixture contains styrene or conjugated diene, one or more iron-based catalysts, an oxidizing agent, and a solvent, and where the product contains a cis-diol or tetraol.

Description

[0001] CROSS-REFERENCE TO RELATED APPLICATIONS

[0002] This application claims the benefit of and priority to U.S. Provisional Application No. 63 / 526,430, filed on July 12, 2023, the entire contents of which are incorporated herein by reference for all purposes. Technical Field

[0003] The present invention relates generally to the field of asymmetric hydroxylation of olefins, and in particular to the asymmetric hydroxylation of styrene, styrene derivatives, and conjugated dienes using iron-based catalysts. Background Art

[0004] There are a large number of olefins in industrial chemistry, and converting olefins into high value-added products is still a hot topic in organic chemistry (Tetrahedron Lett. 2015, 56, 3732; Chem. Rec. 2019, 19, 440; Angew. Chem. Int. Ed. 2020, 59, 7990). Asymmetric cis-dihydroxylation (AD) of olefins is an effective method for constructing vicinal diols that are ubiquitous in natural medicines and active molecules (Chem. Soc. Rev. 2011, 40, 114; Tetrahedron: Asymmetry, 2017, 28, 987; Russ. Chem. Rev, 2019, 88, 1094; Molecules, 2023, 28, 2722). At present, AD reactions are mainly carried out with Os catalysts (such as commercial products AD-mix-α / β developed by Sharpless and his colleagues). Nevertheless, the high toxicity of Os catalysts as well as the high cost and poor atom economy of catalytic systems have caused serious concerns in the pharmaceutical industry and other practical synthetic applications. In addition, the electrophilic nature of Os oxidants favors electron-rich olefins rather than electron-deficient olefins, and the latter substrates usually require higher Os loadings, which leads to more serious Os contamination in the products.

[0005] Several metal catalysts (including Ru, Mn and Fe) and other strategies have been developed in the literature as Os-free cis-dihydroxylation methods for olefins, however, due to the limitations of these methods in terms of substrates, product yields, stereoselectivity (enantioselectivity and cis / trans diol selectivity) and / or chemical selectivity (e.g. diol / epoxide selectivity), it is still challenging for these methods to replace the current Sharpless dihydroxylation reaction (J. Am. Chem. Soc., 2005, 127, 14239; Angew. Chem. Int. Ed. 2008, 47, 1887; Chem. Commun., 2011, 47, 11204; Angew. Chem. Int. Ed. 2016, 55, 10253; Schmidt, S. and Plietker, B. 2017 Dihydroxylations of Olefins and Related Reactions. In Applied Homogeneous Catalysis with Organometallic Compounds, eds B. Cornils, WA Herrmann, M. Beller and R. Paciello). Rieske dioxygenases are a class of enzymes that catalyze biological AD reactions. The non-heme Fe active center has stimulated extensive bioinorganic research in developing Fe-catalyzed AD reactions as green alternatives to sharpless AD reactions. From the perspective of atom economy, the use of H2O2 is also more advantageous than the terminal oxidants (e.g., ferrocyanide) used in Os-catalyzed systems. There are four effective chiral N4 ligands applied to Fe-catalyzed asymmetric cis-dihydroxylation, including 6-Me2-BPMCN, 6-Me2-BPBP, 2-Me2-BQCN, and 2-Me2-BQPN. However, when it comes to styrene substrates, [Fe(R,R-2-Me2-BPMCN)(OTf)2] and Fe(R,R-2-Me2-BQCN)(OTf)2] give diol products with low enantioselectivity (2% ee and 17.5% ee) (Angew. Chem. Int. Ed. 2008, 47, 1887; Angew. Chem. Int. Ed. 2016, 55, 10253). Optically pure 1,2-diols of terminal aromatic olefins are important in biologically active molecules; however, methods and catalysts that provide high reactivity / selectivity are still lacking.

[0006] The asymmetric cis-dihydroxylation of conjugated dienes is an attractive method for producing four consecutive chiral centers. For the mono-dihydroxylation of electron-deficient conjugated dienes, osmium-based catalysts preferentially mono-dihydroxylate the most electron-rich double bonds (J.Am.Chem.Soc.1992,114,7570). It is challenging to simultaneously realize the cis-dihydroxylation of two double bonds and avoid poor regiocontrol and overoxidation. By two separate dihydroxylation reactions catalyzed by osmium-based catalysts, the chiral cis-diols of electron-deficient conjugated dienes are realized [Tetrahedron Letters, 2011,52,6366]. However, there is still a lack of effective asymmetric cis-dihydroxylation of conjugated dienes in a single reaction.

[0007] There remains a need to develop improved methods for the asymmetric cis-dihydroxylation of styrene and conjugated dienes.

[0008] It is therefore an object of the present invention to provide a process for the asymmetric cis-dihydroxylation of styrene and a conjugated diene.

[0009] Another object of the present invention is to provide an iron-based catalyst for catalyzing the asymmetric cis-dihydroxylation of styrene with a conjugated diene.

[0010] Another object of the present invention is to provide a cis-diol product formed by the asymmetric cis-dihydroxylation of styrene and a conjugated diene. Summary of the invention

[0011] Fe(II) complexes have been developed for catalyzing the asymmetric cis-dihydroxylation (AD) of styrene and conjugated dienes. Methods have been developed for asymmetric cis-dihydroxylation (AD) of styrene and conjugated dienes to produce cis-diols of styrene and conjugated dienes and tetraols of conjugated dienes. In some forms, AD of styrene and conjugated dienes catalyzed by Fe(II) complexes using the disclosed methods has high yields and / or high enantioselectivities.

[0012] The methods described herein use an iron-based catalyst (such as one or more Fe(II) complexes, etc.) as a catalyst and use a terminal oxidant (such as H2O2, etc.). In certain forms, the methods described can be carried out under mild reaction conditions (e.g., up to about 30°C and 1atm, such as room temperature and 1atm). In some forms, the methods described can be carried out below 0°C (e.g., about -30°C) and 1atm. The methods described herein have at least the following advantages: (1) cis-diols of styrene and conjugated dienes and tetraols of conjugated dienes can be produced in high yield and high enantioselectivity; (2) the use of biocompatible iron-based catalysts is environmentally friendly and cost-effective; and (3) the waste produced by the reaction is non-toxic.

[0013] The method generally includes: (i) keeping the reaction mixture at a certain temperature for a period of time sufficient to form a product, wherein the reaction mixture contains styrene, styrene derivatives, or conjugated dienes, one or more iron-based catalysts, solvents, and optional oxidants (e.g., hydrogen peroxide). The product contains cis-diols or tetraols. In some forms, the method disclosed herein converts styrene or styrene derivatives into cis-diols by AD reactions. In some forms, the method disclosed herein converts conjugated dienes into cis-diols by AD reactions. In some forms, the method disclosed herein converts conjugated dienes into tetraols by AD reactions.

[0014] In some forms, specific reaction conditions, such as the amount of oxidant used in step (i), the amount of one or more catalysts, the specific catalyst, the reaction temperature, and the reaction time period, etc., can be selected based on the reactants and desired products.

[0015] For example, the reaction mixture contains styrene or a derivative thereof and 0.1 mol% to 20 mol% of an iron catalyst and can be maintained at a temperature below freezing (such as -30°C, etc.) for a period of time in the range of about 20 minutes to about 3 hours, about 30 minutes to about 2 hours, or about 30 minutes to 1 hour (such as about 30 minutes, etc.) to form a product containing cis-diol.

[0016] For example, the reaction mixture contains 1,3-diol and up to 6 mol % of an iron catalyst and can be maintained at room temperature for a period of time ranging from about 20 minutes to about 3 hours, about 30 minutes to about 2 hours, or about 30 minutes to 1 hour, such as about 30 minutes, etc., to form a product containing the cis-diol.

[0017] For example, the reaction mixture contains 1,3-diol and >6 mol % of iron catalyst and can be maintained at room temperature for a period of time ranging from about 30 minutes to about 3 hours, about 1 hour to about 3 hours, or about 1 hour to about 2 hours, such as about 1 hour, etc., to form a product containing a tetraol.

[0018] In addition, in some forms, the iron-based catalyst in the AD reaction can be selected to achieve the desired stereochemistry. For example, when the disclosed method converts a conjugated diene into a cis-diol or tetraol via an AD reaction catalyzed by Fe(S,S-PQCN-6)(OTf)2 as described herein, the cis-diol or tetraol of the conjugated diene can have a (2S, 3R) or (2S, 3R, 4S, 5R) stereochemistry. For example, when the disclosed method converts a conjugated diene into a cis-diol or tetraol via an AD reaction catalyzed by Fe(S,S-2-Me2-BQCN)(OTf)2 as described herein, the cis-diol or tetraol of the conjugated diene can have a (2R, 3S) or (2R, 3S, 4R, 5S) stereochemistry.

[0019] Optionally, the method may also include adding an oxidant to a premix containing a substrate, an iron catalyst, and a solvent to form a reaction mixture before step (i); stirring the reaction mixture before step (i) and / or during step (i); and / or purifying the product after step (i), optionally by column chromatography. Any suitable technique may be used to add the oxidant to the premix, such as rapid injection or continuous injection using a syringe pump at room temperature over a period of time (e.g., about 30 min). In some forms, the specific technique of adding the oxidant may be selected based on the desired product. For example, when the desired product is cis-diol, a syringe pump may be used at room temperature over a suitable period of time (such as a period of time ranging from 20 min to 1 hour, e.g., about 30 min) to add the oxidant in solution form to the premix. For example, when the desired product is tetraol, the oxidant in solution form may be directly added to the premix (i.e., rapid injection) at room temperature. BRIEF DESCRIPTION OF THE DRAWINGS

[0020] Figure 1 is a schematic diagram showing the X-ray crystal structure of [Fe(S,S-PQCN-1)(OTf)2].

[0021] Figure 2 is a schematic diagram showing the X-ray crystal structure of (2R,3S,4R,5S)-5h.

[0022] Figure 3A and 3B is a schematic diagram showing the DFT calculation of the transition state of the asymmetric cis-dihydroxylation of styrene by Fe-dioxo calculated at the B3LYP-D3 / def2-TZVP(PCM) / / B3LYP-D3 / def2-SVP(PCM) level of theory.

[0023] Figure 4The DFT calculations based on the asymmetric cis-dihydroxylation of styrene by a chiral asymmetric Fe-N4 complex are shown at the B3LYP-D3 / def2-TZVP(PCM) / / B3LYP-D3 / def2-SVP(PCM) level of theory. CC Schematic diagram of the proposed correlation between and ee. Summary of the invention

[0025] It should be understood that, unless otherwise stated, the disclosed compounds, compositions and methods are not limited to specific synthetic methods, specific analytical techniques or specific reagents, and can therefore vary. It should also be understood that the terminology used herein is for the purpose of describing specific forms and embodiments only, and is not intended to be limiting.

[0026] As used herein, "substituted" refers to all permissible substituents of the compounds or functional groups described herein. In the broadest sense, permissible substituents include acyclic and cyclic, branched and unbranched, carbocyclic and heterocyclic, aromatic and non-aromatic substituents of organic compounds. Illustrative substituents include, but are not limited to, halogens, hydroxyl groups, or any other organic group containing any number of carbon atoms (preferably 1 to 14 carbon atoms), and optionally containing one or more heteroatoms, such as oxygen, sulfur or nitrogen groups, etc., in a linear, branched or cyclic structural form. Representative substituents include substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted phenyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, substituted or unsubstituted polyaryl, substituted or unsubstituted polyheteroaryl, substituted or unsubstituted aralkyl, halogen, hydroxy, alkoxy, phenoxy, aryloxy, silyl, thiol, alkylthio, substituted alkylthio, phenylthio, arylthio, cyano, isocyano, nitro, substituted or unsubstituted carbonyl, carboxyl, amino, amide, oxo, sulfinyl, sulfonyl, sulfonic acid, phosphonium, phosphinyl, phosphoryl, phosphonyl, amino acid. Such substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted phenyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, substituted or unsubstituted polyaryl, substituted or unsubstituted polyheteroaryl, substituted or unsubstituted aralkyl, halogen, hydroxy, alkoxy, phenoxy, aryloxy, silyl, thiol, alkylthio, substituted alkylthio, phenylthio, arylthio, cyano, isocyano, nitro, substituted or unsubstituted carbonyl, carboxyl, amino, amide, oxo, sulfinyl, sulfonyl, sulfonic acid, phosphonium, phosphoalkyl, phosphoryl, phosphonyl, and amino acid may be further substituted.

[0027] Heteroatoms such as nitrogen and the like may have hydrogen substituents and / or any permissible substituents of the organic compounds described herein that satisfy the valences of the heteroatoms. It is understood that "substitution" or "substituted" includes the implicit condition that such substitution is in accordance with the permissible valences of the substituted atom and the substituent, and that such substitution results in a stable compound, i.e., a compound that does not spontaneously undergo transformations such as rearrangement, cyclization, elimination, etc.

[0028] As used herein, "alkyl" refers to a group of saturated aliphatic groups, including straight chain alkyl groups, branched chain alkyl groups, and cycloalkyl groups (alicyclic groups). In some forms, a straight chain or branched chain alkyl group has 30 or fewer atoms in its main chain (e.g., a straight chain is C1 to C 30 , the branch chain is C3~C 30 ), 20 or less, 15 or less, or 10 or less carbon atoms. Alkyl includes methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, tert-butyl, pentyl, hexyl, heptyl, octyl, decyl, tetradecyl, hexadecyl, eicosyl, tetracosyl, etc. Similarly, cycloalkyl is a non-aromatic carbon-based ring composed of at least three carbon atoms, such as a non-aromatic monocyclic or non-aromatic polycyclic ring containing 3 to 30 carbon atoms, 3 to 20 carbon atoms, or 3 to 10 carbon atoms in its ring structure, and has 5, 6, or 7 carbons in the ring structure. Cycloalkyl containing a polycyclic ring system can have two or more non-aromatic rings in which two or more carbons are common to two adjacent rings (i.e., a "fused cycloalkyl ring"). Examples of cycloalkyl groups include, but are not limited to, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, etc.

[0029] Substituted alkyl refers to an alkyl moiety having one or more substituents replacing hydrogen on one or more carbons of the hydrocarbon backbone. Such substituents can be any of the above substituents, such as halogen (e.g., fluorine, chlorine, bromine or iodine), hydroxyl, carbonyl (e.g., carboxyl, alkoxycarbonyl, formyl or acyl), thiocarbonyl (e.g., thioester, thioacetate or thioformate), aryl, alkoxy, aralkyl, phosphonium, phosphoalkyl, phosphonyl, phosphoryl, phosphate, phosphonate, phosphinate, amino, amido, amidine, imine, cyano, nitro, azido, oxo, sulfhydryl, thiol, alkylthio, silyl, sulfinyl, sulfate, sulfonate, sulfamoyl, sulfonamido, sulfonyl, heterocyclic, aromatic or heteroaromatic moieties. -NRR', wherein R and R' are independently hydrogen, alkyl or aryl, and wherein the nitrogen atom is optionally quaternized; -SR, wherein R is phosphonyl, sulfinyl, silyl, hydrogen, alkyl, or aryl; -CN; -NO2; -COOH; carboxylate; -COR, -COOR, or -CON(R)2, wherein R is hydrogen, alkyl or aryl; imino, silyl, ether, haloalkyl (e.g., -CF3, -CH2-CF3, -CCl3); -CN; -NCOCOCH2CH2; -NCOCOCHCH; and -NCS; and combinations thereof.

[0030] It will be appreciated by those skilled in the art that the moiety substituted on the hydrocarbon chain may itself be substituted if appropriate. For example, the substituents of the substituted alkyl may include halogen, hydroxyl, nitro, thiol, amino, aralkyl, azido, imino, amide, phosphonium, phosphoalkyl, phosphoryl (including phosphonates and phosphinates), oxo, sulfonyl (including sulfates, sulfonamido, sulfamoyl and sulfonates) and silyl groups, as well as ethers, alkylthio, carbonyl (including ketones, aldehydes, carboxylates and esters), haloalkyl, -CN, etc. Cycloalkyl may be substituted in the same manner.

[0031] Unless the number of carbons is otherwise specified, "lower alkyl" as used herein refers to an alkyl group as defined above, but having 1 to 10 carbon atoms, more preferably 1 to 6 carbon atoms in its backbone structure. Likewise, "lower alkenyl" and "lower alkynyl" have similar chain lengths.

[0032] As used herein, "heteroalkyl" refers to an alkyl group or combination thereof containing a straight or branched chain or cyclic carbon containing at least one heteroatom on the carbon backbone. Suitable heteroatoms include, but are not limited to, O, N, Si, P, and S, wherein nitrogen, phosphorus, and sulfur atoms are optionally oxidized, and the nitrogen heteroatom is optionally quaternized. For example, the term "heterocycloalkyl" is a cycloalkyl group as defined above, wherein at least one carbon atom of the ring is substituted with a heteroatom such as, but not limited to, nitrogen, oxygen, sulfur, or phosphorus.

[0033] As used herein, the term "alkenyl" is a hydrocarbon group having a structural formula of 2 to 24 carbon atoms and containing at least one carbon-carbon double bond. Alkenyl groups include straight chain alkenyl groups, branched alkenyl groups, and cycloalkenyl groups. Cycloalkenyl groups are non-aromatic carbon-based rings composed of at least three carbon atoms and at least one carbon-carbon double bond, such as non-aromatic monocyclic or non-aromatic polycyclic rings containing 3 to 30 carbon atoms and at least one carbon-carbon double bond, 3 to 20 carbon atoms and at least one carbon-carbon double bond, or 3 to 10 carbon atoms and at least one carbon-carbon double bond in its ring structure and having 5, 6 or 7 carbons and at least one carbon-carbon double bond in the ring structure. Cycloalkenyl groups containing polycyclic ring systems may have two or more non-aromatic rings (i.e., "fused cycloalkenyl rings") in which two or more carbons are common to two adjacent rings and contain at least one carbon-carbon double bond. Asymmetric structures such as (AB)C=C(C'D) are intended to include E and Z isomers. This is inferred in the structural formulae herein where an asymmetric olefin is present, or may be explicitly indicated by the bond symbol C. The term "alkenyl" as used throughout the specification, examples, and claims is intended to include both "unsubstituted alkenyl" and "substituted alkenyl," the latter referring to alkenyl moieties having one or more substituents replacing hydrogen on one or more carbons of the hydrocarbon backbone. The term "alkenyl" also includes "heteroalkenyl."

[0034] The term "substituted alkenyl" refers to an alkenyl moiety having one or more substituents replacing one or more hydrogen atoms on one or more carbons of a hydrocarbon backbone. Such substituents may be any of the above substituents, such as halogen, azide, alkyl, aralkyl, alkenyl, alkynyl, cycloalkyl, hydroxyl, carbonyl (e.g., carboxyl, alkoxycarbonyl, formyl or acyl), silyl, ether, ester, thiocarbonyl (e.g., thioester, thioacetate, or thioformate), alkoxy, phosphonium, phosphoalkyl, phosphoryl, phosphate, phosphonate, phosphinate, amino (e.g., quaternized amino), amide, amidine, imine, cyano, nitro, azido, oxo, sulfhydryl, alkylthio, sulfate, sulfonate, sulfamoyl, sulfonamido, sulfonyl, heterocyclic, alkylaryl, haloalkyl, -CN, aryl, heteroaryl, polyaryl, polyheteroaryl, and combinations thereof.

[0035] As used herein, "heteroalkenyl" refers to an alkenyl group or combination thereof containing at least one heteroatom containing a straight chain, branched chain, or cyclic carbon. Suitable heteroatoms include, but are not limited to, O, N, Si, P, and S, wherein nitrogen, phosphorus, and sulfur atoms are optionally oxidized, and the nitrogen heteroatom is optionally quaternized. For example, the term "heterocycloalkenyl group" is a cycloalkenyl group in which at least one carbon atom of the ring is substituted with a heteroatom such as, but not limited to, nitrogen, oxygen, sulfur, or phosphorus.

[0036] As used herein, the term "alkynyl group" is a hydrocarbon group having 2 to 24 carbon atoms and a structural formula containing at least one carbon-carbon triple bond. Alkynyl groups include straight chain alkynyl groups, branched chain alkynyl groups, and cycloalkynyl groups. Cycloalkynyl groups are non-aromatic carbon-based rings consisting of at least three carbon atoms and at least one carbon-carbon triple bond, such as non-aromatic monocyclic or non-aromatic polycyclic rings containing 3 to 30 carbon atoms and at least one carbon-carbon triple bond, 3 to 20 carbon atoms and at least one carbon-carbon triple bond, or 3 to 10 carbon atoms and at least one carbon-carbon triple bond in its ring structure, and having 5, 6 or 7 carbons and at least one carbon-carbon triple bond in the ring structure. Cycloalkynyl groups containing a polycyclic ring system may have two or more non-aromatic rings (i.e., "fused cycloalkynyl rings") in which two or more carbons are common to two adjacent rings and contain at least one carbon-carbon triple bond. Asymmetric structures such as (AB)C≡C(C"D) are intended to include both E and Z isomers. This may be inferred in formulae herein where an asymmetric alkyne is present, or it may be explicitly indicated by the bond symbol C. The term "alkynyl" as used throughout the specification, examples and claims is intended to include both "unsubstituted alkynyls" and "substituted alkynyls", the latter referring to alkynyl moieties having one or more substituents replacing a hydrogen on one or more carbons of the hydrocarbon backbone. The term "alkynyl" also includes "heteroalkynyls".

[0037] The term "substituted alkynyl" refers to an alkynyl moiety having one or more substituents replacing one or more hydrogen atoms on one or more carbons of the hydrocarbon backbone. Such substituents can be any of the above substituents, such as halogen, azide, alkyl, aralkyl, alkenyl, alkynyl, cycloalkyl, hydroxyl, carbonyl (e.g., carboxyl, alkoxycarbonyl, formyl or acyl), silyl, ether, ester, thiocarbonyl (e.g., thioester, thioacetate, or thioformate), alkoxy, phosphonium, phosphoalkyl, phosphoryl, phosphate, phosphonate, phosphinate, amino (e.g., quaternized amino), amide, amidine, imine, cyano, nitro, azido, sulfhydryl, alkylthio, sulfate, sulfonate, sulfamoyl, sulfonamido, sulfonyl, heterocyclyl, alkylaryl, haloalkyl, -CN, aryl, heteroaryl, polyaryl, polyheteroaryl, and combinations thereof.

[0038] As used herein, "heteroalkynyl" refers to an alkynyl group or combination thereof containing at least one heteroatom containing a straight chain, branched chain, or cyclic carbon. Suitable heteroatoms include, but are not limited to, O, N, Si, P, and S, wherein nitrogen, phosphorus, and sulfur atoms are optionally oxidized, and the nitrogen heteroatom is optionally quaternized. For example, the term "heterocycloalkynyl group" is a cycloalkynyl group in which at least one carbon atom of the ring is substituted with a heteroatom such as, but not limited to, nitrogen, oxygen, sulfur, or phosphorus.

[0039] As used herein, "aryl" refers to a C4-C4-C4-1-4-cyclic ring containing an aromatic ring and optionally one or more non-aromatic rings.26 The aryl group may be a cyclopentane or a cyclopentane.

[0040] The term "substituted aryl" refers to an aryl group in which one or more hydrogen atoms on one or more aromatic rings are replaced with one or more substituents, including but not limited to halogen, azide, alkyl, aralkyl, alkenyl, alkynyl, cycloalkyl, hydroxy, alkoxy, carbonyl (e.g., ketone, aldehyde, carboxyl, alkoxycarbonyl, formyl or acyl), silyl, ether, ester, thiocarbonyl (e.g., thioester, thioacetate, or thioformate), alkoxy, phosphoryl, phosphate, phosphonate, phosphinate, amino (or quaternized amino), amide, amidine, imine, cyano, nitro, azido, sulfhydryl, imino, alkylthio, sulfate, sulfonate, sulfamoyl, sulfoxide, sulfonamido, sulfonyl, heterocyclyl, alkylaryl, haloalkyl (e.g., -CF3, -CH2-CF3, -CCl3), -CN, aryl, heteroaryl, and combinations thereof.

[0041] "Heterocycle" and "heterocyclyl" are used interchangeably and refer to cyclic groups attached through ring carbon atoms or ring nitrogen atoms of a monocyclic or polycyclic ring system containing 3 to 30 ring atoms, 3 to 20 ring atoms, 3 to 10 ring atoms, or 5 to 6 ring atoms, wherein the polycyclic ring system contains one or more non-aromatic rings and optionally one or more aromatic rings, wherein at least one non-aromatic ring contains carbon and 1 to 4 heteroatoms, each of which is selected from non-peroxide oxygen, sulfur, and N(Y) (where Y is absent or is H), O, C1-C 10 Alkyl, phenyl, or benzyl, and optionally contains 1 to 3 double bonds and is optionally substituted by one or more substituents. According to the definition, heterocyclic groups are different from heteroaryl groups. Heterocyclic rings can be heterocycloalkyl, heterocycloalkenyl, heterocycloalkynyl, etc., such as piperazinyl, piperidinyl, piperidonyl, 4-piperidonyl, dihydrofuran [2,3-b] tetrahydrofuran, morpholinyl, piperazinyl, piperidinyl, piperidonyl, 4-piperidonyl, piperonyl, pyranyl, 2H-pyrrolyl, 4H-quinolizinyl, quinuclidinyl, tetrahydrofuranyl, 6H-1,2,5-thiadiazinyl. The heterocyclic group may be optionally substituted by one or more substituents as defined above for alkyl and aryl.

[0042] The term "heteroaryl" refers to a C3-C4-1,1-diamino-2-nitropropene ring containing an aromatic ring and optionally one or more non-aromatic rings. 26The term "heteroaryl" refers to a ring system that is a monocyclic aromatic ring or a fused ring system in which one or more carbon atoms in the aromatic ring structure have been replaced by heteroatoms. Suitable heteroatoms include, but are not limited to, oxygen, sulfur, and nitrogen. Examples of heteroaryl groups are pyrrole, furan, thiophene, imidazole, oxazole, thiazole, triazole, tetrazole, pyrazole, pyridine, pyrazine, pyridazine, and pyrimidine, etc. Examples of heteroaryl rings include, but are not limited to, benzimidazolyl, benzofuranyl, benzothiofuranyl, benzothiophenyl, benzoxazolyl, benzoxazolinyl, benzothiazolyl, benzotriazolyl, benzotetrazolyl, benzisoxazolyl, benzisothiazolyl, benzimidazolinyl, carbazolyl, 4aH-carbazolyl, carbolinyl, chromanyl, chromenyl, hexazinyl, decahydroquinolinyl, 2H,6H-1,5,2-dithiazinyl, furanyl, furazanyl, imidazolidinyl, , imidazolinyl, imidazolyl, 1H-indazolyl, indolene, indolyl, indolizinyl, indolyl, 3H-indolyl, isatinoyl, isobenzofuranyl, isochromanyl, isoindazolyl, isoindolyl, isoindolyl, isoquinolyl, isothiazolyl, isoxazolyl, methylenedioxyphenyl, naphthyridinyl, octahydroisoquinolyl, 1,2,3-oxadiazolyl, 1,2,4-oxadiazolyl, 1,2,5-oxadiazolyl, 1,3,4-oxadiazolyl, oxazolidinyl, oxazolyl, oxindolyl, pyrimidinyl, phenanthridinyl, phenanthrolinyl, phenazinyl, phenothiazinyl, phenoxathiyl, phenoxazinyl, phthalazinyl, pteridinyl, purinyl, pyrazinyl, pyrazolidinyl, pyrazolinyl, pyrazolyl, pyridazinyl, pyridooxazole, pyridoimidazole, pyridothiazole, pyridinyl, pyridinyl, pyridyl, pyrimid ... The invention also includes pyridinyl, pyrrolidinyl, pyrrolinyl, pyrrolyl, quinazolinyl, quinolyl, quinoxalinyl, tetrahydroisoquinolyl, tetrahydroquinolyl, tetrazolyl, 1,2,3-thiadiazolyl, 1,2,4-thiadiazolyl, 1,2,5-thiadiazolyl, 1,3,4-thiadiazolyl, thianthrenyl, thiazolyl, thienyl, thienothiazolyl, thienooxazolyl, thienoimidazolyl, thiophenyl, and xanthenyl. One or more rings may be substituted as defined below for "substituted heteroaryl".

[0043] The term "substituted heteroaryl" refers to a heteroaryl group in which one or more hydrogen atoms on one or more heteroaryl rings are replaced with one or more substituents, including but not limited to halogen, azide, alkyl, aralkyl, alkenyl, alkynyl, cycloalkyl, hydroxy, alkoxy, carbonyl (e.g., ketone, aldehyde, carboxyl, alkoxycarbonyl, formyl, or acyl), silyl, ether, ester, thiocarbonyl (e.g., thioester, thioacetate, or thioformate), alkoxy, phosphoryl, phosphate, phosphonate, phosphinate, amino (or quaternized amino), amide, amidine, imine, cyano, nitro, azido, sulfhydryl, imino, alkylthio, sulfate, sulfonate, sulfamoyl, sulfoxide, sulfonamido, sulfonyl, heterocyclyl, alkylaryl, haloalkyl (e.g., CF3, -CH2-CF3, -CCl3), -CN, aryl, heteroaryl, and combinations thereof.

[0044] The term "polyaryl" refers to a fused ring system comprising two or more aromatic rings and optionally one or more non-aromatic rings. Examples of polyaryl groups are naphthalene, anthracene, phenanthrene, When the fused ring system contains two or more aromatic rings and optionally one or more non-aromatic rings, wherein one or more carbon atoms on the two or more aromatic ring structures have been replaced by heteroatoms, the fused ring system may be referred to as a "polyheteroaryl". When the fused ring system contains two or more aromatic rings and optionally one or more non-aromatic rings, wherein one or more carbon atoms in the fused ring system are replaced by heteroatoms, the fused ring system may be referred to as a "heteropolyaryl".

[0045] The term "substituted polyaryl" refers to a polyaryl in which one or more aryl groups are substituted with one or more substituents, including but not limited to halogen, azide, alkyl, aralkyl, alkenyl, alkynyl, cycloalkyl, hydroxyl, carbonyl (e.g., carboxyl, alkoxycarbonyl, formyl, or acyl), silyl, ether, ester, thiocarbonyl (e.g., thioester, thioacetate, or thioformate), alkoxy, phosphoryl, phosphate, phosphonate, phosphinate, amino (or quaternized amino), amido, amidine, imine, cyano, nitro, azido, sulfhydryl, alkylthio, sulfate, sulfonate, sulfamoyl, sulfoxide, sulfonamido, sulfonyl, heterocyclyl, alkylaryl, haloalkyl, -CN, aryl, heteroaryl, and combinations thereof. When referring to polyheteroaryl, the chemical moiety may be referred to as a "substituted polyheteroaryl".

[0046] The term "ring" or "cyclic group" refers to a substituted or unsubstituted monocyclic ring or a substituted or unsubstituted polycyclic ring (e.g., those formed by a monocyclic ring system or a fused ring system), such as a substituted or unsubstituted cycloalkyl, a substituted or unsubstituted cycloalkenyl, a substituted or unsubstituted cycloalkynyl, or a substituted or unsubstituted heterocyclyl, having from 3 to 30 carbon atoms where geometric constraints permit. Substituted cycloalkyl, cycloalkenyl, cycloalkynyl, and heterocyclyl are substituted as defined above for alkyl, alkenyl, alkynyl, and heterocyclyl, respectively.

[0047] As used herein, the term "aralkyl" is an aryl or heteroaryl group having an alkyl, alkynyl, or alkenyl group as defined above attached to an aromatic group (e.g., aryl, heteroaryl, polyaryl, or polyheteroaryl). An example of an aralkyl group is a benzyl group.

[0048] The terms "alkoxy" or "alkyloxy", "aryloxy" or "aryloxy" generally describe a radical of the formula -OR v A compound represented by v Including but not limited to substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocyclic radical, substituted or unsubstituted cycloalkenyl, substituted or unsubstituted heterocycloalkenyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, substituted or unsubstituted polyaryl, substituted or unsubstituted polyheteroaryl, substituted or unsubstituted arylalkyl, substituted or unsubstituted assorted alkyl, substituted or unsubstituted alkylaryl, substituted or unsubstituted alkylheteroaryl, substituted or unsubstituted aralkyl, substituted or unsubstituted carbonyl, phosphonium, phosphine, phosphino, sulfinyl, silyl, mercaptan, amide and amino. Exemplary alkoxy groups include methoxy, ethoxy, propoxy, tert-butoxy etc. "low alkoxy" group is an alkoxy group containing 1 to 6 carbon atoms. "ether" is two functional groups covalently linked by oxygen as defined below. Thus, the alkyl substituent that renders the alkyl group an ether is or is similar to an alkoxy group, and can be represented, for example, by one of -O-alkyl, -O-alkenyl, -O-alkynyl, -O-arakyl, -O-aryl, -O-heteroaryl, -O-polyaryl, -O-polyheteroaryl, -O-heterocyclyl, etc.

[0049] The term "substituted alkoxy" refers to an alkoxy group having one or more substituents replacing one or more hydrogen atoms on one or more carbons of the alkoxy backbone. Such substituents can be any of the above substituents, such as halogen, azide, alkyl, aralkyl, alkenyl, alkynyl, cycloalkyl, hydroxyl, carbonyl (e.g., carboxyl, alkoxycarbonyl, formyl or acyl), silyl, ether, ester, thiocarbonyl (e.g., thioester, thioacetate, or thioformate), alkoxy, phosphonium, phosphoalkyl, phosphoryl, phosphate, phosphonate, phosphinate, amino (e.g., quaternized amino), amide, amidine, imine, cyano, nitro, azido, sulfhydryl, alkylthio, oxo, sulfate, sulfonate, sulfamoyl, sulfonamido, sulfonyl, heterocyclyl, alkylaryl, haloalkyl, -CN, aryl, heteroaryl, and combinations thereof.

[0050] As used herein, the term "ether" is a 2 OA 1 Indicates that A 2 and A 1 It may independently be a substituted or unsubstituted alkyl group, a substituted or unsubstituted alkenyl group, a substituted or unsubstituted alkynyl group, a substituted or unsubstituted heterocyclic group, a substituted or unsubstituted aryl group, a substituted or unsubstituted heteroaryl group, a substituted or unsubstituted aralkyl group, a substituted or unsubstituted polyaryl group, a substituted or unsubstituted polyheteroaryl group, a phosphonium group, a phosphane group, a phosphonyl group, a sulfinyl group, a silyl group, a thiol group, a substituted or unsubstituted carbonyl group, an alkoxy group, an amide group, or an amino group as described above.

[0051] As used herein, the term "polyether" is represented by the formula:

[0052]

[0053] Among them A 3 It may independently be a substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, substituted or unsubstituted aralkyl, substituted or unsubstituted polyaryl, substituted or unsubstituted polyheteroaryl, phosphonium, phosphine, substituted or unsubstituted carbonyl, alkoxy, amide, or amino group as described above; g may be a positive integer from 1 to 30.

[0054] The term "phenoxy" is art-recognized and refers to a radical of the formula -OR v A compound wherein R v It is C6H5 (ie -OC-6H5). Those skilled in the art will recognize that phenoxy is a type of aryloxy.

[0055] The term "substituted phenoxy" refers to a phenoxy group as defined above having one or more substituents replacing one or more hydrogen atoms on one or more carbons of a benzene ring. Such substituents include, but are not limited to, halogen, azide, alkyl, aralkyl, alkenyl, alkynyl, cycloalkyl, hydroxyl, carbonyl (e.g., carboxyl, alkoxycarbonyl, formyl, or acyl), silyl, ether, ester, thiocarbonyl (e.g., thioester, thioacetate, or thioformate), alkoxy, phosphonium, phosphoalkyl, phosphoalkyl, phosphoryl, phosphate, phosphonate, phosphinate, amino (e.g., quaternized amino), amide, amidine, imine, cyano, nitro, azido, sulfhydryl, alkylthio, sulfate, sulfonate, sulfamoyl, sulfonamido, sulfonyl, heterocyclic, alkylaryl, haloalkyl, -CN, aryl, heteroaryl, and combinations thereof.

[0056] The terms "aryloxy" and "aryloxy" used interchangeably herein are represented by -O-aryl or -O-heteroaryl, wherein aryl and heteroaryl are as defined herein.

[0057] The terms "substituted aryloxy" and "substituted aryloxy" used interchangeably herein represent an -O-aryl or -O-heteroaryl group having one or more substituents replacing one or more hydrogen atoms on one or more ring atoms of aryl and heteroaryl groups as defined herein. Such substituents can be any of the substituents described above, such as halogen, azide, alkyl, aralkyl, alkenyl, alkynyl, cycloalkyl, hydroxyl, carbonyl (e.g., carboxyl, alkoxycarbonyl, formyl, or acyl), silyl, ether, ester, thiocarbonyl (e.g., thioester, thioacetate, or thioformate), alkoxy, phosphonium, phosphanyl, phosphanyl, phosphoryl, phosphate, phosphonate, phosphinate, amino (e.g., quaternized amino), amide, amidine, imine, cyano, nitro, azido, sulfhydryl, alkylthio, sulfate, sulfonate, sulfamoyl, sulfonamido, sulfonyl, heterocyclyl, alkylaryl, haloalkyl, -CN, aryl, heteroaryl, polyaryl, polyheteroaryl, and combinations thereof.

[0058] As used herein, the term "amino" includes the following groups

[0059]

[0060] wherein E is absent or E is substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted aralkyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, substituted or unsubstituted polyaryl, substituted or unsubstituted polyheteroaryl, substituted or unsubstituted heterocyclyl, wherein independently of E, R x , R xi and R xiiEach independently represents a substituted or unsubstituted alkyl group, a substituted or unsubstituted alkenyl group, a substituted or unsubstituted alkynyl group, a substituted or unsubstituted carbonyl group, a substituted or unsubstituted heterocyclic group, a substituted or unsubstituted aralkyl group (e.g., a substituted or unsubstituted alkylaryl group, a substituted or unsubstituted arylalkyl group), a substituted or unsubstituted aryl group, a substituted or unsubstituted heteroaryl group, a substituted or unsubstituted polyaryl group, a substituted or unsubstituted polyheteroaryl group, a substituted or unsubstituted heterocyclic group, a hydroxyl group, an alkoxy group, a phosphonium group, a phosphine group, a phosphino group, a sulfinyl group, a silyl group, a thiol group, an amide group, an amino group, or -(CH2) m -R"'; R"' represents a hydroxyl group, a substituted or unsubstituted carbonyl group, a substituted or unsubstituted aryl group, a substituted or unsubstituted cycloalkyl group, a substituted or unsubstituted cycloalkenyl group, a substituted or unsubstituted heterocyclyl group, a substituted or unsubstituted aryl group, a substituted or unsubstituted heteroaryl group, a substituted or unsubstituted polyaryl group, a substituted or unsubstituted polyheteroaryl group, an alkoxy group, a phosphonium group, a phosphine group, an amide group, or an amino group; and m is 0 or an integer from 1 to 8. The term "quaternary amino group" also includes groups wherein nitrogen, R x , R xi , and R xii The N + A group forming a heterocyclic or heteroaryl group having 3 to 14 atoms in the ring structure. It will be appreciated by those skilled in the art that the E groups listed above are divalent (e.g., methylene, ethane-1,2-diyl, ethylene-1,2-diyl, 1,4-phenylene, cyclohexane-1,2-diyl).

[0061] The terms "amide" or "amido" are used interchangeably to refer to both "unsubstituted amide" and "substituted amide" and are represented by the following general formula:

[0062]

[0063] wherein E is absent or E is substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted aralkyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, substituted or unsubstituted polyaryl, substituted or unsubstituted polyheteroaryl, or substituted or unsubstituted heterocyclyl, wherein R and R' independently of E each independently represent hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl , substituted or unsubstituted carbonyl, substituted or unsubstituted heterocyclic, substituted or unsubstituted aralkyl (e.g., substituted or unsubstituted alkylaryl, substituted or unsubstituted arylalkyl), substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, substituted or unsubstituted polyaryl, substituted or unsubstituted polyheteroaryl, substituted or unsubstituted heterocyclic, hydroxy, alkoxy, phosphonium, phosphine, phosphino, sulfinyl, silyl, thiol, amide, amino, or -(CH2) m-R"', or R and R' together with the N atom to which they are attached form a heterocyclic ring having 3 to 14 atoms in the ring structure; R"' represents a hydroxyl group, a substituted or unsubstituted carbonyl group, a substituted or unsubstituted aryl group, a substituted or unsubstituted cycloalkyl group, a substituted or unsubstituted cycloalkenyl group, a substituted or unsubstituted heterocyclyl group, a substituted or unsubstituted aryl group, a substituted or unsubstituted heteroaryl group, a substituted or unsubstituted polyaryl group, a substituted or unsubstituted polyheteroaryl group, an alkoxy group, a phosphonium group, a phosphine group, an amide group, or an amino group; and m is zero or an integer ranging from 1 to 8. In some forms, when E is oxygen, a carbamate is formed. It will be understood by those skilled in the art that the E groups listed above are divalent (e.g., methylene, ethane-1,2-diyl, ethylene-1,2-diyl, 1,4-phenylene, cyclohexane-1,2-diyl).

[0064] As used herein, "carbonyl" is art-recognized and includes moieties that can be represented by the following general formula:

[0065]

[0066] wherein X is a bond or represents oxygen or sulfur, and R represents hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbonyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aralkyl (e.g. substituted or unsubstituted alkylaryl, substituted or unsubstituted arylalkyl), substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, substituted or unsubstituted polyaryl, substituted or unsubstituted polyheteroaryl, substituted or unsubstituted heterocyclyl, hydroxy, alkoxy, phosphonium, phosphinyl, amide, amino, or -(CH2) m -R", or a pharmaceutically acceptable salt; E" is absent, or E" is substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted aralkyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, substituted or unsubstituted polyaryl, substituted or unsubstituted polyheteroaryl, substituted or unsubstituted heterocyclyl; R' represents hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aralkyl (e.g., substituted or unsubstituted alkylaryl, substituted or unsubstituted arylalkyl), substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, substituted or unsubstituted polyaryl, substituted or unsubstituted polyheteroaryl, substituted or unsubstituted heterocyclyl, hydroxy, alkoxy, phosphonium, phosphinyl, amide, amino, or -(CH2) m-R"; R" represents a hydroxyl group, a substituted or unsubstituted aryl group, a substituted or unsubstituted cycloalkyl group, a substituted or unsubstituted cycloalkenyl group, a substituted or unsubstituted heterocyclyl group, a substituted or unsubstituted aryl group, a substituted or unsubstituted heteroaryl group, a substituted or unsubstituted polyaryl group, a substituted or unsubstituted polyheteroaryl group, an alkoxy group, a phosphonium group, a phosphine group, an amide group, or an amino group; and m is 0 or an integer ranging from 1 to 8. Such substituents can be any of the substituents described above, such as halogen, azide, alkyl, aralkyl, alkenyl, alkynyl, cycloalkyl, hydroxyl, carbonyl (e.g., carboxyl, alkoxycarbonyl, formyl, or acyl), silyl, ether, ester, thiocarbonyl (e.g., thioester, thioacetate, or thioformate), alkoxy, phosphonium, phosphanyl, phosphoryl, phosphate, phosphonate, phosphinate, amino (e.g., quaternized amino), amide, amidine, imine, cyano, nitro, azido, sulfhydryl, alkylthio, sulfate, sulfonate, sulfamoyl, sulfonamido, sulfonyl, heterocyclyl, alkylaryl, haloalkyl, -CN, aryl, heteroaryl, and combinations thereof. It will be appreciated by those skilled in the art that the E" groups listed above are divalent (e.g., methylene, ethane-1,2-diyl, ethylene-1,2-diyl, 1,4-phenylene, cyclohexane-1,2-diyl). When X is oxygen and R is as defined above, the moiety is also referred to as a carboxyl group. When X is oxygen and R is hydrogen, the formula represents a "carboxylic acid". When X is oxygen and R' is hydrogen, the formula represents a "formatic ester". When X is oxygen and R or R' is not When X is sulfur and R or R' is hydrogen, the formula represents an "ester". In general, when the oxygen atom in the above formula is replaced by a sulfur atom, the formula represents a "thiocarbonyl" group. When X is sulfur and R or R' is not hydrogen, the formula represents a "thioester". When X is sulfur and R is hydrogen, the formula represents a "thioformic acid". When X is sulfur and R' is hydrogen, the formula represents a "thioformate". When X is a bond and R is not hydrogen, the above formula represents a "ketone". When X is a bond and R is hydrogen, the above formula represents an "aldehyde".

[0067] The term "phosphoalkyl" is represented by the formula

[0068]

[0069] wherein E is absent or E is substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted aralkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, substituted or unsubstituted polyaryl, substituted or unsubstituted polyheteroaryl, substituted or unsubstituted heterocyclyl, wherein R is independent of E, vi and R viiEach independently represents hydrogen, a substituted or unsubstituted alkyl group, a substituted or unsubstituted alkenyl group, a substituted or unsubstituted alkynyl group, a substituted or unsubstituted carbonyl group, a substituted or unsubstituted heterocyclic group, a substituted or unsubstituted aralkyl group (e.g., a substituted or unsubstituted alkylaryl group, a substituted or unsubstituted arylalkyl group, etc.), a substituted or unsubstituted aryl group, a substituted or unsubstituted heteroaryl group, a substituted or unsubstituted polyaryl group, a substituted or unsubstituted polyheteroaryl group, a substituted or unsubstituted heterocyclic group, a hydroxyl group, an alkoxy group, a phosphonium group, a phosphine group, a phosphino group, a sulfinyl group, a silyl group, a thiol group, an amide group, an amino group, or -(CH2) m -R"', or R vi and R vii Together with the P atom to which they are attached, they form a heterocyclic ring having 3 to 14 atoms in the ring structure; R'' represents a hydroxyl group, a substituted or unsubstituted carbonyl group, a substituted or unsubstituted aryl group, a substituted or unsubstituted cycloalkyl group, a substituted or unsubstituted cycloalkenyl group, a substituted or unsubstituted heterocyclyl group, a substituted or unsubstituted aryl group, a substituted or unsubstituted heteroaryl group, a substituted or unsubstituted polyaryl group, a substituted or unsubstituted polyheteroaryl group, an alkoxyl group, a phosphonium group, a phosphine group, an amide group, or an amino group; and m is 0 or an integer ranging from 1 to 8. Such substituents may be any of the substituents described above, such as halogen, azide, alkyl, aralkyl, alkenyl, alkynyl, cycloalkyl, hydroxyl, carbonyl (e.g., carboxyl, alkoxycarbonyl) , formyl, or acyl), silyl, ether, ester, thiocarbonyl (e.g., thioester, thioacetate, or thioformate), alkoxy, phosphoryl, phosphate, phosphonate, phosphinate, amino (e.g., quaternized amino), amide, amidine, imine, cyano, nitro, azido, sulfhydryl, alkylthio, sulfate, sulfonate, sulfamoyl, sulfonamido, sulfonyl, heterocyclic, alkylaryl, haloalkyl, -CN, aryl, heteroaryl, polyaryl, polyheteroaryl, and combinations thereof. It will be appreciated by those skilled in the art that the E groups listed above are divalent (e.g., methylene, ethane-1,2-diyl, ethylene-1,2-diyl, 1,4-phenylene, cyclohexane-1,2-diyl).

[0070] The term "phosphonium" is represented by the formula

[0071]

[0072] wherein E is absent or E is substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted aralkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, substituted or unsubstituted polyaryl, substituted or unsubstituted polyheteroaryl, substituted or unsubstituted heterocyclyl, wherein R is independent of E, vi , R vii and R viiiEach independently represents hydrogen, a substituted or unsubstituted alkyl group, a substituted or unsubstituted alkenyl group, a substituted or unsubstituted alkynyl group, a substituted or unsubstituted carbonyl group, a substituted or unsubstituted heterocyclic group, a substituted or unsubstituted aralkyl group (e.g., a substituted or unsubstituted alkylaryl group, a substituted or unsubstituted arylalkyl group, etc.), a substituted or unsubstituted aryl group, a substituted or unsubstituted heteroaryl group, a substituted or unsubstituted polyaryl group, a substituted or unsubstituted polyheteroaryl group, a substituted or unsubstituted heterocyclic group, a hydroxyl group, an alkoxy group, a phosphonium group, a phosphine group, a phosphino group, a sulfinyl group, a silyl group, a thiol group, an amide group, an amino group, or -(CH2) m -R"', or R vi , R vii and R viii The P + The atoms together form a heterocyclic ring having 3 to 14 atoms in the ring structure; R'' represents a hydroxyl group, a substituted or unsubstituted carbonyl group, a substituted or unsubstituted aryl group, a substituted or unsubstituted cycloalkyl group, a substituted or unsubstituted cycloalkenyl group, a substituted or unsubstituted heterocyclyl group, a substituted or unsubstituted aryl group, a substituted or unsubstituted heteroaryl group, a substituted or unsubstituted polyaryl group, a substituted or unsubstituted polyheteroaryl group, an alkoxyl group, a phosphonium group, a phosphine group, an amide group, or an amino group; and m is 0 or an integer ranging from 1 to 8. Such substituents can be any of the substituents described above, such as halogen, azide, alkyl, aralkyl, alkenyl, alkynyl, cycloalkyl, hydroxyl, carbonyl (e.g., carboxyl, alkoxycarbonyl, formyl) group. , or acyl), silyl, ether, ester, thiocarbonyl (e.g., thioester, thioacetate, or thioformate), alkoxy, phosphoryl, phosphate, phosphonate, phosphinate, amino (e.g., quaternized amino), amide, amidine, imine, cyano, nitro, azido, sulfhydryl, alkylthio, sulfate, sulfonate, sulfamoyl, sulfonamido, sulfonyl, heterocyclic, alkylaryl, haloalkyl, -CN, aryl, heteroaryl, polyaryl, polyheteroaryl, and combinations thereof. It will be appreciated by those skilled in the art that the E groups listed above are divalent (e.g., methylene, ethane-1,2-diyl, ethylene-1,2-diyl, 1,4-phenylene, cyclohexane-1,2-diyl).

[0073] The term "phosphono" is represented by the formula

[0074]

[0075] wherein E is absent or E is substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted aralkyl (e.g., substituted or unsubstituted alkylaryl, substituted or unsubstituted arylalkyl, etc.), substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, substituted or unsubstituted polyaryl, substituted or unsubstituted polyheteroaryl, substituted or unsubstituted heterocyclyl, oxygen, alkoxy, aryloxy, or substituted alkoxy, or substituted aryloxy, wherein independently E, R vi and R vii independently hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbonyl, substituted or unsubstituted heterocyclic, substituted or unsubstituted aralkyl (e.g., substituted or unsubstituted alkylaryl, substituted or unsubstituted arylalkyl, etc.), substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, substituted or unsubstituted polyaryl, substituted or unsubstituted polyheteroaryl, substituted or unsubstituted heterocyclic, hydroxy, alkoxy, phosphonium, phosphine, phosphino, sulfinyl, silyl, thiol, amide, amino, or -(CH2) m -R"', or R vi and R vii Together with the P atom to which they are attached, they form a heterocyclic ring having 3 to 14 atoms in the ring structure; R'' represents a hydroxyl group, a substituted or unsubstituted carbonyl group, a substituted or unsubstituted aryl group, a substituted or unsubstituted cycloalkyl group, a substituted or unsubstituted cycloalkenyl group, a substituted or unsubstituted heterocyclyl group, a substituted or unsubstituted aryl group, a substituted or unsubstituted heteroaryl group, a substituted or unsubstituted polyaryl group, a substituted or unsubstituted polyheteroaryl group, an alkoxyl group, a phosphonium group, a phosphine group, an amide group, or an amino group; and m is 0 or an integer ranging from 1 to 8. Such substituents may be any of the substituents described above, such as halogen, azide, alkyl, aralkyl, alkenyl, alkynyl, cycloalkyl, hydroxyl, carbonyl (e.g., carboxyl, alkoxycarbonyl) , formyl, or acyl), silyl, ether, ester, thiocarbonyl (e.g., thioester, thioacetate, or thioformate), alkoxy, phosphoryl, phosphate, phosphonate, phosphinate, amino (e.g., quaternized amino), amide, amidine, imine, cyano, nitro, azido, sulfhydryl, alkylthio, sulfate, sulfonate, sulfamoyl, sulfonamido, sulfonyl, heterocyclic, alkylaryl, haloalkyl, -CN, aryl, heteroaryl, polyaryl, polyheteroaryl, and combinations thereof. It will be appreciated by those skilled in the art that the E groups listed above are divalent (e.g., methylene, ethane-1,2-diyl, ethylene-1,2-diyl, 1,4-phenylene, cyclohexane-1,2-diyl).

[0076] The term "phosphoryl" defines a phosphonyl group wherein E is absent, oxygen, alkoxy, aryloxy, substituted alkoxy, or substituted aryloxy, as defined above and independently of E, Rvi and R vii R is independently hydroxy, alkoxy, aryloxy, substituted alkoxy, or substituted aryloxy, as defined above. As will be appreciated by those of ordinary skill in the art, when E is oxygen, the phosphoryl group cannot be attached to another chemical species, such as to form an oxygen-oxygen bond or other unstable bond. vi and R vii When substituted, the substituents include, but are not limited to, halogen, azide, alkyl, aralkyl, alkenyl, alkynyl, cycloalkyl, hydroxyl, carbonyl (e.g., carboxyl, alkoxycarbonyl, formyl, or acyl), silyl, ether, ester, thiocarbonyl (e.g., thioester, thioacetate, or thioformate), alkoxy, phosphoryl, phosphate, phosphonate, phosphinate, amino (e.g., quaternized amino), amide, amidine, imine, cyano, nitro, azido, sulfhydryl, alkylthio, sulfate, sulfonate, sulfamoyl, sulfonamido, sulfonyl, heterocyclyl, alkylaryl, haloalkyl, -CN, aryl, heteroaryl, polyaryl, polyheteroaryl, and combinations thereof. It will be appreciated by those skilled in the art that the E groups listed above are divalent (e.g., methylene, ethane-1,2-diyl, ethylene-1,2-diyl, 1,4-phenylene, cyclohexane-1,2-diyl).

[0077] The term "sulfinyl" is represented by the formula

[0078]

[0079] wherein E is absent or E is substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted aralkyl (e.g., substituted or unsubstituted alkylaryl, substituted or unsubstituted arylalkyl, etc.), substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted polyaryl, substituted or unsubstituted polyheteroaryl, wherein R, independently of E, represents hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbonyl, substituted or unsubstituted heterocyclic, substituted or unsubstituted aralkyl (e.g., substituted or unsubstituted alkylaryl, substituted or unsubstituted arylalkyl), substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, substituted or unsubstituted polyaryl, substituted or unsubstituted polyheteroaryl, substituted or unsubstituted heterocyclic, hydroxy, alkoxy, phosphonium, phosphine, phosphino, phosphono, silyl, thiol, amide, amino, or -(CH2) m-R"', or E and R together with the S atom to which they are attached form a heterocyclic ring having 3 to 14 atoms in the ring structure; R"' represents a hydroxyl group, a substituted or unsubstituted carbonyl group, a substituted or unsubstituted aryl group, a substituted or unsubstituted cycloalkyl group, a substituted or unsubstituted cycloalkenyl group, a substituted or unsubstituted heterocyclyl group, a substituted or unsubstituted aryl group, a substituted or unsubstituted heteroaryl group, a substituted or unsubstituted polyaryl group, a substituted or unsubstituted polyheteroaryl group, an alkoxy group, a phosphonium group, a phosphine group, an amide group, or an amino group; and m is 0 or an integer ranging from 1 to 8. Such substituents can be any of the substituents described above, such as halogen, azide, alkyl, aralkyl, alkenyl, alkynyl, cycloalkyl, hydroxyl, carbonyl (e.g., carboxyl, alkoxycarbonyl, formyl, or acyl), silyl, ether, ester, thiocarbonyl (e.g., thioester, thioacetate, or thioformate), alkoxy, phosphoryl, phosphate, phosphonate, phosphinate, amino (e.g., quaternized amino), amide, amidine, imine, cyano, nitro, azido, sulfhydryl, alkylthio, sulfate, sulfonate, sulfamoyl, sulfonamido, sulfonyl, heterocyclyl, alkylaryl, haloalkyl, -CN, aryl, heteroaryl, polyaryl, polyheteroaryl, and combinations thereof. It will be appreciated by those skilled in the art that the E groups listed above are divalent (e.g., methylene, ethane-1,2-diyl, ethylene-1,2-diyl, 1,4-phenylene, cyclohexane-1,2-diyl).

[0080] The term "sulfonyl" is represented by the formula

[0081]

[0082] wherein E is absent or E is substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted aralkyl (e.g., substituted or unsubstituted alkylaryl, substituted or unsubstituted arylalkyl, etc.), substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted polyaryl, substituted or unsubstituted polyheteroaryl, wherein R, independently of E, represents hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbonyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aralkyl (e.g., substituted or unsubstituted alkylaryl, substituted or unsubstituted arylalkyl), substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, substituted or unsubstituted polyaryl, substituted or unsubstituted polyheteroaryl, substituted or unsubstituted heterocyclyl, hydroxy, alkoxy, phosphonium, phosphinyl, amide, amino, or -(CH2) m-R"', or E and R together with the S atom to which they are attached form a heterocyclic ring having 3 to 14 atoms in the ring structure; R"' represents a hydroxyl group, a substituted or unsubstituted carbonyl group, a substituted or unsubstituted aryl group, a substituted or unsubstituted cycloalkyl group, a substituted or unsubstituted cycloalkenyl group, a substituted or unsubstituted heterocyclyl group, a substituted or unsubstituted aryl group, a substituted or unsubstituted heteroaryl group, a substituted or unsubstituted polyaryl group, a substituted or unsubstituted polyheteroaryl group, an alkoxy group, a phosphonium group, a phosphine group, an amide group, or an amino group; and m is 0 or an integer ranging from 1 to 8. Such substituents can be any of the substituents described above, such as halogen, azide, alkyl, aralkyl, alkenyl, alkynyl, cycloalkyl, hydroxyl, carbonyl (e.g., carboxyl, alkoxycarbonyl, formyl, or acyl), silyl, ether, ester, thiocarbonyl (e.g., thioester, thioacetate, or thioformate), alkoxy, phosphoryl, phosphate, phosphonate, phosphinate, amino (e.g., quaternized amino), amide, amidine, imine, cyano, nitro, azido, sulfhydryl, alkylthio, sulfate, sulfonate, sulfamoyl, sulfonamido, sulfonyl, heterocyclyl, alkylaryl, haloalkyl, -CN, aryl, heteroaryl, polyaryl, polyheteroaryl, and combinations thereof. It will be appreciated by those skilled in the art that the E groups listed above are divalent (e.g., methylene, ethane-1,2-diyl, ethylene-1,2-diyl, 1,4-phenylene, cyclohexane-1,2-diyl).

[0083] The term "sulfonic acid" refers to a sulfonyl group as defined above wherein R is hydroxy and E is absent or E is substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted alkylaryl, substituted or unsubstituted arylalkyl, substituted or unsubstituted aryl, substituted or unsubstituted polyaryl, substituted or unsubstituted polyheteroaryl, or substituted or unsubstituted heteroaryl. Such substituents can be any of the substituents described above, such as halogen, azide, alkyl, aralkyl, alkenyl, alkynyl, cycloalkyl, hydroxyl, carbonyl (e.g., carboxyl, alkoxycarbonyl, formyl, or acyl), silyl, ether, ester, thiocarbonyl (e.g., thioester, thioacetate, or thioformate), alkoxy, phosphoryl, phosphate, phosphonate, phosphinate, amino (e.g., quaternized amino), amide, amidine, imine, cyano, nitro, azido, sulfhydryl, alkylthio, sulfate, sulfonate, sulfamoyl, sulfonamido, sulfonyl, heterocyclyl, alkylaryl, haloalkyl, -CN, aryl, heteroaryl, polyaryl, polyheteroaryl, and combinations thereof. It will be appreciated by those skilled in the art that the E groups listed above are divalent (e.g., methylene, ethane-1,2-diyl, ethylene-1,2-diyl, 1,4-phenylene, cyclohexane-1,2-diyl).

[0084] The term "sulfate" refers to a sulfonyl group as defined above: wherein E is absent, oxygen, alkoxy, aryloxy, substituted alkoxy or substituted aryloxy, all as defined above, and R is independently hydroxy, alkoxy, aryloxy, substituted alkoxy or substituted aryloxy, all as defined above. As will be appreciated by those of ordinary skill in the art, when E is oxygen, sulfate cannot be connected to another chemical species, such as to form an oxygen-oxygen bond or other unstable bonds, etc. Such substituents can be any of the substituents described above, such as halogen, azide, alkyl, aralkyl, alkenyl, alkynyl, cycloalkyl, hydroxyl, carbonyl (e.g., carboxyl, alkoxycarbonyl, formyl, or acyl), silyl, ether, ester, thiocarbonyl (e.g., thioester, thioacetate, or thioformate), alkoxy, phosphoryl, phosphate, phosphonate, phosphinate, amino (e.g., quaternized amino), amide, amidine, imine, cyano, nitro, azido, sulfhydryl, alkylthio, sulfate, sulfonate, sulfamoyl, sulfonamido, sulfonyl, heterocyclyl, alkylaryl, haloalkyl, -CN, aryl, heteroaryl, polyaryl, polyheteroaryl, and combinations thereof. It will be appreciated by those skilled in the art that the E groups listed above are divalent (e.g., methylene, ethane-1,2-diyl, ethylene-1,2-diyl, 1,4-phenylene, cyclohexane-1,2-diyl).

[0085] The term "sulfonate" refers to a sulfonyl group as defined above: wherein E is oxygen, alkoxy, aryloxy, substituted alkoxy, or substituted aryloxy, all as defined above, and R is independently hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted amino, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aralkyl, substituted or unsubstituted alkylaryl, substituted or unsubstituted arylalkyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, substituted or unsubstituted polyaryl, substituted or unsubstituted polyheteroaryl, -(CH2) m-R"', R"' represents a hydroxyl group, a substituted or unsubstituted carbonyl group, an aryl group, a cycloalkyl ring, a cycloalkenyl ring, a heterocycle, an amide group, an amino group, or a polycycle; and m is zero or an integer ranging from 1 to 8. As will be appreciated by those of ordinary skill in the art, when E is oxygen, the sulfonate cannot be attached to another chemical species, such as to form an oxygen-oxygen bond or other unstable bonds. Such substituents can be any of the substituents described above, such as halogen, azide, alkyl, aralkyl, alkenyl, alkynyl, cycloalkyl, hydroxyl, carbonyl (e.g., carboxyl, alkoxycarbonyl, formyl, or acyl), silyl, ether, ester, thiocarbonyl (e.g., thioester, thioacetate, or thioformate), alkoxy, phosphoryl, phosphate, phosphonate, phosphinate, amino (e.g., quaternized amino), amide, amidine, imine, cyano, nitro, azido, sulfhydryl, alkylthio, sulfate, sulfonate, sulfamoyl, sulfonamido, sulfonyl, heterocyclyl, alkylaryl, haloalkyl, -CN, aryl, heteroaryl, polyaryl, polyheteroaryl, and combinations thereof. It will be appreciated by those skilled in the art that the E groups listed above are divalent (e.g., methylene, ethane-1,2-diyl, ethylene-1,2-diyl, 1,4-phenylene, cyclohexane-1,2-diyl).

[0086] The term "sulfamoyl" refers to a sulfonamide or a sulfonamide represented by the formula

[0087]

[0088] wherein E is absent, or E is substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted aralkyl (e.g., substituted or unsubstituted alkylaryl, substituted or unsubstituted cycloalkyl, etc.), substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, substituted or unsubstituted polyaryl, substituted or unsubstituted polyheteroaryl, substituted or unsubstituted heterocyclyl, wherein R and R' independently of E each independently represent hydrogen, substituted or unsubstituted alkyl, , substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbonyl, substituted or unsubstituted heterocyclic group, substituted or unsubstituted aralkyl (e.g., substituted or unsubstituted alkylaryl, substituted or unsubstituted arylalkyl, etc.), substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, substituted or unsubstituted polyaryl, substituted or unsubstituted polyheteroaryl, substituted or unsubstituted heterocyclic group, hydroxyl, alkoxy, phosphonium, phosphine, amide, amino, or -(CH2) m-R"', or R and R' together with the N atom to which they are attached form a heterocyclic ring having 3 to 14 atoms in the ring structure; R"' represents a hydroxyl group, a substituted or unsubstituted carbonyl group, a substituted or unsubstituted aryl group, a substituted or unsubstituted cycloalkyl group, a substituted or unsubstituted cycloalkenyl group, a substituted or unsubstituted heterocyclyl group, a substituted or unsubstituted aryl group, a substituted or unsubstituted heteroaryl group, a substituted or unsubstituted polyaryl group, a substituted or unsubstituted polyheteroaryl group, an alkoxy group, a phosphonium group, a phosphine group, an amide group, or an amino group; and m is 0 or an integer ranging from 1 to 8. Such substituents can be any of the substituents described above, such as halogen, azide, alkyl, aralkyl, alkenyl, alkynyl, cycloalkyl, hydroxyl, carbonyl (e.g., carboxyl, alkoxycarbonyl, formyl, or acyl), silyl, ether, ester, thiocarbonyl (e.g., thioester, thioacetate, or thioformate), alkoxy, phosphoryl, phosphate, phosphonate, phosphinate, amino (e.g., quaternized amino), amide, amidine, imine, cyano, nitro, azido, sulfhydryl, alkylthio, sulfate, sulfonate, sulfamoyl, sulfonamido, sulfonyl, heterocyclyl, alkylaryl, haloalkyl, -CN, aryl, heteroaryl, polyaryl, polyheteroaryl, and combinations thereof. It will be appreciated by those skilled in the art that the E groups listed above are divalent (e.g., methylene, ethane-1,2-diyl, ethylene-1,2-diyl, 1,4-phenylene, cyclohexane-1,2-diyl).

[0089] The term "silyl group" as used herein is represented by the formula -SiRR'R", wherein R, R' and R" can independently be hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, substituted or unsubstituted aralkyl (e.g., substituted or unsubstituted alkylaryl, substituted or unsubstituted arylalkyl, etc.), substituted or unsubstituted polyaryl, substituted or unsubstituted polyheteroaryl, substituted or unsubstituted carbonyl, phosphonium, phosphoalkyl, phosphono, sulfinyl, thiol, amide, amino, alkoxy, or oxo as described above. Such substituents can be any of the substituents described above, such as halogen, azide, alkyl, aralkyl, alkenyl, alkynyl, cycloalkyl, hydroxyl, carbonyl (e.g., carboxyl, alkoxycarbonyl, formyl, or acyl), silyl, ether, ester, thiocarbonyl (e.g., thioester, thioacetate, or thioformate), alkoxy, phosphoryl, phosphate, phosphonate, phosphinate, amino (e.g., quaternized amino), amide, amidine, imine, cyano, nitro, azido, sulfhydryl, alkylthio, sulfate, sulfonate, sulfamoyl, sulfonamido, sulfonyl, heterocyclyl, alkylaryl, haloalkyl, -CN, aryl, heteroaryl, polyaryl, polyheteroaryl, and combinations thereof.

[0090] The term "thiol" is used interchangeably and is represented by -SR, where R can be hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, substituted or unsubstituted aralkyl (e.g., substituted or unsubstituted alkylaryl, substituted or unsubstituted arylalkyl, etc.), substituted or unsubstituted polyaryl, substituted or unsubstituted polyheteroaryl, substituted or unsubstituted carbonyl, phosphonium, phosphinyl, amido, amino, alkoxy, oxo, phosphono, sulfinyl, or silyl as described above. Such substituents can be any of the substituents described above, such as halogen, azide, alkyl, aralkyl, alkenyl, alkynyl, cycloalkyl, hydroxyl, carbonyl (e.g., carboxyl, alkoxycarbonyl, formyl, or acyl), silyl, ether, ester, thiocarbonyl (e.g., thioester, thioacetate, or thioformate), alkoxy, phosphoryl, phosphate, phosphonate, phosphinate, amino (e.g., quaternized amino), amide, amidine, imine, cyano, nitro, azido, sulfhydryl, alkylthio, sulfate, sulfonate, sulfamoyl, sulfonamido, sulfonyl, heterocyclyl, alkylaryl, haloalkyl, -CN, aryl, heteroaryl, polyaryl, polyheteroaryl, and combinations thereof.

[0091] The disclosed compounds and substituent groups can independently have two or more of the above groups. For example, if the compound or substituent group is a straight chain alkyl group, one hydrogen atom of the alkyl group can be substituted by a hydroxyl group, an alkoxy group, etc. Depending on the selected group, the first group can be incorporated into the second group, or the first group can be suspended (i.e., attached) to the second group. For example, for the phrase "an alkyl group comprising an ester group", the ester group can be incorporated into the main chain of the alkyl group. Alternatively, the ester can be attached to the main chain of the alkyl group. The nature of the selected group will determine whether the first group is embedded or attached to the second group.

[0092] The compounds and substituents may be independently substituted with substituents as described above in the definition of "substituted".

[0093] Numerical ranges disclose each possible number that the range can reasonably cover, and any sub-range and combination of sub-ranges covered therein, respectively. For example, in the carbon range of a given range C3 to C9, the range also discloses C3, C4, C5, C6, C7, C8, and C9, and any sub-range (e.g., C4 to C6) between these numbers, and any possible combination of possible ranges between these values. In another example, a given temperature range can be about 25°C to 30°C, wherein the range also discloses a temperature that can be independently selected from about 25°C, 26°C, 27°C, 28°C, 29°C, and 30°C, and any range (e.g., 26°C to 28°C) between these numbers, and any possible combination of ranges between these values.

[0094] The use of the term "about" is intended to describe values ​​that are approximately within ±10% of the value modified by the term "about". When the term "about" is used before a numerical range (i.e., about 1 to 5) or before a series of numbers (i.e., about 1, 2, 3, 4, etc.), unless otherwise indicated, it is intended to modify both ends of the numerical range and / or each number listed in the entire series.

[0095] The disclosed compounds and substituent groups can independently have two or more of the groups listed above. For example, if the compound or substituent group is a straight chain alkyl group, one hydrogen atom of the alkyl group can be substituted by a hydroxyl group, an alkoxy group, etc. Depending on the selected group, the first group can be incorporated into the second group, or the first group can be suspended (i.e., connected) to the second group. For example, for the phrase "an alkyl group comprising an ester group", the ester group can be introduced into the main chain of the alkyl group. Alternatively, the ester can be connected to the main chain of the alkyl group. The nature of the selected group will determine whether the first group is embedded in or connected to the second group.

[0096] The compounds and substituents may be independently substituted with substituents as described above in the definition of "substituted".

[0097] II. Method for the Asymmetric Cis-Dihydroxylation of Styrene and Conjugated Diolefins

[0098] Methods for asymmetric cis-dihydroxylation ("AD") of olefins (such as styrene or its derivatives and conjugated dienes) to produce cis-diols or tetraols of the olefins have been developed. The methods described herein use an iron-based catalyst (such as one or more Fe(II) complexes, etc.) as a catalyst and an oxidant (such as hydrogen peroxide). In some forms, the AD of styrene or its derivatives and / or conjugated dienes catalyzed by the Fe(II) complex has a high yield (e.g., a yield of ≥14% or ≥30%, such as a yield of 14% to about 99% or 30% to about 99%, etc.) and / or a high enantioselectivity (e.g., an enantiomeric excess ("ee") ≥60%, such as an ee of about 68% to about 99.9% or >99.9%, etc.).

[0099] In some forms, the AD of styrene or its derivatives catalyzed by the Fe(II) complex has a yield ≥30% (such as a yield of 30% to about 99%) and / or an enantioselectivity ≥60% (such as an ee of about 68% to about 99.9% or >99.9%).

[0100] In some forms, the yield of the AD of conjugated dienes catalyzed by the Fe(II) complex is ≥14% or ≥30% (such as a yield of 14% to about 99% or 30% to about 99%, etc.) and / or the enantioselectivity is ≥60% (such as an ee of about 68% to about 99.9% or >99.9%, etc.). In certain forms, the methods described herein can produce cis-diols of olefins in high yields and high enantioselectivities.

[0101] The methods described herein have at least the following advantages: (1) the cis-diols of olefins can be produced in high yields and / or high enantioselectivities; (2) the use of biocompatible iron-based catalysts is environmentally friendly and cost-effective; and (3) the waste products produced by the reaction are non-toxic.

[0102] The methods described herein overcome the disadvantages associated with conventional AD reactions of olefins using Os-based catalysts (e.g., commercial products AD-mix-α / β developed by Sharpless and co-workers, etc.), which are expensive due to the low abundance of osmium metal on Earth and have environmental and health issues due to the generation of toxic waste in superstoichiometric amounts. For example, in AD reactions using osmium-based catalysts, K3Fe(CN)6 is generally added as a terminal oxidant, which produces an equivalent amount of K4Fe(CN)6 waste. A superstoichiometric amount of K2CO3 is also required as an additive in osmium-based catalysts. The methods described herein can use hydrogen peroxide as a terminal oxidant, which is a green oxidant and converts two / four hydroxyl (OH) groups into product molecules with 100% atomic efficiency, and does not require any additives.

[0103] The method generally comprises: (i) keeping a reaction mixture at a temperature for a period of time sufficient to form a product. The reaction mixture contains an olefin (e.g., styrene, a styrene derivative, or a conjugated diene), one or more iron-based catalysts, an oxidant, and a solvent. The product contains a cis-diol (e.g., when the olefin is styrene, a styrene derivative, or a conjugated diene) or a tetraol (e.g., when the olefin is a conjugated diene).

[0104] The reaction mixture can be formed by dissolving an olefin (such as styrene, styrene derivatives or conjugated diene, etc.) and an iron-based catalyst in a solvent before the reaction. Suitable solvents for forming a reaction mixture can dissolve olefins and iron-based catalysts. For example, the solubility of styrene, styrene derivatives or conjugated diene in a solvent is at least 0.01M, while the solubility of an iron-based catalyst in a solvent is at least 0.0015M. Exemplary solvents suitable for forming a reaction mixture include, but are not limited to, alcohols, such as C1 to C6 alcohols, such as methanol, ethanol, propanol, etc.

[0105] Optionally, the method also includes, before step (i), adding an oxidant (e.g., hydrogen peroxide solution) to a premix containing an olefin (e.g., styrene, styrene derivatives, or conjugated dienes, etc.), one or more iron-based catalysts, and a solvent to form a reaction mixture. The oxidant can be added in the form of a solution formed by dissolving the oxidant in an oxidant solvent. The oxidant solvent can be the same or different from the solvent forming the premix. For example, the solvent forming the premix is ​​the same as the oxidant solvent forming the oxidant solution, such as alcohol, for example methanol.

[0106] The oxidant can be added to the premix using any suitable technique. For example, the oxidant in solution form is added to the premix using a syringe pump at room temperature over a suitable period of time (such as a period of time in the range of 20 min to 1 hour, for example about 30 min). For example, the oxidant in solution form is directly added to the premix at room temperature.

[0107] The specific technique for adding the oxidant can be selected based on the desired product. For example, when the desired product is a cis-diol, the oxidant in solution form can be added to the premix at room temperature over a suitable period of time (such as a period of time in the range of 20 min to 1 hour, for example, about 30 min) using a syringe pump. For example, when the desired product is a tetraol, the oxidant in solution form can be directly added to the premix at room temperature.

[0108] Optionally, the method further comprises stirring the reaction mixture before step (i) and / or during step (i); and / or purifying the product after step (i), optionally by column chromatography.

[0109] A. Maintaining the reaction mixture at a temperature for a period of time sufficient to form the product

[0110] Typically, a reaction mixture containing an olefin (such as styrene, a styrene derivative, or a conjugated diene, etc.), one or more iron-based catalysts, and an oxidant disclosed herein in a suitable solvent is maintained at a suitable temperature and for a period of time sufficient to form a product containing the cis-diol or tetraol of the olefin.

[0111] In some forms, specific reaction conditions, such as the amount of oxidant used in step (i), the amount of catalyst, the specific catalyst, reaction temperature, reaction time period, etc., can be selected based on the reactants and desired products.

[0112] In some forms, the methods disclosed herein convert styrene or styrene derivatives into cis-diols by AD reaction. In some forms, the methods disclosed herein convert conjugated dienes into cis-diols by AD reaction. In some forms, the methods disclosed herein convert conjugated dienes into tetraols by AD reaction.

[0113] The olefins (i.e., substrates) described herein (such as styrene, styrene derivatives, and conjugated dienes, etc.) can be synthesized using methods known in the field of organic chemical synthesis or can be commercially available. For example, the target substrate can be synthesized by reacting one or more corresponding reactants in a suitable solvent. The reaction solution containing one or more corresponding reactants can be stirred at a suitable temperature for a suitable time to form a product containing the target substrate. The product containing the target substrate can be purified to separate the target substrate.

[0114] 1. Iron-based catalysts

[0115] The AD reaction of olefins described herein is catalyzed by an iron-based catalyst (optionally more than one iron-based catalyst). For example, the AD reaction of styrene, styrene derivatives, or conjugated dienes in the reaction mixture is catalyzed by one or more Fe(II) complexes. In some forms, the Fe(II) complexes of two or more catalysts in the reaction mixture or each Fe(II) complex may have a structure of Formula IX:

[0116]

[0117] Wherein: (a) J and J' can independently be a bond (single bond, double bond or triple bond), a substituted or unsubstituted alkyl group, a substituted or unsubstituted alkenyl group, a substituted or unsubstituted cyclic group, a substituted or unsubstituted aryl group, or

[0118] or substituted or unsubstituted polyaryl; (b) L1 may be a bond or R 16 , R 16 '、R 17 and R 17 ' may independently be hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted aryl, substituted or unsubstituted polyaryl, or substituted or unsubstituted cyclic group, or R 16 and R 16 'Common and / or R 17 and R 17 'Together with the carbon atoms to which they are attached, they may form a substituted or unsubstituted aryl group, a substituted or unsubstituted polyaryl group, or a substituted or unsubstituted cyclic group, and p may be an integer from 1 to 10, 1 to 8, 1 to 6, 1 to 4, 1 to 3, or 1 or 2; (c) R 18 ~R 24 and R 18 '~R 24 ' may independently be hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted cyclic group, substituted or unsubstituted aryl, or substituted or unsubstituted polyaryl; (d) R25 and R 25 ' can independently be a leaving group; (e)------can be absent or be a bond (single, double or triple); and (f) the substituents can independently be substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted cyclic group, substituted or unsubstituted heterocyclic group, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, substituted or unsubstituted polyaryl, substituted or unsubstituted polyheteroaryl, substituted or unsubstituted aralkyl, carbonyl, halide, hydroxyl, phenoxy, aryloxy, alkylthio, phenylthio, arylthio, cyano, isocyano, alkoxy, nitro, carboxyl, amino, amide, oxo, silyl, sulfinyl, sulfonyl, sulfonic acid, phosphonium, phosphinyl, phosphoryl, phosphonyl, or thiol, or a combination thereof.

[0119] In some forms of Formula IX, R 19 , R 20 and R 21 Can be common and / or R 19 '、R 20 ' and R 21 ' may form together with the carbon atom to which they are attached a substituted or unsubstituted aryl group, a substituted or unsubstituted polyaryl group, or a substituted or unsubstituted cyclic group.

[0120] In some forms, the Fe(II) complex in the reaction mixture or each Fe(II) complex in the two or more catalysts may have a structure of Formula X, XI, or XIII:

[0121]

[0122] Where: (a) L1 can be a bond or R 16 , R 16 '、R 17 and R 17 ' may independently be hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted aryl, substituted or unsubstituted polyaryl, or substituted or unsubstituted cyclic group, or R 16 and R 16 'Common and / or R 17 and R 17 'together with the carbon atom to which they are attached, may form a substituted or unsubstituted aryl group, a substituted or unsubstituted polyaryl group, or a substituted or unsubstituted cyclic group, and p is an integer from 1 to 10, 1 to 8, 1 to 6, 1 to 4, 1 to 3, or 1 or 2; (b) T1' and T2' may independently be a substituted or unsubstituted heteroaryl group, a substituted or unsubstituted heteropolyaryl group, or a substituted or unsubstituted heterocyclic group; (c) R 18, R 23 , R 24 , R 18 '、R 23 ' and R 24 ' may independently be hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted aryl, substituted or unsubstituted alkylaryl, substituted or unsubstituted polyaryl; (d) R 19 and R 19 ' may independently be substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted aryl, substituted or unsubstituted alkylaryl, or substituted or unsubstituted polyaryl; (e) R 25 and R 25 ' may independently be a leaving group; and (f) the substituent may be as defined above for Formula IX.

[0123] In some forms of Formulas IX-XI and XIII, L1 can be a bond, Each occurrence of T' may be a substituted or unsubstituted monocyclic group, a substituted or unsubstituted polycyclic group, a substituted or unsubstituted aryl group, or a substituted or unsubstituted polyaryl group. Each occurrence of R 16 and R 16 ' may independently be a substituted or unsubstituted phenyl group, and p is an integer of 1 to 10, 1 to 8, 1 to 6, 1 to 4, 1 to 3, or 1 or 2.

[0124] In some forms of Formulas IX-XI and XIII, L1 can be Each occurrence of T' is a substituted or unsubstituted monocyclic group (e.g., an unsubstituted monocyclic alkyl group, such as an unsubstituted C3-C6 monocyclic alkyl group), or a substituted or unsubstituted polycyclic group (e.g., an unsubstituted polycyclic alkyl group), and p is an integer from 1 to 3, or 1 or 2, such as 1, etc.

[0125] In some forms of Formulae IX-XI and XIII, R 25 and R 25 ' can independently be a triflate, tosylate, mesylate, halide, nitrate, phosphate, thioether, amino, carboxylate, phenoxide, alkoxy, or amide, such as triflate and the like.

[0126] In some forms of Formulae IX-XI and XIII, R 23 and R 23 ' may be hydrogen, and R 24 and R 24 ' can be unsubstituted C1~C 10Alkyl, unsubstituted C1-C8 alkyl, unsubstituted C1-C6 alkyl, unsubstituted C1-C4 alkyl, unsubstituted C1-C2 alkyl, such as methyl, etc.

[0127] In some forms of Formulae IX-XI and XIII, R 18 It can be unsubstituted C1~C 10 Alkyl, unsubstituted C1-C8 alkyl, unsubstituted C1-C6 alkyl, unsubstituted C1-C4 alkyl, unsubstituted C1-C2 alkyl, such as methyl, etc.

[0128] In some forms of Formulae IX-XI and XIII, R 18 ' can be unsubstituted C1~C 10 alkyl, unsubstituted C1-C8 alkyl, unsubstituted C1-C6 alkyl, unsubstituted C1-C4 alkyl, unsubstituted C1-C3 alkyl (such as methyl, ethyl, isopropyl, etc.), or p and q are independently integers from 0 to 5, and each occurrence of R3 is independently hydrogen or unsubstituted C1-C 10 Alkyl (eg, methyl, ethyl, isopropyl, tert-butyl, etc.), or two adjacent R3 together with the carbon to which they are connected form an unsubstituted aryl or an unsubstituted polyaryl.

[0129] In some forms, the Fe(II) complex used to catalyze the AD of olefins may have the structure of Formula XII, XIV, or XV.

[0130]

[0131] Where: (a) R 26 and R 27 may independently be hydrogen, a substituted or unsubstituted cyclic group, a substituted or unsubstituted aryl group, or a substituted or unsubstituted polyaryl group; (b) R 28 ~R 41 may independently be hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted cyclic group, substituted or unsubstituted aryl, or substituted or unsubstituted polyaryl; (c) R 18 ' can be unsubstituted C1~C 10 alkyl, unsubstituted C1-C8 alkyl, unsubstituted C1-C6 alkyl, unsubstituted C1-C4 alkyl, unsubstituted C1-C3 alkyl (such as methyl, ethyl, isopropyl, etc.), or p and q are independently integers from 0 to 5, and each occurrence of R3 is independently hydrogen or unsubstituted C1-C 10alkyl (e.g., methyl, ethyl, isopropyl, tert-butyl, etc.), or two adjacent R3 and the carbon to which they are attached together form an unsubstituted aryl or unsubstituted polyaryl; and (d) the substituents can independently be substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted cyclic group, substituted or unsubstituted heterocyclic group, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, substituted or unsubstituted polyaryl, substituted or unsubstituted polyheteroaryl, substituted or unsubstituted aralkyl, carbonyl, halide, hydroxyl, phenoxy, aryloxy, alkylthio, phenylthio, arylthio, cyano, isocyano, alkoxy, nitro, carboxyl, amino, amide, oxo, silyl, sulfinyl, sulfonyl, sulfonic acid, phosphonium, phosphoalkyl, phosphoryl, phosphonyl, or thiol, or a combination thereof. In some forms of Formula XII, R 26 and R 27 Not hydrogen.

[0132] In some forms of Formula XII, R 26 and R 27 may independently be a substituted or unsubstituted aryl group, or a substituted or unsubstituted polyaryl group; (b) R 28 ~R 41 (c) the substituents may independently be hydrogen, substituted or unsubstituted alkyl, or substituted or unsubstituted alkenyl; and (c) the substituents may independently be substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, or substituted or unsubstituted alkynyl, or a combination thereof.

[0133] In some forms, for any of Formulas XIV and XV, R 26 and R 27 may independently be hydrogen, substituted or unsubstituted alkyl, or substituted or unsubstituted aryl; (b) R 28 and R 29 may independently be hydrogen, substituted or unsubstituted alkyl, or substituted or unsubstituted alkenyl; (c) R 30 ~R 41 (d) the substituents may independently be hydrogen, or substituted or unsubstituted alkyl; and (d) the substituents may independently be substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, or substituted or unsubstituted alkynyl, or a combination thereof.

[0134] In some forms of Formula XII, (a) R 26 and R 27 may be independently substituted or unsubstituted aryl; (b) R 28 ~R 41 (c) the substituents may independently be hydrogen, unsubstituted alkyl, or unsubstituted alkenyl; and (c) the substituents may independently be unsubstituted alkyl, unsubstituted alkenyl, unsubstituted alkynyl, or a combination thereof.

[0135] In some forms of Formula XII, (a) R 26 and R 27 may independently be unsubstituted aryl; and (b) R 28 ~R 41 and may independently be hydrogen, unsubstituted alkyl, or unsubstituted alkenyl.

[0136] In some forms, for any of Formulae XIV and XV, (a) R 26 and R 27 may be hydrogen, (b) R 28 and R 29 may be independently substituted or unsubstituted alkyl, such as unsubstituted C1-C8 alkyl, and (c) R 30 ~R 40 It may be hydrogen.

[0137] In some forms, the Fe(II) complex in the reaction mixture or each of the two or more catalysts may have the following structure:

[0138]

[0139] Where: (a) L1 can be a bond or R 16 , R 16 '、R 17 and R 17 ' may independently be hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted aryl, substituted or unsubstituted polyaryl, or substituted or unsubstituted cyclic group, or R 16 and R 16 ' and / or R 17 and R 17 ' forms a substituted or unsubstituted aryl group, a substituted or unsubstituted polyaryl group, or a substituted or unsubstituted cyclic group, and p can be an integer of 1 to 10, 1 to 8, 1 to 6, 1 to 5, 1 to 4, 1 to 3, or 1 or 2; (b) R 18 , R 23 , R 24 , R 18 '、R 23 ' and R 24 ' may independently be hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted aryl, substituted or unsubstituted alkylaryl, or substituted or unsubstituted polyaryl; (c) R 19 may be substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted aryl, substituted or unsubstituted alkylaryl, or substituted or unsubstituted polyaryl; (d) R 22, R 22 ' and R 31 ~R 34 may independently be hydrogen, substituted or unsubstituted alkyl, halogen, amino, or alkoxy; (e) R 25 and R 25 ' can independently be a leaving group; and (f) the substituent can independently be a substituted or unsubstituted alkyl, a substituted or unsubstituted alkenyl, a substituted or unsubstituted alkynyl, a substituted or unsubstituted cyclic group, a substituted or unsubstituted heterocyclic group, a substituted or unsubstituted aryl, a substituted or unsubstituted heteroaryl, a substituted or unsubstituted polyaryl, a substituted or unsubstituted polyheteroaryl, a substituted or unsubstituted aralkyl, a carbonyl, a halide, a hydroxyl, a phenoxy, an aryloxy, an alkylthio, a phenylthio, an arylthio, a cyano, an isocyano, an alkoxy, a nitro, a carboxyl, an amino, an amide, an oxo, a silyl, a sulfinyl, a sulfonyl, a sulfonic acid, a phosphonium, a phosphoalkyl, a phosphoryl, a phosphonyl, or a thiol, or a combination thereof.

[0140] In some forms, R 22 , R 22 ' and R 31 ~R 34 can be independently hydrogen, -NRR', methoxy or ethoxy, wherein R and R' can be independently hydrogen or unsubstituted alkyl, such as unsubstituted C1-C6 alkyl, for example methyl. In some forms, R 32 ~R 34 Can be hydrogen. In some forms, the compound can have the structure of Formula VI above.

[0141] In some forms, L1 can be Each occurrence of T' may be a substituted or unsubstituted monocyclic group, or a substituted or unsubstituted polycyclic group, and p is an integer from 1 to 3, or 1 or 2. In some forms, T' may be a substituted or unsubstituted C3-C6 monocyclic alkyl group, and optionally wherein the substituents (when present) may independently be unsubstituted phenyl or phenyl substituted with one or more unsubstituted alkyl groups (such as one or more unsubstituted C1-C6 alkyl groups).

[0142] In some forms, L1 can be Each occurrence of R 16 and R 16 ' may independently be a substituted or unsubstituted phenyl group, and p may be an integer from 1 to 3, or 1 or 2. In some forms, R 16 and R 16 ' may be unsubstituted phenyl.

[0143] In some forms, R 25 and R 25' can independently be triflate, tosylate, mesylate, halide, nitrate, phosphate, thioether, amino, carboxylate, phenoxide, alkoxy, or amide. In some forms, R 25 and R 25 ' can be a triflate.

[0144] In some forms, R 18 It may be an unsubstituted C1-C6 alkyl group, such as methyl or ethyl.

[0145] In some forms, R 18 ' can be unsubstituted C1~C 10 alkyl, unsubstituted C1-C8 alkyl, unsubstituted C1-C6 alkyl, unsubstituted C1-C4 alkyl, unsubstituted C1-C3 alkyl (such as methyl, ethyl, isopropyl, etc.), or X' can be carbon or nitrogen; p and q can independently be integers from 0 to 5, and each occurrence of R3 can independently be hydrogen, a halide (such as fluoride, chloride, bromide), an unsubstituted C1-C 10 alkyl (e.g., methyl, ethyl, isopropyl, tert-butyl, etc.), or unsubstituted phenyl, or two adjacent R3 together with the carbon to which they are attached form an unsubstituted aryl or unsubstituted polyaryl. 18 ' can be methyl or Wherein X' can be nitrogen or carbon, p can be 1 or 2, such as 1, q can be an integer from 1 to 4, and each occurrence of R3 can independently be hydrogen, a halide, an unsubstituted C1-C6 alkyl, an unsubstituted phenyl, or two adjacent R3 together with the carbon to which they are connected form an unsubstituted aryl group.

[0146] In some forms, R 19 can be substituted or unsubstituted alkylene, optionally substituted or unsubstituted methylene or ethylene groups. In some forms, R 19 It may be an unsubstituted methylene group, or a methylene group substituted by an unsubstituted C1-C6 alkyl group, an unsubstituted phenyl group or an unsubstituted C3-C6 monocycloalkyl group.

[0147] In some forms, R 23 and R 23 ' may be hydrogen, and R 24 and R 24 ' can be independently unsubstituted C1~C 10 alkyl, unsubstituted C1-C8 alkyl, unsubstituted C1-C6 alkyl, unsubstituted C1-C4 alkyl, or unsubstituted C1-C2 alkyl, such as methyl. In some forms, R 24 and R 24' can be methyl.

[0148] In some forms, R 24 and R 24 ' may be methyl; and R 22 , R 22 '、R 23 , R 23 ' and R 31 ~R 34 It may be hydrogen.

[0149] In some forms, R 22 and R 22 R' can be independently hydrogen, -NRR', methoxy or ethoxy, wherein R and R' can be independently hydrogen or unsubstituted alkyl, such as unsubstituted C1-C6 alkyl, for example methyl; R 24 and R 24 ' may be methyl; and R 23 , R 23 ' and R 31 ~R 34 It may be hydrogen.

[0150] In some forms, R 31 and R 22 R' may independently be hydrogen, -NRR', methoxy or ethoxy, wherein R and R' may independently be hydrogen or unsubstituted alkyl, such as unsubstituted C1-C6 alkyl, for example methyl; R 24 and R 24 ' may be methyl; and R 22 , R 23 , R 23 ' and R 32 ~R 34 It may be hydrogen.

[0151] Exemplary iron-based catalysts suitable for use in the AD reaction in step (i) are listed below.

[0152]

[0153]

[0154]

[0155] In some forms, the iron-based catalyst suitable for use in the AD reaction in step (i) is any one listed below.

[0156]

[0157]

[0158]

[0159] In some forms, the iron-based catalyst used in the AD reaction in step (i) is:

[0160]

[0161] Typically, the total amount of one or more iron-based catalysts in the reaction mixture is up to 20 mol%, such as in the range of 0.1 mol% to 20 mol%. The total amount of one or more catalysts in the reaction mixture can be calculated using the following formula: mol% of iron-based catalyst=[(total number of moles of one or more iron-based catalysts) / (total number of moles of olefins)]×100%. In some forms, the amount of iron-based catalyst in the AD reaction can be selected to obtain a specific product.

[0162] For example, when the disclosed method converts styrene or a styrene derivative to a cis-diol via an AD reaction, the total amount of the one or more iron-based catalysts in the reaction mixture is at most 10 mol%, at most 8 mol%, at most 6 mol%, at most 5 mol%, at most 3 mol%, at least 0.1 mol%, at least 0.5 mol%, in the range of about 0.1 mol% to about 10 mol%, in the range of about 0.1 mol% to about 8 mol%, in the range of about 0.1 mol% to about 6 mol%, in the range of about 0.1 mol% to about 5 mol%, in the range of about 0.1 mol% to about 3 mol%, in the range of about 0.5 mol% to about 6 mol%, in the range of about 0.5 mol% to about 5 mol%, in the range of about 0.5 mol% to about 3 mol%, in the range of about 1 mol% to about 6 mol%, or in the range of about 1 mol% to about 5 mol%.

[0163] For example, when the disclosed method converts a conjugated diene to a cis-diol via an AD reaction, the total amount of the one or more iron-based catalysts in the reaction mixture is up to 6 mol%, up to 5 mol%, up to 3 mol%, at least 0.1 mol%, at least 0.5 mol%, in the range of about 0.1 mol% to about 6 mol%, in the range of about 0.1 mol% to about 5 mol%, in the range of about 0.1 mol% to about 3 mol%, in the range of about 0.5 mol% to about 6 mol%, in the range of about 0.5 mol% to about 5 mol%, in the range of about 0.5 mol% to about 3 mol%, in the range of about 1 mol% to about 6 mol%, or in the range of about 1 mol% to about 5 mol%.

[0164] In some forms, when the disclosed methods convert conjugated dienes to tetraols via an AD reaction, the total amount of one or more iron-based catalysts in the reaction mixture is >6 mol%, at least 7 mol%, at least 8 mol%, in the range of about 6.5 mol% to about 20 mol%, in the range of about 7 mol% to about 20 mol%, in the range of about 7 mol% to about 15 mol%, in the range of about 6.5 mol% to about 15 mol%, in the range of about 8 mol% to about 20 mol%, in the range of about 8 mol% to about 15 mol%, in the range of about 7 mol% to about 12 mol%, or in the range of about 8 mol% to about 12 mol%, such as about 10 mol%, etc.

[0165] In some forms, the iron-based catalyst in the AD reaction can be selected to achieve the desired stereochemistry. For example, when the disclosed method converts a conjugated diene into a cis-diol or tetraol via an AD reaction catalyzed by Fe(S,S-PQCN-6)(OTf)2 as described above, the cis-diol or tetraol of the conjugated diene can have a (2S, 3R) or (2S, 3R, 4S, 5R) stereochemistry. For example, when the disclosed method converts a conjugated diene into a cis-diol or tetraol via an AD reaction catalyzed by Fe(S,S-2-Me2-BQCN)(OTf)2 as described above, the cis-diol or tetraol of the conjugated diene can have a (2R, 3S) or (2R, 3S, 4R, 5S) stereochemistry.

[0166] The iron-based catalysts described herein and the ligands forming the iron-based catalysts can be synthesized using methods known in the field of organic chemical synthesis. For example, the target Fe (II) complex can be synthesized by reacting the corresponding ligand (optionally more than one corresponding ligand) with an iron precursor in a suitable solvent. Exemplary solvents include organic solvents, such as acetonitrile. The corresponding ligands can be prepared using methods known in the art (such as the methods described in the embodiments). The reaction solution containing one or more corresponding ligands and the iron precursor can be stirred at a suitable temperature (such as room temperature) and optionally under an inert gas atmosphere (such as a nitrogen atmosphere) for a suitable time to form a product containing the target iron-based catalyst. The product containing the target iron-based catalyst can be purified and optionally recrystallized to separate the target iron-based catalyst.

[0167] 2.Convert styrene or its derivatives into cis-diols

[0168] In some forms, the method disclosed herein converts styrene or styrene derivatives into cis-diols by AD reaction. The reaction mixture contains styrene or its derivatives (optionally containing more than one styrene or its derivatives) as a substrate in the catalytic reaction. After step (i), a product containing one or more cis-diols converted from styrene or styrene derivatives in the reaction mixture is formed. In some forms, the product can also contain unreacted substrate, i.e., unreacted styrene or styrene derivatives, and / or an iron-based catalyst.

[0169] In these forms, the reaction mixture is typically maintained at a temperature below 0° C. (e.g., about −30° C.) for a period of time in the range of about 20 minutes to about 3 hours, in the range of about 20 minutes to about 2 hours, or in the range of about 20 minutes to 1 hour (e.g., about 30 min). In these forms, the total molar amount of the oxidant in the reaction mixture is typically about 1 to about 10 times, about 1.5 to about 6 times, or about 1 to about 5 times the total molar amount of styrene or a styrene derivative.

[0170] a. Styrene substrate and cis-diol product

[0171] In some forms, the styrene or styrene derivative in the reaction mixture may have a structure of Formula I, and the cis-diol converted therefrom has a structure of Formula I':

[0172]

[0173] wherein A1 can be substituted aryl, unsubstituted aryl, substituted polyaryl, unsubstituted polyaryl, substituted heteroaryl, unsubstituted heteroaryl, substituted heteropolyaryl, or unsubstituted heteropolyaryl.

[0174] In some forms, the styrene or styrene derivative in the reaction mixture may have a structure of Formula II, and the cis-diol converted therefrom has a structure of Formula II':

[0175]

[0176] wherein: (a) X1-X5 may independently be carbon, nitrogen, oxygen, or sulfur; (b) n1 may be an integer from 0 to 5; (c) each occurrence of R1 may independently be hydrogen, substituted alkyl, unsubstituted alkyl, substituted alkylaryl, unsubstituted alkylaryl, substituted aryl, unsubstituted aryl, substituted heterocycle, unsubstituted heterocycle, hydroxyl, halide, haloalkyl (such as haloalkyl, e.g. -CF3), nitro, amino, amide, alkoxy, cyano, or carbonyl, or two adjacent R1 groups together with the carbon atoms to which they are attached may form a substituted aryl, unsubstituted aryl, substituted polyaryl, unsubstituted polyaryl, substituted heteroaryl, unsubstituted heteroaryl, substituted heteropolyaryl, unsubstituted heteropolyaryl, substituted cycloalkyl, unsubstituted cycloalkyl group, substituted cycloalkyl group, and (d) the substituents, when present, can independently be substituted alkyl, unsubstituted alkyl, substituted cycloalkyl, unsubstituted cycloalkyl groups, substituted cycloalkenyl, unsubstituted cycloalkenyl groups, substituted cycloalkynyl, unsubstituted cycloalkynyl groups, substituted heterocyclic groups, unsubstituted heterocyclic groups, substituted aryl, unsubstituted aryl, substituted heteroaryl, unsubstituted heteroaryl, substituted polyaryl, unsubstituted polyaryl, substituted heteropolyaryl, unsubstituted heteropolyaryl, substituted alkylaryl, unsubstituted aralkyl, haloalkyl, carbonyl, halide, hydroxy, alkoxy, nitro, cyano, amino, amido, oxo, or thiol, or a combination thereof.

[0177] In some forms, each occurrence of R1 can independently be hydrogen, unsubstituted C1-C 10 Alkyl, unsubstituted heterocyclic, unsubstituted C1~C 10 Alkyl-substituted heterocycle, halide, haloalkyl (e.g., -CF3), nitro, cyano, -OR2, -C(=O)OR4, or Or two adjacent R1 groups and the carbon atoms to which they are attached may together form a substituted aryl group or an unsubstituted aryl group, and the substituents are independently unsubstituted C1~C 10 Alkyl, unsubstituted heterocyclic, unsubstituted C1~C 10 Alkyl-substituted heterocycle, halide, haloalkyl (e.g., -CF3), nitro, cyano, -OR2, -C(=O)OR4, or wherein p and q can be independently integers from 0 to 5, and R2 to R4 can be independently hydrogen, unsubstituted C1 to C 10 Alkyl, halide, or -O-(C1~C 10 alkyl).

[0178] In some forms, n1 is not 0, and at least one R1, at least two R1s, or at least three R1s may be electron withdrawing groups. In some forms, n1 is 1, and R1 may be electron withdrawing groups in the meta or para positions. In some forms, n1 is 1, and R1 may be electron withdrawing groups in the ortho position. p and q may independently be integers from 0 to 5, and each occurrence of R3 may independently be hydrogen, unsubstituted C1-C 10 Alkyl, halide, or -O-(C1~C 10 alkyl).

[0179] In some forms, X1 may be nitrogen, and X2-X5 may be carbon.

[0180] In some forms, two adjacent R1 groups together with the carbon atom to which they are attached form a substituted aryl group or an unsubstituted aryl group, and the substituents can independently be unsubstituted C1-C 10 Alkyl, unsubstituted heterocyclic, unsubstituted C1~C 10 Alkyl-substituted heterocyclic group, halide, haloalkyl (e.g., -CF3), nitro, cyano, -OR2, -C(=O)OR4, or p and q may independently be integers from 0 to 5, and R2 to R4 may independently be hydrogen, unsubstituted C1 to C 10 Alkyl, halide, or -O-(C1~C 10 alkyl).

[0181] Exemplary cis-diols converted from styrene or styrene derivatives are listed below.

[0182]

[0183]

[0184] b. Characterization

[0185] The disclosed methods for the asymmetric cis-dihydroxylation of styrene and styrene derivatives can be characterized by the cis-diol yield and the enantiomeric excess ("ee") of the cis-diol in the product.

[0186] Typically, the total yield of cis-diol in the product formed by the AD reaction of styrene or a styrene derivative using the disclosed methods can be at least 40%, at least 50%, in the range of about 40% to about 99%, in the range of about 50% to about 99%, in the range of about 60% to about 99%, in the range of about 70% to about 99%, or in the range of about 80% to about 99%. The yield of cis-diol in the product can be calculated using the following formula: yield of cis-diol = (total number of moles of experimentally obtained cis-diol) / (total number of theoretical moles of cis-diol) × 100%. The total number of experimentally obtained moles of cis-diol can be determined using known methods, such as using NMR (e.g., using a known amount of an internal standard (such as using a known amount of PhTMS as an internal standard) 1 HNMR, 19 F NMR and / or 31 P NMR) spectroscopy.

[0187] In general, the enantiomeric excess ("ee") of the cis-diol or each of the two or more cis-diols in the product formed by the AD reaction of styrene or a styrene derivative using the disclosed methods is at least 60%, at least 70%, at least 75%, at least 80%, up to 100%, in the range of about 60% to 100%, in the range of about 60% to 100%, in the range of about 70% to 100%, in the range of about 80% to 100%, in the range of about 90% to 100%, or in the range of about 95% to 100%, in the range of about 60% to 99%, in the range of about 70% to 99%, in the range of about 80% to 99%, in the range of about 90% to 99%, or in the range of about 95% to 99%. The ee of the cis-diol in the product can be calculated using the formula: ee = [(moles of one enantiomer - moles of the other enantiomer) / total moles of both enantiomers] x 100%. The ee of each cis diol can be determined using known methods, such as using chiral HPLC or a polarimeter. In some forms, the ee of each cis diol can be determined using chiral HPLC.

[0188] In some forms, the above yields and ee's of the cis-diols in the products formed from the AD reaction of styrene and styrene derivatives are obtained using the disclosed methods catalyzed by the Fe(II) complex of Formula VI'.

[0189] Specific exemplary cis-diols obtained using styrene or styrene derivatives as substrates and their corresponding yields and ee values ​​are described in the following examples.

[0190] 2.Conversion of conjugated dienes into cis-diols or tetraols

[0191] In some forms, the method disclosed herein converts conjugated diene into cis-diol or tetraol by AD reaction. The reaction mixture contains conjugated diene (optionally containing more than one conjugated diene) as a substrate in the catalytic reaction. After step (i), a product containing one or more cis-diol or tetraol converted from the conjugated diene in the reaction mixture is formed. In some forms, the product can also contain unreacted substrate, i.e., unreacted conjugated diene, and / or an iron-based catalyst.

[0192] In general, the total molar amount of the oxidant in the reaction mixture is usually about 1 to about 10 times, about 1.5 to about 6 times, or about 1 to about 5 times the total molar amount of the conjugated diene.

[0193] In some forms, the amount of catalyst, reaction temperature, and reaction time period may be selected such that the product of the AD reaction of the conjugated diene is a cis-diol or a tetraol.

[0194] For example, when the desired product of the AD reaction of the conjugated diene is a cis-diol, the total amount of the one or more iron-based catalysts in the reaction mixture can be up to 6 mol%, up to 5 mol%, up to 3 mol%, at least 0.1 mol%, at least 0.5 mol%, in the range of about 0.1 mol% to about 6 mol%, in the range of about 0.1 mol% to about 5 mol%, in the range of about 0.1 mol% to about 3 mol%, in the range of about 0.5 mol% to about 6 mol%, in the range of about 0.5 mol% to about 5 mol%, in the range of about 0.5 mol% to about 3 mol%, in the range of about 1 mol% to about 6 mol%, or in the range of about 1 mol% to about 5 mol%; and the reaction mixture is maintained at room temperature (i.e., about 20°C to about 22°C, at 1 atm) for a period of time in the range of about 20 minutes to about 3 hours, in the range of about 20 minutes to about 2 hours, in the range of about 20 minutes to 1 hour, or in the range of about 20 min to about 50 min (e.g., about 30 min). Furthermore, prior to the AD reaction, the oxidant may be added to a premixture formed of the conjugated diene, the iron-based catalyst, and the solvent using a syringe pump at room temperature over a period of time ranging from 20 min to 1 hour, such as about 30 min.

[0195] For example, when the desired product of the AD reaction of the conjugated diene is a tetraol, the total amount of one or more iron-based catalysts in the reaction mixture is>6mol%, at least 7mol%, at least 8mol%, in the range of about 6.5mol% to about 20mol%, in the range of about 7mol% to about 20mol%, in the range of about 7mol% to about 15mol%, in the range of about 6.5mol% to about 15mol%, in the range of about 8mol% to about 20mol%, in the range of about 8mol% to about 15mol%, in the range of about 7mol% to about 12mol%, or in the range of about 8mol% to about 12mol%, such as about 10mol%; and the reaction mixture can be kept at room temperature for a period of at least 1 hour, in the range of 1 hour to about 5 hours, in the range of 1 hour to about 4 hours, in the range of 1 hour to about 3 hours, in the range of 1 hour to about 2 hours (e.g., 1 hour). In addition, before the AD reaction, the oxidant can be directly added to the premix formed by the conjugated diene, the iron-based catalyst, and the solvent at room temperature.

[0196] a. Conjugated diene substrate and cis-diol product

[0197] In some forms, the conjugated diene in the reaction mixture may have a structure of Formula VII, and the cis-diol converted therefrom has a structure of Formula VII' or VII":

[0198]

[0199] wherein: (a) A2 can be substituted aryl, unsubstituted aryl, substituted polyaryl, unsubstituted polyaryl, substituted heteroaryl, unsubstituted heteroaryl, substituted heteropolyaryl, unsubstituted heteropolyaryl, or carbonyl; (b) R5 can be -C(=O)OR6, R6 is hydrogen, substituted alkyl, unsubstituted alkyl, substituted aryl, unsubstituted aryl, substituted polyaryl, unsubstituted polyaryl, substituted heteroaryl, unsubstituted heteroaryl, substituted heteropolyaryl, unsubstituted heteropolyaryl, substituted alkylaryl, or unsubstituted alkylaryl; (c) R'1 to R'4 can independently be hydrogen, substituted alkyl, unsubstituted alkyl, substituted aryl, unsubstituted aryl, substituted polyaryl, unsubstituted polyaryl, substituted heteroaryl, unsubstituted heteroaryl, substituted heteropolyaryl, unsubstituted heteropolyaryl, substituted alkylaryl, or unsubstituted alkylaryl. and (d) the substituents may independently be substituted alkyl, unsubstituted alkyl, substituted cycloalkyl, unsubstituted cycloalkenyl, unsubstituted cycloalkenyl, substituted cycloalkynyl, unsubstituted cycloalkynyl, substituted heterocyclic, or unsubstituted heterocyclic; and (d) the substituents may independently be substituted alkyl, unsubstituted alkyl, substituted cycloalkyl, unsubstituted cycloalkyl groups, substituted cycloalkenyl, unsubstituted cycloalkenyl groups, substituted cycloalkynyl, unsubstituted cycloalkynyl groups, substituted heterocyclic groups, unsubstituted heterocyclic groups, substituted aryl, unsubstituted aryl, substituted heteroaryl, unsubstituted heteroaryl, substituted polyaryl, unsubstituted polyaryl, substituted heteropolyaryl, unsubstituted heteropolyaryl, substituted alkylaryl, unsubstituted aralkyl, haloalkyl, carbonyl, halide, hydroxy, alkoxy, nitro, cyano, amino, amido, oxo, or thiol, or a combination thereof.

[0200] As described above, in some forms, the iron-based catalyst in the AD reaction can be selected to achieve the desired stereochemistry. For example, when the disclosed method converts a conjugated diene into a cis-diol via an AD reaction catalyzed by Fe(S,S-PQCN-6)(OTf)2 as described above, the cis-diol of the conjugated diene can have a (2S, 3R) stereochemistry, such as a structure of Formula VII'. For example, when the disclosed method converts a conjugated diene into a cis-diol via an AD reaction catalyzed by Fe(S,S-2-Me2-BQCN)(OTf)2 as described above, the cis-diol of the conjugated diene can have a (2R, 3S) stereochemistry, such as a structure of Formula VII", etc.

[0201] b. Characterization of cis-diol products

[0202] The disclosed process for the asymmetric cis-dihydroxylation of conjugated dienes to form cis-diols can be characterized by the cis-diol yield and the enantiomeric excess ("ee") of the cis-diol in the product.

[0203] Typically, the total yield of cis-diols in the product formed by the AD reaction of conjugated dienes using the disclosed methods can be at least 10%, at least 14%, at least 30%, at least 40%, in the range of about 14% to about 99%, in the range of about 30% to about 99%, in the range of about 40% to about 99%, in the range of about 50% to about 99%, in the range of about 60% to about 99%, or in the range of about 70% to about 99%. The yield of cis-diols in the product can be calculated using the method described above for styrene.

[0204] Typically, the enantiomeric excess ("ee") of the cis-diol or each of the two or more cis-diols in the product formed by the AD reaction of a conjugated diene using the disclosed methods is at least 80%, at least 85%, up to 100%, in the range of about 80% to 100%, in the range of about 85% to 100%, in the range of about 90% to 100%, in the range of about 80% to 99.9%, in the range of about 85% to 99.9%, or in the range of about 90% to 99.9%, in the range of about 80% to 99.5%, in the range of about 85% to 99.5%, in the range of about 90% to 99.5%, in the range of about 80% to 99%, or in the range of about 85% to 99%. The ee of the cis-diol in the product can be calculated using the methods described above for styrene (such as using chiral HPLC, etc.).

[0205] In some forms, the above yields and ee's of the cis-diols in the products formed from the AD reaction of conjugated dienes are obtained using the disclosed methods catalyzed with the Fe(II) complex of Formula VI'.

[0206] The following examples describe specific exemplary cis-diols obtained using conjugated dienes as substrates and their corresponding yields and ee values.

[0207] c. Conjugated diene substrate and tetraol product

[0208] In some forms, the conjugated diene in the reaction mixture may have a structure of Formula VII, and the tetraol converted therefrom has a structure of Formula VIII' or VIII":

[0209]

[0210] wherein: (a) A2 can be substituted aryl, unsubstituted aryl, substituted polyaryl, unsubstituted polyaryl, substituted heteroaryl, unsubstituted heteroaryl, substituted heteropolyaryl, unsubstituted heteropolyaryl, or carbonyl; (b) R5 can be -C(=O)OR6, R6 can be hydrogen, substituted alkyl, unsubstituted alkyl, substituted aryl, unsubstituted aryl, substituted polyaryl, unsubstituted polyaryl, substituted heteroaryl, unsubstituted heteroaryl, substituted heteropolyaryl, unsubstituted heteropolyaryl, substituted alkylaryl, or unsubstituted alkylaryl; (c) R'1 to R'4 can independently be substituted alkyl, unsubstituted alkyl, substituted aryl, unsubstituted aryl, substituted polyaryl, unsubstituted polyaryl, substituted heteroaryl, unsubstituted heteroaryl, substituted heteropolyaryl, unsubstituted heteropolyaryl, substituted alkylaryl, or unsubstituted alkylaryl. and (d) the substituents may independently be substituted alkyl, unsubstituted alkyl, substituted cycloalkyl, unsubstituted cycloalkenyl, unsubstituted cycloalkenyl, substituted cycloalkynyl, unsubstituted cycloalkynyl, substituted heterocyclic, or unsubstituted heterocyclic; and (d) the substituents may independently be substituted alkyl, unsubstituted alkyl, substituted cycloalkyl, unsubstituted cycloalkyl groups, substituted cycloalkenyl, unsubstituted cycloalkenyl groups, substituted cycloalkynyl, unsubstituted cycloalkynyl groups, substituted heterocyclic groups, unsubstituted heterocyclic groups, substituted aryl, unsubstituted aryl, substituted heteroaryl, unsubstituted heteroaryl, substituted polyaryl, unsubstituted polyaryl, substituted heteropolyaryl, unsubstituted heteropolyaryl, substituted alkylaryl, unsubstituted aralkyl, haloalkyl, carbonyl, halide, hydroxy, alkoxy, nitro, cyano, amino, amido, oxo, or thiol, or a combination thereof.

[0211] As described above, in some forms, the iron-based catalyst in the AD reaction can be selected to achieve the desired stereochemistry. For example, when the disclosed method converts a conjugated diene into a tetraol via an AD reaction catalyzed by Fe(S,S-PQCN-6)(OTf)2 as described above, the tetraol formed from the conjugated diene can have a (2S, 3R, 4R, 5S) stereochemistry, such as a structure of Formula VIII'. For example, when the disclosed method converts a conjugated diene into a tetraol via an AD reaction catalyzed by Fe(S,S-2-Me2-BQCN)(OTf)2 as described above, the tetraol formed from the conjugated diene can have a (2R, 3S, 4S, 5R) stereochemistry, such as a structure of Formula VIII".

[0212] d. Characterization of Tetrol Products

[0213] The disclosed process for the asymmetric cis-dihydroxylation of conjugated dienes to form tetrols can be characterized by the cis-diol yield and the enantiomeric excess ("ee") of the tetrol in the product.

[0214] Typically, the total yield of tetraols in the product formed by the AD reaction of conjugated dienes using the disclosed methods can be at least 10%, at least 14%, at least 30%, at least 40%, in the range of about 14% to about 99%, in the range of about 30% to about 99%, in the range of about 40% to about 99%, in the range of about 50% to about 99%, in the range of about 60% to about 99%, or in the range of about 70% to about 99%. The yield of tetraols in the product can be calculated using the method described above for styrene.

[0215] Typically, the enantiomeric excess ("ee") of the tetrol or each of the two or more tetrols in the product formed from the AD reaction of the conjugated diene using the disclosed methods is at least 90%, at least 95%, at least 99.9%, >99.9%, up to 100%, in the range of about 90% to 100%, in the range of about 95% to 100%, in the range of about 90% to 99.9%, in the range of about 95% to 99.9%, or in the range of about 99.9% to 100%. The ee of the tetrol in the product can be calculated using the methods described above for styrene (such as using chiral HPLC, etc.).

[0216] In some forms, the above yields and ee's of tetraols in products formed from AD reactions of conjugated dienes are obtained using the disclosed methods catalyzed by Fe(II) complexes of Formula VI'.

[0217] The following examples describe specific exemplary cis-diols obtained using conjugated dienes as substrates and their corresponding yields and ee values.

[0218] e. Structures of conjugated dienes, cis-diols, and tetraols

[0219] In some forms, the conjugated diene in the reaction mixture can have a structure of Formula VII, the corresponding cis-diol in the product can have a structure of Formula VII' or VII", and the corresponding tetraol in the product can have a structure of Formula VIII' or VIII", as described above and shown below.

[0220]

[0221]

[0222] In some forms, A2 may be: OR -C(=O)OR 14, wherein: (a) X'1 to X'6 can independently be carbon, nitrogen, oxygen, or sulfur; (b) n2 and n3 can independently be integers from 0 to 5; (c) each occurrence of R7 and R'7 can independently be hydrogen, substituted alkyl, unsubstituted alkyl, substituted alkylaryl, unsubstituted alkylaryl, substituted aryl, unsubstituted aryl, substituted heterocycle, unsubstituted heterocycle, hydroxy, halide, haloalkyl (such as haloalkyl, e.g. -CF3), nitro, amino, amide, alkoxy, cyano, or (d) R 14 can be hydrogen, substituted alkyl, unsubstituted alkyl, substituted aryl, unsubstituted aryl, substituted polyaryl, unsubstituted polyaryl, substituted heteroaryl, unsubstituted heteroaryl, substituted heteropolyaryl, unsubstituted heteropolyaryl, substituted alkylaryl, or unsubstituted alkylaryl; and (e) the substituents can independently be substituted alkyl, unsubstituted alkyl, substituted cycloalkyl, unsubstituted cycloalkyl, substituted cycloalkenyl, unsubstituted cycloalkenyl, The invention can include, but is not limited to, substituted cycloalkynyl groups, substituted cycloalkynyl groups, unsubstituted cycloalkynyl groups, substituted heterocyclic groups, unsubstituted heterocyclic groups, substituted aryl groups, unsubstituted aryl groups, substituted heteroaryl groups, unsubstituted heteroaryl groups, substituted polyaryl groups, unsubstituted polyaryl groups, substituted heteropolyaryl groups, unsubstituted heteropolyaryl groups, substituted alkylaryl groups, unsubstituted aralkyl groups, haloalkyl groups, carbonyl groups, halide groups, hydroxyl groups, alkoxy groups, nitro groups, cyano groups, amino groups, amido groups, oxo groups, or thiol groups, or combinations thereof.

[0223] In some forms, each occurrence of R7 and R'7 can independently be hydrogen, unsubstituted C1-C 10 Alkyl, unsubstituted heterocyclic, unsubstituted C1~C 10 Alkyl-substituted heterocycle, halide, haloalkyl (e.g., -CF3), nitro, cyano, -OR2, -C(=O)OR4, or Or two adjacent R7 groups or two adjacent R'7 groups together with the carbon atoms to which they are connected may form a substituted aryl group or an unsubstituted aryl group, and the substituents are independently unsubstituted C1~C 10 Alkyl, unsubstituted heterocyclic, unsubstituted C1~C 10 Alkyl-substituted heterocycle, halide, haloalkyl (e.g., -CF3), nitro, cyano, -OR2, -C(=O)OR4, or wherein p and q can be independently integers from 0 to 5, and R2 to R4 can be independently hydrogen, unsubstituted C1 to C 10 Alkyl, halide, or -O-(C1~C 10 alkyl).

[0224] In some forms, each occurrence of R7 and R'7 can independently be hydrogen, unsubstituted C1-C 10 Alkyl, unsubstituted heterocyclic, unsubstituted C1~C 10 Alkyl-substituted heterocycle, halide, haloalkyl (eg, -CF3), or cyano.

[0225] In some forms, X'2-X'5 can be carbon, X'1 can be carbon or nitrogen, and X'6 can be carbon, nitrogen, oxygen, or sulfur.

[0226] In some forms, R6 can be unsubstituted C1-C 10 Alkyl or p' and q' may independently be integers from 0 to 5, and each occurrence of R'3 may independently be hydrogen, unsubstituted C1-C 10 Alkyl, halide, or -O-(C1~C 10 In some forms, R6 can be unsubstituted C1-C8 alkyl, unsubstituted C1-C6 alkyl, unsubstituted C1-C4 alkyl, or And p' may independently be an integer from 0 to 3, from 0 to 2, or from 0 or 1.

[0227] In some forms, R'1 to R'4 can independently be hydrogen, unsubstituted C1 to C 10 alkyl, unsubstituted aryl, or unsubstituted alkylaryl.

[0228] In some forms, R 14 It can be an unsubstituted C1-C8 alkyl, an unsubstituted C1-C6 alkyl, an unsubstituted C1-C4 alkyl, or p' and q' may independently be integers from 0 to 5, and each occurrence of R'3 may independently be hydrogen, unsubstituted C1-C 10 Alkyl, halide, or -O-(C1~C 10 In some forms, R 14 It can be an unsubstituted C1-C4 alkyl or And p' may be an integer from 0 to 3, from 0 to 2, or from 0 or 1.

[0229] For any formula described herein, the alkyl group (when present) can be a straight chain alkyl group, a branched chain alkyl group, or a cyclic alkyl group (monocyclic or polycyclic). The terms "cyclic alkyl group" and "cycloalkyl group" are used interchangeably herein. Exemplary alkyl groups include straight chain C1-C 30 Alkyl, branched chain C4~C 30 Alkyl, cyclic C3~C 30 Alkyl, straight chain C1~C 20 Alkyl, branched chain C4~C 20 Alkyl, cyclic C3~C 20 Alkyl, straight chain C1~C 10 Alkyl, branched chain C4~C 10 Alkyl, cyclic C3~C 10 Alkyl, straight chain C1~C6 alkyl, branched chain C4~C6 alkyl, cyclic C3~C6 alkyl, straight chain C1~C4 alkyl, cyclic C3~C4 alkyl, such as straight chain C1~C 10 , C1-C9, C1-C8, C1-C7, C1-C6, C1-C5, C1-C4, C1-C3, or C1-C2 alkyl groups, branched C3-C9, C3-C9, C3-C8, C3-C7, C3-C6, C3-C5, or C3-C4 alkyl groups, or cyclic C3-C9, C3-C9, C3-C8, C3-C7, C3-C6, C3-C5, or C3-C4 alkyl groups. The cyclic alkyl group may be a monocyclic or polycyclic alkyl group, such as C4-C 30 、C4~C 25 、C4~C 20 、C4~C 18 、C4~C 16 、C4~C 15 、C4~C 14 、C4~C 13 、C4~C 12 、C4~C 10 , C4~C9, C4~C8, C4~C7, C4~C6, or C4~C5 monocyclic or polycyclic alkyl groups, etc.

[0230] For any formula described herein, alkenyl (when present) can be a straight chain alkenyl, a branched chain alkenyl, or a cyclic alkenyl (monocyclic or polycyclic). The terms "cyclic alkenyl" and "cycloalkenyl" are used interchangeably herein. Exemplary alkenyl groups include straight chain C2 to C 30 Alkenyl, branched C4~C 30 Alkenyl, cyclic C3~C 30 Alkenyl, straight chain C2~C 20 Alkenyl, branched C4~C 20 Alkenyl, cyclic C3~C 20 Alkenyl, straight chain C2~C 10Alkenyl, branched C4~C 10 Alkenyl, cyclic C3~C 10 alkenyl, straight-chain C2-C6 alkenyl, branched-chain C4-C6 alkenyl, cyclic C3-C6 alkenyl, straight-chain C2-C4 alkenyl, cyclic C3-C4 alkenyl, such as straight-chain C2-C 10 , C2-C9, C2-C8, C2-C7, C2-C6, C2-C5, C2-C4, C2-C3 alkenyl groups, branched C3-C9, C3-C9, C3-C8, C3-C7, C3-C6, C3-C5, C3-C4 alkenyl groups, or cyclic C3-C9, C3-C9, C3-C8, C3-C7, C3-C6, C3-C5, C3-C4 alkenyl groups, etc. The cyclic alkenyl group can be a monocyclic or polycyclic alkenyl group, such as C4-C 30 、C4~C 25 、C4~C 20 、C4~C 18 、C4~C 16 、C4~C 15 、C4~C 14 、C4~C 13 、C4~C 12 、C4~C 10 , C4~C9, C4~C8, C4~C7, C4~C6, or C4~C5 monocyclic or polycyclic alkenyl, etc.

[0231] For any formula described herein, the alkynyl group (when present) can be a straight chain alkynyl group, a branched chain alkynyl group, or a cyclic alkynyl group (monocyclic or polycyclic). The terms "cyclic alkynyl group" and "cycloalkynyl group" are used interchangeably herein. Exemplary alkynyl groups include straight chain C2-C 30 Alkynyl, branched C4~C 30 Alkynyl, cyclic C3~C 30 Alkynyl, straight chain C2~C 20 Alkynyl, branched C4~C 20 Alkynyl, cyclic C3~C 20 Alkynyl, straight chain C2~C 10 Alkynyl, branched C4~C 10 Alkynyl, cyclic C3~C 10 Alkynyl, straight chain C2-C6 alkynyl, branched chain C4-C6 alkynyl, cyclic C3-C6 alkynyl, straight chain C1-C4 alkynyl, cyclic C3-C4 alkynyl, such as straight chain C2-C 10, C2-C9, C2-C8, C2-C7, C2-C6, C2-C5, C2-C4, C2-C3 alkynyl groups, branched C3-C9, C3-C9, C3-C8, C3-C7, C3-C6, C3-C5, C3-C4 alkynyl groups, or cyclic C3-C9, C3-C9, C3-C8, C3-C7, C3-C6, C3-C5, C3-C4 alkynyl groups, etc. The cyclic alkynyl group can be a monocyclic or polycyclic alkynyl group, such as C4-C 30 、C4~C 25 、C4~C 20 、C4~C 18 、C4~C 16 、C4~C 15 、C4~C 14 、C4~C 13 、C4~C 12 、C4~C 10 , C4~C9, C4~C8, C4~C7, C4~C6, or C4~C5 monocyclic or polycyclic alkynyl groups, etc.

[0232] Exemplary (2S,3R)-cis diols converted from conjugated dienes are listed below.

[0233]

[0234] Exemplary (2R,3S)-cis diols converted from conjugated dienes are listed below.

[0235]

[0236]

[0237] Exemplary (2S,3R,4R,5S)-tetraols converted from conjugated dienes are listed below.

[0238]

[0239] Exemplary (2R,3S,4S,5R)-tetraols converted from conjugated dienes are listed below.

[0240]

[0241] B. Optional Steps

[0242] The disclosed methods may include one or more optional steps, such as adding an oxidizing agent (e.g., hydrogen peroxide) to the reaction mixture before step (i); stirring the reaction mixture before step (i) and / or during step (i); and / or purifying the product after step (i) (optionally by column chromatography).

[0243] 1. Add oxidant

[0244] Optionally, the disclosed method includes the step of adding an oxidant to the premix prior to step (i), and maintaining the reaction mixture at a temperature for a period of time sufficient to form a product containing a cis-diol or tetraol. The premix contains a substrate for forming a reaction mixture, an iron catalyst, and a solvent.

[0245] An exemplary oxidant suitable for use in the disclosed method is hydrogen peroxide. When the oxidant is added to the premix in the form of a solution, the solvent forming the oxidant solution can be the same as or different from the solvent forming the reaction mixture. For example, the hydrogen peroxide solution is formed by mixing hydrogen peroxide with the same solvent as the solvent forming the reaction mixture, such as an alcohol (e.g., methanol, ethanol, propanol, etc.), for example methanol.

[0246] The oxidant in solution form (such as hydrogen peroxide, etc.) can be added to the reaction mixture by quickly depressing a syringe containing the oxidant in solution form (direct addition). Alternatively, the oxidant in solution form (such as hydrogen peroxide, etc.) can be added to the reaction mixture over a period of time by a syringe pump at a suitable flow rate. For example, a hydrogen peroxide solution is added to the premix by a syringe pump at room temperature over a period of time ranging from 20 min to 1 hour (such as about 30 min).

[0247] Typically, after this step, the total molar amount of the oxidant (such as hydrogen peroxide) in the reaction mixture can be about 1 to about 10 times, about 1.5 to about 6 times, or about 2 to about 5 times the total molar amount of the substrate. For example, after the hydrogen peroxide is added to the premix (by rapid injection or over a period of time), the total moles of the oxidant in the reaction mixture are about 1 to about 10 times, about 1.5 to about 6 times, or about 2 to about 5 times (such as about 3 times) the total molar amount of the substrate in the reaction mixture.

[0248] In some forms, a specific technique for adding an oxidant can be selected based on the desired product. For example, when the desired product is a cis-diol, an oxidant in solution form can be added to the premix at room temperature over a suitable period of time (such as a period of time ranging from 20 min to 1 hour, for example, about 30 min) using a syringe pump. For example, when the desired product is a tetraol, an oxidant in solution form can be directly added to the premix at room temperature.

[0249] 2. Stir the reaction mixture

[0250] Optionally, the reaction mixture is stirred before step (i) and / or during step (i), and the reaction mixture is maintained at a temperature for a period of time sufficient to form a product containing a cis-diol or a tetraol. For example, the reaction mixture is stirred at the reaction temperature throughout the reaction period to form a product containing a cis-diol or a tetraol. Techniques for stirring the reaction mixture during the reaction are known, such as by using a mechanical stirring bar, magnetic stirring beads, etc.

[0251] 3. Purification of the product

[0252] Optionally, the disclosed method includes a step of purifying the product to remove impurities (such as unreacted substrate and / or catalyst) in the product, thereby obtaining isolated cis-diols or tetraols after the AD reaction (i.e., step (i)). The product can be purified by known methods, such as using silica gel column chromatography or recrystallization in a dichloromethane / hexane mixture.

[0253] Further understanding of the disclosed substrates, iron-based catalysts, products and methods can be obtained from the following enumerated paragraphs.

[0254] 1. An iron-based catalyst having the following structure:

[0255]

[0256] in:

[0257] (a) L1 is a bond or R 16 , R 16 '、R 17 , and R 17 ' is independently hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted aryl, substituted or unsubstituted polyaryl, or substituted or unsubstituted cyclic group, or R 16 With R 16 ' and / or R 17 With R 17 ' forms a substituted or unsubstituted aryl group, a substituted or unsubstituted polyaryl group, or a substituted or unsubstituted cyclic group, and p is an integer from 1 to 10;

[0258] (b)R 18 , R 23 , R 24 , R 18 '、R 23 ', and R 24 ' is independently hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted aryl, substituted or unsubstituted alkylaryl, or substituted or unsubstituted polyaryl;

[0259] (c)R19 is a substituted or unsubstituted alkyl, a substituted or unsubstituted alkenyl, a substituted or unsubstituted aryl, a substituted or unsubstituted alkylaryl, or a substituted or unsubstituted polyaryl;

[0260] (d) R 22 , R 22 ', and R 31 ~R 34 are independently hydrogen, substituted or unsubstituted alkyl, halogen, amino, or alkoxy;

[0261] (e)R 25 and R 25 ' is independently a leaving group; and

[0262] (f) the substituents are independently substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted cyclic group, substituted or unsubstituted heterocyclic group, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, substituted or unsubstituted polyaryl, substituted or unsubstituted polyheteroaryl, substituted or unsubstituted aralkyl, carbonyl, halide, hydroxy, phenoxy, aryloxy, alkylthio, phenylthio, arylthio, cyano, isocyano, alkoxy, nitro, carboxyl, amino, amide, oxo, silyl, sulfinyl, sulfonyl, sulfonic acid, phosphonium, phosphanyl, phosphoryl, phosphonyl, or thiol, or a combination thereof.

[0263] 2. The iron-based catalyst of paragraph 1, wherein R 22 , R 22 ', and R 31 ~R 34 independently hydrogen, -NRR', methoxy, or ethoxy, wherein R and R' are independently hydrogen or unsubstituted alkyl, such as unsubstituted C1-C6 alkyl, for example methyl.

[0264] 3. The iron-based catalyst of paragraph 1 or 2, wherein R 32 ~R 34 It's hydrogen.

[0265] 4. The iron-based catalyst of paragraph 1, wherein the compound has the following structure:

[0266]

[0267] 5. The iron-based catalyst of any one of paragraphs 1 to 4, wherein L1 is Each occurrence of T′ is a substituted or unsubstituted monocyclic group or a substituted or unsubstituted polycyclic group, and p is an integer from 1 to 3, or 1 or 2.

[0268] 6. The iron-based catalyst of paragraph 5, wherein T' is a substituted or unsubstituted C3-C6 monocycloalkyl group, and optionally wherein the substituents (when present) are independently unsubstituted phenyl or phenyl substituted with one or more unsubstituted alkyl groups (such as one or more unsubstituted C1-C6 alkyl groups).

[0269] 7. The iron-based catalyst of any one of paragraphs 1 to 4, wherein L1 is Each occurrence of R 16 and R 16 ' is independently substituted or unsubstituted phenyl, and p is an integer from 1 to 3, or 1 or 2.

[0270] 8. The iron-based catalyst of paragraph 7, wherein R 16 and R 16 ' is an unsubstituted phenyl group.

[0271] 9. The iron-based catalyst of any one of paragraphs 1 to 8, wherein R 25 and R 25 ' is independently a triflate, tosylate, mesylate, halide, nitrate, phosphate, thioether, amino, carboxylate, phenoxide, alkoxy, or amide.

[0272] 10. The iron-based catalyst of any one of paragraphs 1 to 9, wherein R 25 and R 25 ' is a triflate.

[0273] 11. The iron-based catalyst of any one of paragraphs 1 to 10, wherein R 18 It is an unsubstituted C1-C6 alkyl group, such as methyl or ethyl.

[0274] 12. The iron-based catalyst of any one of paragraphs 1 to 11, wherein R 18 ' is unsubstituted C1~C 10 Alkyl, unsubstituted C1-C8 alkyl, unsubstituted C1-C6 alkyl, unsubstituted C1-C4 alkyl, unsubstituted C1-C3 alkyl, such as methyl, ethyl, isopropyl; or X' is carbon or nitrogen; p and q are independently integers from 0 to 5, and each occurrence of R3 is independently hydrogen, a halide (eg, fluoride, chloride, bromide), an unsubstituted C1-C 10 Alkyl (eg, methyl, ethyl, isopropyl, tert-butyl, etc.), or unsubstituted phenyl, or two adjacent R3 together with the carbon atom to which they are attached form an unsubstituted aryl or unsubstituted polyaryl.

[0275] 13. The iron-based catalyst of any one of paragraphs 1 to 12, wherein R 18 ' is methyl or Wherein X' is nitrogen or carbon, p is 1, q is an integer from 1 to 4, and each occurrence of R3 is independently hydrogen, halide, unsubstituted C1-C6 alkyl, unsubstituted phenyl, or two adjacent R3 together with the carbon to which they are attached form an unsubstituted aryl group.

[0276] 14. The iron-based catalyst of any one of paragraphs 1 to 13, wherein R 19 is a substituted or unsubstituted alkylene group, and optionally is a substituted or unsubstituted methylene group or ethylene group.

[0277] 15. The iron-based catalyst of any one of paragraphs 1 to 14, wherein R 19 It is an unsubstituted methylene group or a methylene group substituted by an unsubstituted C1-C6 alkyl group, an unsubstituted phenyl group or an unsubstituted C3-C6 monocycloalkyl group.

[0278] 16. The iron-based catalyst of any one of paragraphs 1 to 15, wherein R 23 and R 23 ' is hydrogen, and R 24 and R 24 ' are independently unsubstituted C1~C 10 Alkyl, unsubstituted C1-C8 alkyl, unsubstituted C1-C6 alkyl, unsubstituted C1-C4 alkyl, or unsubstituted C1-C2 alkyl, such as methyl, etc.

[0279] 17. The iron-based catalyst of any one of paragraphs 1 to 16, wherein the compound has the structure:

[0280]

[0281]

[0282]

[0283] 18. A process for the asymmetric cis-dihydroxylation of styrene or a derivative thereof catalyzed by an iron-based catalyst according to any one of paragraphs 1 to 17, the process comprising:

[0284] (i) maintaining the reaction mixture at a temperature and for a period of time sufficient to form a product,

[0285] wherein the reaction mixture comprises styrene or a derivative thereof, an iron-based catalyst, an oxidant, and a solvent,

[0286] wherein the product comprises a cis-diol, and

[0287] Optionally, wherein the oxidizing agent is hydrogen peroxide.

[0288] 19. The method of paragraph 18, wherein styrene or a derivative thereof has the following structure:

[0289]

[0290] And the cis-diol has the following structure:

[0291]

[0292] wherein A1 is substituted aryl, unsubstituted aryl, substituted polyaryl, unsubstituted polyaryl, substituted heteroaryl, unsubstituted heteroaryl, substituted heteropolyaryl, or unsubstituted heteropolyaryl.

[0293] 20. The method of paragraph 19, wherein styrene or a derivative thereof has the following structure:

[0294]

[0295] And the cis-diol has the following structure:

[0296]

[0297] in:

[0298] (a) X1-X5 are independently carbon, nitrogen, oxygen, or sulfur;

[0299] (b) n1 is an integer from 0 to 5;

[0300] (c) each occurrence of R is independently hydrogen, substituted alkyl, unsubstituted alkyl, substituted alkylaryl, unsubstituted alkylaryl, substituted aryl, unsubstituted aryl, substituted heterocyclic, unsubstituted heterocyclic, hydroxy, halide, haloalkyl (such as a haloalkyl, e.g., —CF ), nitro, amino, amido, alkoxy, cyano, or carbonyl, or two adjacent R groups together with the carbon atoms to which they are attached form a substituted aryl, unsubstituted aryl, substituted polyaryl, unsubstituted polyaryl, substituted heteroaryl, unsubstituted heteroaryl, substituted heteropolyaryl, unsubstituted heteropolyaryl, substituted cycloalkyl, unsubstituted cycloalkyl group, substituted cycloalkenyl, unsubstituted cycloalkenyl group, substituted cycloalkynyl, unsubstituted cycloalkynyl group, substituted heterocyclic group, or unsubstituted heterocyclic group; and

[0301] (d) the substituents are independently substituted alkyl, unsubstituted alkyl, substituted cycloalkyl, unsubstituted cycloalkyl groups, substituted cycloalkenyl, unsubstituted cycloalkenyl groups, substituted cycloalkynyl, unsubstituted cycloalkynyl groups, substituted heterocyclic groups, unsubstituted heterocyclic groups, substituted aryl, unsubstituted aryl, substituted heteroaryl, unsubstituted heteroaryl, substituted polyaryl, unsubstituted polyaryl, substituted heteropolyaryl, unsubstituted heteropolyaryl, substituted alkylaryl, unsubstituted aralkyl, haloalkyl, carbonyl, halide, hydroxy, alkoxy, nitro, cyano, amino, amido, oxo, thiol, or a combination thereof.

[0302] 21. A process for the asymmetric cis-dihydroxylation of a conjugated diene catalyzed by an iron-based catalyst according to any one of paragraphs 1 to 17, the process comprising:

[0303] (i) maintaining the reaction mixture at a temperature and for a period of time sufficient to form a product,

[0304] wherein the reaction mixture comprises a conjugated diene, an iron-based catalyst, an oxidant, and a solvent,

[0305] wherein the product comprises a cis-diol or a tetraol, and

[0306] Optionally, wherein the oxidizing agent is hydrogen peroxide.

[0307] 22. The process of paragraph 21, wherein the amount of the iron-based catalyst in the reaction mixture is at most 6 mol%, at most 5 mol%, at most 3 mol%, at least 0.1 mol%, at least 0.5 mol%, in the range of about 0.1 mol% to about 6 mol%, in the range of about 0.1 mol% to about 5 mol%, in the range of about 0.1 mol% to about 3 mol%, in the range of about 0.5 mol% to about 6 mol%, in the range of about 0.5 mol% to about 5 mol%, in the range of about 0.5 mol% to about 3 mol%, in the range of about 1 mol% to about 6 mol%, or in the range of about 1 mol% to about 5 mol%.

[0308] 23. The method of paragraph 22, wherein the conjugated diene has the following structure:

[0309]

[0310] And the product contains a cis-diol having the following structure:

[0311]

[0312] in:

[0313] (a) A2 is substituted aryl, unsubstituted aryl, substituted polyaryl, unsubstituted polyaryl, substituted heteroaryl, unsubstituted heteroaryl, substituted heteropolyaryl, unsubstituted heteropolyaryl, or carbonyl;

[0314] (b) R5 is -C(=O)OR6, R6 is hydrogen, substituted alkyl, unsubstituted alkyl, substituted aryl, unsubstituted aryl, substituted polyaryl, unsubstituted polyaryl, substituted heteroaryl, unsubstituted heteroaryl, substituted heteropolyaryl, unsubstituted heteropolyaryl, substituted alkylaryl, or unsubstituted alkylaryl;

[0315] (c) R'1 to R'4 are independently hydrogen, substituted alkyl, unsubstituted alkyl, substituted aryl, unsubstituted aryl, substituted polyaryl, unsubstituted polyaryl, substituted heteroaryl, unsubstituted heteroaryl, substituted heteropolyaryl, unsubstituted heteropolyaryl, substituted alkylaryl, or unsubstituted alkylaryl, substituted cycloalkyl, unsubstituted cycloalkyl, substituted cycloalkenyl, unsubstituted cycloalkenyl, substituted cycloalkynyl, unsubstituted cycloalkynyl, substituted heterocycle, or unsubstituted heterocycle; and

[0316] (d) the substituents are independently substituted alkyl, unsubstituted alkyl, substituted cycloalkyl, unsubstituted cycloalkyl groups, substituted cycloalkenyl, unsubstituted cycloalkenyl groups, substituted cycloalkynyl, unsubstituted cycloalkynyl groups, substituted heterocyclic groups, unsubstituted heterocyclic groups, substituted aryl, unsubstituted aryl, substituted heteroaryl, unsubstituted heteroaryl, substituted polyaryl, unsubstituted polyaryl, substituted heteropolyaryl, unsubstituted heteropolyaryl, substituted alkylaryl, unsubstituted aralkyl, haloalkyl, carbonyl, halide, hydroxy, alkoxy, nitro, cyano, amino, amido, oxo, thiol, or a combination thereof.

[0317] 24. The method of paragraph 21, wherein the amount of iron-based catalyst in the reaction mixture is >6 mol%, at least 7 mol%, at least 8 mol%, in the range of about 6.5 mol% to about 20 mol%, in the range of about 7 mol% to about 20 mol%, in the range of about 7 mol% to about 15 mol%, in the range of about 6.5 mol% to about 15 mol%, in the range of about 8 mol% to about 20 mol%, in the range of about 8 mol% to about 15 mol%, in the range of about 7 mol% to about 12 mol%, or in the range of about 8 mol% to about 12 mol%, such as about 10 mol%.

[0318] 25. The method of paragraph 24, wherein the conjugated diene has the following structure:

[0319]

[0320] And the product contains a tetraol having the following structure:

[0321]

[0322] in

[0323] (a) A2 is substituted aryl, unsubstituted aryl, substituted polyaryl, unsubstituted polyaryl, substituted heteroaryl, unsubstituted heteroaryl, substituted heteropolyaryl, unsubstituted heteropolyaryl, or carbonyl;

[0324] (b) R5 is -C(=O)OR6, R6 is hydrogen, substituted alkyl, unsubstituted alkyl, substituted aryl, unsubstituted aryl, substituted polyaryl, unsubstituted polyaryl, substituted heteroaryl, unsubstituted heteroaryl, substituted heteropolyaryl, unsubstituted heteropolyaryl, substituted alkylaryl, or unsubstituted alkylaryl;

[0325] (c) R'1 to R'4 are independently substituted alkyl, unsubstituted alkyl, substituted aryl, unsubstituted aryl, substituted polyaryl, unsubstituted polyaryl, substituted heteroaryl, unsubstituted heteroaryl, substituted heteropolyaryl, unsubstituted heteropolyaryl, substituted alkylaryl, or unsubstituted alkylaryl, substituted cycloalkyl, unsubstituted cycloalkyl, substituted cycloalkenyl, unsubstituted cycloalkenyl, substituted cycloalkynyl, unsubstituted cycloalkynyl, substituted heterocycle, or unsubstituted heterocycle; and

[0326] (d) the substituents are independently substituted alkyl, unsubstituted alkyl, substituted cycloalkyl, unsubstituted cycloalkyl groups, substituted cycloalkenyl, unsubstituted cycloalkenyl groups, substituted cycloalkynyl, unsubstituted cycloalkynyl groups, substituted heterocyclic groups, unsubstituted heterocyclic groups, substituted aryl, unsubstituted aryl, substituted heteroaryl, unsubstituted heteroaryl, substituted polyaryl, unsubstituted polyaryl, substituted heteropolyaryl, unsubstituted heteropolyaryl, substituted alkylaryl, unsubstituted aralkyl, haloalkyl, carbonyl, halide, hydroxy, alkoxy, nitro, cyano, amino, amido, oxo, thiol, or a combination thereof.

[0327] Further understanding of the disclosed substrates, iron-based catalysts, products and methods can be obtained from the following enumerated paragraphs.

[0328] 1. A method for the asymmetric cis-dihydroxylation of styrene or a derivative thereof, the method comprising:

[0329] (i) maintaining the reaction mixture at a temperature and for a period of time sufficient to form a product,

[0330] wherein the reaction mixture comprises styrene or a derivative thereof, one or more iron-based catalysts, an oxidant, and a solvent, and

[0331] The product comprises cis-diol.

[0332] 2. The method of paragraph 1, further comprising, before step (i), adding an oxidant to a premix comprising styrene or a derivative thereof, one or more iron-based catalysts, and a solvent to form a reaction mixture, and optionally wherein:

[0333] The oxidizing agent is hydrogen peroxide,

[0334] The oxidant is added in the form of a solution comprising the oxidant and a solvent for the oxidant, or

[0335] The oxidant is added using a syringe pump at room temperature over a period of time ranging from 20 min to 1 hour (e.g., about 30 min), or

[0336] Its combination.

[0337] 3. The method of paragraph 1 or 2, wherein the total molar amount of the oxidant in the reaction mixture is about 1 to about 10 times, about 1.5 to about 6 times, or about 1 to about 5 times the total molar amount of styrene or its derivatives.

[0338] 4. The method of any one of paragraphs 1 to 3, wherein the one or more iron-based catalysts each have the following structure:

[0339]

[0340] in:

[0341] (a) J and J' are independently a bond (single, double or triple bond), a substituted or unsubstituted alkyl group, a substituted or unsubstituted alkenyl group, a substituted or unsubstituted cyclic group, a substituted or unsubstituted aryl group, or a substituted or unsubstituted polyaryl group;

[0342] (b) L1 is a bond or R 16 , R 16 '、R 17 , and R 17 ' is independently hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted aryl, substituted or unsubstituted polyaryl, or substituted or unsubstituted cyclic group, or R 16 and R 16 'Common and / or R 17 and R 17 'Together with the carbon atoms to which they are attached, they form a substituted or unsubstituted aryl group, a substituted or unsubstituted polyaryl group, or a substituted or unsubstituted cyclic group, and p is an integer from 1 to 10;

[0343] (c)R 18 ~R24 and R 18 '~R 24 ' is independently hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted cyclic group, substituted or unsubstituted aryl, or substituted or unsubstituted polyaryl;

[0344] (d) R 25 and R 25 ' is independently a leaving group;

[0345] (e) is absent or is a bond (single, double or triple); and

[0346] (f) the substituents are independently substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted cyclic group, substituted or unsubstituted heterocyclic group, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, substituted or unsubstituted polyaryl, substituted or unsubstituted polyheteroaryl, substituted or unsubstituted aralkyl, carbonyl, halide, hydroxy, phenoxy, aryloxy, alkylthio, phenylthio, arylthio, cyano, isocyano, alkoxy, nitro, carboxyl, amino, amide, oxo, silyl, sulfinyl, sulfonyl, sulfonic acid, phosphonium, phosphanyl, phosphoryl, phosphonyl, or thiol, or a combination thereof.

[0347] 5. The method of paragraph 4, wherein R 19 , R 20 , and R 21 Common and / or R 19 '、R 20 ', and R 21 'Together with the carbon atoms to which they are attached, they form a substituted or unsubstituted aryl group, a substituted or unsubstituted polyaryl group, or a substituted or unsubstituted cyclic group.

[0348] 6. The method of any one of paragraphs 1 to 5, wherein the one or more iron-based catalysts each have the following structure:

[0349]

[0350] in:

[0351] (a) L1 is a bond or R 16 , R 16 '、R 17 , and R 17 ' is independently hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted aryl, substituted or unsubstituted polyaryl, or substituted or unsubstituted cyclic group, or R 16 With R 16 ' and / or R 17With R 17 ' forms a substituted or unsubstituted aryl group, a substituted or unsubstituted polyaryl group, or a substituted or unsubstituted cyclic group, and p is an integer from 1 to 10;

[0352] (b) T1' and T2' are independently substituted or unsubstituted heteroaryl, substituted or unsubstituted heteropolyaryl, or substituted or unsubstituted heterocyclic group;

[0353] (c)R 18 , R 23 , R 24 , R 18 '、R 23 ', and R 24 ' is independently hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted aryl, substituted or unsubstituted alkylaryl, or substituted or unsubstituted polyaryl;

[0354] (d) R 19 and R 19 ' is independently substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted aryl, substituted or unsubstituted alkylaryl, or substituted or unsubstituted polyaryl;

[0355] (e)R 25 and R 25 ' is independently a leaving group; and

[0356] (f) the substituents are independently substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted cyclic group, substituted or unsubstituted heterocyclic group, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, substituted or unsubstituted polyaryl, substituted or unsubstituted polyheteroaryl, substituted or unsubstituted aralkyl, carbonyl, halide, hydroxy, phenoxy, aryloxy, alkylthio, phenylthio, arylthio, cyano, isocyano, alkoxy, nitro, carboxyl, amino, amide, oxo, silyl, sulfinyl, sulfonyl, sulfonic acid, phosphonium, phosphanyl, phosphoryl, phosphonyl, or thiol, or a combination thereof.

[0357] 7. The method of paragraph 6, wherein the one or more iron-based catalysts each have the following structure:

[0358]

[0359] 8. The method of paragraph 6, (a) wherein L1 is Each occurrence of T' is a substituted or unsubstituted monocyclic group or a substituted or unsubstituted polycyclic group, and p is an integer from 1 to 3; (b) wherein R 25 and R 25' is independently a triflate, tosylate, mesylate, halide, nitrate, phosphate, thioether, amino, carboxylate, phenoxide, alkoxy, or amide; or (c) or a combination thereof.

[0360] 9. The method of any one of paragraphs 1 to 8, wherein the catalyst has the following structure:

[0361]

[0362]

[0363]

[0364] 10. The method of any of paragraphs 1 to 3, wherein the one or more iron-based catalysts each have the following structure:

[0365]

[0366] in:

[0367] (a)R 26 and R 27 are independently hydrogen, a substituted or unsubstituted cyclic group, a substituted or unsubstituted aryl group, or a substituted or unsubstituted polyaryl group;

[0368] (b)R 28 ~R 41 are independently hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted cyclic group, substituted or unsubstituted aryl, or substituted or unsubstituted polyaryl;

[0369] (c)R 18 ' is unsubstituted C1~C 10 Alkyl, unsubstituted C1-C8 alkyl, unsubstituted C1-C6 alkyl, unsubstituted C1-C4 alkyl, unsubstituted C1-C3 alkyl, such as methyl, ethyl, isopropyl; or p and q are independently integers from 0 to 5, and each occurrence of R3 is independently hydrogen or unsubstituted C1-C 10 Alkyl, or two adjacent R3 together with the carbon to which they are attached form an unsubstituted aryl or unsubstituted polyaryl; and

[0370] (d) the substituents are independently substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted cyclic group, substituted or unsubstituted heterocyclic group, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, substituted or unsubstituted polyaryl, substituted or unsubstituted polyheteroaryl, substituted or unsubstituted aralkyl, carbonyl, halide, hydroxy, phenoxy, aryloxy, alkylthio, phenylthio, arylthio, cyano, isocyano, alkoxy, nitro, carboxyl, amino, amide, oxo, silyl, sulfinyl, sulfonyl, sulfonic acid, phosphonium, phosphinyl, phosphoryl, phosphonyl, or thiol, or a combination thereof. In some forms of Formula XII, R 26 and R 27 Not hydrogen.

[0371] 11. The method of paragraph 10, wherein (a) R 26 and R 27 are independently hydrogen, substituted or unsubstituted alkyl, or substituted or unsubstituted aryl; (b) R 28 and R 29 are independently hydrogen, substituted or unsubstituted alkyl, or substituted or unsubstituted alkenyl; (c) R 30 ~R 41 (d) the substituents are independently hydrogen or substituted or unsubstituted alkyl; and (d) the substituents are independently substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, or substituted or unsubstituted alkynyl, or a combination thereof.

[0372] 12. The method of paragraph 10 or 11, wherein (a) R 26 and R 27 is hydrogen, (b) R 28 and R 29 are independently substituted or unsubstituted alkyl, such as unsubstituted C1-C8 alkyl, and (c) R 30 ~R 40 It's hydrogen.

[0373] 13. The method of any of paragraphs 10 to 12, wherein the one or more iron-based catalysts each have the following structure:

[0374]

[0375] 14. The method according to any one of paragraphs 1 to 13,

[0376] (a) wherein the total amount of the one or more iron-based catalysts in the reaction mixture is up to 10 mol%, up to 8 mol%, up to 6 mol%, up to 5 mol%, up to 3 mol%, at least 0.1 mol%, at least 0.5 mol%, within a range of about 0.1 mol% to about 10 mol%, within a range of about 0.1 mol% to about 8 mol%, within a range of about 0.1 mol% to about 6 mol%, within a range of about 0.1 mol% to about 5 mol%, within a range of about 0.1 mol% to about 3 mol%, within a range of about 0.5 mol% to about 6 mol%, within a range of about 0.5 mol% to about 5 mol%, within a range of about 0.5 mol% to about 3 mol%, within a range of about 1 mol% to about 6 mol%, or within a range of about 1 mol% to about 5 mol%;

[0377] (b) wherein the solvent is an alcohol, optionally a C1-C6 alcohol, such as methanol; or

[0378] (c) wherein the reaction mixture is maintained at a temperature below 0°C (e.g., about -30°C) for a period of time in the range of about 20 minutes to about 3 hours, in the range of about 20 minutes to about 2 hours, or in the range of about 20 minutes to 1 hour (e.g., about 30 min); or

[0379] (d) combinations thereof.

[0380] 15. The method of any one of paragraphs 1 to 14, wherein styrene or a derivative thereof has the following structure:

[0381]

[0382]

[0383] And the cis-diol has the following structure:

[0384]

[0385] wherein A1 is substituted aryl, unsubstituted aryl, substituted polyaryl, unsubstituted polyaryl, substituted heteroaryl, unsubstituted heteroaryl, substituted heteropolyaryl, or unsubstituted heteropolyaryl.

[0386] 16. The method of paragraph 15, wherein styrene or a derivative thereof has the following structure:

[0387]

[0388] And the cis-diol has the following structure:

[0389]

[0390] in:

[0391] (a) X1-X5 are independently carbon, nitrogen, oxygen, or sulfur;

[0392] (b) n1 is an integer from 0 to 5;

[0393] (c) each occurrence of R is independently hydrogen, substituted alkyl, unsubstituted alkyl, substituted alkylaryl, unsubstituted alkylaryl, substituted aryl, unsubstituted aryl, substituted heterocyclic, unsubstituted heterocyclic, hydroxy, halide, haloalkyl (such as a haloalkyl, e.g., —CF ), nitro, amino, amido, alkoxy, cyano, or carbonyl, or two adjacent R groups together with the carbon atoms to which they are attached form a substituted aryl, unsubstituted aryl, substituted polyaryl, unsubstituted polyaryl, substituted heteroaryl, unsubstituted heteroaryl, substituted heteropolyaryl, unsubstituted heteropolyaryl, substituted cycloalkyl, unsubstituted cycloalkyl group, substituted cycloalkenyl, unsubstituted cycloalkenyl group, substituted cycloalkynyl, unsubstituted cycloalkynyl group, substituted heterocyclic group, or unsubstituted heterocyclic group; and

[0394] (d) the substituents are independently substituted alkyl, unsubstituted alkyl, substituted cycloalkyl, unsubstituted cycloalkyl groups, substituted cycloalkenyl, unsubstituted cycloalkenyl groups, substituted cycloalkynyl, unsubstituted cycloalkynyl groups, substituted heterocyclic groups, unsubstituted heterocyclic groups, substituted aryl, unsubstituted aryl, substituted heteroaryl, unsubstituted heteroaryl, substituted polyaryl, unsubstituted polyaryl, substituted heteropolyaryl, unsubstituted heteropolyaryl, substituted alkylaryl, unsubstituted aralkyl, haloalkyl, carbonyl, halide, hydroxy, alkoxy, nitro, cyano, amino, amido, oxo, or thiol, or a combination thereof.

[0395] 17. The method of paragraph 16, wherein each occurrence of R1 is independently hydrogen, unsubstituted C1-C 10 Alkyl, unsubstituted heterocyclic, unsubstituted C1~C 10 Alkyl-substituted heterocycle, halide, haloalkyl (e.g., -CF3), nitro, cyano, -OR2, -C(=O)OR4, or or

[0396] wherein two adjacent R1 groups together with the carbon atom to which they are attached form a substituted aryl group or an unsubstituted aryl group, and the substituents are independently unsubstituted C1 to C 10 Alkyl, unsubstituted heterocyclic, unsubstituted C1~C 10 Alkyl-substituted heterocyclic group, halide, haloalkyl (e.g., -CF3), nitro, cyano, -OR2, -C(=O)OR4, or

[0397] wherein p and q are independently integers from 0 to 5, and R2 to R4 are independently hydrogen, unsubstituted C1 to C 10 Alkyl, halide, or -O-(C1~C 10 alkyl).

[0398] 18. The method of paragraph 16 or 17, wherein n1 is not 0, and at least one R1, at least two R1s, or at least three R1s are electron withdrawing groups.

[0399] 19. The method of paragraph 18, wherein n1 is 1, and R1 is an electron withdrawing group at the meta or para position.

[0400] 20. The method of paragraph 16 or 17, wherein n1 is 1 and R1 is in the ortho position p and q are independently integers from 0 to 5, and each occurrence of R3 is independently hydrogen, unsubstituted C1-C 10 Alkyl, halide, or -O-(C1~C 10 alkyl).

[0401] 21. The method of paragraph 16 or 17, wherein X1 is nitrogen and X2 to X5 are carbon.

[0402] 22. The method of paragraph 21, wherein two adjacent R1 groups together with the carbon atom to which they are attached form a substituted aryl group or an unsubstituted aryl group, and

[0403] The substituents are independently unsubstituted C1-C 10 Alkyl, unsubstituted heterocyclic, unsubstituted C1~C 10 Alkyl-substituted heterocycle, halide, haloalkyl (e.g., -CF3), nitro, cyano, -OR2, -C(=O)OR4, or p and q are independently integers from 0 to 5, and R2 to R4 are independently hydrogen, unsubstituted C1 to C 10 Alkyl, halide, or -O-(C1~C 10 alkyl).

[0404] 23. The method of any one of paragraphs 15 to 22, wherein the cis-diol has the following structure:

[0405]

[0406] 24. The method of any one of paragraphs 1 to 23, further comprising stirring the reaction mixture before step (i) and / or during step (i); or purifying the product after step (i), optionally by column chromatography; or a combination thereof.

[0407] 25. The method according to any one of paragraphs 1 to 24,

[0408] (a) wherein the yield of cis-diol is at least 40%, at least 50%, in the range of about 40% to about 99%, in the range of about 50% to about 99%, in the range of about 60% to about 99%, in the range of about 70% to about 99%, or in the range of about 80% to about 99%; or

[0409] (b) wherein the enantiomeric excess of the cis-diol is at least 60%, at least 70%, at least 75%, at least 80%, up to 100%, within the range of about 60% to 100%, within the range of about 60% to 100%, within the range of about 70% to 100%, within the range of about 80% to 100%, within the range of about 90% to 100%, or within the range of about 95% to 100%, within the range of about 60% to 99%, within the range of about 70% to 99%, within the range of about 80% to 99%, within the range of about 90% to 99%, or within the range of about 95% to 99%, as determined by chiral HPLC; or

[0410] (c) any combination thereof.

[0411] 26. A method for the asymmetric cis-dihydroxylation of a conjugated diene, the method comprising:

[0412] (i) maintaining the reaction mixture at a temperature and for a period of time sufficient to form a product,

[0413] wherein the reaction mixture comprises a conjugated diene, one or more iron-based catalysts, an oxidant, and a solvent, and

[0414] Wherein the product comprises a cis-diol or a tetraol.

[0415] 27. The method of paragraph 26, further comprising, prior to step (i), adding an oxidant to a premix comprising a conjugated diene, one or more iron-based catalysts, and a solvent to form a reaction mixture, and optionally wherein:

[0416] The oxidizing agent is hydrogen peroxide, or

[0417] The oxidant is added in the form of a solution comprising the oxidant and a solvent for the oxidant, or

[0418] Its combination.

[0419] 28. The method of paragraph 26 or 27, wherein the total molar amount of the oxidant in the reaction mixture is about 1 to about 10 times, about 1.5 to about 6 times, or about 1 to about 5 times the total molar amount of the conjugated diene.

[0420] 29. The method of any of paragraphs 26 to 28, wherein the one or more iron-based catalysts each have the following structure:

[0421]

[0422] in:

[0423] (a) J and J' are independently a bond (single, double or triple bond), a substituted or unsubstituted alkyl group, a substituted or unsubstituted alkenyl group, a substituted or unsubstituted cyclic group, a substituted or unsubstituted aryl group, or a substituted or unsubstituted polyaryl group;

[0424] (b) L1 is a bond or R 16 , R 16 '、R 17 , and R 17 ' is independently hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted aryl, substituted or unsubstituted polyaryl, or substituted or unsubstituted cyclic group, or R 16 and R 16 'Common and / or R 17 and R 17 'Together with the carbon atoms to which they are attached, they form a substituted or unsubstituted aryl group, a substituted or unsubstituted polyaryl group, or a substituted or unsubstituted cyclic group, and p is an integer from 1 to 10;

[0425] (c)R 18 ~R 24 and R 18 '~R 24 ' is independently hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted cyclic group, substituted or unsubstituted aryl, or substituted or unsubstituted polyaryl;

[0426] (d) R 25 and R 25 ' is independently a leaving group;

[0427] (e) is absent or is a bond (single, double or triple); and

[0428] (f) the substituents are independently substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted cyclic group, substituted or unsubstituted heterocyclic group, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, substituted or unsubstituted polyaryl, substituted or unsubstituted polyheteroaryl, substituted or unsubstituted aralkyl, carbonyl, halide, hydroxy, phenoxy, aryloxy, alkylthio, phenylthio, arylthio, cyano, isocyano, alkoxy, nitro, carboxyl, amino, amide, oxo, silyl, sulfinyl, sulfonyl, sulfonic acid, phosphonium, phosphanyl, phosphoryl, phosphonyl, or thiol, or a combination thereof.

[0429] 30. The method of paragraph 29, wherein R19 , R 20 , and R 21 Common and / or R 19 '、R 20 ', and R 21 'Together with the carbon atoms to which they are attached, they form a substituted or unsubstituted aryl group, a substituted or unsubstituted polyaryl group, or a substituted or unsubstituted cyclic group.

[0430] 31. The method of paragraph 29 or 30, wherein the one or more iron-based catalysts each have the following structure:

[0431]

[0432] in:

[0433] (a) L1 is a bond or R 16 , R 16 '、R 17 , and R 17 ' is independently hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted aryl, substituted or unsubstituted polyaryl, or substituted or unsubstituted cyclic group, or R 16 With R 16 ' and / or R 17 With R 17 ' forms a substituted or unsubstituted aryl group, a substituted or unsubstituted polyaryl group, or a substituted or unsubstituted cyclic group, and p is an integer from 1 to 10;

[0434] (b) T1' and T2' are independently substituted or unsubstituted heteroaryl, substituted or unsubstituted heteropolyaryl, or substituted or unsubstituted heterocyclic group;

[0435] (c)R 18 , R 19 , R 23 , R 24 , R 18 '、R 19 '、R 23 ', and R 24 ' is independently hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted aryl, substituted or unsubstituted alkylaryl, or substituted or unsubstituted polyaryl;

[0436] (d) R 25 and R 25 ' is independently a leaving group; and

[0437] (e) the substituents are independently substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted cyclic group, substituted or unsubstituted heterocyclic group, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, substituted or unsubstituted polyaryl, substituted or unsubstituted polyheteroaryl, substituted or unsubstituted aralkyl, carbonyl, halide, hydroxy, phenoxy, aryloxy, alkylthio, phenylthio, arylthio, cyano, isocyano, alkoxy, nitro, carboxyl, amino, amide, oxo, silyl, sulfinyl, sulfonyl, sulfonic acid, phosphonium, phosphanyl, phosphoryl, phosphonyl, or thiol, or a combination thereof.

[0438] 32. The method of paragraph 31, wherein the one or more iron-based catalysts each have the following structure:

[0439]

[0440] 33. The method of paragraph 31, (a) wherein L1 is Each occurrence of T' is a substituted or unsubstituted monocyclic group or a substituted or unsubstituted polycyclic group, and p is an integer from 1 to 3; (b) wherein R 25 and R 25 ' is independently a triflate, tosylate, mesylate, halide, nitrate, phosphate, thioether, amino, carboxylate, phenoxide, alkoxy, or amide; or (c) or a combination thereof.

[0441] 34. The method of any one of paragraphs 26 to 33, wherein the catalyst has the following structure:

[0442]

[0443]

[0444]

[0445] 35. The method of any of paragraphs 26 to 28, wherein the one or more iron-based catalysts each have the following structure:

[0446]

[0447] in:

[0448] (a)R 26 and R 27 are independently hydrogen, a substituted or unsubstituted cyclic group, a substituted or unsubstituted aryl group, or a substituted or unsubstituted polyaryl group;

[0449] (b)R 28 ~R 41are independently hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted cyclic group, substituted or unsubstituted aryl, or substituted or unsubstituted polyaryl;

[0450] (c)R 18 ' is unsubstituted C1~C 10 Alkyl, unsubstituted C1-C8 alkyl, unsubstituted C1-C6 alkyl, unsubstituted C1-C4 alkyl, unsubstituted C1-C3 alkyl, such as methyl, ethyl, isopropyl; or p and q are independently integers from 0 to 5, and each occurrence of R3 is independently hydrogen or unsubstituted C1-C 10 Alkyl, or two adjacent R3 together with the carbon to which they are attached form an unsubstituted aryl or unsubstituted polyaryl; and

[0451] (d) the substituents are independently substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted cyclic group, substituted or unsubstituted heterocyclic group, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, substituted or unsubstituted polyaryl, substituted or unsubstituted polyheteroaryl, substituted or unsubstituted aralkyl, carbonyl, halide, hydroxy, phenoxy, aryloxy, alkylthio, phenylthio, arylthio, cyano, isocyano, alkoxy, nitro, carboxyl, amino, amide, oxo, silyl, sulfinyl, sulfonyl, sulfonic acid, phosphonium, phosphinyl, phosphoryl, phosphonyl, or thiol, or a combination thereof. In some forms of Formula XII, R 26 and R 27 Not hydrogen.

[0452] 36. The method of paragraph 35, wherein (a) R 26 and R 27 are independently hydrogen, substituted or unsubstituted alkyl, or substituted or unsubstituted aryl; (b) R 28 and R 29 are independently hydrogen, substituted or unsubstituted alkyl, or substituted or unsubstituted alkenyl; (c) R 30 ~R 41 (d) the substituents are independently hydrogen or substituted or unsubstituted alkyl; and (d) the substituents are independently substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, or substituted or unsubstituted alkynyl, or a combination thereof.

[0453] 37. The method of paragraph 35 or 36, wherein (a) R 26 and R 27 is hydrogen, (b) R 28 and R 29 are independently substituted or unsubstituted alkyl, such as unsubstituted C1-C8 alkyl, and (c) R 30 ~R40 It's hydrogen.

[0454] 38. The method of any of paragraphs 35 to 37, wherein the one or more iron-based catalysts each have the following structure:

[0455]

[0456] 39. The process of any of paragraphs 26 to 38, wherein the total amount of one or more iron-based catalysts in the reaction mixture is at most 6 mol%, at most 5 mol%, at most 3 mol%, at least 0.1 mol%, at least 0.5 mol%, in the range of about 0.1 mol% to about 6 mol%, in the range of about 0.1 mol% to about 5 mol%, in the range of about 0.1 mol% to about 3 mol%, in the range of about 0.5 mol% to about 6 mol%, in the range of about 0.5 mol% to about 5 mol%, in the range of about 0.5 mol% to about 3 mol%, in the range of about 1 mol% to about 6 mol%, or in the range of about 1 mol% to about 5 mol%.

[0457] 40. The method of paragraph 39, wherein the oxidant is added to the premix comprising the conjugated diene, one or more iron-based catalysts, and the solvent using a syringe pump at room temperature over a period of time ranging from 20 min to 1 hour, such as about 30 min.

[0458] 41. The method of paragraph 39 or 40, wherein the reaction mixture is maintained at room temperature for a period of time in the range of about 20 minutes to about 3 hours, in the range of about 20 minutes to about 2 hours, in the range of about 20 minutes to 1 hour, or in the range of about 20 min to about 50 min (such as about 30 min).

[0459] 42. The method of any one of paragraphs 39 to 41, wherein the conjugated diene has the following structure:

[0460]

[0461] And the product contains a cis-diol having the following structure:

[0462]

[0463] in:

[0464] (a) A2 is substituted aryl, unsubstituted aryl, substituted polyaryl, unsubstituted polyaryl, substituted heteroaryl, unsubstituted heteroaryl, substituted heteropolyaryl, unsubstituted heteropolyaryl, or carbonyl;

[0465] (b) R5 is -C(=O)OR6, R6 is hydrogen, substituted alkyl, unsubstituted alkyl, substituted aryl, unsubstituted aryl, substituted polyaryl, unsubstituted polyaryl, substituted heteroaryl, unsubstituted heteroaryl, substituted heteropolyaryl, unsubstituted heteropolyaryl, substituted alkylaryl, or unsubstituted alkylaryl;

[0466] (c) R'1 to R'4 are independently hydrogen, substituted alkyl, unsubstituted alkyl, substituted aryl, unsubstituted aryl, substituted polyaryl, unsubstituted polyaryl, substituted heteroaryl, unsubstituted heteroaryl, substituted heteropolyaryl, unsubstituted heteropolyaryl, substituted alkylaryl, or unsubstituted alkylaryl, substituted cycloalkyl, unsubstituted cycloalkyl, substituted cycloalkenyl, unsubstituted cycloalkenyl, substituted cycloalkynyl, unsubstituted cycloalkynyl, substituted heterocycle, or unsubstituted heterocycle; and

[0467] (d) the substituents are independently substituted alkyl, unsubstituted alkyl, substituted cycloalkyl, unsubstituted cycloalkyl groups, substituted cycloalkenyl, unsubstituted cycloalkenyl groups, substituted cycloalkynyl, unsubstituted cycloalkynyl groups, substituted heterocyclic groups, unsubstituted heterocyclic groups, substituted aryl, unsubstituted aryl, substituted heteroaryl, unsubstituted heteroaryl, substituted polyaryl, unsubstituted polyaryl, substituted heteropolyaryl, unsubstituted heteropolyaryl, substituted alkylaryl, unsubstituted aralkyl, haloalkyl, carbonyl, halide, hydroxy, alkoxy, nitro, cyano, amino, amido, oxo, or thiol, or a combination thereof.

[0468] 43. The method of any one of paragraphs 39 to 42, wherein the catalyst has the following structure:

[0469]

[0470] And the cis-diol has the following structure:

[0471]

[0472] 44. The method of any one of paragraphs 39 to 42, wherein the catalyst has the following structure:

[0473]

[0474] And the cis-diol has the following structure:

[0475]

[0476] 45. The method of any one of paragraphs 42 to 44, wherein:

[0477] (a) the yield of cis-diol is at least 30%, at least 40%, in the range of about 30% to about 99%, in the range of about 40% to about 99%, in the range of about 50% to about 99%, in the range of about 60% to about 99%, or in the range of about 70% to about 99%; or

[0478] (b) the enantiomeric excess of the cis-diol is at least 80%, at least 85%, up to 100%, within the range of about 80% to 100%, within the range of about 85% to 100%, within the range of about 90% to 100%, within the range of about 80% to 99.9%, within the range of about 85% to 99.9%, or within the range of about 90% to 99.9%, within the range of about 80% to 99.5%, within the range of about 85% to 99.5%, within the range of about 90% to 99.5%, within the range of about 80% to 99%, or within the range of about 85% to 99%, as determined by chiral HPLC; or

[0479] (c) any combination thereof.

[0480] 46. ​​The method of any of paragraphs 26 to 38, wherein the total amount of one or more iron-based catalysts in the reaction mixture is >6 mol%, at least 7 mol%, at least 8 mol%, in the range of about 6.5 mol% to about 20 mol%, in the range of about 7 mol% to about 20 mol%, in the range of about 7 mol% to about 15 mol%, in the range of about 6.5 mol% to about 15 mol%, in the range of about 8 mol% to about 20 mol%, in the range of about 8 mol% to about 15 mol%, in the range of about 7 mol% to about 12 mol%, or in the range of about 8 mol% to about 12 mol%, such as about 10 mol%.

[0481] 47. The method of paragraph 46, wherein the oxidizing agent is added directly to a premix comprising the conjugated diene, one or more iron-based catalysts, and a solvent at room temperature to form a reaction mixture.

[0482] 48. The method of paragraph 46 or 47, wherein the reaction mixture is maintained at room temperature for a period of at least 1 hour, in the range of 1 hour to about 5 hours, in the range of 1 hour to about 4 hours, in the range of 1 hour to about 3 hours, in the range of 1 hour to about 2 hours (e.g., 1 hour).

[0483] 49. The method of any one of paragraphs 46 to 48, wherein the conjugated diene has the following structure:

[0484]

[0485] And the product contains a tetraol having the following structure:

[0486]

[0487] in

[0488] (a) A2 is substituted aryl, unsubstituted aryl, substituted polyaryl, unsubstituted polyaryl, substituted heteroaryl, unsubstituted heteroaryl, substituted heteropolyaryl, unsubstituted heteropolyaryl, or carbonyl;

[0489] (b) R5 is -C(=O)OR6, R6 is hydrogen, substituted alkyl, unsubstituted alkyl, substituted aryl, unsubstituted aryl, substituted polyaryl, unsubstituted polyaryl, substituted heteroaryl, unsubstituted heteroaryl, substituted heteropolyaryl, unsubstituted heteropolyaryl, substituted alkylaryl, or unsubstituted alkylaryl;

[0490] (c) R'1 to R'4 are independently substituted alkyl, unsubstituted alkyl, substituted aryl, unsubstituted aryl, substituted polyaryl, unsubstituted polyaryl, substituted heteroaryl, unsubstituted heteroaryl, substituted heteropolyaryl, unsubstituted heteropolyaryl, substituted alkylaryl, or unsubstituted alkylaryl, substituted cycloalkyl, unsubstituted cycloalkyl, substituted cycloalkenyl, unsubstituted cycloalkenyl, substituted cycloalkynyl, unsubstituted cycloalkynyl, substituted heterocycle, or unsubstituted heterocycle; and

[0491] (d) the substituents are independently substituted alkyl, unsubstituted alkyl, substituted cycloalkyl, unsubstituted cycloalkyl groups, substituted cycloalkenyl, unsubstituted cycloalkenyl groups, substituted cycloalkynyl, unsubstituted cycloalkynyl groups, substituted heterocyclic groups, unsubstituted heterocyclic groups, substituted aryl, unsubstituted aryl, substituted heteroaryl, unsubstituted heteroaryl, substituted polyaryl, unsubstituted polyaryl, substituted heteropolyaryl, unsubstituted heteropolyaryl, substituted alkylaryl, unsubstituted aralkyl, haloalkyl, carbonyl, halide, hydroxy, alkoxy, nitro, cyano, amino, amido, oxo, thiol, or a combination thereof.

[0492] 50. The method of any one of paragraphs 46 to 49, wherein the catalyst has the following structure:

[0493]

[0494] And the tetraol has the following structure:

[0495]

[0496] 51. The method of any one of paragraphs 46 to 48, wherein the catalyst has the following structure:

[0497]

[0498] And the tetraol has the following structure:

[0499]

[0500] 52. The method of any one of paragraphs 49 to 51, wherein:

[0501] (a) the yield of the tetraol is at least 30%, at least 40%, in the range of about 30% to about 99%, in the range of about 40% to about 99%, in the range of about 50% to about 99%, in the range of about 60% to about 99%, or in the range of about 70% to about 99%; or

[0502] (b) the enantiomeric excess of the tetraol is at least 90%, at least 95%, at least 99.9%, >99.9%, up to 100%, in the range of about 90% to 100%, in the range of about 95% to 100%, in the range of about 90% to 99.9%, in the range of about 95% to 99.9%, or in the range of about 99.9% to 100%, as determined by chiral HPLC; or

[0503] (c) any combination thereof.

[0504] 53. The method of any one of paragraphs 42 to 52, wherein A2 is

[0505] OR -C(=O)OR 14 ,

[0506] in:

[0507] (a) X'1 to X'6 are independently carbon, nitrogen, oxygen, or sulfur;

[0508] (b) n2 and n3 are independently integers from 0 to 5;

[0509] (c) each occurrence of R7 and R'7 is independently hydrogen, substituted alkyl, unsubstituted alkyl, substituted alkylaryl, unsubstituted alkylaryl, substituted aryl, unsubstituted aryl, substituted heterocyclic, unsubstituted heterocyclic, hydroxy, halide, haloalkyl (such as haloalkyl, e.g., -CF3), nitro, amino, amido, alkoxy, cyano, or carbonyl, or two adjacent R7 groups or two adjacent R'7 groups together with the carbon atoms to which they are attached form a substituted aryl, unsubstituted aryl, substituted polyaryl, unsubstituted polyaryl, substituted heteroaryl, unsubstituted heteroaryl, substituted heteropolyaryl, unsubstituted heteropolyaryl, substituted cycloalkyl, unsubstituted cycloalkyl group, substituted cycloalkenyl, unsubstituted cycloalkenyl group, substituted cycloalkynyl, unsubstituted cycloalkynyl group, substituted heterocyclic group, or unsubstituted heterocyclic group;

[0510] (d) R 14is hydrogen, substituted alkyl, unsubstituted alkyl, substituted aryl, unsubstituted aryl, substituted polyaryl, unsubstituted polyaryl, substituted heteroaryl, unsubstituted heteroaryl, substituted heteropolyaryl, unsubstituted heteropolyaryl, substituted alkylaryl, or unsubstituted alkylaryl; and

[0511] (e) the substituents are independently substituted alkyl, unsubstituted alkyl, substituted cycloalkyl, unsubstituted cycloalkyl groups, substituted cycloalkenyl, unsubstituted cycloalkenyl groups, substituted cycloalkynyl, unsubstituted cycloalkynyl groups, substituted heterocyclic groups, unsubstituted heterocyclic groups, substituted aryl, unsubstituted aryl, substituted heteroaryl, unsubstituted heteroaryl, substituted polyaryl, unsubstituted polyaryl, substituted heteropolyaryl, unsubstituted heteropolyaryl, substituted alkylaryl, unsubstituted aralkyl, haloalkyl, carbonyl, halide, hydroxy, alkoxy, nitro, cyano, amino, amido, oxo, or thiol, or a combination thereof.

[0512] 54. The method of paragraph 53, wherein each occurrence of R7 and R'7 is independently hydrogen, unsubstituted C1-C 10 Alkyl, unsubstituted heterocyclic, unsubstituted C1~C 10 Alkyl-substituted heterocycle, halide, haloalkyl (e.g., -CF3), nitro, cyano, -OR2, -C(=O)OR4, or or

[0513] Two adjacent R7 groups or two adjacent R'7 groups together with the carbon atoms to which they are connected form a substituted aryl group or an unsubstituted aryl group, and the substituents are independently unsubstituted C1-C 10 Alkyl, unsubstituted heterocyclic, unsubstituted C1~C 10 Alkyl-substituted heterocyclic group, halide, haloalkyl (e.g., -CF3), nitro, cyano, -OR2, -C(=O)OR4, or

[0514] wherein p and q are independently integers from 0 to 5, and R2 to R4 are independently hydrogen, unsubstituted C1 to C 10 Alkyl, halide, or -O-(C1~C 10 alkyl).

[0515] 55. The method of paragraph 53 or 54, wherein each occurrence of R7 and R'7 is independently hydrogen, unsubstituted C1-C 10 Alkyl, unsubstituted heterocyclic, unsubstituted C1~C 10 Alkyl-substituted heterocycle, halide, haloalkyl (eg, -CF3), or cyano.

[0516] 56. The method of any of paragraphs 53 to 55, wherein X'2 to X'5 are carbon, X'1 is carbon or nitrogen, and X'6 is carbon, nitrogen, oxygen, or sulfur.

[0517] 57. The method of any one of paragraphs 42 to 56, wherein R6 is unsubstituted C1-C 10 Alkyl or p' and q' are independently integers from 0 to 5, and each occurrence of R'3 is independently hydrogen, unsubstituted C1-C 10 Alkyl, halide, or -O-(C1~C 10 alkyl).

[0518] 58. The method of paragraph 57, wherein R6 is unsubstituted C1-C8 alkyl, unsubstituted C1-C6 alkyl, unsubstituted C1-C4 alkyl, or And p' is an integer from 0 to 3, from 0 to 2, or from 0 or 1.

[0519] 59. The method of any one of paragraphs 42 to 58, wherein R'1 to R'4 are independently hydrogen, unsubstituted C1 to C 10 alkyl, unsubstituted aryl, or unsubstituted alkylaryl.

[0520] 60. The method of any one of paragraphs 53 to 59, wherein R 14 is an unsubstituted C1-C8 alkyl group, an unsubstituted C1-C6 alkyl group, an unsubstituted C1-C4 alkyl group, or p' and q' are independently integers from 0 to 5, and each occurrence of R'3 is independently hydrogen, unsubstituted C1-C 10 Alkyl, halide, or -O-(C1~C 10 alkyl), optionally wherein R 14 is an unsubstituted C1-C4 alkyl group or And p' is an integer from 0 to 3, from 0 to 2, or from 0 or 1.

[0521] 61. The method of any one of paragraphs 42, 43, 45 and 53 to 60, wherein the cis-diol has the structure:

[0522]

[0523] 62. The method of any one of paragraphs 42, 44, 45 and 53 to 60, wherein the cis-diol has the structure:

[0524]

[0525] 63. The method of any one of paragraphs 49, 50 and 52 to 60, wherein the tetraol has the following structure:

[0526]

[0527] 64. The method of any one of paragraphs 49, 51 and 52 to 60, wherein the tetraol has the following structure:

[0528]

[0529] 65. The method of any of paragraphs 26 to 64, wherein the solvent is an alcohol, optionally a C1 to C6 alcohol, such as methanol.

[0530] 66. The method of any one of paragraphs 26 to 65, further comprising stirring the reaction mixture before step (i) and / or during step (i); or purifying the product after step (i), optionally by column chromatography; or a combination thereof.

[0531] The invention will be further understood with reference to the following non-limiting examples. Example

[0532] Example 1. Asymmetric cis-dihydroxylation of styrene and conjugated dienes catalyzed by exemplary Fe(II) complexes

[0533] Materials and methods

[0534] According to the synthesis of asymmetric PDP ligands, asymmetric tetradentate N4 ligands including PQCN-n (n = 1 to 8) were synthesized. PQCN ligands were treated with Fe(OTf)2 in anhydrous THF to obtain the corresponding [Fe(S,S-PQCN-n)(OTf)2] complex in a yield of 60 to 70%. Crystals of [Fe(S,S-PQCN-1)(OTf)2] were obtained by stacking hexane on top of DCM.

[0535] Synthesis of Iron Complex

[0536]

[0537] General steps of L1 synthesis

[0538] Under argon atmosphere, 8-bromo-2-R-quinoline (5mmol), 1,2-diamine skeleton (25mmol), Pd2(dba)3 (5mol%), RAC-BINAP (10mol%) were dissolved in toluene, and then sodium tert-butoxide (5mmol) was added, and the mixture was stirred at 85°C for 24h. After cooling to room temperature, the reaction mixture was filtered through a silica gel plug and concentrated under reduced pressure. The crude residue was purified by silica gel flash chromatography (EA / methanol=3:1v / v) to obtain L1.

[0539] General steps of L2 synthesis

[0540] Under argon atmosphere, a mixture of 6-methylpyridinecarboxaldehyde (1 equivalent) and L1 (1 equivalent) was refluxed in methanol (0.2M) overnight. After cooling to 0 ° C, NaBH4 (3 equivalents) was added in batches. The reaction mixture was kept at 0 ° C for 3h, and after completion, the reaction was quenched with water. The aqueous layer was extracted with EtOAc. Finally, the organic layer was concentrated and purified by silica gel flash chromatography to obtain L2.

[0541] General steps of L3 synthesis

[0542] Under air, 0.5mL CHCOOH was added dropwise to L2 (2.5mmol), 4.3mL formaldehyde (37%wt.% in H2O), NaCNBH3 (1.75g) in CH3CN (25mL) at 0°C. After the mixture was stirred at room temperature overnight, the reaction was diluted with Et2O (50mL) and washed with NaHCO3 aqueous solution (30mL×3). The organic fractions were combined, dried with NaSO4, and concentrated under reduced pressure. The crude product was purified by flash chromatography on silica gel (hexane / Et3N=100:1v / v).

[0543] General procedure for L4 synthesis (Method A)

[0544] Under air, 0.5mL CHCOOH was added dropwise to a solution of L2 (2.5mmol), aldehyde (2.5mmol), NaCNBH (1.75g) in CHCN (25mL) at 0°C. After the mixture was stirred at room temperature overnight, the reaction was diluted with EtO (50mL) and washed with NaHCO aqueous solution (30mL×3). The organic fractions were merged, and dried with NaSO, and concentrated under reduced pressure. The crude product was purified by flash chromatography on silica gel (hexane / EtN=100:1v / v).

[0545] General procedure for L4 synthesis (Method B)

[0546] K2CO3 (1.05 mmol) was added to a solution of L2 (1 mmol) in acetonitrile (60 mL), and the reaction was refluxed. R was then added dropwise 3 Br (1.05mmol). The mixture was refluxed overnight. When the reaction was completed by thin layer chromatography, the reaction was filtered through a short silica gel column (4-5cm), and the filtrate was evaporated to dryness. The crude product was purified by silica gel flash chromatography (hexane / Et3N=100:1v / v).

[0547] The general steps for the synthesis of L5 are the same as those for the synthesis of L3.

[0548] General method for the synthesis of C-1 symmetric iron complexes

[0549] Under argon, L3 (1 eq.) or L5 (1 eq.) and Fe(OTf) (1 eq.) were stirred in THF (0.1 M) overnight. After the reaction was complete, THF was carefully removed under reduced pressure under argon. The crude residue was washed with anhydrous EtO to obtain the pure complex as a yellow solid.

[0550]

[0551] (1S,2S)-N 1 -(2-Methylquinolin-8-yl)-N 2 -(Pyridin-2-ylmethyl)cyclohexane-1,2-diamine

[0552] (Yellow oil, yield 86%) 1 H NMR (500MHz, CD2Cl2) δ8.54(d,J=4.7Hz,1H),7.96(d,J=8.4Hz,1H),7.60(t,J=7.6Hz,1H),7.35(t,J= 8.1Hz,2H),7.26(d,J=8.4Hz,1H),7.17-7.08(m,1H),7.04(d,J=8.1Hz,1H),6.87(d,J=7.7Hz,1H),6.3 2(d,J=8.2Hz,1H),4.06(d,J=14.5Hz,1H),3.95(d,J=14.5Hz,1H),3.48(d,J=6.9Hz,1H),3.23(s,1H), 2.76(s,3H),2.70(td,J=9.3,3.8Hz,1H),2.26(d,J=9.3Hz,2H),1.90-1.69(m,2H),1.50-1.24(m,4H). 13 C NMR (125MHz, CD2Cl2) δ160.34,155.52,149.52,144.76,138.38,136.65,136.57,127.34,127.22,122.54,122 .52,122.10,114.01,105.95,61.66,57.42,54.00,32.47,31.92,26.10,25.46,25.07.HRMS(ESI):m / z([M+H] + )C 22 H 27 The calculated value of N4 is 347.2230, and the measured value is 347.2230.

[0553]

[0554] (1S,2S)-N1 ,N 2 -Dimethyl-N 1 -(2-Methylquinolin-8-yl)-N 2 -(Pyridin-2-ylmethyl)cyclohexane-1,2-diamine

[0555] (Yellow oil, yield 70%) 1 H NMR (400MHz, CD2Cl2) δ8.40(d,J=5.0Hz,1H),7.92(d,J=8.4Hz,1H),7.58(td,J=7.7,1.8Hz,1H),7.43(d,J=8.1Hz, 1H),7.32(t,J=7.8Hz,1H),7.18(d,J=8.4Hz,1H),7.15(d,J=8.1Hz,1H),7.07(d,J=7.6Hz,1H),4.71(td,J=11.0,3. 8Hz,1H),3.87(d,J=14.1Hz,1H),3.62(d,J=14.1Hz,1H),3.01(s,3H),2.84(td,J=10.8,3.6Hz,1H),2.64(s,3H),2. 39-2.26(m,1H),2.00(dt,J=9.4,2.9Hz,1H),1.87(s,3H),1.84-1.76(m,2H),2.07-1.95(m,1H),1.38-1.23(m,3H). 13 C NMR(101MHz,CD2Cl2)δ161.68,155.31,150.43,148.87,142.04,136.82,136.42,128.32,126.19,123.42,121.89,12 1.55,118.13,115.70,66.48,62.73,60.98,36.38,33.43,30.47,26.56,26.34,25.51,24.21.HRMS(ESI):m / z([M+H] + )C 24 H 31 The calculated value of N4 is 375.2543, and the measured value is 375.2543.

[0556]

[0557] (yellow solid, yield 70%) HRMS (ESI): m / z ([M-2OTf] 2+ )For C 24 H 30 The calculated value of FeN4 is 215.0910 and the measured value is 215.0906.

[0558]

[0559] (1S,2S)-N 1 -((6-methylpyridin-2-yl)methyl)-N 2 -(2-Methylquinolin-8-yl)cyclohexane-1,2-diamine

[0560] (Yellow oil, yield 80%) 1 H NMR(400MHz, CDCl3) δ7.96(d,J=8.3Hz,1H),7.51(t,J=7.7Hz,1H),7.32(t,J=8.0Hz,1H) ,7.26(d,J=8.4Hz,1H),7.19(d,J=7.7Hz,1H),7.00(t,J=8.9Hz,2H),6.85(d,J=7.7Hz,1 H),6.19(s,1H),4.06(d,J=14.4Hz,1H),3.92(d,J=14.4Hz,1H),3.55-3.41(m,1H),2.80 -2.66(m,4H),2.49(s,3H),2.35-2.19(m,2H),1.80(d,J=14.1Hz,2H),1.53-1.26(m,4H). 13 C NMR (101MHz, CDCl3) δ159.39,158.66,155.49,143.43,137.97,136.69,136.24,126.88,125.65,1 22.12,120.51,118.56,111.54,105.73,60.83,57.07,52.56,32.23,31.51,25.30,24.65,24.49.

[0561]

[0562] (1S,2S)-N 1 ,N 2 -Dimethyl-N 1 -((6-methylpyridin-2-yl)methyl)-N 2 -(2-Methylquinolin-8-yl)cyclohexane-1,2-diamine

[0563] (Yellow oil, yield 76%) 1H NMR(500MHz,CD2Cl2)δ7.91(d,J=8.4Hz,1H),7.46(t,J=7.7Hz,1H),7.29(t,J=7.8Hz,1H),7.19(dd,J=11.8,8.0Hz,2H), 7.13(d,J=7.9Hz,1H),7.05(d,J=7.7Hz,1H),6.93(d,J=7.6Hz,1H),4.66(td,J=11.1,3.8Hz,1H),3.76(d,J=14.2Hz,1H) ,3.58(d,J=14.2Hz,1H),2.99(s,3H),2.82(td,J=10.8,3.5Hz,1H),2.63(s,3H),2.43(s,3H),2.36-2.28(m,1H),2.06-1 .91(m,1H),1.86-1.74(m,5H),1.68(qd,J=12.1,3.6Hz,1H),1.35-1.26(m,1H),1.25-1.17(m,2H).HRMS(ESI):m / z([M+H] + )C 25 H 33 The calculated value of N4 is 389.2700 and the measured value is 389.2703.

[0564]

[0565] (yellow solid, yield 75%) for C 27 H 32 Elemental analysis of F6FeN4O6S2: calculated values ​​are C43.67, H 4.34, N 7.55, S 8.64, and found values ​​are C, 45.20; H, 4.84; N, 7.53; S, 8.42

[0566]

[0567] (1S,2S)-N 1 -(2-Ethylquinolin-8-yl)-N 2 -((6-methylpyridin-2-yl)methyl)cyclohexane-1,2-diamine

[0568] (Yellow oil, yield 75%) 1H NMR (500MHz, CDCl3) δ7.98 (d, J = 8.3Hz, 1H), 7.50 (t, J = 7.6Hz, 1H), 7.37-7.24 (m, 2H), 7.17 (d, J = 7. 6Hz, 1H), 7.01 (dd, J = 18.9, 7.7Hz, 2H), 6.86 (d, J = 7.6Hz, 1H), 6.24 (d, J = 9.1Hz, 1H), 4.06 (d, J = 14. 3Hz,1H),3.93(d,J=14.3Hz,1H),3.49(dd,J=17.4,10.7Hz,1H),3.02(q,J=7.5Hz,2H),2.78-2.68( m,1H),2.48(s,3H),2.25(d,J=14.6Hz,2H),1.89-1.75(m,2H),1.38(ddd,J=35.5,20.2,8.7Hz,7H).

[0569] 13 C NMR (125MHz, CDCl3) δ160.38,159.72,157.82,144.47,137.88,136.71,136.34,127.12,126.85,121.35,121.09,119. 04,113.74,105.77,61.61,57.10,52.58,32.23,31.93,31.41,25.24,24.61,24.44,13.88.HRMS(ESI):m / z([M+H]+)C 24 H 31 The calculated value of N4 is 375.2543, and the measured value is 375.2543.

[0570]

[0571] (1S,2S)-N1-(2-ethylquinolin-8-yl)-N1,N2-dimethyl-N2-((6-methylpyridin-2-yl)methyl)cyclohexane-1,2-diamine

[0572] (Yellow oil, yield 69%) 1H NMR (400MHz, CD2Cl2) δ7.96 (d, J = 8.4 Hz, 1H), 7.50 (t, J = 7.7 Hz, 1H), 7.38 (t, J = 7.8 Hz, 1H), 7.28-7.11 (m, 4H), 6.96 (d, J = 7.6 Hz, 1H), 4.88 (td, J = 11.0, 3.7 Hz, 1H), 3.83 (d, J = 14.2 Hz, 1H), 3.67 (d, J = 14.2 Hz, 1H),3.07(s,3H),2.99(q,J=7.6Hz,2H),2.88(td,J=10.7,3.3Hz,1H),2.50(s,3H),2.44(d,J=12.3Hz, 1H),2.08-1.98(m,1H),1.86(s,5H),1.80-1.71(m,1H),1.43(t,J=7.6Hz,3H),1.28(t,J=10.5Hz,1H). 13 C NMR(100MHz,CD2Cl2)δ160.76,160.20,157.40,150.46,142.04,137.20,136.71,128.59,126.23,121.23,120.65,120.17,1 18.12,115.58,66.48,62.50,61.26,36.09,33.48,32.73,30.76,26.68,26.32,24.60,24.23,14.31.HRMS(ESI):m / z([M+H] + )C 26 H 35 The calculated value of N4 is 403.2856 and the measured value is 403.2853.

[0573]

[0574] (Yellow solid, yield 73%) HRMS (ESI): m / z ([M-2OTf]2+) C26H34FeN4 calculated value is 229.1061, found value is 229.1061. 28 H 34 The elemental analysis of F6FeN4O6S2 showed calculated values ​​of C 44.45, H 4.53, N 7.41, S 8.48, and the measured values ​​were C 45.20, H 4.84, N 7.53, S8.42.

[0575]

[0576] (1S,2S)-N1-((6-isopropylpyridin-2-yl)methyl)-N2-(2-methylquinolin-8-yl)cyclohexane-1,2-diamine

[0577] (yellow solid, yield 70%) 1H NMR (500MHz, CD2Cl2) δ7.95 (d, J = 8.4 Hz, 1H), 7.52 (t, J = 7.7 Hz, 1H), 7.31 (t, J = 7.9 Hz, 1H), 7.26 (d, J = 8.4 Hz, 1H), 7.13 (d, J = 7.6 Hz, 1H), 6.99 (t, J = 7.9 Hz, 2H), 6.85 (d, J = 7.6 Hz, 1H), 6.25 (d, J = 8.4 Hz, 1H), 4.01 (d, J = 14.2 Hz, 1H), 3.86(d,J=14.2Hz,1H),3.46(d,J=6.9Hz,1H),2.97(s,1H),2.92(dt,J=13.8,6.9Hz,1H),2.72(s,3H),2.70-2.65( m,1H),2.29-2.14(m,2H),1.79(d,J=15.6Hz,2H),1.51-1.40(m,1H),1.39-1.27(m,3H),1.15(d,J=7.0Hz,6H).13C NMR (125MHz, CD2Cl2) δ167.06,160.02,155.95,144.88,138.30,137.06,136.57,127.39,127.25,122.53,119.71,118.85 ,113.85,105.75,62.30,57.53,52.93,36.66,32.78,32.04,25.78,25.47,25.15,22.82,22.76.HRMS(ESI):m / z([M+H]+)C 25 H 33 The calculated value of N4 is 389.2700 and the measured value is 389.2699.

[0578]

[0579] (1S,2S)-N1-((6-isopropylpyridin-2-yl)methyl)-N1,N2-dimethyl-N2-(2-methylquinolin-8-yl)cyclohexane-1,2-diamine

[0580] (Yellow solid, yield 75%) 1H NMR (500MHz, CD2Cl2) δ7.93 (d, J = 8.3 Hz, 1H), 7.54 (t, J = 7.7 Hz, 1H), 7.34 (t, J = 7.8 Hz, 1H), 7.26 (d, J = 7.7 Hz, 1H), 7.18 (dd, J = 13.5, 8.2 Hz, 2H), 7.09 (d, J = 7.7 Hz, 1H), 6.99 (d, J = 7.6 Hz, 1H), 4.72 (td, J = 11.0, 3.4 Hz, 1H), 3. 85(d,J=14.0Hz,1H),3.67(d,J=14.0Hz,1H),3.10-2.93(m,4H),2.87(t,J=10.3Hz,1H),2.69(s,3H),2.39(d,J =12.0Hz,1H),1.90-1.78(d,J=7.2Hz,1H),1.91(s,3H),1.83(s,2H),1.78-1.66(m,1H),1.43-1.16(m,9H).13C NMR (126MHz, CD2Cl2) δ166.51,160.58,155.26,150.57,142.12,136.81,128.34,126.26,121.54,120.64,118.46,118.10,11 5.78,66.32,62.82,61.40,36.82,36.27,33.44,30.66,26.66,26.41,25.60,24.21,23.05,23.04.HRMS(ESI):m / z([M+H]+)C 27 H 37 The calculated value of N4 is 417.3013, and the measured value is 417.3013.

[0581]

[0582] (Yellow solid, yield 76%) HRMS (ESI): m / z ([M-2OTf]2+) C27H36FeN4 calculated value is 236.1139, found value is 236.1134. 39 H 36 The elemental analysis of F6FeN4O6S2 showed calculated values ​​of C 45.20, H 4.71, N 7.27, S 8.32, and the measured values ​​were C 45.16, H 4.98, N 7.34, S8.25.

[0583]

[0584] (1S,2S)-N1-ethyl-N1-((6-methylpyridin-2-yl)methyl)-N2-(2-methylquinolin-8-yl)cyclohexane-1,2-diamine

[0585] (Yellow oil, yield 80%) 1H NMR (400MHz, CD2Cl2) δ7.95 (d, J = 8.3 Hz, 1H), 7.48 (d, J = 7.8 Hz, 1H), 7.35-7.18 (m, 3H), 7.11 (t, J = 7.7 Hz, 1H), 6.96 (d, J = 8.0 Hz, 1H), 6.82 (d, J = 7.5 Hz, 1H), 6.65 (d, J = 7.6 Hz, 1H), 3.84 (d, J = 15.2 Hz, 1H), 3.59 (d, J = 15. 2Hz,1H),3.21(s,1H),2.94-2.81(m,4H),2.77(s,3H),2.57(s,3H),2.40(s,3H),2.14(d,J=12.4Hz,1H),1. 92(d,J=9.4Hz,2H),1.78(d,J=14.7Hz,1H),1.57-1.34(m,1H),1.33-1.15(m,2H),1.06(t,J=7.0Hz,3H).13C NMR(101MHz,CD2Cl2)δ160.68,156.90,155.26,144.97,137.89,136.57,135.91,127.30,126.79,122.33,121.16,119.84 ,113.66,104.65,64.15,56.46,55.62,44.75,34.01,26.57,25.46,25.29,24.56,24.53,14.88.HRMS(ESI):m / z([M+H]+)C 25 H 33 The calculated value of N4 is 389.2700 and the measured value is 389.2692.

[0586]

[0587] (1S,2S)-N1-ethyl-N2-methyl-N1-((6-methylpyridin-2-yl)methyl)-N2-(2-methylquinolin-8-yl)cyclohexane-1,2-diamine

[0588] (yellow oil, yield 70%) 1H NMR (500 MHz, CD2Cl2) δ7.88 (d, J = 8.3 Hz, 1H), 7.37 (t, J = 7.6 Hz, 1H), 7.28 (t, J = 7.8 Hz, 1H), 7.16 (dd, J = 16.3, 8.0 Hz, 2H), 7.09 (d, J = 8.0 Hz, 1H), 6.99 (d, J = 6.4 Hz, 1H), 6.88 (d, J = 7.5 Hz, 1H), 4.92 (td, J = 10.9, 3.7 Hz, 1H), 3.96 (d, J = 14.4 Hz, 1H), 3.41 (d, J =14.2Hz,1H),2.98-2.84(m,4H),2.60(s,3H),2.42(s,3H),2.37(dd,J=12.9,6.7Hz,1H),2.33-2.21(m,2H),2.04(dd,J=10.1 ,3.8Hz,1H),1.83-1.75(m,2H),1.69(qd,J=12.4,3.6Hz,1H),1.38-1.28(m,1H),1.26-1.12(m,2H),0.70(t,J=7.1Hz,3H).13C NMR (125MHz, CD2Cl2) δ160.08,156.59,154.08,148.73,140.69,128.87,126.27,121.43,120.92,119.93,117.72 ,115.42,62.26,57.15,43.76,32.94,31.69,26.71,26.58,25.45,24.78,22.93,13.50.HRMS(ESI):m / z([M+H]+)C 26 H 35 The calculated value of N4 is 403.2856 and the measured value is 403.2852.

[0589]

[0590] (Yellow solid, yield 70%) HRMS (ESI): m / z ([M-2OTf]2+) calculated value for [C26H34FeN4]2+ is 229.1061, found value is 229.1079.

[0591]

[0592] (1S,2S)-N1-isopropyl-N1-((6-methylpyridin-2-yl)methyl)-N2-(2-methylquinolin-8-yl)cyclohexane-1,2-diamine

[0593] (Yellow oil, yield 65%) 1H NMR (400 MHz, CD2Cl2) δ7.97 (d, J = 8.3 Hz, 1H), 7.47 (d, J = 7.8 Hz, 1H), 7.36-7.20 (m, 2H), 7.12 (s, 1H), 6.99 (d, J = 6.3 Hz, 2H), 6.80 (d, J = 7.5 Hz, 1H), 6.62 (d, J = 7.7 Hz, 1H), 4.04-3.67 (m, 2H), 3.19-2.98 (m, 2H), 2.87 (td, J = 10.8, 10 .3,2.9Hz,1H),2.77(s,3H),2.58(d,J=12.9Hz,1H),2.42(s,3H),2.17(d,J=17.7Hz,1H),1.89(d,J=9.3Hz,1H),1 .76(d,J=12.7Hz,1H),1.59(q,J=12.3Hz,1H),1.50-1.33(m,2H),1.22(d,J=6.7Hz,3H),1.14(d,J=6.5Hz,3H).13C NMR(100MHz,CD2Cl2)δ162.15,157.32,155.70,145.52,138.62,136.54,127.31,127.25,122.31,121.06,119.69,113.65 ,105.16,61.98,56.15,52.03,49.79,34.18,29.44,26.86,25.37,25.34,24.56,22.79,19.74.HRMS(ESI):m / z([M+H]+)C 26 H 35 The calculated value of N4 is 403.2856 and the measured value is 403.2854.

[0594]

[0595] (1S,2S)-N1-isopropyl-N2-methyl-N1-((6-methylpyridin-2-yl)methyl)-N2-(2-methylquinolin-8-yl)cyclohexane-1,2-diamine

[0596] (Yellow oil, yield 60%) 1H NMR (500MHz, CD2Cl2) δ7.87 (d, J = 8.3 Hz, 1H), 7.28 (t, J = 7.8 Hz, 1H), 7.22 (t, J = 7.5 Hz, 1H), 7.18 (d, J = 7.7 Hz, 1H), 7.13 (d, J = 8.4 Hz, 1H), 7.09 (d, J = 7.9 Hz, 1H), 6.89 (d, J = 7.8 Hz, 1H), 6.82 (d, J = 7.3 Hz, 1H), 5.03-4.84 (m, 1H), 4.01 (d, J = 14.7 Hz, 1H), 3. 58(d,J=14.6Hz,1H),3.04-2.94(m,1H),2.88(td,J=10.8,3.3Hz,1H),2.78(s,3H),2.58(s,3H),2.43(s,3H),2.14(d,J=9.6 Hz,2H),1.82-1.69(m,2H),1.60(qd,J=12.2,3.7Hz,1H),1.36-1.12(m,4H),0.96(d,J=6.5Hz,3H),0.73(d,J=6.6Hz,3H).13C NMR (125MHz, CD2Cl2) δ162.94,156.76,154.66,150.01,141.91,136.70,136.11,128.54,126.31,121.46,121.38,120.71,117.4 7,115.14,62.47,62.06,52.21,49.53,33.60,30.43,29.13,26.91,26.62,25.38,24.62,23.12,21.03.HRMS(ESI):m / z([M+H]+)C 27 H 37 The calculated value of N4 is 417.3013 and the measured value is 417.3015.

[0597]

[0598] HRMS (ESI): m / z ([M-2OTf]2+) calculated for [C27H36FeN4]2+ is 236.1144, found to be 236.1151.

[0599]

[0600] (1S,2S)-N1-Benzyl-N1-((6-methylpyridin-2-yl)methyl)-N2-(2-methylquinolin-8-yl)cyclohexane-1,2-diamine

[0601] (yellow oil, yield 67%) 1H NMR (400MHz, CD2Cl2) δ7.99 (d, J = 8.3 Hz, 1H), 7.57 (d, J = 7.8 Hz, 1H), 7.51 (d, J = 6.7 Hz, 2H), 7.35 (d, J = 8.4 Hz, 1H), 7.21 (td, J = 10.8, 10.4, 7.4 Hz, 5H), 6.98 (d, J = 9.3 Hz, 1H), 6.86 (d, J = 7.6 Hz, 1H), 6.64 (d, J = 7.6 Hz, 1H), 3.82 (dd, J = 20.3, 14.0 Hz, 2H), 3.59 (dd, J=31.8,14.0Hz,2H),3.33(tt,J=10.4,3.3Hz,1H),2.89(s,3H),2.81-2.69(m,1H),2.53(dt,J=13.0,2.6Hz,1H),2.41(s,3H),2. 28(d,J=11.0Hz,1H),1.91(d,J=13.0Hz,1H),1.73(d,J=13.5Hz,1H),1.57-1.38(m,2H),1.33-1.23(m,1H),1.18-1.02(m,1H).13C NMR(100MHz,CD2Cl2)δ160.62,157.88,155.78,144.67,141.40,138.50,136.77,136.69,129.59,128.67,127.43,127.37 ,127.29,122.45,121.08,119.72,113.30,106.39,62.72,55.79,55.46,54.46,34.16,26.38,25.48,25.25,24.56,23.79.

[0602]

[0603] 1H NMR (400 MHz, dichloromethane-d2) δ7.90 (d, J = 8.4 Hz, 1H), 7.35 (t, J = 7.9 Hz, 2H), 7.31-7.19 (m, 5H), 7.16 (t, J = 7.4 Hz, 3H), 7.00 (d, J = 7.8 Hz, 1H), 6.89 (d, J = 7.5 Hz, 1H), 5.10 (td, J = 10.9, 3.6 Hz, 1H), 4.20 (d, J = 13.7 Hz, 1H), 3.90 (d, J = 12.9 Hz, 1H), 3.51 (d d,J=17.4,13.4Hz,2H),2.83(td,J=10.9,3.2Hz,1H),2.69(s,3H),2.60(s,3H),2.46(s,3H),2.29(d,J=15.3Hz,1H),2.0 5(d,J=15.4Hz,1H),1.84(d,J=18.1Hz,1H),1.75(d,J=15.2Hz,1H),1.54(q,J=14.0,12.2Hz,1H),1.46-1.18(m,3H).13C NMR (100MHz, CD2Cl2) δ161.46,156.99,155.03,149.94,142.01,140.97,136.84,136.46,130.40,128.55,128.29,127.12,126.34,121.55 ,121.17,121.09,118.10,115.83,62.07,60.81,56.39,54.76,33.47,29.63,26.57,26.48,25.31,24.74,24.61.HRMS(ESI):m / z([M+H]+)C 31 H 37 The calculated value of N4 is 465.3013 and the measured value is 465.3018.

[0604]

[0605] (Yellow solid, yield 75%) HRMS (ESI): m / z ([M-2OTf]2+) [C31H36FeN4]2+ calculated value is 260.1145, found value is 260.1141. 33 H 36 Elemental analysis of F6FeN4O6S2[Fe(S,S-PQCN-7)(OTf)2]·H2O: calculated values: C, 47.38; N, 6.70H, 4.58; S, 7.66. Found values: C, 47.80; N, 6.36; H, 4.89; S, 7.90.

[0606]

[0607] (1S,2S)-N1-((6-methylpyridin-2-yl)methyl)-N2-(2-methylquinolin-8-yl)-N1-(naphthalen-1-ylmethyl)cyclohexane-1,2-diamine

[0608] (Yellow oil, yield 80%) 1 H NMR(500MHz, dichloromethane-d2)δ8.24(d,J=8.5Hz,1H),8.03(d,J=8.4Hz,1H),7.80(dd, J=14.2,8.3Hz,2H),7.71(d,J=8.2Hz,1H),7.53(d,J=7.8Hz,1H),7.34(dt,J=24 .0,8.2Hz,5H),7.11(d,J=4.2Hz,1H),7.03(d,J=9.3Hz,1H),6.98(t,J=7.8Hz, 1H),6.89(d,J=7.6Hz,1H),6.71(d,J=7.9Hz,1H),4.27(d,J=13.6Hz,1H),4.18( d,J=13.6Hz,1H),3.95(d,J=14.3Hz,1H),3.82(d,J=14.3Hz,1H),3.57(ddd,J= 14.4,9.1,3.9Hz,1H),2.96-2.87(m,1H),2.84(s,3H),2.57(d,J=14.0Hz,1H),2 .46(s,3H),2.42(d,J=12.4Hz,1H),1.96(d,J=13.2Hz,1H),1.76(d,J=12.4Hz,1 H),1.73-1.60(m,1H),1.57-1.45(m,1H),1.36-1.24(m,1H),1.20-1.07(m,1H). 13 C NMR (125MHz, CD2Cl2) δ160.58,157.49,155.72,144.65,138.51,136.74,136.6 4,135.67,134.23,133.06,128.76,128.24,128.02,127.49,127.34,126.10,12 5.86,125.71,124.70,122.49,121.41,120.43,113.61,104.86,63.70,56.74, 54.89,51.85,33.64,26.43,25.63,25.35,24.60,24.32.HRMS(ESI):m / z([M+H] + )C 34 H37 The calculated value of N4 is 501.3013 and the measured value is 501.3030.

[0609]

[0610] (1S,2S)-N 1 -Methyl-N 2 -((6-methylpyridin-2-yl)methyl)-N 1 -(2-Methylquinolin-8-yl)-N 2 -(Naphthalene-1-ylmethyl)cyclohexane-1,2-diamine

[0611] (Yellow oil, yield 70%) 1 H NMR (400 MHz, dichloromethane-d2) δ 8.06 (d, J = 8.6 Hz, 1H), 7.89 (d, J = 8.3 Hz, 1H), 7.78 (d, J = 8.2 Hz, 1H), 7.73 (d, J = 8.2 Hz, 1H), 7.49 (d, J = 6.9 Hz, 1H), 7.39 (td, J = 7.3, 3.9 Hz, 2H), 7.27 (tt, J = 11.7, 7.7 Hz, 3H), 7.17 (d, J = 7.9 Hz, 1H), 7.12 (d, J = 8.4 Hz, 1H), 6.88 (d, J = 7.5 Hz, 1H), 6.82 (d, J = 7.7 Hz, 1H), 6.77 (d, J=7.7Hz,1H),5.17(td,J=10.9,3.6Hz,1H),4.59(d,J=13.0Hz,1H),4.30( d,J=12.9Hz,1H),3.92(d,J=13.0Hz,1H),3.49(d,J=12.8Hz,1H),2.83(td ,J=10.9,3.2Hz,1H),2.52(s,3H),2.46-2.37(m,4H),2.27(s,3H),1.93-1 .75(m,2H),1.68(d,J=15.5Hz,1H),1.50-1.31(m,2H),1.29-1.02(m,2H). 13C NMR(100MHz,CD2Cl2)δ161.07,156.89,155.10,149.73,142.02,136.86,136.39, 136.27,134.28,133.62,128.99,128.50,128.41,128.03,126.61,126.30,125.8 6,125.56,125.50,122.04,121.58,121.20,118.31,116.38,62.02,60.79,56.72 ,52.74,32.97,29.31,26.53,26.47,25.21,24.61,24.23.HRMS(ESI):m / z([M+H] + )C 35 H 39 The calculated value of N4 is 515.3169 and the measured value is 515.3172.

[0612]

[0613] (Yellow oil, yield 74%) HRMS (ESI): m / z ([M-2OTf]2+) calculated value for [C35H38FeN4]2+ is 285.1217, found value is 285.1201.

[0614]

[0615] (1S,2S)-N 1 -(3,5-di-tert-butylbenzyl)-N 1 -((6-methylpyridin-2-yl)methyl)-N 2 -(2-Methylquinolin-8-yl)cyclohexane-1,2-diamine

[0616] (Yellow oil, yield 65%) 1H NMR (400 MHz, dichloromethane-d2) δ 7.97 (d, J = 8.4 Hz, 1H), 7.71 (d, J = 7.7 Hz, 1H), 7.53 (t, J = 7.7 Hz, 1H), 7.29 (dd, J = 19.1, 8.1 Hz, 2H), 7.14 (d, J = 9.8 Hz, 3H), 6.95 (dd, J = 12.9, 6.1 Hz, 3H), 6.66 (d, J = 7.6 Hz, 1H), 3.96 (d, J = 13.1 Hz, 1H), 3.78 (q, J = 1 4.7Hz,2H),3.56(td,J=10.4,5.2Hz,1H),3.46(d,J=13.1Hz,1H),2.89-2.73(m,4H),2.59-2.41(m,4H),2.30(d,J=1 2.6Hz,1H),1.92(d,J=9.9Hz,1H),1.74(d,J=12.5Hz,1H),1.59-1.40(m,1H),1.34-1.21(m,1H),1.18-0.09(s,19H). 13 C NMR(100MHz,CD2Cl2)δ160.88,157.57,155.77,150.94,144.51,139.51,138.49, 137.00,136.66,127.67,127.30,123.94,122.57,121.46,120.82,120.13,113.3 5,104.47,63.21,56.61,54.54,54.27,54.12,54.00,53.73,53.46,46.82,34.96 ,33.36,31.59,26.40,25.96,25.39,24.66,24.10,12.18.HRMS(ESI):m / z([M+H] + )C 38 H 51 The calculated value of N4 is 563.4108 and the measured value is 563.4115.

[0617]

[0618] (1S,2S)-N 1 -(3,5-di-tert-butylbenzyl)-N 2 -Methyl-N 1 -((6-methylpyridin-2-yl)methyl)-N 2 -(2-Methylquinolin-8-yl)cyclohexane-1,2-diamine

[0619] (Yellow oil, yield 50%) 1H NMR (500 MHz, dichloromethane-d2) δ7.85 (d, J = 8.3 Hz, 1H), 7.35-7.22 (m, 3H), 7.18-7.06 (m, 5H), 6.92 (d, J = 9.1 Hz, 1H), 6.84 (d, J = 7.4 Hz, 1H), 5.10 (td, J = 11.0, 3.7 Hz, 1H), 4.28 (d, J = 13.7 Hz, 1H), 3.82 (d, J = 12.7 Hz, 1H), 3.47 (dd, J = 13. 3,6.2Hz,2H),2.79(td,J=11.0,3.2Hz,1H),2.60(s,3H),2.52(s,3H),2.40(s,3H),2.31-2.21(m,1H),1.94(d,J =12.1Hz,1H),1.81(d,J=10.1Hz,1H),1.70(d,J=12.9Hz,1H),1.48(dd,J=24.1,3.7Hz,1H),1.34-1.25(m,21H). 13 C NMR (125MHz, CD2Cl2) δ161.51,156.84,155.04,150.55,149.83,142.01,139.73,136.81,136.31,128.49,126.27,124.85,121.55,121.14,120. 93,120.85,118.08,115.87,62.12,60.95,56.40,55.55,35.15,33.34, 31.82,29.56,26.63,26.59,25.21,24.84,24.61.HRMS(ESI):m / z([M+H] + )C 39 H 53 The calculated value of N4 is 577.4265 and the measured value is 577.4287.

[0620]

[0621] (yellow solid, yield 30%) HRMS (ESI): m / z ([M-2OTf] 2+ )For [C 39 H 52 FeN4] 2+ The calculated value is 316.1766 and the measured value is 316.1798.

[0622] Characterization of Styrene Diol

[0623]

[0624] (R)-1-phenylethane-1,2-diol

[0625] (colorless oil, 47.0, yield 85%) 1 H NMR (400MHz, CDCl3) δ7.41-7.26(m,5H),4.78(d,J=5.0Hz,1H),3.77-3.54(m,2H),3.36(brs,1H),3.05(brs,1H). 13 C NMR (100 MHz, CDCl3) δ 140.55, 128.64, 128.09, 126.18, 74.82, 68.15. HPLC (Chiralcel OD-3, n-hexane / 2-propanol = 93 / 7, flow rate: 1 ml / min, detection at 210 nm) retention time: t = 16.2 min (main peak) and 25.7 min (secondary peak), 82.9% ee. [α] 20 D =-41.0 (c = 1.4, CHCl3)

[0626]

[0627] (R)-1-(p-Tolyl)ethane-1,2-diol

[0628] (white solid, 33 mg, yield 54%) 1 H NMR (500MHz, CDCl3) δ7.22(d,J=8.1Hz,2H),7.15(d,J=7.9Hz,2H),4.75(dd,J=8.3,3.5Hz,1H),3.80-3.51(m,2H),2.33(s,3H). 13 C NMR (125MHz, CDCl3) δ137.82,129.32,126.15,74.69,68.17,21.24.

[0629] HRMS(ESI):m / z([M+Na] 1+ )C9H 12 The calculated value of NaO2 is 175.0730, and the measured value is 175.0734. HPLC (Chiralcel OD-3, n-hexane / 2-propanol=90 / 10, flow rate: 1 ml / min, detection at 210 nm) retention time: t=8.7 min (main peak) and 9.7 min (secondary peak), 84.1% ee. [α] 20 D =-44.4 (c = 1.0, CHCl3)

[0630]

[0631] (R)-1-(4-(tert-Butyl)phenyl)ethane-1,2-diol

[0632] (white solid, 52.1 mg, yield 60%) 1 H NMR (500MHz, MeOD) δ7.37 (s, 2H), 7.29 (d, J = 7.9 Hz, 2H), 4.66 (t, J = 5.9 Hz, 1H), 3.60 (d, J = 5.9 Hz, 2H), 1.31 (s, 9H). 13 C NMR(125MHz,MeOD)δ151.53,140.22,127.16,126.12,75.76,68.73,35.30,31.80.HRMS(ESI):m / z([M+Na] 1+ )C 12 H 18 The calculated value of NaO2 is 217.1199, and the measured value is 2217.1202. HPLC (Chiralcel OD-3, n-hexane / 2-propanol=95 / 5, flow rate: 1 ml / min, detection at 230 nm) retention time: t=15.8 min (main peak) and 17.3 min (secondary peak), 82.7% ee. [α] 20 D =-36.2 (c = 1.0, CHCl3)

[0633]

[0634] (R)-1-(4-Fluorophenyl)ethane-1,2-diol

[0635] (white solid, 40.6 mg, yield 65%) 1 H NMR (400MHz, CDCl3) δ7.37-7.29(m,2H),7.10-6.99(m,2H),4.81(dd,J=8.2,3.4Hz,1H) ,3.74(dd,J=11.3,3.4Hz,1H),3.62(dd,J=11.3,8.3Hz,1H),2.83(s,1H),2.35(s,1H).

[0636] 13 C NMR(100MHz, CDCl3)δ163.82,161.37,136.34,127.93,127.85,115.67,115.45,74.16,68.18.HRMS(ESI):m / z([M+Na] 1+)Calculated value for C8H9FNaO2: 179.0479, found value: 179.0482. HPLC (Chiralcel OD-3, n-hexane / 2-propanol = 95 / 5, flow rate: 1 ml / min, detection at 210 nm) retention time: t = 22.7 min (main peak) and 25.8 min (secondary peak), 80.1% ee. [α] 19 D =-38.6 (c = 3.9, CHCl3)

[0637]

[0638] (R)-1-(4-Chlorophenyl)ethane-1,2-diol

[0639] (white solid, 46 mg, yield 67%) 1 H NMR (400MHz, CDCl3) δ7.36-7.24(m,4H),4.79(dd,J=8.1,3.3Hz,1H),3.73(dd,J=11.3,3.3Hz,1H),3.60(dd,J=11.3,8.2Hz,1H). 13 C NMR(100MHz, CDCl3)δ139.02,133.87,128.83,127.58,74.13,68.04.HRMS(ESI):m / z([M+Na] 1+ )Calculated value for C8H9ClNaO2: 195.0183, found value: 195.0183. HPLC (Chiralcel OD-3, n-hexane / 2-propanol = 90 / 10, flow rate: 1 ml / min, detection at 210 nm) retention time: t = 9.5 min (main peak) and 10.8 min (secondary peak), 84.1% ee. [α] 20 D =-38.3 (c = 1, CHCl3)

[0640]

[0641] (R)-1-(4-Bromophenyl)ethane-1,2-diol

[0642] (white solid, 53.5 mg, yield 62%) 1 H NMR (500MHz, MeOD) δ7.48 (d, J = 7.7Hz, 2H), 7.30 (d, J = 7.7Hz, 2H), 4.66 (t, J = 5.8Hz, 1H), 3.67-3.55 (m, 2H). 3C NMR(125MHz,MeOD)δ142.71,132.26,129.37,122.07,75.14,68.42.HRMS(ESI):m / z([M+Na] 1+ )Calculated value for C8H9BrNaO2: 238.9678, found value: 238.9676. HPLC (Chiralcel OD-H, n-hexane / 2-propanol = 90 / 10, flow rate: 1 ml / min, detection at 210 nm) retention time: t = 10.2 min (main peak) and 11.1 min (secondary peak), 86.3% ee. [α] 19 D =-30.5 (c = 3.3, CHCl3)

[0643]

[0644] (R)-1-(4-(Trifluoromethyl)phenyl)ethane-1,2-diol

[0645] (white solid, 62.6 mg, yield 76%) 1 H NMR (400 MHz, chloroform-d) δ 7.63 (d, J = 8.0 Hz, 2H), 7.50 (d, J = 8.0 Hz, 2H), 4.90 (dd, J = 8.1, 3.4 Hz, 1H), 3.81 (dd, J = 11.3, 3.5 Hz, 1H), 3.65 (dd, J = 11.2, 8.0 Hz, 1H), 2.72 (s, 1H), 2.10 (s, 1H). 13 C NMR (125MHz, MeOD) δ148.12, 130.57 (q, J = 32.0Hz), 129.01, 126.04 (q, J = 3.8Hz), 125.78 (q, J = 270.8Hz), 75.21, 68.45. 19 FNMR(471MHz,MeOD)δ-63.92.HRMS(ESI):m / z([M+Na] 1+ ) The calculated value of C9H9F3O2Na is 229.0447, and the measured value is 229.0451. HPLC (Chiralcel OD-3, n-hexane / 2-propanol=95 / 5, flow rate: 1 ml / min, detection at 210 nm) retention time: t=48.5 min (main peak) and 52.9 min (secondary peak), 88.5% ee. [α] 20 D =-40.0 (c = 1.4, CHCl3)

[0646]

[0647] (R)-1-(4-Nitrophenyl)ethane-1,2-diol

[0648] (white solid, 61.6 mg, yield 72%) 1 H NMR (500MHz, MeOD) δ8.21 (d, J = 7.8 Hz, 2H), 7.63 (d, J = 8.0 Hz, 2H), 4.81 (t, J = 5.7 Hz, 1H), 3.71-3.59 (m, 2H). 13 C NMR(100MHz,MeOD)δ151.43,148.68,128.49,124.24,74.94,68.27.HRMS(ESI):m / z([M+H] 1+ )C8H 10 The calculated value of NO4 is 184.0604, and the measured value is 184.0609. HPLC (Chiralcel OD-3, n-hexane / 2-propanol=90 / 10, flow rate: 1 ml / min, detection at 210 nm) retention time: t=20.1 min (main peak) and 23.3 min (secondary peak), 89.9% ee. [α] 20 D =-30.4 (c = 0.4, CHCl3)

[0649]

[0650] (R)-1-(3,5-Bis(trifluoromethyl)phenyl)ethane-1,2-diol

[0651] (white solid, 107.5 mg, yield 98%) 1 H NMR (400MHz, CDCl3) δ7.86 (s, 2H), 7.83 (s, 1H), 4.97 (dd, J = 8.1, 3.4Hz, 1H), 3.88 (dd,J=11.1,3.4Hz,1H),3.66(dd,J=11.1,7.8Hz,1H),2.84(s,1H),2.05(s,1H). 13 C NMR (100MHz, MeOD) δ147.31, 132.43 (q, J = 33.1Hz), 128.02, 124.95 (q, J = 271.7Hz), δ 121.98 (t, J = 4.0Hz), 73.36, 68.64. 19 F NMR(377MHz,MeOD)δ-64.33.HRMS(EI):m / z([MF] 1+) Calculated value is 255.0444, found value is 255.0435. HPLC (Chiralcel OD-3, n-hexane / 2-propanol = 95 / 5, flow rate: 1 ml / min, detection at 210 nm) retention time: t = 5.2 min (main peak) and 5.8 min (secondary peak), 94.5% ee. [α] 20 D =-24.6 (c = 0.4, CHCl3)

[0652]

[0653] (R)-1-(m-Tolyl)ethane-1,2-diol

[0654] (white solid, 34.7 mg, yield 57%) 1 H NMR (500MHz, CDCl3) δ7.24 (dd, J=15.2, 7.6Hz, 1H), 7.18-7.07 (m, 3H), 4.76 (dd, J=8.3, 3.0Hz, 1 H),3.71(dd,J=11.4,3.1Hz,1H),3.67-3.58(m,1H),3.44(brs,1H),3.08(brs,1H),2.35(s,3H). 13 C NMR (126MHz,CDCl3)δ140.56,138.31,128.81,128.54,126.86,123.24,74.85,68.18,21.53.HRMS (ESI):m / z([M+Na]1+)Calculated value for C9H12NaO2 is 175.0730, and the found value is 175.0730.HPLC (Chiralcel AY-H, n-hexane / 2-propanol=95 / 5, flow rate: 1ml / min, detection at 220nm)Retention time: t=23.9min (minor peak) and 25.7min (main peak), 84.6%ee. [α] 20 D =-40.0 (c = 1.4, CHCl3)

[0655]

[0656] (R)-1-(3-Fluorophenyl)ethane-1,2-diol

[0657] (white solid, 40.6 mg, yield 65%) 1H NMR (400MHz, CDCl3) δ7.35-7.20(m,1H),7.11-7.01(m,2H),7.00-6.90(m,1H),4.76( dd,J=8.3,3.2Hz,1H),3.92-3.63(m,2H),3.58(dd,J=11.5,8.3Hz,1H),3.31(s,1H). 13 C NMR (100MHz, CDCl3) δ163.04(d,J=246.2Hz), 143.20(d,J=6.9Hz), 130.17(d,J=8.2Hz), 121.71(d,J=2 .9Hz),114.90(d,J=21.1Hz),113.16(d,J=22.0Hz),74.18(d,J=1.8Hz),67.91.HRMS(ESI):m / z([M+Na] 1+ )Calculated value for C8H9FNaO2: 179.0479, found value: 179.0475. HPLC (Chiralcel OD-3, n-hexane / 2-propanol = 90 / 10, flow rate: 1 ml / min, detection at 210 nm) retention time: t = 8.8 min (main peak) and 9.9 min (secondary peak), 85.1% ee. [α] 20 D =-36.5 (c = 1.0, CHCl3)

[0658]

[0659] (R)-1-(3-Chlorophenyl)ethane-1,2-diol

[0660] (white solid, 55 mg, yield 80%) 1 H NMR (500MHz, CDCl3) δ7.30 (s, 1H), 7.27-7.19 (m, 2H), 7.14 (d, J = 4.3Hz, 1H), 4.71 (dd, J = 8.2, 2. 3Hz,1H),4.36(s,1H),3.91(s,1H),3.65(dd,J=11.5,2.6Hz,1H),3.53(dd,J=11.2,8.8Hz,1H). 13 C NMR(125MHz, CDCl3)δ142.60,134.48,129.90,128.12,126.33,124.30,74.14,67.80.HRMS(ESI):m / z([M+Na] 1+)Calculated value for C8H9ClNaO2: 195.0183, found value: 195.0183. HPLC (Chiralcel OD-3, n-hexane / 2-propanol = 90 / 10, flow rate: 1 ml / min, detection at 220 nm) retention time: t = 8.9 min (main peak) and 10.0 min (secondary peak), 85.8% ee. [α] 20 D =-34.6 (c = 2.7, CHCl3)

[0661]

[0662] (R)-1-(3-Bromophenyl)ethane-1,2-diol

[0663] (white solid, 62.2 mg, yield 72%) 1 H NMR (500MHz, CDCl3) δ7.46 (s, 1H), 7.38 (d, J = 7.4Hz, 1H), 7.22-7.11 (m, 2H), 4.75-4. 63(m,1H),4.36(s,1H),3.94(s,1H),3.64(dd,J=11.5,2.3Hz,1H),3.58-3.46(m,1H). 13 C NMR(125MHz, CDCl3)δ142.85,131.05,130.20,129.24,124.79,122.70,74.06,67.80.HRMS(ESI):m / z([M+Na] 1+ )Calculated value for C8H9BrNaO2: 238.9678, found value: 238.9682. HPLC (Chiralcel OD-3, n-hexane / 2-propanol = 90 / 10, flow rate: 1 ml / min, detection at 210 nm) retention time: t = 9.2 min (main peak) and 10.7 min (secondary peak), 84.1% ee. [α] 20 D =-24.6 (c = 0.6, CHCl3)

[0664]

[0665] (R)-1-(3-Nitrophenyl)ethane-1,2-diol

[0666] (white solid, 58.6 mg, yield 80%) 1H NMR (500MHz, MeOD) δ8.29 (s, 1H), 8.13 (d, J = 8.1Hz, 1H), 7.78 (d, J = 7.6Hz, 1H), 7.58 (t, J = 7.9Hz, 1H), 4.81 (t, J = 5.6Hz, 1H), 3.73-3.61 (m, 2H). 13 C NMR(125MHz,MeOD)δ149.60,146.15,133.81,130.35,123.21,122.22,74.64,68.23.HRMS(ESI):m / z([M+Na] 1+ )Calculated value for C8H9NNaO4: 206.0424, found value: 206.0421. HPLC (Chiralcel OD-3, n-hexane / 2-propanol = 90 / 10, flow rate: 1 ml / min, detection at 210 nm) retention time: t = 16.1 min (main peak) and 18.5 min (secondary peak), 91.7% ee. [α] 18 D =-59.3 (c = 0.6, CHCl3)

[0667]

[0668] (R)-1-(Perfluorophenyl)ethane-1,2-diol

[0669] (white solid, 80.3 mg, yield 88%) 1 H NMR (500MHz, CH3OD) δ5.08 (t, J = 6.9 Hz, 1H), 3.90 (dd, J = 11.1, 7.0 Hz, 1H), 3.76 (dd, J = 11.1, 6.8 Hz, 1H). 13 C NMR (500MHz, CH3OD) δ148.15-147.84(m), 145.70-145.26(m), 143.33-142.78(m), 140.78-139.86(m), 137.76-137.34(m), 67.65, 65.27. 19 F NMR (377MHz, CH3OD) δ-144.69--144.85(m),-158.96(t,J=20.0Hz),-165.82(td,J=21.2,8.1Hz).HRMS(EI):m / z([M-CH3OH] 1-) Calculated value for C7H2F5O was 197.0026, found value was 197.0018. HPLC (Chiralcel AYH, n-hexane / 2-propanol=90 / 10, flow rate: 1 ml / min, detection at 210 nm) retention time: t=4.3 min (main peak) and 4.7 min (main peak), 91.6% ee.

[0670]

[0671] (R)-1-(2-Benzylphenyl)ethane-1,2-diol

[0672] (white solid, 72.0 mg, yield 79%) 1 H NMR (400MHz, CDCl3) δ7.51(d,J=7.3Hz,1H),7.33-7.23(m,4H),7.21-7.12(m,2H),7.10(d,J=7.6Hz ,2H),5.02(dd,J=8.4,3.3Hz,2H),4.19-3.88(m,2H),3.60-3.34(m,1H),2.51(s,1H),2.19(s,1H). 13 C NMR(100MHz, CDCl3)δ140.69,138.88,137.61,132.53,128.72,128.69,128.15,127.20,126.68,126.41,71.70,67.40,39.23.HRMS(ESI):m / z([M+Na] 1+ )C 15 H 16 The calculated value of O2Na is 251.1042, and the measured value is 251.1032. HPLC (Chiralcel AD-H, n-hexane / 2-propanol=90 / 5, flow rate: 1 ml / min, detection at 210 nm) retention time: t=30.9 min (main peak) and 33.0 min (secondary peak), 79.9% ee. [α] 20 D =-47.3 (c = 1.0, CHCl3)

[0673]

[0674] (R)-1-([1,1'-biphenyl]-2-yl)ethane-1,2-diol

[0675] (white solid, 61.6 mg, yield 72%) 1H NMR (500MHz, CD3OD) δ7.62 (d, J=7.8Hz, 1H), 7.41 (dd, J=15.6, 8.0Hz, 3H), 7.33 (td, J= 14.7,7.7Hz,4H),7.17(d,J=7.6Hz,1H),4.84(d,J=6.0Hz,1H),3.53(d,J=6.0Hz,2H). 13 C NMR (125MHz, CD3OD) δ142.65,142.47,140.24,130.87,130.41,129.25,128.63,128.30,128.13,127.68,72.04,68.07.HRMS(ESI):m / z([M+Na] 1+ )C 14 H 14 The calculated value of O2Na was 237.0886, and the found value was 237.0879. HPLC (Chiralcel AYH, n-hexane / 2-propanol=90 / 10, flow rate: 1 ml / min, detection at 210 nm) retention time: t=9.9 min (minor peak) and 11,0 min (main peak), 93.1% ee.

[0676] [α] 19 D =-32.4 (c = 1, CHCl3)

[0677]

[0678] (R)-1-(4'-Chloro-[1,1'-biphenyl]-2-yl)ethane-1,2-diol

[0679] (white solid, 86.3 mg, yield 87%) 1 H NMR(500MHz, CDCl3)δ7.61(d,J=7.6Hz,1H),7.38(tt,J=14.6,7.2Hz,4H),7.28- 7.13(m,3H),4.91-4.77(m,1H),3.59(d,J=5.3Hz,2H),2.54(s,1H),2.08(s,1H). 13 C NMR (125MHz, CDCl3) δ140.09,139.16,137.80,133.63,130.66,130.18,128.68,128.33,128.00,126.59,71.11,67.48.HRMS(ESI):m / z([M+Na] 1+ )C 14 H 13The calculated value of ClNaO2 is 271.0496, and the measured value is 271.0499. HPLC (Chiralcel OD-3, n-hexane / 2-propanol=90 / 10, flow rate: 1 ml / min, detection at 210 nm) retention time: t=8.5 min (main peak) and 9.5 min (secondary peak), 94.9% ee. [α] 20 D =-24.0 (c = 1.0, CHCl3)

[0680]

[0681] (R)-1-(3-Methoxyphenyl)ethane-1,2-diol

[0682] (white solid, 45.9 mg, yield 60%) 1 H NMR (400MHz, CDCl3) δ7.26(dd,J=9.7,6.0Hz,1H),6.90(d,J=7.1Hz,2H),6.82(dd,J=8.9,2.0Hz,1H),4.77(dd,J=8 .2,3.3Hz,1H),3.79(s,3H),3.72(dd,J=11.4,3.3Hz,1H),3.62(dd,J=11.4,8.3Hz,1H),3.38(s,1H),2.96(s,1H). 13 C NMR(100MHz, CDCl3)δ159.84,142.34,129.68,118.46,113.43,111.78,74.72,68.14,55.35.HRMS(ESI):m / z([M+Na] 1+ )C9H 12 The calculated value of NaO3 is 191.0679, and the measured value is 191.0680. HPLC (Chiralcel OD-3, n-hexane / 2-propanol=92 / 8, flow rate: 1 ml / min, detection at 230 nm) retention time: t=18.0 min (main peak) and 20.3 min (secondary peak), 87.7% ee. [α] 19 D =-39.4 (c = 1.6, CHCl3)

[0683]

[0684] (R)-1-(2-Bromophenyl)ethane-1,2-diol

[0685] (white solid, 64.7 mg, yield 75%) 1H NMR (400MHz, MeOD) δ7.60(dd,J=7.8,1.5Hz,1H),7.53(dd,J=8.0,0.9Hz,1H),7.36(t,J=7.5Hz,1H),7.16(td ,J=7.8,1.7Hz,1H),5.10(dd,J=7.8,3.1Hz,1H),3.73(dd,J=11.5,3.2Hz,1H),3.46(dd,J=11.5,7.8Hz,1H). 13 C NMR(100MHz,MeOD)δ142.15,133.52,130.08,129.31,128.65,123.00,74.67,67.21.HRMS(ESI):m / z([M+Na] 1+ )Calculated value for C8H9BrNaO2: 238.9678, found value: 238.9676. HPLC (Chiralcel OD-3, n-hexane / 2-propanol = 95 / 5, flow rate: 1 ml / min, detection at 210 nm) retention time: t = 8.3 min (main peak) and 10.4 min (secondary peak), 68.3% ee. [α] 21 D =-29.6 (c = 0.8, CHCl3)

[0686]

[0687] (R)-1-(2-Chlorophenyl)ethane-1,2-diol

[0688] (white solid, 46.1 mg, yield 67%) 1 H NMR (400MHz, CDCl3) δ7.55 (d, J = 7.7Hz, 1H), 7.35-7.10 (m, 2H), 5.22 (d, J = 7.2Hz, 1H), 4.07-3.08 (m, 4H). 13 C NMR(100MHz, CDCl3)δ137.50,132.83,129.48,129.00,127.67,127.19,71.58,66.35.HRMS(ESI):m / z([M+Na] 1+ )Calculated value for C8H9ClO2Na is 195.0183, found value is 195.0182. HPLC (Chiralcel OD-3, n-hexane / 2-propanol=90 / 10, flow rate: 1 ml / min, detection at 210 nm) retention time: t=17.4 min (main peak) and 24.0 min (secondary peak), 75.5% ee. [α] 20 D=-38.4 (c = 2.2, CHCl3)

[0689]

[0690] (R)-1-(o-Tolyl)ethane-1,2-diol

[0691] (white solid, 54.7 mg, yield 90%) 1 H NMR (500MHz, CDCl3) δ7.47(d,J=6.7Hz,1H),7.26-7.18(m,2H),7.15(d,J=6.7Hz,1H),5.04(d,J=8.0Hz,1H),3.85-3.38(m,4H),2.32(s,3H). 13 C NMR(125MHz, CDCl3)δ138.54,134.79,130.47,127.75,126.35,125.73,71.58,66.98,19.07.HRMS(ESI):m / z([M+Na] 1+ )C9H 12 The calculated value of NaO2 is 175.0730, and the measured value is 175.0729. HPLC (Chiralcel OD-H, n-hexane / 2-propanol=90 / 10, flow rate: 1 ml / min, detection at 220 nm) retention time: t=8.0 min (main peak) and 9.7 min (secondary peak), 76.3% ee. [α] 20 D =-51.85 (c = 1.4, CHCl3)

[0692]

[0693] (R)-1-(2',4'-difluoro-[1,1'-biphenyl]-2-yl)ethane-1,2-diol

[0694] (white solid, 85 mg, yield 85%) 1 H NMR(500MHz,MeOD)δ7.65(s,1H),7.44(t,J=7.6Hz,1H),7.34(t,J=7.5Hz,2H),7. 15(d,J=7.0Hz,1H),7.04(t,J=8.5Hz,2H),4.62(s,1H),3.52(s,1H),3.44(s,1H). 13C NMR (125MHz, MeOD) δ165.01 (d, J = 11.7Hz), 163.05 (d, J = 11.7Hz), 141.54 (d, J = 31.9Hz), 134.00 (d, J = 67.8Hz), 131.37, 129.56, 128.43, 127.69 (d, J = 37.5Hz), 125.74 (d, J = 31.0Hz), 112.29 (d, J = 21.9Hz), 104.75 (t, J = 26.3Hz), 72.68, 68.07 (d, J = 41.8Hz). 19 F NMR(471MHz,MeOD)δ-111.50,-111.98,-112.92,-113.06.HRMS(ESI):m / z([M+Na] 1+ )C 14 H 12 The calculated value of F2NaO2 is 273.0698, and the measured value is 273.0703. HPLC (Chiralcel OD-3, n-hexane / 2-propanol=90 / 10, flow rate: 1 ml / min, detection at 230 nm) retention time: t=8.7 min (main peak) and 10.4 min (secondary peak), 91.5% ee. [α] 20 D =-30.8 (c = 2.5, CHCl3)

[0695]

[0696] (R)-1-(Quinolin-2-yl)ethane-1,2-diol

[0697] (white solid, 34.0 mg, yield 45%) 1 H NMR (500MHz, CDCl3) δ8.19(d,J=8.4Hz,1H),8.07(d,J=8.4Hz,1H),7.84(d,J=8.1Hz,1H),7.74(t,J=7.0Hz,1H), 7.56(t,J=7.5Hz,1H),7.43(d,J=8.5Hz,1H),5.03-4.94(m,1H),4.07(dd,J=11.4,3.6Hz,1H),3.93-3.79(m,1H). 13 C NMR (100MHz, CDCl3) δ191.55,175.43,166.26,160.45,157.30,157.20,157.15,154.88,149.52,104.08,95.78.HRMS(ESI):m / z([M+H] 1+ )C11 H 12 The calculated value of NO2 was 190.0863, and the measured value was 190.0864. HPLC (Chiralcel OD-3, n-hexane / 2-propanol=95 / 5, flow rate: 1 ml / min, detection at 250 nm) retention time: t=49.6 min (main peak) and 51.9 min (secondary peak), 97.9% ee.

[0698]

[0699] (R)-1-([1,1'-biphenyl]-3-yl)ethane-1,2-diol

[0700] (white solid, 70.3 mg, yield 82%) 1 H NMR (400MHz, CDCl3) δ7.58(d,J=7.1Hz,3H),7.53(d,J=7.8Hz,1H),7.48-7.39(m,3H),7.3 8-7.30(m,2H),4.89(dd,J=8.2,3.5Hz,1H),3.90-3.54(m,2H),2.81(s,1H),2.29(s,1H). 13 C NMR (100MHz, CDCl3) δ141.72,141.16,141.01,129.15,128.94,127.60,127.32,127.00,125.12,125.03,74.87,68.27.HRMS(ESI):m / z([M+Na] 1+ )C 14 H 14 The calculated value of NaO2 was 237.0886, and the measured value was 237.1011. HPLC (Chiralcel OD-3, n-hexane / 2-propanol=90 / 10, flow rate: 1 ml / min, detection at 210 nm) retention time: t=17.0 min (main peak) and 20.9 min (secondary peak), 87.7% ee.

[0701]

[0702] (R)-4-(1,2-Dihydroxyethyl)benzoic acid methyl ester

[0703] (white solid, 61.2 mg, yield 78%) 1H NMR(400MHz, CDCl3) δ7.98(d,J=8.0Hz,2H),7.40(d,J=8.0Hz,2H),4.84(dd,J=8.3,3.3Hz, 1H), 3.90 (s, 3H), 3.75 (dd, J=11.4, 3.3Hz, 1H), 3.60 (dd, J=11.4, 8.2Hz, 2H), 3.02 (s, 1H). 13 C NMR(100MHz, CDCl3)δ167.11,145.77,129.86,129.65,126.12,74.38,67.88,52.32.HRMS(ESI):m / z([M+H] 1+ )C 10 H 13 The calculated value of O4 was 197.0808, and the measured value was 197.0806. HPLC (Chiralcel OJH, n-hexane / 2-propanol=95 / 5, flow rate: 1 ml / min, detection at 210 nm) retention time: t=69.7 min (main peak) and 74.4 min (secondary peak), 83.3% ee.

[0704]

[0705] (R)-1-(4'-methoxy-[1,1'-biphenyl]-2-yl)ethane-1,2-diol

[0706] (white solid, 39.1 mg, yield 40%) 1 H NMR (400MHz, CDCl3) δ7.57(d,J=7.6Hz,1H),7.44-7.27(m,2H),7.19(d,J=6.7Hz,3H),6.92(d,J =7.9Hz,2H),5.02-4.74(m,1H),3.83(s,3H),3.65-3.45(m,2H),2.77(brs,1H),2.48(brs,1H). 13 C NMR(100MHz, CDCl3)δ158.93,140.93,138.01,133.03,130.43,130.35,127.76,127.70,126.42,113.85,71.22,67.49,55.42.HRMS(ESI):m / z([M+Na] 1+ )C 15 H 16The calculated value of NaO3 was 267.0992, and the measured value was 267.0991. HPLC (Chiralcel OD-3, n-hexane / 2-propanol=90 / 10, flow rate: 1 ml / min, detection at 210 nm) retention time: t=12.9 min (main peak) and 14.9 min (secondary peak), 77.5% ee.

[0707]

[0708] (R)-1-(4-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)ethane-1,2-diol

[0709] (colorless, 59.2 mg, yield 56%) 1 H NMR (400MHz, CDCl3) δ7.81(s,1H),7.77(d,J=7.5Hz,1H),7.51(d,J=7.7Hz,1H),7.40(t,J=7.5Hz,1H),4.8 7(dd,J=8.3,3.5Hz,1H),3.80(d,J=9.3Hz,1H),3.76-3.65(m,1H),2.59(s,1H),2.15(s,1H),1.37(s,12H). 13 C NMR (100MHz, CDCl3) δ140.09,134.33,132.49,129.23,127.96,83.97,75.23,74.75,68.08,24.88,24.84.HRMS(ESI):m / z([M+H] 1+ )C 14 H 21 The calculated value of BNaO4 was 287.1425, and the measured value was 287.1426. HPLC (Chiralcel OD-3, n-hexane / 2-propanol=90 / 10, flow rate: 1 ml / min, detection at 220 nm) retention time: t=7.1 min (main peak) and 8.0 min (secondary peak), 83.1% ee.

[0710] Characterization of Conjugated Diolefin Diols

[0711]

[0712] (2R,3S,E)-2,3-Dihydroxy-5-phenylpent-4-enoic acid ethyl ester

[0713] (colorless oil, 60.5 mg, rr=5 / 1, yield 64%, main product) 1HNMR (400MHz, chloroform-d) δ7.42-7.36(m,2H),7.31(t,J=7.4Hz,2H),7.28-7.22(m,1H),6.70(d,J=15.9Hz,1H),6.34(dd, J=16.0,6.5Hz,1H),4.59(d,J=4.0Hz,1H),4.36-4.19(m,3H),3.31(brs,1H),2.60(brs,1H),1.31(t,J=7.2Hz,3H). 13 C NMR (100 MHz, CDCl3) δ 172.87, 136.33, 132.61, 128.70, 128.10, 127.54, 126.77, 73.96, 73.73, 62.38, 14.29. HPLC (Chiralcel AD-H, n-hexane / 2-propanol=90 / 10, flow rate: 1 ml / min, detection at 210 nm) retention time: t=20.8 min (main peak) and 24.2 min (secondary peak), 95.7% ee.

[0714]

[0715] (2R,3S,E)-5-(2,6-Difluorophenyl)-2,3-dihydroxypent-4-enoic acid ethyl ester

[0716] (white solid, 45.7 mg, yield 42%, main product) 1 H NMR (500MHz, CDCl3) δ7.19-7.10(m,1H),6.86(t,J=8.2Hz,2H),6.69(dt,J=16.4,11.0Hz,2H),4.61(s,1H),4 .31(dd,J=12.8,5.8Hz,2H),4.26(s,1H),3.30(d,J=5.2Hz,1H),2.68(d,J=6.6Hz,1H),1.31(t,J=7.1Hz,3H). 13 C NMR (125MHz, MeOD) δ173.60, δ131.18(t,J=10.6Hz), 118.22(t,J=17.4Hz), 112.80(d,J=26.3 Hz),112.80(d,J=16.5Hz),74.42,74.05,72.99,68.16,60.83,13.95.HRMS(ESI):m / z([M+Na] + )C 13 H 14The calculated value of F2NaO4 is 295.0752, and the measured value is 295.0753. HPLC (Chiralcel AD-H, n-hexane / 2-propanol=90 / 10, flow rate: 1 ml / min, detection at 220 nm) retention time: t=20.9 min (minor peak) and 26.4 min (main peak), 98.5% ee. [α] 20 D =-21.0 (c = 1.6, CHCl3)

[0717]

[0718] (2R,3S,E)-5-(4-bromophenyl)-2,3-dihydroxypent-4-enoic acid ethyl ester

[0719] (white solid, 48.2 mg, yield 50%, rr=3.3 / 1, main product) 1 H NMR (400MHz, CDCl3) δ7.44(d,J=8.4Hz,2H),7.26(d,J=8.4Hz,2H),6.65(d,J=16.0Hz,1H),6.33(dd,J=16.0,6.3Hz,1H),4.59(t, J=5.0Hz,1H),4.36-4.28(m,2H),4.24(dd,J=5.1,2.7Hz,1H),3.18(d,J=5.4Hz,1H),2.42(d,J=7.8Hz,1H),1.32(t,J=7.1Hz,3H). 13 C NMR (101MHz, CDCl3) δ172.78,135.30,131.87,131.39,128.44,128.31,121.97,73.75,73.49,62.53,14.33.HRMS(ESI):m / z([M+Na] + )C 13 H 15 Calculated value of BrNaO4: 337.0046, found value: 337.0046. HPLC (Chiralcel AD-H, n-hexane / 2-propanol = 90 / 10, flow rate: 1 ml / min, detection at 210 nm) retention time: t = 32.3 min (minor peak) and 35.5 min (main peak), 97.9% ee. [α] 20 D =-8.5 (c = 1, CHCl3)

[0720]

[0721] (2R,3S,E)-2,3-Dihydroxy-5-(p-tolyl)pent-4-enoic acid ethyl ester

[0722] (colorless oil, 59 mg, rr=5 / 1, yield 59%, main product) 1 H NMR (400MHz, CDCl3) δ7.34-7.26(m,2H),7.13(d,J=7.7Hz,2H),6.67(d,J=15.9Hz,1H),6.37-6.19(m,1H),4.63-4.52(m,1H) ,4.31(q,J=7.2Hz,2H),4.24(dt,J=4.8,2.2Hz,1H),3.12(d,J=5.7Hz,1H),2.34(s,3H),2.31(s,1H),1.32(t,J=8.0Hz,3H). 13 C NMR (100MHz, CDCl3) δ172.90,138.30,136.27,132.81,128.95,128.63,127.4 6,127.30,124.01,73.91,73.75,62.44,21.51,14.33.HRMS(ESI):m / z([M+Na] + )C 14 H 18 The calculated value of NaO4 was 273.1097, and the measured value was 273.1097. HPLC (Chiralcel AD-H, n-hexane / 2-propanol=90 / 10, flow rate: 1 ml / min, detection at 220 nm) retention time: t=27.2 min (minor peak) and 32.2 min (main peak), 94.0% ee.

[0723]

[0724] (2R,3S,E)-5-(4-Chlorophenyl)-2,3-dihydroxypent-4-enoic acid ethyl ester

[0725] (white solid, 43.8 mg, yield 59%, rr=5 / 1, main product) 1 H NMR (500MHz, CDCl3) δ7.30 (dd, J=18.4, 8.2Hz, 4H), 6.66 (d, J=15.9Hz, 1H), 6.32 (dd, J=16.0, 6.3Hz, 1H), 4.58(s,1H),4.31(dd,J=14.2,7.1Hz,2H),4.24(s,1H),3.23(s,1H),2.48(s,1H),1.32(t,J=7.1Hz,3H). 13C NMR (125MHz, CDCl3) δ172.79,134.88,133.79,131.34,128.91,128.31,127.99,73.83,73.52,62.49,14.32.HRMS(ESI):m / z([M+Na] + )C 14 H 15 The calculated value of ClNaO4 was 293.0551, and the measured value was 293.0550. HPLC (Chiralcel AD-H, n-hexane / 2-propanol=90 / 10, flow rate: 1 ml / min, detection at 210 nm) retention time: t=29.7 min (minor peak) and 31.9 min (main peak), 96.2% ee.

[0726] [α] 20 D =-14.8 (c = 1.3, CHCl3)

[0727]

[0728] (2R,3S)-2,3-Dihydroxy-5,5-diphenylpent-4-enoic acid ethyl ester

[0729] (white solid, 60.6 mg, yield 97%, rr>20 / / 1, main product) 1 H NMR (400MHz, CDCl3) δ7.46-7.31(m,3H),7.30-7.16(m,7H),6.24(d,J=9.5Hz,1H),4.4 6(d,J=9.5Hz,1H),4.29-4.01(m,3H),3.24(s,1H),2.49(s,1H),1.22(t,J=7.0Hz,3H). 13 C NMR (125MHz, CDCl3) δ172.81,145.81,141.67,138.98,129.81,128.41,128.27,12 7.99,127.82,127.79,125.95,74.33,70.67,62.16,14.14.HRMS(ESI):m / z([M+Na] 1+ )C 19 H 20 The calculated value of NaO4 is 335.1254, and the measured value is 335.1253. HPLC (Chiralcel AD-H, n-hexane / 2-propanol=90 / 10, flow rate: 1 ml / min, detection at 210 nm) retention time: t=25.5 min (minor peak) and 34.0 min (main peak), 97.1% ee. [α]20 D =-7.8 (c = 2, CHCl3)

[0730]

[0731] (2R,3S,E)-2,3-Dihydroxy-5-(3-(trifluoromethyl)phenyl)pent-4-enoic acid ethyl ester

[0732] (white solid, 58.6 mg, yield 56%, rr=6.25 / 1, main product) 1 H NMR (500MHz, chloroform-d) δ7.63(s,1H),7.55(d,J=7.6Hz,1H),7.50(d,J=7.6Hz,1H),7.43(t,J=7.7Hz,1H),6.74(d,J=16.0Hz,1H),6.42(dd,J =16.0,6.1Hz,1H),4.62(s,1H),4.31(q,J=7.2Hz,2H),4.26(s,1H),3.31(d,J=5.6Hz,1H),2.62(d,J=7.9Hz,1H),1.32(t,J=7.2Hz,3H). 13 C NMR (125MHz, CDCl3) δ172.75,137.19,131.16(q,J=35.4Hz),131.02,129.94,129.77,129.20,124.62(q,J =3.7Hz),124.18(q,J=272.4Hz),123.39(q,J=3.8Hz),73.80,73.34,62.54,14.28.HRMS(ESI):m / z([M+Na] + )C 14 H 15 The calculated value of F3NaO4 is 327.0815, and the measured value is 327.0815. HPLC (Chiralcel AD-H, n-hexane / 2-propanol=90 / 10, flow rate: 1 ml / min, detection at 210 nm) retention time: t=17.1 min (minor peak) and 20.8 min (main peak), 97.7% ee. [α] 20 D =-11.5 (c = 1.3, CHCl3)

[0733]

[0734] (2R,3S,E)-5-(4-Fluorophenyl)-2,3-dihydroxypent-4-enoic acid ethyl ester

[0735] (white solid, 50 mg, yield 59%, rr=5 / 1, main product) 1 H NMR (400MHz, CDCl3) δ7.37(dd,J=8.5,5.4Hz,2H),7.01(t,J=8.5Hz,2H),6.67(d,J=15.9Hz,1H),6.26(dd,J=15.9,6.5Hz,1H ),4.59(d,J=6.9Hz,1H),4.32(q,J=7.6,7.0Hz,2H),4.24(s,1H),3.16(s,1H),2.37(d,J=7.3Hz,1H),1.32(t,J=7.1Hz,3H). 13 C NMR (100MHz, CDCl3) δ172.85,163.88,161.42,132.51(d,J=3.3Hz),,131.02,128.33(d,J =8.0Hz), 127.33 (d, J = 2.2Hz), 115.66 (d, J = 21.6Hz), 73.75 (d, J = 29.2Hz), 62.45, 14.31. 19 F NMR(377MHz,CDCl3)δ-113.83.HRMS(ESI):m / z([M+Na] 1+ )C 13 H 15 The calculated value of FNaO4 is 277.0847, and the measured value is 277.0847. HPLC (Chiralcel AD-H, n-hexane / 2-propanol=90 / 10, flow rate: 1 ml / min, detection at 210 nm) retention time: t=21.2 min (minor peak) and 29.8 min (main peak), 97.9% ee. [α] 20 D =-12.7 (c = 2.3, CHCl3)

[0736]

[0737] (2R,3S,E)-2,3-Dihydroxy-5-phenylpent-4-enoic acid methyl ester

[0738] (white solid, 43.8 mg, yield 59%, rr=5 / 1, main product) 1H NMR (500MHz, CDCl3) δ7.39 (d, J = 7.7Hz, 2H), 7.31 (t, J = 7.4Hz, 2H), 7.24 (d, J = 6.9Hz, 1H), 6.70 (d, J = 16.0Hz, 1H), 6.34 (dd, J=15.9, 6.5Hz, 1H), 4.60 (d, J=5.7Hz, 1H), 4.27 (s, 1H), 3.84 (s, 3H), 3.29 (s, 1H), 2.57 (s, 1H). 13 C NMR(125MHz, CDCl3)δ173.31,136.31,132.73,128.72,128.15,127.47,126.80,74.02,73.68,53.05.HRMS(ESI):m / z([M+Na] 1+ )C 12 H 14 The calculated value of NaO4 is 245.0784, and the measured value is 245.0781. HPLC (Chiralcel AD-H, n-hexane / 2-propanol=90 / 10, flow rate: 1 ml / min, detection at 210 nm) retention time: t=34.2 min (minor peak) and 37.4 min (main peak), 95.3% ee. [α] 20 D =-19.6 (c = 0.7, CHCl3)

[0739]

[0740] tert-Butyl (2R,3S,E)-2,3-dihydroxy-5-phenylpent-4-enoate

[0741] (white solid, 57.6 mg, yield 60%, rr=10 / 1, main product) 1 H NMR (500MHz, CDCl3) δ7.39 (d, J = 7.3Hz, 1H), 7.31 (t, J = 7.5Hz, 1H), 7.26-7.22 (m, 1H), 6.69 (d, J = 15.9Hz, 1H), 6.33 (dd,J=16.0,6.4Hz,1H),4.52(dd,J=5.4,2.9Hz,1H),4.13(d,J=3.0Hz,1H),3.26(s,1H),2.51(s,1H),1.50(s,9H). 13C NMR (100MHz, CDCl3) δ172.09,136.45,132.40,128.69,128.02,127.82,126.75,83.66,74.02,73.88,28.15.HRMS(ESI):m / z([M+Na] 1+ )C 15 H 20 The calculated value of NaO4 is 287.1254, and the measured value is 287.1253. HPLC (Chiralcel AD-H, n-hexane / 2-propanol=90 / 10, flow rate: 1 ml / min, detection at 210 nm) retention time: t=25.5 min (minor peak) and 30.5 min (main peak), 92.3% ee. [α] 20 D =-16.1 (c = 1, CHCl3)

[0742]

[0743] (white solid, 65.6 mg, yield 62%, rr=8 / 1, main product) 1 H NMR(400MHz, CDCl3) δ7.40-7.20(m,9H),6.66(d,J=15.9Hz,1H),6.30(dd,J=15.9,6.6Hz,1H),5.25 (d,J=2.9Hz,2H),4.60(dd,J=6.8,2.9Hz,1H),4.28(d,J=3.0Hz,1H),3.34(brs,1H),2.70(brs,1H). 13 C NMR (100MHz, CDCl3) δ172.28,136.26,134.95,132.77,128.81,128.78,128.69 ,128.59,128.12,127.29,126.80,74.11,73.77,67.97.HRMS(ESI):m / z([M+Na] + )C 18 H 18 Calculated value of NaO4: 321.1097, 321.1099. HPLC (Chiralcel AD-H, n-hexane / 2-propanol=90 / 10, flow rate: 1 ml / min, detection at 210 nm) retention time: t=43.4 min (minor peak) and 46.6 min (main peak), 96.3% ee. [α] 20 D =-18.2 (c = 1.0, CHCl3)

[0744]

[0745] (2S,3S,E)-5-(Benzofuran-3-yl)-2,3-dihydroxypent-4-enoic acid ethyl ester

[0746] 1 H NMR (400MHz, CDCl3) δ7.87(d,J=7.0Hz,2H),7.58(s,1H),7.45-7.30(m,2H),5.39(d,J=5.1Hz,1H),4. 56(d,J=3.0Hz,1H),4.28(p,J=6.9Hz,3H),3.30(s,1H),2.79(d,J=7.9Hz,1H),1.27(t,J=7.2Hz,2H). 13 C NMR (100MHz, CDCl3) δ169.65,151.89,143.51,125.86,124.41,122.96,119.00,113.41,72.45,67.99,62.22,14.23.HRMS(ESI):m / z([M+Na] + )C 13 H 14 The calculated value of NaO5 is 273.0733, and the measured value is 273.0727. HPLC (Chiralcel AD-H, n-hexane / 2-propanol=90 / 10, flow rate: 1 ml / min, detection at 210 nm) retention time: t=23.9 min (minor peak) and 26.2 min (main peak), 98.5% ee. [α] 20 D =-5.7 (c = 1, CHCl3)

[0747]

[0748] (2S,3S,E)-5-(Benzo[b]thiophen-3-yl)-2,3-dihydroxypent-4-enoic acid ethyl ester

[0749] (colorless oil, 39.8 mg, rr>20 / 1, yield 34%, main product) 1 H NMR (400MHz, CDCl3) δ7.87 (dt, J = 7.4, 1.9Hz, 2H), 7.59 (s, 1H), 7.46-7.33 (m, 2H), 5.46-5.30 (m, 1H), 4. 64-4.47(m,1H),4.38-4.14(m,2H),3.29(d,J=5.4Hz,1H),2.77(d,J=7.8Hz,1H),1.27(t,J=7.2Hz,3H). 13C NMR (100MHz, CDCl3) δ170.66,140.73,136.68,134.16,124.70,124.39,123.11,121.92,72.91,67.22,60.68,14.20.HRMS(ESI):m / z([M+Na] + )C 13 H 14 The calculated value of NaO4S is 289.0505, and the measured value is 289.0505. HPLC (Chiralcel AD-H, n-hexane / 2-propanol=90 / 10, flow rate: 1 ml / min, detection at 220 nm) retention time: t=24.7 min (minor peak) and 27.4 min (main peak), 98.1% ee. [α] 20 D = +10.5 (c = 1, CHCl3)

[0750]

[0751] (2R,3S,E)-5-(4-Cyanophenyl)-2,3-dihydroxypent-4-enoic acid ethyl ester

[0752] (white solid, 78.4 mg, yield 75%) 1 H NMR (400MHz, CDCl3) δ7.61(d,J=8.0Hz,2H),7.48(d,J=8.1Hz,2H),6.74(d,J=16.0Hz,1H),6.47(dd,J=16.0,5.9H z,1H),4.64(s,1H),4.33(q,J=7.1Hz,2H),4.27(d,J=2.7Hz,1H),3.19(s,1H),2.50(s,1H),1.33(t,J=7.1Hz,3H). 13 C NMR (100MHz, CDCl3) δ172.60,140.90,132.60,131.83,130.62,127.26,118.96,112.09,73.58,73.11,62.65,14.33.HRMS(ESI):m / z([M+Na] + )C 14 H 15 The calculated value of NNaO4 is 284.0899, and the measured value is 284.0885. HPLC (Chiralcel AD-H, n-hexane / 2-propanol=90 / 10, flow rate: 1 ml / min, detection at 220 nm) retention time: t=119.7 min (main peak) and 150.2 min (secondary peak), 98.3% ee

[0753] Characterization of Tetrol of Conjugated Dienes

[0754]

[0755] (2R,3S,4S,5R)-6-ethyl-2,3,4,5-tetrahydroxyadipate

[0756] (white solid, 73.6 mg, yield 73%) 1 H NMR (400 MHz, DMSO-d6) δ 5.16 (dd, J = 19.6, 7.5 Hz, 2H), 4.75-4.57 (m, 2H), 4.19 (dd, J = 11.9, 7.5 Hz, 2H), 4.14-3.99 (m, 2H), 3.81 (d, J = 6.3 Hz, 2H), 3.63 (s, 3H), 1.19 (t, J = 7.1 Hz, 3H). HPLC (Chiralcel ADH, n-hexane / 2-propanol = 85 / 15, flow rate: 1 ml / min, detection at 210 nm) retention time: t = 33.5 min (minor peak) and 38.0 min (main peak), > 99.9% ee. [α] 20 D =-5.5 (c = 1, CH3OH) 13 C NMR (100 MHz, DMSO) δ 173.19, 172.68, 72.90, 72.84, 71.18, 69.93, 60.23, 51.56, 14.25. HPLC (Chiralcel AD-H, n-hexane / 2-propanol=85 / 15, flow rate: 1 ml / min, detection at 210 nm) retention time: t=33.5 min (minor peak) and 38.1 min (main peak), >99.9% ee.

[0757]

[0758] (2S,3R,4R,5S)-2,3,4,5-Tetrahydroxyadipate 1-Benzyl 6-ethyl ester

[0759] (white solid, 105 mg, yield 80%) 1 H NMR (400 MHz, methanol-d4) δ 7.46-7.23 (m, 5H), 5.29-5.14 (m, 2H), 4.43 (d, J = 2.1 Hz, 1H), 4.36 (d, J = 2.2 Hz, 1H), 4.22 (q, J = 7.1 Hz, 2H), 4.09 (qd, J = 7.5, 2.1 Hz, 2H), 1.28 (t, J = 7.1 Hz, 3H). 13C NMR(100MHz,MeOD)δ174.16,174.03,137.24,129.49,129.20,129.18,74.20,72.57,72.45,67.84,62.29,14.47.HRMS(ESI):m / z([M+Na] + )C 15 H 20 The calculated value of NaO8 is 351.1050, and the measured value is 351.1055. HPLC (Chiralcel AD-H, n-hexane / 2-propanol=85 / 15, flow rate: 1 ml / min, detection at 210 nm) retention time: t=48.3 min (minor peak) and 58.4 min (main peak), >99.9% ee. [α] 20 D =+13.5(c=1,CH3OH)

[0760]

[0761] (2R,3S,4R,5S)-2,3,4,5-Tetrahydroxy-5-phenylpentanoic acid ethyl ester

[0762] 1 HNMR(400MHz,MeOD)δ7.42(d,J=7.2Hz,2H),7.34(t,J=7.5Hz,2H),7.29-7.22(m,1H),4.81(d,J=5.2H z,1H),4.31(d,J=3.7Hz,1H),4.25-4.10(m,2H),3.77(dt,J=18.7,4.4Hz,2H),1.25(t,J=7.1Hz,3H). 13 C NMR (100 MHz, MeOD) δ 174.11, 143.38, 129.19, 128.50, 128.00, 76.96, 75.07, 73.46, 73.18, 62.22, 14.44. HPLC (Chiralcel ADH, n-hexane / 2-propanol=85 / 15, flow rate: 1 ml / min, detection at 210 nm) retention time: t=25.0 min (minor peak) and 27.3 min (main peak), >99.9% ee

[0763]

[0764] (2R,3S,4R,5S)-2,3,4,5-Tetrahydroxy-5-(3-(trifluoromethyl)phenyl)pentanoic acid ethyl ester

[0765] (white solid, 67.6 mg, yield 50%) 1H NMR (400MHz, MeOD) δ6.88(s,1H),6.79(d,J=7.0Hz,1H),6.71-6.60(m,2H),4.06(d,J=3.7Hz,1H),3.52(d,J= 3.2Hz, 1H), 3.32 (q, J = 7.1Hz, 2H), 2.98 (dd, J = 5.3, 3.2Hz, 1H), 2.91 (t, J = 4.6Hz, 1H), 0.38 (t, J = 7.1Hz, 3H). 13 CNMR(100MHz,MeOD)δ171.78,140.12,131.64,131.35(d,J=31.8Hz),125.81(d,J=271.3Hz) 124.98(q,J= 3.9Hz),124.60(q,J=3.9Hz).δ129.60,76.66,74.04,73.66,73.05,62.68,14.43.HRMS(ESI):m / z([M+Na] + )C 14 H 17 The calculated value of F3NaO6 is 361.0875, and the measured value is 361.0866. HPLC (Chiralcel AD-H, n-hexane / 2-propanol=90 / 10, flow rate: 1 ml / min, detection at 210 nm) retention time: t=23.7 min (minor peak) and 27.5 min (main peak), >99.9% ee. [α] 20 D =+10.2(c=1,CH3OH)

[0766]

[0767] (2R,3S,4R,5S)-5-(2,6-difluorophenyl)-2,3,4,5-tetrahydroxypentanoic acid ethyl ester

[0768] (white solid, 51.4 mg, yield 42%)

[0769] 1 HNMR(400MHz,CD3OD)δ7.42-7.26(m,1H),6.95(t,J=8.5Hz,2H),5.19(d,J=7.8 Hz,1H),4.31-4.07(m,4H),3.50(dd,J=5.2,2.5Hz,1H),1.25(t,J=7.1Hz,3H). 13C NMR(100MHz,CD3OD)δδ173.95,164.06(d,J=8.5Hz),161.59(d,J=8.6Hz),131.17(t,J=10.6Hz),1 18.23(t,J=17.3Hz),113.13-112.55(m),74.45(t,J=2.7Hz),74.04,71.52,67.04,61.48,14.38. 19 F NMR (377MHz, CD3OD) δ-114.21 (t, J = 7.3Hz). HPLC (Chiralcel AD-H, n-hexane / 2-propanol = 85 / 15, flow rate: 1ml / min, detection at 210nm) retention time: t = 27.4min (main peak) and 30.9min (secondary peak), >99.9% ee. [α] 19 D = +6.3 (c = 1, CH3OH)

[0770]

[0771] (2R,3S,4R,5S)-5-(4-bromophenyl)-2,3,4,5-tetrahydroxypentanoic acid ethyl ester

[0772] (white solid, 69.8 mg, yield 50%) 1 H NMR (500MHz, MeOD) δ7.49(d,J=8.4Hz,2H),7.35(d,J=8.5Hz,2H),4.81(d,J=4.5Hz,1H),4. 37(d,J=3.2Hz,1H), 4.21(qd,J=7.2,2.7Hz,2H), 3.84-3.73(m,2H), δ1.26(t,J=7.1Hz,3H). 13 C NMR(125MHz,MeOD)δ173.68,142.85,131.18,128.76,121.97,76.16,74.19,73.31,73.18,62.86,15.18.HRMS(ESI):m / z([M+Na] + )C 13 H 17 Calculated value of BrNaO6 is 371.0101, found value is 371.0096. HPLC (Chiralcel AD-H, n-hexane / 2-propanol=90 / 10, flow rate: 1 ml / min, detection at 210 nm) retention time: t=46.9 min (minor peak) and 60.8 min (main peak), 99.3% ee. [α] 19 D= +9.0 (c = 1, CH3OH)

[0773]

[0774] (2R,3S,4R,5S)-2,3,4,5-Tetrahydroxy-5-(m-tolyl)valerate Ethyl ester

[0775] (white solid, 64.4 mg, yield 55%) 1 H NMR (400MHz, MeOD) δ7.27-7.16(m,3H),7.08(d,J=6.2Hz,1H),4.76(d,J=5.4Hz,1H),4.29(d,J=3.8Hz, 1H),4.22-4.13(m,2H),3.82-3.75(m,1H),3.73(t,J=4.1Hz,1H),2.34(s,3H),1.25(t,J=7.1Hz,3H).. 13 C NMR(100MHz,MeOD)δ174.08,142.39,138.83,129.17,129.11,128.62,125.0 9,76.48,75.15,73.50,72.38,61.30,21.52,14.88.HRMS(ESI):m / z([M+Na] + )C 14 H 20 The calculated value of NaO6 is 307.1152, and the measured value is 307.1155. HPLC (Chiralcel AD-H, n-hexane / 2-propanol=85 / 15, flow rate: 1 ml / min, detection at 210 nm) retention time: t=23.7 min (minor peak) and 27.5 min (main peak), >99.9% ee. [α] 19 D =+10.8(c=1,CH3OH)

[0776]

[0777] (2R,3S,4R,5S)-5-(4-Chlorophenyl)-2,3,4,5-tetrahydroxypentanoic acid ethyl ester

[0778] (white solid, 61 mg, yield 51%) 1H NMR(500MHz,MeOD)δ7.40(d,J=8.1Hz,2H),7.33(d,J=8.0Hz,2H),4.83-4.75(m,1H),4.34(d ,J=3.3Hz,1H),4.25-4.13(m,2H),3.78(d,J=3.7Hz,1H),3.74(s,1H),1.25(t,J=7.1Hz,3H). 13 C NMR(125MHz,MeOD)δ173.72,142.47,134.07,129.57,129.18,76.79,74.24,73.35,73.27,62.27,14.44.HRMS(ESI):m / z([M+Na] + )C 13 H 17 The calculated value of FNaO6 is 327.0606, and the measured value is 327.0603. HPLC (Chiralcel IA, n-hexane / 2-propanol=90 / 10, flow rate: 1 ml / min, detection at 210 nm) retention time: t=40.4 min (minor peak) and 74.9 min (main peak), >99.9% ee. [α] 20 D =+10.4(c=1,CH3OH)

[0779]

[0780] (2R,3S,4R,5S)-5-(4-Fluorophenyl)-2,3,4,5-tetrahydroxypentanoic acid ethyl ester

[0781] (white solid, 57.6 mg, 50% yield) 1 H NMR (500MHz, methanol-d4) δ7.43(dd,J=8.6,5.6Hz,2H),7.06(t,J=8.8Hz,2H),4.82(d,J=3.9Hz,1H),4.3 3(d,J=2.7Hz,1H), 4.18(ddt,J=10.8,6.9,3.8Hz,2H), 3.75(d,J=2.3Hz,2H), 1.26(t,J=7.1Hz,3H). 13 C NMR (101MHz, CD3OD_SPE) δ174.12,164.81,161.98,139.49,129.84,129.76,115.85,115.63,76.89,74.34,73.37,73.27,62.25,14.44. 19F NMR(471MHz,MeOD)δ-117.64.HRMS(ESI):m / z([M+Na] + )C 13 H 17 The calculated value of FNaO6 is 311.0901 and the measured value is 311.0903.

[0782] HPLC (Chiralcel AD-H, n-hexane / 2-propanol=90 / 10, flow rate: 1 ml / min, detection at 210 nm) retention time: t=42.0 min (minor peak) and 46.9 min (main peak), 95.9% ee. [α] 18 D =+10.2(c=1,CH3OH)

[0783]

[0784] (2R,3S,4R,5S)-2,3,4,5-Tetrahydroxy-5-phenylpentanoic acid tert-butyl ester

[0785] (white solid, 60.8 mg, yield 51%) 1 H NMR(500MHz,MeOD)δ7.42(d,J=7.2Hz,2H),7.33(t,J=7.5Hz,2H),7.26(t,J=7.3Hz,1H),4.80(d,J=5.5Hz, 1H),4.17(d,J=4.1Hz,1H),3.79-3.74(m,1H),3.68(t,J=4.2Hz,1H),1.44(s,9H).HRMS(ESI):m / z([M+Na] + )C 15 H 22 The calculated value of NaO6 is 321.1309, and the measured value is 321.1301. HPLC (Chiralcel AD-H, n-hexane / 2-propanol=85 / 15, flow rate: 1 ml / min, detection at 210 nm) retention time: t=20.7 min (minor peak) and 27.9 min (main peak), >99.9% ee. [α] 19 D =+10.6(c=1,CH3OH)

[0786]

[0787] (2R,3S,4R,5S)-2,3,4,5-Tetrahydroxy-5-phenylpentanoic acid benzyl ester

[0788] (white solid, 71.8 mg, yield 54%) 1H NMR (400MHz, MeOD) δ7.41-7.25 (m, 10H), 5.16 (s, 2H), 4.81 (d, J = 4.3Hz, 1H), 4.38 (s, 1H), 3.79 (s, 2H). 13 CNMR(100MHz,MeOD)δ173.43,143.23,137.15,129.50,129.21,129.19,129.1 7,128.47,127.39,76.96,75.12,73.58,73.16,68.22.HRMS(ESI):m / z([M+Na] + )C 18 H 20 The calculated value of NaO6 is 355.1152, and the measured value is 355.1148. HPLC (Chiralcel AD-H, n-hexane / 2-propanol=90 / 10, flow rate: 1 ml / min, detection at 210 nm) retention time: t=74.4 min (minor peak) and 78.4 min (main peak), >99.9% ee. [α] 20 D =+13.9(c=1,CH3OH)

[0789]

[0790] (2R,3S,4R,5S)-2,3,4,5-Tetrahydroxy-5-phenylpentanoic acid methyl ester

[0791] (white solid, 56.3 mg, yield 55%) 1 H NMR(400MHz,MeOD)δ7.42(d,J=7.6Hz,2H),7.33(t,J=7.4Hz,2H),7.26(t,J=7.3Hz,1H),4 .80(d,J=4.7Hz,1H),4.34(s,1H),3.80(dt,J=6.7,4.2Hz,1H),3.76(s,1H),3.72(s,3H). 13 C NMR(100MHz,MeOD)δ169.45,142.67,129.20,128.51,128.00,76.88,75.09,73.49,70.91,52.54.HRMS(ESI):m / z([M+Na] + )C 12 H 16The calculated value of NaO6 is 279.0839, and the measured value is 295.0834. HPLC (Chiralcel IC-3, n-hexane / 2-propanol=85 / 15, flow rate: 1 ml / min, detection at 210 nm) retention time: t=63.7 min (minor peak) and 67.6 min (main peak), >99.9% ee. [α] 20 D =+8.2(c=1,CH3OH)

[0792]

[0793] (2R,3S,4R,5S)-5-(4-Cyanophenyl)-2,3,4,5-tetrahydroxypentanoic acid ethyl ester

[0794] (white solid, 41.3 mg, yield 35%) 1 H NMR (400MHz, CDCl3) δ7.64(d,J=7.9Hz,2H),7.54(d,J=8.0Hz,2H),4.91(d,J=5.1Hz,1H),4.38-4.17(m,3H),4.14-3.13(m,6H),1.26(t,J=7.1Hz,3H). 13 C NMR (101MHz, CDCl3) δ172.43,145.88,132.37,127.68,118.81,111.84,75.99,74.08,72.99,71.24,62.63,14.20.HRMS(ESI):m / z([M+Na] + )C 14 H 17 The calculated value of NNaO6 is 318.0954, and the measured value is 318.0944.

[0795] result

[0796] The structure of the iron catalyst formed by PQCN-n (n = 1 to 8) and BQCN ligands is shown below. X-ray diffraction analysis shows that [Fe(S,S-PQCN-1)(OTf)2] is a cis-α configuration ( Figure 1 ).

[0797]

[0798] Asymmetric iron catalyst was used for asymmetric cis-dihydroxylation of styrene. Under air, 3 equivalents of H2O2 dissolved in methanol were added to a methanol solution containing styrene substrate and 6 mol% catalyst at -30°C by a syringe pump within 30 min. The reaction was then stirred for another 5 h. The results are shown in Table 1. As shown in Table 1, [Fe(S,S-PQCN-1)(OTf)2] gave the cis-diol of styrene in 66% yield and 75% ee. When compared with the reported iron-catalyzed AD of styrene ([Fe(6-Me2-BPBPP)(OTf)2] (Angew. Chem. Int. Ed. 2008, 47, 1887-1889) and [Fe(2-Me2-BQCN)(OTf)2] (Angew. Chem. Int. Ed. 2016, 55, 10253-10257)), the enantioselectivity of the AD reaction of styrene was greatly improved (ee obtained using different catalysts: [Fe(S,S-PQCN-1)(OTf)2] = 75%, [Fe(S,S-PQCN-6) (OTf)2] = 84%; cf. ([Fe(6-Me2-BPBPP)(OTf)2] = 15%, [Fe(2-Me2-BQCN)(OTf)2] = 17.5%). Further screening of the catalysts showed that 4mol% [Fe(S,S-PQCN-6)(OTf)2] gave 89% yield and 80% ee, and 6mol% [Fe(S,S-PQCN-6)(OTf)2] gave 85% yield and 84% ee. When 10mol% [Fe(S,S-PQCN-6)(OTf)2] was used, the product yield dropped to 66%, but the ee value remained unchanged.

[0799] Table 1. Screening of iron complexes in the asymmetric cis-dihydroxylation of styrene

[0800]

[0801]

[0802] [a] Reaction conditions: 1a (0.4 mmol), Fe catalyst (6 mol%), H2O2 (3 equiv., 1.2 mmol, dissolved in 1 mL CH3OH), CH3OH (5 mL) under air at -30°C. [ii] Isolated yield. [c] Enantiomeric excess (ee) determined by chiral HPLC. [d] 4 mol% catalyst. [e] 10 mol% catalyst.

[0803] Various substrates were then investigated following the reaction scheme shown in Table 2. The reaction conditions were as follows: H2O2 (3 eq., 1.2 mmol, dissolved in 1 mL CH3OH) was added to a CH3OH (5 mL) solution containing styrene (1 eq., 0.4 mmol) and [Fe(S,S-PQCN-6)(OTf)2] (6 mol%, 0.024 mmol) using a syringe pump over 30 min; after the addition of H2O2, the reaction was stirred at -30 °C for another 30 min. The products, isolated yields, and ee for each styrene substrate are summarized in Table 2. In general, styrene substrates with one or more electron-withdrawing groups resulted in higher enantioselectivities than substrates with one or more electron-donating groups, but the enantioselectivity decreased slightly when the substituent was at the ortho position (67.5-72.1% ee, 2t and 2u). Interestingly, when there was a benzene ring at the ortho position, the enantioselectivity was significantly improved (91.5-94.9% ee, 2q, 2r, and 2w). For styrenes with electron-withdrawing groups at the meta position, the reaction proceeded well, especially for styrenes with NO2 groups and two CF3 groups (84.3-94.7% ee, 2i-2n and 2s). For substrates with substituents at the para position, the highest ee value was 88.9% (2h; with NO2 group). In addition, excellent enantioselectivity was obtained for 2-vinylquinoline (98% ee, 2x).

[0804] Table 2. AD reactions of various styrenes

[0805]

[0806]

[0807] For the asymmetric cis-dihydroxylation of electron-deficient conjugated dienes, reaction conditions were screened using ethyl (2E,4E)-5-phenylpenta-2,4-dienoate as a model substrate. When 3 mol% [Fe(S,S-PQCN-6)(OTf)2] was used as a catalyst and 2 equivalents of H2O2 were added via a syringe pump within 30 min at room temperature, the cis-diols were obtained with a regioselectivity of >20 / 1, a product yield of 67%, and 91.7% ee. Under these conditions, a series of substrates were tested, all of which gave the corresponding cis-diols (4b-4o) in good yields and high regioselectivities (>20 / 1) and excellent ee values ​​(82.3-99.5%) (Table 3). It should be emphasized that for the osmium catalytic system, the AD reaction preferentially occurs at the C=C bond farthest from the ester group (J. Am. Chem. Soc. 1992, 114, 7570-7571) because the osmium catalytic system prefers the more electron-rich C=C bond. Without being bound by any theory, it is believed that for the iron catalyst described herein, the AD reaction will preferentially occur at the C=C bond closest to the electron-withdrawing ester group, which indicates that the reactivity and uniqueness of the iron catalyst are quite different. Increasing the amount of [Fe(S,S-PQCN-6)(OTf)2] to 10 mol% and increasing H2O2 to 10 equivalents (one-time addition) resulted in the formation of 1,2,3,4-tetraols (5a, 5b) with 14-25% yield and 99.9% ee (Table 4).

[0808] The activity of [Fe(S,S-2-Me2-BQCN)(OTf)2] was also tested in the AD reaction of conjugated dienes (Table 5). Using 5 mol% [Fe(S,S-2-Me2-BQCN)(OTf)2] and adding 3 equivalents of H2O2 by syringe pump within 30 minutes resulted in AD of the double bond close to the ester group as the major product (4a) in 64% yield and 95.7% ee, but with a regioselectivity of 5 / 1. Interestingly, HPLC analysis showed that the stereochemistry of the cis-diol product 4a obtained with [Fe(S,S-2-Me2-BQCN)(OTf)2] was opposite to that of the cis-diol product 4a obtained with [Fe(S,S-PQCN-6)(OTf)2]. Under the conditions of 10 mol% [Fe(S,S-2-Me2-BQCN)(OTf)2] and 3 equivalents of H2O2 added at one time, the reaction gave 1,2,3,4-tetraol 5c in 54% yield and >99.9% ee. The substrate scope was further explored and the results are shown in Table 6. The yield of the tetraol product ranged from 35 to 80% and the ee ranged from 95.7 to 99.9%. The X-ray crystal structure of 5h showed that it has a (2R,3S,4R,5S) configuration ( Figure 2Importantly, when we used a commercially available osmium-based reagent (AD-mix α) to catalyze the AD reaction of ethyl (2E,4E)-5-phenylpenta-2,4-dienoate according to a literature method (J. Org. Chem. 1992, 57, 2768-2771), no tetraol product (5c) was detected from the reaction.

[0809] Table 3. AD of conjugated dienes catalyzed by [Fe(S,S-PQCN-6)(OTf)2] for the formation of cis-diols a

[0810]

[0811] a Reaction conditions for the formation of cis-diol: H2O2 (2 equivalents, 0.8 mmol, dissolved in 667 μL CH3OH) was added to a CH3OH (11.333 mL) solution containing a conjugated diene (1 equivalent, 0.4 mmol) and [Fe(S,S-PQCN-6)(OTf)2] (3 mol%, 0.012 mmol) at room temperature using a syringe pump over 30 minutes. After the addition of H2O2, the reaction mixture was stirred at room temperature for another 30 minutes. The conversion was determined by separating the unreacted substrate. The yield of the isolated product was determined based on the conversion.

[0812] Table 4. AD of conjugated dienes catalyzed by [Fe(S,S-PQCN-6)(OTf)2] for the formation of tetraols b

[0813]

[0814] b Reaction conditions for the formation of tetraols: H2O2 (3 eq., 1.2 mmol, dissolved in 1 mL CH3OH) was added directly to a solution of conjugated diene (1 eq., 0.4 mmol) and [Fe(S,S-PQCN-6)(OTf)2] (10 mol%, 0.04 mmol) in CH3OH (11 mL) at room temperature. The reaction was then stirred at room temperature for an additional 1 h. The yields of the isolated products are shown.

[0815] Table 5. AD of conjugated dienes catalyzed by [Fe(S,S-2-Me2-BQCN)(OTf)2] for the formation of cis-diols c

[0816]

[0817] CReaction conditions: H2O2 (3 eq., 1.2 mmol, dissolved in 1 mL CH3OH) was added to a solution of conjugated diene (1 eq., 0.4 mmol) and [Fe(S,S-2-Me2-BQCN)(OTf)2] (5 mol%, 0.02 mmol) in CH3OH (11 mL) at room temperature using a syringe pump over 30 minutes. The reaction was then stirred at room temperature for an additional 30 minutes.

[0818] Table 6. AD of conjugated dienes catalyzed by [Fe(S,S-2-Me2-BQCN)(OTf)2] for the formation of tetraols d

[0819]

[0820] d Reaction conditions: H2O2 (3 eq., 1.2 mmol, dissolved in 1 mL CH3OH) was added directly to a solution of conjugated diene (1 eq., 0.4 mmol) and [Fe(S,S-2-Me2-BQCN)(OTf)2] (10 mol%, 0.04 mmol) in CH3OH (11 mL) at room temperature. The reaction was then stirred at room temperature for another 1 h. The yield of the isolated product is shown.

[0821] The mechanism of the reaction was investigated by DFT calculations. By using Fe-dioxo species as catalytic intermediates, DFT calculations showed that the favorable (TS 有利 ) and unfavorable (TS 不利 ) enantiomers have transition state energies of 13.0 kcal / mol and 14.2 kcal / mol, respectively. The energy difference of 1.2 kcal / mol corresponds to an ee value of 85% at -30 °C, which shows good agreement with the experimentally determined ee (80-84%). The study found that the energy difference mainly originates from the non-covalent interaction and steric repulsion between the Fe-dioxo species and styrene. TS 有利 Showing the CH···π interaction between the methyl group of pyridine and styrene ( Figure 3A ), while TS 不利 The distance between the methyl group and styrene (H···H distance 2.30 and ) and the less effective π···π interactions (poor overlap between styrene and quinoline, Figure 3B ). Therefore, the TS energy difference between the enantiomers is mainly caused by the interaction between the methyl group of Fe-dioxo and the substrate. Interestingly, we also found that in the optimized d CC There is a very good correlation between the distance between the two methyl groups of the dioxo intermediate and the experimental ee value ( Figure 4 ). This intrinsic structure-property relationship may aid in the design of more efficient catalysts for the enantioselective cis-dihydroxylation of styrene.

[0822] In summary, a series of unsymmetric Fe-N4 complexes were developed that catalyze the asymmetric cis-dihydroxylation of styrene with good to excellent enantioselectivity and product yields, which can serve as green alternatives to osmium-catalyzed AD reactions due to their high toxicity and cost. The iron catalysts and methods disclosed herein provide simple, practical, and sustainable access to chiral cis-diols of electron-deficient conjugated dienes with different substituents in up to 99% yield and up to 99.9% ee.

[0823] References:

[0824] M.-Y.Cao,et al.,Tetrahedron Lett.2015,56,3732-3742.

[0825] Y.Li,et al.,Angew.Chem.,Int.Ed.2020,59,7990-8003.

[0826] J.Lin,et al.,The Chemical Record2019,19,440-451.

[0827] HCKolb, et al., Chem. Rev.1994,94,2483-2547.

[0828] CJ Bataille, et al., Chem.Soc.Rev.2011,40,114-128.

[0829] MM Heravi, et al., Tetrahedron: Asymmetry 2017, 28, 987-1043.

[0830] RVOttenbacher, et al., Russ.Chem.Rev.2019,88,1094-1103.

Claims

1. An iron-based catalyst having the following structure: in: (a) L1 is a bond or R 16 , R 16 '、R 17 , and R 17 ' is independently hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted aryl, substituted or unsubstituted polyaryl, or substituted or unsubstituted cyclic group, or R 16 With R 16 ' and / or R 17 With R 17 ' forms a substituted or unsubstituted aryl group, a substituted or unsubstituted polyaryl group, or a substituted or unsubstituted cyclic group, and p is an integer from 1 to 10; (b)R 18 , R 23 , R 24 , R 18 '、R 23 ' and R 24 ' is independently hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted aryl, substituted or unsubstituted alkylaryl, or substituted or unsubstituted polyaryl; (c)R 19 is a substituted or unsubstituted alkyl, a substituted or unsubstituted alkenyl, a substituted or unsubstituted aryl, a substituted or unsubstituted alkylaryl, or a substituted or unsubstituted polyaryl; (d) R 22 , R 22 ' and R 31 ~R 34 are independently hydrogen, substituted or unsubstituted alkyl, halogen, amino, or alkoxy; (e)R 25 and R 25 ' is independently a leaving group; and (f) the substituents are independently substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted cyclic group, substituted or unsubstituted heterocyclic group, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, substituted or unsubstituted polyaryl, substituted or unsubstituted polyheteroaryl, substituted or unsubstituted aralkyl, carbonyl, halide, hydroxy, phenoxy, aryloxy, alkylthio, phenylthio, arylthio, cyano, isocyano, alkoxy, nitro, carboxyl, amino, amide, oxo, silyl, sulfinyl, sulfonyl, sulfonic acid, phosphonium, phosphanyl, phosphoryl, phosphonyl, or thiol, or a combination thereof.

2. The iron-based catalyst of claim 1, wherein R 22 , R 22 ' and R 31 ~R 34 independently hydrogen, -NRR', methoxy, or ethoxy, wherein R and R' are independently hydrogen or unsubstituted alkyl, such as unsubstituted C1-C6 alkyl, for example methyl.

3. The iron-based catalyst of claim 2, wherein R 32 ~R 34 It's hydrogen.

4. The iron-based catalyst of claim 1, wherein the compound has the following structure:

5. The iron-based catalyst of claim 1, wherein L1 is Each occurrence of T′ is a substituted or unsubstituted monocyclic group or a substituted or unsubstituted polycyclic group, and p is an integer from 1 to 3, or 1 or 2.

6. The iron-based catalyst of claim 5, wherein T' is a substituted or unsubstituted C3-C6 monocyclic alkyl group, and optionally wherein the substituents, when present, are independently unsubstituted phenyl or phenyl substituted with one or more unsubstituted alkyl groups, such as one or more unsubstituted C1-C6 alkyl groups.

7. The iron-based catalyst of claim 1, wherein L1 is Each occurrence of R 16 and R 16 ' is independently substituted or unsubstituted phenyl, and p is an integer from 1 to 3, or 1 or 2.

8. The iron-based catalyst of claim 7, wherein R 16 and R 16 ' is an unsubstituted phenyl group.

9. The iron-based catalyst of claim 1, wherein R 25 and R 25 ' is independently a triflate, tosylate, mesylate, halide, nitrate, phosphate, thioether, amino, carboxylate, phenoxide, alkoxy, or amide.

10. The iron-based catalyst of claim 1, wherein R 25 and R 25 ' is a triflate.

11. The iron-based catalyst of claim 1, wherein R 18 It is an unsubstituted C1-C6 alkyl group, such as methyl or ethyl.

12. The iron-based catalyst of claim 1, wherein R 18 ' is unsubstituted C1~C 10 alkyl, unsubstituted C1-C8 alkyl, unsubstituted C1-C6 alkyl, unsubstituted C1-C4 alkyl, unsubstituted C1-C3 alkyl (such as methyl, ethyl, isopropyl, etc.), or X' is carbon or nitrogen; p and q are independently integers from 0 to 5, and each occurrence of R3 is independently hydrogen, a halide (eg, fluoride, chloride, bromide), an unsubstituted C1-C 10 Alkyl (eg, methyl, ethyl, isopropyl, tert-butyl, etc.), or unsubstituted phenyl, or two adjacent R3 together with the carbon to which they are attached form an unsubstituted aryl or unsubstituted polyaryl.

13. The iron-based catalyst of claim 1, wherein R 18 ' is methyl or Wherein X' is nitrogen or carbon, p is 1, q is an integer from 1 to 4, and each occurrence of R3 is independently hydrogen, halide, unsubstituted C1-C6 alkyl, unsubstituted phenyl, or two adjacent R3 together with the carbon to which they are attached form an unsubstituted aryl group.

14. The iron-based catalyst of claim 1, wherein R 19 is a substituted or unsubstituted alkylene group, and optionally is a substituted or unsubstituted methylene or ethylene group.

15. The iron-based catalyst of claim 1, wherein R 19 It is an unsubstituted methylene group or a methylene group substituted by an unsubstituted C1-C6 alkyl group, an unsubstituted phenyl group, or an unsubstituted C3-C6 monocycloalkyl group.

16. The iron-based catalyst of claim 1, wherein R 23 and R 23 ' is hydrogen, and R 24 and R 24 ' are independently unsubstituted C1~C 10 Alkyl, unsubstituted C1-C8 alkyl, unsubstituted C1-C6 alkyl, unsubstituted C1-C4 alkyl, or unsubstituted C1-C2 alkyl, such as methyl, etc.

17. The iron-based catalyst of claim 1, wherein the compound has the structure:

18. A process for the asymmetric cis-dihydroxylation of styrene or a derivative thereof catalyzed by an iron-based catalyst as claimed in claim 1, the process comprising: (i) maintaining the reaction mixture at a temperature and for a period of time sufficient to form a product, wherein the reaction mixture comprises the styrene or a derivative thereof, the iron-based catalyst, an oxidant, and a solvent, wherein the product comprises cis-diol, and Optionally wherein the oxidizing agent is hydrogen peroxide.

19. The method of claim 18, wherein the styrene or a derivative thereof has the following structure: And the cis-diol has the following structure: wherein A1 is substituted aryl, unsubstituted aryl, substituted polyaryl, unsubstituted polyaryl, substituted heteroaryl, unsubstituted heteroaryl, substituted heteropolyaryl, or unsubstituted heteropolyaryl.

20. The method of claim 19, wherein the styrene or a derivative thereof has the following structure: And the cis-diol has the following structure: in: (a) X1-X5 are independently carbon, nitrogen, oxygen, or sulfur; (b) n1 is an integer from 0 to 5; (c) each occurrence of R is independently hydrogen, substituted alkyl, unsubstituted alkyl, substituted alkylaryl, unsubstituted alkylaryl, substituted aryl, unsubstituted aryl, substituted heterocyclic, unsubstituted heterocyclic, hydroxy, halide, haloalkyl (such as a haloalkyl, e.g., —CF ), nitro, amino, amido, alkoxy, cyano, or carbonyl, or two adjacent R groups together with the carbon atoms to which they are attached form a substituted aryl, unsubstituted aryl, substituted polyaryl, unsubstituted polyaryl, substituted heteroaryl, unsubstituted heteroaryl, substituted heteropolyaryl, unsubstituted heteropolyaryl, substituted cycloalkyl, unsubstituted cycloalkyl group, substituted cycloalkenyl, unsubstituted cycloalkenyl group, substituted cycloalkynyl, unsubstituted cycloalkynyl group, substituted heterocyclic group, or unsubstituted heterocyclic group; and (d) the substituents are independently substituted alkyl, unsubstituted alkyl, substituted cycloalkyl, unsubstituted cycloalkyl groups, substituted cycloalkenyl, unsubstituted cycloalkenyl groups, substituted cycloalkynyl, unsubstituted cycloalkynyl groups, substituted heterocyclic groups, unsubstituted heterocyclic groups, substituted aryl, unsubstituted aryl, substituted heteroaryl, unsubstituted heteroaryl, substituted polyaryl, unsubstituted polyaryl, substituted heteropolyaryl, unsubstituted heteropolyaryl, substituted alkylaryl, unsubstituted aralkyl, haloalkyl, carbonyl, halide, hydroxy, alkoxy, nitro, cyano, amino, amido, oxo, or thiol, or a combination thereof.

21. A process for the asymmetric cis-dihydroxylation of a conjugated diene catalyzed by the iron-based catalyst of claim 1, the process comprising: (i) maintaining the reaction mixture at a temperature and for a period of time sufficient to form a product, wherein the reaction mixture comprises the conjugated diene, the iron-based catalyst, an oxidant, and a solvent, wherein the product comprises a cis-diol or a tetraol, and Optionally wherein the oxidizing agent is hydrogen peroxide.

22. The process of claim 21, wherein the amount of the iron-based catalyst in the reaction mixture is at most 6 mol%, at most 5 mol%, at most 3 mol%, at least 0.1 mol%, at least 0.5 mol%, in the range of about 0.1 mol% to about 6 mol%, in the range of about 0.1 mol% to about 5 mol%, in the range of about 0.1 mol% to about 3 mol%, in the range of about 0.5 mol% to about 6 mol%, in the range of about 0.5 mol% to about 5 mol%, in the range of about 0.5 mol% to about 3 mol%, in the range of about 1 mol% to about 6 mol%, or in the range of about 1 mol% to about 5 mol%.

23. The method of claim 22, wherein the conjugated diene has the following structure: And the product comprises a cis-diol having the following structure: in: (a) A2 is substituted aryl, unsubstituted aryl, substituted polyaryl, unsubstituted polyaryl, substituted heteroaryl, unsubstituted heteroaryl, substituted heteropolyaryl, unsubstituted heteropolyaryl, or carbonyl; (b) R5 is -C(=O)OR6, R6 is hydrogen, substituted alkyl, unsubstituted alkyl, substituted aryl, unsubstituted aryl, substituted polyaryl, unsubstituted polyaryl, substituted heteroaryl, unsubstituted heteroaryl, substituted heteropolyaryl, unsubstituted heteropolyaryl, substituted alkylaryl, or unsubstituted alkylaryl; (c) R'1 to R'4 are independently hydrogen, substituted alkyl, unsubstituted alkyl, substituted aryl, unsubstituted aryl, substituted polyaryl, unsubstituted polyaryl, substituted heteroaryl, unsubstituted heteroaryl, substituted heteropolyaryl, unsubstituted heteropolyaryl, substituted alkylaryl, or unsubstituted alkylaryl, substituted cycloalkyl, unsubstituted cycloalkyl, substituted cycloalkenyl, unsubstituted cycloalkenyl, substituted cycloalkynyl, unsubstituted cycloalkynyl, substituted heterocycle, or unsubstituted heterocycle; and (d) the substituents are independently substituted alkyl, unsubstituted alkyl, substituted cycloalkyl, unsubstituted cycloalkyl groups, substituted cycloalkenyl, unsubstituted cycloalkenyl groups, substituted cycloalkynyl, unsubstituted cycloalkynyl groups, substituted heterocyclic groups, unsubstituted heterocyclic groups, substituted aryl, unsubstituted aryl, substituted heteroaryl, unsubstituted heteroaryl, substituted polyaryl, unsubstituted polyaryl, substituted heteropolyaryl, unsubstituted heteropolyaryl, substituted alkylaryl, unsubstituted aralkyl, haloalkyl, carbonyl, halide, hydroxy, alkoxy, nitro, cyano, amino, amido, oxo, or thiol, or a combination thereof.

24. The method of claim 21, wherein the amount of iron-based catalyst in the reaction mixture is >6 mol%, at least 7 mol%, at least 8 mol%, in the range of about 6.5 mol% to about 20 mol%, in the range of about 7 mol% to about 20 mol%, in the range of about 7 mol% to about 15 mol%, in the range of about 6.5 mol% to about 15 mol%, in the range of about 8 mol% to about 20 mol%, in the range of about 8 mol% to about 15 mol%, in the range of about 7 mol% to about 12 mol%, or in the range of about 8 mol% to about 12 mol%, such as about 10 mol%.

25. The method of claim 24, wherein the conjugated diene has the following structure: And the product comprises a tetraol having the following structure: in (a) A2 is substituted aryl, unsubstituted aryl, substituted polyaryl, unsubstituted polyaryl, substituted heteroaryl, unsubstituted heteroaryl, substituted heteropolyaryl, unsubstituted heteropolyaryl, or carbonyl; (b) R5 is -C(=O)OR6, R6 is hydrogen, substituted alkyl, unsubstituted alkyl, substituted aryl, unsubstituted aryl, substituted polyaryl, unsubstituted polyaryl, substituted heteroaryl, unsubstituted heteroaryl, substituted heteropolyaryl, unsubstituted heteropolyaryl, substituted alkylaryl, or unsubstituted alkylaryl; (c) R'1 to R'4 are independently substituted alkyl, unsubstituted alkyl, substituted aryl, unsubstituted aryl, substituted polyaryl, unsubstituted polyaryl, substituted heteroaryl, unsubstituted heteroaryl, substituted heteropolyaryl, unsubstituted heteropolyaryl, substituted alkylaryl, or unsubstituted alkylaryl, substituted cycloalkyl, unsubstituted cycloalkyl, substituted cycloalkenyl, unsubstituted cycloalkenyl, substituted cycloalkynyl, unsubstituted cycloalkynyl, substituted heterocycle, or unsubstituted heterocycle; and (d) the substituents are independently substituted alkyl, unsubstituted alkyl, substituted cycloalkyl, unsubstituted cycloalkyl groups, substituted cycloalkenyl, unsubstituted cycloalkenyl groups, substituted cycloalkynyl, unsubstituted cycloalkynyl groups, substituted heterocyclic groups, unsubstituted heterocyclic groups, substituted aryl, unsubstituted aryl, substituted heteroaryl, unsubstituted heteroaryl, substituted polyaryl, unsubstituted polyaryl, substituted heteropolyaryl, unsubstituted heteropolyaryl, substituted alkylaryl, unsubstituted aralkyl, haloalkyl, carbonyl, halide, hydroxy, alkoxy, nitro, cyano, amino, amido, oxo, or thiol, or a combination thereof.

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