Method for preparing 4-substituted furanose derivatives

Abstract

The present invention provides a method for preparing a 4-substituted furanoside derivative, comprising the following steps: reacting an aldehyde, carbon monoxide and a silane under catalyst conditions to obtain a silyl-protected 4-substituted furanoside derivative; the catalyst includes a rhodium catalyst; the silane is a silane compound containing at least one Si-H bond. The advantages of the preparation method in the present invention are that the reaction process is simple, and 1,2,3-O-trisilyl-4-aryl / alkyl-substituted furanoside can be obtained only by one-step reaction, and 1,2-O-isopropylidene-4-aryl / alkyl-substituted furanoside which is easier to purify can be obtained by two-step one-pot reaction; the raw materials are simple and easily available, being common aliphatic aldehydes or aromatic aldehydes, silanes and carbon monoxide; the substrate range is wide, and it has good compatibility with various aldehyde substrates, and different substituted 4-aryl / alkyl-substituted furanoside derivatives can be obtained by reacting with different aldehydes.

Description

Technical Field

[0001] The present invention belongs to the technical field of organic synthesis, and particularly relates to a method for preparing 4-substituted furanosyl derivatives. Background Art

[0002] Carbohydrate compounds have wide applications in the pharmaceutical field. As a special carbohydrate compound, 4-substituted furanosyl has great application potential.

[0003] Currently, the synthesis of 4-alkyl furanosyl derivatives mainly starts from glucose or xylose. Using diacetone-D-glucose as the raw material, through deprotection and oxidative cleavage, 5-aldehyde-1,2-O-isopropylidene-α-D-xylofuranose is obtained, and then through the Wittig reaction, 4-alkenyl furanosyl derivatives are obtained, and finally through hydrogenation reduction, 4-alkyl furanosyl derivatives are obtained (Tetrahedron Letters 1978, 19, 2095-2098.; Tetrahedron Letters 1978, 19, 3233-3236). Using 1,2-O-isopropylidene-α-D-xylofuranose as the raw material, first through sulfonylation reaction, 1,2-O-isopropylidene-5-O-p-toluenesulfonyl-α-D-xylofuranose is obtained, and then through nucleophilic substitution reaction with Grignard reagent, 4-alkyl furanosyl derivatives are obtained (Tetrahedron Letters 1978, 19, 3301-3303). In the above two synthesis methods, multiple steps of reactions are required, the synthesis steps are relatively cumbersome, the use of highly active reagents leads to low reaction compatibility, and it is limited to the synthesis of 4-alkyl furanosyl derivatives.

[0004] For 4-aryl furanosyl derivatives, currently, their synthesis is mainly achieved through photocatalytic coupling of glycosyl and aryl. For example, the work published by Gary A. Molander et al. in 2018 (Angew.Chem. Int. Ed. 2018, 57, 6614-6618), in which a 4-(2,6-dimethyl-3,5-ethoxycarbonyl-1,4-dihydropyridine) (DHP) directing group is introduced at the 4-position of the protected furanosyl to obtain a special sugar substrate, and then using 4CzIPN as the photosensitizer and NiBr2·dme / dMeObpy as the catalyst, coupling reaction with aryl bromide occurs under blue light irradiation to obtain 4-alkyl furanosyl. This method has a wide substrate compatibility, but its sugar substrate needs to be pre-synthesized, increasing the synthesis steps, and the reaction requires photocatalysis, resulting in limited application of the reaction. In addition, this reaction is limited to the synthesis of 4-aryl furanosyl derivatives. In other synthesis methods of 4-aryl furanosyl derivatives, the substrates are greatly restricted.

[0005] In summary, the current methods for synthesizing 4-substituted furanoside derivatives have problems such as limited substrates, cumbersome synthesis steps, and the need for pre-synthesis of raw materials. There is still a lack of a simple modular synthesis method for 4-substituted furanoside derivatives. Summary of the Invention

[0006] The object of the present invention is to provide a preparation method for 4-substituted furanoside derivatives. The preparation method in the present invention has short synthesis steps, a simple reaction system, easily accessible raw materials, a wide substrate range, and is conducive to the subsequent research and application of 4-substituted furanoside derivatives.

[0007] The present invention provides a preparation method for 4-substituted furanoside derivatives, comprising the following steps:

[0008] React an aldehyde, carbon monoxide, and a silane under catalyst conditions to obtain a silicon-based protected 4-substituted furanoside derivative;

[0009] The catalyst includes a rhodium catalyst;

[0010] The silane is a silicon hydride containing at least one Si-H bond.

[0011] Preferably, the silane is HSiR 2 R 3 R 4 wherein the R 2 and R 3 and R 4 are independently selected from one or more of substituted or unsubstituted C1-C10 alkyl groups, substituted or unsubstituted C6-C20 aryl groups, substituted or unsubstituted C7-C20 aralkyl groups, and C1-C10 alkoxy groups;

[0012] The substituents in the substituted C1-C10 alkyl group are independently selected from one or more of hydroxyl groups, alkoxy groups, and halogens;

[0013] The substituents in the substituted C6-C20 aryl group are independently selected from one or more of C1-C10 alkoxy groups, C1-C10 alkyl groups, and halogens.

[0014] Preferably, R 2 and R 3 are independently selected from substituted or unsubstituted C1-C10 alkyl groups, and R 4 is selected from substituted or unsubstituted C6-C20 aryl groups;

[0015] The molar ratio of the silane to the aldehyde is (3-10):1.

[0016] Preferably, the reaction is carried out under closed conditions, and the pressure of carbon monoxide is 0.1-10 MPa.

[0017] Preferably, the rhodium catalyst comprises one or more of rhodium compounds with a valence of 0 to +3, and the rhodium compounds include rhodium salts and / or rhodium complexes;

[0018] The molar ratio of the rhodium catalyst to the aldehyde is 1:(5 - 10000).

[0019] Preferably, the reaction is carried out in a solvent, and the solvent includes one or more of ester solvents, cyclic ether solvents, and sulfone solvents;

[0020] The concentration of the aldehyde in the solvent is 0.1 - 1 mol / L.

[0021] Preferably, the temperature of the reaction is 20 - 100 °C, and the time of the reaction is 1 - 16 hours.

[0022] Preferably, the catalyst further comprises a ligand;

[0023] The ligand includes one or more of pyridine compounds, oxazoline compounds, pyrazine compounds, pyrazole compounds, thiazoline compounds, and imine compounds;

[0024] The molar ratio of the ligand to the rhodium atoms in the rhodium catalyst is (1 - 10):1.

[0025] Preferably, the silicon-based protected 4-substituted furanosyl derivative obtained from the reaction is subjected to a conversion reaction under the action of an acid catalyst and a ketone to obtain a 1,2-ketal-protected 4-substituted furanosyl sugar;

[0026] The acid catalyst includes Lewis acids and / or Bronsted acids.

[0027] Preferably, the silicon-based protected 4-substituted furanosyl derivative obtained from the reaction is subjected to a conversion reaction under the action of an acid anhydride to obtain an ester group-protected 4-substituted furanosyl sugar.

[0028] The present invention provides a method for preparing 4-substituted furanoside derivatives, comprising the following steps: reacting an aldehyde, carbon monoxide, and a silane under catalyst conditions to obtain a silyl-protected 4-substituted furanoside derivative; the catalyst includes a rhodium catalyst; the silane is a silahydrocarbon containing at least one Si-H bond. The advantages of the preparation method in the present invention are that the reaction process is simple, and 1,2,3-O-trisilyl-4-aryl / alkyl-substituted furanoside can be obtained through only one-step reaction, and 1,2-O-isopropylidene-4-aryl / alkyl-substituted furanoside that is easier to purify can be obtained through a two-step one-pot reaction; the raw materials are simple and easily available, being common aliphatic aldehydes or aromatic aldehydes, silanes, and carbon monoxide; the substrate range is wide, and it has good compatibility with various aldehyde substrates, and different substituted 4-aryl / alkyl-substituted furanoside derivatives can be obtained by reacting with different aldehydes. In addition, in the 4-aryl / alkyl-substituted furanoside derivatives obtained in the present invention, the 4-position substituent is in a cis position with respect to the 3-position oxygen atom, while the conventional synthesis methods mainly obtain products in which the two are in a trans position. Therefore, the present invention has good application prospects. BRIEF DESCRIPTION OF THE DRAWINGS

[0029] In order to more clearly illustrate the technical solutions in the embodiments of the present invention or the prior art, the following will briefly introduce the drawings required for use in the description of the embodiments or the prior art. Obviously, the drawings in the following description are only the embodiments of the present invention, and for those of ordinary skill in the art, other drawings can be obtained according to the provided drawings without creative efforts.

[0030] Figure 1 It is the crystal structure diagram of compound 37b prepared in Example 8 obtained by single crystal X-ray diffraction of the present invention;

[0031] Figure 2 It is the crystal structure diagram of compound 37b' prepared in Example 8 obtained by single crystal X-ray diffraction of the present invention;

[0032] Figure 3 It is the crystal structure diagram of compound 1c prepared in Example 9 obtained by single crystal X-ray diffraction of the present invention. DETAILED DESCRIPTION OF THE EMBODIMENTS

[0033] The present invention provides a method for preparing 4-substituted furanoside derivatives, comprising the following steps:

[0034] Reacting an aldehyde, carbon monoxide, and a silane under catalyst conditions to obtain a silyl-protected 4-substituted furanoside derivative;

[0035] The catalyst includes a rhodium catalyst;

[0036] The silane is at least a silahydrocarbon containing one Si-H bond.

[0037] In the present invention, under the action of a catalyst, the aldehyde, carbon monoxide and silane undergo a continuous silylformylation reaction of the aldehyde, that is, a silyl group and a formyl group are respectively added to the oxygen end and the carbon end of the carbon-oxygen double bond of the aldehyde to generate an α-silyloxy aldehyde with one more carbon atom, and a silyl-protected 4-substituted furanoside derivative is obtained. Further, through the conversion of a ketone or an acid anhydride, a more stable or more easily separable protected 4-substituted furanoside derivative can be obtained. The reaction process is shown in Formula I:

[0038]

[0039] Formula I.

[0040] In the present invention, the aldehyde is preferably one or more of an aromatic aldehyde, a heteroaromatic aldehyde and an aliphatic aldehyde, and the aldehyde is R 1 CHO, and R 1 is preferably one or more of hydrogen, a substituted or unsubstituted phenyl group, a substituted or unsubstituted heteroaryl group (monocyclic), a substituted or unsubstituted polycyclic aryl group, a substituted or unsubstituted polyheterocyclic aryl group, a substituted or unsubstituted alkyl group, a substituted or unsubstituted cycloalkyl group, a substituted or unsubstituted heterocycloalkyl group and a halogen;

[0041] In the present invention, the "cycloalkyl group" refers to a saturated or partially unsaturated monocyclic all-carbon ring (i.e., a monocyclic cycloalkyl group) or a polycyclic system (i.e., a polycyclic cycloalkyl group). The polycyclic cycloalkyl group includes: a spirocycloalkyl group, a fused cycloalkyl group and a bridged cycloalkyl group. The "spirocycloalkyl group" refers to a polycyclic system in which the rings share a single carbon atom (called a spiro atom). The "fused cycloalkyl group" refers to a polycyclic system in which the rings share two adjacent carbon atoms. The "bridged cycloalkyl group" refers to an all-carbon polycyclic system in which the rings share two non-directly connected carbon atoms. Similarly, the "heterocycloalkyl group" contains at least one heteroatom selected from nitrogen, oxygen and sulfur in the "cycloalkyl group".

[0042] More preferably, R 1 is a substituted or unsubstituted phenyl group having 6 to 20 carbon atoms, a substituted or unsubstituted heteroaryl group (monocyclic) having 5 to 30 carbon atoms, a substituted or unsubstituted polycyclic aryl group having 6 to 20 carbon atoms, a substituted or unsubstituted polyheterocyclic aryl group having 6 to 20 carbon atoms, a substituted or unsubstituted alkyl group having 1 to 10 carbon atoms, a substituted or unsubstituted cycloalkyl group having 3 to 10 carbon atoms, a substituted or unsubstituted heterocycloalkyl group having 3 to 10 carbon atoms;

[0043] The substituents in the above-mentioned substituted phenyl, substituted heteroaryl (monocyclic), substituted fused-ring aryl, substituted fused heteroaryl, substituted alkyl, substituted cycloalkyl and substituted heterocycloalkyl are independently selected from one or more of hydroxyl, C1-C10 alkyl, C1-C10 cycloalkyl, C1-C10 alkoxy, C5-C10 heteroaryl, alkenyl, carbonyl, cyano, silyl, ester group, amino, halogen, nitro, mercapto, acyl, carboxyl and phenyl.

[0044] In the present invention, different 4-position substituted furanose derivatives with different substitutions are obtained by selecting different types of R 1 . Therefore, the types of aldehydes in the present invention are not particularly limited, and those skilled in the art can select according to actual needs.

[0045] In the present invention, the silane serves as a reducing agent in the continuous silylformylation reaction of the aldehyde. The silane is a silicon hydride containing at least one Si-H bond, preferably HSiR 2 R 3 R 4 , wherein, R 2 , R 3 , R 4 are independently selected from substituted or unsubstituted alkyl, substituted or unsubstituted aryl, substituted or unsubstituted aralkyl and alkoxy; preferably, the R 2 , R 3 , R 4 are independently selected from one or more of substituted or unsubstituted C1-C10 alkyl, substituted or unsubstituted C6-C20 aryl, substituted or unsubstituted C7-C20 aralkyl and C1-C10 alkoxy; the substituents in the substituted C1-C10 alkyl are independently selected from one or more of hydroxyl, alkoxy and halogen, such as one or more of methoxy, ethoxy, -Cl, -F and -Br; the substituents in the substituted C6-C20 aryl are independently selected from one or more of C1-C10 alkoxy, C1-C10 alkyl and halogen, such as methoxy, ethoxy, methyl, ethyl, propyl, isopropyl, n-butyl, tert-butyl, -Cl, -F and -Br.

[0046] In the present invention, R 2 , R 3 are independently selected from substituted or unsubstituted C1-C10 alkyl, more preferably one or more of methyl, ethyl, propyl, isopropyl, n-butyl and tert-butyl, R 4Selected from substituted or unsubstituted C6-C20 aryl groups, more preferably phenyl groups, and the phenyl groups may be further substituted by one or more substituent groups selected from the following: C1-C10 alkyl groups such as methyl, ethyl, propyl, isopropyl, n-butyl, tert-butyl, etc.; halogens such as one or several of -Cl, -F, and -Br.

[0047] In the present invention, the molar ratio of the silane to the aldehyde is preferably (3-10):1, more preferably (4-9):1, such as 3:1, 3.5:1, 4:1, 4.5:1, 5:1, 5.5:1, 6:1, 6.5:1, 7:1, 7.5:1, 8:1, 8.5:1, 9:1, 9.5:1, 10:1, and is preferably a range value with any of the above-mentioned values as the upper or lower limit.

[0048] In the present invention, the reaction is preferably carried out under airtight and oxygen-free conditions, more preferably in an airtight reaction vessel such as an autoclave. After adding the liquid and solid materials into the reaction vessel in the present invention, the container is closed, and after filling the reaction vessel with CO at 2-5 MPa and then releasing it to atmospheric pressure, this is repeated 3-5 times to ensure that the oxygen content in the reaction environment is low enough. During the reaction process, the pressure of CO in the system is preferably 0.1-10 MPa, more preferably 4-6 MPa, such as 0.1 MPa, 0.5 MPa, 1 MPa, 1.5 MPa, 2 MPa, 2.5 MPa, 3 MPa, 3.5 MPa, 4 MPa, 4.5 MPa, 5 MPa, 5.5 MPa, 6 MPa, 6.5 MPa, 7 MPa, 7.5 MPa, 8 MPa, 8.5 MPa, 9 MPa, 9.5 MPa, 10 MPa, and is preferably a range value with any of the above-mentioned values as the upper or lower limit.

[0049] In the present invention, the catalyst includes a rhodium catalyst, preferably a rhodium compound with a valence of 0 to +3. The rhodium catalyst can be one or several of rhodium compounds with valences of 0, +1, +2, and +3 in any form. The rhodium compounds include rhodium salts and / or rhodium complexes. The ligand in the rhodium complex is preferably CO, an olefin, or other organic ligands capable of coordinating with Rh. Specifically, the rhodium catalyst is preferably Rh4(CO) 12, one or more of [Rh(COD)Cl]2, [Rh(CO)2Cl]2, [Rh(C2H4)2Cl]2, Rh(COD)2BF4, Rh(OAc)3, and RhCl3. The molar ratio of the rhodium catalyst to the aldehyde is preferably 1:(5 - 10000), more preferably 1:(50 - 5000), such as 1:5, 1:10, 1:20, 1:30, 1:40, 1:50, 1:60, 1:70, 1:80, 1:90, 1:100, 1:200, 1:300, 1:400, 1:500, 1:600, 1:700, 1:800, 1:900, 1:1000, 1:2000, 1:3000, 1:4000, 1:5000, 1:6000, 1:7000, 1:8000, 1:9000, 1:10000, and is preferably a range value with any of the above values as the upper or lower limit.

[0050] In the present invention, the catalyst preferably further includes a ligand. In the absence of a ligand, the reaction can still proceed. After adding a ligand, the yield of the reaction can be improved. The ligand is preferably a nitrogen-containing ligand, more preferably one or more of pyridine compounds, oxazoline compounds, pyrazine compounds, pyrazole compounds, thiazoline compounds, and imine compounds. The pyridine compounds preferably include one or more of pyridine, bipyridine, biquinoline, terpyridine, benzo pyridine, and methylene bispyridine. Specifically, it can be one or more of 2,2-bipyridine and 2,2'-biquinoline. The pyridine, bipyridine, terpyridine, benzo pyridine, methylene bispyridine, oxazoline compounds, pyrazine compounds, pyrazole compounds, thiazoline compounds, and imine compounds can each be further independently substituted by one or more of the following substituents: C1-C10 alkyl, hydroxyl, carboxyl, C6-C20 aryl, ether group, amino, methoxy, cyano, and halogen. The C1-C10 alkyl can be further substituted by halogen. Specifically, one or more of the following compounds can be selected as the ligand:

[0051] 。

[0052] In the present invention, the molar ratio of the ligand to the rhodium atom in the rhodium catalyst is preferably (1 to 10):1, more preferably (2 to 8):1, such as 1:1, 1.5:1, 2:1, 2.5:1, 3:1, 3.5:1, 4:1, 4.5:1, 5:1, 5.5:1, 6:1, 6.5:1, 7:1, 7.5:1, 8:1, 8.5:1, 9:1, 9.5:1, 10:1, and preferably a range value with any of the above-mentioned values as the upper or lower limit.

[0053] In the present invention, the continuous silylformylation reaction of the aldehyde is preferably carried out in a solvent. The solvent preferably includes one or more of ester solvents, cyclic ether solvents, and sulfone solvents. The ester solvents are preferably one or more of ethyl acetate, γ-butyrolactone, ethylene carbonate, propylene carbonate, and valerolactone. The cyclic ether solvents are preferably tetrahydrofuran (THF) and / or 2-methyltetrahydrofuran. The sulfone solvent is preferably sulfolane. The solvent is preferably a dry solvent. The concentration of the aldehyde in the solvent is preferably 0.1 to 1 mol / L, more preferably 0.2 to 0.8 mol / L, such as 0.1 mol / L, 0.2 mol / L, 0.3 mol / L, 0.4 mol / L, 0.5 mol / L, 0.6 mol / L, 0.7 mol / L, 0.8 mol / L, 0.9 mol / L, 1 mol / L, and preferably a range value with any of the above-mentioned values as the upper or lower limit.

[0054] In the present invention, the temperature of the reaction is preferably 20 to 100 °C, more preferably 40 to 80 °C, such as 20 °C, 25 °C, 30 °C, 35 °C, 40 °C, 45 °C, 50 °C, 55 °C, 60 °C, 65 °C, 70 °C, 75 °C, 80 °C, 85 °C, 90 °C, 95 °C, 100 °C, and preferably a range value with any of the above-mentioned values as the upper or lower limit. The reaction time is preferably 12 to 16 hours, more preferably 13 to 15 hours.

[0055] After completing the continuous silylformylation reaction of the aldehyde, the reaction product, the silyl-protected 4-substituted furanosyl derivative, 1,2,3-O-trisilyloxy-4-substituted furanosyl, is obtained. Since this product contains isomers and the NMR is relatively complex, in the present invention, after the reaction is completed, a ketone (R 5 COR 6 ) containing an acid catalyst is added to the reaction system for a conversion reaction to in-situ convert it into the more stable and easier-to-identify 1,2-ketal-protected 4-substituted furanosyl.

[0056] In the present invention, the acid catalyst preferably comprises a Lewis acid and / or a Bronsted acid, more preferably one or more of FeCl3, AlCl3, Al(OTf)3, ZnCl2, Zn(OTf)2, ZrCl4, Y(OTf)3, La(OTf)3, In(OTf)3, Sc(OTf)3, p-toluenesulfonic acid, sulfamic acid, and pyridine p-toluenesulfonate; the molar ratio of the aldehyde to the acid catalyst is preferably 1:(1-100), more preferably 1:(10-80), such as 1:1, 1:10, 1:20, 1:30, 1:40, 1:50, 1:60, 1:70, 1:80, 1:90, 1:100, and is preferably a range value with any of the above-mentioned values as the upper or lower limit.

[0057] In the present invention, the ketone is preferably one or more of acetone, 3-pentanone, cyclobutanone, cyclopentanone, and cyclohexanone. For each mmol of the aldehyde, preferably 2-6 mL of the ketone is added, more preferably 3-5 mL of the ketone is added, such as 2 mL, 3 mL, 4 mL, 5 mL, 6 mL, and is preferably a range value with any of the above-mentioned values as the upper or lower limit.

[0058] In the present invention, the temperature of the conversion reaction is preferably 20-60 °C, more preferably 30-50 °C, such as 20 °C, 25 °C, 30 °C, 35 °C, 40 °C, 45 °C, 50 °C, 55 °C, 60 °C, and is preferably a range value with any of the above-mentioned values as the upper or lower limit; the time of the conversion reaction is preferably 1 min-12 hours, more preferably 5 min-30 min, such as 1 min, 5 min, 10 min, 20 min, 30 min, 40 min, 50 min, 1 hour, 2 hours, 3 hours, 4 hours, 5 hours, 6 hours, 7 hours, 8 hours, 9 hours, 10 hours, 11 hours, 12 hours, and is preferably a range value with any of the above-mentioned values as the upper or lower limit.

[0059] After completing the continuous silylformylation reaction of the aldehyde, an acid anhydride (R 7 COOCOR 7 )), a base, and a fluoride can be added to the system for a conversion reaction to be in-situ converted into an ester group-protected 4-substituted furanoside.

[0060] In the present invention, the acid anhydride is preferably acetic anhydride; for each 1 mmol of the aldehyde, preferably 1-3 mL of the acid anhydride is added. A base and a fluoride also need to be added to the system. The base is preferably pyridine, and for each 1 mmol of the aldehyde, preferably 1-3 g of the base is added; the fluoride is preferably pyridine hydrogen fluoride salt, and for each 1 mmol of the aldehyde, preferably 2-5 mmol of the fluoride is added.

[0061] In the present invention, the temperature of the conversion reaction is preferably 40 to 80 °C, more preferably 50 to 70 °C, such as 40 °C, 45 °C, 50 °C, 55 °C, 60 °C, 65 °C, 70 °C, 75 °C, 80 °C, and is preferably a range value with any of the above values as the upper or lower limit; the time of the conversion reaction is preferably 2 to 6 hours, more preferably 3 to 5 hours.

[0062] The present invention provides a catalytic system composed of a rhodium compound and an optional nitrogen ligand in a certain proportion, and a chemical method for catalyzing the reaction of an aldehyde, a silane, and carbon monoxide in a certain proportion to produce a 4-aryl / alkyl-substituted furanoside derivative. The method in the present invention breaks through the inherent idea that existing synthesis methods of 4-substituted furanoside derivatives all use natural sugar compounds as starting materials for modification, realizes the reaction of converting an aldehyde into a 4-aryl / alkyl-substituted furanoside derivative, takes an aldehyde as the raw material, obtains the target product through a de novo synthesis strategy, provides a new idea, broadens the access route of such compounds, and is beneficial to the subsequent research and application of 4-substituted furanoside derivatives.

[0063] In order to further illustrate the present invention, the following is a detailed description of a preparation method of a 4-substituted furanoside derivative provided by the present invention in combination with examples, but it should not be construed as a limitation to the protection scope of the present invention.

[0064] Explore the influence of reaction conditions on the reaction according to the following steps:

[0065] Under anaerobic conditions, sequentially add a rhodium catalyst [Rh], a ligand, anhydrous tetrahydrofuran into a 25 mL Hastelloy autoclave, stir evenly, then add an aldehyde and a silane, seal the autoclave, fill the autoclave with 3 Mpa CO (>99.99%) and then release the gas, repeat three times to displace the gas in the autoclave, fill with CO again, and then place the autoclave in a preheated oil bath for heating reaction. The obtained product uses mesitylene as an internal standard, and the NMR yield and dr value are measured by nuclear magnetic resonance hydrogen spectrum.

[0066] Or after the reaction is completed, add a solution of a Lewis acid catalyst in a ketone to the reaction solution, stir for a certain time at room temperature to generate the target product, use mesitylene as an internal standard, and measure the NMR yield and dr value by nuclear magnetic resonance hydrogen spectrum.

[0067] Influence of the type of Rh catalyst on the reaction

[0068]

[0069] Table 1 Influence of the type of Rh catalyst on the reaction

[0070]

[0071] Table 1 shows that a variety of Rh salts or Rh complexes can catalyze the reaction, and [Rh(COD)Cl]2 is preferred among them.

[0072] Effect of the type of reducing agent on the reaction

[0073]

[0074] Table 2 Effect of the type of reducing agent on the reaction

[0075]

[0076] Table 2 shows that HSiEtMe2 and HSiPhMe2 can achieve the reaction, and HSiPhMe2 is preferred among them.

[0077]

[0078] Table 3 Effect of the type of silane on the reaction

[0079]

[0080] Table 3 shows that R in the silane can be various aryl or alkyl groups, and preferably, R is a phenyl group.

[0081] Effect of the amount of silane on the reaction

[0082]

[0083] Table 4 Effect of the amount of silane on the reaction (aromatic aldehyde)

[0084]

[0085]

[0086] Table 5 Effect of the amount of silane on the reaction (including conversion reaction)

[0087]

[0088]

[0089] Table 6 Effect of the amount of silane on the reaction (fatty aldehyde)

[0090]

[0091] Tables 4 to 6 show that either too high or too low amount of silane is not conducive to the reaction, and the preferred ratio of silane to aldehyde is 5:1.

[0092] Effect of the amount of catalyst on the reaction

[0093]

[0094] Table 7 Influence of Catalyst Dosage on the Reaction (Aromatic Aldehyde)

[0095]

[0096]

[0097] Table 8 Influence of Catalyst Dosage on the Reaction (Including Conversion Reaction)

[0098]

[0099]

[0100] Table 9 Influence of Catalyst Dosage on the Reaction (Fatty Aldehyde)

[0101]

[0102] Tables 7 - 9 show that within a certain range, the catalyst dosage has little effect on the reaction result, and too low a catalyst dosage is not conducive to the reaction.

[0103] Influence of Ligand Type on the Reaction

[0104]

[0105]

[0106] Table 10 Influence of Ligand Type on the Reaction (Including Conversion Reaction, Phosphine Ligands and Pyridine Ligands)

[0107]

[0108]

[0109]

[0110] Table 11 Influence of Ligand Type on the Reaction (Other Ligands)

[0111]

[0112] Tables 10 and 11 show that the ligand has a certain influence on the reaction result. Among them, phosphine ligands will inhibit the reaction, and some nitrogen ligands play a promoting role in the reaction. Among them, the ligand is preferably L6 (2,2'-biquinoline).

[0113] Influence of Ligand Dosage on the Reaction

[0114]

[0115] Table 12 Influence of Ligand Dosage on the Reaction

[0116]

[0117] Table 12 shows that within a certain range, the amount of ligand used has little effect on the reaction result.

[0118] Effect of temperature on the reaction

[0119]

[0120] Table 13 Effect of temperature on the reaction (aromatic aldehyde)

[0121]

[0122]

[0123] Table 14 Effect of temperature on the reaction (including conversion reaction)

[0124]

[0125]

[0126] Table 15 Effect of temperature on the reaction (fatty aldehyde)

[0127]

[0128] Tables 13 to 15 show that within a certain range, the temperature has little effect on the reaction result, but too high or too low temperature is not conducive to the reaction.

[0129] Effect of carbon monoxide pressure on the reaction

[0130]

[0131] Table 16 Effect of carbon monoxide pressure on the reaction

[0132]

[0133]

[0134] Table 17 Effect of carbon monoxide pressure on the reaction

[0135]

[0136]

[0137] Table 18 Effect of carbon monoxide pressure on the reaction

[0138]

[0139] Tables 16 to 18 show that within a certain range, pressure has little effect on the reaction result, but too low pressure will lead to a poor reaction result.

[0140] Effect of solvent type on the reaction

[0141]

[0142] Table 19 Effect of solvent type on the reaction (including conversion reaction)

[0143]

[0144]

[0145] Table 20 Effect of solvent type on the reaction (fatty aldehyde)

[0146]

[0147] Tables 19 to 20 show that the solvent type has a great influence on the reaction. The reaction can only be carried out in some ester, sulfone and cyclic ether solvents. The preferred solvent is tetrahydrofuran.

[0148] Effect of solvent amount on the reaction

[0149]

[0150] Table 21 Effect of solvent amount on the reaction (aromatic aldehyde)

[0151]

[0152]

[0153] Table 22 Effect of solvent amount on the reaction (fatty aldehyde)

[0154]

[0155] Tables 21 to 22 show that the concentration of aldehyde in the solvent has a certain influence on the reaction. Too high or too low concentration is not conducive to the reaction.

[0156] Effect of acid type on subsequent conversion

[0157]

[0158] Table 23 Effect of acid type on subsequent conversion

[0159]

[0160] Table 23 shows that a variety of Lewis acids can achieve the conversion reaction, and the preferred ones are Sc(OTf)3 and In(OTf)3.

[0161] Effect of the type of ketone on subsequent conversion

[0162]

[0163] Table 24 Effect of the type of ketone on subsequent conversion

[0164]

[0165] Table 24 shows that various ketones can achieve the conversion reaction, and acetone is preferably used among them.

[0166] According to the above exploration of the reaction conditions, 4-substituted furanosyl derivatives with the structures shown in 1b - 81b are prepared. The following are the specific preparation steps and product identifications of eight compounds, namely 1,2 - O - isopropylidene - 4 - phenyl furanoside (1b), 1,2 - O - isopropylidene - 4 - (4 - methoxyphenyl) furanoside (5b), 1,2 - O - isopropylidene - 4 - (4 - trifluoromethylphenyl) furanoside (7b), 1,2 - O - isopropylidene - 4 - (thiophen - 3 - yl) furanoside (49b), 1,2 - O - isopropylidene - 4 - (tetrahydropyran - 4 - yl) furanoside (70b), 1,2 - O - isopropylidene - 4 - (3 - benzoyloxypropyl) furanoside (72b), 1,2 - O - isopropylidene - 4 - (4 - chlorophenyl) furanoside (9b and 9b'), and 1,2 - O - isopropylidene - 4 - (naphthalen - 2 - yl) furanoside (37b and 37b'). For the remaining 73 compounds, different types of aldehydes are used as raw materials and prepared according to the steps in Examples 1 - 8 and the product identifications are carried out.

[0167] Example 1

[0168] Synthesis of 1,2 - O - isopropylidene - 4 - phenyl furanoside (1b), including the following steps:

[0169] Under anaerobic conditions, [Rh(cod)Cl]2 (4.9 mg, 0.01 mmol), 2,2'-biquinoline (biqu) (7.7 mg, 0.03 mmol), and anhydrous tetrahydrofuran (1.0 mL) were successively added to a 25 mL Hastelloy autoclave and stirred evenly. Then, benzaldehyde (1a, 51 μL, d = 1.042 g / mL, 53.1 mg, 0.5 mmol) and dimethylphenylsilane (385 μL, d = 0.889 g / mL, 342.2 mg, 2.5 mmol) were added. The autoclave was sealed, filled with 3 Mpa CO (>99.99%), and then vented. This process was repeated three times to displace the gas inside the autoclave. Then, it was filled with 4 Mpa CO, and the autoclave was placed in an oil bath preheated to 40 °C and heated for 16 h. After the reaction was completed, a solution of In(OTf)3 (56.2 mg, 0.1 mmol) in acetone (4.0 mL) was added to the reaction solution, and it was stirred at room temperature for 10 min to form the target product 1b and the by-product 1b'. Using mesitylene as the internal standard, the total yield of 1b and 1b' was determined to be 80% by 1H NMR, and the ratio of 1b / 1b' (dr value) was 6.2 / 1. The main product 1b (80.2 mg, 68%) was obtained by purification through silica gel chromatography.

[0170]

[0171] 1 H NMR (400 MHz, Chloroform-d) δ 7.44 – 7.37 (m, 4H), 7.36 – 7.29 (m,1H), 6.10 (d, J = 3.6 Hz, 1H), 5.35 (d, J = 2.6 Hz, 1H), 4.67 (d, J = 3.7 Hz,1H), 4.24 (t, J = 2.6 Hz, 1H), 1.57 (s, 3H), 1.37 (s, 3H), 1.31 – 1.26 (m,1H).

[0172] 13 C NMR (101 MHz, Chloroform-d) δ 134.70, 128.88, 128.42, 126.75,111.89, 105.12, 84.79, 82.35, 76.86, 26.95, 26.35.

[0173] Example 2

[0174] Synthesis of 1,2-O-isopropylidene-4-(4-methoxyphenyl)furanose (5b) comprises the following steps:

[0175] Under anaerobic conditions, [Rh(cod)Cl]2 (4.9 mg, 0.01 mmol), 2,2'-biquinoline (biqu) (7.7 mg, 0.03 mmol), and anhydrous tetrahydrofuran (1.0 mL) were successively added to a 25 mL Hastelloy autoclave and stirred evenly. Then, 4-methoxybenzaldehyde (5a, 61 μL, d = 1.121 g / mL, 68.4 mg, 0.5 mmol) and dimethylphenylsilane (385 μL, d = 0.889 g / mL, 342.2 mg, 2.5 mmol) were added. The autoclave was sealed, filled with 3 Mpa CO (>99.99%) and then vented, and this was repeated three times to displace the gas inside the autoclave. Then, it was filled with 4 Mpa CO, and the autoclave was placed in an oil bath preheated to 40 °C and heated for reaction for 16 h. After the reaction was completed, a solution of In(OTf)3 (56.2 mg, 0.1 mmol) in acetone (4.0 mL) was added to the reaction solution, and it was stirred at room temperature for 10 min to form the target product 5b and by-product 5b'. Using mesitylene as the internal standard, the total yield of 5b and 5b' was determined to be 72% by 1H NMR, and the 5b / 5b' (dr value) was 5.0 / 1. The main product 5b (79.8 mg, 60%) was obtained by purification through silica gel chromatography.

[0176]

[0177] 1 H NMR (400 MHz, Chloroform-d) δ 7.32 (d, J = 8.4 Hz, 2H), 6.93 (d, J = 8.6 Hz, 2H), 6.08 (d, J = 3.7 Hz, 1H), 5.31 (d, J = 2.6 Hz, 1H), 4.67 (d, J = 3.7 Hz, 1H), 4.18 (t, J = 2.6 Hz, 1H), 3.81 (s, 3H), 1.57 (s, 3H), 1.37 (s, 3H), 1.30 (d, J = 2.6 Hz, 1H).

[0178] 1313C NMR (101 MHz, Chloroform-d) δ 159.72, 128.05, 126.44, 114.33, 111.80, 105.05, 84.81, 82.12, 76.77, 55.43, 26.95, 26.34.

[0179] Example 3

[0180] Synthesis of 1,2-O-isopropylidene-4-(4-trifluoromethylphenyl)furanose (7b) comprises the following steps:

[0181] Under anaerobic conditions, [Rh(cod)Cl]2 (4.9 mg, 0.01 mmol), 2,2'-biquinoline (biqu) (7.7 mg, 0.03 mmol), and anhydrous tetrahydrofuran (1.0 mL) were successively added to a 25 mL Hastelloy autoclave and stirred evenly. Then 4-trifluoromethylbenzaldehyde (7a, 68 μL, d = 1.275 g / mL, 86.7 mg, 0.5 mmol) and dimethylphenylsilane (385 μL, d = 0.889 g / mL, 342.2 mg, 2.5 mmol) were added. The autoclave was sealed, filled with 3 Mpa CO (>99.99%) and then vented. This was repeated three times to displace the gas in the autoclave, and then filled with 4 Mpa CO. The autoclave was then placed in an oil bath preheated to 45 °C and heated for 16 h. After the reaction was completed, a solution of In(OTf)3 (56.2 mg, 0.1 mmol) in acetone (4.0 mL) was added to the reaction solution and stirred at room temperature for 10 min to form the target product 7b and by-product 7b'. Using mesitylene as the internal standard, the total yield of 7b and 7b' was determined to be 65% by 1H NMR, and the 7b / 7b' (dr value) was 3.3 / 1. The main product 7b (76.8 mg, 50%) was obtained by purification using silica gel chromatography.

[0182]

[0183] 11H NMR (400 MHz, Chloroform-d) δ 7.66 (d, J = 8.0 Hz, 2H), 7.53 (d, J = 8.0 Hz, 2H), 6.11 (d, J = 3.6 Hz, 1H), 5.37 (d, J = 2.7 Hz, 1H), 4.68 (d, J = 3.6 Hz, 1H), 4.32 (t, J = 3.2 Hz, 1H), 1.57 (s, 3H), 1.38 (s, 3H), 1.25 (d, J = 3.6 Hz, 1H).

[0184] 19 19F NMR (376 MHz, Chloroform-d) δ -62.58.

[0185] 13 13C NMR (101 MHz, Chloroform-d) δ 139.21, 130.51 (q, J = 32.5 Hz), 127.21, 125.67 (q, J = 3.9 Hz), 124.13 (q, J = 272.2 Hz), 112.14, 105.07, 84.91, 81.80, 76.91, 26.90, 26.29.

[0186] Example 4

[0187] The synthesis of 1,2-O-isopropylidene-4-(thiophen-3-yl)threofuranose (49b) comprises the following steps:

[0188] Under anaerobic conditions, [Rh(cod)Cl]2 (4.9 mg, 0.01 mmol), 2,2'-biquinoline (biqu) (7.7 mg, 0.03 mmol), and anhydrous tetrahydrofuran (1.0 mL) were successively added to a 25 mL Hastelloy autoclave and stirred evenly. Then, thiophene-3-carbaldehyde (49a, 44 μL, d = 1.280 g / mL, 56.3 mg, 0.5 mmol) and dimethylphenylsilane (385 μL, d = 0.889 g / mL, 342.2 mg, 2.5 mmol) were added. The autoclave was sealed, filled with 3 Mpa CO (>99.99%), and then vented. This process was repeated three times to displace the gas inside the autoclave. Then, it was filled with 4 Mpa CO, and the autoclave was placed in an oil bath preheated to 40 °C and heated for 16 h. After the reaction was completed, a solution of In(OTf)3 (56.2 mg, 0.1 mmol) in acetone (4.0 mL) was added to the reaction solution and stirred at room temperature for 10 min to produce the target product 49b and by-product 49b'. Using mesitylene as the internal standard, the total yield of 49b and 49b' was determined to be 47% by 1H NMR, and the ratio of 49b / 49b' (dr value) was 4.1 / 1. The main product 49b (46.3 mg, 38%) was obtained by purification through silica gel chromatography.

[0189]

[0190] 1 H NMR (400 MHz, Chloroform-d) δ 7.40 – 7.36 (m, 2H), 7.08 – 7.05 (m,1H), 6.06 (d, J = 3.7 Hz, 1H), 5.40 (d, J = 2.6 Hz, 1H), 4.66 (d, J = 3.7 Hz,1H), 4.22 (t, J = 2.8 Hz, 1H), 1.56 (s, 3H), 1.43 – 1.40 (m, 1H), 1.36 (s,3H).

[0191] 13 C NMR (101 MHz, Chloroform-d) δ 135.80, 127.02, 125.94, 123.22,111.91, 104.94, 84.80, 79.95, 76.32, 26.92, 26.33.

[0192] Example 5

[0193] The synthesis of 1,2-O-isopropylidene-4-(tetrahydropyran-4-yl)furanose (70b) comprises the following steps:

[0194] Under anaerobic conditions, [Rh(cod)Cl]2 (4.9 mg, 0.01 mmol), 2,2'-biquinoline (biqu) (7.7 mg, 0.03 mmol), and anhydrous tetrahydrofuran (1.0 mL) were successively added to a 25 mL Hastelloy autoclave, stirred evenly, and then tetrahydropyran-4-carbaldehyde (70a, 52 μL, d = 1.096 g / mL, 57.0 mg, 0.5 mmol) and dimethylphenylsilane (385 μL, d = 0.889 g / mL, 342.2 mg, 2.5 mmol) were added. The autoclave was sealed, filled with 3 Mpa CO (>99.99%), and then vented. This process was repeated three times to displace the gas in the autoclave. Then, it was filled with 6 Mpa CO, and the autoclave was placed in an oil bath preheated to 40 °C and heated for 16 h. After the reaction was completed, a solution of In(OTf)3 (56.2 mg, 0.1 mmol) in acetone (4.0 mL) was added to the reaction solution, and it was stirred at room temperature for 10 min to form the target product 70b and by-product 70b'. Using mesitylene as the internal standard, the total yield of 70b and 70b' was determined to be 54% by 1H NMR, and the 70b / 70b' (dr value) was 5.3 / 1. The main product 70b (56.1 mg, 46%) was obtained by silica gel chromatography purification.

[0195]

[0196] 1 H NMR (400 MHz, Chloroform-d) δ 5.90 (d, J = 3.8 Hz, 1H), 4.50 (d, J = 3.8 Hz, 1H), 4.14 – 4.08 (m, 1H), 3.98 (td, J = 9.9, 8.0, 4.0 Hz, 2H), 3.78 (dd, J = 9.9, 2.5 Hz, 1H), 3.42 (tdd, J = 11.7, 8.5, 2.2 Hz, 2H), 2.02 – 1.86 (m, 2H), 1.79 – 1.35 (m, 7H), 1.31 (s, 3H).

[0197] 1313C NMR (101 MHz, Chloroform-d) δ 111.68, 104.28, 85.32, 84.35, 74.21, 67.84, 67.39, 33.92, 30.82, 28.58, 26.70, 26.28.

[0198] Example 6

[0199] Synthesis of 1,2-O-isopropylidene-4-(3-benzoyloxypropyl)furanose (72b) comprises the following steps:

[0200] Under anaerobic conditions, [Rh(cod)Cl]2 (4.9 mg, 0.01 mmol), 2,2'-biquinoline (biqu) (7.7 mg, 0.03 mmol), and anhydrous tetrahydrofuran (1.0 mL) were successively added to a 25 mL Hastelloy autoclave and stirred evenly. Then, 4-benzoyloxybutyraldehyde (72a, 96.1 mg, 0.5 mmol) and dimethylphenylsilane (385 μL, d = 0.889 g / mL, 342.2 mg, 2.5 mmol) were added. The autoclave was sealed, filled with 3 Mpa CO (>99.99%), and then vented. This process was repeated three times to displace the gas inside the autoclave. Then, it was filled with 6 Mpa CO, and the autoclave was placed in an oil bath preheated to 40 °C and heated for 16 h. After the reaction was completed, a solution of In(OTf)3 (56.2 mg, 0.1 mmol) in acetone (4.0 mL) was added to the reaction solution, and the mixture was stirred at room temperature for 10 min to form the target product 72b and by-product 72b'. Using mesitylene as the internal standard, the total yield of 72b and 72b' was determined to be 63% by 1H NMR, and the 72b / 72b' (dr value) was 2.6 / 1. The main product 72b (73.7 mg, 46%) was obtained by purification using silica gel chromatography.

[0201]

[0202] 11H NMR (400 MHz, Chloroform-d) δ 8.07 – 8.01 (m, 2H), 7.59 – 7.52 (m,1H), 7.43 (dd, J = 8.4, 7.1 Hz, 2H), 5.91 (d, J = 3.8 Hz, 1H), 4.52 (d, J =3.8 Hz, 1H), 4.41 – 4.33 (m, 2H), 4.19 (td, J = 6.7, 2.6 Hz, 1H), 4.09 (d, J= 2.8 Hz, 1H), 2.04 – 1.73 (m, 5H), 1.49 (s, 3H), 1.31 (s, 3H).

[0203] 13 13C NMR (101 MHz, Chloroform-d) δ 166.82, 133.08, 130.39, 129.72,128.50, 111.64, 104.42, 85.49, 80.00, 75.56, 64.88, 26.73, 26.27, 25.68,24.63.

[0204] Example 7

[0205] The synthesis of 1,2-O-isopropylidene-4-(4-chlorophenyl) erythrofuranose (9b and 9b’) comprises the following steps:

[0206] Under anaerobic conditions, [Rh(cod)Cl]2 (49.3 mg, 0.1 mmol), 2,2'-biquinoline (biqu) (76.9 mg, 0.3 mmol), 4-chlorobenzaldehyde (9a, 702.8 mg, 5.0 mmol), and anhydrous tetrahydrofuran (8.0 mL) were successively added to a 25 mL Hastelloy autoclave and stirred evenly. Then, dimethylphenylsilane (3.835 mL, d = 0.889 g / mL, 3.4093 g, 25.0 mmol) was added. The autoclave was sealed, filled with 3 MPa CO (>99.99%), and then vented. This process was repeated three times to displace the gas inside the autoclave. Then, it was filled with 6.5 MPa CO, and the autoclave was placed in an oil bath preheated to 40 °C and heated for 24 h. After the reaction was completed, a solution of In(OTf)3 (562.0 mg, 1.0 mmol) in acetone (40.0 mL) was added to the reaction solution and stirred at room temperature for 20 min to produce the target products 9b and 9b’. Using mesitylene as the internal standard, the total yield of 9b and 9b’ was determined to be 70% by 1H NMR, and the ratio of 9b / 9b’ (dr value) was 3.5 / 1. The white solid product 9b (732.5 mg, 54%) and the colorless oil product 9b’ (198.8 mg, 15%) were obtained by purification through silica gel chromatography.

[0207]

[0208] 9b

[0209] 1 1H NMR (400 MHz, Chloroform-d) δ 7.40 – 7.31 (m, 4H), 6.09 (d, J = 3.7 Hz, 1H), 5.34 – 5.27 (m, 1H), 4.67 (d, J = 3.6 Hz, 1H), 4.24 (s, 1H), 1.57 (s, 3H), 1.37 (s, 3H), 1.25 (s, 1H).

[0210] 13 13C NMR (101 MHz, Chloroform-d) δ 134.20, 133.35, 129.01, 128.23, 112.01, 105.04, 84.84, 81.76, 76.80, 26.91, 26.31.

[0211] 9b’

[0212] 11H NMR (400 MHz, Chloroform-d) δ 7.40 (d, J = 8.3 Hz, 2H), 7.32 (d, J = 8.3 Hz, 2H), 6.00 (d, J = 4.1 Hz, 1H), 4.90 (d, J = 4.2 Hz, 1H), 4.65 – 4.60 (m, 1H), 4.36 (t, J = 4.4 Hz, 1H), 2.36 (d, J = 4.3 Hz, 1H), 1.33 (s, 3H), 1.31 (s, 3H).

[0213] 13 13C NMR (101 MHz, Chloroform-d) δ 137.76, 133.56, 128.56, 127.36, 113.75, 105.30, 87.75, 86.12, 81.28, 26.93, 26.78.

[0214] Example 8

[0215] Synthesis of 1,2-O-isopropylidene-4-(naphthalen-2-yl)threofuranose (37b and 37b') comprises the following steps:

[0216] Under anaerobic conditions, [Rh(cod)Cl]2 (49.3 mg, 0.1 mmol), 2,2'-biquinoline (biqu) (76.9 mg, 0.3 mmol), 2-naphthaldehyde (37a, 702.8 mg, 5.0 mmol), and anhydrous tetrahydrofuran (8.0 mL) were successively added to a 25 mL Hastelloy autoclave and stirred evenly. Then, dimethylphenylsilane (3.835 mL, d = 0.889 g / mL, 3.4093 g, 25.0 mmol) was added. The autoclave was sealed, filled with 3 MPa CO (>99.99%), and then vented. This process was repeated three times to displace the gas inside the autoclave. Then, it was filled with 6.5 MPa CO, and the autoclave was placed in an oil bath preheated to 40 °C and heated for 24 h. After the reaction was completed, a solution of In(OTf)3 (562.0 mg, 1.0 mmol) in acetone (40.0 mL) was added to the reaction solution, and it was stirred at room temperature for 20 min to form the target products 37b and 37b'. Using mesitylene as the internal standard, the total yield of 37b and 37b' was determined to be 59% by 1H NMR, and the ratio of 37b / 37b' (dr value) was 5.4 / 1. The white solid product 37b (702.2 mg, 49%) and the white solid product 37b' (123.8 mg, 9%) were obtained by purification through silica gel chromatography.

[0217]

[0218] 37b

[0219] 1 1H NMR (600 MHz, Chloroform-d) δ 7.94 (s, 1H), 7.89 – 7.83 (m, 3H),7.53 – 7.48 (m, 2H), 7.45 (d, J = 8.6 Hz, 1H), 6.17 (d, J = 3.7 Hz, 1H), 5.53(d, J = 2.7 Hz, 1H), 4.72 (d, J = 3.7 Hz, 1H), 4.35 (t, J = 2.9 Hz, 1H), 1.61(s, 3H), 1.40 (s, 3H), 1.27 (d, J = 2.8 Hz, 1H).

[0220] 13C NMR (101 MHz, Chloroform-d) δ 133.43, 133.34, 132.17, 128.72, 128.17, 127.90, 126.61, 126.41, 126.02, 124.24, 112.00, 105.23, 84.89, 82.53, 76.87, 27.00, 26.39.

[0221] Dissolve 37b (50.0 mg) in 3.0 mL of solvent (petroleum ether / dichloromethane = 5 / 1). Let the solvent slowly evaporate at room temperature. After natural crystallization for 24 hours, crystals of 37b can be obtained. The crystal data of 37b can be obtained by single crystal X-ray diffraction, as Figure 1 shown.

[0222] 37b’ (matched with the literature, Angew. Chem. Int. Ed. 2018, 57, 6614 - 6618.)

[0223] 1 H NMR (400 MHz, Chloroform-d) δ 7.91 (s, 1H), 7.86 – 7.77 (m, 3H), 7.54 (dd, J = 8.7, 1.8 Hz, 1H), 7.50 – 7.42 (m, 2H), 6.04 (d, J = 4.1 Hz, 1H), 5.07 (d, J = 4.5 Hz, 1H), 4.66 (dd, J = 4.2, 1.6 Hz, 1H), 4.46 (td, J = 4.6, 1.5 Hz, 1H), 2.53 (d, J = 4.7 Hz, 1H), 1.33 (s, 6H).

[0224] 13 C NMR (101 MHz, Chloroform-d) δ 136.48, 133.15, 133.04, 128.32, 128.15, 127.78, 126.36, 126.09, 124.90, 123.82, 113.81, 105.27, 87.93, 86.91, 81.33, 27.01, 26.88.

[0225] Dissolve 37b’ (80.0 mg) in 3.0 mL of solvent (petroleum ether / dichloromethane = 5 / 1). Let the solvent slowly evaporate at room temperature. After natural crystallization for 24 hours, crystals of 37b’ can be obtained. Crystal data of 37b’ can be obtained by single crystal X-ray diffraction, as Figure 2 shown.

[0226] Compounds 1b to 53b all react according to the reaction conditions in the following reaction formula. Among them, the separated yield of the main product is outside the parentheses, and the total NMR yield of the main product and by-product as well as the dr value of the two products are inside the parentheses, which are determined by 1H NMR using mesitylene as the internal standard.

[0227]

[0228]

[0229] Compounds 54b to 81b all react according to the reaction conditions in the following reaction formula. Among them, the separated yield of the main product is outside the parentheses, and the total NMR yield of the main product and by-product as well as the dr value of the two products are inside the parentheses, which are determined by 1H NMR using mesitylene as the internal standard.

[0230]

[0231] In the structural formulas of compounds 54b to 81b, the “ ” indicates that this chemical bond can face above or below the paper surface, and both isomers exist simultaneously.

[0232] Example 9

[0233] The synthesis of 1,2,3-tri-O-acetyl-4-phenylfuranose (1c) includes the following steps:

[0234] Under anaerobic conditions, [Rh(cod)Cl]2 (4.9 mg, 0.01 mmol), 2,2'-biquinoline (biqu) (7.7 mg, 0.03 mmol), and anhydrous tetrahydrofuran (1.0 mL) were successively added to a 25 mL Hastelloy autoclave and stirred evenly. Then, benzaldehyde (1a, 51 μL, d = 1.042 g / mL, 53.1 mg, 0.5 mmol) and dimethylphenylsilane (385 μL, d = 0.889 g / mL, 342.2 mg, 2.5 mmol) were added. The autoclave was sealed, filled with 3 Mpa CO (>99.99%), and then vented. This process was repeated three times to displace the gas inside the autoclave. Then, it was filled with 4 Mpa CO, and the autoclave was placed in an oil bath preheated to 40 °C and heated for 16 h. After the reaction was completed, the solvent was removed by rotary evaporation. To the residue, pyridine solution of hydrogen fluoride (70 wt%, 75 μL, d = 1.100 g / mL, 3.0 mmol), pyridine (1.5 mL), and acetic anhydride (1.5 mL) were added, and the mixture was stirred at 60 °C for 4 h to form the target product 1c and by-product 1c'. The main product 1c (79.1 mg, 49%) and 1c' (43.5 mg, 27%) were obtained by purification through silica gel chromatography.

[0235]

[0236] 1c

[0237] 1 H NMR (600 MHz, Chloroform-d) δ 7.35 – 7.27 (m, 5H), 6.27 (s, 1H),5.50 (d, J = 4.6 Hz, 1H), 5.46 (d, J = 4.7 Hz, 1H), 5.30 (s, 1H), 2.19 (s,3H), 2.18 (s, 3H), 1.72 (s, 3H).

[0238] 13 C NMR (151 MHz, Chloroform-d) δ 169.46, 169.16, 168.93, 134.71,128.21, 127.96, 127.30, 99.22, 85.21, 80.16, 74.86, 21.10, 20.72, 20.21.

[0239] Dissolve 1c (50.0 mg) in 3.0 mL of solvent (petroleum ether / ethyl ether = 1 / 1). Let the solvent slowly evaporate at room temperature. After natural crystallization for 24 hours, crystals of 1c can be obtained. The crystal data of 1c can be obtained by single-crystal X-ray diffraction, as Figure 3 shown.

[0240] 1c’

[0241] 1 H NMR (600 MHz, Chloroform-d) δ 7.35 – 7.29 (m, 3H), 7.28 – 7.25 (m,2H), 6.64 (d, J = 4.6 Hz, 1H), 5.62 (dd, J = 6.4, 5.2 Hz, 1H), 5.50 (d, J =6.4 Hz, 1H), 5.41 (t, J = 4.9 Hz, 1H), 2.13 (s, 3H), 2.12 (s, 3H), 1.63 (s,3H).

[0242] 13 C NMR (151 MHz, Chloroform-d) δ 169.71, 169.68, 169.38, 134.43,128.44, 127.99, 127.59, 93.14, 80.96, 75.87, 75.50, 20.93, 20.43, 20.11.

[0243] The above are only the preferred embodiments of the present invention. It should be noted that for those of ordinary skill in the art, without departing from the principle of the present invention, several improvements and refinements can be made, and these improvements and refinements should also be regarded as the protection scope of the present invention.

Claims

1. A method for preparing a 4 - substituted furanoside derivative, comprising the following steps: React an aldehyde, carbon monoxide, and a silane under catalyst conditions to obtain a silyl - protected 4 - substituted furanoside derivative; ； The aldehyde is R 1 CHO, where R 1 is a substituted or unsubstituted phenyl group having 6 to 20 carbon atoms, a substituted or unsubstituted monocyclic heteroaryl group having 5 to 30 carbon atoms, a substituted or unsubstituted fused-ring aryl group having 6 to 20 carbon atoms, a substituted or unsubstituted fused heteroaryl group having 6 to 20 carbon atoms, a substituted or unsubstituted alkyl group having 1 to 10 carbon atoms, a substituted or unsubstituted cycloalkyl group having 3 to 10 carbon atoms, or a substituted or unsubstituted heterocycloalkyl group having 3 to 10 carbon atoms; wherein the substituents in the substituted phenyl group, substituted monocyclic heteroaryl group, substituted fused-ring aryl group, substituted fused heteroaryl group, substituted alkyl group, substituted cycloalkyl group, and substituted heterocycloalkyl group are independently selected from one or more of hydroxyl, an alkyl group having 1 to 10 carbon atoms, a cycloalkyl group having 1 to 10 carbon atoms, an alkoxy group having 1 to 10 carbon atoms, a heteroaryl group having 5 to 10 carbon atoms, alkenyl, cyano, amino, halogen, nitro, mercapto, carboxyl, and phenyl. The catalyst includes a rhodium catalyst, and the rhodium catalyst is selected from one or more of rhodium compounds with a valence of 0 to +3, and the rhodium compounds are selected from rhodium salts and / or rhodium complexes; The catalyst optionally includes a ligand, and the ligand is selected from one or more of pyridine compounds, oxazoline compounds, pyrazine compounds, pyrazole compounds, thiazoline compounds, and imine compounds; The silane is HSiR 2 R 3 R 4 , where the R 2 , R 3 , R 4 are independently selected from one or more of substituted or unsubstituted C1-C10 alkyl groups, substituted or unsubstituted C6-C20 aryl groups, unsubstituted C7-C20 aralkyl groups, and C1-C10 alkoxy groups; The substituents in the substituted C1 - C10 alkyl are independently selected from one or more of hydroxyl, alkoxy, and halogen; The substituents in the substituted C6 - C20 aryl are independently selected from one or more of C1 - C10 alkoxy, C1 - C10 alkyl, and halogen; The reaction is carried out in a solvent, and the solvent is selected from one or more of ester solvents, cyclic ether solvents, and sulfone solvents; The molar ratio of the silane to the aldehyde is (3 - 10):

1.

2. The preparation method according to claim 1, characterized in that, R 2 and R 3 independently selected from substituted or unsubstituted C1-C10 alkyl, and R 4 is selected from substituted or unsubstituted C6-C20 aryl.

3. The preparation method according to claim 1, characterized in that, The reaction is carried out under closed conditions, and the pressure of carbon monoxide is 0.1 - 10 MPa.

4. The preparation method according to claim 1, characterized in that, The molar ratio of the rhodium catalyst to the aldehyde is 1:(5 - 10000).

5. The preparation method according to claim 1, wherein The concentration of the aldehyde in the solvent is 0.1 - 1 mol / L.

6. The preparation method according to claim 1, characterized in that, The temperature of the reaction is 20 - 100 °C, and the reaction time is 1 - 16 hours.

7. According to the preparation method described in claim 1, characterized in that, The molar ratio of the ligand to the rhodium atom in the rhodium catalyst is (1 - 10):

1.

8. The preparation method according to claim 1, characterized in that, Carry out a conversion reaction on the silyl - protected 4 - substituted furanoside derivative obtained by the reaction under the action of an acid catalyst and a ketone to obtain a 1,2 - ketal - protected 4 - substituted furanoside; The acid catalyst is selected from one or more of FeCl3, AlCl3, Al(OTf)3, Zn(OTf)2, ZrCl4, Y(OTf)3, In(OTf)3, Sc(OTf)3, p - toluenesulfonic acid, sulfamic acid, and pyridine p - toluenesulfonate; 9. The preparation method according to claim 1, characterized in that, Carry out a conversion reaction on the silyl - protected 4 - substituted furanoside derivative obtained by the reaction under the action of an acid anhydride to obtain an ester - protected 4 - substituted furanoside.

10. A method for preparing a 4 - substituted furanoside derivative, comprising the following steps: React an aldehyde, carbon monoxide, and a silane under catalyst conditions to obtain a silyl - protected 4 - substituted furanoside derivative; R 1 has one of the following structures: R is H, Me, Ph, t-Bu, OMe, OAc, CF3, F, Cl or Br; ； ； ； ； ； ； ； ； ； ； ； ； ； ； ； ； ； ； ； ； ； ； ； ； ； ； ； ； ； ； ； ； ； ； ； ； ； ； ； ； ； ； ； n=1,2,3,5,7； ; ; ; ; n = 1, 2, 3; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; The dashed line is the bonding site, indicating that the chemical bond faces above or below the paper surface, and both isomers exist simultaneously; The catalyst includes a rhodium catalyst, and the rhodium catalyst is selected from one or more of rhodium compounds with a valence of 0 to +3, and the rhodium compounds are selected from rhodium salts and / or rhodium complexes; The catalyst optionally includes a ligand, and the ligand is selected from one or more of pyridine compounds, oxazoline compounds, pyrazine compounds, pyrazole compounds, thiazoline compounds, and imine compounds; The silane is HSiR 2 R 3 R 4 , where the R 2 , R 3 , R 4 are independently selected from one or more of substituted or unsubstituted C1-C10 alkyl groups, substituted or unsubstituted C6-C20 aryl groups, unsubstituted C7-C20 aralkyl groups, and C1-C10 alkoxy groups; The substituents in the substituted C1 - C10 alkyl are independently selected from one or more of hydroxyl, alkoxy, and halogen; The substituents in the substituted C6 - C20 aryl are independently selected from one or more of C1 - C10 alkoxy, C1 - C10 alkyl, and halogen; The reaction is carried out in a solvent selected from one or more of ester solvents, cyclic ether solvents and sulfone solvents; The molar ratio of the silane to the aldehyde is (3 to 10):1.

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