Method for stereoselectively synthesizing chiral germanium / silicon compound

Abstract

The invention provides a method for stereoselectively synthesizing a chiral germanium / silicon compound, which is characterized in that a sugar redox active acid ester compound I which is easy to synthesize is used as a reaction substrate to be subjected to decarboxylation coupling reaction with a metal zinc reagent compound II, and the chiral germanium / silicon compound is simply and efficiently synthesized. Compared with other synthesis methods in the prior art, the method has the advantages of mild process conditions, easily available raw materials, low cost, high product yield and environmental friendliness, and can be popularized to industrial production; the process disclosed by the invention can also be widely applied to pharmaceutical synthesis and total synthesis of natural products in industrial and academic industries.

Description

Technical Field

[0001] The present invention belongs to the technical field of organic synthesis, and particularly relates to a method for stereoselectively synthesizing chiral germanium / silicon compounds. Background Art

[0002] Atom replacement chemistry plays a crucial role in synthetic chemistry and drug discovery. By atom replacement, the chemical and enzymatic stability of compounds can be improved and drug properties can be enhanced. Research shows that the geometry and composition of glycosidic bonds significantly affect the in vivo stability and binding affinity of sugar mimetics to druggable proteins. Therefore, chemists and medicinal chemists are increasingly inclined to modify glycosidic bonds to enhance functions while maintaining the overall structural integrity. For example, replacing the O-glycoside of KRN 7000 with a C-glycoside significantly increases its antimalarial and melanoma activities by 1000-fold.

[0003] Although C-glycosides have been widely studied, there has been less research on replacing O-glycosides with other Group IVA elements (such as silicon and germanium). Replacing carbon with silicon or germanium in bioactive molecules can significantly enhance bioactivity by optimizing the absorption, distribution, metabolism, excretion, and toxicity profiles. For example, the silicon and germanium analogs of the muscarinic antagonist cyclizine show stronger receptor affinity than the compound itself. Amino alcohols and their derivatives are essential structural units in pharmacologically active natural products, drug ingredients, and agrochemicals. And α- and β-amino organogermanium and organosilicon compounds often appear in drugs, amino acids, and fragrances. Therefore, the synthesis of chiral germanium / silicon-containing carbohydrates, amino alcohols, and diols has important theoretical significance and industrial practical value.

[0004] Currently, there is no method for synthesizing chiral germanium-containing carbohydrates and germanium / silicon-containing amino alcohols. However, there is a method for synthesizing chiral silicon-containing carbohydrates:

[0005] Method 1: Generate a glycosyl potassium intermediate from a C2-silyl-protected glycosyl sulfone under the action of potassium / naphthalene, and further synthesize 1,2-cis-glycosylsilane using a 1,3 O→C silyl migration mechanism.

[0006]

[0007] The limitations of this method are: the reaction conditions are harsh, the sugar types and reaction sites for the reaction are limited, and there is a competitive β-elimination pathway, resulting in a low reaction yield.

[0008] Method 2: Use a highly reactive silyl lithium reagent as a nucleophile to open the ring of a glycosyl epoxide to synthesize 1,2-trans-pyranosylsilane with high anomeric selectivity.

[0009]

[0010] The disadvantages of this method are as follows: the operation is complex, equivalent lithium is required, it is not applicable to furanose, mannose and 2-deoxy sugar, and it can only construct the anomeric C-Si bond.

[0011] As can be seen from the above, at present, the synthetic methods of chiral germanium / silicon compounds are limited, lacking catalytic methods, and the synthetic strategies still face problems such as harsh reaction conditions and low generality.

[0012] Although there are reports on the C(sp 3 )-Ge cross-coupling reaction of nickel-catalyzed germylzinc nucleophile and alkyl bromide, it does not involve the construction of chiral C(sp 3 )-Ge bond. Using silicon zinc or germanium zinc nucleophile to construct chiral C(sp 3 )-Si and C(sp 3 )-Ge bond is still a formidable challenge. Summary of the Invention

[0013] Based on the above technical problems, the present invention provides a method for stereoselective synthesis of chiral germanium / silicon compounds, making the synthesis of chiral germanium / silicon compounds possible. It not only has a simple process, safe operation, but also high yield, good functional group tolerance, strong stereospecificity, and is easy to promote in industrial production.

[0014] A method for stereoselective synthesis of chiral germanium / silicon compounds proposed by the present invention includes: performing a decarboxylative coupling reaction on the NHPI ester shown in Structural Formula I and the metal zinc reagent shown in Structural Formula II to obtain the chiral germanium / silicon compound shown in Structural Formula III;

[0015]

[0016] Among them, R is a glycosyl group, amino alcohol or diol group, and M is an organogermanium or silicon group.

[0017] In the present invention, the chiral germanium / silicon compound is essentially a sugar, amino alcohol or diol containing chiral germanium / silicon.

[0018] Preferably, the glycosyl group is glucose, deoxyglucose, galactose, deoxygalactose, mannose, fructose, ribose, deoxyribose, xylose, arabinose, IPTG, lyxose, fucose, rhamnose, sorbose, tagatose, N-acetylglucosamine, N-acetylgalactosamine, glucosamine, galactosamine or oligosaccharide.

[0019] Preferably, the NHPI ester shown in Structural Formula I includes the compounds shown in the following Structural Formula I', I” or I”':

[0020]

[0021] n is 0 or 1;

[0022] R1 is hydrogen, hydroxyl, amino, glycosyl, alkyl, alkoxy, alkenyl, aryl, ester carbonyl, NH-acyl, azido, mercapto, alkyl mercapto or OP, where P is a hydroxyl protecting group on the glycosyl;

[0023] X is O or NP, where P is an amino protecting group;

[0024] R2 is hydrogen, hydroxyl, amino, alkyl, alkoxy, alkenyl, aryl, ester carbonyl or NH-acyl;

[0025] R3 and R4 are hydrogen, alkyl, alkenyl or aryl.

[0026] Preferably, the zinc metal reagent shown in Structural Formula II includes the compounds shown in the following Structural Formula II' or Structural Formula II":

[0027]

[0028] R4-R6 are each independently alkyl, heterocyclic or aryl, and R7-R9 are each independently alkyl, heterocyclic or aryl.

[0029] Preferably, the decarboxylative coupling reaction is carried out under the reaction conditions of a nickel catalyst, a ligand and an inert gas protection;

[0030] Preferably, the nickel catalyst is at least one of Ni(dtbbpy)Cl2, Ni(DME)Cl2, Ni(DME)Br2, Ni(PPh3)2Cl2, Ni(acac)2, NiCl2, NiBr2 or Ni(OTf)2;

[0031] Preferably, the ligand includes a phosphine-containing ligand and / or a nitrogen-containing ligand. The phosphine-containing ligand is at least one of PCy3, PPh3, Dppp, Dppb, Dppf, Binap, Jackiephos, Xantphos, Xu-Phos, X-Phos or tBuBrettphos, and the nitrogen-containing ligand is at least one of 4,4'-di-tert-butyl-2,2'-bipyridine dtbbpy, bipyridine bpy, 4,4'-dimethoxy-2,2'-bipyridine or 2-(2-oxazolinyl)pyridine.

[0032] Preferably, the solvent for the decarboxylative coupling reaction is at least one of tetrahydrofuran, N,N-dimethylformamide, N,N-dimethylacetamide, 1,4-dioxane, toluene, diethylene glycol dimethyl ether or N-methylpyrrolidone, and preferably a mixed solvent of tetrahydrofuran and N,N-dimethylformamide.

[0033] Preferably, the molar ratio of the NHPI ester shown in Structural Formula I to the zinc metal reagent shown in Structural Formula II is 2-3:1; preferably 2:1.

[0034] Preferably, the decarboxylative coupling reaction is carried out at a temperature of 25-40 °C for 12-24 h.

[0035] The present invention also provides a chiral germanium / silicon compound synthesized by the above method.

[0036] Preferably, the chiral germanium / silicon compound has the following structure:

[0037]

[0038]

[0039] The present invention provides a chiral germanium / silicon compound synthesis process with a wide range of applications, which is suitable for synthesizing various chiral germanium / silicon carbohydrates, amino alcohols and diols. Especially for sugar compounds, whether it is a five-membered ring sugar or a six-membered ring sugar, it has good tolerance.

[0040] The present invention uses the easily synthesized sugar redox-active acid ester compound I as the reaction substrate to carry out a decarboxylative coupling reaction with the metal zinc reagent compound II, and simply and efficiently synthesizes the chiral germanium / silicon compound. Compared with other synthesis methods in the prior art, the process conditions of the present invention are mild, the raw materials are easy to obtain, the cost is low, the product yield is high, and it is environmentally friendly, and can be promoted to industrial production. The process of the present invention can also be widely applied to drug synthesis and total synthesis of natural products in industry and academia.

[0041] For the first time in the present invention, a highly stereoselective decarboxylative C(sp 3 )-Si and C(sp 3 )-Ge cross-coupling reaction of glycosyl NHPI esters with germanium / silicon zinc reagents was established. This method not only provides a powerful catalytic approach for the synthesis of silicon and germanium glycosides, but also solves the long-existing synthetic gap in the preparation of germanium glycosides, demonstrating remarkable versatility and practicality. This method has been successfully applied to more than 60 examples, including challenging substrates such as mannose and 2-deoxy sugar. In addition, it has been extended to the stereoselective synthesis of germanium / silicon-containing drug design building blocks, including germylated and silylated 1,2-amino alcohols and diols. Brief Description of the Drawings

[0042] Figure 1 1H NMR spectrum of triphenyl((2R,3S,4R,5R,6S)-3,4,5-tris(benzyloxy)-6-methoxytetrahydro-2H-pyran-2-yl)germane described in Example 1;

[0043] Figure 213C NMR spectrum of triphenyl((2R,3S,4R,5R,6S)-3,4,5-tris(benzyloxy)-6-methoxytetrahydro-2H-pyran-2-yl)germanium described in Example 1;

[0044] Figure 3 1H NMR spectrum of triphenyl((2R,3S,4S,5R,6R)-3,4,5-tris(benzyloxy)-6-(benzyloxymethyl)tetrahydro-2H-pyran-2-yl)germanium described in Example 11;

[0045] Figure 4 13C NMR spectrum of triphenyl((2R,3S,4S,5R,6R)-3,4,5-tris(benzyloxy)-6-(benzyloxymethyl)tetrahydro-2H-pyran-2-yl)germanium described in Example 11;

[0046] Figure 5 1H NMR spectrum of dimethylphenyl((2R,3S,4R,5R,6S)-3,4,5-tris(benzyloxy)-6-methoxytetrahydro-2H-pyran-2-yl)germanium described in Example 17;

[0047] Figure 6 13C NMR spectrum of dimethylphenyl((2R,3S,4R,5R,6S)-3,4,5-tris(benzyloxy)-6-methoxytetrahydro-2H-pyran-2-yl)germanium described in Example 17;

[0048] Figure 7 1H NMR spectrum of tert-butyl (2S,5S)-2-(tert-butyl)-5-(triphenylgermyl)oxazolidine-3-carboxylate described in Example 21;

[0049] Figure 8 13C NMR spectrum of tert-butyl (2S,5S)-2-(tert-butyl)-5-(triphenylgermyl)oxazolidine-3-carboxylate described in Example 21. Detailed Description of the Invention

[0050] Next, the present invention will be described in detail through specific examples. It should be clearly stated that these examples are for illustrative purposes only and should not be construed as limiting the scope of the present invention.

[0051] In the present invention, the "NHPI ester or redox-active acid ester compound" has the meaning commonly understood by those skilled in the art, that is, a saccharide compound, amino alcohol or diol compound directly connected to phthalimide, such as mannose-NHPI, glucose-NHPI, ribose-NHPI, amino alcohol-NHPI and their various derivatives.

[0052] In the present invention, the "metal zinc reagent" has the meaning commonly understood by those skilled in the art, such as R3SiZnCl and R3GeZnCl.

[0053] In the present invention, the catalyst Ni(dtbbpy)Cl2 or NiCl2(DME)+2-(2-oxazolinyl)pyridine was specifically purchased from Shanghai Haohong Biopharmaceutical Technology Co., Ltd.

[0054] 1 H NMR and 13 13C NMR were measured using Bruker Avance 400 spectrometer and Bruker Avance 500 spectrometer. The test temperature was room temperature, the solvent was deuterated chloroform (CDCl3), and the references were selected as follows: 1 1H NMR: CDCl3 was 7.26 ppm; 13 13C NMR: CHCl3 was 77.16 ppm.

[0055] The raw materials used in the following specific examples are all commercially available, and each reagent is used after being synthesized and purified by means well-known in the art when necessary.

[0056] The synthesis conditions of the chiral germanium compound were optimized to determine the best catalytic reaction system. Specifically, taking the synthesis process of triphenyl((2R,3S,4R,5R,6S)-3,4,5-tris(benzyloxy)-6-methoxytetrahydro-2H-pyran-2-yl)germane as an example, the synthesis route is as follows:

[0057]

[0058] As shown in the above reaction formula, in a glove box filled with argon, the reaction substrate 1 (0.20 mmol), Ni(DME)Cl2 (0.01 mmol), dtbbpy (0.01 mmol), Cy3P (0.01 mmol) and THF / DMF (12 / 1) (1.00 mL) were added to a dried 3 mL vial, and then the reaction substrate 2 (0.10 mmol) was added dropwise. The vial was capped and taken out of the glove box. After stirring the reaction at room temperature for 12 h, the reaction was quenched with water and diluted with ethyl acetate. The organic layer was dried over anhydrous sodium sulfate, filtered, concentrated, and separated and purified by column chromatography. The eluent was petroleum ether and ethyl acetate = 7:1 to obtain the target product 3.

[0059] According to the above method, 22 groups of parallel test groups were set up, and different catalysts, ligands, solvents and the equivalent ratios of reaction substrates 1 and 2 were used respectively to obtain the target product 3, and its yield was calculated. The results are shown in Table 1 below:

[0060] Table 1 Comparison of the yields of target product 3 under different reaction conditions

[0061]

[0062]

[0063] In the above table: The equivalent ratio is the equivalent ratio of reaction substrates 1 and 2; the yield is the isolated yield of target product 3; NiCl2(DME) = nickel chloride dimethoxyethane; dtbbpy = 4,4'-di-tert-butyl-2,2'-dipyridine; THF = tetrahydrofuran; DMF = N,N-dimethylformamide; DMAc = N,N-dimethylacetamide; NMP = N-methylpyrrolidone;

[0064]

[0065] As can be seen from Table 1 above, under the catalytic system of 10.0 mol% Ni(DME)Cl2 and ligands dtbbpy and PCy3 (each 10.0 mol%), the isolated yield of the target product can be as high as 85%, and it has a unique α-stereoselectivity at the non-anomeric C5 position (Table 1, entry 1); however, without adding the metal catalyst Ni(DME)Cl2, the yield of the target product drops to zero, thus confirming the necessity of the nickel catalyst (Table 1, entry 2); when the ligand dtbbpy is not added, the yield of the target product decreases significantly (Table 1, entry 2), and when the ligand PCy3 is not added, the yield of the target product is moderate (Table 1, entry 4); when using the nickel pre-prepared catalysts Ni(dtbbpy)Cl2 or Ni(PCy3)2Cl2, the yield remains basically unchanged (Table 1, entries 5-6); when using other alternative transition metals, including CuTc, PdCl2 or CrCl3, no product is formed (Table 1, entries 7-9), while only trace amounts of products are obtained with Co(DME)Br2 or FeBr (Table 1, entries 10-11); when using other ligands L1-L3 to replace dtbbpy, the yields of the target product all decrease to varying degrees. Among them, when the electro-neutral L1 replaces the electron-rich dtbbpy, the yield decreases slightly, and when the electron-deficient L2 replaces the electron-rich dtbbpy, the yield decreases significantly. In addition, L3 only leads to the formation of trace amounts of products, thus proving that the electronic and structural properties of the nitrogen ligand are crucial (Table 1, entries 12-14); when using phosphine ligands PMe3, PtBu3 and PPh3 to replace PCy3, the yields of the target product also all decrease to varying degrees, confirming the superiority of the PCy3 ligand (Table 1, entries 15-17); solvent screening determined that THF / DMF is the best co-solvent system, and DMF performs better than DMAC and NMP (Table 1, entries 18-20); adjusting the different ratios of reactants cannot increase the yield (Table 1, entries 21-22).

[0066] Based on the above-determined optimal catalytic reaction system, the present invention expands the range of reaction substrates adapted thereto, as specifically shown below:

[0067] Example 1

[0068] Synthesis of Triphenyl((2R,3S,4R,5R,6S)-3,4,5-Tris(benzyloxy)-6-methoxytetrahydro-2H-pyran-2-yl)germane

[0069] In a glove box filled with argon, 1,3-Dioxoisoindol-2-yl ((2S,3S,4S,5R,6S)-3,4,5-Tris(benzyloxy)-6-methoxytetrahydro-2H-pyran-2-carboxylate) (0.2 mmol), Ni(dtbbpy)Cl2 (0.01 mmol), tricyclohexylphosphine (0.01 mmol) and THF / DMF (12:1, 1.00 mL) were added to a dry 3 mL vial. Then, triphenylgermanium zinc chloride (0.1 mmol) was added dropwise. The vial was capped and taken out of the glove box. After stirring the reaction at room temperature for 12 h, the reaction was quenched with water and diluted with ethyl acetate. The organic layer was dried over anhydrous sodium sulfate, filtered, and concentrated. The crude product was separated and purified by column chromatography, and the eluent was petroleum ether and ethyl acetate = 7:1, to obtain 60.2 mg of the purified product with a yield of 85%.

[0070] Characterization data of the target product triphenyl((2R,3S,4R,5R,6S)-3,4,5-tris(benzyloxy)-6-methoxytetrahydro-2H-pyran-2-yl)germane: 1 H NMR(500MHz,CDCl3)δ7.51–7.49(m,6H),7.35–7.27(m,13H),7.25–7.15(m,9H),6.89–6.88(m,2H),4.98(d,J=10.4Hz,1H),4.78–4.70(m,3H),4.64(d,J=12.2Hz,1H),4.58(d,J=3.6Hz,1H),4.42(d,J=11.1Hz,1H),4.03(t,J=9.1Hz,1H),3.74(d,J=10.6Hz,1H),3.69(dd,J=11.0,8.6Hz,1H),3.53(dd,J=9.7,3.7Hz,1H),3.27(s,3H); 1313C NMR (126 MHz, CDCl3) δ 138.5, 138.4, 138.3, 135.8, 135.6, 135.5, 129.1, 128.6, 128.5, 128.4, 128.2, 128.1, 128.0, 127.9, 127.8, 127.3, 99.1, 84.1, 80.6, 79.5, 75.9, 74.2, 73.5, 64.4, 55.7; HRMS (ESI) m / z calcd for C 45 H 44 GeO5Na [M+Na] + 761.2298, found 761.2297。

[0071] Example 2

[0072] Synthesis of Triphenyl((2R,3S,4R,6S)-3,4-bis(benzyloxy)-6-methoxytetrahydro-2H-pyran-2-yl)germane

[0073] Referring to the method described in Example 1, except that 1,3-dioxoisoindol-2-yl ((2S,3S,4R,6S)-3,4-bis(benzyloxy)-6-methoxytetrahydro-2H-pyran-2-carboxylate) was used to replace 1,3-dioxoisoindol-2-yl ((2S,3S,4S,5R,6S)-3,4,5-tris(benzyloxy)-6-methoxytetrahydro-2H-pyran-2-carboxylate), 50.2 mg of the purified product was obtained with a yield of 79%.

[0074] Characterization data of the target product triphenyl((2R,3S,4R,6S)-3,4-bis(benzyloxy)-6-methoxytetrahydro-2H-pyran-2-yl)germane: 1 1H NMR (500 MHz, CDCl3) δ 7.47 (d, J = 7.3 Hz, 6H), 7.29–7.26 (m, 2H), 7.23–7.07 (m, 15H), 6.84–6.83 (m, 2H), 4.69–4.66 (m, 2H), 4.52 (d, J = 11.2 Hz, 1H), 4.45 (d, J = 11.2 Hz, 1H), 4.33 (d, J = 10.9 Hz, 1H), 3.96 (ddd, J = 11.7, 8.4, 4.8 Hz, 1H), 3.69 (d, J = 10.7 Hz, 1H), 3.60 (dd, J = 10.9, 8.5 Hz, 1H), 3.12 (s, 3H), 2.24 (dd, J = 13.1, 4.9 Hz, 1H), 1.63–1.58 (m, 1H); 1313C NMR (126 MHz, CDCl3) δ 138.6, 138.5, 135.9, 135.8, 129.0, 128.5, 128.1, 128.0 (3), 127.8, 127.2, 99.5, 79.7, 79.6, 74.1, 71.6, 65.1, 55.1, 35.5; HRMS (ESI) m / z calcd for C 38 H 38 GeO4Na [M+Na] + 655.1880, found 655.1876。

[0075] Example 3

[0076] Synthesis of Triphenyl((2S,3R,4R,5R,6R)-3,4,5-tris(benzyloxy)-6-methoxytetrahydro-2H-pyran-2-yl)germane

[0077] Referring to the method described in Example 1, except that 1,3-dioxoisoindol-2-yl ((2S,3R,4S,5R,6R)-3,4,5-tris(benzyloxy)-6-methoxytetrahydro-2H-pyran-2-carboxylate) was used to replace 1,3-dioxoisoindol-2-yl ((2S,3S,4S,5R,6S)-3,4,5-tris(benzyloxy)-6-methoxytetrahydro-2H-pyran-2-carboxylate), 44.8 mg of the purified product was obtained with a yield of 61%.

[0078] Characterization data of the target product triphenyl((2S,3R,4R,5R,6R)-3,4,5-tris(benzyloxy)-6-methoxytetrahydro-2H-pyran-2-yl)germane: 1 1H NMR (400 MHz, CDCl3) δ 7.54–7.51 (m, 6H), 7.36–7.26 (m, 11H), 7.25–7.13 (m, 11H), 6.97–6.95 (m, 2H), 4.92 (d, J = 7.9 Hz, 1H), 4.59–4.43 (m, 5H), 4.24 (d, J = 11.6 Hz, 1H), 4.00 (dd, J = 8.0, 2.8 Hz, 1H), 3.87 (d, J = 11.6 Hz, 1H), 3.75–3.69 (m, 2H), 3.18 (s, 3H); 1313C NMR(101MHz,CDCl3)δ138.8,138.7,138.3,135.8,135.7,129.1,128.4(2),128.2,128.1,127.9,127.8,127.6(2),127.5,127.3,102.2,75.4,74.7,72.8,72.5,71.0,64.9,56.0; HRMS(ESI)m / z calcd for C 45 H 44 GeO5Na[M+Na] + 761.2298, found 761.2307。

[0079] Example 4

[0080] Synthesis of Triphenyl((3aR,5aR,8aR,8bS)-2,2,7,7-tetramethyltetrahydro-3aH-bis([1,3]dioxane)[4,5-b:4',5'-d]pyrazin-3a-yl)germane

[0081] Referring to the method described in Example 1, except that 1,3-dioxoisoindol-2-yl((3aR,5aR,8aR,8bS)-2,2,7,7-tetramethyltetrahydro-3aH-bis([1,3]dioxane)[4,5-b:4',5'-d]pyran-3a-carboxylate) was used to replace 1,3-dioxoisoindol-2-yl((2S,3S,4S,5R,6S)-3,4,5-tris(benzyloxy)-6-methoxytetrahydro-2H-pyran-2-carboxylate), 11.3 mg of the purified product was obtained with a yield of 21%.

[0082] Characterization data of the target product triphenyl((3aR,5aR,8aR,8bS)-2,2,7,7-tetramethyltetrahydro-3aH-bis([1,3]dioxane)[4,5-b:4',5'-d]pyrazin-3a-yl)germane: 1 1H NMR(500MHz,CDCl3)δ7.67–7.66(m,6H),7.37–7.33(m,9H),4.61(d,J = 2.6Hz,1H),4.52(dd,J = 8.1,2.6Hz,1H),4.14(dd,J = 7.9,1.9Hz,1H),3.94(dd,J = 12.9,2.1Hz,1H),3.78(dd,J = 12.9,0.9Hz,1H),1.54(s,3H),1.21(s,3H),0.80(s,3H),0.56(s,3H); 1313C NMR (126 MHz, CDCl3) δ 136.7, 135.0, 129.1, 128.1, 108.7, 107.9, 106.2, 73.1, 70.5, 69.8, 61.5, 26.2, 25.9, 23.8, 23.5; HRMS (ESI) m / z calcd for C 29 H 32 GeO5Na [M+Na] + 557.1359, found 557.1342.

[0083] Example 5

[0084] Synthesis of Triphenyl((2R,3S,4R,5S,6S)-3,4,5-Tribenzyloxy-6-methoxytetrahydro-2H-pyran-2-yl)germane

[0085] Referring to the method described in Example 1, except that 1,3-dioxoisoindol-2-yl ((2S,3S,4S,5S,6S)-3,4,5-tribenzyloxy-6-methoxytetrahydro-2H-pyran-2-carboxylate) was used instead of 1,3-dioxoisobenzofuran-2-yl ((2S,3S,4S,5R,6S)-3,4,5-tris(benzyloxy)-6-methoxytetrahydro-2H-pyran-2-carboxylate), 53.3 mg of the purified product was obtained with a yield of 72%.

[0086] Characterization data of the target product triphenyl((2R,3S,4R,5S,6S)-3,4,5-tribenzyloxy-6-methoxytetrahydro-2H-pyran-2-yl)germane: 1 1H NMR (400 MHz, CDCl3) δ 7.56–7.49 (m, 6H), 7.34–7.21 (m, 7H), 7.23–7.15 (m, 12H), 7.13–7.03 (m, 3H), 6.79–6.77 (m, 2H), 4.72–4.63 (m, 2H), 4.65–4.55 (m, 2H), 4.55 (d, J = 11.6 Hz, 1H), 4.50 (d, J = 11.6 Hz, 1H), 4.28 (d, J = 10.9 Hz, 1H), 4.18 (dd, J = 10.9, 8.6 Hz, 1H), 3.90 (dd, J = 8.6, 3.0 Hz, 1H), 3.76 (dd, J = 3.0, 2.0 Hz, 1H), 3.70 (d, J = 10.6 Hz, 1H), 3.15 (s, 3H); 1313C NMR(126MHz,CDCl3)δ138.7,138.6(2),136.0,135.8,128.9,128.5,128.4,128.1,128.0(2),127.9,127.7,127.6,127.2,99.9,82.1,76.1,75.4,74.1,72.7,72.0,65.9,55.2; HRMS(ESI)m / z calcd for C 45 H 44 GeO5Na[M+Na] + 761.2298, found 761.2293。

[0087] Example 6

[0088] Synthesis of Triphenyl((2R,3S,4R,5R)-3,4-bis(benzyloxy)-5-methoxytetrahydrofuran-2-yl)germane

[0089] Referring to the method described in Example 1, except that 1,3-dioxoisoindol-2-yl ((2S,3S,4R,5R)-3,4-bis(benzyloxy)-5-methoxytetrahydrofuran-2-carboxylate) was used to replace 1,3-dioxoisobenzindol-2-yl ((2S,3S,4S,5R,6S)-3,4,5-tris(benzyloxy)-6-methoxytetrahydro-2H-pyran-2-carboxylate), 56.5 mg of the purified product was obtained with a yield of 91%.

[0090] Characterization data of the target product triphenyl((2R,3S,4R,5R)-3,4-bis(benzyloxy)-5-methoxytetrahydrofuran-2-yl)germane: 1 1H NMR(400MHz,CDCl3)δ7.44–7.41(m,6H),7.29–7.07(m,17H),6.86–6.84(m,2H),4.81(s,1H),4.77(d,J = 9.2Hz,1H),4.54(d,J = 12.1Hz,1H),4.44(d,J = 12.1Hz,1H),4.23–4.19(m,2H),4.04(d,J = 11.6Hz,1H),3.59(d,J = 4.4Hz,1H),2.85(s,3H); 13 13C NMR(101MHz,CDCl3)δ137.9,137.6,135.8,135.4,129.1,128.5,128.3(2),128.2,128.0,127.7,106.8,79.9,78.9,74.3,72.4,72.3,54.9; HRMS(ESI)m / z calcd for C37 H 36 GeO4Na[M+Na] + 641.1723, found 641.1724。

[0091] Example 7

[0092] Synthesis of Triphenyl((2S,3R,4R,5R,6S)-3,4,5-Tribenzyloxy-6-(isopropylthio)tetrahydro-2H-pyran-2-yl)germane

[0093] Referring to the method described in Example 1, except that 1,3-dioxoisoindol-2-yl ((2R,3R,4S,5R,6S)-3,4,5-tribenzyloxy-6-(isopropylthio)tetrahydro-2H-pyran-2-carboxylate) was used to replace 1,3-dioxoisobenzindol-2-yl ((2S,3S,4S,5R,6S)-3,4,5-tris(benzyloxy)-6-methoxytetrahydro-2H-pyran-2-carboxylate), 34.5 mg of the purified product was obtained with a yield of 44%.

[0094] Characterization data of the target product triphenyl((2S,3R,4R,5R,6S)-3,4,5-tribenzyloxy-6-(isopropylthio)tetrahydro-2H-pyran-2-yl)germane: 1 H NMR(500MHz,CDCl3)δ7.58–7.55(m,6H),7.37–7.13(m,22H),6.91–6.89(m,2H),5.27(d,J=10.1Hz,1H),5.20(d,J=1.6Hz,1H),4.64–4.60(m,2H),4.54(d,J=12.7Hz,1H),4.38(d,J=12.0Hz,1H),4.06–4.02(m,2H),3.88–3.86(m,1H),3.79(t,J=3.6Hz,1H),3.70(d,J=11.4Hz,1H),2.80–2.74(m,1H),1.18–1.16(m,6H); 13 C NMR(126MHz,CDCl3)δ138.5,138.4,138.1,136.0,135.9,128.8,128.5,128.4,128.0(3),127.8(2),127.6,127.5,127.3,82.9,78.4,75.1,72.3,72.0,70.4,63.2,35.9,23.9,23.5; HRMS(ESI)m / z calcd for C 47 H 48 GeO4SNa[M+Na] +805.2383, found 805.2386。

[0095] Example 8

[0096] Synthesis of Triphenyl((2R,3S,4R,5R,6S)-3,4,5-trimethoxy-6-((2S,3S,4R,5S,6S)-3,4,5-trimethoxy-6-(methoxymethyl)tetrahydro-2H-pyran-2-yl)oxy)tetrahydro-2H-pyran-2-yl)germane

[0097] Referring to the method described in Example 1, except that 1,3-dioxoisoindol-2-yl ((2S,3S,4S,5R,6R)-3,4,5-trimethoxy-6-((2S,3S,4R,5S,6S)-3,4,5-trimethoxy-6-(methoxymethyl)tetrahydro-2H-pyran-2-yl)oxy)tetrahydro-2H-pyran-2-carboxylate was used to replace 1,3-dioxoisobenzofuran-2-yl ((2S,3S,4S,5R,6S)-3,4,5-tris(benzyloxy)-6-methoxytetrahydro-2H-pyran-2-carboxylate), and the eluent was petroleum ether and ethyl acetate = 2:1, 49.8 mg of the purified product was obtained, and the yield was 70%.

[0098] Characterization data of the target product triphenyl((2R,3S,4R,5R,6S)-3,4,5-trimethoxy-6-((2S,3S,4R,5S,6S)-3,4,5-trimethoxy-6-(methoxymethyl)tetrahydro-2H-pyran-2-yl)oxy)tetrahydro-2H-pyran-2-yl)germane: 1 H NMR(500MHz,CDCl3)δ7.55–7.53(m,6H),7.38–7.31(m,9H),5.16(d,J=3.5Hz,1H),5.04(d,J=3.7Hz,1H),4.69(d,J=11.3Hz,1H),3.96–3.93(m,1H),3.63(s,3H),3.60–3.49(m,10H),3.39-3.38(m,6H),3.30(dd,J=11.3,8.5Hz,1H),3.21(dd,J=10.2,9.0Hz,1H),3.14(dd,J=9.6,3.6Hz,1H),3.11(dd,J=9.6,3.7Hz,1H),3.05(s,3H),2.99(s,3H); 13CNMR(126MHz,CDCl3)δ135.7,129.0,128.1,93.2,92.9,84.8,83.5,82.2,81.5,81.4,79.6,71.0,70.3,64.8,60.9,60.8,60.6,59.8,59.3,59.2,58.3.HRMS(ESI)m / z calcd forC 36 H 48 GeO 10 Na[M+Na]+737.2357,found 737.2355。

[0099] Example 9

[0100] Synthesis of Triphenyl((3R,4S,5R,6R)-3,4,5-Tribenzyloxy-6-(benzyloxymethyl)tetrahydro-2H-pyran-2-yl)germane

[0101] Referring to the method described in Example 1, except that 1,3-dioxoisoindol-2-yl ((3R,4S,5R,6R)-3,4,5-tribenzyloxy-6-(benzyloxymethyl)tetrahydro-2H-pyran-2-carboxylate) was used to replace 1,3-dioxoisobenzofuran-2-yl ((2S,3S,4S,5R,6S)-3,4,5-tris(benzyloxy)-6-methoxytetrahydro-2H-pyran-2-carboxylate), 33.2 mg of the purified product was obtained with a yield of 40%.

[0102] Characterization data of the target product triphenyl((3R,4S,5R,6R)-3,4,5-tribenzyloxy-6-(benzyloxymethyl)tetrahydro-2H-pyran-2-yl)germane: α-isomer: 1 H NMR(400MHz,CDCl3)δ7.57–7.55(m,6H),7.37–7.13(m,27H),6.87–6.84(m,2H),4.94(d,J=10.8Hz,1H),4.85–4.81(m,2H),4.72–4.66(m,2H),4.45(d,J=12.3Hz,1H),4.37(d,J=12.3Hz,1H),4.11(d,J=10.2Hz,1H),3.84–3.64(m,6H),3.46(ddd,J=9.7,4.3,1.8Hz,1H); 1313C NMR (126 MHz, CDCl3) δ 138.9, 138.5, 138.4, 138.3, 135.9, 135.8, 129.0, 128.6 (2), 128.4, 128.2, 128.1, 128.0, 127.9, 127.8 (2), 127.7, 127.5, 127.4, 127.3, 89.3, 82.9, 80.0, 79.1, 75.7, 75.3, 74.8, 74.1, 73.6, 69.2; HRMS (ESI) m / z calcd for C 52 H 50 GeO5Na [M+Na] + 851.2768, found 851.2776; β-isomer: 1 1H NMR (400 MHz, CDCl3) δ 7.65–7.62 (m, 6H), 7.37–7.17 (m, 23H), 7.15–7.12 (m, 2H), 7.09–7.06 (m, 2H), 6.96–6.94 (m, 2H), 5.21 (d, J = 6.6 Hz, 1H), 4.65 (d, J = 11.4 Hz, 1H), 4.59–4.54 (m, 2H), 4.47 (d, J = 11.1 Hz, 1H), 4.41–4.33 (m, 4H), 4.00 (dd, J = 7.8, 6.4 Hz, 1H), 3.68–3.55 (m, 4H), 3.49–3.46 (m, 1H); 13 13C NMR (126 MHz, CDCl3) δ 138.8, 138.7, 138.3, 138.0, 137.2, 135.9, 128.9, 128.4 (2), 128.3, 128.2 (2), 128.0 (2), 127.7 (2), 127.6, 127.5 (2), 83.0, 81.1, 77.7, 77.1, 75.1, 74.8, 74.0, 74.0, 73.5, 68.8; HRMS (ESI) m / z calcd for C 52 H 50 GeO5Na [M+Na] + 851.2768, found 851.2767。

[0103] Example 10

[0104] Synthesis of Triphenyl((2R,3R,4S,5S,6R)-3,4,5-Tribenzyloxy-6-(benzyloxymethyl)tetrahydro-2H-pyran-2-yl)germane

[0105] Referring to the method described in Example 1, except that 1,3-dioxoisoindol-2-yl ((3R,4S,5S,6R)-3,4,5-tribenzyloxy-6-(benzyloxymethyl)tetrahydro-2H-pyran-2-carboxylate) was used to replace 1,3-dioxoisoindol-2-yl ((2S,3S,4S,5R,6S)-3,4,5-tris(benzyloxy)-6-methoxytetrahydro-2H-pyran-2-carboxylate), 55.8 mg of the purified product was obtained, and the yield was 68%.

[0106] Characterization data of the target product triphenyl((2R,3R,4S,5S,6R)-3,4,5-tribenzyloxy-6-(benzyloxymethyl)tetrahydro-2H-pyran-2-yl)germane: 1 1H NMR (500 MHz, CDCl3) δ 7.51 (d, J = 7.3 Hz, 6H), 7.28–7.11 (m, 27H), 6.84 (d, J = 7.3 Hz, 2H), 4.91 (d, J = 2.7 Hz, 1H), 4.54–4.47 (m, 4H), 4.39 (d, J = 12.0 Hz, 1H), 4.32 (d, J = 11.9 Hz, 1H), 4.18–4.11 (m, 2H), 4.04–4.00 (m, 1H), 3.95 (d, J = 4.7 Hz, 1H), 3.88 (d, J = 11.2 Hz, 1H), 3.67–3.64 (m, 3H); 13 13C NMR (126 MHz, CDCl3) δ 138.7 (2), 138.6, 138.2, 137.0, 135.8, 128.8, 128.4, 128.2, 128.1, 128.0, 127.8, 127.7 (2), 127.5 (2), 78.5, 75.8, 74.2, 73.3, 73.2, 72.8, 72.5, 69.5, 66.4; HRMS (ESI) m / z calcd for C 52 H 50 GeO5Na [M+Na] + 851.2768, found 851.2780.

[0107] Example 11

[0108] Synthesis of triphenyl((2R,3S,4S,5R,6R)-3,4,5-tribenzyloxy-6-(benzyloxymethyl)tetrahydro-2H-pyran-2-yl)germane

[0109] Referring to the method described in Example 1, except that 1,3-dioxoisoindol-2-yl ((3S,4S,5R,6R)-3,4,5-tribenzyloxy-6-(benzyloxymethyl)tetrahydro-2H-pyran-2-carboxylate) was used to replace 1,3-dioxoisoindol-2-yl ((2S,3S,4S,5R,6S)-3,4,5-tris(benzyloxy)-6-methoxytetrahydro-2H-pyran-2-carboxylate), 40.3 mg of the purified product was obtained with a yield of 48%.

[0110] Characterization data of the target product triphenyl((2R,3S,4S,5R,6R)-3,4,5-tribenzyloxy-6-(benzyloxymethyl)tetrahydro-2H-pyran-2-yl)germane: 1 H NMR(400MHz,CDCl3)δ7.41–7.39(m,6H),7.30–7.13(m,25H),7.06–7.02(m,4H),5.03(d,J=3.9Hz,1H),4.59(d,J=11.6Hz,1H),4.49–4.34(m,5H),4.18(d,J=12.0Hz,1H),4.07(d,J=12.1Hz,1H),3.97(t,J=3.5Hz,1H),3.83(t,J=7.6Hz,1H),3.69–3.52(m,4H); 13 C NMR(101MHz,CDCl3)δ139.0,138.6,138.4,136.0,135.6,134.2,129.2,128.6,128.4(3),128.3,128.2,127.9,127.7,127.6(2),127.5(2),127.4,78.9,77.3,75.5,75.3,73.5,73.3,71.8,71.4,70.9,69.3;HRMS(ESI)m / z calcd forC 52 H 50 GeO5Na[M+Na] + 851.2768,found851.2769。

[0111] Example 12

[0112] Synthesis of triphenyl((2R,4R,5R,6R)-4,5-bis(benzyloxy)-6-(benzyloxymethyl)tetrahydro-2H-pyran-2-yl)germane

[0113] Referring to the method described in Example 1, except that 1,3-dioxoisoindol-2-yl ((4R,5R,6R)-4,5-bis(benzyloxy)-6-(benzyloxymethyl)tetrahydro-2H-pyran-2-carboxylate) was used to replace 1,3-dioxoisobenzofuran-2-yl ((2S,3S,4S,5R,6S)-3,4,5-tris(benzyloxy)-6-methoxytetrahydro-2H-pyran-2-carboxylate), 68.0 mg of the purified product was obtained with a yield of 94%.

[0114] Characterization data of the target product triphenyl((2R,4R,5R,6R)-4,5-bis(benzyloxy)-6-(benzyloxymethyl)tetrahydro-2H-pyran-2-yl)germane: 1 H NMR(400MHz,CDCl3)δ7.63–7.56(m,6H),7.39–7.20(m,24H),5.05(d,J=11.5Hz,0.08H),4.92(dd,J=9.5,3.7Hz,0.92H),4.67–4.40(m,6H),4.22–4.10(m,2H),3.80–3.58(m,3H),2.65–2.56(m,0.08H),2.25–2.19(m,0.92H),2.03–1.97(m,0.92H),1.88–1.83(m,0.08H); 13 C NMR(126MHz,CDCl3)δ138.9,138.8,138.7,136.1,135.5,129.1,128.4(2),128.3,127.7(2),127.6,127.^2,75.8,73.7,73.2,71.9,71.4,67.2,31.7;HRMS(ESI)m / z calcd for C 45 H 44 GeO4Na[M+Na] + 745.2349,found 745.2358.

[0115] Example 13

[0116] Synthesis of triphenyl((2S,3R,4R,5R)-3,4-bis(benzyloxy)-5-(benzyloxymethyl)tetrahydrofuran-2-yl)germane

[0117] Referring to the method described in Example 1, except that 1,3-dioxoisoindol-2-yl ((3R,4R,5R)-3,4-bis(benzyloxy)-5-(benzyloxymethyl)tetrahydrofuran-2-carboxylate) was used to replace 1,3-dioxoisobenzindol-2-yl ((2S,3S,4S,5R,6S)-3,4,5-tris(benzyloxy)-6-methoxytetrahydro-2H-pyran-2-carboxylate), 69.7 mg of the purified product was obtained with a yield of 99%.

[0118] Characterization data of the target product triphenyl((2S,3R,4R,5R)-3,4-bis(benzyloxy)-5-(benzyloxymethyl)tetrahydrofuran-2-yl)germane: 1 H NMR(400MHz,CDCl3)δ7.45–7.43(m,6H),7.30–7.09(m,22H),6.93–6.91(m,2H),4.76(d,J=6.2Hz,1H),4.41–4.29(m,2H),4.30(s,2H),4.27(d,J=11.7Hz,1H),4.19–4.09(m,2H),3.94(dd,J=6.3,5.1Hz,1H),3.50–3.48(m,1H),3.18(d,J=4.8Hz,2H); 13 CNMR(101MHz,CDCl3)δ138.5,137.9,135.7,135.3,129.2,128.4(3),128.3(2),128.2,127.9,127.7,127.6(2),81.5,79.5,78.2,76.1,73.2,71.9,71.8,70.3;HRMS(ESI)m / z calcd for C 44 H 42 GeO4Na[M+Na] + 731.2193,found 731.2197。

[0119] Example 14

[0120] Synthesis of triphenyl((2R,3S,4R,5R)-3,4-bis(benzyloxy)-5-(benzyloxymethyl)tetrahydrofuran-2-yl)germane

[0121] By referring to the method described in Example 1, except that 1,3-dioxoisoindol-2-yl((3S,4R,5R)-3,4-bis(benzyloxy)-5-(benzyloxymethyl)tetrahydrofuran-2-carboxylate) was used instead of 1,3-dioxyisobenzindol-2-yl((2S,3S,4S,5R,6S)-3,4,5-tris(benzyloxy)-6-methoxytetrahydro-2H-pyran-2-carboxylate), 65.3 mg of purified product was obtained with a yield of 92%.

[0122] Characterization data of the target product triphenyl((2R,3S,4R,5R)-3,4-bis(benzyloxy)-5-(benzyloxymethyl)tetrahydrofuran-2-yl)germane: 1 H NMR (500MHz, CDCl3) δ7.58–7.56(m,6H),7.37–7.19(m,22H),6.97(dd,J=6.4,2 .8Hz,2H),4.61(d,J=7.0Hz,1H),4.55(s,2H),4.43(d,J=11.8Hz,1H),4.39–4.3 5(m,2H),4.29(d,J=11.3Hz,1H),4.26–4.23(m,1H),4.18(d,J=11.3Hz,1H),4. 08(t,J=2.9Hz,1H),3.64(dd,J=10.1,6.0Hz,1H),3.58(dd,J=10.1,6.5Hz,1H); 13 CNMR(126MHz, CDCl3)δ138.4,138.0,137.8,135.6(2),129.2,128.5,128.4,128.3(2 ),127.9(2),127.7(3),87.5,86.1,82.7,76.6,73.4,72.1,71.6,69.3; HRMS(ESI)m / z calcd forC 44 H 42 GeO4Na[M+Na] + 731.2193,found731.2194.

[0123] Example 15

[0124] Synthesis of Tri-p-Methylphenyl ((2R,3S,4R,5R,6S)-3,4,5-Tribenzyloxy-6-methoxytetrahydro-2H-pyran-2-yl)germane

[0125] Referring to the method described in Example 1, except that tri-p-methylphenylgermanium zinc chloride was used instead of triphenylgermanium zinc chloride, 56.2 mg of purified product was obtained with a yield of 72%.

[0126] Characterization data of the target product tris(4-methylphenyl)((2R,3S,4R,5R,6S)-3,4,5-tris(benzyloxy)-6-methoxytetrahydro-2H-pyran-2-yl)germane: 1 H NMR(400MHz,CDCl3)δ7.41–7.40(m,6H),7.36–7.15(m,13H),7.11–7.09(m,6H),6.91–6.89(m,2H),4.98(d,J=10.5Hz,1H),4.79–4.74(m,2H),4.71(d,J=10.7Hz,1H),4.65(d,J=12.2Hz,1H),4.60(d,J=3.6Hz,1H),4.39(d,J=11.1Hz,1H),4.06–4.01(m,1H),3.81(d,J=10.7Hz,1H),3.68(dd,J=11.1,8.6Hz,1H),3.52(dd,J=9.7,3.6Hz,1H),3.30(s,3H),2.33(s,9H); 13 C NMR(126MHz,CDCl3)δ138.7,138.6,138.4,135.7,132.1,129.0,128.6,128.5,128.2,128.1,128.0(2),127.9,127.7,127.2,99.0,84.1,80.6,79.6,75.9,74.1,73.4,64.5,55.7,21.6;HRMS(ESI)m / z calcdfor C 48 H 50 GeO5Na[M+Na] + 803.2768,found803.2777。

[0127] Example 16

[0128] Synthesis of methyldiphenyl((2R,3S,4R,5R,6S)-3,4,5-tris(benzyloxy)-6-methoxytetrahydro-2H-pyran-2-yl)germane

[0129] Referring to the method described in Example 1, except that methyldiphenylgermanium zinc chloride was used instead of triphenylgermanium zinc chloride, 47.2 mg of the purified product was obtained with a yield of 77%.

[0130] Characterization data of the target product methyldiphenyl((2R,3S,4R,5R,6S)-3,4,5-tris(benzyloxy)-6-methoxytetrahydro-2H-pyran-2-yl)germane: 11H NMR (500 MHz, CDCl3) δ 7.60–7.58 (m, 2H), 7.50–7.48 (m, 2H), 7.38–7.22 (m, 19H), 7.01–6.99 (m, 2H), 4.99 (d, J = 10.6 Hz, 1H), 4.81–4.74 (m, 3H), 4.67 (d, J = 12.2 Hz, 1H), 4.60 (d, J = 3.5 Hz, 1H), 4.12–4.08 (m, 2H), 4.00 (t, J = 9.1 Hz, 1H), 3.61 (dd, J = 11.2, 8.5 Hz, 1H), 3.54 (dd, J = 9.6, 3.6 Hz, 1H), 3.23 (s, 3H), 0.69 (s, 3H); 13 13C NMR (126 MHz, CDCl3) δ 138.7, 138.4 (2), 137.9, 136.7, 134.9, 134.5, 129.0, 128.8, 128.5 (2), 128.2 (2), 128.1 (2), 127.9, 127.7 (2), 127.4, 98.8, 83.9, 80.7, 79.9, 75.8, 74.2, 73.4, 64.3, 55.2, -5.2; HRMS (ESI) m / z calcd for C 40 H 42 GeO5Na [M+Na] + 699.2142, found 699.2143。

[0131] Example 17

[0132] Synthesis of dimethylphenyl ((2R,3S,4R,5R,6S)-3,4,5-tris(benzyloxy)-6-methoxytetrahydro-2H-pyran-2-yl)germane

[0133] Referring to the method described in Example 1, except that dimethylphenylgermanium zinc chloride was used instead of triphenylgermanium zinc chloride, 25.1 mg of the purified product was obtained with a yield of 41%.

[0134] Characterization data of the target product dimethylphenyl ((2R,3S,4R,5R,6S)-3,4,5-tris(benzyloxy)-6-methoxytetrahydro-2H-pyran-2-yl)germane: 11H NMR (400 MHz, CDCl3) δ 7.48–7.46 (m, 2H), 7.36–7.23 (m, 16H), 7.11–7.09 (m, 2H), 4.96 (d, J = 10.7 Hz, 1H), 4.87 (d, J = 11.0 Hz, 1H), 4.76 (d, J = 12.2 Hz, 1H), 4.72 (d, J = 10.7 Hz, 1H), 4.65 (d, J = 12.1 Hz, 1H), 4.57 (d, J = 3.6 Hz, 1H), 4.32 (d, J = 10.9 Hz, 1H), 3.95 (dd, J = 9.6, 8.5 Hz, 1H), 3.76 (d, J = 11.2 Hz, 1H), 3.52–3.47 (m, 2H), 3.26 (s, 3H), 0.44 (s, 3H), 0.42 (s, 3H); 13 13C NMR (126 MHz, CDCl3) δ 139.2, 138.7, 138.5, 138.4, 133.9, 128.7, 128.6, 128.5, 128.3, 128.2, 128.1(2), 128.0, 127.7, 127.6, 127.5, 98.7, 83.9, 80.7, 80.0, 75.8, 74.2, 73.4, 64.1, 54.9, -4.3, -4.7; HRMS (ESI) m / z calcd for C 35 H 40 GeO5Na [M + Na] + 637.1985, found 637.1982.

[0135] Example 18

[0136] Synthesis of Triphenyl((2R,3S,4R,5R,6S)-3,4,5-tris(benzyloxy)-6-methoxytetrahydro-2H-pyran-2-yl)silane

[0137] Referring to the method described in Example 1, except that triphenylsilylzinc chloride was used instead of triphenylgermanylzinc chloride, and the eluent was petroleum ether and ethyl acetate = 10:1, 13.9 mg of the purified product was obtained with a yield of 20%.

[0138] Characterization data of the target product triphenyl((2R,3S,4R,5R,6S)-3,4,5-tris(benzyloxy)-6-methoxytetrahydro-2H-pyran-2-yl)silane: 11H NMR (400 MHz, CDCl3) δ 7.60–7.57 (m, 6H), 7.41–7.26 (m, 15H), 7.25–7.14 (m, 7H), 6.86–6.84 (m, 2H), 4.96 (d, J = 10.5 Hz, 1H), 4.76 (d, J = 8.8 Hz, 1H), 4.74 (d, J = 7.2 Hz, 1H), 4.67–4.62 (m, 2H), 4.57 (d, J = 3.7 Hz, 1H), 4.29 (d, J = 11.1 Hz, 1H), 4.03 (dd, J = 9.6, 8.6 Hz, 1H), 3.72 (d, J = 10.7 Hz, 1H), 3.64 (dd, J = 11.1, 8.6 Hz, 1H), 3.50 (dd, J = 9.6, 3.6 Hz, 1H), 3.23 (s, 3H); 13 13C NMR (126 MHz, CDCl3) δ 138.7, 138.5, 138.3, 136.6, 133.4, 129.7, 128.6, 128.5, 128.2, 128.1, 128.0 (2), 127.8 (2), 127.3, 99.1, 84.1, 80.7, 79.5, 75.9, 74.2, 73.4, 61.1, 55.8; HRMS (ESI) m / z calcd for C 45 H 44 SiO5Na [M+Na] + 715.2856, found 715.2841.

[0139] Example 19

[0140] Synthesis of methyldiphenyl((2R,3S,4R,5R,6S)-3,4,5-tris(benzyloxy)-6-methoxytetrahydro-2H-pyran-2-yl)silane

[0141] Referring to the method described in Example 1, except that methyldiphenylsilylzinc chloride was used instead of triphenylgermanium zinc chloride, and the eluent was petroleum ether and ethyl acetate = 10:1, 22.3 mg of the purified product was obtained with a yield of 35%.

[0142] Characterization data of the target product methyldiphenyl((2R,3S,4R,5R,6S)-3,4,5-tris(benzyloxy)-6-methoxytetrahydro-2H-pyran-2-yl)silane: 11H NMR (500 MHz, CDCl3) δ 7.67–7.65 (m, 2H), 7.54–7.52 (m, 2H), 7.41–7.27 (m, 12H), 7.25–7.20 (m, 7H), 6.98–6.96 (m, 2H), 4.96 (d, J = 10.6 Hz, 1H), 4.78 (d, J = 2.6 Hz, 1H), 4.75 (s, 1H), 4.73 (d, J = 10.7 Hz, 1H), 4.65 (d, J = 12.2 Hz, 1H), 4.56 (d, J = 3.7 Hz, 1H), 4.06 (d, J = 10.8 Hz, 1H), 4.00–3.96 (m, 1H), 3.90 (d, J = 11.2 Hz, 1H), 3.56 (dd, J = 11.2, 8.6 Hz, 1H), 3.49 (dd, J = 9.5, 3.6 Hz, 1H), 3.14 (s, 3H), 0.60 (s, 3H); 13 13C NMR (126 MHz, CDCl3) δ 138.7, 138.5, 138.4, 135.7, 135.5, 135.1, 134.4, 129.7, 129.4, 128.6, 128.5, 128.2, 128.1(2), 128.0, 127.8, 127.7(2), 127.4, 98.8, 84.0, 80.8, 79.7, 75.9, 74.3, 73.4, 61.6, 55.2, -4.6; HRMS (ESI) m / z calcd for C 40 H 42 SiO5Na [M+Na] + 653.2699, found 653.2690.

[0143] Example 20

[0144] Synthesis of dimethylphenyl ((2R,3S,4R,5R,6S)-3,4,5-tris(benzyloxy)-6-methoxytetrahydro-2H-pyran-2-yl)silane

[0145] Referring to the method described in Example 1, except that dimethylphenylsilyl zinc chloride was used instead of triphenylgermanium zinc chloride, and the eluent was petroleum ether and ethyl acetate = 10:1, 26.2 mg of the purified product was obtained with a yield of 46%.

[0146] Characterization data of the target product dimethylphenyl ((2R,3S,4R,5R,6S)-3,4,5-tris(benzyloxy)-6-methoxytetrahydro-2H-pyran-2-yl)silane: 11H NMR (400 MHz, CDCl3) δ 7.57–7.54 (m, 2H), 7.38–7.24 (m, 16H), 7.12–7.10 (m, 2H), 4.97 (d, J = 10.7 Hz, 1H), 4.88 (d, J = 10.9 Hz, 1H), 4.77 (d, J = 12.2 Hz, 1H), 4.72 (d, J = 10.7 Hz, 1H), 4.66 (d, J = 12.2 Hz, 1H), 4.59 (d, J = 3.6 Hz, 1H), 4.32 (d, J = 10.9 Hz, 1H), 3.95 (dd, J = 9.6, 8.4 Hz, 1H), 3.57 (d, J = 11.3 Hz, 1H), 3.49–3.43 (m, 2H), 3.25 (s, 3H), 0.35 (s, 3H), 0.34 (s, 3H); 13 13C NMR (126 MHz, CDCl3) δ 138.8, 138.5(2), 136.8, 134.4, 129.3, 128.6, 128.5, 128.3, 128.1(2), 127.9(2), 127.7, 127.6, 127.5, 98.6, 84.0, 80.8, 79.6, 75.8, 74.2, 73.4, 61.8, 54.9, -3.8, -4.3; HRMS(ESI) m / z calcd for C 35 H 40 SiO5Na [M+Na] + 591.2543, found 591.2537。

[0147] Example 21

[0148] Synthesis of tert-Butyl (2S,5S)-2-(tert-butyl)-5-(triphenylgermyl)oxazolidine-3-carboxylate

[0149] In an argon-filled glove box, 3-(tert-butyl)-5-(1,3-dioxoisoindolin-2-yl)(2S,5S)-2-(tert-butyl)oxazolidine-3,5-dicarboxylate (0.2 mmol), Ni(DME)Cl2 (0.01 mmol), 2-(2-oxazolinyl)pyridine (0.01 mmol), tricyclohexylphosphine (0.01 mmol) and THF / DMF (12:1, 1.00 mL) were added to a dry 3 mL vial. Then, triphenylgermanium zinc chloride (0.1 mmol) was added dropwise. The vial was capped and taken out of the glove box. After stirring the reaction at room temperature for 12 h, the reaction was quenched with water and diluted with ethyl acetate. The organic layer was dried over anhydrous sodium sulfate, filtered, and concentrated. The crude product was separated and purified by column chromatography using petroleum ether and ethyl acetate = 10:1 as the eluent to obtain 50.3 mg of the purified product with a yield of 94%.

[0150] Characterization data of the target product tert-butyl (2S,5S)-2-(tert-butyl)-5-(triphenylgermyl)oxazolidine-3-carboxylate: 1 1H NMR (500 MHz, CDCl3) δ 7.54–7.52 (m, 6H), 7.40–7.35 (m, 9H), 5.06 (s, 1H), 4.94 (dd, J = 9.0, 7.2 Hz, 1H), 4.24–4.11 (m, 1H), 3.70 (t, J = 9.9 Hz, 1H), 1.35 (s, 9H), 0.97 (s, 9H); 13 13C NMR (126 MHz, CDCl3) δ 154.5, 135.3, 135.1, 129.4, 128.5, 96.2, 72.3, 48.5, 39.0, 28.4, 26.1; HRMS (ESI) m / z calcd for C 30 H 37 GeNO3Na [M+Na] + 556.1883, found 556.1882。

[0151] Example 22

[0152] Synthesis of tert-butyl (2R,5R)-2-(tert-butyl)-5-(triphenylgermyl)oxazolidine-3-carboxylate

[0153] Referring to the method described in Example 21, except that 3-(tert-butyl)-5-(1,3-dioxoisoindolin-2-yl)(2R,5S)-2-(tert-butyl)oxazolidine-3,5-dicarboxylate was used to replace 3-(tert-butyl)-5-(1,3-dioxoisoindolin-2-yl)(2S,5S)-2-(tert-butyl)oxazolidine-3,5-dicarboxylate, 52.1 mg of the purified product was obtained with a yield of 98%.

[0154] Characterization data of the target product tert-butyl (2R,5R)-2-(tert-butyl)-5-(triphenylgermyl)oxazolidine-3-carboxylate: 1 H NMR(500MHz,CDCl3)δ7.55–7.53(m,6H),7.41–7.36(m,9H),5.06(s,1H),4.94(dd,J=9.1,7.1Hz,1H),4.25–4.13(m,1H),3.71(dd,J=10.7,9.1Hz,1H),1.36(s,9H),0.97(s,9H); 13 C NMR(126MHz,CDCl3)δ154.5,135.3,135.1,129.4,128.5,96.2,72.3,48.5,38.9,28.4,26.0;HRMS(ESI)m / z calcd for C 30 H 37 GeNO3Na[M+Na] + 556.1883,found556.1880.

[0155] Example 23

[0156] Synthesis of methyl (4R,5R)-2,2-dimethyl-5-(triphenylgermyl)-1,3-dioxane-4-carboxylate

[0157] Referring to the method described in Example 1, except that 4-(1,3-dioxoisoindolin-2-yl)5-methyl(4S,5S)-2,2-dimethyl-1,3-dioxane-4,5-dicarboxylate was used to replace 1,3-dioxoisoindol-2-yl((2S,3S,4S,5R,6S)-3,4,5-tris(benzyloxy)-6-methoxytetrahydro-2H-pyran-2-carboxylate), and the eluent was petroleum ether and ethyl acetate = 10:1, 44.5 mg of the purified product was obtained with a yield of 97%.

[0158] Characterization data of the target product methyl (4R,5R)-2,2-dimethyl-5-(triphenylgermyl)-1,3-dioxane-4-carboxylate: 11H NMR (500 MHz, CDCl3) δ 7.60–7.58 (m, 6H), 7.43–7.37 (m, 9H), 4.71 (d, J = 9.7 Hz, 1H), 4.56 (d, J = 9.7 Hz, 1H), 3.35 (s, 3H), 1.50 (s, 3H), 1.39 (s, 3H); 13 13C NMR (101 MHz, CDCl3) δ 171.2, 135.5, 134.4, 129.5, 128.4, 111.4, 77.4, 72.0, 52.0, 26.7, 25.1; HRMS (ESI) m / z calcd for C 25 H 26 GeO4Na [M+Na]+ 487.0941, found 487.0938.

[0159] Example 24

[0160] Synthesis of benzyl (4S,5S)-2,2-dimethyl-4-phenyl-5-(triphenylgermyl)oxazolidine-3-carboxylate

[0161] Referring to the method described in Example 1, except that 3-benzyl 5-(1,3-dioxoisoindolin-2-yl) (4S,5R)-2,2-dimethyl-4-phenyloxazolidine-3,5-dicarboxylate was used to replace 1,3-dioxoisobenzindol-2-yl ((2S,3S,4S,5R,6S)-3,4,5-tris(benzyloxy)-6-methoxytetrahydro-2H-pyran-2-carboxylate), and the eluent was petroleum ether and ethyl acetate = 10:1, 58.2 mg of the purified product was obtained with a yield of 94%.

[0162] Characterization data of the target product benzyl (4S,5S)-2,2-dimethyl-4-phenyl-5-(triphenylgermyl)oxazolidine-3-carboxylate: 1 1H NMR (500 MHz, CDCl3) δ 7.37–7.25 (m, 16H), 7.18–6.91 (m, 7.6H), 6.53–6.51 (m, 1.4H), 5.06–4.60 (m, 4H), 1.79–1.69 (m, 6H); 13 13C NMR (126 MHz, CDCl3) δ 152.7, 135.5, 134.8, 129.3, 128.5, 128.3, 127.4, 95.9, 66.6, 65.4, 26.4, 24.8; HRMS (ESI) m / z calcd for C 37 H 35 GeNO3Na [M+Na] +638.1726, found 638.1725。

[0163] Example 25

[0164] Synthesis of benzyl (4R,5R)-2,2,5-trimethyl-4-(triphenylgermyl)oxazolidine-3-carboxylate

[0165] Referring to the method described in Example 1, except that 3-benzyl 4-(1,3-dioxoisoindolin-2-yl)(4S,5R)-2,2,5-trimethyl oxazolidine-3,4-dicarboxylate was used to replace 1,3-dioxoisobenzindol-2-yl ((2S,3S,4S,5R,6S)-3,4,5-tris(benzyloxy)-6-methoxytetrahydro-2H-pyran-2-carboxylate), and the eluent was petroleum ether and ethyl acetate = 10:1, 51.1 mg of the purified product was obtained with a yield of 92%.

[0166] Characterization data of the target product benzyl (4R,5R)-2,2,5-trimethyl-4-(triphenylgermyl)oxazolidine-3-carboxylate: 1 H NMR (500 MHz, CDCl3) δ 7.66–7.34 (m, 15H), 7.27–7.00 (m, 5H), 4.81–4.69 (m, 1.37H), 4.36–4.30 (m, 1H), 3.90 (d, J = 9.5 Hz, 1H), 3.65 (s, 0.63H), 1.67–1.53 (m, 6H), 0.97 (d, J = 5.9 Hz, 3H); 13 C NMR (126 MHz, CDCl3) δ 152.2, 136.4, 135.7, 135.4, 129.2, 128.7, 128.3, 128.0, 94.4, 74.1, 66.1, 54.8, 26.6, 25.3, 19.3; HRMS (ESI) m / z calcd for C 32 H 33 GeNO3Na [M+Na] + 576.1, found 576.1576。

[0167] Example 26

[0168] (3R,7R,7aS)-7-Methoxy-7,7a-dimethyl-3-(triphenylgermyl)tetrahydro-5H-oxazolo[4,3-b]oxazol-5-one synthesis

[0169] Referring to the method described in Example 1, except that 1,3-dioxo-2,3-dihydro-1H-inden-2-yl (3S,7R,7aS)-7-methoxy-7,7a-dimethyl-5-oxotetrahydro-5H-oxazolo[4,3-b]oxazole-3-carboxylate was used to replace 1,3-dioxoisoindol-2-yl ((2S,3S,4S,5R,6S)-3,4,5-tris(benzyloxy)-6-methoxytetrahydro-2H-pyran-2-carboxylate), and the eluent was petroleum ether and ethyl acetate = 10:1, 28.8 mg of the purified product was obtained, and the yield was 59%.

[0170] Characterization data of the target product (3R,7R,7aS)-7-methoxy-7,7a-dimethyl-3-(triphenylgermyl)tetrahydro-5H-oxazolo[4,3-b]oxazol-5-one: 1 HNMR(500MHz,CDCl3)δ7.61(dd,J=7.5,1.9Hz,6H),7.44–7.38(m,9H),4.68(t,J=9.1Hz,1H),4.44(t,J=9.0Hz,1H),4.04(t,J=8.8Hz,1H),3.39(s,3H),1.51(s,3H),0.66(s,3H); 13 C NMR(126MHz,CDCl3)δ162.7,135.6,134.5,129.7,128.6,106.5,101.2,67.1,51.0,50.4,16.2,15.9;HRMS(ESI)m / z calcd for C 26 H 27 GeNO4Na[M+Na] + 514.1050,found514.1056.

[0171] Example 27

[0172] Synthesis of tert-butyl (2S,5S)-2-(tert-butyl)-5-(triphenylsilyl)oxazolidine-3-carboxylate

[0173] Referring to the method described in Example 21, except that triphenylsilylzinc chloride was used to replace triphenylgermylzinc chloride, 12.2 mg of the purified product was obtained, and the yield was 25%.

[0174] Characterization data of the target product tert-butyl (2S,5S)-2-(tert-butyl)-5-(triphenylsilyl)oxazolidine-3-carboxylate: 11H NMR (400 MHz, CDCl3) δ 7.59–7.56 (m, 6H), 7.42–7.34 (m, 9H), 5.07 (s, 1H), 4.76 (dd, J = 9.6, 8.5 Hz, 1H), 4.08–4.04 (m, 1H), 3.65 (t, J = 10.0 Hz, 1H), 1.36 (s, 9H), 0.98 (s, 9H); 13 13C NMR (126 MHz, CDCl3) δ 154.7, 136.1, 135.3, 132.8, 130.0, 128.2, 127.8, 96.4, 69.9, 47.9, 39.1, 28.4, 26.2; HRMS (ESI) m / z calcd for C 30 H 37 SiNO3Na [M+Na] + 510.2440, found 510.2433.

[0175] The reaction substrates, target products, and yields in Examples 1-27 are listed in a table as shown in Table 2 below:

[0176] Table 2 Comparison Table of Reaction Substrates, Target Products, and Yields in Examples 1-27

[0177]

[0178]

[0179]

[0180]

[0181] As can be seen from Table 2 above, under the aforementioned optimized catalytic system, after reacting glycosyl NHPI esters / amino alcohol-based NHPI esters / diol-based NHPI esters with germanium / silicon zinc reagents, various Ge / Si glycosides / amino alcohols / diols can be stereoselectively synthesized.

[0182] For example, glycosyl NHPI esters derived from common pyranosides (including D-glucose, 2-deoxy-D-glucose, D-galactose, D-fructose, and D-mannose) can effectively form C-Ge bonds at the non-anomeric C5 position to generate the corresponding Ge glycosides in good yields, with unique stereoselectivity control. For example, reacting oxazolidine or dioxolane-based NHPI esters with germanium / silicon zinc reagents can form C-Ge bonds or C-Si bonds with excellent yields and stereoselectivity. Thereafter, through hydrolysis, organosilicon and organogermanium compounds of amino alcohols / diols can be formed.

[0183] As described above, the method of the present invention uses redox-active acid ester compounds synthesized from various carboxylic acids as substrates, with commercially available Ni(dtbbpy)Cl2 or NiCl2(DME)+2-(2-oxazolinyl)pyridine as catalysts, to undergo a radical coupling reaction with metal zinc reagent compounds, and react under nitrogen conditions at room temperature to obtain chiral germanium / silicon compounds. The method of the present invention has good tolerance to five-membered ring sugars, six-membered ring sugars, polysaccharides, amino alcohols or active molecule compounds, and is a general synthetic method for chiral germanium / silicon compounds with mild conditions and simple operation.

[0184] Regarding the reaction substrates involved in the above embodiments, namely the NHPI ester shown in Structural Formula I and the metal zinc reagent shown in Structural Formula II, their general synthetic methods are as follows:

[0185]

[0186] Add carboxylic acid (1.00 equivalent), N-hydroxyphthalimide (1.10 equivalents) and DMAP (0.10 equivalent) to a round-bottom flask, then add DCM (0.25 M), stir and mix evenly, and then add DIC (1.10 equivalents) dropwise through a syringe. Stir the reaction until the carboxylic acid is completely consumed (determined by TLC). The reaction time is generally 2 - 12 h. The resulting reaction product is concentrated under reduced pressure and extracted with DCM. The organic layer is dried with Na2SO4, filtered, concentrated, and purified by column chromatography (DCM / hexane / ethyl acetate as the eluent) to obtain the NHPI ester shown in Structural Formula I.

[0187]

[0188] Add lithium cut pieces (4.00 equivalents) and anhydrous THF (1.00 M) to a 25 mL Schlenk flask equipped with a magnetic stir bar, and then add a chloro-germanium compound (1.00 equivalent) dropwise. Stir the reaction at room temperature for 12 h to obtain a germanium-lithium compound solution, the concentration of which is titrated by the Kofron method. Add this germanium-lithium compound solution to another 25 mL Schlenk flask through a syringe. This Schlenk flask is pre-filled with ZnCl2 (1.00 equivalent relative to the titration amount of the germanium-lithium compound) and anhydrous THF (1.00 M). After stirring the reaction at room temperature for 1 h, a germanium-zinc compound solution (controlled concentration 0.35 - 0.50 M) is obtained, which is the metal zinc reagent shown in Structural Formula II, and the concentration of which is titrated by the Knochel method.

[0189]

[0190] In a 25 mL Schlenk flask equipped with a magnetic stir bar, lithium cut pieces (3.00 equivalents) and anhydrous THF (1.00 M) were added. At 0 °C, a chlorosilane compound (1.00 equivalent) was added dropwise, and the reaction was stirred at the same temperature for 13 h to obtain a solution of lithium silicate compound. Its concentration was determined by titration using the Kofron method. At 0 °C, this solution of lithium silicate compound was added to another 25 mL Schlenk flask through a syringe. This Schlenk flask was previously filled with ZnCl2 (1.20 equivalents relative to the titration amount of lithium silicate compound) and anhydrous THF (1.00 M). After stirring and reacting at the same temperature for 1 h, a solution of zinc silicate compound (with a controlled concentration of 0.35 - 0.50 M) was obtained, which is the metal zinc reagent shown in Structural Formula II. Its concentration was determined by titration using the Knochel method.

[0191] For the oxazolidine or dioxolane-based organogermanium / silicon compounds synthesized in the above examples, the corresponding amino alcohol / diol organogermanium / silicon compounds can be obtained through hydrolysis reactions. Taking the hydrolysis reaction of the target product obtained in Example 23 as an example, the specific process is as follows:

[0192] Synthesis of methyl (2R,3R)-2,3-dihydroxy-3-(triphenylgermyl)propionate:

[0193]

[0194] At room temperature, the reaction substrate 4 (0.05 mmol) was added to dichloromethane DCM (1 mL) and dissolved completely. Water (0.1 mL) and trifluoroacetic acid TFA (0.5 mL) were added dropwise, and the reaction was stirred for 6 h. Then, the solvent was removed by distillation under reduced pressure. The resulting concentrate was separated and purified by column chromatography to obtain the crude product. The eluent was hexane and ethyl acetate = 3:1, and 515.3 mg of the purified product was obtained with a yield of 71%.

[0195] Characterization data of the target product methyl (2R,3R)-2,3-dihydroxy-3-(triphenylgermyl)propionate: 1 HNMR(500MHz,CDCl3)δ7.66–7.61(m,6H),7.46–7.36(m,9H),4.80(s,1H),4.39(s,1H),3.78(s,3H),3.21(s,1H),2.07(s,1H); 13 C NMR(126MHz,CDCl3)δ174.5,135.6,134.7,129.5,128.5,73.7,70.2,53.0;HRMS(ESI)m / z calcd for C 22 H 22 GeO4Na[M+Na] +447.0628, found 447.0649.

[0196] As mentioned above, it is only the preferred specific embodiment of the present invention, but the protection scope of the present invention is not limited thereto. Any person skilled in the art within the technical scope disclosed by the present invention, according to the technical solution of the present invention and its inventive concept, makes equivalent substitutions or changes, and should be covered within the protection scope of the present invention.

Claims

1. A method for stereoselectively synthesizing chiral germanium / silicon compounds, characterized in that, Comprising: Performing a decarboxylative coupling reaction between the NHPI ester shown in Structural Formula I and the metal zinc reagent shown in Structural Formula II to obtain the chiral germanium / silicon compound shown in Structural Formula III; Wherein, R is a glycosyl group, an amino alcohol or a diol group, and M is an organogermanium or silicon group.

2. The method for stereoselectively synthesizing a chiral germanium / silicon compound according to claim 1, wherein The glycosyl group is glucose, deoxyglucose, galactose, deoxygalactose, mannose, fructose, ribose, deoxyribose, xylose, arabinose, IPTG, lyxose, fucose, rhamnose, sorbose, tagatose, N-acetylglucosamine, N-acetylgalactosamine, glucosamine, galactosamine or oligosaccharide.

3. The method for stereoselectively synthesizing a chiral germanium / silicon compound according to claim 1 or 2, characterized in that, The NHPI ester shown in Structural Formula I includes compounds shown in the following Structural Formula I', I'' or I''': n is 0 or 1; R1 is hydrogen, hydroxyl, amino, glycosyl, alkyl, alkoxy, alkenyl, aryl, ester carbonyl, NH-acyl, azide, mercapto, alkyl mercapto or OP, and P is a hydroxyl protecting group on the glycosyl group; X is O or NP, and P is an amino protecting group; R2 is hydrogen, hydroxyl, amino, alkyl, alkoxy, alkenyl, aryl, ester carbonyl or NH-acyl; R3, R4 are hydrogen, alkyl, alkenyl or aryl.

4. The method for stereoselectively synthesizing chiral germanium / silicon compounds according to any one of claims 1-3, characterized in that, The metal zinc reagent shown in Structural Formula II includes compounds shown in the following Structural Formula II' or Structural Formula II'': R4-R6 are each independently alkyl, heterocyclic group or aryl, and R7-R9 are each independently alkyl, heterocyclic group or aryl.

5. The method for stereoselectively synthesizing a chiral germanium / silicon compound according to any one of claims 1-4, characterized in that, The decarboxylative coupling reaction is carried out under the reaction conditions of a nickel catalyst, a ligand and an inert gas protection; Preferably, the nickel catalyst is at least one of Ni(dtbbpy)Cl2, Ni(DME)Cl2, Ni(DME)Br2, Ni(PPh3)2Cl2, Ni(acac)2, NiCl2, NiBr2 or Ni(OTf)2; Preferably, the ligand includes a phosphine-containing ligand and / or a nitrogen-containing ligand. The phosphine-containing ligand is at least one of PCy3, PPh3, Dppp, Dppb, Dppf, Binap, Jackiephos, Xantphos, Xu-Phos, X-Phos or tBuBrettphos, and the nitrogen-containing ligand is at least one of 4,4'-di-tert-butyl-2,2'-bipyridine dtbbpy, bipyridine bpy, 4,4'-dimethoxy-2,2'-bipyridine or 2-(2-oxazolinyl)pyridine.

6. The method for stereoselectively synthesizing a chiral germanium / silicon compound according to any one of claims 1-5, characterized in that, The solvent for the decarboxylative coupling reaction is at least one of tetrahydrofuran, N,N-dimethylformamide, N,N-dimethylacetamide, 1,4-dioxane, toluene, diethylene glycol dimethyl ether or N-methylpyrrolidone, and preferably a mixed solvent of tetrahydrofuran and N,N-dimethylformamide.

7. The method for stereoselectively synthesizing a chiral germanium / silicon compound according to any one of claims 1-6, characterized in that, The molar ratio of the NHPI ester shown in Structural Formula I to the metal zinc reagent shown in Structural Formula II is 2-3:1; preferably 2:

1.

8. The method for stereoselectively synthesizing a chiral silicon / germanium compound according to any one of claims 1-7, characterized in that, The temperature of the decarboxylative coupling reaction is 25-40 °C, and the time is 12-24 h.

9. A chiral germanium / silicon compound synthesized by the method according to any one of claims 1-8.

10. The chiral germanium / silicon compound according to claim 8, wherein It is shown in the following structural formula:

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