Asymmetric synthesis method of alpha-chiral ester compound

Abstract

The invention belongs to the technical field of chemical synthesis, and particularly relates to an asymmetric synthesis method of an alpha-chiral ester compound. Comprising the following step: in a solvent, performing asymmetric alpha-protonation and esterification reaction on alpha-alkyl-alpha, beta-unsaturated aldehyde and alcohol as shown in a formula II in the presence of a chiral N-heterocyclic carbene catalyst, alkali and protonic acid to obtain the alpha-chiral ester compound. The invention develops a redox esterification reaction based on chiral N-heterocyclic carbene catalysis, so that the redox esterification reaction can be efficiently suitable for various alpha-alkyl alpha, beta-olefine aldehydes from simple to high steric hindrance and from chain to polycyclic; the catalytic strategy can be directly applied to later directional esterification modification of important natural product derivatives such as oestrone and epiandrosterone, and a powerful tool is provided for research and development of new drugs.

Description

Technical Field

[0001] This invention belongs to the field of chemical synthesis technology, specifically relating to an asymmetric synthesis method for α-chiral ester compounds. Background Technology

[0002] The α-chiral center, especially the chiral methyl group, in carbonyl compounds is a key structural unit constituting many natural products, bioactive molecules, and chiral drugs. Therefore, developing efficient and highly enantioselective methods for constructing such structures is of great significance in the fields of organic synthetic chemistry and drug development.

[0003] Currently, the mainstream strategy for constructing α-chiral centers relies on transition metal-catalyzed asymmetric reactions, such as asymmetric hydrogenation. However, such methods typically require a hydrogen atmosphere and noble metal catalysts (such as ruthenium and rhodium complexes), and have inherent drawbacks such as demanding conditions, limited functional group tolerance, potential metal residues, and a heavy environmental burden. Another strategy is acid catalysis, but when activating unsaturated aldehydes, it is often difficult to precisely control stereochemistry, resulting in poor enantioselectivity and a narrow substrate applicability.

[0004] In recent years, nitrogen-heterocyclic carbene (NHC) has become a highly attractive tool in asymmetric synthesis due to its low toxicity, mild conditions, excellent functional group tolerance, and strong enantiomeric control. NHC catalysis has successfully achieved the construction of various carbon-carbon and carbon-heterobonds, with significant progress, particularly in the conversion of unsaturated aldehydes.

[0005] However, existing NHC catalytic systems are mainly limited to the cyclization or β-position transformation of unsaturated aldehydes, making them difficult to directly use for precise functional group modification of complex natural product skeletons in the later stages, thus limiting their synthetic application value. Summary of the Invention

[0006] To address the aforementioned technical problems, this invention provides an asymmetric synthesis method for α-chiral ester compounds, which efficiently and with high enantioselectivity achieves direct asymmetric α-protonation and esterification reactions of various α-alkyl-α,β-unsaturated aldehydes. Furthermore, it does not require the participation of transition metals, operates under mild conditions, is simple to operate, and exhibits excellent substrate versatility and stereoselectivity.

[0007] This invention provides an asymmetric synthesis method for α-chiral ester compounds, comprising the following steps: In a solvent, α-alkyl-α,β-unsaturated aldehydes are reacted with alcohols of Formula II via asymmetric α-protonation and esterification reactions in the presence of a chiral nitrogen heterocyclic carbene catalyst, a base, and a protic acid to yield α-chiral ester compounds; the α-alkyl-α,β-unsaturated aldehydes are selected from chain-like α-alkylenal or cyclic α-alkylenal; the structural formulas of the α-alkyl-α,β-unsaturated aldehydes are shown in Formula I1, I2, I3, or I4: ; The structural formula of the alcohol represented by Formula II is as follows: ; Among them, R 1 Selected from halogen, methyl, phenyl, diphenylamino, trifluoromethyl, or cyano; R 2 It is selected from methyl, iodine, chlorinated phenyl, bromine-substituted benzyl, thiophene methyl, or ferrocene methyl.

[0008] Preferred asymmetric synthesis method for α-chiral ester compounds: After mixing a protic acid, a base, and a molecular sieve, α-alkyl-α,β-unsaturated aldehydes, an alcohol of formula II, a chiral nitrogen heterocyclic carbene catalyst, and a solvent are added under a protective atmosphere to undergo asymmetric α-protonation and esterification reactions, yielding α-chiral ester compounds.

[0009] Preferably, the molar ratio of α-alkyl-α,β-unsaturated aldehyde and the alcohol represented by formula II is 1:2.

[0010] Preferably, the temperature for the asymmetric α-protonation and esterification reaction is 25℃~60℃, and the time is 48 hours.

[0011] Preferably, the amount of chiral nitrogen heterocyclic carbene catalyst used is 10% of the molar amount of α-alkyl-α,β-unsaturated aldehyde.

[0012] Preferably, the chiral nitrogen heterocyclic carbene catalyst is (5aS,10bR)-2-(2,6-difluorophenyl)-5a,10b-dihydro-4H,6H-indeno[2,1-b][1,2,4]triazolo[4,3-d][1,4]oxazine-2-onium tetrafluoroborate or 2-(2,6-dichlorophenyl)-9-phenyl-5a,10b-dihydro-4H,6H-indeno[2,1-b][1,2,4]triazolo[4,3-d][1,4]oxazine-2-onium tetrafluoroborate.

[0013] It should be noted that different catalytic systems (including catalyst type and reaction temperature) are used for α-alkyl-α,β-unsaturated aldehydes with different structural types to achieve optimal results. The α-alkyl-α,β-unsaturated aldehydes of this invention include the chain-like α-alkylenal shown in Formula I1 and the cyclic α-alkylenal shown in Formulas I2 and I3. When the α-alkyl-α,β-unsaturated aldehyde is a chain-like α-alkylenal, the chiral nitrogen heterocyclic carbene catalyst is 2-(2,6-dichlorophenyl)-9-phenyl-5a,10b-dihydro-4H,6H-indeno[2,1-b][1,2,4]triazolo[4,3-d][1,4]oxazine-2-onium tetrafluoroborate; the temperature for the asymmetric α-protonation and esterification reactions is 60℃~65℃. When the α-alkyl-α,β-unsaturated aldehyde is a cyclic α-alkylenal, the chiral nitrogen heterocyclic carbene catalyst is (5aS,10bR)-2-(2,6-difluorophenyl)-5a,10b-dihydro-4H,6H-indeno[2,1-b][1,2,4]triazolo[4,3-d][1,4]oxazine-2-onium tetrafluoroborate; the temperature for the asymmetric α-protonation and esterification reactions is 20℃~30℃.

[0014] Preferably, the amount of alkali used is 1.5 to 2 times the molar amount of α-alkyl-α,β-unsaturated aldehyde; the alkali is sodium bicarbonate or potassium carbonate.

[0015] Preferably, the amount of protic acid used is 1 to 2 times the molar amount of α-alkyl-α,β-unsaturated aldehyde; the acid is adamantane acid.

[0016] Preferably, the molecular sieve is a 4Å molecular sieve.

[0017] Preferably, the ratio of α-alkyl-α,β-unsaturated aldehyde to solvent is 1 mmol: 10 mL; the solvent is chlorobenzene.

[0018] Preferably, the structural formulas of α-chiral ester compounds are shown in Formula III1, Formula III2, Formula III3 or Formula III4: .

[0019] Compared with the prior art, the present invention has the following technical effects: This invention develops a redox esterification reaction based on chiral nitrogen heterocyclic carbene catalysis. With the synergistic effect of the chiral nitrogen heterocyclic carbene catalyst and the proton acid / base co-catalytic system, it can be efficiently applied to various α-alkyl α,β-enal reactions ranging from simple to highly sterically hindered and from chain to polycyclic. This catalytic strategy can be directly applied to the late-stage targeted esterification modification of important natural product derivatives such as estrone and epiandrolone, providing a powerful tool for new drug development.

[0020] The synthetic method of this invention is applicable to a range of structurally diverse α-substituted unsaturated aldehydes and alcohols, and has successfully prepared various chiral esters (such as halogen-containing and sterically hindered diphenylamino esters) with yields ranging from 67% to 99% and enantiomeric excess values ​​ranging from 68% to 96%, demonstrating its broad applicability. Furthermore, the enaldehyde substrates cover cyclopentenal, benzocyclohexenal, various α-alkyl chain enaldehydes, and even the highly strained benzocycloheptenal; the nucleophiles are compatible with primary and secondary alcohols, phenols, thiophenols, and a variety of bioactive natural alcohols, exhibiting excellent functional group tolerance.

[0021] The catalyst used in this invention is stable, the raw materials are commercially available or easy to prepare, and the reaction does not require special equipment, thus having good experimental operability and potential for process scale-up. Detailed Implementation

[0022] To enable those skilled in the art to better understand and implement the technical solutions of the present invention, the present invention will be further described below in conjunction with specific embodiments.

[0023] Unless otherwise specified, all reagents used in this invention are commercially available, and all methods used are conventional techniques in the art.

[0024] The reaction mechanism of the α-chiral ester compounds of this invention is as follows: Under the action of a base, the chiral nitrogen heterocyclic carbene precursor salt loses HBF4 to generate a free chiral carbene. This chiral carbene acts as a nucleophile, attacking the carbonyl carbon of an α-alkyl-α,β-unsaturated aldehyde to form a high-enol Breslow intermediate. Adamantane acid provides a proton to protonate the β-carbon of the protoenal in the chiral enol intermediate; under the hydrogen bonding of a neighboring chlorine atom, the proton source in the system (adamantane acid or alcohol) stereoselectively transfers from the chiral Si facet and adds to the α-carbon of the protoenal in the enol intermediate. After protonation, a saturated acylazoleonium intermediate with chiral information is generated. At this point, the excess alcohol in the system acts as a nucleophile, attacking the carbonyl carbon of this acylazoleonium intermediate, undergoing transesterification or direct nucleophilic substitution to generate the final α-chiral ester and releasing the chiral nitrogen heterocyclic carbene catalyst, completing the catalytic cycle.

[0025] Example 1 A method for synthesizing (8S,9S,13R,14S,16R)-3-methoxy-13-methyl-7,8,9,11,12,13,14,15,16,17-decahydro-6H-cyclopentan[a]phenanthrene-16-carboxylic acid 2-(thiophene-2-yl)ethyl ester includes the following steps: In a 10 mL reaction tube equipped with a magnetic stir bar, 100 mg of 4 Å molecular sieve, 27 mg of 1-adamantanecarboxylic acid (0.15 mmol, 1.5 equivalents), and 15 mg of sodium bicarbonate (0.18 mmol, 1.8 equivalents) were added sequentially. The substrate 2-(thiophen-2-yl)ethyl-1-ol (25 μL, 0.2 mmol, 2.0 equivalent) was injected via a microsyringe, followed by three purgings with argon gas. After purging with argon gas, (5aS,10bR)-2-(2,6-dichlorophenyl)-9-phenyl-5a,10b-dihydro-4H,6H-indeno[2,1-b][1,2,4]triazolo[4,3-d][1,4]oxazine-2-onium tetrafluoroborate (5.2 mg, 0.01 mmol) and chlorobenzene (1 mL, 0.1 M) were added to the reaction tube, followed by three more purgings with argon gas. The reaction was then pre-stirred at room temperature for 30 min. After the pre-reaction, the substrate (8S,9S,13S,14S)-3-methoxy-13-methyl-7,8,9,11,12,13,14,15-octahydro-6H-cyclopentan[a]phenanthrene-16-carboxaldehyde (29.6 mg, 1 equivalent, 0.1 mmol) was injected into the reaction system using a microsyringe at room temperature, followed by argon purging. The reaction system was then placed in an oil bath at 25°C for 48 h. After the reaction, petroleum ether:ethyl acetate (volume ratio 10:1) was used as the eluent to obtain (8S,9S,13R,14S,16R)-3-methoxy-13-methyl-7,8,9,11,12,13,14,15,16,17-decahydro-6H-cyclopentan[a]phenanthrene-16-carboxylic acid 2-(thiophene-2-yl)ethyl ester, the structure of which is shown below:

[0026] (8S,9S,13R,14S,16R)-3-methoxy-13-methyl-7,8,9,11,12,13,14,15,16,17-decahydro-6H-cyclopentan[a]phenanthrene-16-carboxylic acid 2-(thiophene-2-yl)ethyl ester is a yellow oily liquid with a yield of 99% and an enantiomeric excess of 99%. Its NMR data are as follows: 1H NMR (600 MHz, Chloroform-d) δ 7.24 (d, J = 8.6 Hz, 1H), 7.19 (d, J= 5.1 Hz, 1H), 6.98 (dd, J = 5.2, 3.4 Hz, 1H), 6.91 (d, J = 3.6 Hz, 1H), 6.75(dd, J = 8.6, 2.9 Hz, 1H), 6.67 (d, J = 2.9 Hz, 1H), 4.36 (t, J = 6.6 Hz,2H), 3.81 (s, 3H), 3.21 (t, J = 6.6 Hz, 2H), 3.07 - 2.98 (m, 1H), 2.96 - 2.84(m, 2H), 2.37 - 2.24 (m, 2H), 2.17 - 2.09 (m, 1H), 1.98 - 1.87 (m, 3H), 1.73- 1.28 (m, 7H), 0.83 (s, 3H). 13 C NMR (151 MHz, Chloroform-d) δ 177.16, 157.41,140.03, 137.81, 132.59, 126.73, 126.20, 125.41, 123.86, 113.74, 111.41,64.47, 55.08, 52.57, 45.18, 43.69, 41.92, 39.99, 38.89, 38.17, 29.78, 29.75, 29.32, 27.84, 26.48, 17.70.

[0027] Example 2 A method for synthesizing (3S,5S,8S,9S,10S,13R,14S,16R)-3-methoxy-10,13-dimethylhexadecylhydro-1H-cyclopenta[a]phenanthrene-16-carboxylic acid 2-(thiophene-2-yl)ethyl ester includes the following steps: In a 10 mL reaction tube equipped with a magnetic stir bar, 100 mg of 4 Å molecular sieve, 27 mg of 1-adamantanecarboxylic acid (0.15 mmol, 1.5 equivalents), and 15 mg of sodium bicarbonate (0.18 mmol, 1.8 equivalents) were added sequentially. The substrate 2-(thiophene-2-yl)ethyl-1-ol (25 μL, 0.2 mmol, 2.0 equivalent) was injected via a microsyringe, followed by three purgings with argon gas. After purging with argon gas, ((5aS,10bR)-2-(2,6-dichlorophenyl)-9-phenyl-5a,10b-dihydro-4H,6H-indeno[2,1-b][1,2,4]triazolo[4,3-d][1,4]oxazine-2-onium tetrafluoroborate (5.2 mg, 0.01 mmol) and chlorobenzene (1 mL, 0.1 M) were added to the reaction tube, followed by three more purgings with argon gas. The reaction was then pre-stirred at room temperature for 30 min. After the pre-reaction, the substrate (3S,5S,8R,9S) was injected via a microsyringe at room temperature. (3S,5S,8S,9S,10S,13R,14S,14R)-3-methoxy-10,13-dimethyl-2,3,4,5,6,7,8,9,10,11,12,13,14,15-tetradecanoic acid-1H-cyclopentan[a]phenanthrene-16-carboxaldehyde (31.6 mg, 1 equivalent, 0.1 mmol) was injected into the reaction system, and argon gas was purged again. The reaction system was then placed in an oil bath at 25°C for 48 h. After the reaction, petroleum ether:ethyl acetate (volume ratio 10:1) was used as the eluent to obtain (3S,5S,8S,9S,10S,13R,14S,16R)-3-methoxy-10,13-dimethylhexadecanoic acid-1H-cyclopentan[a]phenanthrene-16-carboxylic acid 2-(thiophene-2-yl)ethyl ester, the structure of which is shown below:

[0028] .

[0029] (3S,5S,8S,9S,10S,13R,14S,16R)-3-methoxy-10,13-dimethylhexadecylhydro-1H-cyclopentan[a]phenanthrene-16-carboxylic acid 2-(thiophene-2-yl)ethyl ester is a yellow oily liquid with a yield of 89% and an enantiomeric excess of 97%. Its NMR data are as follows: 1H NMR (600 MHz, Chloroform-d) δ 7.14 (d, J = 5.2 Hz, 1H), 6.99 -6.89 (m, 1H), 6.84 (s, 1H), 4.28 (t, J = 6.6 Hz, 2H), 3.33 (s, 3H), 3.14 (t,J = 6.8 Hz, 3H), 2.90 (q, J = 10.0 Hz, 1H), 1.98 - 1.90 (m, 1H), 1.87 (d, J =11.2 Hz, 1H), 1.82 - 1.75 (m, 1H), 1.75 - 1.60 (m, 4H), 1.58 - 1.38 (m, 3H),1.36 - 1.10 (m, 8H), 1.09 - 1.02 (m, 1H), 1.01 - 0.89 (m, 2H), 0.79 (s, 3H), 0.73 (s, 3H), 0.70 - 0.62 (m, 1H). 13 C NMR (151 MHz, Chloroform-d) δ 177.27,140.03, 126.73, 125.40, 123.85, 79.72, 64.42, 55.46, 54.34, 53.52, 45.07,44.69, 41.70, 39.91, 38.25, 36.94, 35.83, 35.61, 34.29, 32.13, 30.10, 29.32,28.72, 27.84, 21.00, 17.68, 12.20.

[0030] Example 3 The method for synthesizing (R)-5-methyl-2,3-dihydro-1H-inden-2-carboxylic acid 2-(thiophen-2-yl)ethyl ester includes the following steps: In a 10 mL reaction tube equipped with a magnetic stirrer, 100 mg of 4 Å molecular sieve, 27 mg of 1-adamantanecarboxylic acid (0.15 mmol, 1.5 equivalents), and 15 mg of sodium bicarbonate (0.18 mmol, 1.8 equivalents) were added sequentially. The substrate 2-(thiophene-2-yl)ethyl-1-ol (25 μL, 0.2 mmol, 2.0 equivalents) was injected via a microsyringe, followed by three evacuation-argon purging cycles. After argon purging, ((5aS,10bR)-2-(2,6-dichlorophenyl)-9-phenyl-5a,10b-dihydro-4H,6H-indeno[2,1-b][1,2,4]triazolo[4,3-d][1,4]oxazine-2-onium tetrafluoroborate (5.2 mg, 0.01 mmol) and chlorobenzene (1 mL, 0.1 M) were added, and the reaction was repeated three times. Argon purging was performed, and the reaction was pre-stirred at room temperature for 30 min. After the pre-reaction, 15.8 mg (1 equivalent, 0.1 mmol) of the substrate 5-methyl-1H-indene-2-carboxaldehyde was injected into the reaction system using a microsyringe at room temperature, and argon purging was performed again. The reaction system was then placed in an oil bath at 25 °C for 48 h. After the reaction, petroleum ether and ethyl acetate (volume ratio 20:1) were used as eluents to obtain (R)-5-methyl-2,3-dihydro-1H-indene-2-carboxylic acid 2-(thiophene-2-yl)ethyl ester, the structure of which is shown below:

[0031] .

[0032] (R)-5-methyl-2,3-dihydro-1H-inden-2-carboxylic acid 2-(thien-2-yl)ethyl ester is a yellow oily liquid with a yield of 99% and an enantiomeric excess of 96%. Its NMR data are as follows: 1 H NMR (600 MHz, Chloroform-d) δ 7.20 (dd, J = 5.1, 1.2 Hz, 1H), 7.14 (d, J = 7.7 Hz, 1H), 7.08 (s, 1H), 7.02 (d, J = 7.7 Hz, 1H), 6.99 (dd, J =5.2, 3.4 Hz, 1H), 6.94 - 6.85 (m, 1H), 4.39 (t, J = 6.7 Hz, 2H), 3.38 (p, J =8.4 Hz, 1H), 3.30 - 3.16 (m, 6H), 2.37 (s, 3H). 13C NMR (151 MHz, Chloroform-d)δ 175.21, 141.80, 140.03, 138.57, 136.30, 127.48, 126.93, 125.63, 125.10,124.11, 124.09, 64.88, 43.93, 36.11, 35.84, 29.43, 21.31.

[0033] Example 4 The method for synthesizing (R)-7-methyl-1,2,3,4-tetrahydronaphthyl-2-carboxylic acid 2-(thiophene-2-yl)ethyl ester includes the following steps: In a 10 mL reaction tube equipped with a magnetic stirrer, 100 mg of 4 Å molecular sieve, 27 mg of 1-adamantanecarboxylic acid (0.15 mmol, 1.5 equivalents), and 15 mg of sodium bicarbonate (0.18 mmol, 1.8 equivalents) were added sequentially. The substrate 2-(thiophene-2-yl)ethyl-1-ol (25 μL, 0.2 mmol, 2.0 equivalents) was injected via a microsyringe, followed by three purgings with argon gas. After purging with argon gas, ((5aS,10bR)-2-(2,6-dichlorophenyl)-9-phenyl-5a,10b-dihydro-4H,6H-indeno[2,1-b][1,2,4]triazolo[4,3-d][1,4]oxazine-2-onium tetrafluoroborate (5.2 mg, 0.01 mmol) and chlorobenzene (1 mL, 0.1 M) were added, followed by three more purgings with argon gas. The reaction was purged with argon gas and pre-stirred at room temperature for 30 min. After the pre-reaction, 17.2 mg (1 equivalent, 0.1 mmol) of the substrate 7-methyl-3,4-dihydronaphthyl-2-carboxaldehyde was injected into the reaction system using a microsyringe at room temperature, and argon purging was performed again. The reaction system was then placed in an oil bath at 25 °C for 48 h. After the reaction, petroleum ether and ethyl acetate (volume ratio 20:1) were used as eluents to obtain (R)-7-methyl-1,2,3,4-tetrahydronaphthyl-2-carboxylic acid 2-(thiophene-2-yl)ethyl ester, the structure of which is shown below:

[0034] .

[0035] (R)-7-methyl-1,2,3,4-tetrahydronaphthyl-2-carboxylic acid 2-(thiophene-2-yl)ethyl ester is a yellow oily liquid with a yield of 77% and an enantiomeric excess of 97%. Its NMR data are as follows: 1H NMR (600 MHz, Chloroform-d) δ 7.23 - 7.16 (m, 1H), 7.07 - 6.92 (m,4H), 6.89 (d, J = 3.5 Hz, 1H), 4.38 (t, J = 6.6 Hz, 2H), 3.21 (t, J = 6.6 Hz,2H), 2.99 (d, J = 8.0 Hz, 2H), 2.91 - 2.72 (m, 3H), 2.32 (s, 3H), 2.27 - 2.17(m, 1H), 1.95 - 1.82 (m, 1H). 13 C NMR (151 MHz, Chloroform-d) δ 175.25, 139.95,135.21, 134.63, 132.55, 129.54, 128.68, 126.80, 126.75, 125.50, 123.97,64.62, 40.09, 31.52, 29.33, 28.05, 25.95, 20.89.

[0036] Example 5 The method for synthesizing (R)-7-bromo-1,2,3,4-tetrahydronaphthyl-2-carboxylic acid 2-(thiophen-2-yl)ethyl ester includes the following steps: In a 10 mL reaction tube equipped with a magnetic stirrer, 100 mg of 4 Å molecular sieve, 27 mg of 1-adamantanecarboxylic acid (0.15 mmol, 1.5 equivalents), and 15 mg of sodium bicarbonate (0.18 mmol, 1.8 equivalents) were added sequentially. The substrate 2-(thiophene-2-yl)ethyl-1-ol (25 μL, 0.2 mmol, 2.0 equivalents) was injected via a microsyringe, followed by three evacuation-argon purging cycles. After argon purging, ((5aS,10bR)-2-(2,6-dichlorophenyl)-9-phenyl-5a,10b-dihydro-4H,6H-indeno[2,1-b][1,2,4]triazolo[4,3-d][1,4]oxazine-2-onium tetrafluoroborate (5.2 mg, 0.01 mmol) and chlorobenzene (1 mL, 0.1 M) were added, followed by three more argon purging cycles. Argon purging was performed, and the reaction was pre-stirred at room temperature for 30 min. After the pre-reaction, 25.6 mg (1 equivalent, 0.1 mmol) of the substrate 7-bromo-3,4-dihydronaphthyl-2-carboxaldehyde was injected into the reaction system using a microsyringe at room temperature, and argon purging was performed again. The reaction system was then placed in an oil bath at 25 °C for 48 h. After the reaction, petroleum ether and ethyl acetate (volume ratio 20:1) were used as eluents to obtain (R)-7-bromo-1,2,3,4-tetrahydronaphthyl-2-carboxylic acid 2-(thiophene-2-yl)ethyl ester, the structure of which is shown below:

[0037] .

[0038] (R)-7-bromo-1,2,3,4-tetrahydronaphthyl-2-carboxylic acid 2-(thiophene-2-yl)ethyl ester is a yellow oily liquid with a yield of 74% and an enantiomeric excess of 97%. Its NMR data are as follows: 1 H NMR (600 MHz, Chloroform-d) δ 7.23 (dd, J = 10.5, 2.6 Hz, 2H), 7.18 (dd, J = 5.2, 1.3 Hz, 1H), 6.99 - 6.92 (m, 2H), 6.87 (d, J = 4.3 Hz, 1H), 4.36 (t, J = 6.6 Hz, 2H), 3.19 (t, J = 6.6 Hz, 2H), 2.97 (d, J = 7.8 Hz,2H), 2.85 - 2.70 (m, 3H), 2.19 (tt, J = 9.7, 5.4 Hz, 1H), 1.92 - 1.81 (m,1H). 13C NMR (151 MHz, Chloroform-d) δ 174.71, 139.84, 137.10, 134.60, 131.64,130.39, 128.90, 126.81, 125.50, 124.00, 119.22, 64.72, 39.48, 31.17, 29.28,27.81, 25.45.

[0039] Example 6 The method for synthesizing (R)-2-methyl-3-phenylpropionic acid 4-bromophenylethyl ester includes the following steps: Add 100 mg of 4 Å molecular sieve, 27 mg of 1-adamantanecarboxylic acid (0.15 mmol, 1.5 equivalents), and 20.7 mg of potassium carbonate (0.15 mmol, 1.5 equivalents) to a 10 mL reaction tube equipped with a magnetic stirrer in sequence. The substrate 2-(4-bromophenyl)ethyl-1-ol (28 μL, 0.2 mmol, 2.0 equivalent) was injected using a microsyringe, followed by three purgings with argon gas. After purging with argon gas, (5aS,10bR)-2-(2,6-difluorophenyl)-5a,10b-dihydro-4H,6H-indeno[2,1-b][1,2,4]triazolo[4,3-d][1,4]oxazine-2-onium tetrafluoroborate (4.1 mg, 0.01 mmol) and toluene (1 mL, 0.1 M) were added to the reaction tube, followed by three more purgings with argon gas. The reaction was then pre-stirred at room temperature for 30 min. After the pre-reaction, the substrate (E)-2-methyl-3-phenylpropenal (14 μL, 1 equivalent, 0.1 mmol) was injected into the reaction system using a microsyringe at room temperature, followed by another purging with argon gas. The reaction system was then placed in an oil bath at 60°C and reacted for 48 hours. After the reaction was completed, petroleum ether and ethyl acetate in a volume ratio of 20:1 were used as eluents to obtain (R)-2-methyl-3-phenylpropionic acid 4-bromophenylethyl ester, the structure of which is shown in the following formula:

[0040] .

[0041] (R)-2-methyl-3-phenylpropionic acid 4-bromophenylethyl ester is a yellow oily liquid with a yield of 99% and an enantiomeric excess of 92%. Its NMR data are as follows: 1H NMR (600 MHz, Chloroform-d) δ 7.40 (d, J = 8.1 Hz, 2H), 7.27 (t, J= 7.5 Hz, 2H), 7.21 (t, J = 7.4 Hz, 1H), 7.13 (d, J = 7.5 Hz, 2H), 7.02 (d, J= 7.9 Hz, 2H), 4.22 (tq, J = 11.1, 7.0, 5.8 Hz, 2H), 2.98 (q, J = 13.4, 7.1Hz, 1H), 2.81 (q, J = 6.2 Hz, 2H), 2.72 (q, J = 7.1 Hz, 1H), 2.66 (q, J =13.4, 7.4 Hz, 1H), 1.14 (d, J = 6.9 Hz, 3H). 13C NMR (151 MHz, CDCl3) δ176.02, 139.42, 137.03, 131.66, 130.73, 129.08, 128.47, 126.47, 120.53,64.47, 41.64, 39.86, 34.62, 16.99.

[0042] Example 7 The method for synthesizing (R)-3-(4-chlorophenyl)-2-methylpropionic acid 4-bromophenylethyl ester includes the following steps: Add 100 mg of 4 Å molecular sieve, 27 mg of 1-adamantanecarboxylic acid (0.15 mmol, 1.5 equivalents), and 20.7 mg of potassium carbonate (0.15 mmol, 1.5 equivalents) to a 10 mL reaction tube equipped with a magnetic stirrer in sequence. The substrate 2-(4-bromophenyl)ethyl-1-ol (28 μL, 0.2 mmol, 2.0 equivalent) was injected using a microsyringe, followed by three purgings with argon gas. After purging with argon gas, (5aS,10bR)-2-(2,6-difluorophenyl)-5a,10b-dihydro-4H,6H-indeno[2,1-b][1,2,4]triazolo[4,3-d][1,4]oxazine-2-onium tetrafluoroborate (4.1 mg, 0.01 mmol) and toluene (1 mL, 0.1 M) were added to the reaction tube, followed by three more purgings with argon gas. The reaction was then pre-stirred at room temperature for 30 min. After the pre-reaction, the substrate (E)-3-(4-chlorophenyl)-2-methylpropenal (18.2 mg, 1 equivalent, 0.1 mmol) was injected into the reaction system using a microsyringe at room temperature, followed by another purging with argon gas. The reaction system was then placed in an oil bath at 60°C and reacted for 48 hours. After the reaction was completed, petroleum ether and ethyl acetate in a volume ratio of 20:1 were used as eluents to obtain 4-bromophenylethyl (R)-3-(4-chlorophenyl)-2-methylpropionic acid, the structure of which is shown below:

[0043] .

[0044] (R)-3-(4-chlorophenyl)-2-methylpropionic acid 4-bromophenylethyl ester is a yellow oily liquid with a yield of 86% and an enantiomeric excess of 93%. Its NMR data are as follows: 1H NMR (600 MHz, Chloroform-d) δ 7.43 – 7.39 (m, 2H), 7.25 – 7.20 (m,2H), 7.03 (q, J = 10.2, 8.2 Hz, 4H), 4.22 (t, J = 6.8 Hz, 2H), 2.92 (q, J =13.4, 7.3 Hz, 1H), 2.82 (td, J = 6.9, 2.7 Hz, 2H), 2.65 (qd, J = 33.4, 13.8,7.1 Hz, 2H), 1.12 (d, J = 6.9 Hz, 3H). 13C NMR (151 MHz, CDCl3) δ 175.73,137.85, 136.92, 132.29, 131.67, 130.70, 130.41, 128.59, 120.57, 64.54, 41.53, 39.09, 34.58, 17.03.

[0045] Example 8 The method for synthesizing (R)-3-(4-(diphenylamino)phenyl)-2-methylpropionic acid 4-bromophenylethyl ester includes the following steps: Add 100 mg of 4 Å molecular sieve, 27 mg of 1-adamantanecarboxylic acid (0.15 mmol, 1.5 equivalents), and 20.7 mg of potassium carbonate (0.15 mmol, 1.5 equivalents) to a 10 mL reaction tube equipped with a magnetic stirrer in sequence. The substrate 2-(4-bromophenyl)ethyl-1-ol (28 μL, 0.2 mmol, 2.0 equivalent) was injected using a microsyringe, followed by three purgings with argon gas. After purging with argon gas, (5aS,10bR)-2-(2,6-difluorophenyl)-5a,10b-dihydro-4H,6H-indeno[2,1-b][1,2,4]triazolo[4,3-d][1,4]oxazine-2-onium tetrafluoroborate (4.1 mg, 0.01 mmol) and toluene (1 mL, 0.1 M) were added to the reaction tube, followed by three more purgings with argon gas. The reaction was then pre-stirred at room temperature for 30 min. After the pre-reaction, the substrate (E)-3-(4-(diphenylamino)phenyl)-2-methylpropenal (31.3 mg, 1 equivalent, 0.1 mmol) was injected into the reaction system using a microsyringe at room temperature, followed by another purging with argon gas. The reaction system was then placed in a 60°C oil bath for 48 hours. After the reaction was completed, petroleum ether and ethyl acetate (volume ratio 20:1) were used as eluents to obtain (R)-3-(4-(diphenylamino)phenyl)-2-methylpropionic acid 4-bromophenylethyl ester, the structure of which is shown below:

[0046] .

[0047] (R)-3-(4-(diphenylamino)phenyl)-2-methylpropionic acid 4-bromophenylethyl ester is a yellow oily liquid with a yield of 97% and an enantiomeric excess of 94%. Its NMR data are as follows: 1 H NMR (600 MHz, Chloroform-d) δ 7.43 (d, J = 8.4 Hz, 2H), 7.23 (t, J =7.9 Hz, 4H), 7.07 (d, J = 8.1 Hz, 6H), 7.01 (d, J = 12.1 Hz, 6H), 4.32 – 4.21 (m,2H), 2.95 (q, J = 13.6, 7.3 Hz, 1H), 2.85 (d, J = 7.1 Hz, 2H), 2.73 (q, J = 7.2 Hz, 1H), 2.63 (q, J = 13.7, 7.5 Hz, 1H), 1.17 (d, J = 6.7 Hz, 3H). 13 C NMR(151 MHz, CDCl3) δ 176.09, 147.98, 146.25, 136.98, 133.82, 131.69, 130.78, 129.90,129.30, 124.34, 124.09, 122.67, 120.58, 64.47, 41.62, 39.22, 34.69, 17.00.

[0048] Example 9 The method for synthesizing (R)-2-methyl-3-phenylpropionic acid 4-iodobenzyl ester includes the following steps: In a 10 mL reaction tube equipped with a magnetic stirrer, 100 mg of 4 Å molecular sieve, 27 mg of 1-adamantanecarboxylic acid (0.15 mmol, 1.5 equivalents), and 20.7 mg of potassium carbonate (0.15 mmol, 1.5 equivalents) were added sequentially. The substrate (4-iodophenyl)methanol (46.6 mg, 0.2 mmol, 2.0 equivalents) was injected via a microsyringe, followed by three purgings with argon gas. After purging with argon gas, (5aS,10bR)-2-(2,6-difluorophenyl)-5a,10b-dihydro-4H,6H-indeno[2,1-b][1,2,4]triazolo[4,3-d][1,4]oxazine-2-onium tetrafluoroborate (4.1 mg, 0.01 mmol) and toluene (1 mL, 0.1 M) were added to the reaction tube, followed by three more purgings with argon gas. The reaction was then pre-stirred at room temperature for 30 min. After the pre-reaction, the substrate (E)-2-methyl-3-phenylpropenal (14 μL, 1 equivalent, 0.1 mmol) was injected into the reaction system using a microsyringe at room temperature, followed by argon purging. The reaction system was then placed in a 60°C oil bath for 48 h. After the reaction, petroleum ether and ethyl acetate (20:1 v / v) were used as eluents to obtain (R)-2-methyl-3-phenylpropionic acid 4-iodobenzyl ester, with the structure shown below:

[0049] (R)-2-methyl-3-phenylpropionic acid 4-iodobenzyl ester is a yellow oily liquid with a yield of 94% and an enantiomeric excess of 94%. Its NMR data are as follows: 1 H NMR (600 MHz, Chloroform-d) δ 7.65 (d, J = 8.0 Hz, 2H), 7.25 (d, J =7.3 Hz, 2H), 7.21 (t, J = 7.3 Hz, 1H), 7.14 (d, J = 7.4 Hz, 2H), 6.96 (d, J = 8.0Hz, 2H), 5.04 – 4.96 (m, 2H), 3.01 (q, J = 13.5, 7.5 Hz, 1H), 2.81 (h, J = 7.1Hz, 1H), 2.71 (q, J = 13.5, 7.4 Hz, 1H), 1.19 (d, J = 7.0 Hz, 3H). 13C NMR (151 MHz, CDCl3) δ 175.83, 139.24, 137.71, 135.81, 130.03, 129.06, 128.49, 126.47, 93.86, 65.47, 41.59, 39.90, 17.01.

[0050] Example 10 The method for synthesizing (R)-2-methyl-3-phenylpropionic acid 4-chlorophenylethyl ester includes the following steps: Add 100 mg of 4 Å molecular sieve, 27 mg of 1-adamantanecarboxylic acid (0.15 mmol, 1.5 equivalents), and 20.7 mg of potassium carbonate (0.15 mmol, 1.5 equivalents) to a 10 mL reaction tube equipped with a magnetic stirrer in sequence. The substrate 2-(4-chlorophenyl)ethyl-1-ol (31.2 mg, 0.2 mmol, 2.0 equivalent) was injected using a microsyringe, followed by three purgings with argon gas. After purging with argon gas, (5aS,10bR)-2-(2,6-difluorophenyl)-5a,10b-dihydro-4H,6H-indeno[2,1-b][1,2,4]triazolo[4,3-d][1,4]oxazine-2-onium tetrafluoroborate (4.1 mg, 0.01 mmol) and toluene (1 mL, 0.1 M) were added to the reaction tube, followed by three more purgings with argon gas. The reaction was then pre-stirred at room temperature for 30 min. After the pre-reaction, the substrate (E)-2-methyl-3-phenylpropenal (14 μL, 1 equivalent, 0.1 mmol) was injected into the reaction system using a microsyringe at room temperature, followed by another purging with argon gas. The reaction system was then placed in an oil bath at 60°C and reacted for 48 hours. After the reaction was completed, petroleum ether and ethyl acetate in a volume ratio of 20:1 were used as eluents to obtain 4-chlorophenylethyl (R)-2-methyl-3-phenylpropionic acid, the structure of which is shown below:

[0051] .

[0052] (R)-2-methyl-3-phenylpropionic acid 4-chlorophenylethyl ester is a yellow oily liquid with a yield of 87% and an enantiomeric excess of 91%. Its NMR data are as follows: 1 H NMR (600 MHz, Chloroform-d) δ 7.29 (q, J = 8.5, 8.0 Hz, 4H), 7.23(t, J = 7.3 Hz, 1H), 7.16 (d, J = 7.5 Hz, 2H), 7.10 (d, J= 8.2 Hz, 2H), 4.25 (qt, J = 16.0, 10.7, 5.3 Hz, 2H), 3.00 (q, J = 13.3, 7.1 Hz, 1H), 2.86 (hept, J = 6.9Hz, 2H), 2.74 (h, J = 6.9 Hz, 1H), 2.67 (q, J = 13.4, 7.5 Hz, 1H), 1.15 (d, J = 6.8Hz, 3H). 13 C NMR(151 MHz, CDCl3) δ 176.04, 139.42, 136.50, 132.48, 130.35,129.08, 128.69, 128.47, 126.47, 64.56, 41.65, 39.84, 34.54, 16.99.

[0053] Example 11 A method for synthesizing 4-bromophenylethyl(R)-6,7,8,9-tetrahydro-5H-benzo[7]annulen-6-carboxylic acid ester includes the following steps: Add 100 mg of 4 Å molecular sieve, 27 mg of 1-adamantanecarboxylic acid (0.15 mmol, 1.5 equivalents), and 20.7 mg of potassium carbonate (0.15 mmol, 1.5 equivalents) to a 10 mL reaction tube equipped with a magnetic stirrer in sequence. The substrate 2-(thiophene-2-yl)ethyl-1-ol (25 μL, 0.2 mmol, 2.0 equivalent) was injected using a microsyringe, followed by three purgings with argon gas. After purging with argon gas, (5aS,10bR)-2-(2,6-difluorophenyl)-5a,10b-dihydro-4H,6H-indeno[2,1-b][1,2,4]triazolo[4,3-d][1,4]oxazine-2-onium tetrafluoroborate (4.1 mg, 0.01 mmol) and toluene (1 mL, 0.1 M) were added to the reaction tube, followed by three more purgings with argon gas. The reaction was then pre-stirred at room temperature for 30 min. After the pre-reaction, the substrate 6,7-dihydro-5H-benzo[7]annulene-8-carboxaldehyde (17 mg, 1 equivalent, 0.1 mmol) was injected into the reaction system using a microsyringe at room temperature, followed by another purging with argon gas. The reaction system was then placed in an oil bath at 60°C and reacted for 48 h. After the reaction was completed, petroleum ether and ethyl acetate in a volume ratio of 20:1 were used as eluents to obtain 4-bromophenylethyl(R)-6,7,8,9-tetrahydro-5H-benzo[7]annulene-6-carboxylic acid ester, the structure of which is shown in the following formula:

[0054] .

[0055] 4-Bromophenylethyl(R)-6,7,8,9-tetrahydro-5H-benzo[7]annulen-6-carboxylic acid ester is a yellow oily liquid with a yield of 91% and an enantiomeric excess of 94%. Its NMR data are as follows: 1 H NMR (600 MHz, Chloroform-d) δ 7.48 – 7.41 (m, 2H), 7.18 – 7.04 (m,6H), 4.36 – 4.23 (m, 2H), 3.04 (dd, J = 14.2, 10.1 Hz, 1H), 2.97 – 2.88 (m,3H), 2.87 – 2.73 (m, 2H), 2.46 (t, J = 10.4 Hz, 1H), 2.12 (dt, J = 9.0, 5.0 Hz,1H), 2.04 – 1.95 (m, 1H), 1.89 (qd, J = 11.0, 3.3 Hz, 1H), 1.52 – 1.41 (m, 1H). 13 C NMR(151 MHz, CDCl3) δ 175.59, 143.14, 139.68, 137.03, 131.69, 130.79,129.79, 129.05, 126.78, 126.31, 120.57, 64.50, 44.13, 38.37, 35.90, 34.75,34.68, 26.54.

[0056] Example 12 The method for synthesizing 4-bromophenylethyl(R)-2-(thiophen-2-yl)-6,7,8,9-tetrahydro-5H-benzo[7]annulen-6-carboxylic acid ester includes the following steps: Add 100 mg of 4 Å molecular sieve, 27 mg of 1-adamantanecarboxylic acid (0.15 mmol, 1.5 equivalents), and 20.7 mg of potassium carbonate (0.15 mmol, 1.5 equivalents) to a 10 mL reaction tube equipped with a magnetic stirrer in sequence. The substrate 2-(thiophen-2-yl)ethyl-1-ol (25 μL, 0.2 mmol, 2.0 equivalent) was injected via a microsyringe, followed by three purgings with argon gas. After purging with argon gas, (5aS,10bR)-2-(2,6-difluorophenyl)-5a,10b-dihydro-4H,6H-indeno[2,1-b][1,2,4]triazolo[4,3-d][1,4]oxazine-2-onium tetrafluoroborate (4.1 mg, 0.01 mmol) and toluene (1 mL, 0.1 M) were added to the reaction tube, followed by three more purgings with argon gas. The reaction was then pre-stirred at room temperature for 30 min. After the pre-reaction was completed, the substrate 3-(thiophen-2-yl)-6,7-dihydro-5H-benzo[7]annulen-8-carboxaldehyde (25.4 mg, 1 equivalent, 0.1 mmol) was injected into the reaction system using a microsyringe at room temperature, and argon gas was purged again. The reaction system was then placed in an oil bath at 60 °C for 48 h. After the reaction was completed, 4-bromophenylethyl(R)-2-(thiophen-2-yl)-6,7,8,9-tetrahydro-5H-benzo[7]annulen-6-carboxylic acid ester was obtained using petroleum ether and ethyl acetate in a volume ratio of 20:1 as eluent, and its structure is shown in the following formula:

[0057] .

[0058] 4-Bromophenylethyl(R)-2-(thiophen-2-yl)-6,7,8,9-tetrahydro-5H-benzo[7]annulen-6-carboxylic acid ester is a yellow oily liquid with a yield of 91% and an enantiomeric excess of 93%. Its NMR data are as follows: 1 H NMR (600 MHz, Chloroform-d) δ 7.45 (d, J = 8.4 Hz, 2H), 7.38 – 7.34(m, 2H), 7.30 – 7.24 (m, 2H), 7.14 – 7.05 (m, 4H), 4.29 (qt, J = 10.9, 6.9 Hz, 2H), 3.04 (dd, J = 14.2, 10.1 Hz, 1H), 2.98 – 2.88 (m, 3H), 2.88 – 2.78 (m,2H), 2.47 (tt, J= 10.5, 2.5 Hz, 1H), 2.17 – 2.09 (m, 1H), 2.05 – 1.96 (m, 1H), 1.95 – 1.85 (m, 1H), 1.56 – 1.46 (m, 1H). 13 C NMR (151 MHz, CDCl3) δ 175.42, 144.47, 143.68, 139.08, 137.00, 132.92, 131.69, 130.78, 130.42, 128.03, 126.69, 124.53, 123.74, 122.85, 120.58, 64.52, 44.10, 37.99, 35.95, 34.67, 34.64, 26.48. Example 13

[0059] Example 13 A method for synthesizing 4-bromophenylethyl(R)-2-chloro-6,7,8,9-tetrahydro-5H-benzo[7]annulen-6-carboxylic acid ester includes the following steps: Add 100 mg of 4 Å molecular sieve, 27 mg of 1-adamantanecarboxylic acid (0.15 mmol, 1.5 equivalents), and 20.7 mg of potassium carbonate (0.15 mmol, 1.5 equivalents) to a 10 mL reaction tube equipped with a magnetic stirrer in sequence. The substrate 2-(thiophen-2-yl)ethyl-1-ol (25 μL, 0.2 mmol, 2.0 equivalent) was injected via a microsyringe, followed by three purgings with argon gas. After purging with argon gas, (5aS,10bR)-2-(2,6-difluorophenyl)-5a,10b-dihydro-4H,6H-indeno[2,1-b][1,2,4]triazolo[4,3-d][1,4]oxazine-2-onium tetrafluoroborate (4.1 mg, 0.01 mmol) and toluene (1 mL, 0.1 M) were added to the reaction tube, followed by three more purgings with argon gas. The reaction was then pre-stirred at room temperature for 30 min. After the pre-reaction was completed, the substrate 3-chloro-6,7-dihydro-5H-benzo[7]annulen-8-carboxaldehyde (21 mg, 1 equivalent, 0.1 mmol) was injected into the reaction system using a microsyringe at room temperature, and argon gas was purged again. The reaction system was then placed in an oil bath at 60 °C for 48 h. After the reaction was completed, 4-bromophenylethyl(R)-2-chloro-6,7,8,9-tetrahydro-5H-benzo[7]annulen-6-carboxylic acid ester was obtained using petroleum ether and ethyl acetate in a volume ratio of 20:1 as eluent, and its structure is shown in the following formula:

[0060] .

[0061] 4-Bromophenylethyl(R)-2-chloro-6,7,8,9-tetrahydro-5H-benzo[7]annulen-6-carboxylic acid ester is a yellow oily liquid with a yield of 75% and an enantiomeric excess of 93%. Its NMR data are as follows: 1 H NMR (600 MHz, Chloroform-d) δ 7.43 (d, J = 6.6 Hz, 2H), 7.15 – 7.02(m, 4H), 6.96 (d, J = 7.2 Hz, 1H), 4.33 – 4.20 (m, 2H), 3.02 – 2.94 (m, 1H), 2.93 – 2.85 (m, 3H), 2.82 – 2.67 (m, 2H), 2.42 (d, J = 10.5 Hz, 1H), 2.09 (d, J =13.5 Hz, 1H), 2.00 – 1.82 (m, 2H), 1.46 (q, J = 12.1 Hz, 1H). 13 C NMR(151 MHz, CDCl3) δ 175.19, 144.96, 138.08, 136.96, 132.08, 131.70, 131.14, 130.77,128.95, 126.10, 120.60, 64.55, 43.82, 37.59, 35.66, 34.65, 34.47, 26.20.

[0062] It should be noted that when numerical ranges are involved in this invention, it should be understood that the two endpoints of each numerical range, as well as any value between the two endpoints, can be selected. Since the steps and methods used are the same as in the embodiments, preferred embodiments are described in this invention to avoid redundancy. Although preferred embodiments of this invention have been described, those skilled in the art, once they understand the basic inventive concept, can make other changes and modifications to these embodiments, and all such changes and modifications fall within the scope of this invention.

[0063] Obviously, those skilled in the art can make various modifications and variations to this invention without departing from its spirit and scope. If these modifications and variations fall within the scope of equivalents of this invention, then this invention is also intended to include these modifications and variations.

Claims

1. An asymmetric synthesis method for α-chiral ester compounds, characterized in that, Includes the following steps: In a solvent, α-alkyl-α,β-unsaturated aldehydes and alcohols represented by Formula II undergo asymmetric α-protonation and esterification reactions in the presence of a chiral nitrogen heterocyclic carbene catalyst, a base, and a protic acid to yield α-chiral ester compounds. α-alkyl-α,β-unsaturated aldehydes are selected from chain-like α-alkylenal or cyclic α-alkylenal; the structural formulas of α-alkyl-α,β-unsaturated aldehydes are shown in Formula I1, Formula I2, Formula I3 or Formula I4: ； The structural formula of the alcohol represented by Formula II is as follows: ； Among them, R 1 Selected from halogen, methyl, phenyl, diphenylamino, trifluoromethyl, thiophene, or cyano; R 2 It is selected from methyl, iodine, chlorinated phenyl, bromine-substituted benzyl, thiophene methyl, or ferrocene methyl.

2. The asymmetric synthesis method for α-chiral ester compounds according to claim 1, characterized in that, The asymmetric synthesis method for α-chiral ester compounds is as follows: After mixing a protic acid, a base, and a molecular sieve, α-alkyl-α,β-unsaturated aldehydes, an alcohol of formula II, a chiral nitrogen heterocyclic carbene catalyst, and a solvent are added under a protective atmosphere to undergo asymmetric α-protonation and esterification reactions, yielding α-chiral ester compounds.

3. The asymmetric synthesis method for α-chiral ester compounds according to claim 2, characterized in that, The molar ratio of α-alkyl-α,β-unsaturated aldehyde and the alcohol shown in Formula II is 1:

2.

4. The asymmetric synthesis method for α-chiral ester compounds according to claim 2, characterized in that, The temperature range for asymmetric α-protonation and esterification reactions is 25℃ to 60℃.

5. The asymmetric synthesis method for α-chiral ester compounds according to claim 2, characterized in that, When the α-alkyl-α,β-unsaturated aldehyde is a chain α-alkylenal, the temperature for asymmetric α-protonation and esterification reactions is 60℃~65℃; when the α-alkyl-α,β-unsaturated aldehyde is a cyclic α-alkylenal, the temperature for asymmetric α-protonation and esterification reactions is 20℃~30℃.

6. The asymmetric synthesis method for α-chiral ester compounds according to claim 2, characterized in that, The amount of chiral nitrogen heterocyclic carbene catalyst used is 10% of the molar amount of α-alkyl-α,β-unsaturated aldehyde.

7. The asymmetric synthesis method for α-chiral ester compounds according to claim 2, characterized in that, The chiral nitrogen heterocyclic carbene catalyst is (5aS,10bR)-2-(2,6-difluorophenyl)-5a,10b-dihydro-4H,6H-indeno[2,1-b][1,2,4]triazolo[4,3-d][1,4]oxazine-2-onium tetrafluoroborate or 2-(2,6-dichlorophenyl)-9-phenyl-5a,10b-dihydro-4H,6H-indeno[2,1-b][1,2,4]triazolo[4,3-d][1,4]oxazine-2-onium tetrafluoroborate.

8. The asymmetric synthesis method for α-chiral ester compounds according to claim 2, characterized in that, The base is sodium bicarbonate or potassium carbonate; the protic acid is adamantane.

9. The asymmetric synthesis method for α-chiral ester compounds according to claim 2, characterized in that, The solvent is chlorobenzene or toluene.

10. The asymmetric synthesis method of α-chiral ester compounds according to claim 1, characterized in that, The structural formulas of α-chiral ester compounds are shown in Formula III1, Formula III2, or Formula III3: 。

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