Chiral dialkenyl substituted carboxylic ester compound and asymmetric preparation method thereof

Abstract

The invention discloses a chiral dienyl substituted carboxylic ester compound and an asymmetric preparation method thereof, the chiral dienyl substituted carboxylic ester compound is an optical active compound with a structure as shown in the following formula I, and comprises a stereoisomer with the same chemical general formula: # imgabs0 # in the formula: * represents a chiral carbon atom; the substituent R is selected from hydrogen, C1-10 alkyl or aryl; ar is an aromatic ring or a substituted aromatic ring; r1, R2, R3, R4 and R5 are respectively and independently selected from hydrogen, halogen, C1-10 alkyl or alkoxy; r6 is independently selected from a C1-10 alkyl group or an aryl group; and R7 is independently selected from C1-10 alkyl groups or aryl groups. According to the invention, a chiral isothiourea catalytic electrochemical synthesis system is applied, and the chiral dialkenyl substituted carboxylic ester compound is accurately and rapidly synthesized with high yield, high stereoselectivity and gram-level scale. The preparation method is simple, and has biomedical practicability and industrial application prospects.

Description

Technical Field

[0001] The invention belongs to the technical field of asymmetric organic synthesis, and specifically relates to a chiral diene-substituted carboxylic acid ester compound and an asymmetric preparation method thereof. Background Art

[0002] Carboxylic acids are an important class of chemical raw materials. The functionalization reaction of the α-position of the carbonyl group is an important reaction in organic synthetic chemistry. It can quickly and efficiently convert simple and readily available carboxylic acid derivatives into important compounds with diverse structures. It has been widely used in the fields of medicinal chemistry, polymer chemistry and materials chemistry. On the other hand, 1,3-dienes are unique and important skeletons that are widely present in natural products, bioactive molecules, drugs and functional organic materials. To date, although many asymmetric catalytic methods have been established, the construction of chiral carboxylic acid compounds containing diene skeletons from simple carboxylic acid derivatives through asymmetric catalytic synthesis methods is still a hot topic and difficulty in the field of organic synthesis. Therefore, it is a scientific hotspot worthy of attention to develop an efficient catalytic system to achieve the enantioselective synthesis of chiral diene-substituted carboxylic acid ester compounds, thereby creating richer three-dimensional molecular structures.

[0003] Electrochemical synthesis strategy is a type of green and sustainable synthesis method. Electrochemical synthesis achieves chemical reactions by reactants gaining and losing electrons on electrodes. In principle, no other reagents are used, which greatly reduces material consumption and environmental pollution. In recent years, with the vigorous development of electrochemical asymmetric synthesis strategies, asymmetric electrochemical functionalization reactions involving chiral amines, aldehyde compounds catalyzed by chiral metal complexes, acyl imidazole compounds, and benzoxazole carbonyl compounds have been achieved. However, the development of more types of asymmetric electrochemical catalytic systems, and then the realization of asymmetric electrochemical reactions involving simple carboxylic acid derivatives and the stereoselective control of the process, still face huge challenges. Summary of the invention

[0004] The purpose of the present invention is to provide a chiral diene-substituted carboxylic acid ester compound and an asymmetric preparation method thereof, thereby solving the above-mentioned problems existing in the prior art.

[0005] The chiral diene-substituted carboxylic acid ester compounds of the present invention are optically active compounds having a structure shown in the following formula I, including stereoisomers having the same chemical formula:

[0006] Wherein: * represents a chiral carbon atom; the substituent R is selected from hydrogen, C 1-10 Alkyl or aryl; Ar is an aromatic ring or a substituted aromatic ring; R 1 , R 2 , R 3 , R4 , R 5 , R 6 are independently selected from hydrogen, halogen, C 1-10 A hydrocarbon group or a hydrocarbonoxy group; R 7 Independently selected from C 1-10 Alkyl or aryl.

[0007] The asymmetric preparation method of a chiral diene-substituted carboxylate compound of the present invention uses a substituted allylsilane 1 and a carboxylate derivative 2 as starting materials, an alcohol 3 as a quenching reagent, and a chiral isothiourea as a reaction catalyst. An asymmetric olefination reaction is performed under electrochemical reaction conditions, and a target product I is obtained after separation and purification.

[0008] The synthetic route is as follows:

[0009] In the above formula: * represents a chiral carbon atom; the substituent R is selected from hydrogen, C 1-10 Alkyl or aryl; Ar is an aromatic ring or a substituted aromatic ring; R 1 , R 2 , R 3 , R 4 , R 5 are independently selected from hydrogen, halogen, C 1-10 A hydrocarbon group or a hydrocarbonoxy group; R 6 Independently selected from C 1-10 Alkyl or aryl; R 7 Independently selected from C 1-10 Alkyl or aryl; R 8 Independently selected from C 1-10 Alkyl or aryl.

[0010] The specific steps include: Under a nitrogen atmosphere, in a reaction bottle equipped with electrodes, substituted allylsilane 1, carboxylate derivative 2, alcohol 3, chiral isothiourea catalyst and electrolyte are added, and an organic solvent is added for dissolution, and current electrolysis is applied at -20°C to 70°C for 2-48 hours, and the reaction endpoint is determined by thin layer chromatography spot plate; after the reaction is complete, the solvent is directly removed by reduced pressure distillation, and finally the residue is separated by column chromatography to obtain the target product I.

[0011] During the preparation process of the present invention: The chiral isothiourea catalyst is selected from the following structures:

[0012] Where: * is a carbon chiral center; n is 0 or 1; R 9 , R 10 , R 11 and R 12are independently selected from hydrogen, halogen, substituted or unsubstituted groups: C 1-10 Alkyl, C 3-10 Cycloalkyl, 2-furyl or C 6-20 The aryl group; R 13 Independently selected from C 1-10 Alkyl or aryl.

[0013] The organic solvent is 1,4-dioxane, dichloromethane, dichloroethane, dimethyl sulfoxide, N -Methylpyrrolidone, N , N -dimethylformamide, N , N - dimethylacetamide, ethyl acetate, chloroform, tetrahydrofuran, acetonitrile, toluene, ethylbenzene, fluorobenzene, chlorobenzene, bromobenzene, xylene or trimethylbenzene.

[0014] The electrode is one or two of carbon, carbon cloth, carbon felt, carbon paper, platinum, nickel, reticulated glassy carbon (RVC), glassy carbon (GC), and boron-doped diamond (BDD) electrodes.

[0015] The electrolyte is tetrabutylammonium hexafluorophosphate, tetraethylammonium hexafluorophosphate, tetrabutylammonium tetrafluoroborate, tetraethylammonium tetrafluoroborate, tetrabutylammonium perchlorate or tetrabutylammonium bromide.

[0016] Wherein: the molar ratio of the chiral isothiourea catalyst to the substituted allylsilane 1 is 0.025:1-1:1; the molar equivalent ratio of the substituted allylsilane 1 to the carboxylate derivative 2 is 1:1-1:5; the molar equivalent ratio of the substituted allylsilane 1 to the alcohol 3 is 1:1-1:100; the molar ratio of the substituted allylsilane 1 to the electrolyte is 1:0.1-1:5.

[0017] The present invention provides a method for synthesizing chiral diene-substituted carboxylic acid ester compounds through the key step of electrochemical catalytic asymmetric reaction. The present invention uses substituted allylsilane 1 and carboxylic acid ester derivative 2 as starting materials, alcohol 3 as quenching reagent, chiral isothiourea as reaction catalyst, and undergoes asymmetric olefination reaction under electrochemical reaction conditions, and obtains the target product I after separation and purification. The present invention successfully develops a method for synthesizing chiral diene-substituted carboxylic acid ester compounds, which is easy to prepare chiral diene-substituted carboxylic acid ester compounds with high yield and high optical purity. By using the electrochemical synthesis method, electrons are used instead of traditional oxidants, and the synthesis of chiral diene-substituted carboxylic acid ester compounds can be realized in a green and atom-economic manner, which is beneficial to industrial production. At the same time, 1,3-dienes are unique and important skeletons, which are widely present in natural products, bioactive molecules and functional organic materials (Harned, AM, Volp, KA The sorbicillinoid familyof natural products: Isolation, biosynthesis, and synthetic studies. Nat. Prod. Rep. 2011, 28 , 1790.), and can also be used as an important class of organic synthesis intermediates to construct heterocyclic skeletons through cycloaddition reactions (Chen, J.-R. Hu, X.-Q. Lu, L.-Q. Xiao, W.-J. Formal [4+1]Annulation Reactions in the Synthesis of Carbocyclicand Heterocyclic Systems. Chem. Rev. 2015, 115 , 5301-5365.). Therefore, the synthesis of chiral molecules containing a diene skeleton has important research value and practical significance, which reflects the practicality of the preparation method. DETAILED DESCRIPTION

[0018] The specific embodiments of the present invention are described in detail below. It should be understood that the specific embodiments described herein are only used to illustrate and explain the present invention, and are not used to limit the present invention.

[0019] The endpoints and any values ​​of the ranges disclosed in this article are not limited to the precise ranges or values, and these ranges or values ​​should be understood to include values ​​close to these ranges or values. For numerical ranges, the endpoint values ​​of each range, the endpoint values ​​of each range and the individual point values, and the individual point values ​​can be combined with each other to obtain one or more new numerical ranges, which should be considered as specifically disclosed in this article.

[0020] Example 1: Preparation of Chiral Diene Substituted Carboxylate Compound 4a

[0021] Take a 10mL reaction tube equipped with a stirring magnet and dried, equip it with a carbon electrode as the anode and a platinum electrode as the cathode. Under a nitrogen atmosphere, weigh and add the corresponding compounds 1a (0.1mmol), 2a (0.3mmol), methanol 3a (0.5mmol), chiral isothiourea catalyst (0.01mmol), tetrabutylammonium hexafluorophosphate ( n Bu4NPF6, 0.3 mmol), then a mixed solution of THF / MeCN = 2:1 (3 mL) was added to dissolve it. Then, electrolysis was performed at 25°C with a constant current (1 mA) for 12 hours. After the reaction was complete, the solvent was directly removed by reduced pressure distillation, and finally, petroleum ether / ethyl acetate was mixed in a volume ratio of 50:1 as the eluent, and the dienylation product 4a (55% yield, 97% ee) was separated by column chromatography.

[0022] 1 H NMR (400 MHz, CDCl3)δ 7.26 – 7.16 (m, 7H), 7.13 – 7.06 (m, 2H), 5.56 (dd, J = 6.8, 1.4 Hz, 1H), 5.46 (d, J = 1.6 Hz, 1H), 4.83 (d, J = 1.6Hz, 1H), 4.28 (d, J = 1.4 Hz, 1H), 3.56 (s, 3H), 2.30 (s, 3H), 1.59 (dd, J =6.8, 1.3 Hz, 3H). 13C NMR (100 MHz, CDCl3) δ 172.7, 145.8, 139.3, 137.6, 137.0,136.0, 129.3, 129.2, 128.3, 127.2, 126.4, 126.0, 115.2, 57.1, 52.0, 21.2,14.9.ESI-MS: calculated [C 21 H 22 O2 + Na] + : 329.1512, found: 329.1510. [α] 20 D = +89.4 (c = 0.98, CH2Cl2). The product was analyzed by HPLC to determine theenantiomeric excess: 97% ee (CHIRALPAK IBN-5, n -hexane / i -PrOH = 95 / 5, detector: 254 nm, T = 25 ℃, flow rate: 1 mL / min), t1(minor) = 3.9min, t2(major) = 4.4 min.

[0023] Example 2: Preparation of Chiral Diene Substituted Carboxylate Compound 4b

[0024] Take a 10mL reaction tube equipped with a stirring magnet and dried, equip it with a carbon electrode as the anode and a platinum electrode as the cathode. Under a nitrogen atmosphere, weigh and add the corresponding compounds 1b (0.1mmol), 2a (0.3mmol), methanol 3a (0.5mmol), chiral isothiourea catalyst (0.01mmol), tetrabutylammonium hexafluorophosphate ( n Bu4NPF6, 0.3 mmol), then a mixed solution of THF / MeCN = 2:1 (3 mL) was added to dissolve it. Then, electrolysis was performed at 25°C with a constant current (1 mA) for 12 hours. After the reaction was complete, the solvent was directly removed by vacuum distillation, and finally, petroleum ether / ethyl acetate was mixed in a volume ratio of 50:1 as the eluent, and the dienylation product 4b (56% yield, 97% ee) was separated by column chromatography.

[0025] 1H NMR (500 MHz, CDCl3) δ 7.67 – 7.56 (m, 4H), 7.52 – 7.43 (m, 4H), 7.41 – 7.27 (m, 6H), 5.69 (dd, J = 6.8, 1.4 Hz, 1H), 5.64 (d, J = 1.5 Hz,1H), 5.00 (d, J = 1.5 Hz, 1H), 4.41 (t, J = 1.4 Hz, 1H), 3.66 (s, 3H), 1.70(dd, J = 6.8, 1.3 Hz, 3H). 13 C NMR (125 MHz, CDCl3) δ 172.7, 145.6, 140.8,140.6, 139.1, 137.9, 136.9, 129.3, 128.8, 128.4, 127.4, 127.3, 127.2, 127.0,126.9, 126.4, 116.0, 57.2, 52.0, 15.0.ESI-MS: calculated [C 26 H 24 O2 + Na] + :391.1669, found: 391.1661. [α] 20 D = +94.3 (c = 0.80, CH2Cl2). The product wasanalyzed by HPLC to determine the enantiomeric excess: 97% ee (CHIRALCEL AD, n -hexane / i -PrOH = 95 / 5, detector: 254 nm, T = 25 ℃, flow rate: 1 mL / min), t1(minor) = 4.6 min, t2(major) = 5.0 min.

[0026] Example 3: Preparation of Chiral Diene Substituted Carboxylate Compound 4c

[0027] Take a 10mL reaction tube equipped with a stirring magnet and dried, equip it with a carbon electrode as the anode and a platinum electrode as the cathode. Under a nitrogen atmosphere, weigh and add the corresponding compounds 1c (0.1mmol), 2a (0.3mmol), methanol 3a (0.5mmol), chiral isothiourea catalyst (0.01mmol), tetrabutylammonium hexafluorophosphate ( n Bu4NPF6, 0.3 mmol), then a mixed solution of THF / MeCN = 2:1 (3 mL) was added to dissolve it. Then, electrolysis was performed at 25°C with a constant current (1 mA) for 12 hours. After the reaction was complete, the solvent was directly removed by vacuum distillation, and finally, petroleum ether / ethyl acetate was mixed in a volume ratio of 50:1 as the eluent, and the dienylation product 4c (61% yield, 92% ee) was separated by column chromatography.

[0028] 1 H NMR (400 MHz, CDCl3) δ 7.29 – 7.15 (m,7H), 6.98 – 6.89 (m, 2H), 5.56 (dd, J = 6.8, 1.4 Hz, 1H), 5.42 (d, J = 1.4 Hz, 1H), 4.87 (d, J = 1.4Hz, 1H), 4.25 (d, J = 1.5 Hz, 1H), 3.55 (s, 3H), 1.56 (dd, J = 6.8, 1.3 Hz,3H). 13 C NMR (101 MHz, CDCl3) δ 172.62, 162.58 (d, J = 246.7 Hz), 145.07,138.97, 136.75, 135.09, 129.23, 128.36, 128.26, 128.18, 127.34, 126.44,115.89, 115.42, 115.21, 57.21, 52.02, 14.93. 19 F NMR (376 MHz, CDCl3) δ -114.7.ESI-MS: calculated [C 20 H 19 FO2 + Na] + : 333.1261, found: 333.1265. [α] 20 D=+36.9 (c = 0.67, CH2Cl2).The product was analyzed by HPLC to determine theenantiomeric excess: 92% ee (CHIRALPAK IBN-5, n -hexane / i -PrOH = 98 / 2, detector: 254 nm, T = 25 ℃, flow rate: 1 mL / min), t1(major) = 4.6 min, t2(mior) = 5.3 min.

[0029] Example 4: Preparation of Chiral Diene Substituted Carboxylate Compound 4d

[0030] Take a 10mL reaction tube equipped with a stirring magnet and dry, equip it with a carbon electrode as the anode and a platinum electrode as the cathode. Under a nitrogen atmosphere, weigh and add the corresponding compounds 1d (0.1mmol), 2a (0.3mmol), methanol 3a (0.5mmol), chiral isothiourea catalyst (0.01mmol), tetrabutylammonium hexafluorophosphate ( n Bu4NPF6, 0.3 mmol), then a mixed solution of THF / MeCN = 2:1 (3 mL) was added to dissolve it. Then, electrolysis was performed at 25°C with a constant current (1 mA) for 12 hours. After the reaction was complete, the solvent was directly removed by reduced pressure distillation, and finally, petroleum ether / ethyl acetate was mixed in a volume ratio of 50:1 as an eluent, and the dienylation product 4d (65% yield, 97% ee) was separated by column chromatography.

[0031] 1 H NMR (400 MHz, CDCl3) δ 7.26 – 7.02 (m, 9H), 5.58 (dd, J = 6.8, 1.3Hz, 1H), 5.48 (d, J = 1.7 Hz, 1H), 4.87 (d, J = 1.6 Hz, 1H), 4.28 (d, J = 1.8Hz, 1H), 3.57 (s, 3H), 2.29 (s, 3H), 1.60 (dd, J = 6.8, 1.3 Hz, 1H). 13C NMR(100MHz, CDCl3) δ 172.7, 146.0, 139.3, 138.8, 138.0, 137.0, 129.2, 128.6,128.4, 128.3, 127.2, 126.1, 123.7, 115.9, 57.0, 52.0, 21.5, 14.9.ESI-MS:calculated [C 21 H 22 O2 + Na] + : 329.1512, found: 329.1517. [α] 20 D = +54.6 (c =0.76, CH2Cl2). The product was analyzed by HPLC to determine the enantiomericexcess: 97% ee(CHIRALCEL OJ-H, n -hexane / i -PrOH = 70 / 30, detector: 254 nm, T =25 ℃, flow rate: 1 mL / min), t1(major) = 5.2 min, t2(minor) = 9.6 min.

[0032] Example 5: Preparation of Chiral Diene Substituted Carboxylate Compound 4e

[0033] Take a 10mL reaction tube equipped with a stirring magnet and dry, equip it with a carbon electrode as the anode and a platinum electrode as the cathode. Under a nitrogen atmosphere, weigh and add the corresponding compounds 1e (0.1mmol), 2a (0.3mmol), methanol 3a (0.5mmol), chiral isothiourea catalyst (0.01mmol), tetrabutylammonium hexafluorophosphate ( n Bu4NPF6, 0.3 mmol), then a mixed solution of THF / MeCN = 2:1 (3 mL) was added to dissolve it. Then, electrolysis was performed at 25°C with a constant current (1 mA) for 12 hours. After the reaction was complete, the solvent was directly removed by vacuum distillation, and finally, petroleum ether / ethyl acetate was mixed in a volume ratio of 50:1 as the eluent, and the dienylation product 4e (67% yield, 94% ee) was separated by column chromatography.

[0034] 1H NMR (400 MHz, CDCl3) δ 7.34 – 7.21 (m, 5H), 7.01 – 6.89 (m, 3H), 5.63 (dd, J = 6.7, 1.3 Hz, 1H), 5.52 (d, J = 1.7 Hz, 1H), 4.89 (d, J = 1.7Hz, 1H), 4.32 (d, J = 1.3 Hz, 1H), 3.62 (s, 3H), 2.30 (s, 6H), 1.66 (dd, J =6.7, 1.3 Hz, 3H). 13 C NMR (100 MHz, CDCl3) δ 172.8, 146.0, 139.4, 138.8, 137.9,137.1, 129.5, 129.2, 128.3, 127.2, 126.0, 124.4, 115.7, 57.0, 52.0, 21.4,14.9.ESI-MS: calculated [C 22 H 24 O2 + Na] + : 343.1669, found: 343.1660. [α] 20 D = +82.2 (c = 0.64, CH2Cl2). The product was analyzed by HPLC to determine theenantiomeric excess: 94% ee(CHIRALCEL OJ-H, n -hexane / i -PrOH = 70 / 30, detector: 254 nm, T = 25 ℃, flow rate: 1 mL / min), t1(major) = 4.0 min, t2(mior) = 4.9 min.

[0035] Example 6: Preparation of Chiral Diene Substituted Carboxylate Compound 4f

[0036] Take a 10mL reaction tube equipped with a stirring magnet and dry, equip it with a carbon electrode as the anode and a platinum electrode as the cathode. Under a nitrogen atmosphere, weigh and add the corresponding compound 1f (0.1mmol), 2a (0.3mmol), methanol 3a (0.5mmol), chiral isothiourea catalyst (0.01mmol), tetrabutylammonium hexafluorophosphate ( n Bu4NPF6, 0.3 mmol), then a mixed solution of THF / MeCN = 2:1 (3 mL) was added to dissolve it. Then, electrolysis was performed at 25°C with a constant current (1 mA) for 12 hours. After the reaction was complete, the solvent was directly removed by vacuum distillation, and finally, petroleum ether / ethyl acetate was mixed in a volume ratio of 50:1 as the eluent, and the dienylation product 4f (63% yield, 97% ee) was separated by column chromatography.

[0037] 1 H NMR (400 MHz, CDCl3) δ 7.85 – 7.76 (m, 4H), 7.52 – 7.28 (m, 8H), 5.52 (dd, J = 6.8, 1.4 Hz, 1H), 5.41 (d, J = 1.4 Hz, 1H), 4.85 (d, J = 1.4Hz, 1H), 4.27 (d, J = 1.3 Hz, 1H), 3.65 (s, 3H), 1.53 (dd, J = 6.8, 1.3 Hz,3H). 13 C NMR (100 MHz, CDCl3) δ 173.8, 146.5, 140.1, 139.1, 136.4, 131.4,130.7, 128.2, 127.1, 126.4, 126.1, 125.7, 125.4, 124.7, 124.7, 124.1, 123.0,116.3, 57.7, 52.5, 15.3.ESI-MS: calculated [C 24 H 22 O2 + Na] + : 365.1512, found:365.1510. [α] 20 D= +52.9 (c = 0.69, CH2Cl2).The product was analyzed by HPLC to determine the enantiomeric excess: 97% ee (CHIRALPAK IBN-5, n -hexane / i -PrOH =95 / 5, detector: 254 nm, T = 25 ℃, flow rate: 1 mL / min), t1(major) = 4.5 min, t2(mior) = 5.1 min.

[0038] Example 7: Preparation of 4g of chiral diene-substituted carboxylate compound

[0039] Take a 10mL reaction tube equipped with a stirring magnet and dried, equip it with a carbon electrode as the anode and a platinum electrode as the cathode. Under a nitrogen atmosphere, weigh and add the corresponding compound 1g (0.1mmol), 2a (0.3mmol), methanol 3a (0.5mmol), chiral isothiourea catalyst (0.01mmol), tetrabutylammonium hexafluorophosphate ( n Bu4NPF6, 0.3 mmol), then a mixed solution of THF / MeCN=2:1 (3 mL) was added to dissolve it. Then, electrolysis was performed at 25°C with a constant current (1 mA) for 12 hours. After the reaction was complete, the solvent was directly removed by reduced pressure distillation, and finally, petroleum ether / ethyl acetate was mixed in a volume ratio of 50:1 as an eluent, and 4 g of dienylation product (60% yield, 94% ee) was obtained by column chromatography separation.

[0040] 1 H NMR (500 MHz, CDCl3) δ 7.34 – 7.29 (m, 2H), 7.27 – 7.15 (m, 8H), 5.51 (d, J = 1.3 Hz, 1H), 5.44 (d, J = 1.6 Hz, 1H), 4.84 (d, J = 1.6 Hz, 1H), 4.26 (s, 1H), 3.56 (s, 3H), 1.99 (d, J = 7.4 Hz, 2H), 1.29 (q, J = 7.4 Hz,2H), 0.77 (t, J= 7.4 Hz, 3H). 13 C NMR (125 MHz, CDCl3) δ 172.7, 146.2, 139.0,138.2, 137.0, 132.0, 129.3, 128.4, 128.3, 127.8, 127.2, 126.6, 115.9, 57.0,51.9, 31.2, 22.9, 13.9.ESI-MS: calculated [C 22 H 24 O2 + Na] + : 343.1669, found:343.1665. [α] 20 D = +75.7 (c = 0.70, CH2Cl2). The product was analyzed by HPLC to determine the enantiomeric excess: 94% ee(CHIRALPAK IBN-5, n -hexane / i -PrOH= 95 / 5, detector: 254 nm, T = 25 ℃, flow rate: 1 mL / min), t1(minor) = 3.9min, t2(major) = 4.4 min.

[0041] Example 8: Preparation of Chiral Diene Substituted Carboxylate Compound 4h

[0042] Take a 10mL reaction tube equipped with a stirring magnet and dry, equip it with a carbon electrode as the anode and a platinum electrode as the cathode. Under a nitrogen atmosphere, weigh and add the corresponding compound 1h (0.1mmol), 2a (0.3mmol), methanol 3a (0.5mmol), chiral isothiourea catalyst (0.01mmol), tetrabutylammonium hexafluorophosphate ( n Bu4NPF6, 0.3 mmol), then a mixed solution of THF / MeCN=2:1 (3 mL) was added to dissolve it. Then, electrolysis was performed at 25°C with a constant current (1 mA) for 12 hours. After the reaction was complete, the solvent was directly removed by reduced pressure distillation, and finally, petroleum ether / ethyl acetate was mixed in a volume ratio of 50:1 as an eluent, and the dienylation product 4h (50% yield, 93% ee) was separated by column chromatography.

[0043] 1H NMR (400 MHz, CDCl3) δ 7.31 – 7.07 (m, 13H), 7.02 – 6.94 (m, 2H), 5.53 (dd, J = 7.3, 1.3 Hz, 1H), 5.39 (d, J = 1.6 Hz, 1H), 4.71 (d, J = 1.6Hz, 1H), 4.22 (d, J = 1.2 Hz, 1H), 3.56 (s, 3H), 2.57 (t, J = 7.2 Hz, 2H),2.39 – 2.29 (m, 2H). 13 C NMR (100 MHz, CDCl3) δ 172.6, 146.0, 141.6, 138.9,138.8, 136.8, 131.1, 129.3, 128.7, 128.5, 128.3, 128.2, 127.8, 127.3, 126.6,125.8, 116.0, 56.9, 52.0, 36.0, 31.3.ESI-MS: calculated [C 27 H 26 O2 + Na] + :405.1825, found: 405.1820. [α] 20 D = +80.4 (c = 0.75, CH2Cl2). The product wasanalyzed by HPLC to determine the enantiomeric excess: 93% ee(CHIRALPAK IBN-5, n -hexane / i -PrOH = 90 / 10, detector: 254 nm, T = 25 ℃, flow rate: 1 mL / min), t1(minor) = 4.3 min, t2(major) = 4.9 min.

[0044] Example 9: Preparation of Chiral Diene Substituted Carboxylate Compound 4i

[0045] Take a 10mL reaction tube equipped with a stirring magnet and dry, equip it with a carbon electrode as the anode and a platinum electrode as the cathode. Under a nitrogen atmosphere, weigh and add the corresponding compounds 1a (0.1mmol), 2b (0.3mmol), methanol 3a (0.5mmol), chiral isothiourea catalyst (0.01mmol), tetrabutylammonium hexafluorophosphate ( n Bu4NPF6, 0.3 mmol), then a mixed solution of THF / MeCN = 2:1 (3 mL) was added to dissolve it. Then, electrolysis was performed at 25°C with a constant current (1 mA) for 12 hours. After the reaction was complete, the solvent was directly removed by reduced pressure distillation, and finally, petroleum ether / ethyl acetate was mixed in a volume ratio of 50:1 as the eluent, and the dienylation product 4i (68% yield, 92% ee) was separated by column chromatography.

[0046] 1 H NMR (400 MHz, CDCl3) δ 7.38 – 7.28 (m, 5H), 7.25 – 7.20 (m, 2H), 7.03 – 6.93 (m, 2H), 5.65 (dd, J = 6.9, 1.4 Hz, 1H), 5.55 (d, J = 1.5 Hz,1H), 4.91 (d, J = 1.5 Hz, 1H), 4.31 (s, 1H), 3.64 (s, 3H), 1.68 (dd, J = 6.8,1.3 Hz, 3H). 13 C NMR (100 MHz, CDCl3) δ 172.66, 162.16 (d, J = 245.6 Hz),145.81, 139.23, 138.88, 130.93, 130.85, 128.56, 127.90, 126.57, 126.10,116.34, 115.29, 115.08, 56.37, 52.10, 14.99. 19 F NMR (376 MHz, CDCl3) δ -115.43.ESI-MS: calculated [C 20 H 19 FO2 + Na] + : 333.1261, found: 333.1267.[α] 20 D=+44.9 (c = 0.98, CH2Cl2).The product was analyzed by HPLC to determine theenantiomeric excess: 92% ee (CHIRALCEL AD-H, n -hexane / i -PrOH = 99 / 1, detector: 254 nm, T = 25 ℃, flow rate: 1 mL / min), t1(minor) = 12.6 min, t2(major) = 14.6 min.

[0047] Example 10: Preparation of Chiral Diene Substituted Carboxylate Compound 4j

[0048] Take a 10mL reaction tube equipped with a stirring magnet and dried, equip it with a carbon electrode as the anode and a platinum electrode as the cathode. Under a nitrogen atmosphere, weigh and add the corresponding compounds 1a (0.1mmol), 2c (0.3mmol), methanol 3a (0.5mmol), chiral isothiourea catalyst (0.01mmol), tetrabutylammonium hexafluorophosphate ( n Bu4NPF6, 0.3 mmol), then a mixed solution of THF / MeCN=2:1 (3 mL) was added to dissolve it. Then, electrolysis was performed at 25°C with a constant current (1 mA) for 12 hours. After the reaction was complete, the solvent was directly removed by reduced pressure distillation, and finally, petroleum ether / ethyl acetate mixed in a volume ratio of 50:1 was used as the eluent, and the dienylation product 4j (58% yield, 90% ee) was separated by column chromatography.

[0049] 1 H NMR (400 MHz, CDCl3) δ 7.45 – 7.38 (m, 2H), 7.37 – 7.28 (m, 5H), 7.18 – 7.11 (m, 2H), 5.66 (dd, J = 6.8, 1.4 Hz, 1H), 5.55 (d, J = 1.5 Hz,1H), 4.91 (d, J = 1.5 Hz, 1H), 4.29 (d, J = 1.4 Hz, 1H), 3.63 (s, 3H), 1.68(dd, J = 6.8, 1.4 Hz, 3H).13 C NMR (100 MHz, CDCl3) δ 172.3, 145.7, 138.9,138.8, 136.0, 131.5, 131.1, 128.6, 127.9, 126.6, 126.4, 121.4, 116.5, 56.5,52.2, 15.0.ESI-MS: calculated [C 20 H 19 BrO2 + Na] + : 393.0461, found: 393.0465.[α] 20 D = +70.6 (c = 0.75, CH2Cl2). The product was analyzed by HPLC to determine the enantiomeric excess: 90% ee (CHIRALPAK IA, n -hexane / i -PrOH =99 / 1, detector: 254 nm, T = 25 ℃, flow rate: 1 mL / min), t1(major) = 9.8 min, t2(minor) = 11.1 min.

[0050] Example 11: Preparation of Chiral Diene Substituted Carboxylate Compound 4k

[0051] Take a 10 mL reaction tube equipped with a stirring magnet and dry, equip it with a carbon electrode as the anode and a platinum electrode as the cathode. Under a nitrogen atmosphere, weigh and add the corresponding compounds 1a (0.1 mmol), 2d (0.3 mmol), methanol 3a (0.5 mmol), chiral isothiourea catalyst (0.01 mmol), tetrabutylammonium hexafluorophosphate ( n Bu4NPF6, 0.3 mmol), then a mixed solution of THF / MeCN=2:1 (3 mL) was added to dissolve it. Then, electrolysis was performed at 25°C with a constant current (1 mA) for 12 hours. After the reaction was complete, the solvent was directly removed by reduced pressure distillation, and finally, petroleum ether / ethyl acetate was mixed in a volume ratio of 50:1 as an eluent, and the dienylation product 4k (66% yield, 94% ee) was separated by column chromatography.

[0052] 1H NMR (400 MHz, CDCl3) δ 7.40 – 7.28 (m, 5H), 7.19 – 7.08 (m, 4H), 5.62 (dd, J = 6.8, 1.4 Hz, 1H), 5.56 (d, J = 1.5 Hz, 1H), 4.97 (d, J = 1.5Hz, 1H), 4.31 (s, 1H), 3.61 (s, 3H), 2.33 (s, 3H), 1.65 (dd, J = 6.8, 1.3 Hz,3H). 13 C NMR (100 MHz, CDCl3) δ 172.9, 146.0, 139.2, 139.0, 136.9, 133.8,129.1, 128.5, 127.7, 126.5, 126.1, 116.1, 56.7, 51.9, 21.1, 14.9.ESI-MS:calculated [C 21 H 22 O2 + Na] + : 329.1512, found: 329.1516. [α] 20 D = +77.1 (c =0.80, CH2Cl2).The product was analyzed by HPLC to determine the enantiomericexcess: 94% ee (CHIRALPAK IA, n -hexane / i -PrOH = 90 / 10, detector: 254 nm, T =25 ℃, flow rate: 1 mL / min), t1(minor) = 7.2 min, t2(major) = 7.7 min.

[0053] Example 12: Preparation of Chiral Diene Substituted Carboxylate Compound 41

[0054] Take a 10 mL reaction tube equipped with a stirring magnet and dry, equip it with a carbon electrode as the anode and a platinum electrode as the cathode. Under a nitrogen atmosphere, weigh and add the corresponding compounds 1a (0.1 mmol), 2e (0.3 mmol), methanol 3a (0.5 mmol), chiral isothiourea catalyst (0.01 mmol), tetrabutylammonium hexafluorophosphate ( n Bu4NPF6, 0.3 mmol), then a mixed solution of THF / MeCN = 2:1 (3 mL) was added to dissolve it. Then, electrolysis was performed at 25°C with a constant current (1 mA) for 12 hours. After the reaction was complete, the solvent was directly removed by reduced pressure distillation, and finally, petroleum ether / ethyl acetate was mixed in a volume ratio of 50:1 as the eluent, and the dienylation product 4l (64% yield, 96% ee) was separated by column chromatography.

[0055] 1 H NMR (400 MHz, CDCl3) δ 7.41 – 7.29 (m, 7H), 7.22 – 7.18 (m, 2H), 5.63 (dd, J = 6.8, 1.3 Hz, 1H), 5.58 (d, J = 1.6 Hz, 1H), 4.99 (d, J = 1.5Hz, 1H), 4.32 (d, J = 1.4 Hz, 1H), 3.61 (s, 3H), 1.65 (dd, J = 6.8, 1.3 Hz, 3H), 1.31 (s, 9H). 13 C NMR (100 MHz, CDCl3) δ 171.4, 148.6, 144.7, 137.7,132.3, 127.4, 127.0, 126.3, 125.1, 124.8, 123.8, 114.5, 55.3, 50.4, 29.9,13.5.ESI-MS: calculated [C 24 H 28 O2 + Na] + : 371.1982, found: 371.1980. [α] 20 D= +47.5 (c = 0.67, CH2Cl2). The product was analyzed by HPLC to determine theenantiomeric excess: 96% ee(CHIRALCEL AD-H, n -hexane / i -PrOH = 90 / 10, detector: 254 nm, T = 25 ℃, flow rate: 1 mL / min), t1(minor) =6.5 min, t2(major) = 7.0 min.

[0056] Example 13: Preparation of Chiral Diene Substituted Carboxylate Compound 4m

[0057] Take a 10 mL reaction tube equipped with a stirring magnet and dry, equip it with a carbon electrode as the anode and a platinum electrode as the cathode. Under a nitrogen atmosphere, weigh and add the corresponding compounds 1a (0.1 mmol), 2f (0.3 mmol), methanol 3a (0.5 mmol), chiral isothiourea catalyst (0.01 mmol), tetrabutylammonium hexafluorophosphate ( n Bu4NPF6, 0.3 mmol), then a mixed solution of THF / MeCN=2:1 (3 mL) was added to dissolve it. Then, electrolysis was performed at 25°C with a constant current (1 mA) for 12 hours. After the reaction was complete, the solvent was directly removed by vacuum distillation, and finally, petroleum ether / ethyl acetate was mixed in a volume ratio of 50:1 as the eluent, and the dienylation product 4m (59% yield, 91% ee) was separated by column chromatography.

[0058] 1 H NMR (400 MHz, CDCl3)δ 7.64 – 7.51 (m, 4H), 7.48 – 7.28 (m, 10H), 5.71 (dd, J = 6.8, 1.3 Hz, 1H), 5.59 (d, J = 1.5 Hz, 1H), 5.00 (d, J = 1.5Hz, 1H), 4.40 (d, 1H), 3.65 (s, 3H), 1.69 (dd, J = 6.8, 1.3 Hz, 3H). 13C NMR(100 MHz, CDCl3) δ 171.2, 144.5, 139.3, 138.7, 137.6, 137.5, 134.5, 128.2,127.3, 127.0, 126.3, 125.8, 125.6, 125.6, 125.1, 124.9, 114.7, 55.4, 50.6,13.5.ESI-MS: calculated [C 26 H 24 O2 + Na] + : 391.1669, found: 391.1666. [α] 20 D = +89.6 (c = 0.55, CH2Cl2).The product was analyzed by HPLC to determine theenantiomeric excess: 91% ee(CHIRALCEL AD-H, n -hexane / i -PrOH = 90 / 10, detector: 254 nm, T = 25 ℃, flow rate: 1 mL / min), t1(minor) = 8.8 min, t2(major) = 9.8 min.

[0059] Example 14: Preparation of Chiral Diene Substituted Carboxylate Compound 4n

[0060] Take a 10 mL reaction tube equipped with a stirring magnet and dry, equip it with a carbon electrode as the anode and a platinum electrode as the cathode. Under a nitrogen atmosphere, weigh and add the corresponding compound 1a (0.1 mmol), 2g (0.3 mmol), methanol 3a (0.5 mmol), chiral isothiourea catalyst (0.01 mmol), tetrabutylammonium hexafluorophosphate ( n Bu4NPF6, 0.3 mmol), then a mixed solution of THF / MeCN = 2:1 (3 mL) was added to dissolve it. Then, electrolysis was performed at 25°C with a constant current (1 mA) for 12 hours. After the reaction was complete, the solvent was directly removed by reduced pressure distillation, and finally, petroleum ether / ethyl acetate was mixed in a volume ratio of 50:1 as an eluent, and the dienylation product 4n (71% yield, 91% ee) was separated by column chromatography.

[0061] 1H NMR (400 MHz, CDCl3) δ 7.43 – 7.27 (m, 5H), 7.24 – 7.17 (m, 1H), 7.13 – 7.03 (m, 3H), 5.62 (dd, J = 6.8, 1.4 Hz, 1H), 5.57 (d, J = 1.6 Hz,1H), 4.99 (d, J = 1.5 Hz, 1H), 4.32 (d, J = 1.5 Hz, 1H), 3.62 (s, 3H), 2.33(s, 3H), 1.66 (dd, J = 6.8, 1.4 Hz, 3H). 13 C NMR (100 MHz, CDCl3) δ 172.8,146.1, 139.1, 139.0, 137.9, 136.7, 129.9, 128.5, 128.2, 128.1, 127.8, 126.5,126.3, 126.3, 116.1, 57.1, 52.0, 21.5, 14.9.ESI-MS: calculated [C 21 H 22 O2 + Na] + :329.1512, found: 329.1510. [α] 20 D = +73.9 (c = 0.64, CH2Cl2).The product wasanalyzed by HPLC to determine the enantiomeric excess: 91% ee (CHIRALPAK IB, n -hexane / i -PrOH = 99 / 1, detector: 254 nm, T = 25 ℃, flow rate: 1 mL / min), t1(minor) = 7.1 min, t2(major) = 8.8 min.

[0062] Example 15: Preparation of Chiral Diene Substituted Carboxylate Compound 4o

[0063] Take a 10 mL reaction tube equipped with a stirring magnet and dry, equip it with a carbon electrode as the anode and a platinum electrode as the cathode. Under a nitrogen atmosphere, weigh and add the corresponding compound 1a (0.1 mmol), 2h (0.3 mmol), methanol 3a (0.5 mmol), chiral isothiourea catalyst (0.01 mmol), tetrabutylammonium hexafluorophosphate ( n Bu4NPF6, 0.3 mmol), then a mixed solution of THF / MeCN = 2:1 (3 mL) was added to dissolve it. Then, electrolysis was performed at 25°C with a constant current (1 mA) for 12 hours. After the reaction was complete, the solvent was directly removed by vacuum distillation, and finally, petroleum ether / ethyl acetate was mixed in a volume ratio of 50:1 as the eluent, and the dienylation product 4o (54% yield, 92% ee) was separated by column chromatography.

[0064] 1 H NMR (400 MHz, CDCl3) δ 7.85 – 7.76 (m, 3H), 7.68 (s, 1H), 7.52 –7.28 (m, 8H), 5.68 (dd, J = 6.8, 1.4 Hz, 1H), 5.55 (d, J = 1.5 Hz, 1H), 4.98(d, J = 1.6 Hz, 1H), 4.52 (s, 1H), 3.65 (s, 3H), 1.68 (dd, J = 6.8, 1.3 Hz,3H). 13 C NMR (100 MHz, CDCl3) δ 172.8, 146.0, 139.1, 139.1, 134.4, 133.4,132.7, 128.6, 128.1, 128.0, 127.9, 127.7, 127.4, 126.7, 126.7, 126.1, 126.0,116.3, 57.3, 52.1, 15.0.ESI-MS: calculated [C 24 H 22 O2 + Na] + : 365.1512, found:365.1514. [α] 20 D= +73.4 (c = 0.69, CH2Cl2).The product was analyzed by HPLC todetermine the enantiomeric excess: 92% ee (CHIRALPAK IA, n -hexane / i -PrOH =99 / 1, detector: 254 nm, T = 25 ℃, flow rate: 1 mL / min), t1(minor) = 12.9min, t2(major) = 15.1 min。

Claims

1. A chiral diene-substituted carboxylic acid ester compound, characterized in that An optically active compound having a structure shown in the following formula I, including stereoisomers having the same chemical formula: ； Wherein: * represents a chiral carbon atom; the substituent R is selected from hydrogen, C 1-10 Alkyl or aryl; Ar is an aromatic ring or a substituted aromatic ring; R 1 , R 2 , R 3 , R 4 , R 5 , R 6 are independently selected from hydrogen, halogen, C 1-10 A hydrocarbon group or a hydrocarbonoxy group; R 7 Independently selected from C 1-10 Alkyl or aryl.

2. The asymmetric preparation method of the chiral diene-substituted carboxylic acid ester compound according to claim 1, characterized in that: Using substituted allylsilane 1 and carboxylate derivative 2 as starting materials, alcohol 3 as quenching reagent, and chiral isothiourea as reaction catalyst, an asymmetric olefination reaction is carried out under electrochemical reaction conditions, and the target product I is obtained after separation and purification; The synthetic route is as follows: ； In the above formula: * represents a chiral carbon atom; the substituent R is selected from hydrogen, C 1-10 Alkyl or aryl; Ar is an aromatic ring or a substituted aromatic ring; R 1 , R 2 , R 3 , R 4 , R 5 are independently selected from hydrogen, halogen, C 1-10 A hydrocarbon group or a hydrocarbonoxy group; R 6 Independently selected from C 1-10 Alkyl or aryl; R 7 Independently selected from C 1-10 Alkyl or aryl; R 8 Independently selected from C 1-10 Alkyl or aryl.

3. The asymmetric preparation method according to claim 2, characterized in that The steps include: Under a nitrogen atmosphere, in a reaction bottle equipped with electrodes, substituted allylsilane 1, carboxylate derivative 2, alcohol 3, chiral isothiourea catalyst and electrolyte are added, and an organic solvent is added for dissolution, and current electrolysis is applied at -20°C to 70°C for 2-48 hours, and the reaction endpoint is determined by thin layer chromatography spot plate; after the reaction is complete, the solvent is directly removed by reduced pressure distillation, and finally the residue is separated by column chromatography to obtain the target product I.

4. The asymmetric preparation method according to claim 2 or 3, characterized in that: The chiral isothiourea catalyst is selected from the following structures: ； Where: * is a carbon chiral center; n is 0 or 1; R 9 , R 10 , R 11 and R 12 are independently selected from hydrogen, halogen, substituted or unsubstituted groups: C 1-10 Alkyl, C 3-10 Cycloalkyl, 2-furyl or C 6-20 The aryl group; R 13 Independently selected from C 1-10 Alkyl or aryl.

5. The asymmetric preparation method according to claim 2 or 3, characterized in that: The electrolyte is tetrabutylammonium hexafluorophosphate, tetraethylammonium hexafluorophosphate, tetrabutylammonium tetrafluoroborate, tetraethylammonium tetrafluoroborate, tetrabutylammonium perchlorate or tetrabutylammonium bromide.

6. The asymmetric preparation method according to claim 2 or 3, characterized in that: The molar ratio of the chiral isothiourea catalyst to the substituted allylsilane 1 is 0.025:1-1:1; the molar equivalent ratio of the substituted allylsilane 1 to the carboxylate derivative 2 is 1:1-1:5; the molar equivalent ratio of the substituted allylsilane 1 to the alcohol 3 is 1:1-1:100; and the molar ratio of the substituted allylsilane 1 to the electrolyte is 1:0.1-1:

5.

7. The asymmetric preparation method according to claim 3, characterized in that: The organic solvent is 1,4-dioxane, dichloromethane, dichloroethane, dimethyl sulfoxide, N -Methylpyrrolidone, N , N -dimethylformamide, N , N - dimethylacetamide, ethyl acetate, chloroform, tetrahydrofuran, acetonitrile, toluene, ethylbenzene, fluorobenzene, chlorobenzene, bromobenzene, xylene or trimethylbenzene.

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