Chiral dicarbonyl compound and asymmetric preparation method thereof

Abstract

The invention discloses a chiral dicarbonyl compound and an asymmetric preparation method thereof, and the chiral dicarbonyl 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; n is 0, 1 or 2; 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 micromolecular chiral isothiourea catalyst is applied to catalyze electrochemical asymmetric alkylation reaction as a key step, and the chiral dicarbonyl 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 dicarbonyl compound and an asymmetric preparation method thereof. Background Art

[0002] Carboxylate structures are widely present in biology, chemistry and materials science. In the field of organic synthesis, it is particularly important to modify the asymmetric α position of simple ester compounds. At the same time, compounds containing chiral dicarbonyl structures are important components of many biologically active natural products and drug molecule intermediates. Therefore, the asymmetric synthesis of such compounds has always been a research focus. Although a variety of asymmetric catalytic methods have been successfully developed, the efficient synthesis of chiral dicarbonyl compounds using simple carboxylic acid derivatives through asymmetric catalysis is still a challenging topic. Therefore, the development of an efficient catalytic system to achieve high enantioselective synthesis of chiral dicarbonyl compounds has important research value in organic synthetic chemistry.

[0003] With the rapid development of science and technology and the continuous and in-depth research of scientific researchers, the field of electrochemical synthesis has flourished and gradually become the forefront of modern organic chemical synthesis. Compared with traditional organic chemical synthesis, electrochemical synthesis has many advantages: 1. Mild reaction conditions and energy saving. 2. Avoid the use of a large number of toxic and dangerous oxidants and reductants, reduce environmental pollution, and comply with the strategy of green development. 3. During the reaction, the reaction rate and reaction process can be changed by controlling and adjusting the current and voltage. 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 new electrocatalytic asymmetric synthesis strategies to promote the generation of key active free radical intermediates and achieve stereoselective control has extremely high synthetic difficulty and far-reaching research value.

[0004] Chiral dicarbonyl compounds are a class of key intermediates that can be used to construct bioactive molecules. They have biopharmaceutical synthesis value and can be used to produce chiral natural products such as calyxolane A and ent -calyxolane B. However, the direct synthesis of chiral dicarbonyl compounds by one-step reaction is still an unsolved scientific problem. Therefore, it is urgent to develop a new catalytic system to directly synthesize chiral dicarbonyl compounds, starting from simple and readily available carboxylic acid derivatives, to achieve a general strategy for the synthesis of structurally diverse chiral dicarbonyl compounds in high yield and high enantioselectivity in an accurate and rapid manner, and to apply it to the chiral natural products calyxolane A and ent The precise synthesis of -calyxolane B demonstrates the practicality of this preparation method and provides a new synthetic platform for the exploration and development of bioactive molecules. Summary of the invention

[0005] The purpose of the present invention is to provide a chiral dicarbonyl compound and an asymmetric preparation method thereof, thereby solving the above-mentioned problems existing in the prior art.

[0006] The chiral dicarbonyl compound of the present invention is an optically active compound having a structure shown in the following formula I, including stereoisomers having the same chemical formula:

[0007] In the formula: * represents a chiral carbon atom; n is 0, 1 or 2; 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 are independently selected from hydrogen, C 1-10 Alkyl or aryl; R 7 Independently selected from C 1-10 Alkyl or aryl.

[0008] The asymmetric preparation method of chiral dicarbonyl compounds of the present invention uses carboxylate derivatives 1 and enol silyl ether compounds 2 as starting materials, alcohol 3 as a quenching reagent, chiral isothiourea as a reaction catalyst, undergoes an asymmetric alkylation reaction under electrochemical reaction conditions, and obtains the target product I after separation and purification.

[0009] The synthetic route is as follows:

[0010] In the above formula: * represents a chiral carbon atom; n is 0, 1 or 2; 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.

[0011] The specific steps include: Under a nitrogen atmosphere, in a reaction bottle equipped with electrodes, a carboxylate derivative 1, an enol silyl ether compound 2, an alcohol 3, a chiral isothiourea catalyst and an electrolyte are added, and an organic solvent is added for dissolution, and current electrolysis is applied at -40°C to 80°C for 2-60 hours, and the reaction endpoint is determined by a thin layer chromatography 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.

[0012] During the preparation process of the present invention: The chiral isothiourea catalyst is a commercially available catalyst selected from the following structures:

[0013] 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.

[0014] The electrolyte is one of tetrabutylammonium hexafluorophosphate, tetraethylammonium hexafluorophosphate, tetramethylammonium hexafluorophosphate, tetrabutylammonium tetrafluoroborate, tetrabutylammonium perchlorate, tetraethylammonium perchlorate, tetraethylammonium tetrafluoroborate, tetrabutylammonium chloride and tetrabutylammonium bromide.

[0015] The organic solvent is 1,4-dioxane, dichloromethane, dichloroethane, dimethyl sulfoxide, N -Methylpyrrolidone, N , N -dimethylformamide, N , N - dimethylacetamide, ethyl acetate, chloroform, methanol, tetrahydrofuran, acetonitrile, toluene, ethylbenzene, fluorobenzene, chlorobenzene, bromobenzene, xylene or trimethylbenzene.

[0016] 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.

[0017] Wherein: the molar ratio of the chiral isothiourea catalyst to the enol silyl ether compound 2 is 0.03:1-1:1; the molar equivalent ratio of the enol silyl ether compound 2 to the carboxylate derivative 1 is 1:0.5-1:5; the molar equivalent ratio of the enol silyl ether compound 2 to the alcohol 3 is 1:1-1:100; the molar ratio of the enol silyl ether compound 2 to the electrolyte is 1:0.1-1:5.

[0018] The present invention provides a method for synthesizing chiral dicarbonyl compounds through the key step of electrochemical catalytic asymmetric reaction. The present invention uses carboxylic acid ester derivatives 1 and enol silyl ether compounds 2 as starting materials, alcohol 3 as quenching reagent, and chiral isothiourea as reaction catalyst. Under electrochemical reaction conditions, an asymmetric alkylation reaction is performed, and the target product I is obtained after separation and purification. The present invention successfully develops a method for synthesizing chiral dicarbonyl compounds, which is easy to prepare chiral dicarbonyl compounds with high yield and high optical purity. In addition, starting from this type of compound, through multi-step transformation, the natural product calyxolane A and ent The asymmetric total synthesis of -calyxolane B demonstrates the practicality of this preparation method and provides a new synthetic platform for the exploration and development of bioactive molecules. DETAILED DESCRIPTION

[0019] 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.

[0020] 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.

[0021] Example 1: Preparation of chiral dicarbonyl compound 4a

[0022] 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 an argon atmosphere, weigh and add the corresponding compounds 1a (0.3 mmol), 2a (0.1 mmol), methanol 3a (0.5 mmol), chiral isothiourea catalyst (0.01 mmol), tetrabutylammonium hexafluorophosphate ( n Bu 4 NPF 6, 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 (1.0 mA) for 8 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 corresponding chiral dicarbonyl compound 4a (57% yield, 95% ee) was separated by column chromatography.

[0023] 1 H NMR (500 MHz, CDCl 3 ) δ 8.00-7.94 (m, 2H), 7.70-7.52 (m, 1H), 7.48-7.41 (m, 2H), 7.31-7.21 (m, 2H), 7.19-7.10 (m, 2H), 4.26 (dd, J = 10.3, 4.1Hz, 1H), 3.93 (dd, J = 18.0, 10.3 Hz, 1H), 3.69 (s, 3H), 3.25 (dd, J = 18.0,4.1 Hz, 1H), 2.33 (s, 3H). 13 C NMR (100 MHz, CDCl 3 ) δ 197.9, 174.2, 137.4,136.6, 135.5, 133.4, 129.7, 128.7, 128.2, 127.8, 52.5, 46.1, 43.0, 21.2. ESI-MS: calculated [C 18 H 18 O 3 + Na] + : 305.1148, found: 305.1145. [α] 20 D = +97.5 (c =0.53, CH 2 Cl 2 ). The product was analyzed by HPLC to determine the enantiomericexcess: 95% ee (CHIRALPAK IC, n -hexane / i -PrOH = 70 / 30, detector: 254 nm, T =25 ℃, flow rate: 1 mL / min), t1 (minor) = 7.4 min, t 2 (major) = 8.2 min.

[0024] Example 2: Preparation of Chiral Dicarbonyl Compound 4b

[0025] 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 an argon atmosphere, weigh and add the corresponding compounds 1b (0.3 mmol), 2a (0.1 mmol), methanol 3a (0.5 mmol), chiral isothiourea catalyst (0.01 mmol), tetrabutylammonium hexafluorophosphate ( n Bu 4 NPF 6 , 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 (1.0 mA) for 8 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 corresponding chiral dicarbonyl compound 4b (67% yield, 97% ee) was separated by column chromatography.

[0026] 1 H NMR (500 MHz, CDCl 3 ) δ 7.98-7.95 (m, 2H), 7.58-7.53 (m, 1H), 7.45(m, 2H), 7.30-7.23 (m, 2H), 7.22-7.18 (m, 2H), 4.27 (dd, J = 10.4, 4.0 Hz,1H), 3.94 (dd, J = 18.0, 10.4 Hz, 1H), 3.69 (s, 3H), 3.25 (dd, J = 18.0, 4.0Hz, 1H), 2.89 (d, J = 6.9 Hz, 1H), 1.24 (d, J = 6.9 Hz, 6H). 13 C NMR (100 MHz, CDCl 3) δ 197.9, 174.2, 148.3, 136.5, 135.7, 133.4, 128.7, 128.2, 127.8,127.1, 52.4, 46.0, 43.1, 33.9, 24.1. ESI-MS: calculated [C 20 H 22 O 3 + Na] + :333.1461, found: 333.1455. [α] 20 D = +67.4 (c = 0.66, CH 2 Cl 2 ). The product wasanalyzed by HPLC to determine the enantiomeric excess: 97% ee (CHIRALPAK IC, n -hexane / i -PrOH = 70 / 30, detector: 254 nm, T = 25 ℃, flow rate: 1 mL / min),t 1 (minor) = 6.5 min, t 2 (major) = 7.3 min.

[0027] Example 3: Preparation of chiral dicarbonyl compound 4c

[0028] 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 an argon atmosphere, weigh and add the corresponding compounds 1c (0.3 mmol), 2a (0.1 mmol), methanol 3a (0.5 mmol), chiral isothiourea catalyst (0.01 mmol), tetrabutylammonium hexafluorophosphate ( n Bu 4 NPF 6 , 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 (1.0 mA) for 8 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 corresponding chiral dicarbonyl compound 4c (80% yield, 96% ee) was separated by column chromatography.

[0029] 1 H NMR (500 MHz, CDCl 3 ) δ 8.00-7.94 (m, 2H), 7.62-7.53 (m, 1H), 7.49-7.42 (m, 2H), 7.39-7.29 (m, 2H), 7.10-6.98 (m, 2H), 4.29 (dd, J = 10.0, 4.4Hz, 1H), 3.91 (dd, J = 18.0, 9.9 Hz, 1H), 3.70 (s, 3H), 3.27 (dd, J = 18.0,4.4 Hz, 1H). 13 C NMR (100 MHz, CDCl 3 ) δ 197.55, 173.89, 162.32 (d, J = 246.4Hz), 136.43, 134.18 (d, J = 3.1 Hz), 133.55, 129.58 (d, J = 8.1 Hz), 128.78,128.21, 115.92 (d, J = 21.3 Hz), 52.55, 45.70, 42.86. 19 F NMR (471 MHz, CDCl 3 )δ -114.9. ESI-MS: calculated [C 17 H 15 FO 3 + Na] + : 309.0897, found: 309.0899. [α] 20 D = +76.6 (c = 0.68, CH 2 Cl 2 ). The product was analyzed by HPLC to determinethe enantiomeric excess: 96% ee (CHIRALPAK IC, n -hexane / i -PrOH = 70 / 30,detector: 254 nm, T = 25 ℃, flow rate: 1 mL / min), t 1(minor) = 5.4 min, t 2 (major) = 6.5 min.

[0030] Example 4: Preparation of Chiral Dicarbonyl Compound 4d

[0031] 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 an argon atmosphere, weigh and add the corresponding compounds 1d (0.3 mmol), 2a (0.1 mmol), methanol 3a (0.5 mmol), chiral isothiourea catalyst (0.01 mmol), tetrabutylammonium hexafluorophosphate ( n Bu 4 NPF 6 , 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 (1.0 mA) for 8 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 corresponding chiral dicarbonyl compound 4d (71% yield, 94% ee) was separated by column chromatography.

[0032] 1 H NMR (500 MHz, CDCl 3 ) δ 8.01-7.92 (m, 2H), 7.62-7.54 (m, 1H), 7.51-7.42 (m, 2H), 7.36-7.26 (m, 4H), 4.28 (dd, J = 9.9, 4.4 Hz, 1H), 3.91 (dd, J = 18.0, 9.9 Hz, 1H), 3.70 (s, 3H), 3.27 (dd, J = 18.0, 4.5 Hz, 1H). 13 C NMR (125 MHz, CDCl 3 ) δ 197.4, 173.6, 136.9, 136.4, 133.6, 133.6, 129.4, 129.2,128.8, 128.2, 52.6, 45.8, 42.7, 29.8. ESI-MS: calculated [C 17 H 15 C1O 3 + Na] +:325.0602, found: 325.0594. [α] 20 D = +29.9 (c = 0.70, CH 2 Cl 2 ). The product wasanalyzed by HPLC to determine the enantiomeric excess: 94% ee (CHIRALPAK IC, n -hexane / i -PrOH = 90 / 10, detector: 240 nm, T = 25 ℃, flow rate: 1 mL / min),t 1 (minor) = 9.8 min, t 2 (major) = 10.6 min .

[0033] Example 5: Preparation of Chiral Dicarbonyl Compound 4e

[0034] 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 an argon atmosphere, weigh and add the corresponding compounds 1e (0.3 mmol), 2a (0.1 mmol), methanol 3a (0.5 mmol), chiral isothiourea catalyst (0.01 mmol), tetrabutylammonium hexafluorophosphate ( n Bu 4 NPF 6 , 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 (1.0 mA) for 8 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 corresponding chiral dicarbonyl compound 4e (71% yield, 95% ee) was separated by column chromatography.

[0035] 1 H NMR (400 MHz, CDCl 3 ) δ 8.00-7.90 (m, 2H), 7.64-7.53 (m, 1H), 7.52-7.39 (m, 4H), 7.30-7.19 (m, 2H), 4.27 (dd, J= 9.9, 4.5 Hz, 1H), 3.90 (dd, J = 18.0, 9.9 Hz, 1H), 3.69 (s, 3H), 3.27 (dd, J = 18.0, 4.5 Hz, 1H). 13 C NMR (100 MHz, CDCl 3 ) δ 197.4, 173.6, 137.5, 136.4, 133.6, 132.1, 129.7, 128.8,128.2, 121.7, 52.6, 45.9, 42.6. ESI-MS: calculated [C 17 H 15 B O 3 + Na] + :369.0097, found: 369.0100. [α] 20 D = +76.2 (c = 0.78, CH 2 Cl 2 ). The product wasanalyzed by HPLC to determine the enantiomeric excess: 95% ee (CHIRALPAK IC, n -hexane / i -PrOH = 90 / 10, detector: 254 nm, T = 25 ℃, flow rate: 1 mL / min),t 1 (minor) = 10.5 min, t 2 (major) = 11.3 min.

[0036] Example 6: Preparation of Chiral Dicarbonyl Compound 4f

[0037] 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 an argon atmosphere, weigh and add the corresponding compound 1f (0.3 mmol), 2a (0.1 mmol), methanol 3a (0.5 mmol), chiral isothiourea catalyst (0.01 mmol), tetrabutylammonium hexafluorophosphate ( n Bu 4 NPF 6, 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 (1.0 mA) for 8 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 corresponding chiral dicarbonyl compound 4f (75% yield, 97% ee) was separated by column chromatography.

[0038] 1 H NMR (500 MHz, CDCl 3 ) δ 8.02-7.94 (m, 2H), 7.60-7.53 (m, 1H), 7.49-7.42 (m, 2H), 7.28-7.21 (m, 1H), 7.18-7.13 (m, 2H), 7.13-7.07 (m, 1H), 4.27(dd, J = 10.4, 3.9 Hz, 1H), 3.95 (dd, J = 18.0, 10.4 Hz, 1H), 3.70 (s, 3H), 3.25 (dd, J = 18.0, 4.0 Hz, 1H), 2.36 (s, 3H). 13 C NMR (100 MHz, CDCl 3 ) δ197.8, 174.1, 138.8, 138.4, 136.5, 133.4, 129.0, 128.7, 128.6, 128.5, 128.2,125.0, 52.5, 46.4, 43.0, 21.6. ESI-MS: calculated [C 18 H 18 O 3 + Na] + : 305.1148, found: 305.1148. [α] 20 D = +74.3 (c = 0.68, CH 2 Cl 2 ). The product was analyzed byHPLC to determine the enantiomeric excess: 97% ee (CHIRALPAK IC, n -hexane / i-PrOH = 70 / 30, detector: 254 nm, T = 25 ℃, flow rate: 1 mL / min), t 1 (major) =7.7 min, t 2 (minor) = 8.4 min.

[0039] Example 7: Preparation of 4g of chiral dicarbonyl compounds

[0040] 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 an argon atmosphere, weigh and add the corresponding compound 1g (0.3 mmol), 2a (0.1 mmol), methanol 3a (0.5 mmol), chiral isothiourea catalyst (0.01 mmol), tetrabutylammonium hexafluorophosphate ( n Bu 4 NPF 6 , 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 (1.0 mA) for 8 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 corresponding chiral dicarbonyl compound 4g (56% yield, 96% ee) was separated by column chromatography.

[0041] 1 H NMR (500 MHz, CDCl 3 ) δ 8.02-7.93 (m, 2H), 7.60-7.51 (m, 1H), 7.50-7.41 (m, 2H), 7.31-7.22 (m, 1H), 6.96-6.86 (m, 2H), 6.86-6.80 (m, 1H), 4.27(dd, J = 10.4, 3.9 Hz, 1H), 3.94 (dd, J = 18.0, 10.4 Hz, 1H), 3.81 (s, 3H), 3.70 (s, 3H), 3.26 (dd, J = 18.0, 4.0 Hz, 1H). 13 C NMR (125 MHz, CDCl 3) δ197.7, 173.8, 160.1, 140.0, 136.5, 133.5, 130.1, 128.7, 128.2, 120.2, 113.7,113.0, 55.4, 52.5, 46.5, 42.9 ESI-MS: calculated [C 18 H 18 O 4 + Na] + : 321.1097, found: 321.1102. [α] 20 D = +80.9 (c = 0.56, CH 2 Cl 2 ). The product was analyzed byHPLC to determine the enantiomeric excess: 96% ee (CHIRALPAK IE, n -hexane / i -PrOH = 80 / 20, detector: 254 nm, T = 25 ℃, flow rate: 1 mL / min), t 1 (major) =12.2 min, t 2 (minor) = 13.0 min.

[0042] Example 8: Preparation of Chiral Dicarbonyl Compound 4h

[0043] 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 an argon atmosphere, weigh and add the corresponding compound 1h (0.3 mmol), 2a (0.1 mmol), methanol 3a (0.5 mmol), chiral isothiourea catalyst (0.01 mmol), tetrabutylammonium hexafluorophosphate ( n Bu 4 NPF 6 , 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 (1.0 mA) for 8 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 corresponding chiral dicarbonyl compound 4h (67% yield, 90% ee) was separated by column chromatography.

[0044] 1 H NMR (500 MHz, CDCl 3 ) δ 8.02-7.93 (m, 2H), 7.61-7.54 (m, 1H), 7.51-7.41 (m, 2H), 7.35-7.27 (m, 1H), 7.17-7.11 (m, 1H), 7.10-7.05 (m, 1H), 7.02-6.95 (m, 1H), 4.30 (dd, J = 10.2, 4.2 Hz, 1H), 3.93 (dd, J = 18.0, 10.1 Hz,1H), 3.71 (s, 3H), 3.29 (dd, J = 18.0, 4.2 Hz, 1H). 13 C NMR (125 MHz, CDCl 3 ) δ197.39, 173.49, 163.07 (d, J = 247.2 Hz), 140.76 (d, J = 7.4 Hz), 136.33,133.59, 130.54 (d, J = 8.3 Hz), 128.79, 128.22, 123.75 (d, J = 2.8 Hz),115.02 (d, J = 22.1 Hz), 114.71 (d, J = 21.1 Hz), 52.64, 46.17, 42.67. 19 F NMR(471 MHz, CDCl 3 ) δ -112.21. ESI-MS: calculated [C 17 H 15 FO 3 + Na] + : 309.0897,found: 309.0896. [α] 20 D = +82.3 (c = 0.64, CH 2 Cl 2). The product was analyzed byHPLC to determine the enantiomeric excess: 90% ee (CHIRALPAK IB, n -hexane / i -PrOH = 90 / 10, detector: 254 nm, T = 25 ℃, flow rate: 1 mL / min), t 1 (minor) =8.0 min, t 2 (major) = 9.1 min.

[0045] Example 9: Preparation of Chiral Dicarbonyl Compound 4i

[0046] 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 an argon atmosphere, weigh and add the corresponding compounds 1i (0.3 mmol), 2a (0.1 mmol), methanol 3a (0.5 mmol), chiral isothiourea catalyst (0.01 mmol), tetrabutylammonium hexafluorophosphate ( n Bu 4 NPF 6 , 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 (1.0 mA) for 8 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 corresponding chiral dicarbonyl compound 4i (63% yield, 90% ee) was separated by column chromatography.

[0047] 1 H NMR (400 MHz, CDCl 3 ) δ 8.01-7.94 (m, 2H), 7.62-7.53 (m, 1H), 7.51-7.42 (m, 2H), 7.36 (m, 1H), 7.30-7.20 (m, 3H), 4.28 (dd, J = 10.1, 4.2 Hz,1H), 3.93 (dd, J = 18.1, 10.1 Hz, 1H), 3.71 (s, 3H), 3.27 (dd, J = 18.0, 4.2 Hz, 1H).13 C NMR (100 MHz, CDCl 3 ) δ 197.3, 173.4, 140.4, 136.3, 134.8, 133.6,130.3, 128.8, 128.2, 128.1, 128.0, 126.3, 52.6, 46.1, 42.6. ESI-MS:calculated [C 17 H 15 C1O 3 + Na] + : 325.0602, found: 325.0598. [α] 20 D = +84.9 (c =0.63, CH 2 Cl 2 ). The product was analyzed by HPLC to determine the enantiomericexcess: 90% ee (CHIRALPAK IB, n -hexane / i -PrOH = 90 / 10, detector: 254 nm, T =25 ℃, flow rate: 1 mL / min), t 1 (minor) = 8.3 min, t 2 (major) = 9.3 min.

[0048] Example 10: Preparation of Chiral Dicarbonyl Compound 4j

[0049] 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 an argon atmosphere, weigh and add the corresponding compounds 1j (0.3 mmol), 2b (0.1 mmol), methanol 3a (0.5 mmol), chiral isothiourea catalyst (0.01 mmol), tetrabutylammonium hexafluorophosphate ( n Bu 4 NPF 6, 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 (1.0 mA) for 8 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 corresponding chiral dicarbonyl compound 4j (85% yield, 97% ee) was separated by column chromatography.

[0050] 1 H NMR (400 MHz, CDCl 3 ) δ 7.91-7.83 (m, 2H), 7.39-7.31 (m, 4H), 7.31-7.26 (m, 1H), 7.26-7.25 (m, 1H), 7.24-7.22 (m, 1H), 4.29 (dd, J = 10.3, 4.1Hz, 1H), 3.92 (dd, J = 17.9, 10.3 Hz, 1H), 3.70 (s, 3H), 3.25 (dd, J = 17.9,4.1 Hz, 1H), 2.40 (s, 3H). 13 C NMR (100 MHz, CDCl 3 ) δ 197.4, 174.1, 144.3,138.6, 134.1, 129.4, 129.0, 128.3, 128.0, 127.7, 52.5, 46.5, 42.8, 21.8.ESI-MS: calculated [C 18 H 18 O 3 + Na] + : 305.1148, found: 305.1151. [α] 20 D = +94.3 (c =0.80, CH 2 Cl 2 ). The product was analyzed by HPLC to determine the enantiomericexcess: 97% ee (CHIRALPAK IB, n -hexane / i-PrOH = 70 / 30, detector: 254 nm, T =25 ℃, flow rate: 1 mL / min), t 1 (minor) = 5.7 min, t 2 (major) = 7.2 min.

[0051] Example 11: Preparation of Chiral Dicarbonyl Compound 4k

[0052] 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 an argon atmosphere, weigh and add the corresponding compounds 1j (0.3 mmol), 2c (0.1 mmol), methanol 3a (0.5 mmol), chiral isothiourea catalyst (0.01 mmol), tetrabutylammonium hexafluorophosphate ( n Bu 4 NPF 6 , 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 (1.0 mA) for 8 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 corresponding chiral dicarbonyl compound 4k (77% yield, 98% ee) was separated by column chromatography.

[0053] 1 H NMR (400 MHz, CDCl 3 ) δ 8.01-7.90 (m, 2H), 7.45-7.31 (m, 4H), 7.31-7.26 (m, 1H), 6.96-6.88 (m, 2H), 4.29 (dd, J = 10.3, 4.1 Hz, 1H), 3.97 – 3.83(m, 4H), 3.69 (s, 3H), 3.23 (dd, J = 17.8, 4.1 Hz, 1H). 13 C NMR (100 MHz, CDCl 3 ) δ 196.2, 174.1, 163.8, 138.6, 130.5, 129.6, 129.0, 128.0, 127.6,113.9, 55.6, 52.4, 46.6, 42.6. ESI-MS: calculated [C18 H 18 O 4 + Na] + : 321.1097, found: 321.1093. [α] 20 D = +54.6 (c = 0.76, CH 2 Cl 2 ). The product was analyzed byHPLC to determine the enantiomeric excess: 98% ee (CHIRALPAK IC, n -hexane / i -PrOH = 90 / 10, detector: 260 nm, T = 25 ℃, flow rate: 1 mL / min), t 1 (minor) =32.3 min, t 2 (major) = 34.1 min.

[0054] Example 12: Preparation of Chiral Dicarbonyl Compound 41

[0055] 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 an argon atmosphere, weigh and add the corresponding compounds 1j (0.3 mmol), 2d (0.1 mmol), methanol 3a (0.5 mmol), chiral isothiourea catalyst (0.01 mmol), tetrabutylammonium hexafluorophosphate ( n Bu 4 NPF 6 , 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 (1.0 mA) for 8 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 corresponding chiral dicarbonyl compound 4l (75% yield, 97% ee) was separated by column chromatography.

[0056] 1 H NMR (400 MHz, CDCl 3) δ 7.97-7.88 (m, 2H), 7.48-7.45 (m, 2H), 7.39-7.32 (m, 4H), 7.31-7.26 (m, 1H), 4.31 (dd, J = 10.3, 4.2 Hz, 1H), 3.93 (dd, J = 18.0, 10.2 Hz, 1H), 3.69 (s, 3H), 1.34 (s, 9H). 13 C NMR (100 MHz, CDCl 3 ) δ197.4, 174.0, 157.2, 138.6, 134.0, 129.0, 128.2, 128.0, 127.6, 125.7, 52.4,46.5, 42.8, 35.3, 31.2. ESI-MS: calculated [C 21 H 24 O 3 + Na] + : 347.1618, found:347.1614. [α] 20 D = +80.4 (c = 0.75, CH 2 Cl 2 ). The product was analyzed by HPLC to determine the enantiomeric excess: 97% ee (CHIRALPAK IC, n -hexane / i -PrOH =90 / 10, detector: 254 nm, T = 25 ℃, flow rate: 1 mL / min), t 1 (minor) = 12.7min, t 2 (major) = 15.3 min.

[0057] Example 13: Preparation of Chiral Dicarbonyl Compound 4m

[0058] 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 an argon atmosphere, weigh and add the corresponding compounds 1j (0.3 mmol), 2e (0.1 mmol), methanol 3a (0.5 mmol), chiral isothiourea catalyst (0.01 mmol), tetrabutylammonium hexafluorophosphate ( n Bu 4 NPF 6 , 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 (1.0 mA) for 8 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 corresponding chiral dicarbonyl compound 4m (82% yield, 98% ee) was separated by column chromatography.

[0059] 1 H NMR (400 MHz, CDCl 3 ) δ 8.07-8.02 (m, 2H), 7.70-7.65 (m, 2H), 7.65-7.59 (m, 2H), 7.49-7.43 (m, 2H), 7.43-7.33 (m, 5H), 7.33-7.27 (m, 1H), 4.33(dd, J = 10.3, 4.0 Hz, 1H), 3.98 (dd, J = 18.0, 10.3 Hz, 1H), 3.71 (s, 3H), 3.30 (dd, J = 18.0, 4.1 Hz, 1H). 13 C NMR (125 MHz, CDCl 3 ) δ 197.4, 174.0,146.1, 139.9, 138.5, 135.2, 129.1, 128.8, 128.4, 128.0, 127.7, 127.4, 127.4,52.5, 46.5, 43.0. ESI-MS: calculated [C 23 H 20 O 3 + Na] + : 367.1305, found:367.1306. [α] 20 D = +75.7 (c = 0.70, CH 2 Cl2 ). The product was analyzed by HPLCto determine the enantiomeric excess: 98% ee (CHIRALPAK IC, n -hexane / i -PrOH =70 / 30, detector: 254 nm, T = 25 ℃, flow rate: 1 mL / min), t 1 (major) = 9.8min, t 2 (minor) = 12.1 min.

[0060] Example 14: Preparation of Chiral Dicarbonyl Compound 4n

[0061] 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 an argon atmosphere, weigh and add the corresponding compounds 1j (0.3 mmol), 2f (0.1 mmol), methanol 3a (0.5 mmol), chiral isothiourea catalyst (0.01 mmol), tetrabutylammonium hexafluorophosphate ( n Bu 4 NPF 6 , 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 (1.0 mA) for 8 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 corresponding chiral dicarbonyl compound 4n (68% yield, 95% ee) was separated by column chromatography.

[0062] 1 H NMR (400 MHz, CDCl 3 ) δ 8.05-7.95 (m, 2H), 7.42-7.32 (m, 4H), 7.32-7.27 (m, 1H), 7.15-7.08 (m, 2H), 4.29 (dd, J = 10.4, 4.0 Hz, 1H), 3.92 (dd, J = 17.9, 10.4 Hz, 1H), 3.70 (s, 3H), 3.23 (dd, J = 17.9, 4.0 Hz, 1H).13 C NMR (100 MHz, CDCl 3 ) δ 196.21, 173.96, 166.03 (d, J = 255.2 Hz), 138.35, 132.98(d, J = 3.1 Hz), 130.88 (d, J = 9.5 Hz), 129.10, 127.93, 127.76, 115.87 (d, J = 22.0 Hz), 52.52, 46.48, 42.85. 19 F NMR (376 MHz, CDCl 3 ) δ -104.8. ESI-MS:calculated [C 17 H 15 FO 3 + Na] + : 309.0897, found: 309.0898. [α] 20 D = +82.2 (c =0.64, CH 2 Cl 2 ). The product was analyzed by HPLC to determine the enantiomericexcess: 95% ee (CHIRALPAK IC, n -hexane / i -PrOH = 90 / 10, detector: 254 nm, T =25 ℃, flow rate: 1 mL / min), t 1 (major) = 9.1 min, t 2 (mior) = 10.3 min.

[0063] Example 15: Preparation of Chiral Dicarbonyl Compound 4o

[0064] 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 an argon atmosphere, weigh and add the corresponding compounds 1j (0.3 mmol), 2g (0.1 mmol), methanol 3a (0.5 mmol), chiral isothiourea catalyst (0.01 mmol), tetrabutylammonium hexafluorophosphate ( nBu 4 NPF 6 , 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 (1.0 mA) for 8 hours. After the reaction was complete, the solvent was directly removed by reduced pressure distillation, and finally, a mixture of petroleum ether and ethyl acetate in a volume ratio of 50:1 was used as the eluent, and the corresponding chiral dicarbonyl compound 4o (63% yield, 95% ee) was separated by column chromatography.

[0065] 1 H NMR (500 MHz, CDCl 3 ) δ 7.94-7.88 (m, 2H), 7.46-7.40 (m, 2H), 7.38-7.32 (m, 4H), 7.32-7.27 (m, 1H), 4.29 (dd, J = 10.1, 3.7 Hz, 1H), 3.91 (dd, J = 17.9, 10.3 Hz, 1H), 3.70 (s, 3H), 3.22 (dd, J = 17.9, 3.8 Hz, 1H). 13 C NMR (100 MHz, CDCl 3 ) δ 196.6, 173.9, 139.9, 138.3, 134.8, 129.6, 129.1, 129.1,127.9, 127.8, 52.5, 46.4, 42.9. ESI-MS: calculated [C 17 H 15 C1O 3 + Na] + :325.0602, found: 325.0609. [α] 20 D = +73.9 (c = 0.64, CH 2 Cl 2 ). The product wasanalyzed by HPLC to determine the enantiomeric excess: 95% ee (CHIRALPAK IG, n -hexane / i-PrOH = 90 / 10, detector: 254 nm, T = 25 ℃, flow rate: 1 mL / min),t 1 (minor) = 14.6 min, t 2 (major) = 16.1 min.

[0066] Example 16: Preparation of Chiral Dicarbonyl Compound 4p

[0067] 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 an argon atmosphere, weigh and add the corresponding compounds 1j (0.3 mmol), 2h (0.1 mmol), methanol 3a (0.5 mmol), chiral isothiourea catalyst (0.01 mmol), tetrabutylammonium hexafluorophosphate ( n Bu 4 NPF 6 , 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 (1.0 mA) for 8 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 corresponding chiral dicarbonyl compound 4p (56% yield, 95% ee) was separated by column chromatography.

[0068] 1 H NMR (400 MHz, CDCl 3 ) δ 7.86-7.78 (m, 2H), 7.58-7.50 (m, 1H), 7.50-7.40 (m, 2H), 7.39-7.27 (m, 5H), 6.97-6.82 (m, 2H), 3.79 (dd, J = 8.3, 7.0Hz, 1H), 3.68 (s, 3H), 3.16-3.04 (m, 1H), 2.84-2.72 (m, 1H). 13 C NMR (100 MHz, CDCl 3 ) δ 190.7, 173.5, 145.3, 138.0, 137.7, 132.9, 129.0, 128.7, 128.7,128.1, 128.0, 127.8, 52.4, 50.6, 36.6. ESI-MS: calculated [C19 H 18 O 3 + Na] + :317.1148, found: 317.1144. [α] 20 D = +52.0 (c = 0.55, CH 2 Cl 2 ). The product wasanalyzed by HPLC to determine the enantiomeric excess: 95% ee (CHIRALPAK IC, n -hexane / i -PrOH = 70 / 30, detector: 254 nm, T = 25 ℃, flow rate: 1 mL / min),t 1 (minor) = 9.0 min, t 2 (major) = 10.1 min.

[0069] Example 17: Preparation of Chiral Dicarbonyl Compound 4q

[0070] 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 an argon atmosphere, weigh and add the corresponding compounds 1j (0.3 mmol), 2i (0.1 mmol), methanol 3a (0.5 mmol), chiral isothiourea catalyst (0.01 mmol), tetrabutylammonium hexafluorophosphate ( n Bu 4 NPF 6 , 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 (1.0 mA) for 8 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 corresponding chiral dicarbonyl compound 4q (51% yield, 97% ee) was separated by column chromatography.

[0071] 1 H NMR (400 MHz, CDCl 3) δ 7.96-7.90 (m, 2H), 7.70-7.61 (m, 4H), 7.54-7.45 (m, 2H), 7.44-7.36 (m, 2H), 7.35-7.27 (m, 4H), 6.96-6.91 (m, 2H), 3.81(dd, J = 8.3, 7.0 Hz, 1H), 3.69 (s, 3H), 3.19-3.01 (m, 1H), 2.92-2.75 (m,1H). 13 C NMR (100 MHz, CDCl 3 ) δ 190.1, 173.5, 145.7, 145.2, 140.0, 138.0,136.4, 129.3, 129.1, 129.0, 128.3, 128.1, 128.0, 127.8, 127.4, 127.3, 52.4,50.6, 36.6. ESI-MS: calculated [C 25 H 22 O 3 + Na] + : 393.1461, found: 393.1460. [α] 20 D = +22.4 (c = 0.63, CH 2 Cl 2 ). The product was analyzed by HPLC to determine the enantiomeric excess: 97% ee (CHIRALPAK IC, n -hexane / i -PrOH = 70 / 30, detector: 300 nm, T = 25 ℃, flow rate: 1 mL / min), t 1 (minor) = 13.6 min, t 2 (major) = 16.5 min.

[0072] Example 18: Preparation of Chiral Dicarbonyl Compound 4r

[0073] 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 an argon atmosphere, weigh and add the corresponding compounds 1j (0.3 mmol), 2j (0.1 mmol), methanol 3a (0.5 mmol), chiral isothiourea catalyst (0.01 mmol), tetrabutylammonium hexafluorophosphate ( n Bu 4 NPF 6 , 0.3 mmol), and 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 (1.0 mA) for 8 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 corresponding chiral dicarbonyl compound 4r (76% yield, 93% ee) was separated by column chromatography.

[0074] 1 H NMR (400 MHz, CDCl 3 ) δ 7.39-7.14 (m, 9H), 6.59 (dt, J = 15.8, 6.8Hz,1H), 6.47 (dt, J = 15.8, 1.2 Hz, 1H), 3.74 (t, J = 7.7 Hz, 1H), 3.67 (s,3H), 3.10-2.98 (m, 1H), 2.80-2.68 (m, 1H), 2.33 (s, 3H) 13 C NMR (100 MHz, CDCl 3 ) δ 196.4, 173.4, 146.7, 138.6, 137.9, 137.1, 132.6, 131.3, 130.6,129.0, 128.3, 128.0, 127.8, 125.4, 52.4, 50.5, 36.4, 20.3. ESI-MS: calculated[C 20 H 20 O 3 + Na] + : 331.1305, found: 331.1298. [α] 20 D = +62.0 (c = 0.78, CH 2 Cl 2).The product was analyzed by HPLC to determine the enantiomeric excess: 93% ee(CHIRALPAK IC, n -hexane / i -PrOH = 70 / 30, detector: 254 nm, T = 25 ℃, flowrate: 1 mL / min), t 1 (minor) = 9.0 min, t 2 (major) = 10.9 min.

[0075] Example 19: Preparation of Chiral Dicarbonyl Compound 4s

[0076] 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 an argon atmosphere, weigh and add the corresponding compounds 1j (0.3 mmol), 2k (0.1 mmol), methanol 3a (0.5 mmol), chiral isothiourea catalyst (0.01 mmol), tetrabutylammonium hexafluorophosphate ( n Bu 4 NPF 6 , 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 (1.0 mA) for 8 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 corresponding chiral dicarbonyl compound 4s (40% yield, 97% ee) was separated by column chromatography.

[0077] 1 H NMR (400 MHz, CDCl 3 ) δ 9.51 (d, J = 7.9 Hz, 1H), 7.39-7.24 (m, 6H), 7.06-6.95 (m, 1H), 6.39-6.23 (m, 1H), 6.19-6.01 (m, 2H), 3.72-3.68 (m, 1H), 3.67 (s, 3H), 3.04-2.92 (m, 1H), 2.75-2.63 (m, 1H). 13 C NMR (100 MHz, CDCl 3) δ193.9, 173.5, 151.9, 142.5, 138.0, 131.1, 130.8, 129.0, 127.9, 127.8, 52.4,51.0, 36.9. ESI-MS: calculated [C 15 H 16 O 3 + Na] + : 267.0992, found: 267.0995. [α] 20 D = +75.4 (c = 0.31, CH 2 Cl 2 ). The product was analyzed by HPLC to determine the enantiomeric excess: 97% ee (CHIRALPAK IC, n -hexane / i -PrOH = 70 / 30, detector: 254 nm, T = 25 ℃, flow rate: 1 mL / min), t 1 (minor) = 12.5 min, t 2 (major) = 13.8 min.

[0078] Example 20: Preparation of Chiral Dicarbonyl Compound 4t

[0079] 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 an argon atmosphere, weigh and add the corresponding compounds 1j (0.3 mmol), 2a (0.1 mmol), ethanol 3b (0.5 mmol), chiral isothiourea catalyst (0.01 mmol), tetrabutylammonium hexafluorophosphate ( n Bu 4 NPF 6 , 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 (1.0 mA) for 8 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 corresponding chiral dicarbonyl compound 4t (73% yield, 94% ee) was separated by column chromatography.

[0080] 1 H NMR (500 MHz, CDCl 3 ) δ 8.00-7.94 (m, 2H), 7.63-7.53 (m, 1H), 7.50-7.42 (m, 2H), 7.40-7.32 (m, 4H), 7.32-7.26 (m, 1H), 4.28 (dd, J = 10.4, 4.0Hz, 1H), 4.20 (dq, J = 10.8, 7.2 Hz, 1H), 4.11 (dq, J = 10.8, 7.1 Hz, 1H),3.95 (dd, J = 18.0, 10.4 Hz, 1H), 3.26 (dd, J = 18.0, 4.0 Hz, 1H), 1.21 (t, J = 7.1 Hz, 3H). 13 C NMR (125 MHz, CDCl 3 ) δ 197.8, 173.5, 138.6, 136.5, 133.4,129.0, 128.7, 128.2, 127.9, 127.6, 61.2, 46.6, 42.9, 14.2. ESI-MS: calculated[C 18 H 18 O 3 + Na] + : 305.1148, found: 305.1148. [α] 20 D = +52.9 (c = 0.69, CH 2 Cl 2 ).The product was analyzed by HPLC to determine the enantiomeric excess: 94% ee(CHIRALPAK IC, n -hexane / i -PrOH = 70 / 30, detector: 254 nm, T = 25 ℃, flowrate: 1 mL / min), t 1 (minor) = 6.7 min, t 2 (major) = 8.2 min。

[0081] Example 21: Natural product calyxolane A and ent Asymmetric preparation of -calyxolane B

[0082]

[0083] 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 an argon atmosphere, weigh and add the corresponding compounds 1j (0.3 mmol), 2a (0.1 mmol), 3a (0.5 mmol), chiral isothiourea catalyst (0.01 mmol), tetrabutylammonium hexafluorophosphate ( n Bu 4 NPF 6 , 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 (1.0 mA) for 8 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 corresponding chiral dicarbonyl compound 4u (75% yield, 96% ee) was separated by column chromatography.

[0084] 1 H NMR (400 MHz, CDCl 3 ) δ 8.02-7.90 (m, 2H), 7.68-7.50 (m, 1H), 7.52-7.43 (m, 2H), 7.39-7.31 (m, 4H), 7.32-7.27 (m, 1H), 4.30 (dd, J = 10.4, 4.0Hz, 1H), 3.96 (dd, J = 18.0, 10.3 Hz, 1H), 3.70 (s, 3H), 3.28 (dd, J = 18.1,4.0 Hz, 1H). 13 C NMR (100 MHz, CDCl 3 ) δ 197.7, 174.0, 138.5, 136.5, 133.4,129.1, 128.7, 128.2, 128.0, 127.7, 52.5, 46.5, 42.9. ESI-MS: calculated[C 17 H 16 O 3+ Na] + : 291.0992, found: 291.0991. [α] 20 D = +89.4 (c = 0.98, CH 2 Cl 2 ).The product was analyzed by HPLC to determine the enantiomeric excess: 96% ee(CHIRALPAK IC, n -hexane / i -PrOH = 70 / 30, detector: 254 nm, T = 25 ℃, flowrate: 1 mL / min), t 1 (minor) = 7.6 min, t 2 (major) = 8.2 min.

[0085]

[0086] BH 3 THF (0.9 mol / L, 0.56 mL, 5.0 eq) was added to a Schlenk tube containing 4u (96% ee, 26.8 mg, 0.1 mmol), and the solution was stirred at 25 °C for 8 hours, then carefully quenched with MeOH. The resulting mixture was concentrated and dissolved in DCM (2.0 mL), then washed with BF at 25 °C. 3 ·Et 2 O (25 µL, 2.0 eq) for 2 h. 4 The reaction was quenched with Cl and extracted with DCM (3×5 mL). The combined organic extracts were washed with anhydrous Na 2 SO 4 The mixture was dried, filtered and concentrated. The natural product calyxolane A (6, 31% yield, 95% ee) and ent -calyxolane B (7, 41% yield, 96% ee).

[0087] Calyxolane A: 1 H NMR (400 MHz, CDCl 3 ) δ 7.70-6.91 (m, 10H), 5.16 (dd, J= 7.8, 5.8 Hz, 1H), 4.44-4.35 (m, 1H), 3.87 (t, J = 8.2 Hz, 1H), 3.46 (p, J =7.8 Hz, 1H), 2.41 (dt, J = 12.4, 7.7 Hz, 1H), 2.32-2.19 (m, 1H). 13 C NMR (100MHz, CDCl 3 ) δ 143.7, 142.2, 128.8, 128.5, 127.5, 127.3, 126.8, 125.6, 80.7,75.3, 44.5, 42.8. ESI-MS: calculated [C 16 H 16 O + Na] + : 247.1093, found:247.1088. [α] 20 D = +35.4 (c = 0.23, CH 2 Cl 2 ). The product was analyzed by HPLCto determine the enantiomeric excess: 95% ee (CHIRALPAK IB, n -hexane / i -PrOH =99 / 1, detector: 210.1 nm, T = 25 ℃, flow rate: 1 mL / min), t 1 (major) = 9.4min, t 2 (minor) = 11.0 min。

[0088] ent -calyxolane B: 1 H NMR (400 MHz, CDCl 3 ) δ 7.77-6.94 (m, 9H), 5.04-4.89 (m, 1H), 4.28 (ddt, J = 8.4, 5.8, 2.8 Hz, 1H), 3.94 (ddt, J = 8.5, 5.9,2.9 Hz, 1H), 3.61-3.52 (m, 1H), 2.68 (tq,J = 9.7, 3.0 Hz, 1H), 2.01-1.87 (m,1H). 13 C NMR (100 MHz, CDCl 3 ) δ 142.8, 141.8, 128.8, 128.6, 127.6, 127.4,126.8, 125.9, 82.0, 75.2, 46.2, 43.9. ESI-MS: calculated [C 16 H 16 O + Na] + :247.1093, found: 247.1093. [α] 20 D = +43.9 (c = 0.30, CH 2 Cl 2 ). The product wasanalyzed by HPLC to determine the enantiomeric excess: 96% ee (CHIRAL OD, n -hexane / i -PrOH = 90 / 10, detector: 210.3 nm, T = 25 ℃, flow rate: 1 mL / min),t 1 (major) = 6.5 min, t 2 (minor) = 8.2 min。

Claims

1. A chiral dicarbonyl compound, which is an optically active compound having a structure shown in the following formula I, including stereoisomers having the same chemical formula: ； In the formula: * represents a chiral carbon atom; n is 0, 1 or 2; 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 are independently selected from hydrogen, C 1-10 Alkyl or aryl; R 7 Independently selected from C 1-10 Alkyl or aryl.

2. A method for asymmetric preparation of chiral dicarbonyl compounds according to claim 1, characterized in that: Using carboxylic acid ester derivative 1 and enol silyl ether compound 2 as starting materials, alcohol 3 as quenching reagent, and chiral isothiourea as reaction catalyst, an asymmetric alkylation 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; n is 0, 1 or 2; 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 preparation method according to claim 2, characterized in that The steps include: Under a nitrogen atmosphere, in a reaction bottle equipped with electrodes, a carboxylate derivative 1, an enol silyl ether compound 2, an alcohol 3, a chiral isothiourea catalyst and an electrolyte are added, and an organic solvent is added for dissolution, and current electrolysis is applied at -40°C to 80°C for 2-60 hours, and the reaction endpoint is determined by a thin layer chromatography 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 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 preparation method according to claim 2 or 3, characterized in that: The electrolyte is one of tetrabutylammonium hexafluorophosphate, tetraethylammonium hexafluorophosphate, tetramethylammonium hexafluorophosphate, tetrabutylammonium tetrafluoroborate, tetrabutylammonium perchlorate, tetraethylammonium perchlorate, tetraethylammonium tetrafluoroborate, tetrabutylammonium chloride and tetrabutylammonium bromide.

6. The preparation method according to claim 2 or 3, characterized in that: The molar ratio of the chiral isothiourea catalyst to the enol silyl ether compound 2 is 0.03:1-1:1; The molar equivalent ratio of the enol silyl ether compound 2 to the carboxylate derivative 1 is 1:0.5-1:5; the molar equivalent ratio of the enol silyl ether compound 2 to the alcohol 3 is 1:1-1:100; and the molar ratio of the enol silyl ether compound 2 to the electrolyte is 1:0.1-1:

5.

7. The 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, methanol, tetrahydrofuran, acetonitrile, toluene, ethylbenzene, fluorobenzene, chlorobenzene, bromobenzene, xylene or trimethylbenzene.

8. The preparation method according to claim 3, characterized in that: The electrode is one or two of carbon, carbon cloth, carbon felt, carbon paper, platinum, nickel, mesh glassy carbon, glassy carbon, and boron-doped diamond electrodes.

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