Chiral alpha-aryloxy benzoxazole acetate compound and synthesis method thereof

Abstract

The invention discloses a chiral alpha-aryloxy benzoxazole acetate compound and a synthesis method thereof, and the chiral alpha-aryloxy benzoxazole acetate compound is an optically active compound with a structure as shown in the following formula I, and comprises a stereoisomer with the same chemical general formula. According to the method, a complex formed by a chiral ligand and metal is used as a catalyst, an electrochemical catalysis asymmetric aryloxylation reaction is used as a key step, and the target chiral compound is accurately and efficiently synthesized with high yield and high stereoselectivity. The preparation method is simple, reaction conditions are mild, atom economy is excellent, and the prepared chiral alpha-aryloxy benzoxazole acetate compound has good biological activity potential, can be widely applied to the field of drug intermediate synthesis and has remarkable biomedical practicability and industrial large-scale production prospects.

Description

Technical Field

[0001] This invention belongs to the field of asymmetric organic synthesis technology, specifically relating to a chiral α-aryloxybenzoxazole acetate compound and its synthesis method. Background Technology

[0002] CO structural fragments are fundamental building blocks of many functional molecules, commonly found in bioactive substances and advanced materials. Achieving efficient and stereoselective construction of these chemical bonds has been a key scientific challenge in organic synthesis. Current catalytic systems primarily employ a pre-functionalized reactant coupled with a stoichiometric oxidant, which, while yielding some results, has significant limitations in terms of synthetic economy and environmental friendliness. Against this backdrop, precise asymmetric transformations directly from the carbon-hydrogen bond, particularly for aliphatic C(sp) bonds, are crucial. 3 The selective functionalization of α-H bonds represents an ideal direction for the development of synthetic methodologies. While this strategy has yielded successful examples in constructing C-C and CN bonds, it has encountered a unique technical bottleneck in constructing CO bonds—how to achieve excellent chiral control while ensuring reaction efficiency and avoiding side reactions such as excessive oxidation has become a core challenge that urgently needs to be overcome. The lag in research on this transformation pathway contrasts sharply with the prevalence of CO bonds in functional molecules, highlighting the crucial value of developing new methods.

[0003] Electrochemical conversion technology has become one of the most promising frontiers in organic synthesis. The core innovation of this method lies in directly utilizing an external electric field to control the redox potential of the reaction system, using electrons as the most atom-economical "clean reagent" to achieve precise activation and conversion of organic substrates. This technological paradigm, in addition to its excellent ability to control reaction selectivity, also exhibits multi-dimensional advantages: it eliminates dependence on traditional stoichiometric oxidants or reductants, reducing chemical waste at the source and aligning with the concept of green synthesis; simultaneously, the electrode materials in electrochemical reaction devices are typically low-cost and reusable, possessing excellent industrialization potential. In recent years, with the increasing demand for asymmetric synthesis, the application of electrochemical strategies in this high-value field has rapidly expanded, demonstrating unique stereochemical control potential and providing unprecedented tools for the efficient construction of complex chiral molecules, indicating the continued and far-reaching development potential of this direction.

[0004] Monophenols are widely found in nature and generally possess unique biological activities, such as antioxidant, antibacterial, and anticancer properties. Since the efficacy of unmodified monophenols extracted from nature is significantly reduced or even inactivated when applied directly to the human body, structural modification is necessary to address the deficiencies in their biological activity and drug-like properties. Furthermore, the optical configuration of drug molecules often has a significant impact on their biological activity. Therefore, asymmetric modification of monophenols is a crucial area of ​​research. Currently, the modification of monophenols generally involves esterification to form carboxylic acid phenolic esters, utilizing sp... 3 The direct formation of asymmetric CO bonds from CH bonds with phenol is challenging, often requiring pre-functionalization of the substrate for coupling strategies. Therefore, developing a method using sp... 3 The synthetic system of direct aryloxylation of CH bonds to achieve asymmetric modification of monophenol compounds has important research value in the fields of organic synthetic chemistry and medicinal chemistry. Summary of the Invention

[0005] The purpose of this invention is to provide a chiral α-aryloxybenzoxazole acetate compound and its synthesis method, thereby solving the above-mentioned problems existing in the prior art.

[0006] The chiral α-aryloxybenzoxazole acetate compounds of the present invention are optically active compounds having the structure shown in Formula I, including stereoisomers having the same general chemical formula:

[0007] ;

[0008] In the formula: * represents a chiral carbon atom; Ar 1 and Ar 2 The components are independently selected from phenyl or substituted aromatic rings, wherein the substituents of the substituted aromatic rings are halogens, heteroatoms (O, S, etc.), or C1-C. 10 Alkyl or C1-C 10 Alkoxy; R 1 and R 2 Selected independently from C 1-10 The hydrocarbon group or hydrocarbon oxygen group.

[0009] The present invention discloses an asymmetric preparation method for chiral α-aryloxybenzoxazole acetate compounds, using compounds 1 and 2 as starting materials, and a complex formed by a chiral ligand and a metal catalyst precursor as a reaction catalyst. The reaction is carried out in an electrochemical redox reaction system in an organic solvent at a temperature of 0-60°C, and the target product I is obtained after separation and purification.

[0010] The synthesis route is shown below:

[0011] ;

[0012] In the formula: * represents a chiral carbon atom; Ar 1 and Ar 2 The components are independently selected from phenyl or substituted aromatic rings, wherein the substituents of the substituted aromatic rings are halogens, heteroatoms (O, S, etc.), or C1-C. 10 Alkyl or C1-C 10 Alkoxy; R 1 and R 2 Selected independently from C 1-10 The hydrocarbon group or hydrocarbon oxygen group.

[0013] Specifically, the steps include the following:

[0014] In an air or inert gas atmosphere, compound 1, compound 2, metal catalyst precursor, chiral ligand, ferrocene compound, acid, base and electrolyte are added to a reaction flask equipped with electrodes, and an organic solvent is added for dissolution. Electrolysis is carried out at 0-60℃ for 24-48 hours, and the reaction endpoint is determined by thin-layer chromatography. After the reaction is complete, the mixture is concentrated and separated by column chromatography to obtain the target product I.

[0015] During the preparation process of this invention:

[0016] The metal catalyst precursor is one or more of the following: nickel acetate, nickel chloride, nickel bromide, nickel trifluoromethanesulfonate, cobalt acetate, cobalt trifluoromethanesulfonate, bismuth trifluoromethanesulfonate, indium chloride, titanium triisopropoxychloride, tetra(acetonitrile)copper tetrafluoroborate, Raney nickel, nickel acetylacetonate, tetra(acetonitrile)copper hexafluorophosphate, lithium iodide, tetra(acetonitrile)copper perchlorate, nickel dimethoxyethane chloride, cuprous iodide, cuprous chloride, cuprous trifluoromethanesulfonate toluene complex, bis-(1,5-cyclooctadiene)nickel, silver acetate, silver carbonate, zinc dibromide, silver trifluoromethanesulfonate, silver perchlorate, silver tetrafluoroborate, lithium bromide, silver oxide, and scandium trifluoromethanesulfonate.

[0017] The chiral ligands are selected from compounds with the following structures:

[0018] ;

[0019] In the formula: * represents the chiral carbon center; n is 1, 2, 3, or 4; R 3 R 4 and R 5 Selected independently from C 1-10 Alkyl or aryl; Ar 3 Ar 4 and Ar 5 The components are independently selected from phenyl or substituted aromatic rings, wherein the substituents of the substituted aromatic rings are halogens or C1-C. 10 Alkyl or C1-C 10 Alkoxy;

[0020] The ferrocene compounds have the following structures:

[0021] ;

[0022] In the formula: R 6 Selected from hydrogen, halogen, carboxyl, acyl, or the following groups, substituted or unsubstituted: C 1-10 Alkyl or C 6-20 Aryl groups.

[0023] The acid is one or more of sulfuric acid, nitric acid, hydrochloric acid, oxalic acid, phosphoric acid, boric acid, formic acid, acetic acid, trifluoroacetic acid, benzoic acid, substituted benzoic acid, and phenylacetic acid.

[0024] The base is one or more of triethylamine, ethylenediamine, diisopropylethylamine, lithium bis(trimethylsilylamine), potassium bis(trimethylsilylamine), cesium carbonate, potassium carbonate, potassium phosphate, sodium hydroxide, potassium hydroxide, sodium tert-butoxide, potassium tert-butoxide, pyridine, quinine ring, or 1,8-diazabicyclo[5.4.0]undec-7-ene.

[0025] The electrolyte is one or more of the following: lithium carbonate, lithium chloride, lithium perchlorate, lithium hexafluorophosphate, lithium bis(trifluoromethanesulfonyl)imide, tetraphenylphosphonium bromide, tetrabutylammonium tetrafluoroborate, tetrabutylammonium hexafluorophosphate, tetraethylammonium hexafluorophosphate, tetramethylammonium hexafluorophosphate, tetrabutylammonium perchlorate, tetraethylammonium perchlorate, tetraethylammonium tetrafluoroborate, tetrabutylammonium chloride, and tetrabutylammonium bromide.

[0026] The organic solvent is one or a mixture of two or more of the following: dichloromethane, trifluoroethanol, 1,4-dioxane, 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.

[0027] The electrode is one or two of the following: carbon, carbon cloth, carbon felt, carbon paper, platinum, nickel, mesh glassy carbon, glassy carbon, and boron-doped diamond electrode.

[0028] in:

[0029] The molar equivalence ratio of the metal catalyst precursor to the chiral ligand is 1:1 to 1:4; the molar equivalence ratio of the metal catalyst precursor to compound 1 is 1:1 to 1:30; the molar equivalence ratio of compound 1 to compound 2 is 1:0.33 to 1:10; the molar equivalence ratio of compound 1 to ferrocene compounds is 1:0.1 to 1:10; the molar concentration of the acid is 0 to 1 mol / L; the molar concentration of the base is 0 to 1 mol / L; the molar concentration of the electrolyte is 0.01 to 1 mol / L; and the molar concentration of compound 1 in the system is 0.01 to 1 mol / L.

[0030] This invention utilizes a complex formed by a chiral ligand and a metal as a catalyst, and employs an electrochemically catalyzed asymmetric aryloxylation reaction as the key step to synthesize the target chiral compound with high yield, high stereoselectivity, precision, and high efficiency. The preparation method of this invention is simple, the reaction conditions are mild, and the atom economy is excellent. The prepared chiral α-aryloxybenzoxazole acetate compounds possess good bioactivity potential and can be widely applied in the synthesis of pharmaceutical intermediates, demonstrating significant biomedical applicability and prospects for industrial-scale production. Detailed Implementation

[0031] The following provides a detailed description of specific embodiments of the present invention. It should be understood that the specific embodiments described herein are for illustrative and explanatory purposes only and are not intended to limit the scope of the invention.

[0032] The endpoints and any values ​​of the ranges disclosed herein 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 the various ranges, the endpoint values ​​of the various ranges and individual point values, and individual point values ​​can be combined with each other to obtain one or more new numerical ranges, which should be considered as specifically disclosed herein.

[0033] The present invention will be described in detail below through embodiments.

[0034] Example 1: Preparation of α-aryloxybenzoxazole acetate compound 3a

[0035]

[0036] Under an argon atmosphere, in a dry 10 mL reaction tube equipped with a magnetic stir bar, a carbon electrode was used as the anode and a platinum electrode as the cathode. Nickel acetate (0.01 mmol) and a chiral ligand (0.01 mmol) were added. The corresponding compounds 1a (0.1 mmol), 2a (0.3 mmol), ferrocene (0.01 mmol), cesium carbonate (0.1 mmol), benzoic acid (0.1 mmol), and tetrabutylammonium tetrafluoroborate (…) were then weighed and added sequentially.n Bu4NBF4 (0.3 mmol) was dissolved in a 2.0:1.0 mixture of dichloromethane and trifluoroethanol (3 mL), followed by the addition of the pre-stirred catalyst solution. Electrolysis was then performed at 25 °C under constant current (2.0 mA) for 24 hours. After complete reaction, the solvent was removed by vacuum distillation, and the corresponding α-aryloxybenzoxazole acetate compound 3a (71% yield, 99% ee) was obtained by column chromatography using a 40:1 volume ratio of petroleum ether and ethyl acetate as eluent.

[0037] 1 H NMR (500 MHz, CDCl3) δ 7.84-7.70 (m, 1H), 7.61-7.50 (m, 1H), 7.37(tt, J = 7.5, 5.8 Hz, 2H), 6.96 (d, J = 8.4 Hz, 2H), 6.77 (d, J = 8.5 Hz,2H), 2.23 (s, 3H), 2.01 (s, 3H), 1.44 (s, 9H). 13 C NMR (125 MHz, CDCl3) δ168.1, 163.9, 152.3, 151.0, 140.7, 133.3, 129.8, 125.9, 124.7, 120.9, 120.8,111.2, 83.6, 80.2, 27.9, 21.8, 20.8. ESI-MS: calculated [C 21 H 23 NO4 + Na] + :376.1519, found: 376.1519. [α] 20 D = +94.56 (c = 0.52, CH2Cl2). The product wasanalyzed by HPLC to determine the enantiomeric excess: 99% ee. (CHIRALPAK IC,hexane / i-PrOH = 90 / 10, detector: 256 nm, T = 25 ℃, flow rate: 1 mL / min), t1(major) = 5.20 min, t2(minor) = 6.23 min.

[0038] Example 2: Preparation of α-aryloxybenzoxazole acetate compound 3b

[0039]

[0040] Under an argon atmosphere, in a dry 10 mL reaction tube equipped with a magnetic stirrer, a carbon electrode was used as the anode and a platinum electrode as the cathode. Nickel acetate (0.01 mmol) and a chiral ligand (0.01 mmol) were added. Then, the corresponding compounds 1a (0.1 mmol), 2b (0.3 mmol), ferrocene (0.01 mmol), cesium carbonate (0.1 mmol), benzoic acid (0.1 mmol), and tetrabutylammonium tetrafluoroborate (…) were weighed and added sequentially. n Bu4NBF4 (0.3 mmol) was dissolved in a 2.0:1.0 mixture of dichloromethane and trifluoroethanol (3 mL), followed by the addition of the pre-stirred catalyst solution. Electrolysis was then performed at 25 °C under constant current (2.0 mA) for 24 hours. After complete reaction, the solvent was removed by vacuum distillation, and the α-aryloxybenzoxazole acetate compound 3b (58% yield, 98% ee) was obtained by column chromatography using a 40:1 volume ratio of petroleum ether and ethyl acetate as eluent.

[0041] 1 H NMR (500 MHz, CDCl3) δ 7.86-7.73 (m, 1H), 7.63-7.54 (m, 1H), 7.38(tt, J = 7.4, 5.8 Hz, 2H), 7.24-7.10 (m, 2H), 7.08-6.97 (m, 1H), 6.95-6.80(m, 2H), 2.05 (s, 3H), 1.43 (s, 9H). 13 C NMR (125 MHz, CDCl3) δ 168.0, 163.8,154.7, 151.0, 140.7, 129.3, 125.9, 124.8, 123.6, 120.8, 120.7, 111.2, 83.7,80.2, 27.9, 22.1. ESI-MS: calculated [C 20 H 21 NO4 + Na] + : 362.1316, found:362.1362. [α] 20 D= +56.02 (c = 0.46, CH2Cl2). The product was analyzed by HPLCto determine the enantiomeric excess: 98% ee. (CHIRALPAK IE, hexane / i-PrOH =98 / 2, detector: 256 nm, T = 25 ℃, flow rate: 1 mL / min), t1(minor) = 10.83min, t2(major) = 11.52 min.

[0042] Example 3: Preparation of α-aryloxybenzoxazole acetate compound 3c

[0043]

[0044] Under an argon atmosphere, in a dry 10 mL reaction tube equipped with a magnetic stirrer, a carbon electrode was used as the anode and a platinum electrode as the cathode. Nickel acetate (0.01 mmol) and a chiral ligand (0.01 mmol) were added. The corresponding compounds 1a (0.1 mmol), 2c (0.3 mmol), ferrocene (0.01 mmol), cesium carbonate (0.1 mmol), benzoic acid (0.1 mmol), and tetrabutylammonium tetrafluoroborate (…) were then weighed and added sequentially. n Bu4NBF4 (0.3 mmol) was dissolved in a 2.0:1.0 mixture of dichloromethane and trifluoroethanol (3 mL), followed by the addition of the pre-stirred catalyst solution. Electrolysis was then performed at 25 °C under constant current (2.0 mA) for 24 hours. After complete reaction, the solvent was removed by vacuum distillation, and the α-aryloxybenzoxazole acetate compound 3c (69% yield, 98% ee) was obtained by column chromatography using a 40:1 volume ratio of petroleum ether and ethyl acetate as eluent.

[0045] 1 H NMR (500 MHz, CDCl3) δ 7.84-7.77 (m, 1H), 7.62-7.53 (m, 1H), 7.42-7.32 (m, 2H), 7.18 -7.11 (m, 1H), 6.93 (ddd, J = 12.5, 7.5, 1.7 Hz, 2H), 6.68(dd, J = 7.9, 1.4 Hz, 1H), 2.33 (s, 3H), 2.02 (s, 3H), 1.43 (s, 9H). 13C NMR(125 MHz, CDCl3) δ 168.2, 164.4, 153.3, 151.1, 140.8, 131.2, 130.8, 126.5,125.8, 124.7, 123.2, 120.8, 118.5, 111.2, 83.6, 80.5, 27.8, 21.9, 16.8. ESI-MS: calculated [C 21 H 23 NO4 + Na] + : 376.1519, found: 376.1526. [α] 20 D = +41.76 (c= 1.03, CH2Cl2). The product was analyzed by HPLC to determine theenantiomeric excess: 98% ee. (CHIRALPAK IE, hexane / i-PrOH = 95 / 5, detector:256 nm, T = 25 ℃, flow rate: 1 mL / min), t1(minor) = 5.64 min, t2(major) =6.13 min.

[0046] Example 4: Preparation of α-aryloxybenzoxazole acetate compound 3d

[0047]

[0048] Under an argon atmosphere, in a dry 10 mL reaction tube equipped with a magnetic stirrer, a carbon electrode was used as the anode and a platinum electrode as the cathode. Nickel acetate (0.01 mmol) and a chiral ligand (0.01 mmol) were added. The corresponding compounds 1a (0.1 mmol), 2d (0.3 mmol), ferrocene (0.01 mmol), cesium carbonate (0.1 mmol), benzoic acid (0.1 mmol), and tetrabutylammonium tetrafluoroborate (…) were weighed and added sequentially. nBu4NBF4 (0.3 mmol) was dissolved in a 2.0:1.0 mixture of dichloromethane and trifluoroethanol (3 mL), followed by the addition of the pre-stirred catalyst solution. Electrolysis was then performed at 25 °C under constant current (2.0 mA) for 24 hours. After complete reaction, the solvent was removed by vacuum distillation, and the α-aryloxybenzoxazole acetate compound 3d (65% yield, 99% ee) was obtained by column chromatography using a 40:1 volume ratio of petroleum ether and ethyl acetate as eluent.

[0049] 1 H NMR (500 MHz, CDCl3) δ 7.81-7.74 (m, 1H), 7.60-7.54 (m, 1H), 7.42-7.33 (m, 2H), 7.04 (t, J = 7.9 Hz, 1H), 6.82 (d, J = 7.5 Hz, 1H), 6.76 (t, J= 2.1 Hz, 1H), 6.66 (dd, J = 8.2, 2.5 Hz, 1H), 2.22 (s, 3H), 2.04 (s, 3H), 1.43 (s, 9H). 13 C NMR (125 MHz, CDCl3) δ 168.1, 163.9, 154.7, 151.0, 140.7,139.4, 129.0, 125.8, 124.7, 124.4, 121.5, 120.8, 117.3, 111.1, 83.7, 80.1,27.9, 22.0, 21.4. ESI-MS: calculated [C 21 H 23 NO4 + Na] + : 376.1519, found:376.1525. [α] 20 D = +0.5556 (c = 0.65, CH2Cl2). The product was analyzed by HPLCto determine the enantiomeric excess: 99% ee. (CHIRALPAK IC, hexane / i-PrOH =90 / 10, detector: 256 nm, T = 25 ℃, flow rate: 1 mL / min), t1(major) = 4.60min, t2(minor) = 5.21 min.

[0050] Example 5: Preparation of α-aryloxybenzoxazole acetate compound 3e

[0051]

[0052] Under an argon atmosphere, in a dry 10 mL reaction tube equipped with a magnetic stirrer, a carbon electrode was used as the anode and a platinum electrode as the cathode. Nickel acetate (0.01 mmol) and a chiral ligand (0.01 mmol) were added. The corresponding compounds 1a (0.1 mmol), 2e (0.3 mmol), ferrocene (0.01 mmol), cesium carbonate (0.1 mmol), benzoic acid (0.1 mmol), and tetrabutylammonium tetrafluoroborate (…) were then weighed and added sequentially. n Bu4NBF4 (0.3 mmol) was dissolved in a 2.0:1.0 mixture of dichloromethane and trifluoroethanol (3 mL), followed by the addition of the pre-stirred catalyst solution. Electrolysis was then performed at 25 °C under constant current (2.0 mA) for 24 hours. After complete reaction, the solvent was removed by vacuum distillation, and the α-aryloxybenzoxazole acetate compound 3e (63% yield, 98% ee) was obtained by column chromatography using a 40:1 volume ratio of petroleum ether and ethyl acetate as eluent.

[0053] 1 H NMR (500 MHz, CDCl3) δ 7.83-7.71 (m, 1H), 7.64-7.51 (m, 1H), 7.43-7.35 (m, 2H), 6.94 -6.65 (m, 4H), 2.02 (s, 3H), 1.44 (s, 9H). 13 C NMR (125MHz, CDCl3) δ 167.9, 163.4, 160.2, 158.3, 150.9, 150.5, 150.5, 140.6, 126.0,124.9, 122.8, 122.7, 120.9, 115.9, 115.7, 111.1, 83.8, 80.6, 27.9, 22.0. 19 FNMR (471 MHz, CDCl3) δ -119.4. ESI-MS: calculated [C 20 H 20 FNO4 + Na] + : 380.1268, found: 380.1263. [α] 20D = +63.52 (c = 0.80, CH2Cl2). The product was analyzed by HPLC to determine the enantiomeric excess: 98% ee. (CHIRALPAK IC, hexane / i-PrOH = 95 / 5, detector: 254 nm, T = 25 ℃, flow rate: 1 mL / min), t1(major) =4.65 min, t2(minor) = 5.12 min.

[0054] Example 6: Preparation of α-aryloxybenzoxazole acetate compound 3f

[0055]

[0056] Under an argon atmosphere, in a dry 10 mL reaction tube equipped with a magnetic stirrer, a carbon electrode was used as the anode and a platinum electrode as the cathode. Nickel acetate (0.01 mmol) and a chiral ligand (0.01 mmol) were added. The corresponding compounds 1a (0.1 mmol), 2f (0.3 mmol), ferrocene (0.01 mmol), cesium carbonate (0.1 mmol), benzoic acid (0.1 mmol), and tetrabutylammonium tetrafluoroborate (…) were then weighed and added sequentially. n Bu4NBF4 (0.3 mmol) was dissolved in a 2.0:1.0 mixture of dichloromethane and trifluoroethanol (3 mL), followed by the addition of the pre-stirred catalyst solution. Electrolysis was then performed at 25 °C under constant current (2.0 mA) for 24 hours. After complete reaction, the solvent was removed by vacuum distillation, and the α-aryloxybenzoxazole acetate compound 3F (55% yield, 98% ee) was obtained by column chromatography using a 40:1 volume ratio of petroleum ether and ethyl acetate as eluent.

[0057] 1 H NMR (500 MHz, CDCl3) δ 7.84-7.72 (m, 1H), 7.66-7.50 (m, 1H), 7.45-7.35 (m, 2H), 7.21 -7.07 (m, 2H), 6.95-6.78 (m, 2H), 2.05 (s, 3H), 1.44 (s,9H). 13C NMR (125 MHz, CDCl3) δ 167.7, 163.2, 153.4, 150.9, 140.6, 129.3,128.8, 126.1, 124.9, 122.0, 120.9, 111.2, 84.0, 80.4, 27.9, 22.2. ESI-MS:calculated [C 20 H 20 ClNO4 + Na] + : 396.0973, found: 396.0976. [α] 20 D = +38.70 (c =0.63, CH2Cl2). The product was analyzed by HPLC to determine the enantiomericexcess: 98% ee. (CHIRALPAK IE, hexane / i-PrOH = 99.5 / 0.5, detector: 254 nm, T= 25 ℃, flow rate: 1 mL / min), t1(minor) = 16.78 min, t2(major) = 19.13 min.

[0058] Example 7: Preparation of 3g of α-aryloxybenzoxazole acetate compound

[0059]

[0060] Under an argon atmosphere, in a dry 10 mL reaction tube equipped with a magnetic stirrer, a carbon electrode was used as the anode and a platinum electrode as the cathode. Nickel acetate (0.01 mmol) and a chiral ligand (0.01 mmol) were added. The corresponding compounds 1a (0.1 mmol), 2 g (0.3 mmol), ferrocene (0.01 mmol), cesium carbonate (0.1 mmol), benzoic acid (0.1 mmol), and tetrabutylammonium tetrafluoroborate (…) were weighed and added sequentially. n Bu4NBF4 (0.3 mmol) was dissolved in a 2.0:1.0 mixture of dichloromethane and trifluoroethanol (3 mL), followed by the addition of the pre-stirred catalyst solution. Electrolysis was then performed at 25 °C under constant current (2.0 mA) for 24 hours. After complete reaction, the solvent was removed by vacuum distillation, and the α-aryloxybenzoxazole acetate compound (3 g, 57% yield, 98% ee) was obtained by column chromatography using a 40:1 volume ratio of petroleum ether and ethyl acetate as eluent.

[0061] 1 H NMR (500 MHz, CDCl3) δ 7.81-7.74 (m, 1H), 7.60-7.54 (m, 1H), 7.39(tt, J = 7.5, 5.8 Hz, 2H), 7.28 (dd, J = 8.8, 6.7 Hz, 2H), 6.84-6.74 (m, 2H), 2.05 (s, 3H), 1.44 (s, 9H). 13 C NMR (125 MHz, CDCl3) δ 167.7, 163.2, 153.9,150.9, 140.6, 132.3, 126.1, 124.9, 122.3, 120.9, 116.3, 111.2, 84.0, 80.3,27.9, 22.2. ESI-MS: calculated [C 20 H 20 BrNO4 + Na] + : 440.0468, found: 440.0467.[α] 20 D = +41.66 (c = 0.49, CH2Cl2). The product was analyzed by HPLC to determine the enantiomeric excess: 98% ee. (CHIRALPAK IC, hexane / i-PrOH = 99 / 1, detector: 254 nm, T = 25 ℃, flow rate: 1 mL / min), t1(major) = 6.69 min, t2(minor) = 7.74 min.

[0062] Example 8: Preparation of α-aryloxybenzoxazole acetate compounds (3h)

[0063]

[0064] Under an argon atmosphere, in a dry 10 mL reaction tube equipped with a magnetic stirrer, a carbon electrode was used as the anode and a platinum electrode as the cathode. Nickel acetate (0.01 mmol) and a chiral ligand (0.01 mmol) were added. The corresponding compounds 1a (0.1 mmol), 2h (0.3 mmol), ferrocene (0.01 mmol), cesium carbonate (0.1 mmol), benzoic acid (0.1 mmol), and tetrabutylammonium tetrafluoroborate (…) were weighed and added sequentially. n Bu4NBF4 (0.3 mmol) was dissolved in a 2.0:1.0 mixture of dichloromethane and trifluoroethanol (3 mL), followed by the addition of the pre-stirred catalyst solution. Electrolysis was then performed at 25 °C under constant current (2.0 mA) for 24 hours. After complete reaction, the solvent was removed by vacuum distillation, and the corresponding α-aryloxybenzoxazole acetate compounds were obtained by column chromatography using a 40:1 volume ratio of petroleum ether and ethyl acetate as eluent (75% yield, 99% ee) for 3 hours.

[0065] 1 H NMR (500 MHz, CDCl3) δ 7.82-7.72 (m, 1H), 7.58 (dd, J=7.2, 1.9Hz, 1H), 7.38 (pd, J=7.4, 1.5Hz, 2H), 6.86-6.78 (m, 2H), 6.74-6.65 (m,2H), 3.71 (s, 3H), 1.98 (s, 23H), 1.44 (s, 9H). 13 C NMR (125 MHz, CDCl3) δ168.2, 163.8, 156.2, 151.0, 147.9, 140.6, 125.9, 124.8, 122.9, 120.8, 114.3,111.2, 83.6, 80.6, 55.6, 27.9, 21.6. ESI-MS: calculated [C 21 H 23 NO5 + H] + :370.1649, found: 370.1650. [α] 20 D= +105.42 (c = 1.07, CH2Cl2). The product wasanalyzed by HPLC to determine the enantiomeric excess: 99% ee. (CHIRALPAK IC,hexane / i-PrOH = 90 / 10, detector: 236 nm, T = 25 ℃, flow rate: 1 mL / min), t1(major) = 7.45 min, t2(minor) = 9.35 min.

[0066] Example 9: Preparation of α-aryloxybenzoxazole acetate compound 3i

[0067]

[0068] Under an argon atmosphere, in a dry 10 mL reaction tube equipped with a magnetic stirrer, a carbon electrode was used as the anode and a platinum electrode as the cathode. Nickel acetate (0.01 mmol) and a chiral ligand (0.01 mmol) were added. The corresponding compounds 1a (0.1 mmol), 2i (0.3 mmol), ferrocene (0.01 mmol), cesium carbonate (0.1 mmol), benzoic acid (0.1 mmol), and tetrabutylammonium tetrafluoroborate (…) were then weighed and added sequentially. n Bu4NBF4 (0.3 mmol) was dissolved in a 2.0:1.0 mixture of dichloromethane and trifluoroethanol (3 mL), followed by the addition of the pre-stirred catalyst solution. Electrolysis was then performed at 25 °C under constant current (2.0 mA) for 24 hours. After complete reaction, the solvent was removed by vacuum distillation, and the α-aryloxybenzoxazole acetate compound 3i (76% yield, 99% ee) was obtained by column chromatography using a 40:1 volume ratio of petroleum ether and ethyl acetate as eluent.

[0069] 1 H NMR (500 MHz, CDCl3) δ 7.83-7.75 (m, 1H), 7.62-7.56 (m, 1H), 7.44-7.34 (m, 2H), 7.17 (d, J = 8.8 Hz, 2H), 6.79 (d, J = 8.8 Hz, 2H), 2.03 (s,3H), 1.43 (s, 9H), 1.24 (s, 9H). 13C NMR (125 MHz, CDCl3) δ 168.1, 164.0,152.1, 151.0, 146.4, 140.7, 126.1, 125.8, 124.7, 120.8, 120.2, 111.2, 83.6,80.1, 34.3, 31.5, 27.9, 21.8. ESI-MS: calculated [C 24 H 29 NO4 + Na] + : 418.1989, found: 418.1896. [α] 20 D = +54.77 (c = 1.39, CH2Cl2). The product was analyzed by HPLC to determine the enantiomeric excess: 99% ee. (CHIRALPAK IC, hexane / i-PrOH = 90 / 10, detector: 254 nm, T = 25 ℃, flow rate: 1 mL / min), t1(major)= 5.17 min, t2(minor) = 6.07 min.

[0070] Example 10: Preparation of α-aryloxybenzoxazole acetate compound 3j

[0071]

[0072] Under an argon atmosphere, in a dry 10 mL reaction tube equipped with a magnetic stirrer, a carbon electrode was used as the anode and a platinum electrode as the cathode. Nickel acetate (0.01 mmol) and a chiral ligand (0.01 mmol) were added. Then, the corresponding compounds 1a (0.1 mmol), 2j (0.3 mmol), ferrocene (0.01 mmol), cesium carbonate (0.1 mmol), benzoic acid (0.1 mmol), and tetrabutylammonium tetrafluoroborate (…) were weighed and added sequentially. nBu4NBF4 (0.3 mmol) was dissolved in a 2.0:1.0 mixture of dichloromethane and trifluoroethanol (3 mL), followed by the addition of the pre-stirred catalyst solution. Electrolysis was then performed at 25 °C under constant current (2.0 mA) for 24 hours. After complete reaction, the solvent was removed by vacuum distillation, and the α-aryloxybenzoxazole acetate compound 3j (80% yield, 98% ee) was obtained by column chromatography using a 40:1 volume ratio of petroleum ether and ethyl acetate as eluent.

[0073] 1 H NMR (500 MHz, CDCl3) δ 7.82-7.77 (m, 1H), 7.61-7.57 (m, 1H), 7.53-7.47 (m, 2H), 7.43 -7.34 (m, 6H), 7.31-7.26 (m, 1H), 7.00-6.94 (m, 2H), 2.10(s, 3H), 1.45 (s, 9H). 13 C NMR (125 MHz, CDCl3) δ 167.9, 163.7, 154.2, 151.0,140.7, 140.5, 136.5, 128.8, 128.0, 127.1, 126.9, 125.9, 124.8, 120.8, 120.8,111.2, 83.8, 80.3, 27.9, 22.1. ESI-MS: calculated [C 26 H 25 NO4 + Na] + : 438.1676, found: 438.1681. [α] 20 D = 57.96 (c = 0.89, CH2Cl2). The product was analyzed byHPLC to determine the enantiomeric excess: 98% ee. (CHIRALPAK IC, hexane / i-PrOH = 90 / 10, detector: 254 nm, T = 25 ℃, flow rate: 1 mL / min), t1(major) =5.30 min, t2(minor) = 6.10 min.

[0074] Example 11: Preparation of α-aryloxybenzoxazole acetate compound 3k

[0075]

[0076] Under an argon atmosphere, in a dry 10 mL reaction tube equipped with a magnetic stirrer, a carbon electrode was used as the anode and a platinum electrode as the cathode. Nickel acetate (0.01 mmol) and a chiral ligand (0.01 mmol) were added. The corresponding compounds 1a (0.1 mmol), 2k (0.3 mmol), ferrocene (0.01 mmol), cesium carbonate (0.1 mmol), benzoic acid (0.1 mmol), and tetrabutylammonium tetrafluoroborate (…) were then weighed and added sequentially. n Bu4NBF4 (0.3 mmol) was dissolved in a 2.0:1.0 mixture of dichloromethane and trifluoroethanol (3 mL), followed by the addition of the pre-stirred catalyst solution. Electrolysis was then performed at 25 °C under constant current (2.0 mA) for 24 hours. After complete reaction, the solvent was removed by vacuum distillation, and the α-aryloxybenzoxazole acetate compound 3K (50% yield, 96% ee) was obtained by column chromatography using a 40:1 volume ratio of petroleum ether and ethyl acetate as eluent.

[0077] 1 H NMR (400 MHz, CDCl3) δ 7.76 (dd, J = 6.8, 2.4 Hz, 1H), 7.63-7.57(m, 1H), 7.37 (tt, J = 7.5, 5.8 Hz, 2H), 7.05-6.99 (m, 1H), 6.95 (dd, J =7.8, 1.6 Hz, 1H), 6.84-6.73 (m, 2H), 3.48 (s, 3H), 1.96 (s, 3H), 1.46 (s,9H). 13 C NMR (100 MHz, CDCl3) δ 168.2, 164.2, 153.1, 151.1, 143.3, 140.8,125.7, 125.3, 124.6, 123.7, 120.7, 120.6, 112.4, 111.1, 83.4, 80.5, 55.8,27.9, 20.9. ESI-MS: calculated [C 21 H 23 NO5 + Na] + : 392.1468, found: 392.1472.[α] 20 D= +71.23 (c = 0.88, CH2Cl2). The product was analyzed by HPLC to determine the enantiomeric excess: 96% ee. (CHIRALPAK IC, hexane / i-PrOH = 90 / 10, detector: 254 nm, T = 25 ℃, flow rate: 1 mL / min), t1(major) = 7.52 min,t2(minor) = 9.02 min.

[0078] Example 12: Preparation of α-aryloxybenzoxazole acetate compound 3l

[0079]

[0080] Under an argon atmosphere, in a dry 10 mL reaction tube equipped with a magnetic stirrer, a carbon electrode was used as the anode and a platinum electrode as the cathode. Nickel acetate (0.01 mmol) and a chiral ligand (0.01 mmol) were added. The corresponding compounds 1a (0.1 mmol), 2l (0.3 mmol), ferrocene (0.01 mmol), cesium carbonate (0.1 mmol), benzoic acid (0.1 mmol), and tetrabutylammonium tetrafluoroborate (…) were then weighed and added sequentially. n Bu4NBF4 (0.3 mmol) was dissolved in a 2.0:1.0 mixture of dichloromethane and trifluoroethanol (3 mL), followed by the addition of the pre-stirred catalyst solution. Electrolysis was then performed at 25 °C under constant current (2.0 mA) for 24 hours. After complete reaction, the solvent was removed by vacuum distillation, and the resulting α-aryloxybenzoxazole acetate compound 31 (76% yield, 99% ee) was obtained by column chromatography using a 40:1 volume ratio of petroleum ether and ethyl acetate as eluent.

[0081] 1 H NMR (400 MHz, CDCl3) δ 7.82-7.72 (m, 1H), 7.62-7.53 (m, 1H), 7.43-7.31 (m, 2H), 6.89 (d, J = 8.2 Hz, 1H), 6.72 (d, J = 2.6 Hz, 1H), 6.57 (dd, J= 8.2, 2.7 Hz, 1H), 2.14 (s, 3H), 2.12 (s, 3H), 2.01 (s, 3H), 1.44 (s, 9H).13 C NMR (100 MHz, CDCl3) δ 168.2, 164.0, 152.4, 151.0, 140.7, 137.6, 131.9,130.1, 125.8, 124.7, 122.4, 120.8, 117.9, 111.1, 83.6, 80.1, 27.9, 21.7,19.9, 19.0. ESI-MS: calculated [C 22 H 25 NO4 + Na] + : 390.1676, found: 390.1684.[α] 20 D = +73.8 (c = 0.99, CH2Cl2). The product was analyzed by HPLC to determine the enantiomeric excess: 99% ee. (CHIRALPAK IC, hexane / i-PrOH = 90 / 10, detector: 254 nm, T = 25 ℃, flow rate: 1 mL / min), t1(major) = 5.32 min,t2(minor) = 6.38 min.

[0082] Example 13: Preparation of α-aryloxybenzoxazole acetate compound 3m

[0083]

[0084] Under an argon atmosphere, in a dry 10 mL reaction tube equipped with a magnetic stirrer, a carbon electrode was used as the anode and a platinum electrode as the cathode. Nickel acetate (0.01 mmol) and a chiral ligand (0.01 mmol) were added. The corresponding compounds 1a (0.1 mmol), 2m (0.3 mmol), ferrocene (0.01 mmol), cesium carbonate (0.1 mmol), benzoic acid (0.1 mmol), and tetrabutylammonium tetrafluoroborate (…) were then weighed and added sequentially. nBu4NBF4 (0.3 mmol) was dissolved in a 2.0:1.0 mixture of dichloromethane and trifluoroethanol (3 mL), followed by the addition of the pre-stirred catalyst solution. Electrolysis was then performed at 25 °C under constant current (2.0 mA) for 24 hours. After complete reaction, the solvent was removed by vacuum distillation, and the α-aryloxybenzoxazole acetate compound 3m (63% yield, 99% ee) was obtained by column chromatography using a 40:1 volume ratio of petroleum ether and ethyl acetate as eluent.

[0085] 1 H NMR (500 MHz, CDCl3) δ 7.82-7.76 (m, 1H), 7.74 (d, J = 8.0 Hz, 1H), 7.69 (d, J = 9.0 Hz, 1H), 7.62-7.54 (m, 4H), 7.42-7.33 (m, 1H), 7.27-7.23 (m,1H), 7.15 (dd, J = 9.0, 2.5 Hz, 1H), 2.13 (s, 3H), 1.44 (s, 9H). 13 C NMR (125MHz, CDCl3) δ 168.0, 163.7, 152.5, 151.0, 140.7, 134.0, 130.2, 129.4, 127.7,127.3, 126.4, 125.9, 124.8, 121.6, 120.9, 115.5, 111.2, 83.8, 80.4, 27.9,22.2. ESI-MS: calculated [C 24 H 23 NO4 + Na] + : 412.1519, found: 412.1523. [α] 20 D =+39.23 (c = 1.08, CH2Cl2). The product was analyzed by HPLC to determine theenantiomeric excess: 99% ee. (CHIRALPAK IC, hexane / i-PrOH = 90 / 10, detector:254 nm, T = 25 ℃, flow rate: 1 mL / min), t1(major) = 5.02 min, t2(minor) =5.53 min.

[0086] Example 14: Preparation of α-aryloxybenzoxazole acetate compound 3n

[0087]

[0088] Under an argon atmosphere, in a dry 10 mL reaction tube equipped with a magnetic stirrer, a carbon electrode was used as the anode and a platinum electrode as the cathode. Nickel acetate (0.01 mmol) and a chiral ligand (0.01 mmol) were added. The corresponding compounds 1a (0.1 mmol), 2n (0.3 mmol), ferrocene (0.01 mmol), cesium carbonate (0.1 mmol), benzoic acid (0.1 mmol), and tetrabutylammonium tetrafluoroborate (…) were then weighed and added sequentially. n Bu4NBF4 (0.3 mmol) was dissolved in a 2.0:1.0 mixture of dichloromethane and trifluoroethanol (3 mL), followed by the addition of the pre-stirred catalyst solution. Electrolysis was then performed at 25 °C under constant current (2.0 mA) for 24 hours. After complete reaction, the solvent was removed by vacuum distillation, and the α-aryloxybenzoxazole acetate compound 3n was obtained by column chromatography using a 40:1 volume ratio of petroleum ether and ethyl acetate as eluent (63% yield, 99% ee).

[0089] 1 H NMR (400 MHz, CDCl3) δ 7.81-7.73 (m, 1H), 7.61-7.54 (m, 1H), 7.42-7.34 (m, 2H), 7.14 -7.06 (m, 2H), 6.88-6.80 (m, 2H), 2.40 (s, 3H), 2.04 (s,3H), 1.44 (s, 9H). 13 C NMR (100 MHz, CDCl3) δ 167.8, 163.5, 152.6, 150.9,140.6, 132.8, 128.4, 125.9, 124.8, 121.4, 120.8, 111.1, 83.8, 80.3, 27.9,22.0, 16.9. ESI-MS: calculated [C 21 H 23 NO4S + Na] + : 408.1240, found: 408.1232.[α] 20 D= +64.73 (c = 1.00 CH2Cl2). The product was analyzed by HPLC to determine the enantiomeric excess: 99% ee. (CHIRALPAK IA, hexane / i-PrOH = 90 / 10, detector: 254 nm, T = 25 ℃, flow rate: 1 mL / min), t1(minor) = 5.75 min,t2(major) = 6.82 min.

[0090] Example 15: Preparation of α-aryloxybenzoxazole acetate compound 3o

[0091]

[0092] Under an argon atmosphere, in a dry 10 mL reaction tube equipped with a magnetic stirrer, a carbon electrode was used as the anode and a platinum electrode as the cathode. Nickel acetate (0.01 mmol) and a chiral ligand (0.01 mmol) were added. The corresponding compounds 1a (0.1 mmol), 2o (0.3 mmol), ferrocene (0.01 mmol), cesium carbonate (0.1 mmol), benzoic acid (0.1 mmol), and tetrabutylammonium tetrafluoroborate (…) were then weighed and added sequentially. n Bu4NBF4 (0.3 mmol) was dissolved in a 2.0:1.0 mixture of dichloromethane and trifluoroethanol (3 mL), followed by the addition of the pre-stirred catalyst solution. Electrolysis was then performed at 25 °C under constant current (2.0 mA) for 24 hours. After complete reaction, the solvent was removed by vacuum distillation, and the α-aryloxybenzoxazole acetate compound 3o (78% yield, 99% ee) was obtained by column chromatography using a 40:1 volume ratio of petroleum ether and ethyl acetate as eluent.

[0093] 1H NMR (400 MHz, CDCl3) δ 7.85 (ddd, J = 7.5, 1.5, 0.7 Hz, 1H), 7.73 (ddd, J = 7.7, 1.4, 0.7 Hz, 1H), 7.67-7.62 (m, 2H), 7.46-7.36 (m, 2H), 7.36-7.31 (m, 1H), 7.31-7.23 (m, 1H), 7.14 (t, J = 7.8 Hz, 1H), 7.07-7.02 (m, 1H), 2.11 (s, 3H), 1.47 (s, 9H). 13 C NMR (100 MHz, CDCl3) δ 167.7, 163.5, 156.1,151.3, 148.4, 140.8, 139.5, 127.3, 126.5, 125.9, 124.7, 124.1, 123.1, 122.9,120.8, 120.7, 120.3, 116.6, 111.7, 111.2, 83.8, 80.9, 27.9, 21.5. ESI-MS:calculated [C 26 H 23 NO5 + Na] + : 452.1468, found: 452.1467. [α] 20 D = 31.84 (c =1.15, CH2Cl2). The product was analyzed by HPLC to determine the enantiomericexcess: 99% ee. (CHIRALPAK IC, hexane / i-PrOH = 90 / 10, detector: 254 nm, T =25 ℃, flow rate: 1 mL / min), t1(major) = 5.23 min, t2(minor) = 5.76 min.

[0094] Example 16: Preparation of α-aryloxybenzoxazole acetate compound 3p

[0095]

[0096] Under an argon atmosphere, in a dry 10 mL reaction tube equipped with a magnetic stirrer, a carbon electrode was used as the anode and a platinum electrode as the cathode. Nickel acetate (0.01 mmol) and a chiral ligand (0.01 mmol) were added. The corresponding compounds 1b (0.1 mmol), 2h (0.3 mmol), ferrocene (0.01 mmol), cesium carbonate (0.1 mmol), benzoic acid (0.1 mmol), and tetrabutylammonium tetrafluoroborate (…) were then weighed and added sequentially. n Bu4NBF4 (0.3 mmol) was dissolved in a 2.0:1.0 mixture of dichloromethane and trifluoroethanol (3 mL), followed by the addition of the pre-stirred catalyst solution. Electrolysis was then performed at 25 °C under constant current (2.0 mA) for 24 hours. After complete reaction, the solvent was removed by vacuum distillation, and the α-aryloxybenzoxazole acetate compound 3p (72% yield, 94% ee) was obtained by column chromatography using a 40:1 volume ratio of petroleum ether and ethyl acetate as eluent.

[0097] 1 H NMR (400 MHz, CDCl3) δ 7.80-7.75 (m, 1H), 7.59 (dd, J = 7.3, 1.8Hz, 1H), 7.40 (pd, J = 7.4, 1.5 Hz, 2H), 6.83-6.77 (m, 2H), 6.73-6.67 (m,2H), 3.86 (s, 3H), 3.71 (s, 3H), 2.02 (s, 3H). 13 C NMR (100 MHz, CDCl3) δ169.9, 163.1, 156.4, 151.0, 147.4, 140.5, 126.1, 124.9, 123.1, 120.9, 114.4,111.3, 80.5, 77.5, 77.2, 76.8, 55.6, 53.6, 21.6. ESI-MS: calculated [C 18 H 17 NO5+ Na] + : 350.0999, found: 350.0998. [α] 20 D= +116.69 (c = 0.46, CH2Cl2). Theproduct was analyzed by HPLC to determine the enantiomeric excess: 94% ee.(CHIRALPAK IC, hexane / i-PrOH = 80 / 20, detector: 254 nm, T = 25 ℃, flow rate:1 mL / min), t1(major) = 7.96 min, t2(minor) = 10.24 min.

[0098] Example 17: Preparation of α-aryloxybenzoxazole acetate compound 3q

[0099]

[0100] Under an argon atmosphere, in a dry 10 mL reaction tube equipped with a magnetic stirrer, a carbon electrode was used as the anode and a platinum electrode as the cathode. Nickel acetate (0.01 mmol) and a chiral ligand (0.01 mmol) were added. The corresponding compounds 1c (0.1 mmol), 2h (0.3 mmol), ferrocene (0.01 mmol), cesium carbonate (0.1 mmol), benzoic acid (0.1 mmol), and tetrabutylammonium tetrafluoroborate (…) were weighed and added sequentially. n Bu4NBF4 (0.3 mmol) was dissolved in a 2.0:1.0 mixture of dichloromethane and trifluoroethanol (3 mL), followed by the addition of the pre-stirred catalyst solution. Electrolysis was then performed at 25 °C under constant current (2.0 mA) for 24 hours. After complete reaction, the solvent was removed by vacuum distillation, and the α-aryloxybenzoxazole acetate compound 3q (70% yield, 98% ee) was obtained by column chromatography using a 40:1 volume ratio of petroleum ether and ethyl acetate as eluent.

[0101] 1 H NMR (400 MHz, CDCl3) δ 7.79-7.74 (m, 1H), 7.58-7.53 (m, 1H), 7.38(tt, J = 7.4, 5.8 Hz, 2H), 7.31-7.23 (m, 5H), 6.80-6.75 (m, 2H), 6.69-6.63(m, 2H), 5.29 (s, 2H), 3.70 (s, 3H), 2.02 (s, 3H). 13C NMR (100 MHz, CDCl3) δ169.2, 163.1, 156.3, 150.9, 147.5, 140.5, 135.0, 128.6, 128.5, 128.3, 126.1,124.9, 123.0, 120.9, 114.3, 111.2, 80.5, 68.0, 55.6, 21.6. ESI-MS: calculated[C 24 H 21 NO5 + Na] + : 426.1312 found: 426.1311. [α] 20 D = +70.74 (c = 1.12, CH2Cl2).The product was analyzed by HPLC to determine the enantiomeric excess: 98%ee. (CHIRALPAK IC, hexane / i-PrOH = 80 / 20, detector: 256 nm, T = 25 ℃, flowrate: 1 mL / min), t1(major) = 10.79 min, t2(minor) = 13.21 min.

[0102] Example 18: Preparation of α-aryloxybenzoxazole acetate compound 3r

[0103]

[0104] Under an argon atmosphere, in a dry 10 mL reaction tube equipped with a magnetic stirrer, a carbon electrode was used as the anode and a platinum electrode as the cathode. Nickel acetate (0.01 mmol) and a chiral ligand (0.01 mmol) were added. The corresponding compounds 1d (0.1 mmol), 2a (0.3 mmol), ferrocene (0.01 mmol), cesium carbonate (0.1 mmol), benzoic acid (0.1 mmol), and tetrabutylammonium tetrafluoroborate (…) were weighed and added sequentially. nBu4NBF4 (0.3 mmol) was dissolved in a 2.0:1.0 mixture of dichloromethane and trifluoroethanol (3 mL), followed by the addition of the pre-stirred catalyst solution. Electrolysis was then performed at 25 °C under constant current (2.0 mA) for 24 hours. After complete reaction, the solvent was removed by vacuum distillation, and the α-aryloxybenzoxazole acetate compound 3r (76% yield, 99% ee) was obtained by column chromatography using a 40:1 volume ratio of petroleum ether and ethyl acetate as eluent.

[0105] 1 H NMR (400 MHz, CDCl3) δ 7.75 (d, J = 2.1 Hz, 1H), 7.50 (d, J = 8.7Hz, 1H), 7.36 (dd, J = 8.7, 2.1 Hz, 1H), 7.01-6.95 (m, 2H), 6.76 (d, J = 8.5Hz, 2H), 2.24 (s, 3H), 2.00 (s, 3H), 1.43 (s, 9H). 13 C NMR (100 MHz, CDCl3) δ167.8, 165.3, 152.1, 149.5, 141.8, 133.4, 130.3, 129.9, 126.3, 120.8, 111.9,83.8, 80.2, 27.9, 21.8, 20.8. ESI-MS: calculated [C 21 H 22 ClNO4 + Na] + : 410.1129, found: 410.1132. [α] 20 D = +70.59 (c = 0.68, CH2Cl2). The product was analyzed by HPLC to determine the enantiomeric excess: 99% ee. (CHIRALPAK IC, hexane / i-PrOH = 95 / 5, detector: 254 nm, T = 25 ℃, flow rate: 1 mL / min), t1(major) =5.72 min, t2(minor) = 7.22 min.

[0106] Example 19: Preparation of α-aryloxybenzoxazole acetate compound 3s

[0107]

[0108] Under an argon atmosphere, in a dry 10 mL reaction tube equipped with a magnetic stirrer, a carbon electrode was used as the anode and a platinum electrode as the cathode. Nickel acetate (0.01 mmol) and a chiral ligand (0.01 mmol) were added. The corresponding compounds 1f (0.1 mmol), 2a (0.3 mmol), ferrocene (0.01 mmol), cesium carbonate (0.1 mmol), benzoic acid (0.1 mmol), and tetrabutylammonium tetrafluoroborate (…) were weighed and added sequentially. n Bu4NBF4 (0.3 mmol) was dissolved in a 2.0:1.0 mixture of dichloromethane and trifluoroethanol (3 mL), followed by the addition of the pre-stirred catalyst solution. Electrolysis was then performed at 25 °C under constant current (2.0 mA) for 24 hours. After complete reaction, the solvent was removed by vacuum distillation, and the α-aryloxybenzoxazole acetate compound 3S (71% yield, 98% ee) was obtained by column chromatography using a 40:1 volume ratio of petroleum ether and ethyl acetate as eluent.

[0109] 1 H NMR (400 MHz, CDCl3) δ 7.68 (d, J = 8.5 Hz, 1H), 7.59 (d, J = 1.9Hz, 1H), 7.35 (dd, J = 8.5, 1.9 Hz, 1H), 6.97 (d, J = 8.1 Hz, 2H), 6.78-6.73(m, 2H), 2.24 (s, 3H), 2.00 (s, 3H), 1.44 (s, 9H). 13 C NMR (100 MHz, CDCl3) δ167.9, 164.6, 152.1, 151.1, 139.4, 133.4, 131.6, 129.9, 125.6, 121.4, 120.9,111.8, 83.8, 80.2, 27.9, 21.8, 20.8. ESI-MS: calculated [C 21 H 22 ClNO4 + Na] + :410.1129, found: 410.1130. [α] 20 D= +64.52 (c = 0.63 CH2Cl2). The product wasanalyzed by HPLC to determine the enantiomeric excess: 98% ee. (CHIRALPAK IC,hexane / i-PrOH = 95 / 5, detector: 254 nm, T = 25 ℃, flow rate: 1 mL / min), t1(major) = 5.72 min, t2(minor) = 7.36 min.

[0110] Example 20: Preparation of α-aryloxybenzoxazole acetate compound 3t

[0111]

[0112] Under an argon atmosphere, in a dry 10 mL reaction tube equipped with a magnetic stirrer, a carbon electrode was used as the anode and a platinum electrode as the cathode. Nickel acetate (0.01 mmol) and a chiral ligand (0.01 mmol) were added. The corresponding compounds were then weighed and added sequentially: 1 g (0.1 mmol), 2 h (0.3 mmol), ferrocene (0.01 mmol), cesium carbonate (0.1 mmol), benzoic acid (0.1 mmol), and tetrabutylammonium tetrafluoroborate (…). n Bu4NBF4 (0.3 mmol) was dissolved in a 2.0:1.0 mixture of dichloromethane and trifluoroethanol (3 mL), followed by the addition of the pre-stirred catalyst solution. Electrolysis was then performed at 25 °C under constant current (2.0 mA) for 24 hours. After complete reaction, the solvent was removed by vacuum distillation, and the α-aryloxybenzoxazole acetate compound 3t (71% yield, 95% ee) was obtained by column chromatography using a 40:1 volume ratio of petroleum ether and ethyl acetate as eluent.

[0113] 1 H NMR (500 MHz, CDCl3) δ 7.79-7.73 (m, 1H), 7.58-7.53 (m, 1H), 7.41-7.32 (m, 2H), 6.81 -6.75 (m, 2H), 6.69-6.63 (m, 2H), 3.69 (s, 3H), 2.53(hept, J = 7.2 Hz, 2H), 1.42 (s, 9H), 1.10 (t, J = 7.4 Hz, 3H). 13C NMR (125MHz, CDCl3) δ 167.1, 163.3, 155.6, 150.7, 148.5, 140.6, 125.8, 124.7, 121.5,120.8, 114.2, 111.1, 83.5, 83.5, 55.6, 28.2, 27.9, 7.8. ESI-MS: calculated[C 22 H 25 NO5 + Na] + : 406.1625, found: 406.1634. [α] 20 D = 76.42 (c = 0.69, CH2Cl2).The product was analyzed by HPLC to determine the enantiomeric excess: 95%ee. (CHIRALPAK IA, hexane / i-PrOH = 80 / 20, detector: 254 nm, T = 25 ℃, flowrate: 1 mL / min), t1(minor) = 5.24 min, t2(major) = 5.94 min.

[0114] Example 21: Preparation of α-aryloxybenzoxazole acetate compound 3u

[0115]

[0116] Under an argon atmosphere, in a dry 10 mL reaction tube equipped with a magnetic stirrer, a carbon electrode was used as the anode and a platinum electrode as the cathode. Nickel acetate (0.01 mmol) and a chiral ligand (0.01 mmol) were added. The corresponding compounds 1h (0.1 mmol), 2a (0.3 mmol), ferrocene (0.01 mmol), cesium carbonate (0.1 mmol), benzoic acid (0.1 mmol), and tetrabutylammonium tetrafluoroborate (…) were weighed and added sequentially. nBu4NBF4 (0.3 mmol) was dissolved in a 2.0:1.0 mixture of dichloromethane and trifluoroethanol (3 mL), followed by the addition of the pre-stirred catalyst solution. Electrolysis was then performed at 25 °C under constant current (2.0 mA) for 24 hours. After complete reaction, the solvent was removed by vacuum distillation, and the α-aryloxybenzoxazole acetate compound 3u (50% yield, 90% ee) was obtained by column chromatography using a 40:1 volume ratio of petroleum ether and ethyl acetate as eluent.

[0117] 1 H NMR (400 MHz, CDCl3) δ 7.80-7.73 (m, 1H), 7.59-7.52 (m, 1H), 7.43-7.32 (m, 2H), 7.30 -7.21 (m, 2H), 7.21-7.11 (m, 3H), 6.99-6.92 (m, 2H), 6.84-6.76 (m, 2H), 2.93-2.71 (m, 4H), 2.22 (s, 3H), 1.44 (s, 9H). 13 C NMR (100 MHz, CDCl3) δ 167.0, 163.1, 152.7, 150.8, 140.9, 140.6, 132.7, 129.8, 128.6,128.5, 126.2, 125.9, 124.8, 120.9, 119.5, 111.1, 83.8, 82.4, 37.1, 29.7,27.9, 20.7. ESI-MS: calculated [C 28 H 29 NO4 + Na] + : 466.1989, found: 466.1990.[α] 20 D = +44.34 (c = 0.39, CH2Cl2). The product was analyzed by HPLC to determine the enantiomeric excess: 90% ee. (CHIRALPAK IA, hexane / i-PrOH = 95 / 5, detector: 245 nm, T = 25 ℃, flow rate: 1 mL / min), t1(minor) = 6.01 min, t2(major) = 8.62 min.

[0118] Variable control experiment:

[0119] All conditions in this experiment were modified from the specific operations in Example 1. The results and the corresponding modifications are shown in the table below:

[0120]

[0121]

Claims

1. A chiral α-aryloxybenzoxazole acetate compound, characterized in that... Optically active compounds having the following formula I, including stereoisomers thereof having the same chemical formula: ； wherein: * represents a chiral carbon atom; Ar 1 and Ar 2 are each independently selected from phenyl or a substituted aromatic ring, the substituents of which are halogen, a heteroatom, a C1-C 10 alkyl group or a C1-C 10 alkoxy group; R 1 and R 2 are each independently selected from a C 1-10 hydrocarbyl or hydrocarboxy group.

2. The asymmetric preparation method of the chiral α-aryloxy benzoxazole acetic acid ester compound in claim 1, characterized in that: The compound 1 and the compound 2 are used as starting materials, a complex of a chiral ligand and a metal catalyst precursor is used as a reaction catalyst, the reaction is carried out in an electrochemical oxidation-reduction reaction system in an organic solvent at a temperature of 0-60℃, and the target product I is obtained after separation and purification. The synthesis route is as follows: ； wherein: * represents a chiral carbon atom; Ar 1 and Ar 2 are each independently selected from phenyl or a substituted aromatic ring, the substituents of which are halogen, heteroatom, C1-C 10 alkyl or C1-C 10 alkoxy; R 1 and R 2 are each independently selected from C 1-10 hydrocarbyl or hydrocarboxy.

3. The method of claim 2, wherein The method comprises the following steps: In an air or inert gas atmosphere, the compound 1, the compound 2, the metal catalyst precursor, the chiral ligand, the ferrocene compound, the acid, the base and the electrolyte are added into a reaction bottle with an electrode, and an organic solvent is added for dissolution, current electrolysis is carried out at 0-60℃ for 24-48 hours, the reaction endpoint is determined by a thin layer chromatography point plate, after the reaction is completed, concentration is carried out, and column chromatography is used for separation to obtain the target product I.

4. The preparation method in claim 3, characterized in that: The metal catalyst precursor is one or two or more of nickel acetate, nickel chloride, nickel bromide, nickel trifluoromethanesulfonate, cobalt acetate, cobalt trifluoromethanesulfonate, bismuth trifluoromethanesulfonate, indium chloride, titanium chloride triisopropoxide, copper tetrafluoroborate tetra(acetonitrile), Raney nickel, nickel acetylacetonate, copper tetrafluoroborate tetra(acetonitrile), lithium iodide, copper tetrafluoroborate tetra(acetonitrile), lithium bromide, cuprous iodide, cuprous chloride, cuprous trifluoromethanesulfonate toluene complex, bis-(1,5-cyclooctadiene) nickel, silver acetate, silver carbonate, zinc dibromide, silver trifluoromethanesulfonate, silver perchlorate, silver tetrafluoroborate, lithium bromide, silver oxide, scandium triflate.

5. The preparation method in claim 3, characterized in that: The chiral ligand is selected from the following compounds: ； wherein: * is a carbon chiral center; n is 1, 2, 3, or 4; R 3 , R 4 , and R 5 are each independently selected from C 1-10 alkyl or aryl; Ar 3 , Ar 4 , and Ar 5 are each independently selected from phenyl or a substituted aromatic ring, the substituents of which are halo, C1-C 10 alkyl, or C1-C 10 alkoxy.

6. The preparation method in claim 3, characterized in that: The ferrocene compound has the following structure: ； wherein: R is selected from hydrogen, halogen, carboxyl, acyl, or a substituted or unsubstituted group selected from C 6 alkyl or C 1-10 alkyl or C 6-20 aryl.

7. The preparation method in claim 3, characterized in that: The acid is one or two or more of sulfuric acid, nitric acid, hydrochloric acid, oxalic acid, phosphoric acid, boric acid, formic acid, acetic acid, trifluoroacetic acid, benzoic acid, substituted benzoic acid, phenylacetic acid.

8. The preparation method in claim 3, characterized in that: The base is one or two or more of triethylamine, ethylenediamine, diisopropylethylamine, lithium bis(trimethylsilyl)amide, potassium bis(trimethylsilyl)amide, cesium carbonate, potassium carbonate, potassium phosphate, sodium hydroxide, potassium hydroxide, sodium tert-butoxide, potassium tert-butoxide, pyridine, quinuclidine or 1,8-diazabicyclo[5.4.0]undec-7-ene.

9. The preparation method in claim 3, characterized in that: The electrolyte is one or more of lithium carbonate, lithium chloride, lithium perchlorate, lithium hexafluorophosphate, lithium bis(trifluoromethanesulfonyl)imide, tetraphenylphosphonium bromide, tetrabutylammonium tetrafluoroborate, tetrabutylammonium hexafluorophosphate, tetraethylammonium hexafluorophosphate, tetramethylammonium hexafluorophosphate, tetrabutylammonium perchlorate, tetraethylammonium perchlorate, tetraethylammonium tetrafluoroborate, tetrabutylammonium chloride, tetrabutylammonium bromide.

10. The preparation method according to any one of claims 3-9, characterized in that: the molar equivalent ratio of the metal catalyst precursor and the chiral ligand is 1:1-1:4; the molar equivalent ratio of the metal catalyst precursor and compound 1 is 1:1-1:30; the molar equivalent ratio of compound 1 and compound 2 is 1:0.33-1:10; the molar equivalent ratio of compound 1 and the ferrocene compound is 1:0.1-1:10; the molar concentration of the acid is 0-1 mol / L; the molar concentration of the base is 0-1 mol / L; the molar concentration of the electrolyte is 0.01-1 mol / L; and the molar concentration of compound 1 in the system is 0.01-1 mol / L.

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