Application of sulfoximine as hydrogen atom transfer catalyst in photocatalytic carbon-carbon bond construction

Abstract

The invention discloses an application of sulfoximine as a hydrogen atom transfer catalyst in photocatalytic carbon-carbon bond construction. The sulfoximine is used for realizing a coupling reaction of a heteroatom ortho-position C-H bond and electron-deficient olefin. The bottleneck that an existing HAT reagent is high in oxidation site, insufficient in structural adjustability and the like is solved, and the heteroatom (N, O, S)-1, 2, 4-triazole-1-carboxylic acid is obtained through a hydrogen atom transfer catalyst based on NH-sulfoximine. A C (sp3)-H bond at the ortho-position of (S, S) is further subjected to a coupling reaction with electron-deficient olefin such as benzyl ester group (-COOBn), diethyl phosphate group (-PO (OEt) 2), bis (t-butyloxycarbonyl) amino methyl ester group, glycidyl ester group, L-menthyl ester group, amino-acid ester derivative group and the like.

Description

Technical Field

[0001] The present invention relates to the technical field of organic synthetic chemistry, and in particular to application of sulfoximine as a hydrogen atom transfer catalyst in photocatalytic carbon-carbon bond construction. Background Art

[0002] In the field of organic synthetic chemistry, the coupling reaction of heteroatom ortho-CH bonds with electron-deficient olefins remains at the core of modern synthetic methodology research due to its unique value in molecular scaffold construction and functionalization. This reaction mode directly activates inert CH bonds, which are difficult to access with traditional strategies, avoiding the tedious pre-functionalization steps and providing an attractive route for the efficient synthesis of complex molecules such as natural products, pharmaceuticals, and functional materials.

[0003] In recent years, breakthroughs have been made in nitrogen-centered hydrogen atom transfer (HAT) reagent systems, such as quinuclidine derivatives, azides, and 1,2,3-triazolium amides. These reagents, with their high electrophilicity, exhibit a certain ability to functionalize aliphatic C-H bonds intermolecularly, enabling the selective activation of inert C-H sites that are difficult to achieve with traditional strategies.

[0004] However, existing HAT reagents have several significant shortcomings. For one thing, their oxidation potential is too high. This is because the molecular structure of the reagent determines the distribution of the electron cloud, requiring a high energy level to excite the reaction. This not only increases the energy consumption and cost of the reaction, but can also lead to side reactions, reducing the selectivity and yield of the reaction. Summary of the Invention

[0005] The present invention aims to overcome the shortcomings of the prior art by providing a method for using a sulfoximine as a hydrogen atom transfer catalyst in photocatalytic carbon-carbon bond construction. Under photocatalytic conditions, a coupling reaction between a heteroatom ortho-C-H bond and an electron-deficient olefin is achieved. The present invention utilizes readily available electron-deficient olefins and heteroatom ortho-C-H bonds as raw materials, eliminating the need for any additives and achieving the coupling reaction via a simple synthetic route. The coupling products synthesized using the present method have promising development potential and application prospects in the fields of organic synthesis and biopharmaceutical materials.

[0006] The technical solutions provided by the present invention are as follows:

[0007] <First Aspect>

[0008] A sulfoximine is used as a hydrogen atom transfer catalyst in photocatalytic carbon-carbon bond construction to achieve the coupling reaction of heteroatom ortho-CH bonds with electron-deficient olefins.

[0009] The heteroatom is one of N, O and S.

[0010] The corresponding substrate of the CH bond at the ortho position of the heteroatom is at least one selected from tetrahydrofuran, tetrahydrothiophene, a piperidine derivative, 1,3-benzodioxolane or corresponding derivatives thereof.

[0011] The general formula of the electron-deficient olefin is CH2=CH-EWG, wherein EWG is an electron-withdrawing group;

[0012] The EWG includes one or more of the following groups: benzyl ester group (-COOBn), diethyl phosphate group (-PO(OEt)2), bis(tert-butyloxycarbonyl)aminomethyl ester group, glycidyl ester group, L-menthyl ester group, and amino acid ester derivative group.

[0013] Preferably, the heteroatom is N or O.

[0014] Preferably, EWG is benzoyl carboxylate (-COOBn).

[0015] <Second Aspect>

[0016] A method for coupling a heteroatom ortho-CH bond with an electron-deficient olefin comprises the following steps:

[0017] S1. Under the protection of an inert gas, a compound containing a heteroatom, an electron-deficient olefin, a photocatalyst, a sulfoximine hydrogen atom transfer catalyst, a base, and a solvent are mixed, and the reaction is carried out under visible light irradiation; the heteroatom is selected from at least one of N, O, and S, and the electron-deficient olefin has an electron-withdrawing group EWG;

[0018] S2, extracting the reaction product of S1 with an organic solvent, washing the organic layer (using brine to wash, mainly to wash away some water-soluble impurities and some residual inorganic salts in the organic layer), and then drying with anhydrous sodium sulfate to absorb moisture in the organic layer;

[0019] S3. The organic layer is concentrated to obtain a crude product; the crude product is purified to obtain the target coupling product.

[0020] The crude product was purified by silica gel column chromatography using petroleum ether / ethyl acetate as eluent to obtain the desired coupling product.

[0021] The structural formula of the coupling product is:

[0022] Wherein: X is one or more of N, O, and S; EWG is one or more selected from the group consisting of benzyl ester (-COOBn), diethyl phosphate (-PO(OEt)2), bis(tert-butyloxycarbonyl)aminomethyl ester, glycidyl ester, L-menthyl ester, and amino acid ester derivative groups.

[0023] Preferably, X is N or O.

[0024] Preferably, EWG is benzoyl carboxylate (-COOBn).

[0025] In S1, the sulfoximine hydrogen atom transfer catalyst is phenylbenzylsulfoximine, and its amount is 10-30% of the molar amount of the reaction substrate. Preferably, the molar concentration of the reaction substrate is 10-20%.

[0026] The structural formula of the phenylbenzyl sulfoximine is as follows:

[0027]

[0028] In S1, the photocatalyst includes 4CzIPN, and its amount is 5-15% of the molar amount of the reaction substrate;

[0029] And / or, the base comprises potassium phosphate trihydrate, and its amount is 1.2-2.0 equivalents based on the molar amount of the reaction substrate.

[0030] In S1, the solvent includes acetonitrile, the reaction temperature is 20-30° C., the illumination condition is blue light with a wavelength of 450-470 nm, and the reaction time is 24-48 hours.

[0031] The general formula of the electron-deficient olefin is CH2=CH-EWG, wherein EWG is selected from one or more of the following groups:

[0032] benzyl ester group (-COOBn), diethyl phosphate group (-PO(OEt)2), bis(tert-butyloxycarbonyl)aminomethyl ester group, glycidyl ester group, L-menthyl ester group, amino acid ester derivative group.

[0033] Preferably, X is N or O.

[0034] Preferably, EWG is benzoyl carboxylate (-COOBn).

[0035] As one embodiment of the present invention, the present invention provides a method for coupling a heteroatom ortho-CH bond with an electron-deficient olefin, comprising the following steps:

[0036] (1) Under nitrogen protection, a Schlenk tube is used as a reaction vessel, a heteroatom-ortho-CH bond substrate and an electron-deficient olefin are put into a reaction solvent, and then a photocatalyst, a sulfoximine hydrogen atom transfer catalyst and a base are added, stirred and mixed at room temperature, and the reaction vessel is placed under blue light irradiation to react;

[0037] (2) Monitor by thin layer chromatography until the starting material disappears completely, add ethyl acetate to the reaction mixture, wash the resulting reaction solution with brine, and dry it over anhydrous sodium sulfate; concentrate the organic layer to obtain a crude product;

[0038] (3) The crude product was purified by silica gel column chromatography using petroleum ether / ethyl acetate as eluent to obtain the desired coupling product.

[0039] Preferably, in step (1), the structural formula of the coupling product is:

[0040] Wherein: X is selected from one or more of N, O, and S; EWG is selected from one or more of benzyl ester, phosphate, bis(tert-butoxycarbonyl)aminomethyl ester, glycidyl ester, L-menthyl ester, and amino acid derivatives.

[0041] Preferably, X is N or O.

[0042] Preferably, EWG is benzoyl carboxylate (-COOBn).

[0043] Preferably, in step (1), the ratio of the electron-deficient olefin to the reaction solvent (acetonitrile solvent) is 0.1-0.3 mmol: 1.0-2.0 mL.

[0044] Preferably, in step (2), the stirring system is irradiated with blue light (450-470 nm) at room temperature for 24-48 hours.

[0045] Preferably, in step (3), the volume ratio of petroleum ether to ethyl acetate is 10:1.

[0046] The reaction mechanism adopted by the method of the present invention is exemplified as follows:

[0047]

[0048] Wherein: X is at least one of N, O, and S; EWG is one or more of benzyl ester, phosphate, bis(tert-butoxycarbonyl)aminomethyl ester, glycidyl ester, L-menthyl ester, and amino acid derivative groups;

[0049] The HAT structural formula is as follows:

[0050]

[0051] 4CzIPN is a photocatalyst.

[0052] Using readily available sulfides as raw materials, a novel sulfoximine hydrogen atom transfer catalyst was used to successfully achieve an efficient coupling reaction between heteroatom (N, O, S) ortho-CH and electron-deficient olefins.

[0053] <Third Aspect>

[0054] The compound A prepared by the preparation method described in the second aspect has the following general structural formula:

[0055]

[0056] Wherein, X is selected from O, S, and N; and EWG is selected from benzyl ester group (-COOBn), diethyl phosphate group (-PO(OEt)2), bis(tert-butyloxycarbonyl)aminomethyl ester group, glycidyl ester group, L-menthyl ester group, and amino acid ester derivative group.

[0057] The compound A is selected from any of the following substances: benzyl 3-(tetrahydrofuran-2-yl)propionate, diethyl 2-(tetrahydrofuran-2-yl)ethyl)phosphonate, methyl 2-(bis(tert-butoxycarbonyl)amino)-3-(tetrahydrofuran-2-yl)propionate, oxirane-2-ylmethyl 3-(benzo[d][1,3]dioxol-2-yl)-2-methylpropanoate, tert-butyl 2-(3-(benzyloxy)-3-oxopropyl)piperidine-1-carboxylate, benzyl 3-(tetrahydrothiophen-2-yl)propionate, (1S,6R)-2-isopropyl-6-methylcyclohexyl 3-(tetrahydrofuran-2-yl)propionate, and ethyl (3-(benzo[d][1,3]dioxolan-2-yl)propionyl)-L-leucinate.

[0058] Compared with the prior art, the present invention has the following outstanding substantive features and significant advantages:

[0059] 1. The present invention utilizes inexpensive and readily available sulfide raw materials to successfully synthesize the structurally simple and readily available NH-sulfoximine as a novel hydrogen atom transfer catalyst. Without the addition of sulfoximine as a hydrogen atom transfer reagent, the target product was obtained with a yield of only 13%. However, when NH-sulfoximine was added to the reaction system, the reaction yield significantly increased to 85%, achieving efficient coupling of heteroatom ortho-CH bonds with electron-deficient olefins.

[0060] 2. The coupling product synthesized by the method of the present invention has good development potential and application prospects in the fields of organic synthesis, biomedicine and materials. BRIEF DESCRIPTION OF THE DRAWINGS

[0061] Other features, objects and advantages of the present invention will become more apparent upon reading the detailed description of non-limiting embodiments with reference to the following drawings:

[0062] Figure 1 Benzyl 3-(tetrahydrofuran-2-yl)propionate 1 H NMR.

[0063] Figure 2 Benzyl 3-(tetrahydrofuran-2-yl)propionate 13 C NMR.

[0064] Figure 3 2-(tetrahydrofuran-2-yl)ethyl)phosphonic acid diethyl ester 1 H NMR.

[0065] Figure 4 2-(tetrahydrofuran-2-yl)ethyl)phosphonic acid diethyl ester 13 C NMR.

[0066] Figure 5 methyl 2-(bis(tert-butoxycarbonyl)amino)-3-(tetrahydrofuran-2-yl)propionate 1 H NMR.

[0067] Figure 6 methyl 2-(bis(tert-butoxycarbonyl)amino)-3-(tetrahydrofuran-2-yl)propionate 13 C NMR.

[0068] Figure 7 Oxiran-2-ylmethyl 3-(benzo[d][1,3]dioxol-2-yl)-2-methylpropionate 1 HNMR.

[0069] Figure 8 Oxiran-2-ylmethyl 3-(benzo[d][1,3]dioxol-2-yl)-2-methylpropionate 13 CNMR.

[0070] Figure 9 tert-Butyl 2-(3-(benzyloxy)-3-oxopropyl)piperidine-1-carboxylate 1 HNMR.

[0071] Figure 10 tert-Butyl 2-(3-(benzyloxy)-3-oxopropyl)piperidine-1-carboxylate 13 C NMR.

[0072] Figure 11 Benzyl 3-(tetrahydrothiophen-2-yl)propionate 1 HNMR.

[0073] Figure 12 Benzyl 3-(tetrahydrothiophen-2-yl)propionate 13 C NMR.

[0074] Figure 13 (1S,6R)-2-isopropyl-6-methylcyclohexyl 3-(tetrahydrofuran-2-yl) propionate 1 HNMR.

[0075] Figure 14(1S,6R)-2-isopropyl-6-methylcyclohexyl 3-(tetrahydrofuran-2-yl) propionate 13 C NMR.

[0076] Figure 15 (3-(Benzo[d][1,3]dioxolan-2-yl)propionyl)-L-leucine ethyl ester 1 H NMR.

[0077] Figure 16 (3-(Benzo[d][1,3]dioxolan-2-yl)propionyl)-L-leucine ethyl ester 13 C NMR. DETAILED DESCRIPTION

[0078] The present invention will be described in detail below with reference to the examples. The following examples will help those skilled in the art to further understand the present invention, but are not intended to limit the present invention in any form. It should be noted that those skilled in the art may make several adjustments and improvements without departing from the scope of the present invention. These all fall within the scope of protection of the present invention.

[0079] Example 1

[0080] A method for preparing benzyl 3-(tetrahydrofuran-2-yl)propionate comprises the following steps:

[0081] (1) Under nitrogen protection, tetrahydrofuran (288.5 mg, 4.0 mmol), benzyl acrylate (32.4 mg, 0.2 mmol), 4CzIPN (15.8 mg, 10 mol%), phenylbenzylsulfoximine (9.3 mg, 20 mol%), potassium phosphate trihydrate (79.8 mg, 0.3 mmol) and acetonitrile (1.5 mL) were added sequentially to a 10 mL Schlenk tube and stirred at room temperature under blue light (450-470 nm).

[0082] (2) After stirring for 36 h, ethyl acetate (5.0 mL) was added to the reaction mixture, and the resulting solution was washed with brine (10.0 mL) and dried over anhydrous sodium sulfate; the organic layer was concentrated on a rotary evaporator to obtain a crude product;

[0083] (3) The crude product was purified by silica gel column chromatography using a mixed solvent of petroleum ether and ethyl acetate in a volume ratio of 30:1 as the eluent to obtain a colorless oily substance (40.0 mg, 85% yield), namely, benzyl 3-(tetrahydrofuran-2-yl)propionate, with the structural formula:

[0084] The basic parameters of the compound are as follows:

[0085] 1 H NMR (400 MHz, CDCl3): δ7.37–7.30 (m, 5H), 5.12 (s, 2H), 3.87–3.79 (m, 2H), 3.73–3.67 (m, 1H), 2.58–2.37 (m, 2H), 2.02–1.94 (m, 1H), 1.91–1.81 (m, 4H), 1.51–1.42 (m, 1H); the spectrum is shown in Figure 2. Figure 1 ;

[0086] 13 C NMR (101MHz,CDCl3):δ173.6,136.2,128.7,128.3,78.3,67.8,66.3,31.3,30.8,25.8; spectrum as shown Figure 2 .

[0087] Example 2

[0088] A method for preparing diethyl 2-(tetrahydrofuran-2-yl)ethyl)phosphonate comprises the following steps:

[0089] (1) Under nitrogen protection, tetrahydrofuran (288.5 mg, 4.0 mmol), diethyl vinyl phosphate (32.8 mg, 0.2 mmol), 4CzIPN (15.8 mg, 10 mol%), phenylbenzylsulfoximine (9.3 mg, 20 mol%), potassium phosphate trihydrate (79.8 mg, 0.3 mmol) and acetonitrile (1.5 mL) were added sequentially to a 10 mL Schlenk tube and stirred at room temperature under blue light (450-470 nm).

[0090] (2) After stirring for 36 h, ethyl acetate (5.0 mL) was added to the reaction mixture, and the resulting solution was washed with brine (10.0 mL) and dried over anhydrous sodium sulfate; the organic layer was concentrated on a rotary evaporator to obtain a crude product;

[0091] (3) The crude product was purified by silica gel column chromatography using a mixed solvent of petroleum ether and ethyl acetate in a volume ratio of 2:1 as the eluent to obtain a colorless oily product (23.9 mg, 51% yield), namely, diethyl 2-(tetrahydrofuran-2-yl)ethyl)phosphonate, with the structural formula:

[0092] The basic parameters of the compound are as follows:

[0093] 1H NMR (400 MHz, CDCl3): δ4.12–4.01 (m, 4H), 3.85–3.78 (m, 2H), 3.72–3.67 (m, 1H), 2.00–1.69 (m, 7H), 1.50–1.40 (m, 1H), 1.29 (t, J = 7.1 Hz, 6H); the spectrum is shown in Figure 2. Figure 3 ;

[0094] 13 C NMR (101MHz,CDCl3):δ79.0,67.9,61.6(3),61.5(7),31.1,28.5,25.8,23.2,21.8,16.5; spectrum as shown Figure 4 .

[0095] Example 3

[0096] A method for preparing methyl 2-(bis(tert-butoxycarbonyl)amino)-3-(tetrahydrofuran-2-yl)propionate comprises the following steps:

[0097] (1) Under nitrogen protection, tetrahydrofuran (288.5 mg, 4.0 mmol), methyl 2-(bis(tert-butoxycarbonyl)amino)acrylate (60.2 mg, 0.2 mmol), 4CzIPN (15.8 mg, 10 mol%), phenylbenzylsulfoximine (9.3 mg, 20 mol%), potassium phosphate trihydrate (79.8 mg, 0.3 mmol) and acetonitrile (1.5 mL) were added sequentially to a 10 mL Schlenk tube and stirred at room temperature under blue light (450-470 nm).

[0098] (2) After stirring for 36 h, ethyl acetate (5.0 mL) was added to the reaction mixture. The resulting solution was washed with brine (10.0 mL) and dried over anhydrous sodium sulfate. The organic layer was concentrated on a rotary evaporator to obtain a crude product.

[0099] (3) The crude product was purified by silica gel column chromatography using a mixed solvent of petroleum ether and ethyl acetate in a volume ratio of 10:1 as the eluent to obtain a colorless oily substance (dr = 1:1.5, diastereomers, 57.4 mg, yield 75%), namely methyl 2-(bis(tert-butoxycarbonyl)amino)-3-(tetrahydrofuran-2-yl)propanoate, with the structural formula:

[0100] The basic parameters of the compound are as follows:

[0101] 1H NMR (400 MHz, CDCl3): δ5.09–5.05 (m, 0.55H), 5.03–5.01 (m, 0.35H), 3.98–3.91 (m, 0.37H), 3.86–3.76 (m, 1.56H), 3.71–3.63 (m, 4H), 2.36–2.22 (m, 1H), 2.09–1.91 (m, 2H), 1.90–1.77 (m, 2H), 1.46 (s, 19H); the spectrum is shown in Figure 2. Figure 5

[0102] 13 C NMR (101MHz,CDCl3):δ171.6,171.4,152.0(4),151.9(7),83.1,76.8,75.6,67.7,67.5,56.3,56.2,52.3,52.2,36.5,36.0,31.6,31.4,28.0(5),28.0(0),25.8,25.5; spectrum as shown Figure 6 .

[0103] Example 4

[0104] A method for preparing oxiran-2-ylmethyl 3-(benzo[d][1,3]dioxol-2-yl)-2-methylpropionate comprises the following steps:

[0105] (1) Under nitrogen protection, 1,3-benzoxane (488.5 mg, 4.0 mmol), glycidyl methacrylate (28.4 mg, 0.2 mmol), 4CzIPN (15.8 mg, 10 mol%), phenylbenzylsulfoximine (9.3 mg, 20 mol%), potassium phosphate trihydrate (79.8 mg, 0.3 mmol) and acetonitrile (1.5 mL) were added sequentially to a 10 mL Schlenk tube and stirred at room temperature under blue light (450-470 nm).

[0106] (2) After stirring for 36 h, ethyl acetate (5.0 mL) was added to the reaction mixture. The resulting solution was washed with brine (10.0 mL) and dried over anhydrous sodium sulfate. The organic layer was concentrated on a rotary evaporator to obtain a crude product.

[0107] (3) The crude product was purified by silica gel column chromatography using a mixed solvent of petroleum ether and ethyl acetate in a volume ratio of 30:1 as the eluent to obtain a colorless oily substance (42.9 mg, 81% yield), namely, oxirane-2-ylmethyl 3-(benzo[d][1,3]dioxol-2-yl)-2-methylpropanoate, with the structural formula:

[0108] The basic parameters of the compound are as follows:

[0109] 1 H NMR (400 MHz, CDCl3): 6.82–6.75 (m, 4H), 6.20–6.16 (m, 1H), 4.46–4.38 (m, 1H), 3.99–3.90 (m, 1H), 3.22–3.14 (m, 1H), 2.91–2.81 (m, 2H), 2.65–2.60 (m, 1H), 2.49–2.40 (m, 1H), 2.09–2.00 (m, 1H), 1.30 (d, J = 7.1 Hz, 3H); the spectrum is shown in FIG. Figure 7 .

[0110] 13 C NMR (101 MHz, CDCl3): δ 175.6, 147.5, 121.7, 109.8, 108.7, 65.4, 49.4, 44.7, 38.04, 34.4, 17.9; the spectrum is shown in Figure 2. Figure 8 .

[0111] HRMS(ESI)m / z:calcd for C 14 H 17 O5[M+H] + 265.1071,found 265.1067.

[0112] Example 5

[0113] A method for preparing tert-butyl 2-(3-(benzyloxy)-3-oxopropyl)piperidine-1-carboxylate comprises the following steps:

[0114] (1) Under nitrogen protection, 1-tert-butyloxycarbonylpiperidine (370.5 mg, 4.0 mmol), benzyl acrylate (32.4 mg, 0.2 mmol), 4CzIPN (15.8 mg, 10 mol%), phenylbenzylsulfoximine (9.3 mg, 20 mol%), potassium phosphate trihydrate (79.8 mg, 0.3 mmol) and acetonitrile (1.5 mL) were added sequentially to a 10 mL Schlenk tube and stirred at room temperature under blue light (450-470 nm).

[0115] (2) After stirring for 36 h, ethyl acetate (5.0 mL) was added to the reaction mixture. The resulting solution was washed with brine (10.0 mL) and dried over anhydrous sodium sulfate. The organic layer was concentrated on a rotary evaporator.

[0116] (3) The crude product was purified by silica gel column chromatography using a mixed solvent of petroleum ether and ethyl acetate in a volume ratio of 30:1 as the eluent to obtain a colorless oily substance (59.7 mg, 90% yield), namely tert-butyl 2-(3-(benzyloxy)-3-oxopropyl)piperidine-1-carboxylate, with the structural formula:

[0117] The basic parameters of the compound are as follows:

[0118] 1 H NMR (400 MHz, CDCl3): δ7.37–7.27 (m, 5H), 5.11 (s, 2H), 4.25 (br, 1H), 3.96 (br, 1H), 2.74 (t, J = 13.3 Hz, 1H), 2.41–2.24 (m, 2H), 2.16–2.01 (m, 1H), 1.72–1.66 (m, 1H), 1.64–1.47 (m, 6H), 1.43 (s, 9H); the spectrum is shown in FIG. Figure 9 .

[0119] 13 C NMR (101 MHz, CDCl3): δ173.4, 155.2, 136.1, 128.6, 128.3(3), 128.3(0), 79.4, 66.3, 31.3, 28.5, 25.6, 25.0, 19.1; the spectrum is shown in Figure 2. Figure 10 .

[0120] Example 6

[0121] A method for preparing benzyl 3-(tetrahydrothiophen-2-yl)propionate comprises the following steps:

[0122] (1) Under nitrogen protection, tetrahydrothiophene (352.7 mg, 4.0 mmol), benzyl acrylate (32.4 mg, 0.2 mmol), 4CzIPN (15.8 mg, 10 mol%), phenylbenzylsulfoximine (9.3 mg, 20 mol%), potassium phosphate trihydrate (79.8 mg, 0.3 mmol) and acetonitrile (1.5 mL) were added sequentially to a 10 mL Schlenk tube and stirred at room temperature under blue light (450-470 nm).

[0123] (2) After stirring for 36 h, ethyl acetate (5.0 mL) was added to the reaction mixture, and the resulting solution was washed with brine (10.0 mL) and dried over anhydrous sodium sulfate. The organic layers were combined and concentrated on a rotary evaporator to obtain a crude product;

[0124] (3) The crude product was purified by silica gel column chromatography using a mixed solvent of petroleum ether and ethyl acetate in a volume ratio of 60:1 as the eluent to obtain a colorless oily substance (20.5 mg, 59% yield), namely, benzyl 3-(tetrahydrothiophen-2-yl)propionate, with the structural formula:

[0125] The basic parameters of the compound are as follows:

[0126] 1 H NMR (400 MHz, CDCl3): δ7.38–7.31 (m, 5H), 5.11 (s, 2H), 3.39–3.32 (m, 1H), 2.92–2.81 (m, 2H), 2.54–2.38 (m, 2H), 2.11–1.99 (m, 3H), 1.95–1.77 (m, 2H), 1.63–1.56 (m, 1H); the spectrum is shown in Figure 2. Figure 11 .

[0127] 13 C NMR (101MHz, CDCl3): δ173.2, 136.1, 128.7, 128.4, 66.4, 48.4, 37.2, 33.6, 32.7, 32.4, 30.3. The spectrum is shown in Figure 12 .

[0128] Example 7

[0129] A method for preparing (1S,6R)-2-isopropyl-6-methylcyclohexyl 3-(tetrahydrofuran-2-yl) propionate comprises the following steps:

[0130] (1) Under nitrogen protection, tetrahydrofuran (288.5 mg, 4.0 mmol), L-menthyl acrylate (40.0 mg, 0.2 mmol), 4CzIPN (15.8 mg, 10 mol%), phenylbenzylsulfoximine (9.3 mg, 20 mol%), potassium phosphate trihydrate (79.8 mg, 0.3 mmol) and acetonitrile (1.5 mL) were sequentially added in a 10 mL Schlenk tube and stirred at room temperature under blue light (450-470 nm).

[0131] (2) After stirring for 36 h, ethyl acetate (5.0 mL) was added to the reaction mixture. The resulting solution was washed with brine (10.0 mL) and dried over anhydrous sodium sulfate. The organic layer was concentrated on a rotary evaporator to obtain a crude product.

[0132] (3) The crude product was purified by silica gel column chromatography using a mixed solvent of petroleum ether and ethyl acetate in a volume ratio of 30:1 as the eluent to obtain a colorless oily substance (32.5 mg, 58% yield), namely (1S,6R)-2-isopropyl-6-methylcyclohexyl 3-(tetrahydrofuran-2-yl) propionate, with the structural formula:

[0133] The basic parameters of the compound are as follows:

[0134] 1 H NMR (400 MHz, CDCl3): δ4.70–4.63 (m, 1H), 3.86–3.78 (m, 2H), 3.73–3.66 (m, 1H), 2.47–2.30 (m, 2H), 2.00–1.93 (m, 2H), 1.91–1.79 (m, 5H), 1.69–1.62 (m, 2H), 1.52–1.42 (m, 2H), 1.38–1.32 (m, 1H), 1.10–0.93 (m, 2H), 0.89–0.86 (m, 7H), 0.74 (d, J = 7.0, 3H); the spectrum is shown in FIG. Figure 13 .

[0135] 13 C NMR (101 MHz, CDCl3): δ 173.3, 78.4, 74.2, 67.8, 47.1, 41.0, 34.4, 31.7, 31.5, 31.2, 30.9, 26.3, 25.8, 23.5, 22.1, 20.9, 16.4; Figure 14 .

[0136] HRMS(ESI)m / z:calcd for C 17 H 31 O3[M+H] + 283.2268,found 283.2264.

[0137] Example 8

[0138] A method for preparing (3-(benzo[d][1,3]dioxolan-2-yl)propionyl)-L-leucine ethyl ester comprises the following steps:

[0139] (1) Under nitrogen protection, 1,3-benzoxane (97.5 mg, 0.4 mmol), acryloyl-L-leucine ethyl ester (42.6 mg, 0.2 mmol), 4CzIPN (15.8 mg, 10 mol%), phenylbenzylsulfoximine (9.3 mg, 20 mol%), potassium phosphate trihydrate (79.8 mg, 0.3 mmol) and acetonitrile (1.5 mL) were added sequentially to a 10 mL Schlenk tube and stirred at room temperature under blue light (450-470 nm).

[0140] (2) After stirring for 36 h, ethyl acetate (5.0 mL) was added to the reaction mixture. The resulting solution was washed with brine (10.0 mL) and dried over anhydrous sodium sulfate. The organic layer was concentrated on a rotary evaporator to obtain a crude product.

[0141] (3) The crude product was purified by silica gel column chromatography using a mixed solvent of petroleum ether and ethyl acetate in a volume ratio of 10:1 as the eluent to obtain a yellow solid (36.5 mg, 60% yield), namely (3-(benzo[d][1,3]dioxolan-2-yl)propionyl)-L-leucine ethyl ester, with the structural formula: Melting point: 53-55℃.

[0142] The basic parameters of the compound are as follows:

[0143] 1 H NMR (400 MHz, CDCl3): δ 6.81–6.74 (m, 4H), 6.19 (t, J = 4.2 Hz, 1H), 5.99 (br, 1H), 4.65–4.58 (m, 1H), 4.17 (q, J = 7.1 Hz, 2H), 2.48–2.42 (m, 2H), 2.36–2.28 (m, 2H), 1.67–1.59 (m, 2H), 1.56–1.47 (m, 1H), 1.26 (t, J = 7.1 Hz, 3H), 0.93 (dd, J = 6.2, 3.8 Hz, 6H); the spectrum is shown in FIG. Figure 15 .

[0144] 13 C NMR (101 MHz, CDCl3): δ173.2, 171.4, 147.7, 121.6, 110.4, 108.5(9), 108.5(7), 61.5, 50.9, 41.9, 29.9, 29.3, 25.0, 22.9, 22.1, 14.2; the spectrum is shown in Figure 2. Figure 16 .

[0145] HRMS(ESI)m / z:calcd for C 18 H26 NO5[M+H] + 336.1806, found 336.1803.

[0146] In summary, the heteroatom ortho-CH bond of the above embodiment is coupled with the electron-deficient olefin to form the compound having the structural formula: X is N, O, or S; and EWG is a benzyl ester, phosphate, bis(tert-butyloxycarbonyl)aminomethyl, glycidyl ester, L-menthyl ester, or an amino acid derivative. The above examples of the present invention utilize readily available sulfoximines as novel hydrogen atom transfer catalysts to achieve coupling of heteroatom ortho-CH bonds with electron-deficient olefins, synthesizing a series of biologically active substances. This method offers advantages such as simple reaction operation and readily available, inexpensive raw materials, and has significant development potential and application prospects in the fields of organic synthesis, biopharmaceuticals, and materials science.

[0147] The above describes the embodiments of the present invention, but the present invention is not limited to the above embodiments. Various changes can be made according to the purpose of the invention. Any changes, modifications, substitutions, combinations or simplifications made according to the spirit and principles of the technical solution of the present invention should be equivalent replacement methods. As long as they comply with the purpose of the invention and do not deviate from the technical principles and inventive concepts of the present invention, they belong to the scope of protection of the present invention.

[0148] The above describes the specific embodiments of the present invention. It should be understood that the present invention is not limited to the above specific embodiments, and those skilled in the art may make various variations or modifications within the scope of the claims, which do not affect the essence of the present invention.

Claims

1. A use of sulfoximine as a hydrogen atom transfer catalyst in photocatalytic carbon-carbon bond construction, characterized in that: Used to achieve coupling reactions between heteroatom ortho-CH bonds and electron-deficient alkenes.

2. The use according to claim 1, characterized in that The heteroatom is one of N, O, and S; And / or, the general formula of the electron-deficient olefin is CH2=CH-EWG, wherein EWG is selected from one or more of the following groups: benzyl ester group, diethyl phosphate group, bis(tert-butyloxycarbonyl)aminomethyl ester group, glycidyl ester group, L-menthyl ester group, and amino acid ester derivative group.

3. A method for coupling a heteroatom ortho-CH bond with an electron-deficient olefin, characterized in that: The following steps are involved: S1. Under the protection of an inert gas, a compound containing a heteroatom, an electron-deficient olefin, a photocatalyst, a sulfoximine hydrogen atom transfer catalyst, a base, and a solvent are mixed, and the reaction is carried out under visible light irradiation; the heteroatom is selected from at least one of N, O, and S, and the electron-deficient olefin has an electron-withdrawing group EWG; S2, extracting the reaction product of S1 with an organic solvent, washing the organic layer, and drying; S3. The organic layer is concentrated to obtain a crude product; the crude product is purified to obtain the target coupling product.

4. The coupling method of heteroatom ortho-CH bonds and electron-deficient olefins according to claim 3, characterized in that: In S1, the sulfoximine hydrogen atom transfer catalyst includes phenylbenzylsulfoximine, and its usage amount is 10-30% of the molar amount of the reaction substrate.

5. The method according to claim 3, characterized in that In S1, the photocatalyst includes 4CzIPN, and its amount is 5-15% of the molar amount of the reaction substrate; And / or, the base comprises potassium phosphate trihydrate, and its amount is 1.2-2.0 equivalents based on the molar amount of the reaction substrate.

6. The method according to claim 3, characterized in that In S1, the solvent includes acetonitrile, the reaction temperature is 20-30° C., the illumination condition is blue light with a wavelength of 450-470 nm, and the reaction time is 24-48 hours.

7. The method according to claim 3, characterized in that In S1, the compound containing heteroatoms is selected from at least one of tetrahydrofuran, tetrahydrothiophene, piperidine derivatives, 1,3-benzodioxolane and corresponding derivatives thereof.

8. The method according to claim 3, characterized in that In S1, the general formula of the electron-deficient olefin is CH2=CH-EWG, wherein EWG is selected from one or more of the following groups: benzyl ester group, diethyl phosphate group, bis(tert-butyloxycarbonyl)aminomethyl ester group, glycidyl ester group, L-menthyl ester group, and amino acid ester derivative group.

9. The compound prepared by the preparation method according to any one of claims 3 to 8, characterized in that: The general structural formula of the compound is shown below: Wherein, X is selected from at least one of O, S, and N; and EWG is selected from one or more of a benzyl ester group, a diethyl phosphate group, a bis(tert-butyloxycarbonyl)aminomethyl ester group, a glycidyl ester group, an L-menthyl ester group, and an amino acid ester derivative group.

10. The compound according to claim 9, characterized in that: The compound is selected from any one of the following compounds: Benzyl 3-(tetrahydrofuran-2-yl)propionate, diethyl 2-(tetrahydrofuran-2-yl)ethyl)phosphonate, methyl 2-(bis(tert-butoxycarbonyl)amino)-3-(tetrahydrofuran-2-yl)propionate, oxiran-2-ylmethyl 3-(benzo[d][1,3]dioxol-2-yl)-2-methylpropanoate, tert-butyl 2-(3-(benzyloxy)-3-oxopropyl)piperidine-1-carboxylate, benzyl 3-(tetrahydrothiophen-2-yl)propionate, (1S,6R)-2-isopropyl-6-methylcyclohexyl 3-(tetrahydrofuran-2-yl)propionate, ethyl (3-(benzo[d][1,3]dioxol-2-yl)propionyl)-L-leucinate.

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