Photocatalytic synthesis method of asymmetric disulfide

Abstract

The invention discloses a photocatalytic synthesis method of asymmetric disulfide, and belongs to the field of catalytic preparation of fine chemicals. The preparation method comprises the following steps: by taking a tetrasulfide compound as an electron donor and electron-deficient olefin as an electron acceptor, adding a photosensitizer and a reduction quenching agent, and reacting in an organic solvent; under the irradiation of blue light, a reduction state species of the photosensitizer is generated through the quenching effect of a reduction quenching agent on the photosensitizer, disulfide negative ions are generated through reduction of a tetrasulfide compound, conjugate addition of olefin is completed, and the asymmetric disulfide compound is obtained. According to the invention, a green and friendly photocatalysis means is adopted, the reaction condition is mild, the required raw materials are cheap and easy to obtain, the reaction operation is simple, the disulfide modification of various drugs and polypeptide molecules can be realized, and sulfydryl molecules such as cysteine are not required to be used in the construction of disulfide bonds.

Description

Technical Field

[0001] The invention relates to a photocatalytic synthesis method of an asymmetric disulfide, and belongs to the field of catalytic preparation of fine chemicals. Background Art

[0002] The importance of disulfides is not limited to applications in synthetic chemistry, but also covers fields such as biology, materials, and pharmacy (as shown below). Due to their flexibility and reversibility, disulfides serve as key linker types for regulating proteins in various biochemical processes and key cleavage sites for the release of antibody-drug conjugate (ADC) warheads. The disulfide-rich ring structure has a unique redox potential, making it a promising active cathode material in lithium-sulfur batteries. In addition, due to the unique pharmacological and physicochemical properties of disulfide bonds, disulfide units are also widely present in biologically active natural products and drugs. Therefore, how to quickly and efficiently achieve the synthesis of disulfides, especially the synthesis of asymmetric disulfides, has received widespread attention.

[0003]

[0004] Since the 1970s, chemical transformations catalyzed by visible light have attracted great attention. Visible light is ubiquitous in nature and has a wide energy spectrum (absorption wavelength is 400-700nm). It is an ideal energy donor for green and sustainable development. In the past decade, as the global demand for green production and manufacturing has become increasingly urgent, the molecular synthesis and preparation of visible light catalysis has developed rapidly. How to effectively utilize the energy of visible light to achieve a variety of chemical transformations usually requires the use of photocatalysts. Currently, commonly used organic dyes (acridinium salt derivatives, dicyanobenzene derivatives), transition metal chelates (iridium, ruthenium, etc.), tungsten oxide (tungstate), etc., use metal examples or organic dyes to achieve electron transfer or energy transfer under the excitation of visible light to complete the corresponding transformation.

[0005] In 2020, the Pratt group used [Ir(dF(CF3)ppy)2(dtbbpy)]PF6 as a photosensitizer, tetrasulfide compounds as sulfur sources, Barton esters or Glorius oxime ethers to generate alkyl radicals, and then substituted (S H 2) reaction, and synthesized a series of asymmetric sulfides (J.Am.Chem.Soc.2020,142,10284). In 2022, Professor Studer used aldehydes or fatty alkanes to produce carbonyl radicals or alkyl radicals under the condition of sodium tungstate as a photocatalyst, and also achieved similar substitution reactions to construct asymmetric sulfides (Nat.Commun.2022,13,3886) (Scheme a).

[0006] Scheme a: Free radical substitution (SH 2) The process is as follows:

[0007]

[0008] Scheme b: Difunctionalization of olefins:

[0009]

[0010] On the other hand, the difunctionalization of double bonds promoted by photocatalytic systems has recently become a promising alternative method for obtaining disulfides. For example, the disulfurization reaction of olefins achieved by blue light excitation of the SS bond homolysis of sulfone disulfide can synthesize a series of β-sulfonyl disulfides (Scheme b) (Angew. Chem. Int. Ed. 2023, 62, e202302861). Despite these remarkable advances, the disulfurization reaction achieved by conjugate addition using photochemical reduction to generate disulfide anions has not yet been reported. Summary of the invention

[0011] The present invention aims to provide a photocatalytic synthesis method of an asymmetric disulfide, which uses photocatalysis to generate disulfide anions and realizes the synthesis of an asymmetric disulfide compound.

[0012] The reaction process of the present invention is: under blue light irradiation, the tetrasulfide donor can be reduced to generate disulfide anions with strong nucleophilic ability through the photoredox chemical process of the photosensitizer, and the corresponding disulfide intermediates are formed through conjugated addition with electron-deficient olefins, and further protons are captured to form an asymmetric disulfide ether structure. In this process, the disulfide anions are generated by photocatalytic single-electron reduction. The process is as follows:

[0013]

[0014] The present invention provides a photocatalytic synthesis method of an asymmetric disulfide, wherein a tetrasulfide compound is used as an electron donor, an electron-deficient olefin is used as an electron acceptor, a photosensitizer and a reduction quencher are added, and a reaction is carried out in an organic solvent; under blue light irradiation, the photosensitizer is subjected to reduction quenching by the reduction quencher to generate a reduced species of the photosensitizer, the tetrasulfide compound is reduced to generate a disulfide anion, and conjugate addition to the olefin is completed to obtain an asymmetric disulfide compound. The technical core of the present invention is to utilize the light excitation of the photosensitizer to produce an excited state Ir*(III), and to generate a reduced state Ir(II) through a reduction quenching process, to reduce the tetrasulfide compound to generate a disulfide anion, and to complete conjugate addition to the olefin to obtain an asymmetric disulfide structure compound.

[0015] The reaction equation is as follows:

[0016]

[0017] The structural formula of tetrasulfide is:

[0018]

[0019] Wherein R is one of an alkyl group, an aryl group, a sugar group, and an amino acid group;

[0020] The structural formula of an electron-deficient olefin is:

[0021]

[0022] Wherein EWG is one of the functional groups with strong electron-withdrawing effect such as ester group, amide group, carboxyl group, nitro group, cyano group, sulfone group and pyridine group; R 1 It is one of the functional groups of H, F, NHBoc, NHAc, NHBz, NPhth, and N(Boc)2;

[0023] The reduction quencher can be one of triphenylphosphine, trialkylsilyl, trialkylamine, diisopropylethylamine, and N,N-dimethylaniline;

[0024] The photosensitizer can be one of Ir(ppy)3, [Ir(dF(CF3)ppy)2(bpy)]PF6, [Ir(dF(CF3)ppy)2(dtbbpy)]PF6, and [Ir(pF(Me)ppy)2(dtbbpy)]PF6.

[0025] In the above reaction, the wavelength of blue light irradiation is 400-470nm of visible light, preferably 450nm blue light; the power is 1-30W, preferably 12W;

[0026] The above reaction temperature is 0-100°C, preferably 25°C; the reaction time is 1-12h, preferably 4h;

[0027] The organic solvent can be selected from ethyl acetate, methanol, acetonitrile, N,N-dimethylformamide, tetrahydrofuran, ether, dichloromethane, toluene, preferably dichloromethane; the amount of the organic solvent used is: 5-15 mL of solvent for 1 mmol of tetrasulfide compound.

[0028] In the above reaction, the molar ratio of the tetrasulfide compound, the electron-deficient olefin, the reduction quencher and the photosensitizer is 1:(1-3):(3-6):(0.005-0.1), preferably 1:1.5:3:0.01.

[0029] The reaction mechanism of the present invention is as follows:

[0030] Under blue light irradiation, the photosensitizer [Ir(III)] absorbs energy from the initial irradiation to the excited state [Ir(III)]*(E red=[III / II] = 1.32 V vs SCE), which can be quenched by tertiary amine reducing agents to generate α-aminoalkyl radical anion A and a strong reduced Ir(II) photosensitizer. On the one hand, the strong reducing ability of the reduced iridium catalyst [Ir(II)] promotes the one-electron reduction of tetrasulfide 1a (E red =-1.23V vs SCE), followed by fragmentation to produce persulfide radicals and disulfide anions. The persulfide radicals can quickly dimerize under blue light to regenerate tetrasulfide 1a, while the disulfide anions combine with electron-deficient olefins to form adduct B. On the other hand, the generated tertiary amine radical cation A completes the proton transfer process of B through deprotonation, ultimately generating product 3a.

[0031]

[0032] Beneficial effects of the present invention:

[0033] (1) The present invention adopts a green and friendly photocatalytic method to achieve the synthesis of asymmetric disulfide compounds. The reaction conditions are mild, the required raw materials are cheap and readily available, the reaction operation is simple, and the functional group tolerance is good;

[0034] (2) The asymmetric disulfide compounds prepared by the present invention can be used for the disulfide post-modification of various marketed drugs and polypeptide protein structures, and no sulfhydryl molecules such as cysteine ​​are required in the construction of these disulfide bonds. DETAILED DESCRIPTION

[0035] Below in conjunction with the following specific examples, the present invention is further described in detail, and the protection content of the present invention is not limited to the following examples. Without departing from the spirit and scope of the inventive concept, the changes and advantages that can be thought of by those skilled in the art are all included in the present invention, and are protected by the attached claims. The process, conditions, reagents, experimental methods, etc. for implementing the present invention, except for the content specifically mentioned below, are all common knowledge and common common sense in the art, and the present invention has no special restrictions. The data provided in the following examples include specific operations, reaction conditions, reaction products, and data characterization of products.

[0036] Embodiment 1:

[0037] Methyl N,N-bis(tert-butyloxycarbonyl)-S-(tert-butylthio)cysteine ​​ester (3a)

[0038]

[0039] In a 100 mL flask, tert-butyl tetrasulfide (0.97 g, 4 mmol, 1 equiv), N,N-bis-tert-butyloxycarbonyl dehydroalanine methyl ester (1.83 g, 6 mmol, 1.5 equiv), tris(2-phenylpyridine)iridium (20 mg, 0.02 mmol, 0.5 mol%) and triethylamine (2.02 g, 12 mmol, 3.0 equiv) were added and dissolved in dichloromethane (20 mL). The reaction mixture was stirred at 25 ° C for 4 hours under the irradiation of blue LED light (12 W, 450 nm). After the reaction was completed, the blue light was removed, the solvent was removed by rotary evaporation, and the crude product was purified by column chromatography to obtain product 3a (1.37 g, 81%).

[0040] Yield: 76.1mg (90%); time: 4h; yellow liquid; TLC, Rf=0.20 (PE:EtOAc=10:1); 1 HNMR (CDCl3,400

[0041] MHz): δ5.22(q,1H),3.71(s,3H),3.44(dd,J=12.0,8.0Hz,2H),3.19-3.13(m,1H),1.49(s,18H),1.32(s,9H); 13 C NMR (CDCl3, 100MHz): δ170.31, 151.70, 83.29, 57.77, 52.37, 47.88, 40.96, 29.82, 27.92.

[0042] Example 2: Ethyl 3-(tert-butyldisulfanyl)-2-(1,3-dioxoisoindol-2-yl)propanoate (3b)

[0043]

[0044] Tert-butyl tetrasulfide 1a (0.2mmol, 1 equivalent), N-phthalamido dehydroalanine ethyl ester 2b (0.4mmol, 2 equivalents), tris(2-phenylpyridine)iridium (0.002mmol, 1mol%) and triethylamine (0.6mmol, 3.0 equivalents) were dissolved in dichloromethane (2ml). The reaction mixture was irradiated under blue light (12W, 450nm) and stirred at 25°C for 4 hours. After the raw material was completely consumed, the solvent was removed in vacuo and the crude product was purified by flash column chromatography to obtain product 3b.

[0045] Yield: 43.3mg (98%); time: 4h; yellow liquid; TLC, R f =0.20 (PE:EtOAc=5:1); 1H NMR

[0046] (CDCl3,400MHz): δ7.87-7.85(m,2H),7.74-7.72(m,2H),5.23(q,1H),4.21-4.19(m,2H),3.49-3.46(q,2H),1.30(s,9H),1.23-1,20(q,3H); 13 C NMR (CDCl3, 100MHz): δ168.24,167.40,134.13,131.74,123.53,62.13,51.42,48.07,38.01,29.78,13.99.HRMS(ESI)m / z calcd.for C 17 H 22 NO4S2[M+H] + :368.0990,found:368.0982.

[0047] Example 3: Methyl N,N-bis(tert-butyloxycarbonyl)-S-(tert-butylthio)cysteine ​​ester (3c)

[0048]

[0049] Tert-butyl tetrasulfide 1a (0.2mmol, 1 equivalent), N-tert-butyloxycarbonyl dehydroalanine methyl ester 2c (0.2mmol, 1 equivalent), 4,4′-bis(1,1-dimethylethyl)-2,2′-bipyridyl N1,N1′]bis[3,5-difluoro-2-[5-(trifluoromethyl)-2-pyridyl N]phenyl-C]iridium(III) hexafluorophosphate (0.002mmol, 1mol%) and triethylamine (0.6mmol, 3.0 equivalent) were dissolved in dichloromethane (1ml). The reaction mixture was irradiated under blue light (12W, 450nm) and stirred at 25°C for 4 hours. After the raw material was completely consumed, the solvent was removed in vacuo and the crude product was purified by flash column chromatography to obtain product 3c.

[0050] Yield:29.1mg(45%); time:4h; yellow liquid; TLC, R f =0.20 (PE:EtOAc=20:1); 1 H NMR

[0051] (CDCl3,400MHz): δ5.32-5.25(q,1H),4.52-4.48(q,1H),3.70(s,3H),3.09-2.90(m,2H),1.38(s,9H),1.24(s,9H); 13C NMR (CDCl3, 100MHz): δ171.45,171.25,155.13,80.03,53.18,52.54,52.51,48.14,42.60,30.82,29.75,28.30.

[0052] Example 4: S-((Triisopropylsilyl)ethynyl)4-methoxybenzenesulfonate (3d)

[0053]

[0054] Tert-butyl tetrasulfide 1a (0.2mmol, 1 equivalent), N-benzoyl dehydroalanine methyl ester 2d (0.3mmol, 1.5 equivalents), 4,4′-bis(1,1-dimethylethyl)-2,2′-bipyridyl N1,N1′]bis[3,5-difluoro-2-[5-(trifluoromethyl)-2-pyridyl N]phenyl-C]iridium(III) hexafluorophosphate (0.002mmol, 1mol%) and triethylamine (0.6mmol, 3.0 equivalents) were dissolved in dichloromethane (3ml). The reaction mixture was irradiated under blue light (12W, 450nm) and stirred at 25°C for 4 hours. After the raw material was completely consumed, the solvent was removed in vacuo and the crude product was purified by flash column chromatography to obtain product 3d.

[0055] Yield: 230.1mg (46%); time: 4h; yellow liquid; TLC, Rf=0.20 (PE:EtOAc=10:1); 1 H NMR

[0056] (CDCl3,400MHz): δ7.78-7.76(m,2H),7.46-7.36(m,3H),7.04(d,J=8.0Hz,1H),5.04-5.00(m,1H),3.74(s,3H),3.24(q,2H),1.25(s,9H); 13 C NMR (CDCl3, 100MHz): δ170.98,166.97,133.72,131.90,128.64,127.21,52.76,52.63,48.38,42.13,30.85,29.73.HRMS(ESI)m / z calcd.for C 15 H 21 NO3S2Na[M+H] + :350.0861,found:350.0862.

[0057] Example 5: Methyl N-acetyl-S-(tert-butylthio)cysteine ​​ester (3e)

[0058]

[0059] Tert-butyl tetrasulfide 1a (0.2mmol, 1 equivalent), N-acetyl dehydroalanine methyl ester 2e (0.3mmol, 1.5 equivalents), 4,4′-bis(1,1-dimethylethyl)-2,2′-bipyridyl N1,N1′]bis[3,5-difluoro-2-[5-(trifluoromethyl)-2-pyridyl N]phenyl-C]iridium(III) hexafluorophosphate (0.002mmol, 1mol%) and triphenylphosphine (0.6mmol, 3.0 equivalents) were dissolved in dichloromethane (5ml). The reaction mixture was irradiated under blue light (12W, 450nm) and stirred at 25°C for 4 hours. After the raw material was completely consumed, the solvent was removed in vacuo and the crude product was purified by flash column chromatography to obtain product 3e.

[0060] Yield:24.4mg(46%); time:4h; yellow liquid; TLC, R f =0.20 (PE:EtOAc=10:1); 1 H NMR

[0061] (CDCl3,400MHz): δ4.90-4.86(q,1H),3.78(s,3H),3.21-3.01(m,2H),2.06(s,3H),1.31(s,9H); 13 C NMR (CDCl3, 100MHz): δ171.20,170.97,169.79,169.77,52.69,52.06,51.86,48.30,42.15,30.80,29.72,23.22.HRMS(ESI)m / z calcd.for C 17 H 26 ClO2S2Si[M+H] + :389.0827,found:389.0826.

[0062] Example 6: Methyl 3-(tert-butyldisulfide)propionate (3f)

[0063]

[0064] Tert-butyl tetrasulfide 1a (0.2mmol, 1 equivalent), methyl acrylate 2f (0.3mmol, 1.5 equivalents), 4,4′-bis(1,1-dimethylethyl)-2,2′-bipyridyl N1,N1′]bis[3,5-difluoro-2-[5-(trifluoromethyl)-2-pyridyl N]phenyl-C]iridium(III) hexafluorophosphate (0.002mmol, 1mol%) and triethylamine (0.6mmol, 3.0 equivalents) were dissolved in dichloromethane (1ml). The reaction mixture was irradiated under blue light (12W, 450nm) and stirred at 25°C for 4 hours. After the raw material was completely consumed, the solvent was removed in vacuo and the crude product was purified by flash column chromatography to obtain the product 3f.

[0065] Yield:40.7mg(98%); time:4h; yellow liquid; TLC, R f =0.20 (PE:EtOAc=15:1); 1 H NMR

[0066] (CDCl3, 400MHz): δ3.63(s,3H),2.86(t,J=8.0Hz,2H),2.65(t,J=8.0Hz,2H),1.27(s,9H); 13 C NMR(CDCl3,100MH / z):δ172.28,,51.81,47.96,34.85,34.09,29.93.HRMS(ESI)m / z calcd.for C 10 H 18 O3S2Na[M+Na] + :273.0595,found:273.0595.

[0067] Example 7: 3-(tert-Butyldisulfide)-N-(prop-2-yn-1-yl)propionamide (3 g)

[0068]

[0069] Tert-butyl tetrasulfide 1a (0.2mmol, 1 equivalent), propargyl acrylate 2g (0.4mmol, 2 equivalents), 4,4′-bis(1,1-dimethylethyl)-2,2′-bipyridine N1,N1′]bis[3,5-difluoro-2-[5-(trifluoromethyl)-2-pyridyl N]phenyl-C]iridium hexafluorophosphate (III) (0.002mmol, 1mol%) and triethylamine (0.6mmol, 3.0 equivalents) were dissolved in dichloromethane (1ml). The reaction mixture was irradiated under blue light (12W, 450nm) and stirred at 25°C for 4 hours. After the raw material was completely consumed, the solvent was removed in vacuo, and the crude product was purified by flash column chromatography (PE / EtOAc=1:15) to obtain 3g of the product.

[0070] Yield:39.7mg(86%); time:4h; yellow liquid; TLC, R f =0.20 (PE:EtOAc=10:1); 1 H NMR

[0071] (CDCl3, 400MHz): δ4.08-4.06(m,2H),2.96(t,J=8.0Hz,2H),2.60(t,J=8.0Hz,2H),2.25-2.24(m,1H),1.35(s,9H); 13 C NMR (CDCl3, 100MHz): δ170.60,79.37,71.74,48.17,35.86,35.21,29.96,29.29.HRMS(ESI)m / z calcd.for C 10 H 17 NOS2Na[M+Na] + :254.0649,found:254.0647.

[0072] Example 8: 2-Bromoethyl 3-(tert-butyldisulfide)propionate (3h)

[0073]

[0074] Tert-butyl tetrasulfide 1a (0.2mmol, 1 equivalent), 2-bromoethyl acrylate 2h (0.4mmol, 2 equivalents), 4,4′-bis(1,1-dimethylethyl)-2,2′-bipyridyl N1,N1′]bis[3,5-difluoro-2-[5-(trifluoromethyl)-2-pyridyl N]phenyl-C]iridium hexafluorophosphate (III) (0.002mmol, 1mol%) and triethylamine (0.6mmol, 3.0 equivalents) were dissolved in dichloromethane (1ml). The reaction mixture was irradiated under blue light (12W, 450nm) and stirred at 25°C for 4 hours. After the raw material was completely consumed, the solvent was removed in vacuo and the crude product was purified by flash column chromatography to obtain the product 3h.

[0075] Yield:46.8mg(78%); time:4h; yellow liquid; TLC, R f =0.20 (PE:EtOAc=5:1); 1 H NMR

[0076] (CDCl3,400MHz): δ4.43-4.40(m,2H),3.53-3.30(m,2H),2.94(t,J=8.0Hz,2H),2.77(t,J=8.0Hz,2H),1.34(s,9H); 13 C NMR(CDCl3,100MHz): δ171.27,63.89,47.94,34.61,34.00,29.86,28.49.HRMS(ESI)m / z calcd.for C9H 17 BrO2S2[M+Na] + :322.9751,found:322.9747.

[0077] Example 9: 3-(tert-Butyldisulfide)-N-(2-hydroxyethyl)propionamide (3i)

[0078]

[0079] Tert-butyl tetrasulfide 1a (0.2mmol, 1 equivalent), 2-hydroxyethyl acrylate 2i (0.4mmol, 2 equivalents), 4,4′-bis(1,1-dimethylethyl)-2,2′-bipyridyl N1,N1′]bis[3,5-difluoro-2-[5-(trifluoromethyl)-2-pyridyl N]phenyl-C]iridium hexafluorophosphate (III) (0.002mmol, 1mol%) and trimethylamine (0.6mmol, 3.0 equivalents) were dissolved in dichloromethane (1ml). The reaction mixture was irradiated under blue light (12W, 450nm) and stirred at 25°C for 4 hours. After the raw material was completely consumed, the solvent was removed in vacuo, and the crude product was purified by flash column chromatography (PE / EtOAc=1:15) to obtain product 3i.

[0080] Yield:42.2mg(89%); time:4h; yellow liquid; TLC, R f =0.20 (PE:EtOAc=5:1); 1 H NMR

[0081] (CDCl3, 400MHz): δ6.38 (s, 1H), 3.74-3.71 (m, 2H), 3.45-3.41 (m, 2H), 3.16 (s, 1H), 2.98-2.95 (m, 2H), 2.61 (t, J = 8.0Hz, 2H), 1.34 (s, 9H); 13 C NMR(CDCl3,100MHz): δ172.19,61.90,48.20,42.45,36.00,35.55,29.94.HRMS(ESI)m / z calcd.for C9H 19 NO2S2[M+Na] + :260.0755,found:260.0751.

[0082] Example 10: Methyl 3-(tert-butyldisulfide)-2-fluoropropionate (3j)

[0083]

[0084] Tert-butyl tetrasulfide 1a (0.2mmol, 1 equivalent), methyl 2-fluoroacrylate 2i (0.4mmol, 2 equivalents), 4,4′-bis(1,1-dimethylethyl)-2,2′-bipyridyl N1,N1′]bis[3,5-difluoro-2-[5-(trifluoromethyl)-2-pyridyl N]phenyl-C]iridium(III) hexafluorophosphate (0.002mmol, 1mol%) and triethylamine (0.6mmol, 3.0 equivalents) were dissolved in dichloromethane (1ml). The reaction mixture was irradiated under blue light (12W, 450nm) and stirred at 25°C for 4 hours. After the raw material was completely consumed, the solvent was removed in vacuo and the crude product was purified by flash column chromatography to obtain product 3j.

[0085] Yield:20.3mg(45%); time:4h; yellow liquid; TLC, R f =0.20 (PE:EtOAc=20:1); 1 H NMR

[0086] (CDCl3,400MHz): δ5.23-5.08(m,1H),3.83(s,3H),3.25-3.06(m,2H),1.35(s,9H); 13 C NMR (CDCl3, 100MHz): δ168.95,168.72,88.05,86.18,52.73,48.33,42.27,29.82; 19 F NMR(CDCl3,376MHz):δ190.30.HRMS(ESI)m / z calcd.for C8H 15 FO2S2Na[M+Na] + :249.0395,found:249.0405.

[0087] Example 11: 3-(tert-Butyldisulfide)-N-phenylpropionamide (31)

[0088]

[0089] Tert-butyl tetrasulfide 1a (0.2mmol, 1 equivalent), N-phenylacrylamide 2l (0.4mmol, 2 equivalents), 4,4′-bis(1,1-dimethylethyl)-2,2′-bipyridyl N1,N1′]bis[3,5-difluoro-2-[5-(trifluoromethyl)-2-pyridyl N]phenyl-C]iridium(III) hexafluorophosphate (0.002mmol, 1mol%) and triethylamine (0.6mmol, 3.0 equivalents) were dissolved in dichloromethane (2ml). The reaction mixture was irradiated under blue light (12W, 450nm) and stirred at 25°C for 4 hours. After the raw material was completely consumed, the solvent was removed in vacuo and the crude product was purified by flash column chromatography to obtain the product 3l.

[0090] Yield:47.8mg(89%); time:4h; yellow solid; TLC, R f =0.20 (PE:EtOAc=10:1); 1 H NMR

[0091] (CDCl3,400MHz): δ7.64(s,1H),7.51(d,J=8.0Hz,2H),7.29(dd,J=8.0,8.0Hz, 2H),7.10(t,J=8.0Hz,1H),3.04-3.01(m,2H),2.77-2.74(m,2H),1.34(s,9H); 13 C NMR (CDCl3, 100MHz): δ169.36,137.61,128.93,124.36,119.97,48.21,37.00,35.25,29.90.HRMS(ESI)m / z calcd.for C 13 H 19 NOS2Na[M+Na] + :292.0806,found:292.0804.

[0092] Example 12: 3-(tert-Butyldisulfide)-N-(4-vinylphenyl)propionamide (3m)

[0093]

[0094] Tert-butyl tetrasulfide 1a (0.2mmol, 1 equivalent), N-(4-vinyl)phenylacrylamide 2m (0.4mmol, 2 equivalents), 4,4′-bis(1,1-dimethylethyl)-2,2′-bipyridyl N1,N1′]bis[3,5-difluoro-2-[5-(trifluoromethyl)-2-pyridyl N]phenyl-C]iridium hexafluorophosphate (III) (0.002mmol, 1mol%) and triethylamine (0.6mmol, 3.0 equivalents) were dissolved in dichloromethane (2ml). The reaction mixture was irradiated under blue light (12W, 450nm) and stirred at 25°C for 4 hours. After the raw material was completely consumed, the solvent was removed in vacuo, and the crude product was purified by flash column chromatography (PE / EtOAc=1:15) to obtain the product 3m.

[0095] Yield:39.5mg(67%); time:4h; yellow liquid; TLC, R f =0.20 (PE:EtOAc=5:1); 1 H NMR

[0096] (CDCl3,400MHz): δ7.49(s,1H),7.47(s,1H),7.37(s,1H),7.35(s,1H),6.70-6.63(m,1H),5 .68(d,J=20Hz,1H),5.19(d,J=12Hz,1H),3.05-3.02(s,2H),2.78-2.75(m,2H),1.35(s,9H); 13 C NMR (CDCl3, 100MHz): δ169.17,137.21,136.08,133.82,126.85,119.84,113.11,48.32,37.14,35.24,29.99.HRMS(ESI)m / z calcd.for C 15 H 22 NOS2[M+H] + :296.1143,found:296.1154.

[0097] Example 13: 1-(tert-Butyl)-2-phenylethyl disulfane-sulfur dioxide (3n)

[0098]

[0099] Tert-butyl tetrasulfide 1a (0.2mmol, 1 equivalent), phenyl alkenyl sulfone 2n (0.4mmol, 2 equivalents), 4,4′-bis(1,1-dimethylethyl)-2,2′-bipyridyl N1,N1′]bis[3,5-difluoro-2-[5-(trifluoromethyl)-2-pyridyl N]phenyl-C]iridium hexafluorophosphate (III) (0.002mmol, 1mol%) and triethylamine (0.6mmol, 3.0 equivalents) were dissolved in dichloromethane (2ml). The reaction mixture was irradiated under blue light (12W, 450nm) and stirred at 25°C for 4 hours. After the raw material was completely consumed, the solvent was removed in vacuo, and the crude product was purified by flash column chromatography (PE / EtOAc=1:15) to give product 3n.

[0100] Yield:44.7mg(77%); time:4h; yellow liquid; TLC, R f =0.20 (PE:EtOAc=10:1); 1 H NMR

[0101] (CDCl3, 400MHz): δ7.86-7.84(m,2H),7.63-7.59(m,1H),7.52(t,J=8.0Hz,2H),3.41-3.37(m,2H),2.85-2.81(m,2H),1.19(s,9H); 13 C NMR(CDCl3,100MHz): δ138.66,133.95,129.38,128.05,55.69,48.47,31.09,29.79.HRMS(ESI)m / z calcd.forC 12 H 18 O2S3Na[M+Na] + :313.0367,found:313.0362.

[0102] Example 14: 3-(tert-Butyldisulfide)propionitrile (3o)

[0103]

[0104] Tert-butyl tetrasulfide 1a (0.2mmol, 1 equivalent), acrylonitrile 2o (0.4mmol, 2 equivalents), 4,4′-bis(1,1-dimethylethyl)-2,2′-bipyridyl N1,N1′]bis[3,5-difluoro-2-[5-(trifluoromethyl)-2-pyridyl N]phenyl-C]iridium(III) hexafluorophosphate (0.002mmol, 1mol%) and triethylamine (0.6mmol, 3.0 equivalents) were dissolved in dichloromethane (2ml). The reaction mixture was irradiated under blue light (12W, 450nm) and stirred at 25°C for 4 hours. After the raw material was completely consumed, the solvent was removed in vacuo, and the crude product was purified by flash column chromatography (PE / EtOAc=1:15) to obtain the product 3o.

[0105] Yield:32.5mg(93%); time:4h; yellow liquid; TLC, R f =0.20 (PE:EtOAc=10:1); 1 H NMR

[0106] (CDCl3,400MHz): δ2.80-2.80(m,2H),2.71-2.68(m,2H),1.28(s,9H); 13 C NMR (CDCl3, 100MHz): δ118.23, 48.54, 34.56, 29.92, 17.83.

[0107] Example 15: 3-[2-(tert-Butyldisulfide)ethyl]pyridine (3p)

[0108]

[0109] Tert-butyl tetrasulfide 1a (0.2mmol, 1 equivalent), 2-vinylpyridine 2p (0.4mmol, 2 equivalents), 4,4′-bis(1,1-dimethylethyl)-2,2′-bipyridine N1,N1′]bis[3,5-difluoro-2-[5-(trifluoromethyl)-2-pyridyl N]phenyl-C]iridium hexafluorophosphate (III) (0.002mmol, 1mol%) and triethylamine (0.6mmol, 3.0 equivalents) were dissolved in dichloromethane (2ml). The reaction mixture was irradiated under blue light (12W, 450nm) and stirred at 25°C for 4 hours. After the raw material was completely consumed, the solvent was removed in vacuo, and the crude product was purified by flash column chromatography (PE / EtOAc=1:15) to obtain the product 3p.

[0110] Yield:15.9mg(35%); time:4h; yellow liquid; TLC, R f =0.20 (PE:EtOAc=10:1);1 H NMR

[0111] (CDCl3,400MHz): δ8.55(s,1H),7.64-7.59(m,1H),7.20-7.13(m,2H),3.18-3.08(m,4H),1.34(s,9H); 13 C NMR(CDCl3,100MH / z): δ159.69,149.38,136.48,123.49,121.54,47.92,39.84,37.74,29.98.HRMS(ESI)m / z calcd.for C 12 H 25 O2S2Si[M+H] + :293.1060,found:293.1064.

[0112] Example 16: Ethyl 2-(1,3-dioxoisoindolin-2-yl)-3-((2-methyl-4-oxopentan-2-yl)disulfanyl)propanoate (3q)

[0113]

[0114] 1,1-Dimethyl-2-acetyltetrasulfide 1b (0.2mmol, 1 equivalent), N-phthalamido dehydroalanine ethyl ester 2b (0.4mmol, 2 equivalents), 4,4′-bis(1,1-dimethylethyl)-2,2′-bipyridyl N1,N1′]bis[3,5-difluoro-2-[5-(trifluoromethyl)-2-pyridyl N]phenyl-C]iridium(III) hexafluorophosphate (0.002mmol, 1mol%) and triethylamine (0.6mmol, 3.0 equivalents) were dissolved in dichloromethane (2ml). The reaction mixture was irradiated under blue light (12W, 450nm) and stirred at 25°C for 4 hours. After the starting material was completely consumed, the solvent was removed in vacuo and the crude product was purified by flash column chromatography to obtain the product 3q.

[0115] Yield: 61.1mg (66%); time: 4h; yellow liquid; TLC, R f =0.20 (PE:EtOAc=5:1); 1 H NMR

[0116] (CDCl3,400MHz): δ7.88-7.86(m,2H),7.76-7.73(m,2H),5.21(dd,J=8,4Hz,1H),4.21(dd,J =8,4Hz,2H),3.50(t,J=4Hz,2H),2.74(s,1H),2.13(s,1H),1.41(s,6H),1.24-1.21(m,4H); 13 C NMR(CDCl3,100MHz): δ206.31,168.09,167.42,134.23,131.73,123.62,62 .27,53.13,51.45,49.47,38.14,32.05,27.09,26.88,14.02.HRMS(ESI)m / z calcd.forC 19 H 23 NO5S2Na[M+Na] + :432.0915,found:432.0917.

[0117] Example 17: 2-Bromoethyl-3-(tert-butyldisulfanyl)propionate (3r)

[0118]

[0119] 1,1-Dimethyl-1-(2-oxo-4-methyl)cyclohexyltetrasulfide 1c (0.2mmol, 1 equivalent), N-phthalamido dehydroalanine ethyl ester 2b (0.4mmol, 2 equivalents), 4,4′-bis(1,1-dimethylethyl)-2,2′-bipyridyl N1,N1′]bis[3,5-difluoro-2-[5-(trifluoromethyl)-2-pyridyl N]phenyl-C]iridium(III) hexafluorophosphate (0.002mmol, 1mol%) and triethylamine (0.6mmol, 3.0 equivalents) were dissolved in dichloromethane (2ml). The reaction mixture was irradiated under blue light (12W, 450nm) and stirred at 25°C for 4 hours. After the raw material was completely consumed, the solvent was removed in vacuo and the crude product was purified by flash column chromatography to obtain product 3r.

[0120] Yield:46.8mg(78%); time:4h; yellow liquid; TLC, R f =0.20 (PE:EtOAc=5:1); 1 H NMR

[0121] (CDCl3,400MHz)(isomer ratio=1:1):δ7.82-7.80(m,2H),7.70-7.68(m,2H),5.20-5.13(m,1H),4.19 -4.14(m,2H),3.42-3.40(m,2H),2.60-2.55(m,1H),2.38-2.33(m,1H),2.24 -2.20(m,1H),2.03-2.00(m,1H),1.83-1.78(m,2H),1.54(s,1.5H),1.51(s, 1.5H),1.35(s,1.5H),1.31(s,1.5H),1.19-1.15(m,4H),0.97-0.92(m,3H); 13 C NMR (CDCl3, 100MHz): δ210.80,168.21,167.45,134.23,131.82,123.65,62.28,56.56,53.19,52.32,51.72,51 .35,37.96,37.63,36.85,34.46,34.43,29.78,29.63,26.91,22.64,22.46,22.25,14.10,14.08.HRMS(ESI)m / z calcd.for C 23 H 29 NO5S2Na[M+Na] + :486.1385,found:486.1387.

[0122] Example 18: Ethyl 3-(cyclohexyldisulfanyl)-2-(1,3-dioxoisoindolin-2-yl)propanoate (3s)

[0123]

[0124] Cyclohexyltetrasulfide 1d (0.2mmol, 1 equivalent), N-phthalamido dehydroalanine ethyl ester 2b (0.4mmol, 2 equivalents), 4,4′-bis(1,1-dimethylethyl)-2,2′-bipyridyl N1,N1′]bis[3,5-difluoro-2-[5-(trifluoromethyl)-2-pyridyl N]phenyl-C]iridium(III) hexafluorophosphate (0.002mmol, 1mol%) and triethylamine (0.6mmol, 3.0 equivalents) were dissolved in dichloromethane (2ml). The reaction mixture was irradiated under blue light (12W, 450nm) and stirred at 25°C for 4 hours. After the raw material was completely consumed, the solvent was removed in vacuo and the crude product was purified by flash column chromatography to obtain the product 3s.

[0125] Yield: 61.3mg (78%); time: 4h; yellow liquid; TLC, R f =0.20 (PE:EtOAc=15:1); 1 H NMR

[0126] (CDCl3, 400MHz): δ7.90-7.87(m,2H),7.77-7.75(m,2H),5.26(t,J=8Hz,1H),4.26-4.20(m,2H),3.49(d,J=8Hz,2H), 2.79-2.73(m,1H),1.98(d,J=8Hz,2H),1.76(d,J=8Hz,2H),1.61(d,J=8Hz,1H),1.42-1.30(m,5H),1.26-1.23(m,3H); 13 C NMR (CDCl3, 100MHz): δ168.22,167.49,134.23,133.09,131.72,123.62,118.87,62.26,51.23,41.83,36.66,14.05.HRMS(ESI)m / z calcd.for C 19 H 23 NO4S2Na[M+Na] + :416.0966,found:416.0977.

[0127] Example 19: Ethyl 2-(1,3-dioxoisoindolin-2-yl)-3-((3-methylbutan-2-yl)disulfanyl)propanoate (3t)

[0128]

[0129] 1,2-Dimethylpropyl tetrasulfide 1e (0.2mmol, 1 equivalent), N-phthalamido dehydroalanine ethyl ester 2b (0.4mmol, 2 equivalents), 4,4′-bis(1,1-dimethylethyl)-2,2′-bipyridyl N1,N1′]bis[3,5-difluoro-2-[5-(trifluoromethyl)-2-pyridyl N]phenyl-C]iridium(III) hexafluorophosphate (0.002mmol, 1mol%) and diisopropylethylamine (0.6mmol, 3.0 equivalents) were dissolved in dichloromethane (2ml). The reaction mixture was irradiated under blue light (12W, 450nm) and stirred at 25°C for 4 hours. After the raw material was completely consumed, the solvent was removed in vacuo and the crude product was purified by flash column chromatography to obtain the product 3t.

[0130] Yield:54.1mg(71%); time:4h; yellow liquid; TLC, R f =0.20 (PE:EtOAc=15:1); 1 H NMR

[0131] (CDCl3,400MHz): δ7.82-7.80(m,2H),7.69-7.67(m,2H),5.22-5.17(m,1H),4.19-4.14(m,2H), 3.41(d,J=8Hz,2H),2.77-2.72(m,1H),1.87-1.82(m,1H),1.19-1.15(m,6H),0.90-0.83(m,6H); 13 C NMR (CDCl3, 100MHz): δ168.35,167.52,134.23,131.81,123.63,62.26,53.40,53.19,51.44,51. 37,37.23,36.94,31.95,31.88,20.33,20.24,17.98,17.97,16.43,16.27,14.10.HRMS(ESI)m / z calcd.for C 18 H 24 NO4S2[M+H] + :382.1147,found:382.1159.

[0132] Example 20: Ethyl 3-(allyldisulfanyl)-2-(1,3-dioxoisoindolin-2-yl)propanoate (3u)

[0133]

[0134] Allyl tetrasulfide 1f (0.2mmol, 1 equivalent), N-phthalamido dehydroalanine ethyl ester 2b (0.4mmol, 2 equivalents), 4,4′-bis(1,1-dimethylethyl)-2,2′-bipyridyl N1,N1′]bis[3,5-difluoro-2-[5-(trifluoromethyl)-2-pyridyl N]phenyl-C]iridium(III) hexafluorophosphate (0.002mmol, 1mol%) and triethylamine (0.6mmol, 3.0 equivalents) were dissolved in dichloromethane (2ml). The reaction mixture was irradiated under blue light (12W, 450nm) and stirred at 25°C for 4 hours. After the raw material was completely consumed, the solvent was removed in vacuo and the crude product was purified by flash column chromatography to obtain the product 3u.

[0135] Yield:40.7mg(55%); time:4h; yellow liquid; TLC, R f =0.20 (PE:EtOAc=15:1); 1 H NMR

[0136] (CDCl3,400MHz): δ7.82-7.80(m,2H),7.70-7.68(m,2H),5.20-5.13(m,1H),4.19-4.14(m,2H),3.42-3.40(m,2H),2.60-2.55(m,1H),2.38-2.3 3(m,1H),2.24-2.20(m,1H),2.03-2.00(m,1H),1.83-1.78(m,2H),1.46 (s,3H),1.35(s,1H),1.27(s,3H),1.19-1.15(m,4H),0.97-0.92(m,3H); 13 C NMR (CDCl3, 100MHz): δ210.80,168.21,167.45,134.23,131.82,123.65,62.28,56.56,53.19,52.32,51.72,51 .35,37.96,37.63,36.85,34.46,34.43,29.78,29.63,26.91,22.64,22.46,22.25,14.10,14.08.HRMS(ESI)m / z calcd.forC 16 H 17 NO4S2Na[M+Na] + :374.0497,found:374.0499.

[0137] Example 21: Ethyl 3-(benzyldisulfanyl)-2-(1,3-dioxoisoindolin-2-yl)propanoate (3v)

[0138]

[0139] Benzyl tetrasulfide 1g (0.2mmol, 1 equivalent), N-phthalamido dehydroalanine ethyl ester 2b (0.4mmol, 2 equivalents), 4,4′-bis(1,1-dimethylethyl)-2,2′-bipyridyl N1,N1′]bis[3,5-difluoro-2-[5-(trifluoromethyl)-2-pyridyl N]phenyl-C]iridium hexafluorophosphate (III) (0.002mmol, 1mol%) and N,N-dimethylaniline (0.6mmol, 3.0 equivalents) were dissolved in dichloromethane (2ml). The reaction mixture was irradiated under blue light (12W, 450nm) and stirred at 25°C for 4 hours. After the raw material was completely consumed, the solvent was removed in vacuo and the crude product was purified by flash column chromatography to obtain the product 3v.

[0140] Yield:22.5mg(28%); time:4h; yellow liquid; TLC, R f =0.20 (PE:EtOAc=10:1); 1 H NMR

[0141] (CDCl3,400MHz): δ7.87-7.85(m,2H),7.75-7.72(m,2H),7.32-7.28(m,5H),5.16-5.12(m,1H), 4.21-4.16(m,2H),3.97-3.87(m,2H),3.29-3.22(m,1H),3.08-3.03(m,1H),1.22(t,J=8Hz,3H); 13 C NMR(CDCl3,100MHz):13C NMR (101MHz, CDCl3) δ168.08,167.44,136.98,134.18,131.75,129.28,128.5 6,127.50,123.62,123.58,62.14,51.13,43.21,36.07,14.05.HRMS(ESI)m / z calcd.for C 20 H 20 NO4S2[M+H] + :402.0834,found:402.0821.

[0142] Example 22: Ethyl 2-(1,3-dioxoisoindolin-2-yl)-3-(p-tolyldisulfanyl)propionate (3w)

[0143]

[0144] p-Tolyl tetrasulfide 1h (0.2mmol, 1 equivalent), N-phthalamido dehydroalanine ethyl ester 2b (0.4mmol, 2 equivalents), 4,4′-bis(1,1-dimethylethyl)-2,2′-bipyridyl N1,N1′]bis[3,5-difluoro-2-[5-(trifluoromethyl)-2-pyridyl N]phenyl-C]iridium(III) hexafluorophosphate (0.002mmol, 1mol%) and N,N-dimethylaniline (0.6mmol, 3.0 equivalents) were dissolved in dichloromethane (2ml). The reaction mixture was irradiated under blue light (12W, 450nm) and stirred at 25°C for 4 hours. After the raw material was completely consumed, the solvent was removed in vacuo and the crude product was purified by flash column chromatography to obtain the product 3w.

[0145] Yield: 60.1mg (78%); time: 4h; yellow liquid; TLC, R f =0.20 (PE:EtOAc=10:1); 1 H NMR

[0146] (CDCl3,400MHz): δ7.82-7.80(m,2H),7.70-7.68(m,2H),5.20-5.13(m,1H),4.19-4.14(m,2H),3.42-3.40(m,2H),2.60-2.55(m,1H),2.38-2.3 3(m,1H),2.24-2.20(m,1H),2.03-2.00(m,1H),1.83-1.78(m,2H),1.46 (s,3H),1.35(s,1H),1.27(s,3H),1.19-1.15(m,4H),0.97-0.92(m,3H); 13 C NMR (CDCl3, 100MHz): δ210.80,168.21,167.45,134.23,131.82,123.65,62.28,56.56,53.19,52.32,51.72,51 .35,37.96,37.63,36.85,34.46,34.43,29.78,29.63,26.91,22.64,22.46,22.25,14.10,14.08.HRMS(ESI)m / z calcd.forC 20 H 20 NO4S2[M+H] + :402.0834,found:402.0827.

[0147] Example 23: Ethyl 2-(1,3-dioxoisoindolin-2-yl)-3-((4-fluorophenyl)disulfanyl)propanoate (3x)

[0148]

[0149] p-Fluorophenyltetrasulfide 1i (0.2mmol, 1 equivalent), N-phthalamido dehydroalanine ethyl ester 2b (0.4mmol, 2 equivalents), 4,4′-bis(1,1-dimethylethyl)-2,2′-bipyridyl N1,N1′]bis[3,5-difluoro-2-[5-(trifluoromethyl)-2-pyridyl N]phenyl-C]iridium hexafluorophosphate (III) (0.002mmol, 1mol%) and N,N-dimethylaniline (0.6mmol, 3.0 equivalents) were dissolved in dichloromethane (2ml). The reaction mixture was irradiated under blue light (12W, 450nm) and stirred at 25°C for 4 hours. After the raw material was completely consumed, the solvent was removed in vacuo and the crude product was purified by flash column chromatography to obtain the product 3x.

[0150] Yield:64.8mg(80%); time:4h; yellow liquid; TLC, R f =0.20 (PE:EtOAc=10:1); 1 H NMR

[0151] (CDCl3, 400MHz): δ7.82-7.72(m,4H),7.38-7.35(m,2H),6.85(t,J=8Hz,2H),4.96(dd,J=8,4Hz ,1H),4.21-4.19(m,2H),3.78(dd,J=16,12Hz,1H),3.64(dd,J=12,4Hz,1H),1.21(t,J=4Hz,3H); 13 C NMR (CDCl3, 100MHz): δ167.87,167.38,163.52,161.05,134.20,131.63,128.83,123.47,116.19,115.97,62.28,52.33,34.57,14.06.HRMS (ESI) m / z calcd.for C 19 H 16 FNO4S2Na[M+Na] + :428.0403,found:428.0415.

[0152] Example 24: Ethyl 2-(1,3-dioxoisoindolin-2-yl)-3-(thiophen-2-yldisulfanyl)propanoate (3y)

[0153]

[0154] 2-Thienyltetrasulfide 1j (0.2mmol, 1 equivalent), olefin 2b (0.4mmol, 2 equivalents), 4,4′-bis(1,1-dimethylethyl)-2,2′-bipyridyl N1,N1′]bis[3,5-difluoro-2-[5-(trifluoromethyl)-2-pyridyl N]phenyl-C]iridium(III)hexafluorophosphate (0.002mmol, 1mol%) and N,N-dimethylaniline (0.6mmol, 3.0 equivalents) were dissolved in dichloromethane (2ml). The reaction mixture was irradiated under blue light (12W, 450nm) and stirred at 25°C for 4 hours. After the starting material was completely consumed, the solvent was removed in vacuo and the crude product was purified by flash column chromatography to give the product 3y.

[0155] Yield:47.1mg(60%); time:4h; yellow liquid; TLC, R f =0.20 (PE:EtOAc=10:1); 1 H NMR

[0156] (CDCl3,400MHz): δ7.89-7.75(m,4H),7.32-7.17(m,2H),6.91-6.89(m,1H),5.0 0(dd,J=12,4Hz,1H),4.21-4.16(m,2H),3.71-3.57(m,2H),1.21(t,J=8Hz,3H); 13 C NMR (CDCl3, 100MHz): δ167.96,167.57,135.50,134.24,131.99,131.77,130.41,127.63,123.62,62.30,51.89,37.66,14.07.HRMS(ESI)m / z calcd.for C 17 H 16 NO4S3[M+H] + :394.0241,found:394.0268.

[0157] Example 25: 2-(Acetoxymethyl)-6-((2-(bis(tert-butyloxycarbonyl)amino)-3-methoxy-3-oxopropyl)disulfanyl)tetrahydro-2H-pyran-3,4,5-triyl triacetate (3z)

[0158]

[0159] 2,3,4,6-tetraacetylglucose tetrasulfide 1k (0.2mmol, 1 equivalent), N,N-bis-tert-butyloxycarbonyl dehydroalanine methyl ester 2a (0.4mmol, 2 equivalents), 4,4′-bis(1,1-dimethylethyl)-2,2′-bipyridyl N1,N1′]bis[3,5-difluoro-2-[5-(trifluoromethyl)-2-pyridyl N]phenyl-C]iridium(III) hexafluorophosphate (0.002mmol, 1mol%) and N,N-dimethylaniline (0.6mmol, 3.0 equivalents) were dissolved in dichloromethane (2ml). The reaction mixture was irradiated under blue light (12W, 450nm) and stirred at 25°C for 4 hours. After the raw material was completely consumed, the solvent was removed in vacuo and the crude product was purified by flash column chromatography to obtain the product 3z.

[0160] Yield:73.9mg(53%); time:4h; yellow solid; TLC, R f =0.20 (PE:EtOAc=1:1); 1 HNMR

[0161] (CDCl3,400MHz): δ5.49(dd,J=12,4Hz,1H),5.39(t,J=8Hz,1H),5.31-5.24(m,2H),4.55(d,J=8Hz,1H),4.36(dd,J=12,4Hz,1H) ,4.05(d,J=16Hz,1H),3.80-3.75(m,1H),3.70(s,3H),3.52-3.45(m,2H),2.07(s,3H),2.02(s,6H),1.99(s,3H),1.52(s,18H); 13 C NMR (CDCl3, 100MHz): δ170.85,170.04,169.41,169.03,152.08,83.52,76.39,74.21,68.7 3,67.86,62.12,58.04,52.38,42.51,29.72,28.02,20.71,20.63.HRMS(ESI)m / zcalcd.for C 28 H 43 O 15 S2Na[M+Na] + :720.1972,found:720.1969.

[0162] Example 26: (3-tert-Butyldisulfide)-2-(1,3-dioxoisoindole-2-)-propionyl-D-tryptophanyl-D-leucine methyl ester (4)

[0163]

[0164] Tert-butyl tetrasulfide 1a (0.2mmol, 1 equivalent), Dha-Typ-Leu tripeptide (0.4mmol, 2 equivalents), 4,4′-bis(1,1-dimethylethyl)-2,2′-bipyridyl N1,N1′]bis[3,5-difluoro-2-[5-(trifluoromethyl)-2-pyridyl N]phenyl-C]iridium(III) hexafluorophosphate (0.002mmol, 1mol%) and triethylamine (0.6mmol, 3 equivalents) were dissolved in dichloromethane (2ml). The reaction mixture was irradiated under blue light (12W, 450nm) and stirred at 25°C for 4 hours. After the raw material was completely consumed, the solvent was removed in vacuo and the crude product was purified by flash column chromatography (PE / EtOAc=1:15) to obtain product 4. Yield: 117.4mg (90%); time: 4h; yellow liquid; TLC, R f =0.20 (PE:EtOAc=2:1); 1 H NMR(CDCl3,400MHz)(isomer ratio=1.7:1.3):δ8.20(d,J=20.0Hz,1H),7.84-7.82(m,1H),7.75-7.68(m,3H),7.52(s ,1H),7.13-7.10(m,1H),7.05-7.02(m,1H),6.90-6.85(m,2H),6.38(s,1H),5.22-5.14( m,1H),4.79-4.69(m,1H),4.51-4.40(m,1H),3.65(s,3H),3.53-3.34(m,3H),3.11(dd,J =16.0,8.0Hz,1H),1.53-1.43(m,2H),1.27(s,9H),1.43-1.36(m,1H),0.86-0.61(m,6H); 13C NMR(CDCl3,100MHz):δ172.7,170.5,170.5,167.8,167.5,136.2,135.9,134.4,134.3,131.6,131.4,127.2,127.1,123.8,123.7,122.2,122.2,120.0,119.8,118.8,117.9,111.2,111.0,110.2,109.6,54.3,54.2,53.3,53.1,52.2,50.9,48.3,48.2,41.1,40.8,38.1,37.9,29.8,29.8,27.9,27.0,24.7,24.5,22.9,22.6,21.9,21.8.HRMS(ESI)m / z calcd.for C 33 H 40 N4O6S2Na[M+Na] + :675.2287,found:675.2288。

Claims

1. A photocatalytic synthesis method of an asymmetric disulfide, characterized in that: A tetrasulfide compound is used as an electron donor, an electron-deficient olefin is used as an electron acceptor, a photosensitizer and a reduction quencher are added, and the reaction is carried out in an organic solvent; under the irradiation of blue light, the photosensitizer is quenched by the reduction quencher to generate a reduced species of the photosensitizer, the tetrasulfide compound is reduced to generate a disulfide anion, and the conjugate addition to the olefin is completed to obtain an asymmetric disulfide compound.

2. The photocatalytic synthesis method of asymmetric disulfide according to claim 1, characterized in that: The structural formula of tetrasulfide is: ； Wherein R is one of an alkyl group, an aryl group, a sugar group, and an amino acid group; The structural formula of an electron-deficient olefin is: ； Wherein EWG is one of the functional groups with strong electron-withdrawing effect such as ester group, amide group, carboxyl group, nitro group, cyano group, sulfone group and pyridine group; R 1 It is one of the functional groups selected from H, F, NHBoc, NHAc, NHBz, NPhth, and N(Boc)2.

3. The photocatalytic synthesis method of asymmetric disulfide according to claim 1, characterized in that: The reduction quencher is one of triphenylphosphine, trialkylsilyl, trialkylamine, diisopropylethylamine and N,N-dimethylaniline.

4. The photocatalytic synthesis method of asymmetric disulfide according to claim 1, characterized in that: The photosensitizer is one of Ir(ppy)3, [Ir(dF(CF3)ppy)2(bpy)]PF6, [Ir(dF(CF3)ppy)2(dtbbpy)]PF6, and [Ir(pF(Me)ppy)2(dtbbpy)]PF6.

5. The photocatalytic synthesis method of asymmetric disulfide according to claim 1, characterized in that: The wavelength of blue light irradiation is visible light 400-470 nm, and the power is 1-30 W.

6. The photocatalytic synthesis method of asymmetric disulfide according to claim 5, characterized in that: The wavelength of blue light irradiation is 450 nm; the power is 12W.

7. The photocatalytic synthesis method of asymmetric disulfide according to claim 1, characterized in that: The reaction temperature is 0-100°C, and the reaction time is 1-12 hours.

8. The photocatalytic synthesis method of asymmetric disulfide according to claim 1, characterized in that: The organic solvent is one of ethyl acetate, methanol, acetonitrile, N,N-dimethylformamide, tetrahydrofuran, ether, dichloromethane and toluene. The amount of the organic solvent is: 5-15 mL of the solvent is used for 1 mmol of the tetrasulfide compound.

9. The photocatalytic synthesis method of asymmetric disulfide according to claim 1, characterized in that: The molar ratio of the tetrasulfide compound, the electron-deficient olefin, the reduction quencher and the photosensitizer is 1:(1-3):(3-6):(0.005-0.1).

10. The photocatalytic synthesis method of asymmetric disulfide according to claim 9, characterized in that: The molar ratio of the tetrasulfide compound, the electron-deficient olefin, the reduction quencher and the photosensitizer is 1:1.5:3:0.01.

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