A method for the photocatalytic preparation of beta-amino sulfides

Abstract

This invention discloses a method for preparing β-aminosulfides using visible light catalysis, belonging to the field of organic synthesis technology. Under a protective atmosphere, a thiamine compound of formula I and a terminal olefin II react in a toluene or dichloromethane organic solvent with TDPZ as a visible light catalyst at 25°C under visible light irradiation until complete reaction. The β-aminosulfide of formula III is obtained after separation and purification. This invention features high atom economy, a broad substrate range unrestricted by the electronic properties of substituents, the use of a metal-free TDPZ photocatalyst, low catalyst dosage, mild reaction conditions, rapid and efficient reaction, high yield, high regioselectivity, and is environmentally friendly.

Description

Technical Field

[0001] This invention belongs to the field of synthetic technology, specifically relating to a method for preparing β-aminosulfides by visible light photocatalysis. Background Technology

[0002] β-Aminosulfides are widely found in bioactive compounds and have significant biological importance. Therefore, developing a green, environmentally friendly, and efficient method for synthesizing β-aminosulfides is of great significance in green organic synthetic chemistry research.

[0003] There are two main traditional methods: the first involves using a thionium salt intermediate, where the alkene acts as a nucleophile, followed by ring-opening with another nucleophile (Chem. Eur. J., 2009, 15, 11737; J. Org. Chem., 2016, 81, 2252; Org. Biomol. Chem., 2017, 15, 1998; Org. Biomol. Chem., 2017, 15, 5258); the second method, less common, involves adding a sulfur radical to the alkene, followed by single-electron oxidation and coupling with an additional nucleophile (Org. Lett., 2015, 17, 5444; J. Org. Chem., 2019, 84, 15373; Org. Chem. Front., 2022, 9, 4536). These strategies rely on three-component systems involving olefins, sulfur (S), and nitrogen (N) sources, thus generally suffering from operational inconvenience and poor atom economy. Furthermore, the formation of key intermediates in bifunctionalization processes, such as thionium or carbocations, limits the use of electron-neutral olefins; currently, there are no reports demonstrating the application of electron-deficient olefins in the synthesis of β-aminosulfides. In addition, the thioamination of α,α-disubstituted electron-neutral olefins is valuable for constructing highly crowded amine compounds, but this area is still underdeveloped. This may be due to steric hindrance and the tendency of in-situ formed carbocations to undergo 1,2-elimination, making nitrogen nucleophilic coupling difficult.

[0004] In view of the above, this invention patent selects a suitable photosensitizer, TDPZ, and utilizes readily available thiamines as effective bifunctional reagents for olefins, thus inventing a pioneering two-component method. Specifically, the photosensitizer is excited under light irradiation, and through energy transfer to the thiamine, both N-radicals and S-radicals are formed, thereby achieving highly regioselective addition synthesis of various valuable β-aminosulfides, including those with sterically hindered amine groups, into electron-neutral and electron-deficient olefins. Summary of the Invention

[0005] The purpose of this invention is to overcome the shortcomings of existing technologies and provide a method for the preparation of β-aminosulfides by visible light photocatalysis. This method uses simple and broad-ranging reaction substrates, operates under mild reaction conditions, involves no heavy metals, is completely atom-economical, exhibits good regioselectivity, and achieves high yields.

[0006] To achieve the above objectives, the present invention adopts the following technical solution:

[0007] A method for the visible light photocatalytic preparation of β-aminosulfides comprises the following steps: Under an argon atmosphere, thiamine compound I and terminal olefin II react in an organic solvent using TDPZ as a visible light catalyst at 20–30°C under visible light irradiation until complete reaction. The resulting β-aminosulfide III is then separated and purified.

[0008]

[0009] R 1 It is an alkyl or aryl group, R 2 R is an aryl group or a hydrogen atom. 3 R 4 It can be a hydrogen atom, alkyl, aryl, heteroaryl, ester, or amide group.

[0010] Furthermore, the molar ratio of the thiamine compound I to the terminal olefin II is 1:2, and the amount of organic photocatalyst TDPZ added is 1.0% of the molar amount of compound I.

[0011] The maximum wavelength of the visible light is λ. em max =399nm, specifically the visible light comes from 1 to 2 3W blue LED lights.

[0012] Furthermore, R 1 for R 2 For phenyl, R 3 For H, Cyclopropyl, phenyl, benzyl, R 4 H, methyl, COOMe, COOPh

[0013] Or R 3 R 4 Together Wherein, L1 is H, 2-Me, 3-Me, 4-Me, 4-F, 4-Cl, 4-Br, 2,6-dimethyl, n is 1, 2, 3, 4, 5, m is 0, 1, 2, 3, p is 0, 1, 2, 3, 4, 5, q is 1, 2, 3, 4, 5, and R is H, 3-Cl, 3,4-Cl2, 4-OMe, 4-CF3, 4-F, 4-Cl, 4-Br, 4-Me, 4-Ph.

[0014] The β-aminosulfide prepared by the above method.

[0015] Compared with the prior art, the beneficial effects of the method of the present invention are as follows:

[0016] This invention utilizes a metal-free TDPZ photocatalyst in the reaction, resulting in extremely low catalyst dosage, high catalytic efficiency, mild reaction conditions, stability, high efficiency, simple operation, environmental friendliness, high product conversion rate, and good regioselectivity. Compared with existing synthetic methods, the most significant advantages of this invention are its high atom economy; broad substrate scope unrestricted by the electronegativity of substituents; use of a metal-free TDPZ photocatalyst, low catalyst dosage, mild reaction conditions, rapid and efficient reaction, high yield, high regioselectivity, and environmental friendliness. This invention can modify some steroid hormones (such as estrone, pregnenolone, etc.), and some of the products obtained are bioactive substances (such as Na+). v 1.4-Progenitor of channel blockers and regulators of hormone receptors. Detailed Implementation

[0017] The technical solution of the present invention will be further described in detail below with reference to the embodiments, but the scope of protection of the present invention is not limited thereto.

[0018] In the following examples, the organic photocatalyst TDPZ was prepared according to the literature (Yu Zhao, Chenhao Zhang, Kek FooChin, Oldˇrich Pytela, Guo Wei, Hongjun Liu, Filip Bures*, Zhiyong Jiang*. RSCAdv., 2014, 4, 30062).

[0019] Example 1

[0020] The specific preparation steps for 4-methoxy-N-(2-phenyl-1-(phenylthio)propane-2-yl)aniline are as follows:

[0021]

[0022] 150.0 μL (0.001 mmol, 0.01 equiv) of TDPZ solution (prepared by dissolving 5.88 mg of DPZ in 3.0 mL of toluene) was added to a 25 mL Schlenk tube, and the solvent was removed under vacuum. Then, 0.10 mmol of N-(4-methoxyphenyl)-S-phenylthiamine and 0.20 mmol of 1-propen-2-ylbenzene were added, followed by 3.0 mL of purified and dried toluene. The reaction mixture was then subjected to a series of steps: freezing at -80°C for 3–5 min, vacuuming, argon protection, and restoring to room temperature (generally, this process was repeated three times). The reaction flask was placed in a 25°C incubator and stirred for 30 hours under irradiation with a 3W blue LED lamp (2.0 cm from the reaction flask; maximum wavelength of the LED lamp was 399 nm). After the reaction was complete, the solvent was evaporated using a rotary evaporator, and the product 1 (90% yield) was obtained by direct column chromatography (volume ratio, n-hexane / ethyl acetate = 100–5:1). The NMR data are as follows: 1 HNMR(300MHz, CDCl3)δ7.59(d,J=7.6Hz,2H),7.43–7.35(m,4H),7.34–7.26(m,3H),7.26–7.17(m,1 H),6.67–6.60(m,2H),6.45–6.33(m,2H),4.27(s,1H),3.71(s,3H),3.58–3.40(m,2H),1.75(s,3H); 13 C NMR (75MHz, CDCl3) δ 152.6, 146.2, 139.6, 136.8, 130.2, 129.2, 128.8, 127.1, 126.6, 126.3, 117.8, 114.4, 59.5, 55.7, 49.3, 25.1; High-resolution data: HRMS (ESI) m / z 350.1570 (M+H + ),calc.for C 22 H 24 NOS 350.1573.

[0023] Example 2

[0024] The specific preparation steps for 4-methoxy-N-(2-phenyl-1-(4-chlorophenylthio)propane-2-yl)aniline are as follows:

[0025]

[0026] In this embodiment, N-(4-methoxyphenyl)-S-phenylthiamine in Example 1 was replaced with N-(4-methoxyphenyl)-S-4-chlorophenylthiamine, and the other steps were the same as in Example 1, yielding product 2, a green oily substance with a yield of 71%. The NMR data are as follows:1 H NMR(300MHz,CD2Cl2)δ7.59–7.51(m,2H),7.40–7.32(m,2H),7.32–7.19(m,5H),6.6 1–6.54(m,2H),6.33–6.25(m,2H),3.65(s,3H),3.48(q,J=12.7Hz,2H),1.67(s,3H); 13 CNMR (75MHz, CD₂Cl₂) δ 152.9, 146.2, 139.7, 135.9, 132.4, 131.5, 129.3, 129.0, 127.3, 126.5, 117.8, 114.5, 59.5, 55.8, 48.5, 26.3; High-resolution data: HRMS (ESI) m / z 384.1179 (M+H + ),calc.for C 22 H 23 ClNOS 384.1183.

[0027] Example 3

[0028] The specific preparation steps for 4-methoxy-N-(2-phenyl-1-(3-methylphenylthio)propane-2-yl)aniline are as follows:

[0029]

[0030] In this embodiment, N-(4-methoxyphenyl)-S-phenylthiamine in Example 1 was replaced with N-(4-methoxyphenyl)-S-3-methylphenylthiamine, and the other steps were the same as in Example 1, yielding product 3, a green oily substance with a yield of 53%. The NMR data are as follows: 1 H NMR (300MHz, CDCl3) δ7.57(d,J=7.7Hz,2H),7.36(t,J=7.5Hz,2H),7.31–7.24(m,1H),7.16(d,J=7.4Hz,3H),7.00(d,J=6.6H z,1H),6.61(d,J=8.5Hz,2H),6.31(d,J=8.5Hz,2H),4.32(s,1H),3.68(s,3H),3.50–3.32(m,2H),2.30(s,3H),1.70(s,3H); 13C NMR (75MHz, CDCl3) δ 152.5, 146.3, 139.7, 139.0, 136.5, 130.9, 129.0, 128.8, 127.5, 127.3, 127.1, 126.3, 117.8, 114.4, 59.5, 55.7, 49.3, 25.2, 21.4; High-resolution data: HRMS (ESI) m / z 364.1729 (M+H + ),calc.for C 23 H 26 NOS 364.1730.

[0031] Example 4

[0032] The specific preparation steps for N-(1-(benzo[d]thiazo-2-ylthio)-2-phenylpropane-2-yl)-4-methoxyaniline are as follows:

[0033]

[0034] In this embodiment, N-(4-methoxyphenyl)-S-phenylthiamine in Example 1 was replaced with S-(benzo[d]thiazol-2-yl)-N-(4-methoxyphenyl)thiamine, and the other steps were the same as in Example 1, yielding product 4, a yellowish-brown oily substance with a yield of 47%. The NMR data are as follows: 1 H NMR (300MHz, CDCl3) δ7.91(d,J=8.1Hz,1H),7.75(d,J=7.9Hz,1H),7.62(d,J=7.5Hz,2H),7.47(d,J=7.5Hz,1H),7.44–7.37(m,2H),7. 31(td,J=7.3,4.9Hz,2H),6.60(d,J=8.6Hz,2H),6.33(d,J=8.8Hz,2H),5.00(s,1H),3.97(q,J=13.6Hz,2H),3.66(s,3H),1.80(s,3H); 13 C NMR (75MHz, CDCl3) δ 167.5, 152.9, 152.2, 145.2, 139.4, 135.6, 128.8, 127.2, 126.5, 126.3, 124.5, 121.5, 121.2, 117.3, 114.4, 59.4, 55.7, 46.5, 26.2; High-resolution data: HRMS (ESI) m / z 407.1246 (M+H + ),calc.for C 23 H 22 N2OS2407.1243.

[0035] Example 5

[0036] The specific preparation steps for 4-methoxy-N-(2-phenyl-1-(propanethio)propane-2-yl)aniline are as follows:

[0037]

[0038] In this embodiment, N-(4-methoxyphenyl)-S-phenylthiamine in Example 1 was replaced with N-(4-methoxyphenyl)-S-propylthiohydroxylamine, and the solvent toluene was replaced with dichloromethane. The other steps were the same as in Example 1, yielding product 5, a yellowish-brown oily substance with a yield of 58%. The NMR data are as follows: 1 H NMR (300MHz, CDCl3) δ7.55(d,J=7.4Hz,2H),7.35(t,J=7.3Hz,2H),7.27(d,J=8.3Hz,1H),6.61(d,J=8.5Hz,2H),6.34(d,J=8.5Hz,2H ),4.40(s,1H),3.68(s,3H),2.97(q,J=12.8Hz,2H),2.38(t,J=7.3Hz,2H),1.66(s,3H),1.56(q,J=7.4Hz,2H),0.94(t,J=7.3Hz,3H); 13 C NMR (75MHz, CDCl3) δ 152.5, 146.5, 140.0, 128.7, 127.0, 126.3, 117.7, 114.4, 59.1, 55.7, 47.6, 36.1, 24.8, 23.3, 13.5; High-resolution data: HRMS (ESI) m / z 316.1732 (M+H + ),calc.for C 19 H 26 NOS 316.1730.

[0039] Example 6

[0040] The specific preparation steps for N-(2-phenyl-1-(phenylthio)propane-2-yl)aniline are as follows:

[0041]

[0042] In this embodiment, N-(4-methoxyphenyl)-S-phenylthiamine in Example 1 was replaced with N,S-diphenylthiamine, and the other steps were the same as in Example 1, yielding product 6, a green oily substance with a yield of 67%. The NMR data are as follows: 1H NMR(300MHz, CDCl3)δ7.54(d,J=6.9Hz,2H),7.36(t,J=8.4Hz,4H),7.31–7.24(m,3H),7.24–7.16(m,1H),7.0 0(t,J=7.9Hz,2H),6.65(t,J=7.3Hz,1H),6.33(d,J=8.0Hz,2H),4.59(s,1H),3.52–3.34(m,2H),1.77(s,3H); 13 C NMR (75MHz, CDCl3) δ 145.8, 145.7, 136.7, 130.3, 129.2, 128.9, 128.8, 127.2, 126.7, 126.2, 117.9, 116.0, 59.2, 49.7, 24.8; High-resolution data: HRMS (ESI) m / z 320.1466 (M+H + ),calc.for C 21 H 22 NS 320.1467.

[0043] Example 7

[0044] The specific preparation steps for N-(2-(benzo[d][1,3]dioxane-5-yl)-1-(phenylthio)propane-2-yl)-4-methoxyaniline are as follows:

[0045]

[0046] In this embodiment, 1-propen-2-ylbenzene in Example 1 was replaced with 5-(propen-1-en-2-yl)benzo[d][1,3]dioxane, and the other steps were the same as in Example 1, yielding product 7, a yellowish-brown oily substance with a yield of 66%. NMR data are as follows: 1 H NMR (300MHz, CDCl3) δ7.40–7.34(m,2H),7.30–7.24(m,2H),7.23–7.15(m,1H),7.09(d,J=1.9Hz,1H),6.99(dd,J=8.2,1.9Hz,1H),6 .78(d,J=8.2Hz,1H),6.66–6.59(m,2H),6.39–6.30(m,2H),5.95(s,2H),4.28(s,1H),3.69(s,3H),3.43–3.28(m,2H),1.66(s,3H); 13C NMR (75MHz, CDCl3) δ 152.6, 148.2, 146.6, 140.3, 139.6, 136.7, 130.2, 129.1, 126.6, 119.3, 117.8, 114.4, 108.3, 107.3, 101.2, 59.3, 55.7, 49.6, 25.0; High-resolution data: HRMS (ESI) m / z 394.1472 (M+H + ),calc.for C 23 H 24 NO3S 394.1471.

[0047] Example 8

[0048] The specific preparation steps for 4-methoxy-N-(2-(naphthyl-2-yl)-1-(phenylthio)propane-2-yl)aniline are as follows:

[0049]

[0050] In this embodiment, 1-propen-2-ylbenzene in Example 1 was replaced with 2-(propen-1-en-2-yl)naphthalene, and the other steps were the same as in Example 1, yielding product 8, a yellowish-brown oily substance with a yield of 83%. The NMR data are as follows: 1 H NMR(300MHz, CDCl3)δ7.98(s,1H),7.86(d,J=8.9Hz,3H),7.79(d,J=8.7Hz,1H),7.57–7.47(m,2H),7.41(d,J=7.6Hz,2H),7.28(t,J=7 .0Hz,2H),7.24–7.15(m,1H),6.60(d,J=8.7Hz,2H),6.37(d,J=8.5Hz,2H),4.41(s,1H),3.68(s,3H),3.62–3.47(m,2H),1.82(s,3H); 13 C NMR (75MHz, CDCl3) δ 152.5, 143.8, 139.5, 136.6, 133.4, 132.5, 130.1, 129.0, 128.4, 128.2, 127.5, 126.4, 126.0, 125.9, 124.7, 124.6, 117.8, 114.3, 59.5, 55.5, 49.0, 25.0; High-resolution data: HRMS (ESI) m / z 400.1732 (M+H + ),calc.for C 26 H 26 NOS 400.1730.

[0051] Example 9

[0052] The specific preparation steps for 4-methoxy-N-(1-phenylthio-2-(thiophen-2-yl)propane-2-yl)aniline are as follows:

[0053]

[0054] In this embodiment, 1-propen-2-ylbenzene in Example 1 was replaced with 2-(propen-1-en-2-yl)thiophene, and the other steps were the same as in Example 1, yielding product 9, a yellow oily substance with a yield of 57%. The NMR data are as follows: 1 H NMR (300MHz, CD2Cl2) δ7.37(d,J=7.5Hz,2H),7.31–7.25(m,3H),7.21(d,J=7.2Hz,1H),6.97(d,J=3.3Hz,2H),6.62(d,J= 8.6Hz,2H),6.43(d,J=8.6Hz,2H),4.32(s,1H),3.67(s,3H),3.58(d,J=12.9Hz,1H),3.46(d,J=13.0Hz,1H),1.70(s,3H); 13 C NMR (75MHz, CD₂Cl₂) δ 153.6, 153.3, 139.4, 136.9, 130.3, 129.4, 127.2, 126.8, 125.4, 123.7, 119.0, 114.5, 59.0, 55.8, 49.0, 26.6; High-resolution data: HRMS (ESI) m / z 356.1133 (M+H + ),calc.for C 20 H 22 NOS2356.1137.

[0055] Example 10

[0056] The specific preparation steps for N-(1,2-diphenyl-3-(phenylthio)propane-2-yl)-4-methoxyaniline are as follows:

[0057]

[0058] In this embodiment, 1-propen-2-ylbenzene in Example 1 was replaced with propylene-2-ene-1,2-dimethyldibenzene, and one 3W blue LED lamp was replaced with two 3W blue LED lamps. The other steps were the same as in Example 1, yielding product 10, a yellowish-brown oily substance with a yield of 52%. The NMR data are as follows: 1H NMR(300MHz, CD2Cl2)δ7.40–7.35(m,2H),7.34–7.26(m,3H),7.19(d,J=4.3Hz,4H),7.17–7.05(m,4H),6.80–6.73(m,2H),6.61–6.54(m,2H), 6.34–6.26(m,2H),4.13(s,1H),3.69(d,J=12.1Hz,1H),3.65(s,3H),3.51(d,J=12.9Hz,1H),3.45(d,J=12.0Hz,1H),3.25(d,J=12.9Hz,1H); 13 C NMR (75MHz, CD₂Cl₂) δ 152.5, 143.9, 139.6, 137.1, 136.4, 131.1, 129.8, 129.1, 128.6, 128.1, 127.4, 127.0, 126.3, 117.2, 114.6, 62.3, 55.8, 45.4, 42.0; High-resolution data: HRMS (ESI) m / z 426.1883 (M+H + ), calc.forC 28 H 28 NOS 426.1886.

[0059] Example 11

[0060] The specific preparation steps for 4-methoxy-N-(2-phenyl-1-(phenylthio)hept-6-en-2-yl)aniline are as follows:

[0061]

[0062] In this embodiment, 1-propen-2-ylbenzene in Example 1 was replaced with 1,6-heptadien-2-ylbenzene, and the other steps were the same as in Example 1, yielding product 11, a yellowish-brown oily substance with a yield of 75%. The NMR data are as follows: 1H NMR(300MHz, CDCl3)δ7.50(d,J=7.6Hz,2H),7.35(t,J=7.6Hz,2H),7.32–7.16(m ,5H),7.18–7.12(m,1H),6.58(d,J=8.8Hz,2H),6.31(d,J=8.8Hz,2H),5.71–5.5 1(m,1H),4.91(d,J=5.7Hz,1H),4.86(s,1H),4.06(s,1H),3.75(d,J=12.5Hz,1H ),3.68(s,3H),3.62(d,J=12.4Hz,1H),2.12–1.81(m,4H),1.17(p,J=7.7Hz,2H); 13 C NMR (75MHz, CDCl3) δ 152.6, 144.5, 139.3, 138.5, 137.0, 130.4, 128.9, 128.6, 127.0, 126.8, 126.4, 117.8, 114.9, 114.4, 61.9, 55.7, 42.3, 40.6, 33.8, 23.0; High-resolution data: HRMS (ESI) m / z 404.2040 (M+H + ), calc.forC 25 H 28 NOS 404.2043.

[0063] Example 12

[0064] The specific preparation steps for N-(1-cyclopropyl-1-phenyl-2-(phenylthio)ethyl)-4-methoxyaniline are as follows:

[0065]

[0066] In this embodiment, 1-propen-2-ylbenzene in Example 1 was replaced with 1-cyclopropylvinylbenzene, and the other steps were the same as in Example 1, yielding product 12, a yellowish-brown oily substance with a yield of 46%. The NMR data are as follows: 1 H NMR(300MHz, CDCl3)δ7.5(d,J=7.1Hz,2H),7.37–7.25(m,5H),7.2(t,J=7.5Hz,2H),7.1(t,J=7.2Hz,1H),6.6–6.6(m,2H),6.4–6.3(m,2H) ,4.3(s,1H),3.9(d,J=12.4Hz,1H),3.7(d,J=12.4Hz,1H),3.7(s,3H),1.7–1.6(m,1H),0.5–0.4(m,1H),0.4–0.2(m,2H),0.1–-0.0(m,1H);13 C NMR (75MHz, CDCl3) δ 152.3, 141.4, 139.3, 137.6, 129.8, 128.9, 128.2, 128.0, 127.2, 126.1, 117.6, 114.4, 62.0, 55.7, 44.2, 21.6, 1.9, 1.5; High-resolution data: HRMS (ESI) m / z 376.1730 (M+H + ),calc.for C 24 H 26 NOS 376.1730.

[0067] Example 13

[0068] The specific preparation steps for N-(2-((2,6-dimethylphenyl)thio)-1-phenylethyl)-4-methoxyaniline are as follows:

[0069]

[0070] In this embodiment, N-(4-methoxyphenyl)-S-phenylthiamine in Example 1 was replaced with S-(2,6-dimethylphenyl)-N-(4-methoxyphenyl)phenylthiamine, 1-propen-2-ylbenzene was replaced with styrene, and the solvent toluene was replaced with dichloromethane. The other steps were the same as in Example 1, yielding product 13, which is Na. v A precursor to a 1,4-channel blocker, present as a yellow oily substance with a yield of 54%. NMR data are as follows: 1 H NMR(300MHz, CDCl3) δ7.30(d,J=3.4Hz,4H),7.25–7.19(m,1H),7.16–7.07(m,3H),6.66(d,J=8.6Hz,2H),6.38(d,J=8.4Hz,2H), 4.30(s,1H),4.17(dd,J=9.8,3.8Hz,1H),3.69(s,3H),3.08(dd,J=13.6,3.9Hz,1H),2.90(dd,J=13.4,9.6Hz,1H),2.49(s,6H); 13 C NMR (126MHz, CDCl3) δ 152.4, 143.1, 141.6, 132.8, 128.9, 128.6, 128.5, 127.6, 126.5, 124.5, 115.0, 114.8, 59.1, 55.8, 43.5, 22.1; High-resolution data: HRMS (ESI) m / z 364.1727 (M+H + ),calc.for C 23 H 26NOS 364.1730.

[0071] Example 14

[0072] The specific preparation steps for (S)-N-(4-methoxyphenyl)-1-((phenylthio)methyl)-2,3-dihydro-1H-inden-1-amine are as follows:

[0073]

[0074] In this embodiment, 1-propen-2-ylbenzene in Example 1 was replaced with 1-methylene-2,3-dihydro-1H-indenene, and the other steps were the same as in Example 1, yielding product 14, a yellowish-brown oily substance with a yield of 53%. The NMR data are as follows: 1 H NMR(300MHz, CDCl3)δ7.41(d,J=7.9Hz,2H),7.34–7.26(m,5H),7.24–7.17(m,2H),6.66–6.57(m,2H),6.34–6.24(m,2H),4 .36(s,1H),3.68(s,3H),3.34(s,2H),2.99–2.89(m,2H),2.52(dt,J=13.5,9.1Hz,1H),2.16(ddd,J=13.4,6.5,4.6Hz,1H); 13 C NMR (75MHz, CDCl3) δ 152.8, 146.4, 142.5, 139.4, 136.7, 130.0, 129.2, 128.2, 126.9, 126.6, 125.4, 123.9, 118.4, 114.4, 68.9, 55.7, 46.1, 32.9, 29.5; High-resolution data: HRMS (ESI) m / z 362.1573 (M+H + ),calc.for C 23 H 24 NOS 362.1573.

[0075] Example 15

[0076] The specific preparation steps for (S)-N-(4-methoxyphenyl)-4-((phenylthio)methyl)thiochromane-4-amine are as follows:

[0077]

[0078] In this embodiment, 1-propen-2-ylbenzene in Example 1 was replaced with 4-methylenethiochromane, and the other steps were the same as in Example 1, yielding product 2, a yellowish-brown oily substance with a yield of 55%. The NMR data are as follows: 1H NMR (300MHz, CDCl3) δ7.72(d,J=7.9Hz,1H),7.49(d,J=7.6Hz,2H),7.40–7.24(m,4 H),7.18–7.08(m,2H),7.03(t,J=7.2Hz,1H),6.63(d,J=8.5Hz,2H),6.26(d,J=8.5H z,2H),4.44(s,1H),3.68(s,3H),3.60(d,J=13.4Hz,1H),3.26–3.14(m,2H),2.84( dt,J=13.0,4.1Hz,1H),2.67(td,J=13.7,4.1Hz,1H),2.27(dt,J=14.2,3.7Hz,1H); 13 C NMR (75MHz, CDCl3) δ 152.5, 138.6, 137.1, 135.8, 133.1, 130.8, 129.4, 128.2, 127.6, 127.2, 126.9, 124.9, 117.5, 114.5, 57.6, 55.7, 46.8, 28.1, 23.9; High-resolution data: HRMS (ESI) m / z 394.1294 (M+H + ),calc.for C 23 H 24 NOS2 394.1294.

[0079] Example 16

[0080] The specific preparation steps for methyl 2-((4-methoxyphenyl)amino)-2-phenyl-3-(phenylthio)propionate are as follows:

[0081]

[0082] In this embodiment, 1-propen-2-ylbenzene in Example 1 was replaced with methyl 2-phenylacrylate, and the other steps were the same as in Example 1, yielding product 16, a yellow oily substance with a yield of 54%. The NMR data are as follows: 1 H NMR (300MHz, CDCl3) δ7.60 (d, J=7.2Hz, 2H), 7.42–7.28 (m, 5H), 7.25–7.10 (m, 3H), 6.6 3–6.55(m,2H),6.36–6.27(m,2H),5.25(s,1H),4.07(s,2H),3.68(s,3H),3.47(s,3H); 13C NMR (75MHz, CDCl3) δ 172.7, 152.8, 139.9, 137.5, 135.8, 131.1, 128.9, 128.2, 127.1, 126.8, 117.7, 114.5, 67.6, 55.7, 53.0, 39.9; High-resolution data: HRMS (ESI) m / z 394.1465 (M+H + ), calc.forC 23 H 24 NO3S 394.1471.

[0083] Example 17

[0084] The specific preparation steps for 4-methoxy-N-(1-phenyl-2-(phenylthio)-1-(pyridin-2-yl)ethyl)aniline are as follows:

[0085]

[0086] In this embodiment, 1-propen-2-ylbenzene in Example 1 was replaced with 1-phenylvinylpyridine, and the other steps were the same as in Example 1, yielding product 17, a yellow oily substance with a yield of 86%. The NMR data are as follows: 1 H NMR(300MHz, CDCl3)δ8.59(dt,J=4.8,1.4Hz,1H),7.71–7.56(m,2H),7.37–7.28(m,2H),7.25–7.08( m,4H),6.69–6.58(m,2H),6.41–6.29(m,2H),3.74–3.67(m,4H),3.64(d,J=13.0Hz,1H),1.71(s,3H); 13 C NMR (75MHz, CDCl3) δ 164.6, 153.0, 148.9, 139.0, 137.0, 136.7, 130.0, 129.0, 126.2, 122.0, 121.7, 118.7, 114.4, 61.6, 55.7, 45.6, 25.9; High-resolution data: HRMS (ESI) m / z 351.1520 (M+H + ),calc.for C 21 H 23 N2OS 351.1526.

[0087] Example 18

[0088] The specific preparation steps for 4-methoxy-N-(1-(phenylthio)-2-(thiazolyl-2-yl)propyl)aniline are as follows:

[0089]

[0090] In this embodiment, 1-propen-2-ylbenzene in Example 1 was replaced with 2-(1-propen-2-yl)thiazole, and the other steps were the same as in Example 1, yielding product 18, a yellow oily substance with a yield of 82%. The NMR data are as follows: 1 H NMR (300MHz, CDCl3) δ7.72(d,J=3.3Hz,1H),7.34(d,J=7.3Hz,2H),7.30(d,J=3.3Hz,1H),7.25–7.13(m,3H) ,6.72–6.62(m,2H),6.50–6.40(m,2H),4.50(s,1H),3.76–3.69(m,4H),3.63(d,J=13.3Hz,1H),1.75(s,3H); 13 C NMR (75MHz, CDCl3) δ 178.7, 153.9, 142.5, 137.9, 136.3, 130.3, 129.1, 126.7, 120.6, 119.7, 114.4, 61.3, 55.6, 46.0, 26.4; High-resolution data: HRMS (ESI) m / z 357.1090 (M+H + ),calc.for C 19 H 21 N2OS2357.1084.

[0091] Example 19

[0092] The specific preparation steps for 4-methoxy-N-(2-(1-methyl-1H-benzo[d]imidazol-2-yl)-1-(phenylthio)propyl)aniline are as follows:

[0093]

[0094] In this embodiment, 1-propen-2-ylbenzene in Example 1 was replaced with 1-methyl-2-(1-propen-2-yl)-1H-imidazolium, and the other steps were the same as in Example 1, yielding product 19, a yellow oily substance with a yield of 95%. The NMR data are as follows: 1 HNMR(300MHz, CDCl3)δ7.81(td,J=5.0,1.9Hz,1H),7.39–7.27(m,5H),7.24–7.08(m,3H),6.55(d,J=8.7Hz,2 H),6.24–6.14(m,2H),4.17(s,1H),3.99(d,J=14.6Hz,3H),3.90(d,J=13.8Hz,1H),3.64(s,2H),1.79(s,3H); 13C NMR (75MHz, CDCl3) δ 156.4, 153.2, 141.9, 138.8, 137.0, 136.3, 130.4, 129.0, 126.6, 122.9, 122.2, 119.8, 117.1, 114.9, 109.5, 58.3, 55.6, 43.6, 31.6, 25.9; High-resolution data: HRMS (ESI) m / z 404.1791 (M+H + ),calc.for C 24 H 26 N3OS404.1790.

[0095] Example 20

[0096] The specific preparation steps for (R)-N-(4-cyano-3-(trifluoromethyl)phenyl)-3-((4-fluorophenyl)thio)-2-((4-methoxyphenyl)amino)-2-phenylpropionamide are as follows:

[0097]

[0098] In this embodiment, N-(4-methoxyphenyl)-S-phenylthiamine in Example 1 was replaced with S-(4-fluorophenyl)-N-(4-methoxyphenyl)thiohydroxylamine, and 1-propen-2-ylbenzene was replaced with N-(4-cyano-3-(trifluoromethyl)phenyl)-2-phenylacrylamide. Other steps were the same as in Example 1, yielding product 20. This compound is a precursor for regulating hormone receptors, is a yellow oil, and has a yield of 72%. NMR data are as follows: 1 H NMR (300MHz, CDCl3) δ9.17(s,1H),7.91(s,1H),7.78–7.68(m,2H),7.60(d,J=7.4Hz,2H),7.37(q,J=7.8,7.4Hz,3H),6.99(dd,J=8.4,5 .4Hz,2H),6.75(dd,J=17.0,8.5Hz,4H),6.59(d,J=8.5Hz,2H),4.79(s,1H),4.10(d,J=8.9Hz,1H),3.89(d,J=13.9Hz,1H),3.72(s,3H); 19 F NMR (471MHz, CDCl3) δ -62.21. 13C NMR (75MHz, CDCl3) δ 171.7, 162.1 (d, J = 247.6Hz), 154.6, 141.7, 138.5, 136.6, 135.9, 134.2 (d, J = 32.9Hz), 133.5 (d, J = 8.2Hz), 130.4 (d, J = 3.5Hz), 129.3, 128.8, 125.9, 121.9, 118.9, 117.4 (q, J = 4.9Hz), 116.0 (d, J = 21.9Hz), 115.5, 115.1, 104.8, 68.6, 55.7, 41.1; High-resolution data: HRMS (ESI) m / z 566.1520 (M+H + ),calc.for C 30 H 24 F4N3O2S 566.1520.

[0099] Example 21

[0100] The specific preparation steps for methyl (R)-2-((4-methoxyphenyl)amino)-2-phenyl-3-(propylthio)propionate are as follows:

[0101]

[0102] In this embodiment, N-(4-methoxyphenyl)-S-phenylthiamine in Example 1 was replaced with N-(4-methoxyphenyl)-S-propylthiamine, and 1-propen-2-ylbenzene was replaced with methyl 2-phenylacrylate. The other steps were the same as in Example 1, yielding product 21, a yellow oily substance with a yield of 42%. The NMR data are as follows: 1 H NMR (300MHz, CDCl3) δ7.60(d,J=8.1Hz,2H),7.44–7.28(m,3H),6.62(d,J=8.4Hz,2H),6.35(d,J=8.4Hz,2H),5.1 6(s,1H),3.70(s,3H),3.67(s,3H),3.62(s,2H),2.35(t,J=7.3Hz,2H),1.56–1.39(m,2H),0.86(t,J=7.3Hz,3H); 13 C NMR (75MHz, CDCl3) δ 173.2, 152.6, 140.1, 138.1, 128.8, 128.0, 127.1, 117.4, 114.6, 68.0, 55.7, 53.2, 36.7, 35.3, 23.2, 13.4; High-resolution data: HRMS (ESI) m / z 360.1627 (M+H + ),calc.for C 20 H26 NO3S 360.1628.

[0103] Example 22

[0104] The specific preparation steps for (8R,9S,13S,14S)-3-(2-((4-methoxyphenyl)amino)-1-(phenylthio)propyl)-13-methyl-6,7,8,9,11,12,13,14,15,16-decahydro-17H-cyclopentan[a]phenanthren-17-one are as follows:

[0105]

[0106] In this embodiment, 1-propen-2-ylbenzene in Example 1 was replaced with (8R,9S,13S,14S)-13-methyl-3-(1-propen-2-yl)-6,7,8,9,11,12,13,14,15,16-decahydro-17H-cyclopentanene-17-one. The other steps were the same as in Example 1, yielding product 22, a green oily substance with a yield of 68% and a dr ratio of 1:1. The NMR data are as follows: 1 H NMR (300MHz, CDCl3) δ7.35(d,J=7.8Hz,2H),7.26(m,5H),7.19(d,J=7.1Hz,1H),6.62(d,J=8.7Hz,2H),6.36(d,J=8.4Hz,2H),3.69(s,3H),3 .49–3.31(m,2H),2.94–2.83(m,3H),2.61–2.39(m,2H),2.37–2.25(m ,1H),2.23–1.94(m,5H),1.67(s,3H),1.64–1.38(m,6H),0.93(s,3H); 13 C NMR (75MHz, CDCl3) δ 152.6, 143.5, 139.6, 138.5, 136.8, 136.7, 130.1, 129.1, 126.8, 126.5, 125.7, 123.7, 118.1, 114.3, 59.3, 55.7, 50.7, 49.1 (d, J = 13.3Hz), 48.2, 44.5, 38.2, 36.0, 31.7, 29.8, 26.7, 25.7, 25.1 (d, J = 14.6Hz), 21.7, 14.0. High-resolution data: HRMS (ESI) m / z 526.2770 (M+H+), calc. for C 34 H 40 NO2S 526.2774.

[0107] Example 23

[0108] The specific preparation steps for (3S,8S,9S,10R,13S,14S,17S)-17-acetyl-10,13-dimethyl-2,3,4,7,8,9,10,11,12,13,14,15,16,17-tetradecano-1H-cyclopentan[a]phenanthren-3-yl 2-((4-methoxyphenyl)amino)-2-methyl-3-(phenylthio)propionate methyl ester are as follows:

[0109]

[0110] In this embodiment, 1-propen-2-ylbenzene in Example 1 was replaced with (3S,8S,9S,10R,13S,14S,17S)-17-acetyl-10,13-dimethyl-2,3,4,7,8,9,10,11,12,13,14,15,16,17-tetradecano-1H-cyclopentaphenanthren-3-ylmethyl methacrylate. The other steps were the same as in Example 1, yielding product 23, a white solid with a melting point of 72.9–73.5 °C, a yield of 99%, and a dr ratio of 1:1. NMR data are as follows: 1 H NMR(300MHz, CDCl3) δ7.59(d,J=7.5Hz,2H),7.39–7.27(m,5H),7.24–7.09(m,3H),6.57(d,J=8.5 Hz,2H),6.31(d,J=7.8Hz,2H),5.29(dd,J=12.4,4.8Hz,1H),5.14(s,1H),4.51(tq,J=7.3,4.7Hz, 1H),4.13–4.00(m,2H),3.67(s,3H),2.52(t,J=8.6Hz,1H),2.23–2.14(m,1H),2.11(s,3H),2.08 –1.88(m,3H),1.84–1.51(m,6H),1.52–1.33(m,4H),1.33–0.94(m,5H),0.91(s,3H),0.61(s,3H); 13C NMR (75MHz, CDCl3) δ209.7,171.6,152.6,140.1,140.1,139.4,139.3,137.8,136.3,136.3 ,130.7,130.7,128.9,128.9,128.8,128.0,127.0,126.6,126.6,122.6,117.4,117.3,114 .5,76.0,67.7,67.6,63.8,56.9,55.7,49.9,44.1,39.8,38.8,37.4,37.4,36.9,36.8,36.6,36.6,31.9,31.8,31.7,27.3,27.2,24.6,22.9,21.1,19.4,13.3; High-resolution data is: HRMS(ESI) m / z 678.3599 (M+H + ),calc.for C 43 H 52 NO4S 678.3612.

[0111] Example 24

[0112]

[0113] KF (0.18 mmol) was dissolved in a mixed solution of acetonitrile and water. M-methylchloroperoxybenzoic acid (0.18 mmol) was added in portions at 0 °C. After stirring for 30 minutes, compound 16 (0.1 mmol) from Example 16 was added, and the mixture was stirred at room temperature. After the reaction was complete, the reaction mixture was neutralized with sodium bicarbonate, followed by extraction with ethyl acetate. The combined organic phases were dried over anhydrous sodium sulfate and concentrated under vacuum. The resulting solution was purified by silica gel column chromatography with petroleum ether / ethyl acetate (15 / 1 to 5 / 1) to give sulfone 25 in 85% yield.

[0114] The prepared sulfone 25 (0.085 mmol) was dissolved in 3.0 mL of acetonitrile. A solution of cerium ammonium nitrate (CAN, 0.37 mmol) dissolved in 2.0 mL of water was added at 0 °C. The mixture was then stirred at room temperature for 2 hours. The solution was treated with 2N hydrochloric acid to approximately pH 1. The aqueous phase was extracted with ethyl acetate (3 × 4 mL) to remove impurities, and then alkalized with a saturated sodium bicarbonate solution. The resulting suspension was extracted again with dichloromethane (3 × 6 mL). After drying with anhydrous sodium sulfate, the solvent was removed by rotary evaporation to obtain product 24, a white solid with a melting point of 58.5–58.7 °C and a yield of 55%. NMR data are as follows: 1H NMR(300MHz,CD2Cl2)δ7.84(d,J=7.9Hz,2H),7.68–7.61(m,1H),7.54(t,J=7.6Hz,2H) ,7.48–7.42(m,2H),7.34–7.26(m,3H),4.15(d,J=14.3Hz,1H),3.74(d,J=16.2Hz,4H); 13 CNMR (75MHz, DMSO) δ 173.2, 141.3, 141.2, 133.6, 129.2, 128.4, 127.9, 127.6, 125.6, 63.7, 62.1, 52.6; High-resolution data: HRMS (ESI) m / z 320.0951 (M+H + ),calc.for C 16 H 18 NO4S 320.0961.

Claims

1. A method for the photocatalytic production of β-amino sulfides, characterized in that, The thiamine compound I and the terminal olefin II are reacted completely under irradiation of visible light at 20-30 DEG C in an organic solvent under an argon atmosphere with TDPZ as a visible light catalyst to obtain the target β-amino sulfide III by separation and purification, ， R 1 is an alkyl group or an aryl group, R 2 is an aryl group or a hydrogen atom, R 3 , R 4 is a hydrogen atom, an alkyl group or an aryl group or a heteroaryl group or an ester group or an amide group.

2. The method of claim 1, wherein the method is a method of photocatalytic production of β- aminosulfides by visible light, characterized in that, The molar ratio of the thiamine compound I and the terminal olefin II is 1:2, and the amount of the organic light catalyst TDPZ added is 1.0% of the molar amount of the compound I.

3. The method of claim 1, wherein the method is a method of photocatalytic production of β- aminosulfides by visible light. The maximum wavelength of the visible light is λ em max = 399 nm, the visible light is provided by 1-2 3W blue LED lamps.

4. The method of claim 1, wherein the method is a method of photocatalytic production of β- aminosulfides by visible light. The organic solvent is toluene or dichloromethane.

5. The method of claim 1, wherein the method is performed using visible light. 5 R 1 for , , , ;R 2 For H, phenyl, , ;R 3 For H, , Cyclopropyl, phenyl, benzyl, , R 4 H, methyl, , , , , , COOMe, COOPh , , , , , , , , , , Or R 3 R 4 Together , , Wherein, L1 is H, 2-Me, 3-Me, 4-Me, 4-F, 4-Cl, 4-Br, 2,6-dimethyl, n is 0, 1, 2, 3, 4, 5, m is 0, 1, 2, 3, 4, 5, p is 0, 1, 2, 3, 4, 5, q is 1, 2, 3, 4, 5, and R is H, 3-Cl, 3,4-Cl2, 4-OMe, 4-CF3, 4-F, 4-Cl, 4-Br, 4-Me, 4-Ph.

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