Synlett 2020; 31(18): 1838-1842
DOI: 10.1055/s-0040-1707299
letter

Triphosgene/Sodium Organosulfinate System: A General and Efficient Electrophilic Thiolation of Silylenol Ethers and Electron-Rich Heteroaromatics

Hai-jun Gao
,
Yu-xin Gu
,
Zhe-fei Wang
,
Yan-qin Yuan
,
Yan Wang
,
Sheng-rong Guo
Department of Chemistry, Lishui University, Lishui, 323000, P. R. of China   Email: yuanyq5474@lsu.edu.cn   Email: guosr9609@lsu.edu.cn
› Author Affiliations
This work was supported by the Natural Science Foundation of Zhejiang Province (No. LY19B020001, LY18B020004) and the Special Foundation for Young Scientists of Lishui, Zhejiang (2018RC09).


Abstract

An efficient and practical approach to electrophilic thiolation was developed by using commercially available triphosgene as a reductant and the appropriate alkyl- or arylsulfinates, which were transformed in situ into electrophilic RSCl intermediates in the presence of triphosgene. This procedure represents a general and powerful approach for the synthesis of α-(trifluoromethyl)thio-substituted ketones and thiolated electron-rich heteroaromatic compounds.

Supporting Information



Publication History

Received: 30 July 2020

Accepted after revision: 31 August 2020

Article published online:
08 October 2020

© 2020. Thieme. All rights reserved

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  • 11 Electrophilic Trifluoromethylthiolation of Silyl Enol Ethers; General Procedure A 10 mL Schlenk tube equipped with a magnetic stirring bar was charged with F3CSO2Na (0.4 mmol), the appropriate silyl enol ether (0.2 mmol), and MeCN (1 mL), and the mixture was stirred at –78 °C for the initial time. A solution of triphosgene (0.4 mmol) in MeCN (1 mL) was then added slowly from a syringe. After 1 h at –78 °C, the mixture was warmed to rt over 1 h, then diluted with CH2Cl2 (20 mL). The mixture was washed 5% aq NaHCO3 (10 mL), and the combined organic phase was dried (Na2SO4) and concentrated under reduced pressure. The residue was purified by column chromatography (silica gel). 1-Phenyl-2-[(trifluoromethyl)sulfanyl]ethanone (2a) Yellow oil; yield: 40.9 mg (93%). 1H NMR (300 MHz, CDCl3): δ = 7.96 (d, J = 6.8 Hz, 2 H), 7.65 (t, J = 6.8 Hz, 1 H), 7.54 (t, J = 6.8 Hz, 2 H), 4.53 (s, 2 H). 13C NMR (75 MHz, CDCl3): δ = 192.1 (s), 134.7 (s), 134.3 (d, J = 1.5 Hz), 130.7 (q, J = 306.4 Hz), 129.0 (s), 128.5 (s), 38.5 (q, J = 1.8 Hz). HRMS (EI-TOF): m/z [M]+ calcd for C9H7F3OS: 220.0170; found: 220.0162. Electrophilic Thiolation of Indoles or N-Methylpyrrole; General Procedure A 10 mL Schlenk tube equipped with a magnetic stirring bar was charged with RSO2Na (0.4 mmol) and the appropriate indole or N-methylpyrrole (0.2 mmol). The tube was then evacuated and backfilled with dry N2 (this operation was repeated three times), and the mixture was stirred at –78 °C for the initial time. A solution of triphosgene (0.4 mmol) in MeCN (1 mL) was added slowly from a syringe, and the mixture was stirred at –78 °C for 1 h. When the reaction was complete, the mixture was warmed to rt and diluted with CH2Cl2 (20 mL). The mixture was then washed with 5% aq NaHCO3 (10 mL), and the combined organic phase was dried (Na2SO4) and concentrated under reduced pressure. The residue was purified by column chromatography (silica gel). 3-[(Difluoromethyl)sulfanyl]-1-methyl-1H-indole (4a) Yellow oil; yield: 37.9 mg (89%). 1H NMR (300 MHz, CDCl3): δ = 7.80 (d, J = 7.8 Hz, 1 H), 7.42–7.20 (m, 4 H), 6.67 (t, J = 57.7 Hz, 1 H), 3.83 (s, 3 H). 13C NMR (75 MHz, DMSO-d 6): δ = 137.31, 136.14, 130.50, 122.82, 121.15 (t, J = 275 Hz), 120.98, 119.47, 109.82, 94.28, 33.23. MS (EI): m/z = 213.1 [M]+. HRMS (EI-TOF): m/z [M]+ calcd for C10H9F2NS: 213.0424; found: 213.042.