Trifluoromethylthiolation of Arenes using Lewis acid and Lewis base dual catalysis

Waddell, L. J.N., Wilson, C. and Sutherland, A. (2024) Trifluoromethylthiolation of Arenes using Lewis acid and Lewis base dual catalysis. Journal of Organic Chemistry, 89(2), pp. 1275-1284. (doi: 10.1021/acs.joc.3c02571) (PMID:38156642)

Abstract

Incorporation of the highly lipophilic trifluoromethanesulfenyl group into bioactive molecules facilitates transport through lipid membranes, and thus, CF3S-containing compounds are important for drug discovery. Although reagents and procedures have been reported for arene trifluoromethylthiolation, methods are still required that are applicable to a diverse substrate scope and can be performed under mild conditions. Here, we describe a rapid and efficient approach for the trifluoromethylthiolation of arenes by catalytic activation of N-trifluoromethylthiosaccharin using a combination of iron(III) chloride and diphenyl selenide. This dual catalytic process allowed regioselective functionalization of a wide range of arenes and N-heterocycles under mild conditions and was used for the trifluoromethylthiolation of bioactive compounds such as tyrosine and estradiol.

• Item Type: Articles
• Additional Information: Financial support from EPSRC (studentship to L.J.N.W., EP/T517896/1) and the University of Glasgow is gratefully acknowledged.
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Wilson, Dr Claire and Sutherland, Professor Andrew and Waddell, Mr Lachlan
• Authors: Waddell, L. J.N., Wilson, C., and Sutherland, A.
• College/School: College of Science and Engineering > School of Chemistry
• Journal Name: Journal of Organic Chemistry
• Publisher: American Chemical Society
• ISSN: 0022-3263
• ISSN (Online): 1520-6904
• Published Online: 29 December 2023
• Copyright Holders: Copyright: © 2023 The Authors
• First Published: First published in Journal of Organic Chemistry 89(2):1275–1284
• Publisher Policy: Reproduced under a Creative Commons licence
• Data DOI: 10.5517/ccdc.csd.cc2hd7hn

Project Code	Award No	Project Name	Principal Investigator	Funder's Name	Funder Ref	Lead Dept
312561		EPSRC DTP 2020/21	Christopher Pearce	Engineering and Physical Sciences Research Council (EPSRC)	EP/T517896/1	Research and Innovation Services