Synthesis of phenoxathiins using an iron-catalysed C–H thioarylation

Dodds, A. C. and Sutherland, A. (2022) Synthesis of phenoxathiins using an iron-catalysed C–H thioarylation. Organic and Biomolecular Chemistry, 20(8), pp. 1738-1748. (doi: 10.1039/D2OB00022A) (PMID:35142330)

Abstract

Phenoxathiins are an important class of sulfur-containing heterocycle, found as the core component in numerous pharmaceutically active agents and materials. Despite this importance, there are relatively few methods for the synthesis of these heterocycles that avoid complex starting materials, harsh conditions or precious transition metals. We report a two-step synthesis of phenoxathiins from phenols using iron and copper-mediated reactions. The first step involves the accelerated ortho-thioarylation of phenols using N-(2-bromophenylthio)succinimide, catalysed by the Lewis acid, iron(III) triflimide and the Lewis base, bis(4-methoxyphenyl)sulfane. In the second step, the thioarylated products were converted to a series of phenoxathiins using a copper-mediated, Ullmann-type, C–O bond forming cyclisation reaction. The synthetic utility of this two-step approach for the preparation of biologically relevant phenoxathiins was demonstrated using natural product-based phenols.

• Item Type: Articles
• Additional Information: Financial support from The Carnegie Trust for the Universities of Scotland (Ph.D. studentship to A.C.D.) and the University of Glasgow is gratefully acknowledged.
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Dodds, Miss Amy and Sutherland, Professor Andrew
• Authors: Dodds, A. C., and Sutherland, A.
• College/School: College of Science and Engineering > School of Chemistry
• Journal Name: Organic and Biomolecular Chemistry
• Publisher: Royal Society of Chemistry
• ISSN: 1477-0520
• ISSN (Online): 1477-0539
• Published Online: 08 February 2022
• Copyright Holders: Copyright © 2022 The Royal Society of Chemistry
• First Published: First published in Organic and Biomolecular Chemistry 20(8): 1738-1748
• Publisher Policy: Reproduced under a Creative Commons licence