Thioarylation of anilines using dual catalysis: two-step synthesis of phenothiazines

Dodds, A. C., Puddu, S. and Sutherland, A. (2022) Thioarylation of anilines using dual catalysis: two-step synthesis of phenothiazines. Organic and Biomolecular Chemistry, 20(28), pp. 5602-5614. (doi: 10.1039/D2OB01082H) (PMID:35796590)

Abstract

A two-step synthesis of phenothiazines has been developed using a dual-catalytic ortho-thioarylation reaction of anilines as the key step. Activation of N-(2-bromophenylthio)succinimide was achieved using the super Lewis acid, iron(III) triflimide and the Lewis base, diphenyl selenide, resulting in an accelerated and efficient ortho-thioarylation reaction of various protected aniline derivatives and less reactive, unprotected analogues. The thioarylated adducts were then cyclised to the desired phenothiazines using either an Ullmann-Goldberg or Buchwald-Hartwig coupling reaction. The dual catalytic thioarylation and copper(I)-catalysed cyclisation approach was used for the four-step synthesis of methopromazine, a neuroleptic agent with antipsychotic activity.

• 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., Puddu, S., 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: 06 July 2022
• Copyright Holders: Copyright © 2022 The Royal Society of Chemistry
• First Published: First published in Organic and Biomolecular Chemistry 20(28): 5602-5614
• Publisher Policy: Reproduced under a Creative Commons License