Stitching β-Ketothioamides with N-Tosylbenzoquinone Imine: Transition-Metal Free Site-Selective Domino Synthesis of 2-Amino-3-aroyl-5-sulfonamide Substituted Benzo[b]furans

Abstract

Benzofuran derivatives are core components in many biologically active natural and synthetic compounds including approved drugs. Herein, an easy-to-access and TM-free, one-pot, three-step synthesis of 2-amino-3-aroyl-5-sulfonamide substituted benzo[b]furans bearing many functional groups of different electronic and steric nature using thioamides (as a 2C synthon) and N-tosylbenzoquinone imine (as a CCO unit partner) at room temperature in open air is presented for the first time. The reaction proceeds via deprotonation/Michael addition/cyclization/aromatization cascades forming two new (CC and CO) bonds and one ring, liberating only H₂S as a byproduct. High resolution mass spectrometry study endorses the key intermediates involved during reaction, validating excellent regio- and chemoselectivity. This protocol will not only provide an efficient and scalable method to access diverse benzo[b]furans that could be adaptable to late-stage functionalization but also enrich the research domain of thioamides.