Continuous flow synthesis of functionalized biaryl compounds via a benzyne intermediate

Abstract

A continuous flow protocol for the preparation of benzyne was developed utilizing readily accessible 1-bromo-2-iodobenzene and iPrMgCl·LiCl. The halogen–magnesium exchange and subsequent elimination reactions were conducted at temperatures of 0 °C and 80 °C, respectively, resulting in the generation of a highly reactive benzyne intermediate within minutes. The in situ generated benzyne can be efficiently employed in the continuous flow synthesis of functionalized biaryl compounds, including a series of ligands commonly utilized in Buchwald–Hartwig cross-coupling reactions.