Experimental and computational insights into the mechanism of the copper(i)-catalysed sulfonylative Suzuki-Miyaura reaction

Callum G J Hall; Helen F Sneddon; Peter Pogány; David M Lindsay; William J Kerr

doi:10.1039/d3sc01337e

Experimental and computational insights into the mechanism of the copper(i)-catalysed sulfonylative Suzuki-Miyaura reaction

Chem Sci. 2023 May 31;14(24):6738-6755. doi: 10.1039/d3sc01337e. eCollection 2023 Jun 21.

Authors

Callum G J Hall^{1

2}, Helen F Sneddon¹, Peter Pogány¹, David M Lindsay², William J Kerr²

Affiliations

¹ Medicines Design, GlaxoSmithKline Gunnels Wood Road, Stevenage SG1 2NY England UK.
² Department of Pure and Applied Chemistry, University of Strathclyde 295 Cathedral Street, Glasgow G1 1XL Scotland UK w.kerr@strath.ac.uk.

Abstract

A mechanistic study into the copper(i)-catalysed sulfonylative Suzuki-Miyaura reaction, incorporating sulfur dioxide, is described. Utilising spectroscopic and computational techniques, an exploration into the individual components of the competing catalytic cycles is delineated, including identification of the resting state catalyst, transmetalation of arylboronic acid onto copper(i), the sulfur dioxide insertion process, and the oxidative addition of aryl halide to Cu^I. Studies also investigated prominent side-reactions which were uncovered, including a competing copper(ii)-catalysed mechanism. This led to an additional proposed and connected Cu^I/Cu^II/Cu^III catalytic cycle to account for by-product formation.