Trace amounts of palladium catalysed the Suzuki–Miyaura reaction of deactivated and hindered aryl chlorides

Abstract

Electron-rich and hindered aryl chlorides are the most challenging substrates in Suzuki–Miyaura cross-coupling (SMC) reactions. Herein, we report a highly efficient catalytic system for the SMC reaction using trace amounts of commercially available catalysts [Pd(PPh₃)₄/(t-Bu)PCy₂; Pd loading as low as 9.5 × 10⁻⁵ mol%]. This catalytic system can efficiently couple deactivated and sterically hindered aryl chlorides with various substituted phenylboronic acids, even in one-pot multiple coupling reactions (yield of products up to 92%). The impact of solvents on SMC reactions and the mechanisms of by-product formation in aryl boronic acid couplings are analyzed using density functional theory (DFT). Utilizing trace amounts of commercially available catalysts avoids complex synthesis, reduces costs, and minimizes metal residues.