Cation−π Interactions in the Benzylic Arylation of Toluenes with Bimetallic Catalysts

Abstract

A method to directly arylate toluene derivatives with aryl bromides to generate diarylmethanes, which are important building blocks in drug discovery, is described. In this method, KN(SiMe₃)₂ in combination with a (NIXANTPHOS)Pd catalyst accomplished the deprotonative activation of toluene derivatives to permit cross-coupling with aryl bromides. Good to excellent yields are obtained with a range of electron-rich to neutral aryl bromides. Both electron-rich and electron-poor toluene derivatives are well tolerated, and even 2-chlorotoluene performs well, providing a platform for introduction of additional functionalization. This discovery hinges on the use of a main group metal to activate toluene for deprotonation by means of a cation-π interaction, which is secured by a bimetallic K(NIXANTPHOS)Pd assembly. Mechanistic and computational studies support acidification of toluene derivatives by the K⁺-cation- π interaction, which may prove pertinent in the development of other, new reaction systems.