Traceless imidate-directed oxidative decarboxylative arylation of electron-deficient aromatic rings enabled by Pd–Ag bimetallic catalysis

Abstract

Summary

We report a strategic merger of traceless directing group–assisted C–H activation with oxidative decarboxylative arylation, enabling the one-pot synthesis of highly electron-deficient biaryl nitriles. Temporary masking of nitriles as aryl imidates facilitates efficient ortho-C–H activation, followed by in situ traceless elimination to regenerate the nitrile functionality. Mechanistic studies indicate cooperative Pd–Ag catalysis, wherein palladium promotes imidate-directed ortho-C–H activation and silver mediates decarboxylation of aryl carboxylic acids to forge the biaryl bond. The synthetic utility of this method is demonstrated through downstream elaboration to a zephycandidine A natural product analogue and anti-prion derivatives.