Nickel electrocatalytic C(sp3)-C(sp3) cross-coupling from activated carboxylic acids and amines.

Abstract

Carbon-carbon bond-forming reactions are central to medicinal chemistry efforts. Methods that utilise abundant and structurally diverse building blocks can accelerate chemical space exploration in drug discovery. Herein, we report an electrochemical deaminative-decarboxylative cross-coupling reaction to form C(sp3)-C(sp3) bonds, which draws from widely available alkyl carboxylic acids and amines. Our method achieves cross-coupling between alkyl radicals generated from secondary alkyl pyridinium salts and redox-active esters to access valuable functionalized saturated heterocycles. The protocol is compatible with telescoped substrate pre-activation to facilitate synthetic utility. We describe electrochemical reaction characterization and a mechanistic hypothesis for cross-coupling selectivity in the absence of radical-sorting reagents.