Nickel-mediated alkyl-, acyl-, and sulfonylcyanation of [1.1.1]propellane

Abstract

The replacement of traditional functional groups with polycyclic scaffolds has been increasingly rewarding in medicinal chemistry programs. Over the decades, 1,3-disubstituted bicyclo[1.1.1]pentanes (BCPs) have demonstrated the potential for being competent bioisosteres for aryl-, alkyl- and alkynyl substructures. Although highly desired, mild and versatile synthetic methods to access synthetically valuable BCP-containing building blocks remain limited. Herein, a versatile way to access bridgehead substituted BCP nitriles, a useful BCP building block, is described, enabled by the unexpected selectivity of nickel in the multi-component radical cyanation. Commodity materials including carboxylic acids, amines, sulfonyl chlorides, and alkyl chlorides are engaged to provide a broad spectrum of substituted BCP nitriles in a single-step, multi-component fashion.