Nickel-Mediated Alkyl-, Acyl-, and Sulfonylcyanation of [1.1.1]Propellane.

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]pen-tanes (BCPs) have demonstrated potential for being competent bio-isosteres 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 selec-tivity of nickel in the multi-component radical cyanation. Commod-ity 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.