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Updated: Jul 13, 2025

Metal-free Synthesis of Ynones from Acyl Chlorides and Potassium Alkynyltrifluoroborate Salts
Published on: February 24, 2015
Nickel-Mediated Alkyl-, Acyl-, and Sulfonylcyanation of [1.1.1]Propellane
Weizhe Dong1, Sebastian Keess2, Gary A Molander1,3
1Roy and Diana Vagelos Laboratories, Department of Chemistry, University of Pennsylvania, 231 S. 34th Street, Philadelphia, Pennsylvania 19104-6323, United States.
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.
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