Mechanistic Studies on the Gold(I)-Catalyzed Cyclization of N-Propargyl Benzamide Derivatives

Abstract

The gold(I)-catalyzed cyclization of N-propargyl benzamide has been a popular benchmark reaction for the study of gold catalysis for over two decades. Literature consensus denotes the protodeauration step as rate-limiting, bringing certain assumptions with regards to ligand, anion, and solvent choice. The work described below reveals a solvent-dependent rate-limiting step, calling for a possible recontextualization of this common test reaction and the implications for its continued use. Further work details the study of generated off-cycle degradation products of gold catalysts, the degradation of gold catalysts in the cyclization of carbamate analogues, as well as the synthesis of bisbiphenyl phosphine ligands to limit the formation of these products. Despite the details of its kinetics being more complex than previously understood, the cyclization of N-propargyl benzamide still proves useful in studying the impact of media, substrate, and ligand on the performance of new and old gold catalysts.