Development and Mechanistic Studies of the Iridium-Catalyzed C-H Alkenylation of Enamides with Vinyl Acetates: A Versatile Approach for Ketone Functionalization.

Abstract

Ketone functionalization is a cornerstone of organic synthesis. Herein, we describe the development of an intermolecular C-H alkenylation of enamides with the feedstock chemical vinyl acetate to access diverse functionalized ketones. Enamides derived from various cyclic and acyclic ketones reacted efficiently, and a number of sensitive functional groups were tolerated. In this iridium-catalyzed transformation, two structurally and electronically similar alkenes-enamide and vinyl acetate-underwent selective cross-coupling through C-H activation. No reaction partner was used in large excess. The reaction is also pH- and redox-neutral with HOAc as the only stoichiometric by-product. Detailed experimental and computational studies revealed a reaction mechanism involving 1,2-Ir-C migratory insertion followed by syn-β-acetoxy elimination, which is different from that of previous vinyl acetate mediated C-H activation reactions. Finally, the alkenylation product can serve as a versatile intermediate to deliver a variety of structurally modified ketones.