Direct Regio- and Diastereoselective Synthesis of δ-Lactams from Acrylamides and Unactivated Alkenes Initiated by Rh^III-Catalyzed C−H Activation

We report a Rh^III-catalyzed regio- and diastereoselective synthesis of δ-lactams from readily available acrylamide derivatives and unactivated alkenes. The reaction provides a rapid route to a diverse set of δ-lactams in good yield and stereoselectivity, which serve as useful building blocks for substituted piperidines. The regioselectivity of the reaction with unactivated terminal alkene is significantly improved by using Cp^t ligand on the Rh^III catalyst. The synthetic utility of the reaction is demonstrated by the preparation of a potential drug candidate containing a trisubstituted piperidine moiety. Mechanistic studies show that the reversibility of the C−H activation depends on the choice of Cp ligand on the Rh^III catalyst. The irreversible C−H activation is observed and becomes turnover-limiting with [Cp^tRhCl₂]₂ as catalyst.