Direct Regio‐ and Diastereoselective Synthesis of <i>δ</i>‐Lactams from Acrylamides and Unactivated Alkenes Initiated by Rh<sup>III</sup>‐Catalyzed C−H Activation
Sumin Lee, Natthawat Semakul, Tomislav Rovis
Abstract
Abstract 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 t RhCl 2 ] 2 as catalyst.