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

ABSTRACT: We report a Rh^III -catalyzed regio- and diastereoselective synthesis of ?-lactams from readily available acrylamide derivatives and unactivated alkenes. The reaction provides a rapid route to a diverse set of ?-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 RhCl₂ ]₂ as catalyst.

SUBMITTER: Lee S 

PROVIDER: S-EPMC7097884 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature