Catalytic Enantioselective Intramolecular Aza‐Michael Addition to α,β‐Unsaturated Esters
Abstract
ABSTRACT A bifunctional iminophosphorane (BIMP)‐catalyzed enantioselective intramolecular aza‐Michael reaction of sulfonamides to tethered α,β‐unsaturated esters is described. Reactivity toward traditionally challenging ester Michael acceptors is achieved through careful catalyst design, enabling the synthesis of enantioenriched pyrrolidines, piperidines, and indoline derivatives in excellent yields (up to 99%) and enantiomeric ratios (up to 97.5:2.5 er) under operationally simple conditions. The broad reaction scope demonstrates excellent tolerance to variation in the sulfonamide group, the Michael acceptor, and substituents on the tether in between. Furthermore, the synthetic utility of the method is highlighted by gram‐scale reactions at reduced catalyst loadings and by downstream derivatization of multiple enantiopure products.
Article Details
Authors (6)
Evan G. W. Rutter
Department of Chemistry Chemistry Research Laboratory University of Oxford Oxford UK
Cameron J. MacRae
Department of Chemistry Chemistry Research Laboratory University of Oxford Oxford UK
Haoran Xiong
Department of Chemistry Chemistry Research Laboratory University of Oxford Oxford UK
Daniel Rozsar
Department of Chemistry Chemistry Research Laboratory University of Oxford Oxford UK
Katherine F. P. Clarke
Department of Chemistry Chemistry Research Laboratory University of Oxford Oxford UK
Darren J. Dixon