Diastereoselective direct amidation/aza-Michael cascade reaction to synthesize cis-1,3-disubstituted isoindolines

Abstract A convenient and efficient base-promoted cascade reaction for the synthesis of cis-1,3-disubstituted isoindolines has been reported herein. We discovered that various N-protected imines bearing a Michael acceptor react smoothly with several nitrogenous nucleophiles in the presence of 1,8-diazabicyclo[5.4.0]-7-undecene under mild conditions. cis-1,3-Disubstituted isoindolines bearing aminal functionality were assembled as a single diastereomer in moderate to good yields (52%–94%). This cascade process features the direct amidation of imines followed by the intramolecular aza-Michael reaction.