Asymmetric Synthesis of Polyfunctionalized Pyrrolidines via a Thiourea Catalyzed Domino Mannich/Aza-Michael Reaction

The domino Mannich/aza-Michael reaction of gamma-malonate-substituted alpha,beta-unsaturated esters with N-protected arylaldimines has been achieved. Catalyzed by bifunctional thioureas, 2,5-cis-configured polysubstituted pyrrolidines are obtained in good to excellent yields (76-99%), enantioselectivities (75-94%) and excellent diastereoselectivities (de >95%). The pure stereoisomers are available by crystallization and removal of the racemates.