Stereoselective Kinugasa/Aldol Cyclization: Synthesis of Enantioenriched Spirocyclic ß-Lactams.

ABSTRACT

We report an enantioselective copper-catalyzed Kinugasa/aldol domino reaction. This strategy enables access to a range of spirocyclic ß-lactam pyrrolidinones in a stereoselective fashion. Under mild reaction conditions, prochiral alkyne-tethered ketones are coupled with nitrones to enable the facile construction of two spirofused ring systems containing three continuous stereocenters with excellent enantioselectivity. Also disclosed are post-transformation modifications demonstrating potential downstream functionalization of the spirocyclic molecules.