Enantioselective 1,3-Dipolar Cycloaddition Reaction between Diazoacetates and α-Substituted Acroleins:  Total Synthesis of Manzacidin A

Abstract

A titanium BINOLate catalyzed asymmetric 1,3-dipolar cycloaddition reaction between alpha-substituted acroleins and alkyl diazoacetates has been developed. With this methodology in hand, chiral 2-pyrazolines containing a quaternary stereogenic center were obtained in high to excellent enantioselectivities (up to 95% ee). The synthetic utility of the optically enriched 2-pyrazoline thus obtained was demonstrated in the short synthesis of manzacidin A.