Bifunctional amino sulfonohydrazide catalyzed direct asymmetric Mannich reaction of cyclic ketimines with ketones: highly diastereo- and enantioselective construction of quaternary carbon stereocenters.

A bifunctional amino sulfonohydrazide which contains multiple sites for hydrogen bonding with substrates was found to enhance reactivity and enantioselectivity in the direct asymmetric Mannich reaction of N-sulfonyl cyclic ketimines with ketones. In this efficient transformation, not only methyl ketones but also cyclic ketones can be employed to provide a general methodology to construct tetrasubstituted α-amino ester in a stereoselective manner. The synthetic utility of a substituted amino ester product is demonstrated by the synthesis of biologically active spirotetrahydrofuran.