Remote Asymmetric Induction by the Vinylogous Mukaiyama Aldol Reactions with ketene-N,O-acetal

Abstract

We found that the chiral ketene-N,O-acetal (1), prepared from α,β-unsaturated chiral imide, underwent a highly regio- and diastereoselective TiCl₄-mediated vinylogous Mukaiyama aldol reaction with carbonyl compounds. The stereochemical sense of these reactions can be regarded as a formal 1,6- and 1,6,7-asymmetric induction, and high selectivity in such a remote asymmetric inductions are quite unusual. From a synthetic point of view, this methodology can provide a one-step construction of δ-hydroxy-αγ-dimethyl-α,β-unsaturated carbonyl unit that can be seen in many natural products. We would like to report the scope, limitation, and application of this methodology.