Asymmetric catalysis of epoxide ring-opening reactions

Abstract

The discovery of the metal salen-catalyzed asymmetric ring-opening (ARO) of epoxides is chronicled. A screening approach was adopted for the identification of catalysts for the addition of TMSN3 to meso-epoxides, and the chiral (salen)CrN3 complex was identified as optimal. Kinetic and structural studies served to elucidate the mechanism of catalysis, which involves cooperative activation of both epoxide and azide by two different metal centers. Covalently linked bimetallic complexes were constructed off the basis of this insight, and shown to catalyze the ARO with identical enantioselectivity, but 1-2 orders of magnitude greater reactivity than the monomeric analogues. Extraordinarily high selectivity is observed in the kinetic resolution of terminal epoxides using the (salen)CrN3/TMSN3 system. A search for a practical method for the kinetic resolution reaction led to the discovery of highly enantiomerselective hydrolytic ring-opening using corresponding (salen)-Co(III) catalyst. This system displays extraordinary substrate generality, and allows practical access to enantiopure terminal epoxides on both laboratory and industrial scales.