The development of practical catalysts for asymmetric epoxide ring opening reactions

1-Aryloxy-2-alcohols are synthesized in high yield and enantiomeric excess via the kinetic resolution of terminal epoxides catalyzed by chiral (salen)Co(III) complexes. Optimization of reaction conditions resulted in the identification of a highly active and recyclable catalyst that is available in two steps from inexpensive, commercially available materials. Epoxides and phenols with a wide range of steric and electronic properties participate in the reaction. Epibromohydrin undergoes dynamic kinetic resolution to provide the corresponding phenoxy-bromohydrin in >99% ee.; Structural, kinetic and spectroscopic studies on the kinetic resolution support a cooperative bimetallic mechanism. In the rate-limiting and enantiodetermining step, phenoxide is delivered from (salen)Co(aryloxide) to the Lewis acid-activated epoxide of a (salen)Co(epoxide) complex. Binding constants for the enantiomeric epoxide substrates indicate that the selectivity observed is a result of a difference in reactivity between the enantiomers when bound to cobalt and not a result of differential binding strength of the two enantiomers.; Highly active catalysts were designed to exploit the cooperative bimetallic mechanism common to many epoxide ring-opening reactions. Novel oligomeric salen ligands and their cobalt appear to enforce proximity of metal centers, and render bimetallic reactions intramolecular. Oligomeric (salen)Co complexes show substantial enhancements in rate and enantioselectivity relative to monomeric (salen)Co complexes for asymmetric epoxide ring opening reactions. The asymmetric hydrolysis of meso epoxides, and the kinetic resolution of terminal epoxides with water, alcohols and phenols are described. The oligomeric catalysts are readily prepared from commercially available materials without chromatographic purification. Mass spectral analysis indicates that the catalyst mixture consist of cyclic structures with 2–7 metal binding sites. Discrete components of the catalyst mixture have been synthesized, and it was shown that the cyclic trimer was more active and enantioselective than the cyclic dieter or tetramer. Possible origins for the enhanced reactivity and selectivity displayed by the oligomeric catalysts are discussed.