Evaluation of enantiopure and non-enantiopure Co(III)-salen catalysts and their counter-ion effects in the hydrolytic kinetic resolution (HKR) of racemic epichlorohydrin

Hydrolytic kinetic resolution (HKR) resolves racemic epoxides using water as the nucleophile and is most often catalyzed by chiral Co(III)-salens.1 Previous studies have shown that the counter-ion of the Co(III)-salen has a direct effect on rate of HKR; when catalyzed by a 50:50 mix of (R,R)-Co(III)-salen-OH and (R,R)-Co(III)-salen-SbF6, the fastest HKR rates occurred. It has further been shown that the enantioselectivity is primarily associated with the reaction of (R,R)-Co(III)-salen-OH on the activated epoxide. Based on the aforementioned origin of selectivity, a catalyst containing a 50:50 mix of (R,R)-Co(III)-salen-OH and (±)-trans-Co(III)-salen-SbF6 could, in principle, give high activities and enantioselectivities for HKR comparable to a mixed counter-ion system containing both (R,R)-Co(III)-salens. Here, a series of experiments are described that demonstrate that highly selective catalysis is only achieved using 100% enantiopure ligand, and mixtures of (R,R)-Co(III)-salen and (±)-trans-Co(III)-salen yield lower activity and selectivity. Control experiments demonstrate this is due to rapid counter-ion scrambling under reaction conditions, precluding the possibility of effectively co-utilizing enantiopure (expensive) and racemic (inexpensive) catalysts with differing counter-ions. The mechanistic investigations resolving the counter-ion scrambling are consistent with the currently accepted mechanism for catalysis, involving cooperative activity of two Co(III)-salen species that activate the epoxide and water in the reaction.

Graphical abstractFigure optionsDownload full-size imageDownload high-quality image (85 K)Download as PowerPoint slideHighlights► HKR catalysis via molecular Co(III)-salen systems was studied. ► Co(III)-salens with 50% enantiopure ligand and nucleophilic counter-ions were used. ► This approach did not lead to enantioselective HKR catalysis. ► Counter-ion scrambling between Co centers occurred under reaction conditions. ► A novel way to regenerate deactivated polymer-supported Co(III) complexes was found.