Kinetic Evaluation of Cooperative [Co(salen)] Catalysts in the Hydrolytic Kinetic Resolution of rac-Epichlorohydrin

A wide variety of [Co(salen)] catalysts with different structures designed to enhance salen-salen cooperative interactions have been reported as catalysts for the hydrolytic kinetic resolution (HKR) of epoxides. However, the myriad catalysts have been evaluated under inconsistent experimental conditions, at different catalyst loadings, at different temperatures, with various epoxides and in several different laboratories, making rigorous comparisons between the catalysts impossible. To this end, 12 representative catalysts from our studies, as well as catalysts originally described by others, are reported in the HKR of epichlorohydrin under rigorously identical conditions. The comparison of the reactivity and selectivity of the different catalysts indicates that the soluble, oligomeric [Co(salen)] catalysts with cyclic frameworks impart the highest activity and enantio-selectivity (>99% ee, k(rel)>99) in this representative reaction, requiring very short reaction times (<30 min), including the most active catalyst reported to date for the target reaction. In general, it is found that soluble polymer or oligomer-supported catalysts are more active than insoluble supported catalysts under the conditions used. Among the insoluble catalysts, a polymer resin supported [Co(salen)] catalyst with excellent enantioselectivity (>99% ee, k(rel)>99) and medium reaction time (222 min), is the most active and selective of the class. The lessons demonstrated herein regarding design of active and selective catalysts offer useful insights into refining design strategies for other related cooperative catalytic reactions, suggesting emphases on catalyst flexibility and solubility under reaction conditions.