(399a) Role of Counterion Replacement on the Deactivation of Co-Salen Catalysts in the Hydrolytic Kinetic Resolution of Epichlorohydrin

The hydrolytic kinetic resolution (HKR) of terminal epoxides using Co-salen catalysts provides a convenient route to the synthesis of enantioenriched chiral compounds by selectively converting one enantiomer of the racemic mixture (with a maximum 50% yield and 100% ee). The utilization of water as the nucleophile makes this reaction straightforward to perform at a relatively low cost. The proposed mechanism for the HKR of terminal epoxides involves the cooperativity of two Co-salen complexes, where one Co metal center activates the electrophile (epoxide) and the other Co metal center activates the nucleophile (water). Hence, the observed rate depends on the square of the catalyst concentration. With this mechanism in mind, researchers have developed polymeric Co-salen catalysts that exhibit activities 1-2 orders of magnitude greater than that of the monomeric Co-salen catalyst. Recently, we have designed an oligo(cyclo-octene) supported Co-salen catalyst, with the idea that the presence of multiple Co-salen units as side chains on the oligomeric catalyst can enhance the reactivity and enantioselectivity in the HKR reaction. Most of these multimeric, homogeneous catalysts, as well as supported catalysts, are difficult to synthesize and need to be regenerated after the reaction. The general mode of catalyst deactivation has been reported in the literature to be the change of the active Co(III) salen complex to an inactive Co(II) salen complex. However, no detailed spectroscopic studies have been carried out to confirm this suggestion. Moreover, the mechanism of the proposed Co reduction is not clear.

In this work, we investigated the mode of catalyst deactivation during the HKR of epichlorohydrin by conducting recycling studies of homogeneous Co-salen catalysts without catalyst regeneration and following the chemical state of the catalyst by UV-Vis and X-ray spectroscopy. Although an active Co(III) salen catalyst deactivated substantially after multiple cycles without regeneration, the catalyst maintained its +3 oxidation state throughout the runs. Thus, deactivation of Co-salen during HKR was not the result of Co reduction. Results from various catalyst pretreatment tests as well as from catalysts containing various counterions (acetate, tosylate, chloride) indicated that gradual replacement of the Co-salen counterions with hydroxyl during the reaction deactivated the catalyst. The extent of counterion replacement by hydroxyl was influenced by the exposure time, the presence of epichlorohydrin and the nucleophilicity of the counterion. An oligo(cyclo-octene) supported Co-OAc salen catalyst, which was 25 times more active than the traditional Jacobsen Co-salen catalyst, was recycled multiple times with negligible deactivation.