Investigation of deactivation of cobalt-salen catalysts in the hydrolytic kinetic resolution of terminal epoxides

Asymmetric catalysis is used to produce a variety of enantiomers, which are of great value to the society. The hydrolytic kinetic resolution (HKR) of racemic 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 yield of 50% and enantiomeric excess (ee) of >99%. 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. Hence, the observed rate depends on the square of the catalyst concentration. With this mechanism in mind, researchers have developed different oligomeric or polymeric Co-salen catalysts that exhibit activities 1--2 orders of magnitude greater than that of the monomeric Co-salen catalyst. 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 project, we have studied in detail the deactivation of both homogeneous and supported Co-salen catalysts in the HKR of terminal epoxides. Possible modes of deactivation of homogeneous Jacobsen's Co-salen catalyst during the HKR of epichlorohydrin were explored by UV-Vis spectroscopy, IR spectroscopy, X-ray absorption spectroscopy and electrospray ionization mass spectrometry combined with recycling studies. In addition, the role of the Co-salen counterion on the HKR reaction mechanism, catalytic activity, enantioselectivity and stability was explored. Different counterions with varying nucleophilicities were used to elucidate when a bimetallic or monometallic transition state is formed during the HKR of a terminal epoxide and how the nature of the reaction path (mono vs bimetallic) affects the observed catalyst lifetime. Deactivation of various soluble as well as insoluble multimeric Co-salen catalysts were also investigated in the HKR of epichlorohydrin.