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Rational Design Supplemented by Serendipitous Discovery Highly Active and Enantioselective Support-Tethered Co(III)-Salen Complexes for the Hydrolytic Kinetic Resolution of Epoxides

Xiaolai Zheng1, Nam T. S. Phan1, Marcus Weck2, and Christopher W. Jones1. (1) Chemical & Biomolecular Engineering, Georgia Institute of Technology, Chemistry and Biochemistry, 311 Ferst Dr., Atlanta, GA 30332, (2) Chemistry and Biochemistry, Georgia Institute of Technology, 770 State St., Atlanta, GA 30332

The dynamic kinetic resolution of enantiomers is rapidly becoming an important method for the production of chiral building blocks for fine chemicals and pharmaceuticals. In this method, a racemic compound is resolved to an enantiomerically pure form by selectively converting one enantiomer of the racemic mixture (with a maximum 50% yield and 100% ee). A significant limitation of this method, however, is that the catalysts employed are often homogeneous metal complexes composed of expensive transition metals and chiral ligands. Furthermore, an added problem is that the catalysts routinely have a very short activity window before the catalytic properties (activity, enantioselectivity) begin to degrade.

Using the literature supposition that epoxide ring-opening reactions promoted by the Co-Salen system utilize mechanisms that are bimolecular in metal complex, we sought to design an active and enantioselective supported analogue. Hypothesizing that the supported catalyst must allow enough complex mobility to facilitate formation of the bimolecular transition state, soluble polymer-supported catalysts were targeted. Here we describe two rationally designed supported Co-Salen catalysts for hydrolytic kinetic resolution (HKR) reactions, including a (i) soluble poly(styrene) supported catalyst [1] and an (ii) insoluble poly(styrene)-silica hybrid catalyst [2]. Both catalysts are active and selective in the HKR of rac-epichlorohydrin. Additionally, in a quest to design and even more flexible analogue, we serendipitously discovered a unique Ru-catalyzed ring-expanding metathesis polymerization process by which cyclooctene is oligomerized/expanded into larger rings. By this route, cyclic oligomers with 16, 24, 32, etc. carbon atoms are prepared, with one Co-Salen tethered every 8 carbon atoms down the chain. This cyclic-oligomeric catalyst is demonstrated to be the most active enantioselective HKR catalyst known for a variety of epoxides [3].

[1] Zheng, Jones, Weck Chem. Eur J. 2006, 12, 576. [2] Phan, Zheng, Weck, Jones, manuscript in preparation. [3] Zheng, Jones, Weck, manuscript submitted.