(455d) Enantioselective Catalysis by Engineering Cooperative Interactions between Tethered Metal Complexes: The Role of Linker Length and Flexibility in the Co-Salen Catalyzed Hkr of Epoxides

The 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. Recently, we described a new, highly active and enantioselective cyclic oligomer-tethered Co-Salen catalyst useful in the hydrolytic kinetic resolution (HKR) of epoxides. This catalyst was prepared by a rare Ru-catalyzed ring-expanding metathesis polymerization process by which salen-functionalized cyclooctene monomers were oligomerized/expanded into larger rings. By this route, cyclic oligomers with 16, 24, 32, etc. carbon atoms were prepared, with one Co-Salen tethered every 8 carbon atoms down the chain. This cyclic-oligomeric catalyst was demonstrated to be the most active enantioselective HKR catalyst known for a variety of epoxides [1]. Most recently, we have focused on the role of the length and flexibility of the tether in allowing for the cooperative interactions between tethered metal complexes. Systematic variation of the linker structure has elucidated clear trends in the role of flexibility and length on the metal complex cooperativity in this supported catalyst system [2].

The cause of catalyst deactivation during these reactions has also been uncovered, and these results will be reported in a parallel presentation [3].

[1] Zheng, Jones, Weck, J. Am. Chem. Soc. 2007, 129, 1105. [2] Zheng, Jones, Weck, manuscript in preparation. [3] Jain, Zheng, Jones, Weck, Davis, Inorg. Chem. submitted.