Enantioselective organocatalysis is an important alternative to asymmetric organometallic and enzyme catalysis because organocatalysts are robust and easy to handle, and they often accomplish transformations in high enantiomeric excess . One example is the organocatalytic desymmetrization (ASD) of cyclic anhydrides, the products of which have been used in the synthesis of natural products and pharmaceuticals, such as the neuropathic pain medication, pregabalin. To improve the enantioselectivity of the ASD reactions, a better understanding of the interaction between catalyst and substrate is needed. We are studying the mechanism of this reaction by designing and preparing stable transition state analogues (TSA) for the transformation, and examining their interactions with chiral catalysts. This work has primarily focused on the synthesis of a TSA and its resolution into individual enantiomers by fractional recrystallization. After successful resolution of the enantiomers, we will study the catalyst-substrate interactions and determine binding constants using NMR spectroscopy. The results can be used to verify the computational models of such ASD reactions, which can then be utilized to improve catalyst designs for higher enantioselectivity.

Synthesis of a transition state analog for mechanistic study of catalytic enantioselective reactions

249th National Meeting (2015)

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