Asymmetric desymmetrization (ASD) reactions are useful in organic synthesis because they introduce chirality to achiral feedstock. Cinchona alkaloid-based catalysts have shown high enantioselectivity in the methanolysis of meso cyclic anhydrides. Despite the practical utility of these reactions, little is known about the actual substrate-catalyst interactions that account for the enantioselectivities. We prepared transition state analogues (TSAs) that mimic the structure of each enantiomer of the substrate’s putative tetrahedral transition states leading to the enantiomeric products. The TSAs are being studied by NMR in order to gather information about the energies and interactions of each TSA enantiomer with the catalyst. We are using diffusion ordered spectroscopy (DOSY) experiments to indirectly compare TSA-catalyst binding energies by studying the diffusion rate of each TSA enantiomer in the presence of the catalyst. We also report on our preliminary nuclear Overhauser effect spectroscopy (NOESY) experiments aimed at gaining information on the interactions between each TSA enantiomer and the catalyst. We hope that these findings will progress our understanding of the mechanisms of cinchona alkaloid-based catalysts for better-informed catalyst design.

Transition state analogues as mechanistic probes for asymmetric desymmetrization by cinchona alkaloid-based catalysts

253rd National Meeting (2017)

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