The use of chiral organocatalysts in the reaction of cyclic anhydrides to induce enantioselectivity has become increasingly popular. Organocatalysts are significantly cheaper and easier to work with than enzymatic or organometallic catalysts, but their mechanisms are not fully understood. Therefore, research from a theoretical point of view is extremely appealing. Our research involves using density functional theory to understand the reactivity and mechanism behind the organocatalytic desymmetrization reaction of a cyclic anhydride with methanol and a quinine-derived organocatalyst. Thus far we have succeeded in locating diastereomeric transition states leading to each enantiomer. Interestingly, we have discovered that there are are two possible mechanistic pathways for each enantiomer. Our most recent results indicate that the major enantiomer forms through a step-wise pathway involving two transition states, and the minor one is formed through a concerted pathway. This concerted pathway involves both the nucleophilic attack of the methanol and the ring-opening of the anhydride simultaneously. These exciting results are now fueling further research into why the catalyst works in this manner. Our hope is to continue using density functional theory to test out manipulations of the catalyst in order to enhance its enantioselectivity.

Exploring the mechanisms of enantioselective organocatalytic reactions: A DFT study

249th National Meeting (2015)

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