Computational Investigation on the Origin of Atroposelectivity for the Cinchona Alkaloid Primary Amine-Catalyzed Vinylogous Desymmetrization of N-(2-t-Butylphenyl)maleimides

Mechanistic studies clarifying how chiral primary amines control the stereochemistry of vinylogous processes are rare. We report a density functional theory (DFT) computational study for the comprehension of the reaction mechanism of the vinylogous atroposelective desymmetrization of N-(2-t-butylaryl)maleimide catalyzed by 9-amino(9-deoxy) epi-quinine. Our results illustrate how the origin of the atroposelectivity was realized by the catalyst through steric and dispersion interactions. The role of N-Boc-L-Ph-glycine was crucial for the formation of a closed transition-state geometry and the activation of both reaction partners.

Automated summary

A computational study using density functional theory was conducted to understand the mechanism of atroposelective desymmetrization of N-(2-t-butylaryl)maleimide catalyzed by 9-amino(9-deoxy) epi-quinine. The results showed that the atroposelectivity was achieved through steric and dispersion interactions of the catalyst. The crucial role of N-Boc-L-Ph-glycine was identified in forming a closed transition-state geometry and activating the reaction partners.