Computational Insights into Cinchona-Based Phase Transfer Catalysis for Asymmetric Conjugate Cyanation

The synthesis of asymmetric organic molecules has experienced a huge development over the last few decades. Phase-transfer catalysis has been proven to be one of the most powerful methods for these asymmetric transformations. However, the study of the mechanism of these catalysts and the different interactions that they can establish with the reactants has failed to keep pace. In the present study, the conjugate cyanation of two different α,β-unsaturated ketones are studied in the presence of a well-known alkaloid quinine-derived PTC, along with different modifications. The study includes the comparison of different binding modes between the catalysts and the different reactants, the mechanistic study of the reaction and the analysis of the non-covalent interactions established within the complexes and their role in the global enantioselectivity of the process.