Chiral Guanidium Salt-Catalyzed Asymmetric Ring-Opening of Aliphatic Cyclic Carbonate via Enantioselective Proton Transfer

Abstract

The asymmetric ring-opening of aliphatic cyclic carbonates represents a strategically important, yet challenging, transformation for accessing chiral building blocks and polymeric materials. Herein, we present a novel methodology enabling the enantioselective desymmetrization of aliphatic cyclic carbonates using morpholine as the nucleophile and chiral bicyclic guanidinium salt as the catalyst under mild conditions. The protocol exhibits exceptional substrate tolerance, providing a diverse array of alkyl- and aromatic-substituted products with excellent yield and high enantioselectivity (97:3). Notably, it also enables the parallel kinetic resolution of racemic unsymmetrical alkyl-substituted cyclic carbonates with superior selectivity. The stereochemical outcome is supported by density functional theory (DFT) studies, which reveal a cooperative mechanism involving chiral guanidinium cation–solvent interactions that stabilize the transition state for the enantioselective 1,3-proton transfer step.