Conformational Control of Chiral Amido-Thiourea Catalysts Enables Improved Activity and Enantioselectivity

While aryl pyrrolidinoamido-thioureas derived from α-amino acids are effective catalysts in a number of asymmetric transformations, they exist as mixtures of slowly interconverting amide rotamers. Herein, the compromising role of amide bond isomerism is analyzed experimentally and computationally. A modified catalyst structure that exists almost exclusively as a single amide rotamer is introduced. This modification is shown to result in improved reactivity and enantioselectivity by minimizing competing reaction pathways.