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.