Abstract

A feature possessed by many of the most powerful synthetic methods is consistent performance across a wide range of substrate combinations. In asymmetric catalysis, the challenge of achieving such generality is compounded by the challenge of needing to achieve a high level of geometric precision in the reaction mechanism. Nonetheless, some general asymmetric catalytic reactions have been identified, and we have sought to understand the basis for that generality. Perhaps more remarkable, privileged chiral catalysts—structures that have been demonstrated to induce high levels of enantioselectivity across a variety of mechanistically distinct reactions—have also been identified and have proven profoundly enabling to the discovery of new asymmetric catalytic reactions. This lecture will describe approaches to the elucidation and discovery of general catalytic systems, including the development of a specific, new class of privileged chiral catalysts: dual H-bond donors (HBDs) bearing aryl-pyrrolidino-tert-leucine motifs. Detailed case studies on the mechanism of enantioinduction with these catalysts highlight the cooperative features of these simple organic molecules that are likely responsible for the privileged nature of this scaffold.