Atroposelective Chan-Evans-Lam Amination

The synthetic control of atropoisomerism along C─N bonds is a major challenge, and methods that allow C─N atroposelective bond formation are rare. This is a problem because each atropoisomer can feature starkly differentiated biological properties. Yet, among the three most practical and applicable classical amination methods available: 1) the Cu-catalyzed Ullmann-Goldberg reaction, 2) the Pd-catalyzed Buchwald-Hartwig reaction, and 3) the Cu-catalyzed Chan-Evans-Lam reaction, none has truly been rendered atroposelective at the newly formed C─N bond. The first ever Chan-Evans-Lam atroposelective amination is herein described with a simple copper catalyst and new PyrOx chiral ligand. This method constitutes a change of paradigm in the field.