Copper–Nitroxyl-Catalyzed α-Oxygenation of Cyclic Secondary Amines Including Application to Late-Stage Functionalization
Christopher M. Hanneman, Jack Twilton, Melissa N. Hall, Nicole C. Goodwin, Jennifer M. Elward, Tessa Lynch‐Colameta, Shannon S. Stahl
Abstract
-unprotected/unsubstituted piperidines and related heterocycles have limited precedent despite their potential to impact medicinal chemistry and organic synthesis. Herein, we report a Cu/nitroxyl co-catalyzed method for direct conversion of cyclic secondary amines to the corresponding lactams via aerobic dehydrogenation and oxidative coupling with water. The mild reaction conditions tolerate diverse functional groups, enabling application to molecules that cover broad chemical space. The method is showcased in selective functionalization of building blocks and complex molecules, including late-stage functionalization of bromodomain inhibitors.