Late-Stage Functionalization of Hydroxamic Acid Pharmaceuticals through Oxidative C-N Bond Formation

A mild, copper-catalyzed protocol is used for the oxidative activation of pharmaceuticals bearing hydroxamic acid functionalities. The aerobic dehydrogenation generates reactive nitroso intermediates that smoothly and selectively undergo trapping with olefins leading to the N -allylated products through ene-type reactions. Moreover, in presence of 1,3-dienes, [4+2]-cycloadditions provide access to bicyclic hydroxamate derivatives. The methodology is effective across a set of structurally diverse active pharmaceutical ingredients covering a broad application range from inflammation to cancer and neuromuscular diseases.