Copper-mediated etherification via aryl radicals generated from triplet states

Abstract

Carbon–heteroatom (C–X) cross-coupling is a common method for bond-forming reactions in chemistry but the more electronegative the heteroatom X is, the more challenging the bond formation becomes. Although reductive elimination from Cu(III) intermediates to form C–X bonds is generally a facile reaction, oxidative addition of Cu(I) into the carbon–(pseudo)halide bond of aryl (pseudo)halides is energetically challenging. Therefore, cross-coupling reactions of aryl halides with a variety of nucleophiles is currently out of reach for methods based on copper. Here we present a strategy to bypass the high-barrier oxidative addition step to aryl halides by the generation of aryl radicals from triplet states. Photoinduced energy transfer to, or direct excitation of, aryl halides even enables the use of aryl chlorides as electrophilic coupling partners. This strategy allows for the use of alcohols, amines and fluoride as nucleophiles and expands the scope of copper-mediated cross-coupling chemistry.