Copper-Catalyzed α-Arylation of Nitroalkanes with (Hetero)aryl Bromides/Iodides.

Abstract

α-Aryl substituted nitroalkanes are valuable synthetic building blocks that can be easily converted into α-aryl substituted aldehydes, ketones, carboxylic acids, as well as amines. Herein, an efficient Cu/oxalamide-catalyzed coupling between nitroalkanes and (hetero)aryl halides (Br, I) was developed to direct access highly diverse α-aryl substituted nitroalkanes. Compared with the current state of art, this protocol is more environmentally friendly and practical for synthetic chemists. This approach is characterized by a broad substrate scope on both nitroalkane part (primary nitroalkanes and nitromethane) and sp2 halide part ((hetero)aryl bromides/iodides and alkenyl bromides/iodides). The excellent functional group tolerance was observed, which would enable real world synthetic applications. More importantly, TON of current transformation reached to 3640, when some aryl iodides were used as coupling partners. This represents currently the highest catalyst turnover for transition-metal catalyzed α-arylation of nitroalkanes. Furthermore, the successful application in late-stage modification of complex molecules and synthesis of a known retinoid X receptor (RXR) antagonist exemplified its synthetic potential.