Copper/Nitroxyl-Catalyzed Oxidative Coupling of Methanol and Amines to Formamides.

Methanol is a prominent basic C1 synthon in organic synthesis. Methods for direct coupling of methanol through C-N bond formation have limited precedents, despite their wide potential applications in organic and medicinal chemistry. Herein, we report a bisbenzoxazoline-Cu/nitroxyl-catalyzed method for aerobic oxidative coupling of methanol and amines for the direct synthesis of formamides. Secondary and primary amines were explored in this reaction, providing broad access to tertiary and secondary formamides, respectively. This easily available catalyst system is not sensitive to water and shows high functional group tolerance and broad synthetic utility for late-stage modification of various bioactive complex drugs.