Copper-Catalyzed N-Aryl-beta-enaminonitrile Synthesis Utilizing Isocyanides as the Nitrogen Source

A novel synthetic protocol for N-aryl-beta-enaminonitriles, which are useful building blocks for heterocycle synthesis, was developed using isocyanides as the nitrogen source. Using copper-catalyzed one-step reactions between isocyanides and benzyl cyanides under mild conditions, diverse N-aryl-beta-enaminonitriles could be synthesized in excellent yields and with high atom-efficiency. N-Alkyl-beta-enaminonitriles were also synthesized in good yields. A mechanism involving an imidoyl-copper intermediate was proposed based on mechanistic studies and previous reports. In addition, we demonstrated that a synthesized N-aryl-beta-enaminonitrile could be utilized for the synthesis of a beta-keto nitrile compound and 3-aminopyrazole.