Catalytic Chemo- and Regioselective Radical Carbocyanation of 2-Azadienes for the Synthesis of alpha-Amino Nitriles

alpha-Amino nitriles are versatile structural motifs in a variety of biologically active compounds and pharmaceuticals and they serve as valuable building blocks in synthesis. The preparation of alpha- and beta-functionalized alpha-amino nitriles from readily available scaffolds, however, remains challenging. Herein is reported a novel dual catalytic photoredox/coppercatalyzed chemo- and regioselective radical carbocyanation of 2-azadienes to access functionalized alpha-amino nitriles by using redox-active esters (RAEs) and trimethylsilyl cyanide. This cascade process employs a broad scope of RAEs and provides the corresponding alpha-amino nitrile building blocks in 50-95% yields (51 examples, regioselectivity > 95 : 5). The products were transformed into prized alpha-amino nitriles and alpha-amino acids. Mechanistic studies suggest a radical cascade coupling process.