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

ABSTRACT

α-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 α- and ß-functionalized α-amino nitriles from readily available scaffolds, however, remains challenging. Herein is reported a novel dual catalytic photoredox/copper-catalyzed chemo- and regioselective radical carbocyanation of 2-azadienes to access functionalized α-amino nitriles by using redox-active esters (RAEs) and trimethylsilyl cyanide. This cascade process employs a broad scope of RAEs and provides the corresponding α-amino nitrile building blocks in 50-95 % yields (51 examples, regioselectivity >95 5). The products were transformed into prized α-amino nitriles and α-amino acids. Mechanistic studies suggest a radical cascade coupling process.