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 β‐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.

Radical C(sp3)–S Coupling for the Synthesis of α-Amino Sulfides

“…2-Azaallyl anions as versatile precursors of amine syntheses have attracted the interest of organic chemists . Since the pioneering studies of Murphy, Walsh, Chruma, and our group demonstrated 2-azaallyl anions served as super electron donors (SEDs), they have been applied in the construction of C–C bonds through transition-metal-free radical cross-coupling with various electrophiles, which has enabled the synthesis of multifunctional amines (Scheme a) . More recently, we developed the transition-metal-free C­(sp 3 )–H/C­(sp 3 )–H coupling of saturated heterocycles and cycloalkanes with 2-azaallyl anions by a combination of single-electron transfer (SET) and hydrogen atom transfer (HAT) processes (Scheme b) .…”