Catalytic Cyanation of C-N Bonds with CO₂/NH₃

Cyanation of benzylic C-N bonds is useful in the preparation of important α-aryl nitriles. The first general catalytic cyanation of α-(hetero)aryl amines, analogous to the Sandmeyer reaction of anilines, was developed using reductive cyanation with CO₂/NH₃. A broad array of α-aryl nitriles was obtained in high yields and regioselectivity by C-N cleavage of intermediates as ammonium salts. Good tolerance of functional groups such as ethers, CF₃, F, Cl, esters, indoles, and benzothiophenes was achieved. Using ¹³CO₂, a ¹³C-labeled tryptamine homologue (five steps, 31% yield) and Cysmethynil (six steps, 37% yield) were synthesized. Both electronic and steric effects of ligands influence the reactivity of alkyl nickel species with electrophilic silyl isocyanates and thus determine the reactivity and selectivity of the cyanation reaction. This work contributes to the understanding of the controllable activation of CO₂/NH₃ and provides the promising potential of the amine cyanation reaction in the synthesis of bio-relevant molecules.