Photoinduced Nickel-Catalyzed Homolytic C(sp³)–N Bond Activation of Isonitriles for Selective Carbo- and Hydro-Cyanation of Alkynes

Abstract

The exploration of strong chemical bonds as synthetic handles offers new disconnection strategies for the synthesis of functionalized molecules via transition metal catalysis. However, the slow oxidative addition rate of these covalent bonds to a transition metal center hampers their synthetic utility. Here, we report a C(sp 3 )−N bond activation strategy that bypasses thermodynamically challenging 2e − or 1e − oxidative addition via a distinct pathway in nickel catalysis. This strategy leverages a previously unknown activation pathway of photoinduced inner-sphere charge transfer of low-valent nickel(isonitriles), triggering a C(sp 3 )−N bond cleavage distal to the metal−ligand interaction to deliver nickel(cyanide) and versatile alkyl radicals. Utilizing this catalytic strategy, the selective intermolecular 1,2-carbocyanation reaction of alkynes with alkyl isonitriles as both alkylating and cyanating agents can be achieved, delivering a wide array of trisubstituted alkenyl nitriles with excellent atom-economy, regio-, and stereoselectivity under mild conditions. Furthermore, Markovnikov-selective hydrocyanation of aliphatic alkynes can be accomplished through the synergistic action of a photocatalyst utilizing isonitriles as the cyanation agents. Mechanistic investigations support the photogeneration of low-valent Ni(isonitrile) complexes that undergo photochemical homolysis of the C(sp 3 )−N bond to engage catalytic cyanation with alkynes.