Nickel/Lewis Acid-Catalyzed Carbocyanation of Unsaturated Compounds

Abstract

Abstract Addition reactions of the organic and cyano groups of nitriles through cleavage of the C–CN bonds, namely carbocyanation, have been developed using nickel/Lewis acid (LA) cooperative catalysis. Originally, the reaction was performed with a nickel catalyst alone and was limited to the use of aryl and allyl cyanides as the nitrile substrates. By employing LA cocatalysts, the rate of the arylcyanation was accelerated significantly and the scope of nitriles used in the reaction across alkynes was expanded to include alkenyl, alkynyl, and alkyl cyanides. The high chemo-, regio-, and stereoselectivities of the alkyne–carbocyanation reactions were highlighted by the syntheses of biologically active compounds including the synthetic precursor of P-3622 and plaunotol, which possess defined tri- or tetrasubstituted ethene structures. Intramolecular arylcyanation of alkenes was also achieved by cooperative catalysis. Mechanistic studies on this particular transformation allowed us to identify several reaction intermediates, which revealed the modes of the cooperative catalysis derived from nickel- and aluminum-based LA. Intramolecular arylcyanation was achieved in an enantioselective manner using optically active bidentate phosphorus ligands, affording a protocol to introduce both a quaternary stereocenter and a cyano functionality without by-product generation.