Pd-catalyzed cyanation of arenediazonium tetrafluoroborate derivatives with 2-(piperidin-1-yl)acetonitrile as a cyano source under mild conditions

Abstract

The present study reports an organic cyano reagent (CN), 2-(piperidin-1-yl)acetonitrile which can cyanate commercially aryldiazonium tetrafluoroborate derivatives with a palladium catalyst under mild reaction conditions. A large substrate scope for the Pd-catalyzed cyanation of aromatic diazonium substrates was found, yielding nitrile-containing products in medium to high yields (59%‒92%). This methodlogy was employed for the preparation of etravirine and for the transformations of 2-cyanoindole which are used as anti-AIDS, NMDA receptor antagonists and have a high potential against mutant HIV strains. The mechanism of this Pd-catalyzed cyanation of aryldiazonium tetrafluoroborate derivatives involved CN- ions and was proved by paper indicator strategy. However, this Pd/(Me3Si)2 system has been identified to cleave C−CN bonds at low temperature and transferred the CN group to aryl rings of diazonium substrates in one pot.