Photoinduced Nickel-Catalyzed Cascade Cyclization and Cyanation of Functionalized Alkynes

Abstract

Abstract We report a photoinduced nickel-catalyzed cyclization/cyanation of functionalized alkynes using 2-(diisopropylamino)acetonitrile as a practical cyanide surrogate. Under mild conditions with Cat. 1, KI, Zn, and 395 nm LED irradiation, the reaction affords diverse cyano-containing heterocycles, including indole-3-carbonitriles, benzofuran carbonitriles, benzo[b]thiophene carbonitriles, and isocoumarin/isochromene carbonitrile derivatives. The method avoids the direct use of highly toxic cyanide sources such as KCN, HCN, and TMSCN while providing synthetically useful nitrile-containing products for further derivatization. Control experiments support the requirement for the nickel catalyst, iodide, zinc, and light, and are consistent with a photoassisted, low-valent nickel pathway involving a nickel–cyanide species and iodide-assisted substrate activation. DFT calculations comparing competing oxygen-tethered cyclization pathways indicate that the benzofuran-forming pathway to 2-phenylbenzofuran-3-carbonitrile (3g) is favored over the isochromene-forming pathway to 1-oxo-3-phenyl-1H-isochromene-4-carbonitrile (3h). This work provides a mild and practical platform for accessing cyano-functionalized heterocycles and offers mechanistic insight into the regioselectivity of photoinduced nickel-catalyzed cyclization/cyanation.