Nickel-catalyzed asymmetric reductive arylcyanation of alkenes with acetonitrile as the cyano source

Abstract

An efficient method for Ni-catalyzed asymmetric reductive arylcyanation of alkenes is developed for the synthesis of chiral 3-cyanomethyl oxindoles featuring all-carbon quaternary stereocenters in high enantioselectivities and yields. Remarkably, acetonitrile is employed as a cheap and readily available cyano source via β-carbon elimination assisted by Zn(OTf)₂, which will not release free cyanide anions into the system. This strategy prevents the competitive coordination of cyanide anions with the metal center, which would usually erode the enantioselectivity. In addition, this method finds valuable applications in the asymmetric synthesis of the natural alkaloids (−)-physostigmine, the drug used for the treatment of glaucoma and Alzheimer's disease, and (−)-esermethole.