Surprising and Highly Efficient Use of Methylmagnesium Chloride as a Non-Nucleophilic Base in the Deprotonation and Alkylation of sp³ Centres Adjacent to Nitriles

Methylmagnesium chloride (MeMgCl) is a key reagent in research and industry typically as a nucleophile. In this article we develop the use of MeMgCl as a non-nucleophilic base in conjunction with catalytic amounts of an amine mediator. Specifically, we use the base to deprotonate α to a variety of nitriles in alkylation reactions, applying it to the synthesis of a wide variety of tertiary and quaternary nitriles, including examples where we successively and successfully added three different substituents on the carbon α to the nitrile. This method is generally applicable, high yielding and much greener than existing methods, and it has considerable advantages for industrial application.