Zinc chloride-catalyzed Grignard addition reaction of aromatic nitriles

Abstract

In the alkyl addition reaction of aromatic nitriles using Grignard reagents, ketones are formed after hydrolysis. However, this addition reaction is often slow compared to that using reactive organolithium(I) reagents. In this study, we improved the reaction by using zinc(II)ates, which are generated in situ using Grignard reagents and zinc chloride (ZnCl₂) as a catalyst. As a result, the corresponding ketones and amines were obtained via hydrolysis and reduction, respectively, in good yields under mild reaction conditions. Scale-up reactions are also demonstrated. Interestingly, using a catalytic amount of ZnCl₂ was more effective than using a stoichiometric amount of zinc(II)ates. Possible transition states are proposed on the basis of the active zinc(II)ate species, and DFT calculations were carried out to elucidate a plausible reaction mechanism.