How to inverse the chemoselectivity of nucleophilic addition by using a Lewis acid/Brønsted base pair catalyst: A theoretical view

Regulating the reactivity of nucleophiles is important in synthetic chemistry. As a weaker nucleophile is also a stronger Brønsted acid, it can be selectively deprotonated by a Brønsted base to give an anionic species that shows higher reactivity. Following this idea, the reactivity of nucleophiles can be controlled by using an appropriate Lewis acid/Brønsted base pair catalyst. Cuprous/aminolithium catalyzed hydrofunctionalization of acrylonitrile with an alcohol and an amine were chosen as model reactions. As the acidity of the alcohol is significantly higher than that of amine, the former is more easily deprotonated. Therefore, an alcohol shows higher reactivity than an amine in the presence of a Lewis acid/Brønsted base pair catalyst, reversing the selectivity trend.