Water-promoted dehydrative coupling of 2-aminopyridines in heptane via a borrowing hydrogen strategy

Abstract

A synthetic method for dehydrative N-benzylation promoted by water molecules in heptane using a π-benzylpalladium system has been developed. The presence of water significantly accelerates carbon–nitrogen bond formation, which is accomplished in an atom-economical process to afford the corresponding N-monobenzylated products. A crossover experiment afforded H/D scrambled products, which is consistent with a borrowing hydrogen mechanism. Kinetic isotope effect measurements revealed that benzylic carbon–hydrogen bond cleavage was the rate-determining step.