Borrowing hydrogen amination: Whether a catalyst is required?

Abstract

Borrowing hydrogen amination (or borrowing hydrogen N-alkylation) is a powerful method for the formation of C-N bonds, which is widely used in academy and industry. In contrast to a common opinion, this process can be carried out without transition metal catalysts under basic conditions at a rather low temperature. Through the systematic experimental investigation, we developed a general model that allows one to predict the optimal conditions for borrowing hydrogen N-alkylation for a particular substrate and to determine if a transition metal catalyst is required. Low Bordwell acidity of the amine, the low dielectric constant of the solvent, and the presence of air in the system were found to be the key factors for successful catalyst-free N-alkylation at low temperatures. Our results also shows the challenging substrates and highlights the directions for further development of the transition metal catalysts.