Selective nitrogen insertion into aryl alkanes

Abstract

Molecular structure-editing through nitrogen insertion offers more efficient and ingenious pathways for the synthesis of nitrogen-containing compounds, which could benefit the development of synthetic chemistry, pharmaceutical research, and materials science. Substituted amines, especially nitrogen-containing alkyl heterocyclic compounds, are widely found in nature products and drugs. Generally, accessing these compounds requires multiple steps, which could result in low efficiency. In this work, a molecular editing strategy is used to realize the synthesis of nitrogen-containing compounds using aryl alkanes as starting materials. Using derivatives of O-tosylhydroxylamine as the nitrogen source, this method enables precise nitrogen insertion into the Csp2-Csp3 bond of aryl alkanes. Notably, further synthetic applications demonstrate that this method could be used to prepare bioactive molecules with good efficiency and modify the molecular skeleton of drugs. Furthermore, a plausible reaction mechanism involving the transformation of carbocation and imine intermediates has been proposed based on the results of control experiments.