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.