Selective Ring-Opening Amination of Isochromans and Tetrahydroisoquinolines

Abstract

The molecular structure-editing through selective C-C bond cleavage allows for the precise modification of molecular structures and opens up new possibilities in chemical synthesis. By strategically cleaving C-C bonds and editing the molecular structure, more efficient and versatile pathways for the synthesis of complex compounds could be designed, which brings significant implications for drug development and materials science. o-Aminophenethyl alcohols and amines are the essential key motifs in bioactive and functional material molecules. The traditional synthesis of these compounds usually requires multiple steps which could generate inseparable isomers and induce low efficiencies. By leveraging a molecular editing strategy, we herein reported a selective ring-opening amination of isochromans and tetrahydroisoquinolines for the efficient synthesis of o-aminophenethyl alcohols and amines. This innovative chemistry allows for the precise cleavage of C-C bonds under mild transition metal-free conditions. Notably, further synthetic application demonstrated that our method could provide an efficient approach to essential components of diverse bioactive molecules.

Keywords: Amination; C−C Bond Cleavage; Molecular Editing; Rearrangement Reaction; Transition-Metal Free.