Synthesis of Substituted Tetralins via Nitrogen Deletion/Diels-Alder Cascade Reaction.

Abstract

Skeletal editing is an important approach for the modification and diversification of biologically active molecules. The utilization of nitrogen deletion strategies in skeletal editing has recently emerged as a new method for compound modification. Here, we report an unexpected nitrogen deletion in isoindolines. Contrary to the anticipated outcome of cyclobutane formation via intramolecular radical couplings, the nitrogen deletion of isoindoline triggers a Diels-Alder cycloaddition facilitated by the in situ formation of ortho-xylylene to yield tetraline. Inspired by this reaction, we developed a new strategy for synthesizing substituted tetralins, employing isoindoline, nitrogen deletion reagent (anomeric amide), and dienophiles. This methodology demonstrates a new pathway for tetralin synthesis and the modification and diversification of isoindolines.