Synthesis of Substituted\nTetralins via Nitrogen Deletion/Diels–Alder\nCascade Reaction

Skeletal editing\nis an important approach for the modification\nand diversification of biologically active molecules. The utilization\nof nitrogen deletion strategies in skeletal editing has recently emerged\nas a new method for compound modification. Here, we report an unexpected\nnitrogen deletion in isoindolines. Contrary to the anticipated outcome\nof cyclobutane formation via intramolecular radical couplings, the\nnitrogen deletion of isoindoline triggers a Diels–Alder cycloaddition\nfacilitated by the in situ formation of <i>ortho</i>-xylylene\nto yield tetraline. Inspired by this reaction, we developed a new\nstrategy for synthesizing substituted tetralins, employing isoindoline,\nnitrogen deletion reagent (anomeric amide), and dienophiles. This\nmethodology demonstrates a new pathway for tetralin synthesis and\nthe modification and diversification of isoindolines.