Regio- and Chemoselective Synthesis of Spiro Cyclobutane-Isobenzofuranimines via Cascade Oxycyclization and [2 + 2] Cycloaddition of o-Alkynolbenzamides

A Lewis acid-mediated approach has been developed for the regio- and chemoselective synthesis of highly substituted spirocyclic cyclobutane-isobenzofuranimines. The methodology features a cascade sequence comprising a Meyer-Schuster rearrangement, [2 + 2] cycloaddition, and an intramolecular oxycyclization of o-alkynolbenzamides, furnishing functionalized dispiro cyclobutane derivatives in good to excellent yields. Notably, the cyclobutane framework is constructed through a regioselective intermolecular head-to-head interaction of the allene intermediates. The isobenzofuranimine subunit is formed chemoselectively via the nucleophilic attack of the amide oxygen at the C-C unsaturation. Furthermore, late-stage modification includes the synthesis of dispiro cyclobutane-isobenzofuranones in high yields. Photophysical studies reveal that these dispiro cyclobutane scaffolds exhibit notable photoluminescence in the visible region.