Cascade reactions of HDDA-benzynes with tethered cyclohexadienones: strain-driven events originating from ortho-annulated benzocyclobutenes

Abstract

Intramolecular net [2 + 2] cycloadditions between benzyne intermediates and an electron-deficient alkene to give benzocyclobutene intermediates are relatively rare. Benzynes are electrophilic and generally engage nucleophiles or electron-rich π-systems. We describe here reactions in which an alkene of a tethered enone traps thermally generated benzynes in a variety of interesting ways. The number of atoms that link the benzyne to C4 of a cyclohexa-2,5-dienone induces varying amounts of strain in the intermediates and products. This leads to a variety of different reaction outcomes by way of various strain-releasing events that are mechanistically intriguing. This work demonstrates an underappreciated class of strain that originates from the adjacent fusion of two rings to both C1–C2 and C2–C3 of a benzenoid ring – i.e. ‘ortho-annulation strain’. DFT computations shed considerable light on the mechanistic diversions among various reaction pathways as well as allow more fundamental evaluation of the strain in a homologous series of ortho-annulated carbocycles.