A Cascade of Strain-Driven Events Converting Benzynes to Alkynylbenzocyclobutenes to 1,3-Dien-5-ynes to Cyclic Allenes to Benzocyclohexadienones

Here, we report a strain-promoted cascade reaction that proceeds via multiple strained intermediates, ultimately driven by the high potential energy inherent in alkyne triple bonds (C≡C). More specifically, four alkynes (three from an HDDA benzyne precursor and the fourth from a conjugated enyne reaction partner) are transformed into eight of the skeletal carbons in the benzocyclohexadienone products. The reaction pathway proceeds sequentially via strained benzyne, benzocyclobutene, and cyclic allene intermediates. DFT computations suggest that the slowest step following benzyne generation is the 4π-electrocyclic ring-opening of the alkynylbenzocyclobutene to a 1,3-dien-5-yne (an alkynylxylylene) intermediate. The activation energy for the subsequent 6π-electrocyclic ring-closure is lower than that for related acyclic dienynes because of the aromaticity that is being regained in the transition structure. Finally, the isolation of the benzocyclohexadienone products rather than their phenolic tautomers is notable.