Structural Complexity Through Multicomponent Cycloaddition Cascades Enabled by Dual-Purpose, Reactivity Regenerating 1,2,3-Triene Equivalents

Multicomponent reactions allow for more bond-forming events per synthetic operation, enabling more step and time economical conversion of simple starting materials to complex and thus value-added targets. These processes invariably require that reactivity be relayed from intermediate to intermediate over several mechanistic steps until a termination event produces the final product. Here we report a multicomponent process in which a novel 1,2,3-butatriene equivalent (TMSBO: TMSCH(2)C≡CCH(2)OH) engages chemospecifically as a two-carbon alkyne component in a metal-catalyzed [5+2] cycloaddition with a vinylcyclopropane to produce an intermediate cycloadduct. Under the reaction conditions, this intermediate undergoes a remarkably rapid 1,4-Peterson elimination, producing a reactive four-carbon diene intermediate that is readily intercepted in either a metal-catalyzed or thermal [4+2] cycloaddition. TMSBO thus serves as an yne-to-diene transmissive reagent coupling two powerful and convergent cycloadditions - the homologous Diels-Alder and Diels-Alder cycloadditions - through a vinylogous Peterson elimination, and enabling flexible access to diverse polycycles.