Reactivity and stereoselectivity of 6π and nazarov electrocyclizations of bridged bicyclic trienes and divinyl ketones.

Abstract

The 6π electrocyclizations and Nazarov cyclizations of a series of bridged bicyclic substrates were modeled with the M06-2X density functional and the def2-TZVPP basis set, and the factors responsible for the reactivities of these substrates and the stereoselectivities of their ring closures were identified. The ring closures of these bridged bicyclic trienes are up to a million-fold faster (ΔΔG(⧧) = 10 kcal mol(-1)) than that of 1,3,5-hexatriene, despite the absence of any activating functional groups. Three effects, preorganization, predistortion, and a CH π interaction, are responsible for this sizable difference in reactivity. Stereoselectivity is partially controlled by torsional effects, but for highly exo selective electrocyclizations, it is reinforced by a second effect (either a CH π interaction or a steric clash). The absence of this second effect in the ring closures of several divinyl ketones explains the reduced selectivity of these ring closures. In one case, a divinyl ketone (ketone 6) undergoes Nazarov cyclization to yield the endo product preferentially. For this example, through-space interaction of a nonconjugated alkene with the divinyl ketone π system in the endo transition state and a steric effect override the intrinsic exo selectivity.