IMPACT OF SUBSTITUENT MODIFICATIONS ON THE ATROPSELECTIVITY CHARACTERISTICS OF AN ANIONIC OXY-COPE RING EXPANSION

The phenomenon of atropisomerism is critically examined in the tricyclic E,syn,up enolates derived from anionic oxy-Cope rearrangement of 1-vinyl-2-cyclohexenyl-7,7-dimethyl-exo-norbornan-2-ols, as well as the ketones derived from their protonation and methylation. In all cases studied, the [3,3] sigmatropic shift proceeds with 100% stereoselectivity via the endo-chair transition-state option. The E and syn stereochemistry is established during chirality transfer at this stage. The "oxygen-up" conformation stems directly from the structural features inherent in the starting alcohols. In the unsubstituted example and with certain substitution patterns in the original cyclohexene ring, the E,syn,up enolates are seen to be thermodynamically unstable relative to their E,syn,down atropisomers, such that products result exclusively by electrophilic capture of the latter. By suitable substitution, the barrier to this preequilibrium can be sufficiently heightened so that products resulting from the E,syn,up species can be obtained. Kinetic studies involving several ketone congeners were carried out to show that the predescribed effects persist in neutral analogues as well. Epoxidation of the double bond in one example was shown to continue the trend. The global findings provide unusual insight into those factors that a most responsible for control of atropisomerism in a medium-ring setting.