The oxy-Cope rearrangement of aldol products has been studied both experimentally and theoretically to gain insight into the aspects that are responsible for the exceptional rate and diastereoselectivity of this process. Kinetic studies as well as DFT calculations convincingly show that the activation barrier of this process is mainly dependent on the electronic nature of the oxy-substituent, with electron-withdrawing O-substituents raising this barrier. The diastereoselectivity, however, remains uniformly high for all derivatives investigated and steric factors are proposed to account for the selectivity to a large extent. The poor diastereoselectivity in the case of the anti-aldols was also found in our calculations and it appears to result from unfavorable gauche interactions between the oxy and carboximide groups in the transition state.

Kinetic measurements and DFT calculations on the Cope rearrangement of 3-oxy-1,5-dienes with a syn-aldol structure reveal a close correlation between the activation barrier and the electronic nature of the oxy-substituent, which reflects the exceptional rate and diastereoselectivity of the [3,3]-sigmatropic rearrangement. Steric factors are proposed to account for the diastereoselectivity.