Ene Reaction - Regioselection

Regioselection

Just as in the case of any cycloaddition, the success of an ene reaction is largely determined by the steric accessibility of the ene allylic hydrogen. In general, methyl and methylene H atoms are abstracted much more easily than methine hydrogens. In thermal ene reactions, the order of reactivity for the abstracted H atom is primary> secondary> tertiary, irrespective of the thermodynamic stability of the internal olefin product. In Lewis-acid promoted reactions, the pair enophile/Lewis acid employed determines largely the relative ease of abstraction of methyl vs. methylene hydrogens.

The orientation of ene addition can be predicted from the relative stabilization of the developing partial charges in an unsymmetrical transition state with early formation of the σ bond. The major regioisomer will come from the transition state in which transient charges are best stabilized by the orientation of the ene and enophile.