The Exocyclic Effect:  Protecting Group Strategy to Enhance Stereoselectivity in Hydrogen Transfer Reactions of Acyclic Free Radicals

To enhance the diastereoselectivity of the hydrogen transfer reaction of acyclic substrates bearing 1,2- or 1,3-diols, the feasibility of a strategy employing bifunctional protecting groups has been demonstrated. This strategy is based upon the “exocyclic effect” or the significant improvement of anti-selectivity exhibited by the reductions of substrates in which the two substituents (R₁ and Y) at the stereogenic center α to the radical center are linked together. A rationale for the excellent facial discrimination of these exocyclic radicals is offered based on an analysis of transition state models, which considers both steric and electronic factors.