Stereoelectronic effects and the kinetic acidities of diastereotopic hydrogens

Abstract

A general qualitative treatment is proposed which accounts for the relative reactivities of diastereotopic hydrogens adjacent to a heteroatom in proton transfer, hydride transfer, and hydrogen atom transfer reactions. This treatment focuses on the structures of the reactive intermediates formed in such reactions, which can be predicted or understood in terms of qualitative molecular orbital arguments, and on the manner in which these intermediates will undergo readdition of H+, H−, or H•. The procedure has been tested, for the specific case of proton transfer reactions, by a direct computational approach to the energy differences between diastereomeric transition states of reactions HO− + CH3X → H2O + −CH2X (X = sulfide, sulfoxide, sulfone, sulfonium). The computations support the qualitative treatment, and are in all cases in near quantitative agreement with the extensive experimental data concerning the diastereotopic selectivities exhibited in these systems.