Stereoselection without Steric Effect but Controlled by Electronic Effect: Important Contribution of Ground State

Stereoselectivity controlled by an electronic effect but not by a steric effect is presented. A modern concept of stereochemistry is proposed where stereochemistry is controlled by acceleration of the reaction instead of deceleration, as has been proposed based on classical concept. The mechanism of (net) hydride transfer from a dihydronicotinamide adenine dinucleotide (NADH)/dihydronicotinamide adenine dinucleotide phosphate (NADPH) analogue to certain oxidizing agents is discussed in relation to this modern stereochemistry concept. The reaction involves a preassociation complex where the stereochemistry of the reaction is defined. Only a complex that has appropriate intermolecular arrangement can proceed to the transition state. The difference in free energy between the two stereoisomers of the preassociation complex contributes to almost all of the difference in the free energy of activation for the stereoisomers in the transition state, then to the ratio of stereoisomers in the product. Thus, the transition state does not participate in determining the stereochemistry of the reaction. Similarities between the present and enzymatic reactions from the viewpoint of the reaction scheme are also suggested.