MECHANISM AND TRANSITION-STATE STRUCTURE OF HYDRIDE-TRANSFER REACTIONS MEDIATED BY NAD(P)H - MODELS

Article abstract of DOI:10.1016/S0040-4020(01)87504-9

The energy to transfer one electron from NAD(P)H and related 1,4-dihydropyridines to a series of substrates is calculated and compared with the experimental activation energy for transfer of a hydride equivalent between these species.It is concluded that single electron-transfer (SET) cannot occur as a primary step in the overall hydride-transfer process except for substrates with very strong one-electron oxidizing properties.A simple valence-bond configuration mixing (VBCM) model is presented, that rationalizes the general occurrence of concerted hydride transfer as the lowest energy reaction-pathway and furthermore explains why the activtion energy of such a concerted pathway is often linearly related to that of a -hypothetical- SET process.For one intramolecular and two related, intermolecular hydride-transfer reactions the temperature dependence of the primary kinetic isotope effect (TDKIE) was studied.For the intramolecular reaction, where a face to face orientation of the reactants is enforced, the TDKIE parameters suggest the occurence of a bent hydride-transfer pathway.For both intermolecular reactions, however, a linear transition-state geometry is indicated.MNDO calculations of the reaction profile for hydride transfer from a 1,4-dihydropyridine to either a positively charged substrate (i.e. the pyridinium-ion) or to a neutral substrate (i.e. 1,1-dicyanoethylene) confirm, that a linear transition-state geometry is favoured, unless the system is geometrically restrained to prevent such a geometry.The MNDO calculations furthermore indicate that in a linear transition-state almost unimpeded rotation can occur about the C...H...C axis.This rotation interconverts the relative orientation of the reactants between parallel-exo and tilted-endo, which may have important consequences for the interpretation of the stereochemical outcome of reactions involving (pro)chiral reactants.