Geometrical preferences for general acid-catalysed hydride transfer: comparative theoretical study of transition structures for reduction of formaldehyde

Abstract

The geometries of transition structures (TSs) for acid-catalysed hydride reduction of formaldehyde have been determined using several different theoretical methods. In each case hydride transfer (HT) and proton transfer (PT) occur in roughly perpendicular planes. The TS for the simplest system, with methylamine as the hydride donor and ammonium as the proton donor, exists in three conformations differing in the orientation of methylamine about the axis for HT; the preferred conformer has been studied using the AM1, PM3, HF/3-21G, HF/6-31G** and MP2/6-31G** methods. TSs with dihydropyridine as the hydride donor and with imidazolium as the proton donor have been studied using the AM1, PM3 and HF/3-21G methods, and show very similar overall structural features. Most of the TSs are for concerted HT and PT, but the PM3 method predicts some reactions to be stepwise with rate-determining HT. All the TSs show PT to be very much more advanced than HT. The preferred distance between the donor and acceptor carbon atoms for HT is about 2.6 Å for a system bearing an overall positive charge in the HT moiety. As compared with more sophisticated models for the mechanism of reduction by lactate dehydrogenase, the use of very simple models does not materially alter the nature of the TS, which seems to be a rather structurally robust entity.