Jack Duflos

Broadening in the scope of NADH models by using chiral and non chiral pyrrolo [2,3-bl pyridine derivatives.

Abstract Non cliral and chiral NADH models in the pyrrolo [2,3-b] pyridine series have been synthesized. These reagents 1) allow reductions of substrates previously found to be non reducible with similar reagents, 2) can give either one enantiomer or the other during the reduction of a prochiral ketone depending on the experimental conditions, 3) can be used in the synthesis of chiral precursors of target molecules obtained with good enantiomeric excesses.

Stereoselectivity of hydrogen transfer with chiral NADH models as a function of configuration and conformation

Abstract NADH model compounds bearing chiral amide groups have been synthesized. One of these models, 3 , possessed the 1,6-naphtyridinone structure and the key step of its synthesis was a cross coupling reaction which was optimized on the basis of consideration of the mechanism. In this bicyclic model 3 , the amide carbonyl dipole is forced in a transoid orientation. In model 1 , the free rotation around the C-3-CO amide bond is not hindered contrary to the behavior of model 2 , where the presence of a methyl group on the nitrogen of the amide moiety is sufficient to force the carbonyl group to be out of the plane. The NMR spectra of these compounds and their precursors were studied from which it could be assumed that model 2 and its derivatives could have two conformers due to the restricted rotation of the amide moiety. Model 3 reduced methyl benzoylformate with a good enantioselectivity (e.e.= 85 %).

Improvement in the enantioselectivity of the hydrogen transfer with NADH models bearing amino alcohols as chiral auxiliaries

Chiral amino alcohols have been linked to the γ-carbonyl group of the 5,7-dihydrothieno[2,3b]pyridines (4a–d). These models are much more easily handled in mild conditions than common NADH models. The factors affecting enantiomeric excess have been studied, e.g, influence of temperature, polarity of solvents, magnesium concentration, and hydrogen bonding. By appropriate modifications of the chiral auxiliary, the rigidity of the ternary complex: model–Mg2+–substrate involved has been enhanced. In this way a high enantiomeric excess has been obtained.