Asymmetric hydrogenation reaction pathways

The problems which remain in understanding and interpreting rhodium asymmetric hydrogenation arise from a persistent lack of information on the presumed rhodium dihydride without which the pathway between the enamide complex and the turnover limiting TS for H2 addition (i.e. the step in which the enantioselectivity of the reaction is set) remains opaque, and hence the overall understanding is elusive. [52]... 

The reaction pathway for rhodium-catalyzed asymmetric hydrogenation of enamides is described and intermediates are defined in solution by P-31, C-13, and H-l NMR. The stereochemical relationship of bound enamide to rhodium alkyl and to the product of hydrogenation is demonstrated. Experiments involving the addition of HD to a variety of olefins in the presence of rhodium biphosphine catalysts suggest that a concerted addition of hydrogen to olefin and metal may occur in appropriate cases. 

Enantiomeric excess and catalytic activity of the asymmetric hydrogenation of ethyl pyruvate over (-)cinchonidine modified Pt/carrier catalysts depend significantly on the specific Pt surface area This is due to the morphology of the Pt particles and to surface chemical Pt/support interaction. Thus, reaction pathway control is possible by varying these parameters. 

When our studies commenced it had been assumed that the mechanism of asymmetric hydrogenation by chelating rhodium phosphine complexes followed a similar pathway. It has been demonstrated, however, that the timing is quite different, and that oxidative addition of hydrogen to metal does not occur in the initial stages of reaction. This conclusion follows from studies on the phosphorus-31 NMR spectra of hydrogenated complex solutions made separately by Halpern,... 

BisP ligands are highly active and enantioselective for the hydrogenation of many classes of substrates. As noted in the mechanistic discussion, studies on asymmetric hydrogenation by rhodium catalysts of terf-Bu-BisP have provided evidence that these reactions occur through the "hydrogen-first" pathway even though the complexes are cationic. ... 

Rhodium-Diphosphine Catalysts. The mechanism of rhodium-catalyzed asymmetric hydrogenation is one of the most intensively investigated and best understood. Reaction pathways have been accurately studied both experimentally and theoretically (138,162,213-221). In early studies, Halpern (222) and Brown (214) established that the hydrogenation proceeds according to the reaction sequence presented in Figure 51 for the hydrogenation of a dehydroamino acid with a chiral diphosphine-rhodium complex. Many variants on both catalyst and reactant have been described. Stereoselectivity takes place via the difference in reactivity of the involved diastereomeric square-planar... 

Scheme 1.26 Different reaction pathways in asymmetric hydrogenation of enamides 13 and 16. (Reprinted with permission from Gridnev, I. D. et al.,/. Am. Chem. Soc., 123, 5268-5276. Copyright 2001 American Chemical Society.)...

Enantioselection in asymmetric hydrogenation of esters of -dehydroamino acids Computahons of the enantioselective step in the asymmetric hydrogenation of five representahve esters of 3-dehydroamino acids were carried out recently. Compehhon of two 3-dihydride pathways and two unsaturated pathways was considered (Scheme 1.32, Figure 1.12). In Figure 1.12 one can see that there are three characteristic values that determine the enanhoselechvity of the catalytic reaction AG difference in... 

Scheme 1.46 A revised catalytic cycle for the asymmetric transfer hydrogenation of aromatic ketones in propan-2-ol by the Noyori-Ikariya (pre)catalyst 2 demonstrates crossover of the reaction pathways the product is obtained via a H"/H+ outer-sphere hydrogenation mechanism and/or step-wise metal-ligand bifunctional mechanism (see text). Formation of the major enantiomeric product is shown. (Adapted from Dub, P. A. et al., /. Am. Chem. Soc., 135, 2604-2619. Copyright 2013 American Chemical Society.)...

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