Asymmetric hydrogenation enantioselection mechanism

For the mechanism of asymmetric hydrogenation, see Halpem, J. Asymmetric Catalytic Hydrogenation Mechanism and Origin of Enantioselection in Morri-sion, J. D. ed. Asymmetric Synthesis, Academic Press, New York, 1985, vol. 5. 

Key words ONIOM, hydrogenation, enantioselectivity, asymmetric catalysis, DFT, reaction mechanism, chiral phosphine, ab initio, valence bond, oxidative addition, migratory insertion, reductive elimination. 

Two alternative postulates for enantioselection may be proposed. In the first all four diastereomers are formed in varying amounts, and the relative amounts are determined by their respective thermodynamic stabilities. Assuming approximately equal amounts of each diastereomer to be present, if one of them has a transition state that is about 2.5 kcal lower in energy than the transition states of the others, more than 90% enantioselection for 9.51 would result. The proposed mechanism for enantioselection is thus similar to that of asymmetric hydrogenation (see Section 9.3.1). In the second postulate only one such diastereomer is produced that is, the thermodynamic stability of one of the diastereomers is higher than that of the others. The stable diastereomer owing to its steric and electronic characteristics is converted to 9.51 in an enantioselec-tive manner. 

Zhou explored the asymmetric hydrogenation of 2,3 disubstituted quinolines. They thought that the hydrogenation mechanism of 2,3 disubstituted quinolines was somewhat different from that of 2 substituted quinolines (Scheme 10.20) [3]. For the hydrogenation of 2 substituted quinoline, the hydrogenation of C=N bond is the enantioselectivity controlled step (Scheme 10.19, H-I), while the enantioselectivity controlled step of 2,3 disubstituted quinolines is the isomerization of enamine to imine and the hydrogenation of C=N bond, which is in fact a dynamic kinetic... 

According to the mechanism of transition metal catalyzed asymmetric hydro genation of N acetyl enamines, N acetyl group is considered indispensable for the substrates to form a chelate complex with the metal of catalyst, which is important for the enantiocontrol of reaction. However, there is no N acetyl group in N,N dialkyl enamines to form such a chelate complex in the catalytic asymmetric hydrogenation, resulting in a low enantioselectivity. 

The invention of Ru-binap dicarboxylate complexes extends the scope of asymmetric hydrogenations . Simple acyclic acids are hydrogenated with enantioselectivities from 80 to 100%. The procedure is applicable to /3,y-unsaturated carboxylic acids with about 80% e.e. . Deuterium incorporation indicates that a mechanism involving a metal monohydride complex operates. An amino group on the chiral phosphine ligand enhances the efficacy of ferrocenylphosphine-Rh complexes toward trisubstituted acyclic acids . 

On the Mechanism of Stereoselection in Rh-Catalyzed Asymmetric Hydrogenation A General Approach for Predicting the Sense of Enantioselectivity ... 

Maris, M., Huck, W.R., Mallat, T., Baiker, A. (2003) Palladium-catalized asymmetric hydrogenation of fiiran carboxylic acids, J. Catal. 219,52-58. Huck, W.R., Buergi, T., Mallat, T., Baiker, A. (2003) Palladium catalysed enantioselective hydrogenation of 2-pyrones evidence for competing reaction mechanism, J. Catal. 219, 41-51. 

Complete clarity in the subject of asymmetric hydrogenation by immobilized metal complexes has not, as yet, been achieved. Each of three aspects has to be understood in this connection (i) the coordination chemistry of the triple complexes, (ii) the mechanism of catalytic hydrogenation and (iii) the reason for enantioselectivity. 

The first irreversible enantiodifferentiating step would determine asymmetric induction Landis, C.R. and Halpern, J. (1987) Asymmetric hydrogenation of methyl (Z)-a-acetamidocinnamate catalyzed by [l,2-bis(phenyl-o-anisoyl)phosphino)ethane]rhodium(I) kinetics, mechanism and origin of enantioselection. J. Am. Chem. Soc., 109, 1746-54. 

This is the classical asymmetric hydrogenation mechanism, taught in every course on enantioselective homogeneous catalysis. By the end of 1990s, each step of this mechanism had been studied in detail, including the preparation and characterisation of all the intermediates, with the exception of dihydride complexes 14, whose detection remained elusive. ... 

As described previously, the first commercial application of asymmetric hydrogenation was the Monsanto process for the manufacture of L-Dopa, developed by Knowles (Equation 10.23). L-Dopa is used to treat Parkinson s disease. For these reasons, Halpem and Brown studied the mechanism of this enantioselective process, and the results of these studies were particularly enlightening about how physical organic principles apply to asymmetric catalysis. This process was used as a case study in Chapter 14 to present how enantioselectivity is controlled. The findings are reiterated briefly here. 

Noteworthy, this mechanism of enantioselection explains well the absence of the temperature effect on the optical yield in the asymmetric hydrogenation of 4 catalyzed by the Rh-TangPhos catalyst. Indeed, in the case when the ee is determined by the difference in the free energies of the diastereomeric transition states, significant dependence of the optical yields on the temperature is usually observed due to the natural temperature variation of the rate constants. On the other hand, the structure of the catalyst implying facile formation of the chelate cycle in a less hindered quadrant and impossibility of similar transformation with the chelate cycle forming in hindered quadrant, remains the same at any temperature. Hence, the almost perfect enantioselectivity can be observed either in catalytic or low-temperature stoichiometric reaction (>99% ee in both cases). 

Further research showed convincingly that the RhL2 species are likely to be responsible for the enantioselective catalysis that makes the mechanisms of the asymmetric hydrogenation catalyzed by Rh complexes with mono- or diphosphine ligands similar. 

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