Enantioselective hydrogenation mechanism

Describe, in general, an enantioselective hydrogenation mechanism in the presence of a chiral-modified metal/support catalyst. 

An especially important case is the enantioselective hydrogenation of a-amidoacrylic acids, which leads to a-aminoacids.29 A particularly detailed study has been carried out on the mechanism of reduction of methyl Z-a-acetamidocinnamate by a rhodium catalyst with a chiral diphosphine ligand DIPAMP.30 It has been concluded that the reactant can bind reversibly to the catalyst to give either of two complexes. Addition of hydrogen at rhodium then leads to a reactive rhodium hydride and eventually to product. Interestingly, the addition of hydrogen occurs most rapidly in the minor isomeric complex, and the enantioselectivity is due to this kinetic preference. 

Fig. 5.1. Mechanism of ruthenium catalyzed enantioselective hydrogenation of a-acetamidoacrylate esters. Reproduced from J. Am. Chem. Soc124, 6649 (2002), by permission of the American Chemical Society.

Fig. 5.4. Schematic mechanism for enantioselective hydrogenation of methyl acetamidocinnamate (MAC) over a cationic ruthenium catalyst. Reproduced...

The concerted delivery of protons from OH and hydride from RuH found in these Shvo systems is related to the proposed mechanism of hydrogenation of ketones (Scheme 7.15) by a series of ruthenium systems that operate by metal-ligand bifunctional catalysis [86]. A series of Ru complexes reported by Noyori, Ohkuma and coworkers exhibit extraordinary reactivity in the enantioselective hydrogenation of ketones. These systems are described in detail in Chapters 20 and 31, and mechanistic issues of these hydrogenations by ruthenium complexes have been reviewed [87]. 

Gridnev et al. studied the mechanism of the enantioselective hydrogenation of enamides with Rh-BisP" and Rh-MiniPHOS catalysts [22]. 

The mechanism of enantioselective hydrogenation by rhodium complexes has been reviewed on several occasions, including a recent detailed publication by the present author [14]. In addition, much of the contemporary work by Gridnev and Imamoto has been reviewed, as described below. Consequently, details of the older studies will be cited only briefly to provide the necessary context, after which the post-1998 developments will be discussed in detail. For a mature field, it is surprising how much new and significant information has been reported during the past five years. 

The enhanced synthetic potential of rhodium-complex-catalyzed enantioselective hydrogenation provided by these advances in ligand design has led to renewed interest in the reaction mechanism, and here we highlight four recent topics (i) the extended base of reactive intermediates (ii) an improved quadrant model for ligand-substrate interactions (iii) computational approaches to mechanism and (iv) (bis)-monophosphine rhodium complexes in enantioselective hydrogenation. These are discussed in turn. 

The accepted mechanism for hydrogenation of alkenes by Wilkinson s catalyst involves the addition of dihydrogen prior to coordination of the alkene, followed by migratory insertion [31]. The new demonstrations of the existence of solvate dihydride complexes inevitably raise the question as to whether the same mechanism can apply in rhodium enantioselective hydrogenation. The evidence in support of this possibility is analyzed in more detail later. 

Since there are unresolved issues in the fine detail of reaction mechanism, it is worth recalling an earlier publication on reactive intermediates in iridium hydrogenation [61]. In general, conventional Ir diphosphine complexes turnover slowly or not at all when enantioselective hydrogenation of standard substrates is attempted, and essentially all the practical and useful recent synthetic contri-... 

Far more ruthenium-complex-catalyzed enantioselective hydrogenation has been directed towards ketone reduction rather than alkene reduction. Recent studies carried out on the mechanism of C=C hydrogenation has been rather limited. 

Fig. 31.15 Mechanism of the enantioselective hydrogenation of enamides by Ru BINAP, giving the opposite stereochemical course to the corresponding Rh catalyst. Note the heterolytic nature of the addition process with one of the two hydrogens arising from solvent.

Fig. 31.17 (a) Experimental observation of dihydrides in the PHOXIr+ system by NMR (S = THF). (b) The DFT-derived mechanism for Ir-catalyzed enantioselective hydrogenation involving the sequential addition of two molecules of dihydrogen, with a single H-atom transfer from each one (S = CH2CI2). 

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