Asymmetric hydrogenation Rh-catalyzed

In 1968, the first homogeneous asymmetric hydrogenation was reported independently by Homer and Knowles (8). The Wilkinson complex and related complexes modified by the incorporation of a chiral tertiary phosphine, such as P(C6H5)(n-C3H7)(CH3), catalyzed the hydrogenation of certain hydrocarbon olefins in optical yields of 3-15%. 

SCHEME 2. Hydrogenation of alkenes catalyzed by the Wilkinson complex. 

SCHEME 3. Enantioselective hydrogenation of a-(acylamino)acrylic acids. 

Enantioselectivity is drastically reduced by carrying out the reaction at high initial hydrogen pressure. For example, the reaction of (Z)-a-(benzamido)cinnamic acid in ethanol under initial H2 pressure of 4 atm gives the saturated product in 96-100% optical yield the same reaction at 50 atm produces only a 71 % yield. 

Hydrogenation systems frequently contain a variety of catalytically active metal complexes that exhibit different degrees of enantioface differentiation. For example, the reaction of (Z)-ct-(benzamido)cinnamic acid in the presence of preformed [Rh((/ )-binap)(CH30H)2]C104 pro- 

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Scheme 22. Examples of Rh-catalyzed asymmetric hydrogenation reactions of dehydroammo esters...

Scheme 25. Rh-catalyzed asymmetric hydrogenation reactions leading to a biologically active compound...

Scheme 27. Example of the Rh-catalyzed asymmetric hydrogenation reaction of ethenephosphonate...

Scheme 12 Reductive cyclization of acetylenic aldehydes via Rh-catalyzed asymmetric hydrogenation...

Compared to the great advance achieved in the Rh-catalyzed asymmetric hydrogenation, the Ru-catalyzed asymmetric hydrogenation of ct-dehydroamino acid derivatives takes a different mechanistic pathway,215 and little success has been made. 

Figure 6-5. Proposed mechanism for weak-base-promoted Rh-catalyzed asymmetric hydrogenation. Reprinted with permission by Wiley-YCH Verlag GmbH, Ref. 4. 

Chiral monodentate phosphites and phosphoramidites are also effective ligands for Rh-catalyzed asymmetric hydrogenation of enamide substrates. As seen in the structure of MonoPhos illustrated in Figure 1.2, combination of the mod-ihed BINOF backbone and the amine part gives a structural variety to this type of ligand. Combinatorial methods are effective for optimization of the chiral structures.Elucidation of the hydrogenation mechanism catalyzed by the MonoPhos-Rh complex is in progress." ... 

We note that there are NMR-based kinetic studies on zirconocene-catalyzed pro-pene polymerization [32], Rh-catalyzed asymmetric hydrogenation of olefins [33], titanocene-catalyzed hydroboration of alkenes and alkynes [34], Pd-catalyzed olefin polymerizations [35], ethylene and CO copolymerization [36] and phosphine dissociation from a Ru-carbene metathesis catalyst [37], just to mention a few. 

Selected derivatives of the ligands and complexes described above have been tested in catalytic applications. Early tests with bidentate P,P or P,N ligands such as 4, 6, and 8 in Rh-catalyzed asymmetric hydrogenation were disappointing, with ee values below 20%. However, as was demonstrated mainly by the Fu group, phosphaferrocene derivatives do have the potential for successful applications in asymmetric catalytic reactions, provided the phosphaferrocene is endowed with sufficient steric bulk. Examples are depicted in Eig. 1.5.8 the Cp derivative 32,... 

Table 2.3 Rh-catalyzed asymmetric hydrogenation of the derivatives of methyl (Z)-2- ...

The new ligands were evaluated in the Rh-catalyzed asymmetric hydrogenation of benchmark substrates methyl a-N-acetamidoacrylate (7), methyl a-(2)-N-acetamidocinnamate (8) and dimethyl itaconate (9) (Table 2.3). For all three substrates, catalyst performance was superior in CH2CI2. Differences of up to 83% ee compared to otherwise identical reactions conducted in MeOH could be noted, giving... 

Some of the phosphine ligands used for the Rh-catalyzed asymmetric hydrogenation of a-(acylamino)acrylic acids are shown in Scheme 4... 

Rh-Catalyzed Asymmetric Hydrogenation of 9 and 11 Using BINOL-Based Phosphite Ligands3... 

K. Rossen, Ru- and Rh-Catalyzed Asymmetric Hydrogenations Recent Surprises from an Old Reaction, Angew. Chem. Int. Ed. Engl. 2001, 40, 4611 4613. 

Although the Rh-catalyzed asymmetric hydrogenations of prochiral enamides have been extensively studied and excellent results have been frequently achieved, the catalytic asymmetric hydrogenations of 2-arylacrylic acids have been less successful. Until recently most catalyst systems gave only moderate optical yields for the 2-arylpropionic acid products (77). An important breakthrough in the study of these reactions was reported by Noyori et al. By using Ru(BINAP)(OAc)2 as a catalyst precursor, these researchers obtained excellent optical yields in the asymmetric hydrogenation of 2-(6 -methoxy-2 -naphthyl)acrylic acid (72). 

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