Chiral metal-complex catalysts

The first industrially interesting production of a chiral pharmaceutical with a chiral metal complex catalyst is the asymmetric hydrogenation of cinnamic acid derivatives to give L-DOPA, see Fig. 6.21. 

On the other hand, if aluminosilicates are used as supports for chiral metal complex catalysts, they might reveal a contribution to asymmetric action as was found in the case of the hydrogenation catalyst [CoSalen] complex supported on hectorite... 

These developments were achieved despite the known technological difficulties associated with the practical use of homogeneous chiral metal-complex catalysts. They have low durabilities and repeatabilities, the chiral phosphine ligands are difficult to synthesize, the catalytic complexes are not recoverable fi om reaction mixtures, and the most effective catalysts based on rhodium complexes are very cjqiensive to synthesize. 

Chira.lHydrogena.tion, Biological reactions are stereoselective, and numerous dmgs must be pure optical isomers. Metal complex catalysts have been found that give very high yields of chiral products, and some have industrial appHcation (17,18). The hydrogenation of the methyl ester of acetamidocinnamic acid has been carried out to give a precusor of L-dopa, ie, 3,4-dihydroxyphenylalanine, a dmg used in the treatment of Parkinson s disease. 

Many chiral metal complexes with Lewis acid properties have been developed and applied to the asymmetric Diels-Alder reaction. High enantioselectivity is, of course, one of the goals in the development of these catalysts. Enantioselectivity is not, however, the only factor important in their design. Other important considerations are ... 

A number of enantioselective hydrogenation reactions in ionic liquids have also been described. In all cases reported so far, the role of the ionic liquid was mainly to open up a new, facile way to recycle the expensive chiral metal complex used as the hydrogenation catalyst. 

Enantiometrically pure alcohols are important and valuable intermediates in the synthesis of pharmaceuticals and other fine chemicals. A variety of synthetic methods have been developed to obtain optically pure alcohols. Among these methods, a straightforward approach is the reduction of prochiral ketones to chiral alcohols. In this context, varieties of chiral metal complexes have been developed as catalysts in asymmetric ketone reductions [ 1-3]. However, in many cases, difficulties remain in the process operation, and in obtaining sufficient enantiomeric purity and productivity [2,3]. In addition, residual metal in the products originating from the metal catalyst presents another challenge because of the ever more stringent regulatory restrictions on the level of metals allowed in pharmaceutical products [4]. An alternative to the chemical asymmetric reduction processes is biocatalytic transformation, which offers... 

Experimental evidence of the —S03" H0Si— interaction have been obtained from IR, Rh K-edge EXAFS, and CP MAS 3 IP NMR studies. These supported catalysts have been tested for the hydrogenation and hydroformylation of alkenes. No Rh leaching was observed.128-130 An extension to the immobilization of chiral metal complexes for asymmetric hydrogenation is reported below. 

Kureshy developed a polymer-based chiral Mn-salen complex (Figure 21). Copolymerization of styrene, divinylbenzene, and 4-vinylpyridine generated highly cross-linked (50%) porous beads loaded with pyridine ligands at 3.8 mmol g-1. Once the polymer was charged with the metal complex catalyst, enantioselective epoxidation of styrene derivatives was achieved with ee values in the range 16 46%. 79... 

Chiral porphyrin metal complex catalysts have also received much attention. In this situation, the flat, symmetrical porphyrin structure must be modified dramatically in order to incorporate dissymmetry. This has been achieved through strapping techniques. " Some examples are shown in Figure 11.7. 

Over the last years, one of the most studied DCR has been the asymmetric version of the cycloaddition of nitrones with alkenes. This reaction leads to the construction of up to three contiguous asymmetric carbon centers (Scheme 4). The resulting five-membered isoxazolidine derivatives may be converted into amino alcohols, alkaloids, or p-lactams. Several chiral metal complexes have been used as catalysts for this process [13-15, 18-22]. However, the employment of iridium derivatives is very scarce. 

Doyle et al. have demonstrated the catalyst-dependent diastereoselectivity in Rh(ii) complex-catalyzed reaction of cinnamyl methyl ether 36 and ethyl diazoacetate 35 (Scheme 6). " The change of the diastereoselectivity of the products 38a and 38b with different Rh(ii) catalyst provides strong evidence that Rh(ii) catalyst is associated with the ylide in the rearrangement process. The moderately high level of asymmetric induction (4-69% ee) is also observed with allyl iodide (Equation (4)). In this case, the chiral metal complex must be in the product-forming step, because free iodo ylide is achiral. 

Asymmetric induction in the ylide formation/[l,2]-shift has also been studied with chiral metal complexes. Katsuki and co-workers examined the reaction of ( )-2-phenyloxetane with 0.5 equiv. of /< //-butyl diazoacetate in the presence of Gu(i) catalyst. With chiral bipyridine ligand 53, trans- and m-tetrahydrofurans 54 and 55 are obtained with 75% and 81% ee, respectively (Equation (6)). This asymmetric ring expansion was applied by the same group to their enantioselective synthesis of translactone. 

For reviews of chiral transition metal complex catalysts, see Brunner Top. Stereochem. 1988, 18. 129-247, Hayashi Kumada Acc. Chem. Res. 1982, 15, 395-401. 

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