Homogeneous chiral catalysts for

Following Wilkinson s discovery of [RhCl(PPh3)3] as an homogeneous hydrogenation catalyst for unhindered alkenes [14b, 35], and the development of methods to prepare chiral phosphines by Mislow [36] and Horner [37], Knowles [38] and Horner [15, 39] each showed that, with the use of optically active tertiary phosphines as ligands in complexes of rhodium, the enantioselective asymmetric hydrogenation of prochiral C=C double bonds is possible (Scheme 1.8). 

Chiral quaternary ammonium salts in solid state have also been used as catalysts for the enantioselective addition of diethylzinc to aldehydes (Scheme 2-45).112 In most cases, homogeneous chiral catalysts afford higher enantio-selectivities than heterogeneous ones. Scheme 2-45 presents an unusual asymmetric reaction in which chiral catalysts in the solid state afford much higher enantioselectivities than its homogeneous counterpart.112... 

A classical example is the development of soluble chiral catalysts for homogenous asymmetric hydrogenation. The story began with the discovery of Wilkinson s catalyst [4]. In 1968, Horner [5] and Knowles [6], independently, reported the feasibility of asymmetric hydrogenations in the presence of optically active Wilkinson-type catalyst. Although the optical yields were rather low, further studies in this direction were the basis of the success of Monsanto s asymmetric synthesis of the anti-Parkinson s drug L-DOPA. The key steps of the synthesis are outlined in Scheme 11.1. 

Enantioselective synthesis is a topic of undisputable importance in current chemical research and there is a steady flow of articles, reviews and books on almost every aspect involved. The present overview will concentrate on the application of solid chiral catalysts for the enantioselective synthesis of chiral molecules which are a special class of fine chemicals. Included is an account on our own work with the cinchona-modified Pt catalysts. Excluded is the wide field of immobilized versions of active homogeneous complexes or of bio-catalysts. During the preparation of this survey, several reviews have been found to be very informative [1-14]. 

Lastly, a comment is warranted on the cut-off of 90% e.e. employed by Jacobsen and Finney. By today s standards, such a level of enantioselectivity is much too low considering that the FDA, for new processes to enantiomerically pure pharmaceutical intermediates, demands a separate toxicological investigation for every by-product above the level of 1%, even the undesired enantiomer, an e.e. value of 98% should represent the lower bound. A value of 99% would be preferable and good biocatalytic processes feature an enantiomeric excess of > 99.5%. While such performance levels should serve as standard, many homogeneous chiral catalysts show enantioselectivities of 90-95% e.e., so a cut-off of 90% serves as a bias towards such catalysts. 

Our approach was to enlarge the intrazeolitic cavities in order to generate superior hosts for bulky homogeneous chiral catalysts. Mesopores created this way are completely surrounded by micropores and offer additional advantages. The entrapped metal complex can move freely and is more accessible during catalysis and even sterically demanding transition states can be formed within the individual pores. 

When comparing chemical and biocatalytic methods, one could say that, especially for asymmetric oxidations, enzymatic methods enter the scene. This is most evident in the area of asymmetric Baeyer-Villiger oxidation, where biocatalysts take the lead and homogeneous chiral catalysts lag far behind in terms of ee values. Significant progress can be expected in the area of biocatalysis due to the advancement in enzyme production technologies and the possibility of tailor-made enzymes. 

A more direct approach to the enantioselective hydrogenation of a prochiral group involves the use of a chiral catalyst for the reaction. " At present most of these reactions are run using chiral homogeneous catalysts but the... 

Figure 1.2 Schematic representation ofthe strategies for immobilizing homogeneous chiral catalysts with solid supports.

Hoveyda and Schrock developed chiral Mo complexes [145, 146] which have been used successfully as chiral catalysts for enantioselective olefin methathesis. A polymer-supported version of the chiral Mo complex 232 was also prepared. The supported chiral complex delivers appreciable levels of reactivity and excellent enantioselectivity [147] with, in most cases, the chiral catalyst providing as high levels of enantioselectivity as the corresponding homogeneous variant. For example, 236 was obtained in quantitative conversion in 30 min with 98% ee by using the polymeric catalyst 232 (Scheme 3.77). 

During the past two decades the homogeneous and heterogeneous catalytic enan-hoselective addition of organozinc compounds to aldehydes has attracted much attention because of its potential in the preparation of optically active secondary alcohols [69]. Chiral amino alcohols (such as prolinol) and titanium complexes of chiral diols (such as TADDOL and BINOL) have proved to be very effective chiral catalysts for such reactions. The important early examples included Bolm s flexible chiral pyridyl alcohol-cored dendrimers [70], Seebach s chiral TADDOL-cored Frechet-type dendrimers [28], Yoshida s BINOL-cored Frechet-type dendrimers [71] and Pu s structurally rigid and optically active BlNOL-functionalized dendrimers [72]. All of these dendrimers were used successfully in the asymmetric addition of diethylzinc (or allyltributylstannane) to aldehydes. 

All of catalytic enantioselective alkylations of imines that have been described up to this point used homogeneous chiral catalysts. In an effort to facilitate the separation process of the product from the reaction mixture, Soai and co-workers have employed copolymers of norephedrine for the enantioselective addition of diethylzinc to a phosphinoyl imine [35c]. 

Polymeric membranes also show potential for application in the area of chiral catalysis. Here metallocomplexes find use as homogeneous catalysts, since they show high activity and enantioselectivity. They are expensive, however, and their presence in the final product is undesirable they must be, therefore, separated after the reaction ends. Attempts have been made to immobilize these catalysts on various supports. Immobilization is a laborious process, however, and often the catalyst activity decreases upon immobilization. An alternative would be a hybrid process, which combines the homogeneous catalytic reactor with a nanofiltration membrane system. Smet et al. [2.98] have presented an example of such an application. They studied the hydrogenation of dimethyl itaconate with Ru-BINAP as a homogeneous chiral catalyst. The nanofiltration membrane helps separate the reaction products from the catalyst. Two different configurations can be utilized, one in which the membrane is inserted in the reactor itself, and another in which the membrane is extraneous to the reactor. Ru-BINAP is known to be an excellent hydrogenation catalyst... 

In a newsletter in 2000, Dow CMS announced it had joined forces with the Center for AppHed Catalysis to speed the commerdahzation of sohd-supported homogeneous chiral catalysts [104]. However, in the information given on the homepage of the Center for Applied Catalysis dated 2002, Johnson Matthey is marketing these catalysts [105]. Johnson Matthey, on the other hand, an-... 

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