Homogeneous chiral catalyst

In most cases homogeneous chiral catalysts afford higher enantioselectivities than heterogenous catalysts. Nevertheless, the development of heterogeneous chiral catalysts has attracted increasing interest because workup of the reaction, and recovery of often valuable chiral auxiliaries by simple filtration, is more convenient than in the case of homogeneous catalysts. 

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... 

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. 

Heterogeneous chiral catalysts are useful because of the easier separation of catalyst from the product and recovery process than homogeneous chiral catalysts. Heterogeneous chiral catalysts supported on polystyrene-type resin catalyse the highly enantioselective addition of dialkylzincs to aldehydes.17... 

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. 

The approach exploiting a chiral centre that is already in the synthon is effective in a number of cases. The chiral moiety in the synthon diverts a reaction at a nearby prochiral centre in favour of one enantiomer (asymmetric induction). An excellent example of the latter is the Schollkopf method (4 in Scheme 6.3, see also 5 in Scheme 6.7) hydrogenation of azlactones (3 in Scheme 6.3) using a homogeneous chiral catalyst is one route illustrating the former approach. Use of chiral five-membered heterocyclic compounds (e.g., 6 and 7) offers an alternative successful approach to asymmetric amino-acid synthesis. 

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

By immobilising homogeneous chiral catalysts on the inner surface of porous solids, considerations like separability, re-use and selectivity may be addressed... 

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-... 

In principle, in the use of the self-supporting strategy for heterogenization of homogeneous chiral catalysts, the stereochemical characteristics of the multitopic... 

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