Chiral catalyst, properties

The 4-thiazolidinyl phosphonates 143 (Scheme 44) are known for their therapeutical properties, in particular as anti-inflammatory agents [5,89]. Their asymmetric synthesis by hydrophosphonylation of 3-thiazolines has been described using various chiral auxiliaries chiral phosphites such as (2S,4i )-2H-2-oxo-5,5-dimethyl-4-phenyl-l,3,2-dioxaphosphorinane (de = 2-8%) [90] or BINOL-phos-phite (de = 65-90%) [91] and also chiral catalyst such as titanium or lanthanide chiral complexes (ee = 29-98%) [92]. Hydrophosphonylation of C2-chiral3-thi-azolines has also been performed (de = 32-38%) [93]. 

Because the chiral cyclopropane subunit is present in a wide range of natural and synthetic products showing important biological properties, asymmetric construction of the cyclopropane moiety via asymmetric cyclopropanation is of commercial interest. Many chiral catalysts and chiral ligands have been pre-... 

The electronic properties of chiral catalysts were examined. Condensation of the optically active 1,2-diphenylethylenediamine with appropriate C5(5 )-substituted terf-butyl salicylaldehyde derivatives followed by complexation with mangane-se(III) center led to the corresponding catalysts 12a-12e. Then three model substrates, 2,2-dimethylchromene, cA-(3-methylstyrene, and cA-2,2-dimethyl-3-hexene, were subjected to enantioselective expoxidation catalyzed by 5-substituted... 

This unique phenomenon provides a powerful strategy in the molecular design of chiral catalysts that is, the requisite chirality can be served by the simple binaphthyl moiety, while an additional structural requirement for fine-tuning of reactivity and selectivity can be fulfilled by an easily modifiable achiral biphenyl structure. This certainly obviates the use of two chiral units, and should be appreciated in the synthesis of a variety of chiral catalysts with different steric and/or electronic properties. Actually, quaternary ammonium bromide possessing a sterically demanding substituent such as (S)-12b can be easily prepared, and benzylation with (S)-12b as catalyst gave 9 in 95% yield with 92% ee. Further, theenantioselectivity was enhanced to 95% ee with (S)-12c as a catalyst [12]. 

A kinetic resolution is a chemical reaction in which one enantiomer of a racemate reacts faster than the other. Most kinetic resolutions of pharmaceutical compounds are catalyzed processes. Catalysts used in a kinetic resolution must be chiral. Binding of a chiral catalyst with a racemic material can form two different diastereomeric complexes. Since the complexes are diastereomers, they have different properties different rates of formation, stabilities, and rates of reaction. The products form from the diastereomeric substrate-catalyst complexes at different rates. Therefore, a chiral catalyst is theoretically able to separate enantiomers by reacting with one enantiomer faster than the other. The catalysts used in kinetic resolutions are often enzymes. Enzymes are constructed from chiral amino acids and often differentiate between enantiomeric substrates. 

Tables IX and X also reveal some dramatic differences between NMPP and MDPP. These ligands are diastereomers more precisely, they are epimers since they differ only in configuration at C-3. It is quite reasonable that these ligands should behave differently, since diastereomers have different chemical and physical properties, although sometimes only slightly different. However, NMDPP and MDPP generate considerably disparate behavior both in terms of the activity and the chiral influence of the catalysts derived from them. Toward every substrate examined thus far the MDPP catalyst has had a very low activity, much lower activity than the NMDPP catalyst. Also, the MDPP catalyst generally gave much lower asymmetric bias than the NMDPP catalyst, and was the only chiral catalyst to give an archiral product11 (two examples).

While the relatively low cost of many amino acids does not seem to justify the preparation of supported catalysts derived from them, other reasons may drive the immobilization of chiral catalysts, such as those mentioned above and the possibility of experimenting with different solubility properties, easy separation of the products from the catalysts and the catalyst s recyclability. The immobilization of these compounds on a support can also be seen as an attempt to develop a minimalistic version of an enzyme, with the amino acid playing the role of the enzyme s active site and the polymer that of an oversimplified peptide backbone not directly involved in catalytic activity. 

In the 1980 s there was a great increase in the development and use of enzymatic procedures by synthetic chemists.6 Previously regarded more as scientific curiosities of limited scope than of practical utility, biological-chemical transformations are now used regularly by synthetic chemists. The ability to induce optical activity in molecules where none existed before is the most useful property of these chiral catalysts. Hydrolase enzymes are generally preferred over other kinds of enzymes for transformations of this nature because they are more easily handled and do not require cofactors for activity. In cases where enantiotopic differentiation between ester functions is desired, prochiral meso diesters are more efficient substrates than racemic esters. In the former case it is possible for all starting material to be converted into a single enantiomer, whereas in the latter example only enzymatic resolution is possible. 

Enantiomers display a sensory and biological activity differentiation. Their sensory properties are not univocal. Differences in the character of odours of enantiomers eonfirm the supposition that the enzymatic theory perception is based on the activity of enzymes and odour substances. Systemic enzymes being a chiral catalyst of the highest efficiency act in an enantioselective way, and hence the considerable differentiation in biological effects (various odours). 

The potential of enzymes as catalysts in asymmetric synthesis has been recognised for many years.2-i2 Rate acceleration and stereoseiectivity, together with techniques for the iow-cost production and the rational alteration of their properties, make enzymes attractive as chiral catalysts in organic synthesis. Enzyme-catalyzed reactions have been categorised into six main groups ll as shown in Table 1. Three of them, oxido-reductases, hydrolases, and lyases have been found useful in organic synthesis. 

During the past 20 years, solid-supported organic catalysts have become powerful synthetic tools readily available to the chemical community. The reasons for developing an immobihzed version of a chiral catalyst go weU beyond the simple-yet still fundamental-aspect of the recovery and recycling of the precious catalytic species. Catalyst stabihty, structural characterization, catalytic behavior, new or different solubihty properties, simphfication of the reaction work-up, catalyst discovery and optimization, use in environmentally friendly or green solvents are all issues that may be converhently addressed working with supported systems. 

Inspired by the seminal report of Nagel [34], which described a very active and selective Rh-pyrphos catalyst attached covalently to sihca gel, Pugin and colleagues have developed the modular toolbox which his depicted schematically in Figure 12.4. The main elements of their system are functionalized chiral diphosphines, where three different hnkers are based on isocyanate chemistry and various carriers [37, 45, 58]. This approach allows for a systematic and rapid access to a variety of immobilized chiral catalysts, with the possibility of adapting their catalytic and technical properties to specific needs. 

It is the view of the present authors that the most important problem here is the high complexity of many heterogeneous systems, because this leads to poor predictability of the catalytic properties. Additional problems with immobilized chiral catalysts include not only their lack of commercially availability but also the very high costs involved in their preparation. 

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