Enantioimpure catalysts

Blackmond, D. G. Kinetic Resolution Using Enantioimpure Catalysts Mechanistic Considerations of Complex Rate Laws. J. Am. Chem. 

When a kinetic resolution is carried out using enantioimpure catalysts which do not interact with one another, the reaction network (Figure 5.25) must be expanded. 

Recently, the concept of kinetic resolution has been extended to the case where enantioimpure catalysts are used. Kagan discovered the first examples of nonlinear effects in asymmetric catalysis, where there was no proportionality between the ee of the auxiliary and the ee of product (Figure 5.27) and gave some mathematical models to discuss these effects. The nonlinear effect (NLE) originates from the formation of diastereomeric species when the chiral auxiliary is not enantiomerically pure, either inside or outside the catalytic cycle. The observed effects were classified as (+)-NLE and (-)-NLE where "asymmetric amplification" and "asymmetric depletion" respectively occured. 

Figure 5.28. Scheme for kinetic resolution mechanism with two homochiral (catRR and catSS) and one heterochiral (cat/JS) catalyst species (D.G. Blackmond, Kinetic resolution using enantioimpure catalysts mechanistic considerations of complex rate laws, J. Am. Chem. Soc., 123 (2001) 545). 

Since the early times of stereochemistry, the phenomena related to chirality ( dis-symetrie moleculaire, as originally stated by Pasteur) have been treated or referred to as enantiomericaUy pure compounds. For a long time the measurement of specific rotations has been the only tool to evaluate the enantiomer distribution of an enantioimpure sample hence the expressions optical purity and optical antipodes. The usefulness of chiral assistance (natural products, circularly polarized light, etc.) for the preparation of optically active compounds, by either resolution or asymmetric synthesis, has been recognized by Pasteur, Le Bel, and van t Hoff. The first chiral auxiliaries selected for asymmetric synthesis were alkaloids such as quinine or some terpenes. Natural products with several asymmetric centers are usually enantiopure or close to 100% ee. With the necessity to devise new routes to enantiopure compounds, many simple or complex auxiliaries have been prepared from natural products or from resolved materials. Often the authors tried to get the highest enantiomeric excess values possible for the chiral auxiliaries before using them for asymmetric reactions. When a chiral reagent or catalyst could not be prepared enantiomericaUy pure, the enantiomeric excess (ee) of the product was assumed to be a minimum value or was corrected by the ee of the chiral auxiliary. The experimental data measured by polarimetry or spectroscopic methods are conveniently expressed by enantiomeric excess and enantiomeric... 

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