Asymmetric reactions kinetic resolution

Molybdenum catalysts that contain enantiomerically pure diolates are prime targets for asymmetric RCM (ARCM). Enantiomerically pure molybdenum catalysts have been prepared that contain a tartrate-based diolate [86], a binaph-tholate [87], or a diolate derived from a traris-1,2-disubstituted cyclopentane [89, 90], as mentioned in an earlier section. A catalyst that contains the diolate derived from a traris-1,2-disubstituted cyclopentane has been employed in an attempt to form cyclic alkenes asymmetrically via kinetic resolution (inter alia) of substrates A and B (Eqs. 45,46) where OR is acetate or a siloxide [89,90]. Reactions taken to -50% consumption yielded unreacted substrate that had an ee between 20% and 40%. When A (OR=acetate) was taken to 90% conversion, the ee of residual A was 84%. The relatively low enantioselectivity might be ascribed to the slow interconversion of syn and anti rotamers of the intermediates or to the relatively floppy nature of the diolate that forms a pseudo nine-membered ring containing the metal. 

Vongvilai P, Larsson R, Ramstrom O (2008) Direct asymmetric dynamic kinetic resolution by combined lipase catalysis and nitroaldol (Henry) reaction. Adv Synth Catal 350 448 152... 

The multitude of terms in the literature, describing the outcome of a given chemical transformation, is a result of the need to emphasize a particular characteristic or selective aspect of a given transformation, e.g. stereoselectivity of the process, optical purity of the product(s), the generation or destruction of an asymmetric center during the transformation, etc.. Asymmetric synthesis, chiral synthesis, asymmetric induction, asymmetric destruction, kinetic resolution, asymmetric desymmetrization are such terms - ones that have described well, specific aspects of a wide variety of reactions. To date, there has been no attempt to depict all of these aspects as parts of a "big picture." Indeed, the problem of a systematic universal classification of chemical transformations has remained unsolved. 

In contrast to a conventional kinetic resolution of a racemate, asymmetrization of prochiral and meso compounds can give 100% theoretical yield. Still, the ratio of biocatalyzed asymmetrizations vs. kinetic resolutions has been reported to be only 1 4 [112]. Similar to a dynamic kinetic resolution, the enantiomeric purity of the product of an asymmetrization reaction remains constant and is independent of the extent of conversion. The enantiomeric excess of the product (e.e.p) is given by... 

EinaHy, kinetic resolution of racemic olefins and aHenes can be achieved by hydroboration. The reaction of an olefin or aHene racemate with a deficient amount of an asymmetric hydroborating agent results in the preferential conversion of the more reactive enantiomer into the organoborane. The remaining unreacted substrate is enriched in the less reactive enantiomer. Optical purities in the range of 1—65% have been reported (471). 

Enzyme-Catalyzed Asymmetric Synthesis. The extent of kinetic resolution of racemates is determined by differences in the reaction rates for the two enantiomers. At the end of the reaction the faster reacting enantiomer is transformed, leaving the slower reacting enantiomer unchanged. It is apparent that the maximum product yield of any kinetic resolution caimot exceed 50%. 

Kinetic Resolutions. From a practical standpoint the principal difference between formation of a chiral molecule by kinetic resolution of a racemate and formation by asymmetric synthesis is that in the former case the maximum theoretical yield of the chiral product is 50% based on a racemic starting material. In the latter case a maximum yield of 100% is possible. If the reactivity of two enantiomers is substantially different the reaction virtually stops at 50% conversion, and enantiomericaHy pure substrate and product may be obtained ia close to 50% yield. Convenientiy, the enantiomeric purity of the substrate and the product depends strongly on the degree of conversion so that even ia those instances where reactivity of enantiomers is not substantially different, a high purity material may be obtained by sacrificing the overall yield. 

Both reactions were carried out under two-phase conditions with the help of an additional organic solvent (such as iPrOH). The catalyst could be reused with the same activity and enantioselectivity after decantation of the hydrogenation products. A more recent example, again by de Souza and Dupont, has been reported. They made a detailed study of the asymmetric hydrogenation of a-acetamidocin-namic acid and the kinetic resolution of methyl ( )-3-hydroxy-2-methylenebu-tanoate with chiral Rh(I) and Ru(II) complexes in [BMIM][BF4] and [BMIM][PFg] [55]. The authors described the remarkable effects of the molecular hydrogen concentration in the ionic catalyst layer on the conversion and enantioselectivity of these reactions. The solubility of hydrogen in [BMIM][BF4] was found to be almost four times higher than in [BMIM][PFg]. 

Alternatively, epoxides can be formed with concomitant formation of a C-C bond. Reactions between aldehydes and various carbon nucleophiles are an efficient route to epoxides, although the cis. trans selectivity can be problematic (see Section 9.1.4). Kinetic resolution (see Section 9.1.5.2) or dihydroxylation with sequential ring-closure to epoxides (see Section 9.1.1.3) can be employed when asymmetric epoxidation methods are unsatisfactory. 

A very interesting approach to optically active sulphoxides, based on a kinetic resolution in a Pummerer-type reaction with optically active a-phenylbutyric acid chloride 269 in the presence of /V,A -dimethyIaniline, was reported by Juge and Kagan332 (equation 149). In contrast to the asymmetric reductions discussed above, this procedure afforded the recovered sulphoxides in optical yields up to 70%. Chiral a, /1-unsaturated sulphoxides 270 were prepared via a kinetic resolution elaborated by Marchese and coworkers333. They found that elimination of HX from racemic /i-halogenosulphoxides 271 in the presence of chiral tertiary amines takes place in an asymmetric way leading to both sulphoxides 270 and 271, which are optically active (optical yields up to 20%) with opposite configurations at sulphur (equation 150). 

Table 4.20 Asymmetric Diels-Alder reactions via enzymatic kinetic resolution...

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