Optical purity product

Enzyme-based processes for the resolution of chiral amines have been widely reported [2, 3] and are used in the manufacture of pharmaceuticals, for example, BASF s process for chiral benzylic amine intermediates. Scheme 13.1 [4]. The methods used are enantioselective hydrolysis of an amide and enantioselective synthesis of an amide, both of which are kinetic resolutions. For high optical purity products the processes depend upon a large difference in the catalyzed reaction rates of each enantiomer. 

Kinetic resolution is the least expensive alternative, compared to chiral chemistry, creation of diastereoisomers, or separation devices such as membranes. Additionally, it produces the highest optical purity product of all these methods. 

One of the newer and more fmitful developments in this area is asymmetric hydroboration giving chiral organoboranes, which can be transformed into chiral carbon compounds of high optical purity. Other new directions focus on catalytic hydroboration, asymmetric aHylboration, cross-coupling reactions, and appHcations in biomedical research. This article gives an account of the most important aspects of the hydroboration reaction and transformations of its products. For more detail, monographs and reviews are available (1—13). 

High demands are placed on the substrate material of disk-shaped optical data storage devices regarding the optical, physical, chemical, mechanical, and thermal properties. In addition to these physical parameters, they have to meet special requirements regarding optical purity of the material, processing characteristics, and especially in mass production, economic characteristics (costs, processing). The question of recyclabiUty must also be tackled. 

For the construction of oxygen-functionalized Diels-Alder products, Narasaka and coworkers employed the 3-borylpropenoic acid derivative in place of 3-(3-acet-oxypropenoyl)oxazolidinone, which is a poor dienophile in the chiral titanium-catalyzed reaction (Scheme 1.55, Table 1.24). 3-(3-Borylpropenoyl)oxazolidinones react smoothly with acyclic dienes to give the cycloadducts in high optical purity [43]. The boryl group was converted to an hydroxyl group stereospecifically by oxidation, and the alcohol obtained was used as the key intermediate in a total synthesis of (-i-)-paniculide A [44] (Scheme 1.56). 

Scheeren et al. reported the first enantioselective metal-catalyzed 1,3-dipolar cycloaddition reaction of nitrones with alkenes in 1994 [26]. Their approach involved C,N-diphenylnitrone la and ketene acetals 2, in the presence of the amino acid-derived oxazaborolidinones 3 as the catalyst (Scheme 6.8). This type of boron catalyst has been used successfully for asymmetric Diels-Alder reactions [27, 28]. In this reaction the nitrone is activated, according to the inverse electron-demand, for a 1,3-dipolar cycloaddition with the electron-rich alkene. The reaction is thus controlled by the LUMO inone-HOMOaikene interaction. They found that coordination of the nitrone to the boron Lewis acid strongly accelerated the 1,3-dipolar cycloaddition reaction with ketene acetals. The reactions of la with 2a,b, catalyzed by 20 mol% of oxazaborolidinones such as 3a,b were carried out at -78 °C. In some reactions fair enantioselectivities were induced by the catalysts, thus, 4a was obtained with an optical purity of 74% ee, however, in a low yield. The reaction involving 2b gave the C-3, C-4-cis isomer 4b as the only diastereomer of the product with 62% ee. 

With l-alkyl-3-alkoxyallylstannanes, effective asymmetric induction occurs to give (E)-syn-products consistent with an antiperiplanar, antarafacial S t process. The optical purity of the products parallels that of the stannane106. 

The same reaction utilizing chlorotriisopropoxytitanium gives a lower yield and optical purity of the (Z)-anti product ( + )-4 (yield 33% 64% ee). Utilization of tetraisopropoxytita-nium causes complete racemization16. The reaction of (Z)-l-methylbutenyltitanium with both enantiomers of 2-( er/-butyldimethylsilyloxy)propanal proceeds only very sluggishly with approximately 20% yield99. The results are best explained by the assumption of a (twist)boat transition state. 

The (Z)-configuration of the enol ether however is a prerequisite for both high. yyn-selecting and high optical purity of the products23. When, on the other hand, (Z)-2-benzyloxy-l-ethyl-thio-l-trimethylsilyloxy-l-propene is allowed to react with 2-propional in the presence of the diamine 2, the anti-aldol product is obtained in 92% ee42. 

The optical purities were determined solely from the optical rotations of the (/ -cyanohydrins thus obtained. Only for (/ )-a-hydroxybcnzeneacetonitrile, available from benzaldehyde, was an optical purity determined by comparison with the natural product. Variation of the reaction conditions (pH, temperature, concentration) in water/ethanol led to no appreciable improvementsl4. The use of organic solvents that are not miscible with water, but in which the enzyme-catalyzed reaction can still take place, resulted in suppression of the spontaneous addition to a significant extent, whereas the enzyme-catalyzed formation of cyanohydrins was only slightly slower (Figure l)13. 

Recently, this procedure was slightly modified by using sodium cyanide and an equivalent amount of the hydrochloride of the chiral amine, instead of adding acetic acid46, which resulted in a slightly improved yield and optical purity of the product. 

Posner and coworkers have published a series of papers in which they described a successful application of the Michael reaction between a variety of carbanionic reagents and chiral cycloalkenone sulphoxides 557 to the synthesis of chiral organic compounds (for reviews see References 257, 649, 650). In several cases products of very high optical purity can be obtained. Subsequent removal of the sulphinyl group, serving as a chiral adjuvant, leads to optically active 3-substituted cycloalkenones 558 (equation 356 Table 27). 

The submitters report obtaining the product in 99% yield. The enantiomeric excess of the Mosher ester of 3 was measured to be 98% using a Chiralcel OD column (40% 2-propanol/hexane). This optical purity measurement substantiated the optical purity assessment made by 111 NMR studies of 3 and racemic 3 prepared using a different method3. Addition of the chiral shift reagent tris[3-(heptafluoropropylhydroxymethylene)-(+)-camphorato]europium (III) resulted in clear resolution of the respective aromatic proton signals for the two enantiomers, which was demonstrated with the racemate. Under similar conditions, NMR analysis of 3 showed that within the detectable limits of the experiment (ca. <3%), there was none of the disfavored enantiomer. 

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