Optical purity substrate

An advantage that sulfonate esters have over alkyl halides is that their prepara tion from alcohols does not involve any of the bonds to carbon The alcohol oxygen becomes the oxygen that connects the alkyl group to the sulfonyl group Thus the configuration of a sulfonate ester is exactly the same as that of the alcohol from which It was prepared If we wish to study the stereochemistry of nucleophilic substitution m an optically active substrate for example we know that a tosylate ester will have the same configuration and the same optical purity as the alcohol from which it was prepared... 

The same cannot be said about reactions with alkyl halides as substrates The conver Sion of optically active 2 octanol to the corresponding halide does involve a bond to the chirality center and so the optical purity and absolute configuration of the alkyl halide need to be independently established... 

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). 

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. 

Resolution of Racemic Amines and Amino Acids. Acylases (EC3.5.1.14) are the most commonly used enzymes for the resolution of amino acids. Porcine kidney acylase (PKA) and the fungaly3.spet i//us acylase (AA) are commercially available, inexpensive, and stable. They have broad substrate specificity and hydrolyze a wide spectmm of natural and unnatural A/-acyl amino acids, with exceptionally high enantioselectivity in almost all cases. Moreover, theU enantioselectivity is exceptionally good with most substrates. A general paper on this subject has been pubUshed (106) in which the resolution of over 50 A/-acyl amino acids and analogues is described. Also reported are the stabiUties of the enzymes and the effect of different acyl groups on the rate and selectivity of enzymatic hydrolysis. Some of the substrates that are easily resolved on 10—100 g scale are presented in Figure 4 (106). Lipases are also used for the resolution of A/-acylated amino acids but the rates and optical purities are usually low (107). 

These are major disadvantage of the esterase resolution process. Since die optimum pH of die enzymic reaction is generally on the alkaline side, die esters used as substrates are non-enzymatically hydrolysed and die optical purity of die L-amino adds obtained is generally low. Also the substrate has to be protected at the amino group in most cases in order to prevent formation of diketopiperasines. The esterase method is not attractive in practice and to the best of our knowledge is not used on an industrial scale. 

The addition of an achiral organometallic reagent (R M) to a chiral carbonyl compound 1 (see Section 1.3.1.1.) leads to a mixture of diastercomers 2 (syn/anti) which can be either racemic, or enantiomerically enriched or pure, depending on whether the substrates are race-mates or pure enantiomers. This section incorporates only those reactions starting from optically pure a-amino aldehydes, however, optical purity of the starting material has not been demonstrated in all cases. 

The synthesis of 4-alkyl-y-butyrolactones 13 and 5-alkyl-<5-valerolactones 14 can be achieved in high enantiomeric excess by alkylation of ethyl 4-oxobutanoate and ethyl 5-oxopentanoate (11, n = 2, 3). The addition of diethylzinc, as well as dimethylzinc, leads to hydroxy esters 12 in high optical purity. When methyl esters instead of ethyl esters are used as substrates, the enantioselectivity of the addition reaction is somewhat lower. Alkaline hydrolysis of the hydroxy esters 12, followed by spontaneous cyclization upon acidification, leads to the corresponding y-butyro- and -valerolactones32. 

In an ideal DKR, where the substrate stays racemic throughout the reaction process, the optical purity depends only on the enantiomeric ratio (E) (ee =(E— 1)/ (E +1)), and is independent of the extent of conversion. The enantiomeric excess of the product formed under racemizing conditions is equal to the initial enantiomeric... 

In case of primary alcohol substrates, biooxidation can also proceed to the carboxylic acid, enabling a facile separation of the chiral products by simple extraction. Whole-cells of Gluconobacter oxydans were utilized to produce S-2-phenylpro-panoic acid and R-2-phenylpropionic alcohol in excellent yields and optical purities (Scheme 9.4) [46]. 

Stereoselective oxygen transfer to the sulphur atom of alkyl aryl sulphides catalyzed by 2-flavoenzyme monooxygenases afforded optically active sulphoxides in high optical yields . For instance, with ethyl p-tolyl sulphide as substrate cyclohexanone monooxygenase from Actinetobacter produces predominantly (— )-(S)-sulphoxide with 64% e.e. In contrast, FAD-containing dimethylaniline monooxygenase purified from hog liver microsomes affords (+ )-(i )-enantiomer of this sulphoxide with 90% optical purity . ... 

When re-alkyl ethynyl ketones were tested as the substrate of LBADH, the preferred stereochemistry and optical purity of the resulting propargylic alcohol were dependent upon the size of the alkyl group (Figure 7.26) [71]. 

For Z-a-benzoylaminocinnamic acid and methyl ester substrates, with various donor and acceptor substituents in the phenyl ring, there was no correlation between the Hammett o--values of para substituents and optical purity of the product (239). The DIOP systems hydrogenate Z isomers more rapidly than E isomers, and induce a greater optical bias. N-Acetyl substrates always gave higher optical purities than the JV-benzoyl substrates, and similarly acid substrates were better than the corresponding methyl esters (239). 

The bulk of the ester group has little effect on optical purity of N-acetylphenylalanine ester products formed from the dehydro substrates using the C-4 catalyst, and with this or the DIOP system, variation of the substituent in the phenyl ring of the N-acetylphenylalanine precursors also had little effect (242). 

Remarkable success has been achieved by Fryzuk and Bosnich (247) using the complex [Rh(5,5-chiraphos)(COD)]+, where the chiral ligand 25,55-bis(diphenylphosphino)butane, a diphosphine chiral at carbons (25), is readily synthesized from 2R,3R-butane diol. TheZ-isomers of the prochiral a-N-acylaminoacrylic acid substrates were hydrogenated at ambient conditions to / -products with very high enantiomeric excess indeed, leucine and phenylalanine derivatives were obtained in complete optical purity. Catalytic deuteration was shown to lead to pure chiral f3-carbon centers as well as a-carbon centers in the leucine and phenylal-... 

The resolution of rac-20 represents a less common form of catalytic kinetic resolution (parallel kinetic resolution) [9]. In conventional kinetic resolution, one substrate enantiomer reacts preferably to leave behind the unreacted isomer in high optical purity (e.g., rac-18 (k)-19 in Scheme 4). In this instance, both starting material enantiomers undergo catalytic alkylation to give constitutional isomers. Since both enantiomers are consumed simultaneously, as the reaction proceeds, the amount of slow enantiomer (relative to the unreacted fast enantiomer) does not increase. Therefore, product ee remains high, even at relatively high conversions. 

The IPA system does not require a co-solvent, but one can be used if this proves advantageous. In the TEAF system a solvent is normally used, though neat TEAF or formic acid can be used if required. The solvent can have a large effect on the reaction rate and optical purity of the product this may in part be because the substrate seems to bind by weak electrostatic interactions with the catalyst, and is also partly due to the pH of the system. Solvents have a dramatic effect on the ionization of formic acid for example, in water the piCa is 3.7, but in DMF it is 11.5. This is because formation of the formate anion becomes less favorable with less polar solvents (see Table 35.2). The piCa of triethy-lamine is far less sensitive. As a consequence, formic acid and triethylamine may remain unreacted and not form a salt. The variation in formic acid piCa can also have a significant impact on the catalyst and substrate, particularly when this is an imine. 

Typically, solvents are screened to identify one that gives optimal results. Assuming that the substrate and catalyst are soluble, solvent polarities varying from alkanes, aromatics, halogenated, ethers, acetonitrile, esters, alcohols, dipolar aprotic to water have been used. An example of this, using a ketone and the rhodium cp TsDPEN catalyst, is shown in Table 35.3. Further optimization of this reaction improved the enantiomeric excess to 98%. A second example involved the reduction of 4-fluoroacetophenone in this case the enantioselectivity was largely unaffected but the rate of reduction changed markedly with solvent. Development of this process improved the optical purity to 98.5% e.e. 

In a still less basic solvent, HFIP, a considerable amount of the rearranged product 23 was obtained even in the presence of base. Interestingly, compound 23 obtained was largely racemized, although 23 was the exclusive product and retained the optical purity of the substrate in a neutral HFIP without added base.12 So, the racemization cannot be ascribed to the intermediate formation of the primary cation 20. Trapping experiments support the formation of cycloheptyne 39 as an intermediate (eq 16).18... 

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