Optical purity partial

Alkylated 4,5-dihydrooxazoles are hydrolyzed by aqueous sulfuric acid (4N, 3.5 h, reflux) to give / -aminoaIkylalkanoale hydrochlorides which precipitate from the aqueous solution. Further heating provides the chiral carboxylic acids in 62-67% optical purity. Partial racemization of the ester (5-10%) has been observed during hydrolysis14. 

With the stcrically constrained /(-amino alcohols N-P asymmetric amplification phenomena were observed similar to the effects found with 3-e.Y0-(dimethylamino)isoborneol (vide supra). Thus, alkylation of benzaldehyde with diethylzinc, catalyzed by a partially resolved catalyst N-P, gives 1-phenyl-1-propanol with an enantiomeric excess, which impressively exceeds the optical purity of the catalyst employed12. 

Preparation of the appropriate optically active sulfmate ester is initially required for reaction with a Grignard or other organometallic reagent. If the method is to produce homochiral sulfoxides, the precursor sulfmate ester must be optically pure. An exception to this statement occurs if the reaction yields a partially racemic sulfoxide which can be recrystallized to complete optical purity. 

It is well known that spontaneous resolution of a racemate may occur upon crystallization if a chiral molecule crystallizes as a conglomerate. With regard to sulphoxides, this phenomenon was observed for the first time in the case of methyl p-tolyl sulphoxide269. The optical rotation of a partially resolved sulphoxide (via /J-cyclodextrin inclusion complexes) was found to increase from [a]589 = + 11.5° (e.e. 8.1%) to [a]589 = +100.8 (e.e. 71.5%) after four fractional crystallizations from light petroleum ether. Later on, few optically active ketosulphoxides of low optical purity were converted into the pure enantiomers by fractional crystallization from ethyl ether-hexane270. This resolution by crystallization was also successful for racemic benzyl p-tolyl sulphoxide and t-butyl phenyl sulphoxide271. 

A different non-classical approach to the resolution of sulphoxides was reported by Mikolajczyk and Drabowicz269-281. It is based on the fact that sulphinyl compounds very easily form inclusion complexes with /1-cyclodextrin. Since /1-cyclodextrin as the host molecule is chiral, its inclusion complexes with racemic guest substances used in an excess are mixtures of diastereoisomers that should be formed in unequal amounts. In this way a series of alkyl phenyl, alkyl p-tolyl and alkyl benzyl sulphoxides has been resolved. However, the optical purities of the partially resolved sulphoxides do not exceed 22% after... 

Partial photochemical decomposition of racemic alkyl aryl sulphoxides in the presence of chiral amines as sensitizers gave non-decomposed sulphoxides in optically active form with optical purity of about 3%339. The report340 on the use of cholesteric liquid crystalline reaction media to change the enantiomeric composition of racemic sulphoxides at high temperatures could not be reproduced341. 

In accord with the current interest in stereochemistry at phosphorus a number of optical studies on phosphonous derivatives have been carried out. Benschop and his group have achieved a partial resolution of alkyl alkylphosphinates (133) by stereospecific inclusion in cycloamyloses. Optical purities in the range 20—80% were obtained. 

The first reductive kinetic resolution of racemic sulphoxides was reported by Balenovic and Bregant. They found that L-cysteine reacted with racemic sulphoxides to produce a mixture of L-cystine, sulphide and non-reduced optically active starting sulphoxide (equation 147). Mikojajczyk and Para reported that the reaction of optically active phosphonothioic acid 268 with racemic sulphoxides used in a 1 2 ratio gave the non-reduced optically active sulphoxides, however, with a low optical purity (equation 148). It is interesting to note that a clear relationship was found between the chirality of the reducing P-thioacid 268 and the recovered sulphoxide. Partial asymmetric reduction of racemic sulphoxides also occurs when a complex of LiAlH with chiral alcohols , as well as a mixture of formamidine sulphinic acid with chiral amines, are used as chiral reducing systems. ... 

Partially resolved samples of certain compounds show enantiomeric NMR nonequivalence in an otherwise achiral medium, and do so in magnitudes proportional to their enantiomeric purity. This phenomenon, termed self-induced nonequivalence or autononequivalence, has been observed for compounds shown in Table 12. Dihydroquinine (44) was the first of these examples to be reported (14). Figure 6 shows portions of the 100 MHz spectra of optically pure, naturally occurring dihydroquinine, a 1 1 mixture of the natural product and synthetic racemate, and the racemate alone, all at approximately the same concentration in CDCI3 solution. The three spectra are different Figure 6b shows nonequivalence for the H2, Hy, Hg, and H9 resonances, the intensities corresponding to the optical purity of the sample (33%, e.e.). 

An intermediate case between the polymerization of enantiomerically pure and racemic monomers is the polymerization of a partially resolved mixture of enantiomers with variable optical purity. Two processes are distinguishable, depending on whether polymerization occurs in the presence of an achiral (or racemic) or of a chiral (optically active) catalyst. 

The growth rates of crystals with partially broken surfaces or with fines adhered to it were larger in both directions than those of smooth surface. Further, the optical purities of crystals with broken surfaces and with fines adhered on the surfaces were lower than those with smooth surfaces. From these results, the kinetics of growth of D-SCMC crystals and the mechanism of inclusion of impurity during their growth process was considered. 

A method for determining optical purities of less than one percent for secondary alcohols has been published, and Mislow has observed a partial resolution which may serve to distinguish between a meso and a racemic host product when a derived inclusion compound is recrystallized from an enantiomerically enriched guest solvent. ... 

Despite the highly selective alkylations of azaenolates, the optical purity of the final products is rather low in several cases, due to partial racemization during hydrolysis of the alkylated imines. In general, racemization occurs very fast in basic media, whereas in acidic solutions, especially in two-phase systems, the degree of racemization is rather low and depends on the nature of the carbonyl compounds. 

As an alternative, the amino ester hydrochloride precipitate can be collected and neutralized with aqueous sodium hydrogen carbonate to generate the corresponding A-/i-hydroxyalkyl carboxamides. Crystallization of the amides results in partial resolution. Finally, acidic hydrolysis (4 N hydrochloric acid, 3 h) provides the desired chiral acids in slightly lower yields, but higher optical purities (73 84%)14,... 

In a similar way Wijnberg et al. 4,54) used an optically active heptaheterohelicene viz. [7JBBSBSBS, partially resolved from (—)-a-pinene (optical purity 7.5 %) as a starting compound for the preparation of an optically active undecaheterohelicene... 

Problem 7.20 Optically pure (S)-(-i-)-CH3CHBr-n-CjH,3 has [a] = -1-36.0°. A partially racemized sample having a specific rotation of -i-30° is reacted with dilute NaOH to form (R)-(-)-CH,CH(OH)-n-CsH,3 ([ ] =-5. 97°), whose specific rotation is -10.3° when optically pure, (a) Write an equation for the reaction using projection formulas, (b) Calculate the percent optical purity of reactant and product, (c) Calculate percentages of racemization and inversion, (d) Calculate percentages of frontside and backside attack, (e) Draw a conclusion concerning the reactions of 2° alkyl halides. (/) What change in conditions would increase inversion ... 

Similar observations were made in the dimethylketene adducts of partially resolved cyclonona-1,2-diene and cyclotrideca-1,2-diene (see Table 1). A total synthesis of isocaryophyllene was carried out using the dimethylketene adduct of the partially resolved allene 74 as an intermediate. However, in all of these cases the enantioselectivity of these processes was not determined since the optical purity of the products were not established. 

Some of the earlier studies using partially resolved allenes (1,3-dimethylallene and l,3-di-/ert-butylailene) in cycloadditions with dimethylketene and terf-butylcyanoketene reported some asymmetric induction in the resulting 2-alkylidenecyclobutanones,2 3 however, no optical purity measurements were reported. Furthermore, these reactions arc of limited value due to partial racemization accompanying the intermediacy of zwitterionic intermediates (see Section 1.3.3.). 

A characteristic example of these reactions is the conversion of propargylgylicine to the dehydroproline derivative shown in 3.45. Unfortunately under efficient coupling conditions the enantiopurity of the product is only mediocre due to partial racemization, while the conservation of the optical purity is accompanied by mediocre yields.56... 

Since the optical purity of the starting materials and the molar rotations of the pure optically active products are unknown, it is not possible to assay any partial racemization. In most instances the molar rotation of the products is as large as or larger than the starting material. It is probable that no racemization took place in these reactions, but it is impossible to state this unequivocally without a knowledge of the relationship between the rotatory dispersion curves and visible spectra of the products and starting materials. 

Sublimation. Such effects can also be seen in solid-gas interphase. Scheme 30 shows the consequences of fractional sublimation of partially resolved L-mandelic acid (47). The optical purity could be enhanced or reduced, depending on the optical purity of the starting material. Since the eutectic point of mandelic acid is obtained with about a 75 25 enantiomer ratio, such a mixture is more readily sublimed than the racemate or conglomerate. Scheme 30 gives other examples of optical enrichment by sublimation. Phenyl 1-phenyl-1-propyl sulfide in 6% ee affords the sublimed compound in 74% ee, but the residue is... 

Kinetic resolution of chiral aUylic alcohols.7 Partial (at least 60% conversion) asymmetric epoxidation can be used for kinetic resolution of chiral allylic alcohols, particularly of secondary allylic alcohols in which chirality resides at the carbinol carbon such as 1, drawn in accordance with the usual enantioface selection rule (Scheme I). (S)-l undergoes asymmetric epoxidation with L-diisopropyl tartrate (DIPT) 104 times faster than (R)-l. The optical purity of the recovered allylic alcohol after kinetic resolution carried to 60% conversion is often > 90%. In theory, any degree of enantiomeric purity is attainable by use of higher conversions. Secondary allylic alcohols generally conform to the reactivity pattern of 1 the (Z)-allylic alcohols are less satisfactory substrates, particularly those substituted at the /1-vinyl position by a bulky substituent. 

The influence of temperature and carbon monoxide partial pressure on the optical purity of the products is different, depending on the type of ligand used and on the molar ratio between ligand and metal. In the hydroformylation of styrene by [Rh(CO)2Cl]2 and (R)-BzMePhP the effect of the Pco was studied 34) at 110 °C and at 50 atm pH. For ratios L /M of 2 and 3, the optical yield shows a maximum at about 70 atm pOT in the range 0-100 atm, and at higher L /M ratio, the maximum appears at higher pressures for a L /M ratio of 4 there is practically no difference in the optical yield observed in experiments carried out at pco of 30 and 70 atm 34). 

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