Alcohols optically pure, formation

Since electron-donating substituents at the phosphorus atom favor addition reactions over olefination reactions, addition of 9 to aldehydes leads to the exclusive formation of the silyl-pro-tected allylic alcohols 10. No reaction products arising from Wittig alkenylation could be detected. The ylides (R,S)-9 and (S.S)-9 and their enantiomers were prepared from the corresponding optically pure l-[2-(diphenylphosphino)ferrocenyl]-A,A -dimethylethanamine diastereomers 7 via the phosphonium salts 8. 

The above sequence was demonstrated on racemic onti-mercaptol alcohol 14 as well on a small amount of optically pure 14 (separated by chiral HPLC separation) and the chiral centers of 14 were completely retained, as expected (Scheme 5.6) [8]. With proof of concept for the ring formation strategy, some efforts were put into developing a chiral synthesis of 14, as shown in Scheme 5.7. 

As was mentioned previously, certain disubstituted styrene ethers can be efficiently resolved through the Zr-catalyzed kinetic resolution. As illustrated in Eq. 7, optically pure cycloheptenyl ether 64c is obtained by the Zr-catalyzed process. The successful catalytic resolution makes the parent alcohol and the derived benzyl ether derivatives 64a and 64b accessible in the optically pure form as well. However, this approach cannot be successfully applied to all the substrates shown in Table 1. Lor example, under identical conditions, cyclopentenyl susbstrate 60b is recovered in only 52% ee after 60% conversion. Cycloheptenyl substrates shown in entry 4 undergo significant decomposition under the Zr-catalyzed carbomagnesation conditions. These observations indicate that future work should perhaps be directed towards the development of a chiral metathesis catalyst that effects the chromene formation and resolves the two styrene ether enantiomers simultaneously. 

Hydrolysis of optically pure bromide 100 a in dioxane/water gives the optically pure alcohol. This is consistent with the transannular p-xylylene ring participating in carbonium ion formation only through tz-g charge delocalization (iz-c resonance) of the type 104 rather than by direct participation in replacement of bromide via a transannularly bridged ion such as 102a. In the latter case, racemization would be expected to take place ... 

Intramolecular rhodium-catalyzed carbamate C-H insertion has broad utility for substrates fashioned from most 1° and 3° alcohols. As is typically observed, 3° and benzylic C-H bonds are favored over other C-H centers for amination of this type. Stereospecific oxidation of optically pure 3° units greatly facilitates the preparation of enantiomeric tetrasubstituted carbinolamines, and should find future applications in synthesis vide infra). Importantly, use of PhI(OAc)2 as a terminal oxidant for this process has enabled reactions with a class of starting materials (that is, 1° carbamates) for which iminoiodi-nane synthesis has not proven possible. Thus, by obviating the need for such reagents, substrate scope for this process and related aziridination reactions is significantly expanded vide infra). Looking forward, the versatility of this method for C-N bond formation will be advanced further with the advent of chiral catalysts for diastero- and enantio-controlled C-H insertion. In addition, new catalysts may increase the range of 2° alkanol-based carbamates that perform as viable substrates for this process. 

There are two ways by which a chiral auxiliary can be attached to a molecule of interest in order to insure that it crystallizes in a chiral space group—covalently and ionically. The covalent approach requires little explanation, typical examples being ester or amide formation between the achiral carboxylic-acid-containing photoreactant and an optically pure alcohol or amine. The ionic attachment is similarly straightforward, consisting of salt formation between the carboxylic-acid-containing reactant and an optically pure amine. In this case, the resulting chiral ammonium ion is referred to as an ionic chiral auxiliary. 

Table III presents separation data for R-(+)-MTPA derivatives of some 4-hydroxyacid esters obtained from chiral -lactones. The esterified alcoholic substituent strongly influenced the separation. Since the oc-values for the separation of R-(+)-MTPA derivatives of methyl-esters were very low, the lactones were converted to 4-hydroxyacid ethylesters by interesterification with so-diumethylate. Although base line separation was not attained (using a 30 m column), the method could be applied to control the formation of optically pure -lactones and 4-hydroxyacid esters during microbiological processes (13). ...

Figure 3. Formation of optically pure alcohols by stereospecific reduction of ketones and asymmetric hydrolysis of racemic acetates (DB 210, 30 m/0.33 mm i.d.).

Capillary gas chromatographic determination of optical purities, investigation of the conversion of potential precursors, and characterization of enzymes catalyzing these reactions were applied to study the biogenesis of chiral volatiles in plants and microorganisms. Major pineapple constituents are present as mixtures of enantiomers. Reductions, chain elongation, and hydration were shown to be involved in the biosynthesis of hydroxy acid esters and lactones. Reduction of methyl ketones and subsequent enantioselective metabolization by Penicillium citrinum were studied as model reactions to rationalize ratios of enantiomers of secondary alcohols in natural systems. The formation of optically pure enantiomers of aliphatic secondary alcohols and hydroxy acid esters using oxidoreductases from baker s yeast was demonstrated. 

Formation of Optically Pure Secondary Alcohols bv Yeast Alcohol Dehydrogenase... 

Formation of the 3j8-acetoxyeti-5-enic esters has been used to obtain optically pure samples of (+)- and (—)-tran5-verbenoP and to resolve an alcohol intermediate in the synthesis of the witchweed seed germination stimulant (+)-strigol. A general synthesis of thiol esters from carboxylic acids, exemplified by the formation of the n-propylthio-, isopropylthio-, and t-butylthio-esters of cholic acid, comprises reaction with diethyl chlorophosphate-triethylamine, followed by the thallium(i) salt of the appropriate thiol. 

The Simmons-Smith cyclopropanation of the same 3-(2-phenylcydopropyl)prop-2-enol (110) in its racemic form afforded an inseparable mixture of and a t/-bicyclopropanes 111 in a 1.3 1 ratio. Therefore, the Charette protocol (p 286) was used first to prepare the required allylic alcohol in its optically pure form and the cyclopropanation was carried out in the presence of the tartrate derived dioxaborolane 93. By using (+)- and (— )-tartrate derived dioxaborolane 93, both the syn- and antf-bicyclopropyls 111 were obtained. The diastereoselectivities observed in their formation were consistently greater than 12 1. ... 

Photochemical conversion of an amino(cyclopropyl)carbene (obtained from cyclopro-pyl(methoxy)carbene with optically pure D,i.-erythro amino alcohols) gave a cyclopropyl-substituted lactone, e.g. formation of 13, which upon hydrogenolysis gave a chiral cyclopropyl-glycine system.The reaction proceeds via a ketene complex. 

The Merck Frosst approach to optically pure 11,12-LTA4 employs the versatile route from 2-deoxy-D-ribose (Scheme 4.12)." The tosylate 29 was prepared from the methyl furanoside, and Wittig reaction with hexylidene triphenylphosphorane resulted in the in situ formation of epoxy alcohol 30, which does not rearrange under the reaction conditions. The Paine rearrangement occurs upon treatment of 30 with MeONaTMeOH to epoxy alcohol 31, which is then carried on in a similar fashion to the LTA4 route to optically pure 11,12-LTA4. 

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