S-2-Octanol

As an example of an enantiospecific acylation in organic solvent with the irreversible acyl donor vinyl laurate (see Fig. 3), only the (R)-enantiomer is acylated, while the (S)-2-octanol is obtained directly in 69% yield, a purity 99% and with an excellent enantiomeric ratio S R 99.5 0.5 (as determined by chiral GC-analysis). The selectivity of the forward reaction, catalyzed by a lipase in MTBE, is thereby maximized, because the use of the enolester precludes the reverse reaction. Batches of about 70 kg are produced routinely and the technology can be easily transferred to larger sizes. 

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Hydrolysis of (/ )-( —)-2-bromooctane by the Sn2 mechanism yields optically active (S)-(+)-2-octanol. The 2-octanol obtained by hydrolysis of racemic 2-bromooctane is not optically active. 

BINAL-H reagents 45 are not effective in the enantioselective reduction of dialkyl ketones.53 For example, reaction of benzyl methyl ketone with (S)-45 gives (S )-l-phenyl-2-propanol in only 13% ee (71% yield). Reaction of 2-octanone with (R)-45 produces (S )-2-octanol in 24% ee (67% yield).53 This drop of ee values in the reaction may be explained by the lower energy difference between the favored transition state 48 and unfavored transition state 49 caused by the lack of the above-mentioned n-n repulsion between the reductant and the substrate dialkyl ketone. 

Strain (whole cells) Time (h) Conversion (%) Ee (S)-2-octanol (%) f-value... 

The conversion of heptyl 3,3-dimethyl-l-oxa-4-azaspiro[4.5]decane-4-carboxylate into (S)-2-octanol demonstrates the easy availability of chiral secondary alcohols by this method42. 

The example given in the text illustrates inversion of configuration in the SN2 hydrolysis of (S)-( 1 )-2-bromooctane, which yields (R)-(-)-2-octanol. The hydrolysis of (R)-( )-2-bromooctanc exactly mirrors that of its enantiomer and yields (S>(+)-2-octanol. 

In Section 8.14 of the text we are told that optically pure (S )-( I )-1-methylheptyl /Holuenesulfonate is prepared from optically pure (S)-(+)-2-octanol having a specific rotation [a]o +9.9°. The conversion of an alcohol to a p-toluenesulfonate proceeds with complete retention of configuration. Hydrolysis of this /Holuenesulfonate with inversion of configuration therefore yields optically pure (R)-(-)-2-octanol of [ ]d -9.9°. 

In addition to this, that an interesting novel emulsion membrane reactor concept overcomes the difficulties of the large solvent volume otherwise required for the reduction of poorly soluble ketones [30]. 2-Octanone was reduced by a carbonyl reductase from Candida parapsilosis to (S)-2-octanol with > 99.5 % ee and total turnover number of 124 - the 9-fold value of that obtained in a classical enzyme reactor. 

The resolution of the racemic mixture of 2-octanol and of other secondary alcohols (2-butanol, 2-pentanol, 2-hexanol, and 2-heptanol) by direct esterification in organic solvent was studied by using lyophiUzed mycelia of R. oryzae CBS112.07 as catalysts [18]. The profile of the resolution of (R,S)-2-octanol under optimized conditions (lg/1 of alcohol and equimolar butanoic acid as acylating agent in n-heptane, 30g/l of dry biocatalyst, and 30 °C) is shown in Figure 6.1. 

Use of (S)-( +)-2-octanol of high optical activity in this reaction led to (RH—)-2-octylamine with high optical purity. The reaction thus proceeds with nearly complete inversion of configuration of the alkyl group. 

Figure 5.5 Linear relationships between concentrations (mg/L) of aroma compounds evaluated in 7 different wines by GC-FID analysis after XAD-2 enrichment and the Ax/Ai.s. ratios (i.s. 2-octanol) after Kaltron liquid-liquid extraction [some scores could be hidden)...

Table 5.4 Repeatability of four extractions of free aroma compounds from different wines using a polyhydroxylated styrene-divinylbenzene (ISOLUTE ENV+) cartridge, and comparison with mean values of data of two repeated extractions by polystyrene resin XAD-2. Value Ax/Ai.s. after GC analysis i.s. 2-octanol.

The opposite enantiomer (R)-2-octanol is obtained in 77% yield after removal of the acyl group, as shown in Fig. 4. The purity of >99% and the enantiomeric ratio of R S>99.5 0.5 (determined by chiral GC) is also excellent. The acylated (R)-2-octanol is obtained as the first intermediate in the above-mentioned lipase-catalyzed reaction in MTBE and has to be separated from unreacted (S)-2-octanol. 

Asymmetric Meerwein-Ponndorf disproportionation (78) with (+)-(S)-2-octanol led to assignment of the R configuration to the doubly bridged bi-phenyldiketone (60). This was further confirmed by stereochemical correlation based on X-ray diffraction data (79). These correlations have been extended to... 

The latter reagent is most effective for aromatic ketones an alkyl ketone. 2-octanone, gives (S)-2-octanol with only 4% asymmetric induction. 

The chiral alcohols are mainly employed as esters or enol ethers. Esters with carboxylic acids can be obtained by any convenient esterification technique. Dienol ethers were obtained by transetherification with the ethyl enol ether of a 1,3-diketone, followed by Wittig reaction8 silyldienol ethers were obtained by the method of Danishefsky11-12 and simple enol ethers by mercury-catalyzed transetherification13. Esters and enol ethers have been used as chiral dienophiles or dienes in diastereoselective Diels-Alder reactions (Section D. 1.6.1.1.1.1.). (R)-l-Phenylethanol [(R)-4] has been used for enantioselective protonation (Section C.) and the (S)-enantiomer as chiral leaving group in phenol ethers for the synthesis of binaphthols (Section B.2.) the phenol ethers are prepared as described for menthol in the preceding section. (S)-2-Octanol [(S)-2] has found applications in the synthesis of chiral allenes (Section B.I.). 

As a new option, for the bioconversion of poorly soluble substrates the classical EMR-concept can be extended to an Emulsion Membrane Reactor , comprising a separate chamber for emulsification (with a hydrophilic ultrafiltration membrane), an EMR-Ioop with a normal ultrafiltration module, and a circulation pump. This approach has been successfully demonstrated for the enzymatic reduction of poorly soluble ketones [107]. Using this device, e.g., for the enantioselective reduction of 2-octanone to (S)-2-octanol (e.e. >99.5%) with a carbonyl reductase from Candida parapsilosis under NADH-regeneration with FDH/for-mate, the total turnover number was increased by a factor 9 as compared with the classical EMR. 

Optical intereonversion of sec-alcohols. This reaction can be accomplished readily by treatment of the salt (a, above) with trichloroacetic acid and triethyl-amine to give the ester 2, with inverted configuration. Alkaline hydrolysis of 2 then affords the alcohol 3. A typical example is the conversion of (R)-(—)-2-octanol into (S)-( + )-2-octanol, formulated in equation (I). 

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