Resolution of optically active alcohols

Since the addition of dialkylzinc reagents to aldehydes can be performed enantioselectively in the presence of a chiral amino alcohol catalyst, such as (-)-(1S,2/ )-Ar,A -dibutylnorephedrine (see Section 1.3.1.7.1.), this reaction is suitable for the kinetic resolution of racemic aldehydes127 and/or the enantioselective synthesis of optically active alcohols with two stereogenic centers starting from racemic aldehydes128 129. Thus, addition of diethylzinc to racemic 2-phenylpropanal in the presence of (-)-(lS,2/ )-Ar,W-dibutylnorephedrine gave a 75 25 mixture of the diastereomeric alcohols syn-4 and anti-4 with 65% ee and 93% ee, respectively, and 60% total yield. In the case of the syn-diastereomer, the (2.S, 3S)-enantiomer predominated, whereas with the twtf-diastereomer, the (2f ,3S)-enantiomer was formed preferentially. 

The separation of amino acids into particular enantiomers was the subject of mass spectrometric studies but also ESI MS was applied to determine by kinetic resolution the enantiomeric excess of optically active alcohols and amines in nanoscale by diastereoselective derivatization with optically active acids [38], This method has several distinctive features among others, easily available chiral acids can be used (the authors used A -benzoyl proline derivatives), no chromatographic separations are required, it is insensitive to certain impurities, it is fast and requires only small amount of substrate (10 nmol or less). The method can take an advantage when accuracy of enantiomeric excess measurement is sufficient within 10% limits. 

RESOLUTION OF sec.-OCTYL ALCOHOL (d/-2-OCTA-NOL) INTO ITS OPTICALLY ACTIVE COMPONENTS (d- AND f-2-OCTANOL)... 

Optically Active Alcohols and Esters. In addition to the hydrolysis of esters formed by simple alcohols described above, Hpases and esterases also catalyze the hydrolysis of a wide range of esters based on more complex and synthetically useful cycHc and acycHc alcohols (Table 5). Although the hydrolysis of acetates often gives the desirable resolution, to achieve maximum selectivity and reaction efficiency, comparison of various esters is recommended. 

Hie same autliors also studied tlie alkylation of alkynyl epoxides for fornialion of optically active a-aUenic alcohols under kinetic resolution ctmdilions fSdieme 8.29) [54]. 

Table 9 Result of one-pot preparation method of optically active sec-alcohols (65a,b, 65e-i) by a combination of reduction of ketone and enantiomeric resolution in a water susupension medium... 

Mikolajczyk and coworkers have summarized other methods which lead to the desired sulfmate esters These are asymmetric oxidation of sulfenamides, kinetic resolution of racemic sulfmates in transesterification with chiral alcohols, kinetic resolution of racemic sulfinates upon treatment with chiral Grignard reagents, optical resolution via cyclodextrin complexes, and esterification of sulfinyl chlorides with chiral alcohols in the presence of optically active amines. None of these methods is very satisfactory since the esters produced are of low enantiomeric purity. However, the reaction of dialkyl sulfites (33) with t-butylmagnesium chloride in the presence of quinine gave the corresponding methyl, ethyl, n-propyl, isopropyl and n-butyl 2,2-dimethylpropane-l-yl sulfinates (34) of 43 to 73% enantiomeric purity in 50 to 84% yield. This made available sulfinate esters for the synthesis of t-butyl sulfoxides (35). 

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. ... 

Another method for determining the absolute configurations of secondary alcohols is Horeau s method, which is based on kinetic resolution. As shown in Scheme 1-14, an optically active alcohol reacts with racemic 2-phenylbutanoic anhydride (54), and an optically active 2-phenylbutanoic acid (52) is obtained after hydrolysis of the half-reacted anhydride. 

Oxidative kinetic resolution of secondary alcohols mediated with a catalytic amount of optically active binaphthyl-type iV-oxyl has been performed with high selectivity". Also, it has mediated oxidative asymmetric desymmetrization of primary alcohols with good selectivity (equation 25)". ... 

The first example of kinetic resolution catalyzed by an organometallic compound was the partially enantiomer-selective polymerization of racemic propylene oxide induced with a diethylzinc optically active alcohol system (50). 

Optically Active Acids ami Esters. Enannoselcctive hydrolysis of esters of simple alcohols is a common method for the production of pure enantiomers of esters or Ihe corresponding acids. Lipases, esterases, and proteases accept a wide variety of esters and convert them to the corresponding acids, often in a highly cnantiosclectivc manner. Lipasc-cutulyzed kinetic resolutions are often practical for the preparation of optically active pharmaceuticals. 

By combination of two processes of chemical reaction and optical resolution, a novel one-pot preparation method of optically active. vcc-alcohols becomes available. When these processes are accomplished in a water suspension medium, these are really green and sustainable procedure. Some these examples are described. 

Miyamoto, H., Yasaka, S., Takaoka, R, Tanaka, K., and Toda, F. (2001) One-pot Preparation of Optically Active sec-Alcohols, Epoxides, and Sulfoxides by a Combination of Synthesis and Enantiomeric Resolution with Optically Active Hosts in a Water Suspension Medium, Eanantiomer, 6, 51-55. 

The kinetic resolution of racemic secondary alcohols via enantioselective benzoylation using Ph3Bi(OAc)2, CO, AgOAc, and a chiral Pd(n) catalyst has been investigated (Equation (135)).220,220a Of the chiral P- and A-ligands tested, the planar chirality of an optically active oxazolynylferrocenylphosphane has shown some positive effects on the enantioselectivity. 

Wilson RM, Jen WS, MacMillan DWC (2005) Enantioselective organocatalytic intramolecular Diels-Alder reactions. The asymmetric synthesis of solana-pyrone D. J Am Chem Soc 127 11616-11617 Xie JH, Zhou ZT, Kong WL, Zhou QL (2007) Ru-catalyzed asymmetric hydrogenation of racemic aldehydes via dynamic kinetic resolution efficient synthesis of optically active primary alcohols. J Am Chem Soc 129 1868-1869... 

This procedure required but one resolution of the acetylenic alcohol 40 which then served to resolve the remaining chiral portion of the molecule. The resolution of octyn-3-ol 40 therefore was the start of the synthesis of the optically active 7-oxaprostanoids. Reaction of the racemic octyn-3-ol 40 with phthalic anhydride gave the phthalyl acid 41 which formed the crystalline salt 42 by reaction with ( )-o -phenethylamine with the absolute configuration shown. 

By using high resolution capillary gas chromatography, the scope of use of these reagents, which were initially introduced for NMR-analysis (5J and for GC separation of secondary alcohols (6), was enlarged considerably (7,j3). The application of these methods to the analysis of optically active compounds formed during microbiological processes and to the determination of the enantiomeric composition of chiral aroma constituents in some tropical fruits is described in this paper. 

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