Optical resolution of alcohols

Table 4. Optical resolution of alcohols (50 - 56) by complexation with the host 8a or 9a.

Okamoto, Y., Cao, Z.-K., Aburatani, R., and Hatada, K. (1987) Optical resolution of alcohols as carbamates by HPLC on cellulose tris(phenylcarbamate) derivatives, Bull. Chem. Soc. Jpn. 60, 3999-4003. 

Optical resolution of alcohol 532, an intermediate in the total synthesis of gibberdhc acid, was effected through chromatographic separation of the derived diastereo-meric carbamate 533, prepared from the corresponding alcohol 532 with phosgene in the presence of pyridine, DMAP, and (—)-a-phenylethylamine at 25 °C [385]. 

Menthol ester (20) with (l/ S)-frans-2,2-dimethyl-3-(2,2-dichloroethenyl) cyclopropanecarboxylic acid (19) has been utilized to produce ( R)-trans-2, 2-dimethyl-3-(2,2-dichloroethenyl) cyclopropanecarboxylic acid (21), an acid moiety of transfluthrin (22) [9]. Matsuo et al. surveyed various optically active secondary alcohols for their potential in the optical resolution of (lRS)-trans-chrysanthemic acid [10] (Scheme 2). 

Kinetic optical resolution of racemic alcohols and carboxylic acids by enzymatic acyl transfer reactions has received enormous attention in recent years56. The enzymes generally employed are commercially available lipases and esterases, preferentially porcine liver esterase (PLE) or porcine pancreatic lipase (PPL). Lipases from microorganisms, such as Candida cylindracea, Rhizopus arrhizus or Chromobacterium viscosum, are also fairly common. A list of suitable enzymes is found in reference 57. Standard procedures are described in reference 58. Some examples of the resolution of racemic alcohols are given39. 

Amines containing a chiral carbon atom in the aliphatic residue attached to the nitrogen atom are of considerable interest to the coordination chemist as, when coordinated, these ligands can induce chirality in the metal-ligand chromophore. The recent compilation27 on the methods of optical resolution of more than 1000 amines and amino alcohols (Chapter 20.3) is an excellent resource. 

Cr(CO)3 coordinates from either the top or bottom side of aromatic rings, bearing two different substituents in ortho or meta position, so that the enantiomers 285 and 286 are obtained. Optical resolution of the enantiomers is carried out by recrystallization, or column chromatography. The racemic complex of benzyl alcohol derivative 287 was separated to 288 and 289 by lipase-catalysed acetylation [68]. Enzymes recognize Cr(CO)3 as a bulky group. Chiral Cr(CO)3-arene complexes are used for asymmetric synthesis [68a]. 

For example, when a suspension of powdered optically active host 3a was mixed with racemic 1-phenylethanol (4a) in a 1 1 molar ratio and stirred at room temperature for 6 h, a 2 1 inclusion complex was formed. When the filtered solid complex was heated in vacuo, it gave (—)-4a (95 % ee, 85 % yield). For the host compounds 3a-c, approximately the same ee (78-99.9 %) and high yield (75-93 %) could be achieved in the resolution of alcohols of the 4 and 5 series in water and hexane. It has been found that introducing... 

For example, when powdered host 27 was mixed with volatile rac-but-3-yn-2-ol (29) and left for 24 h, a 1 1 inclusion complex with (+1-29 was formed. The alcohol can be removed from the complex by heating in vacuo yielding 29 of 59 % ee and 77 % yield. A second complexation, followed by distillation in vacuo, gave (+)-29 of 99 % ee and 28 % yield. The best resolution of rac-29 reported to date was by enzymatic esterification, and gave chiral alcohol at 70 % ee and 31% yield [49], Host 27 could be used for optical resolution of rac-2-hexanol... 

Mravik et al. published further application of DBTACa salt in optical resolution of different a-alkoxyalcohols. [25] An achiral (7) and three racemic (8, 9, 10) a-alkoxyalcohols were tested in coordination complex formation reactions (Scheme 5). All the resolutions were carried out in 95 % ethyl alcohol or alcohol/acetone mixtures starting from one mole of DBTACa salt and four (or more) moles of racemic alcohols. 

Compared with DBTA, there are only two methyl groups more in DPTTA but this small change in the structure causes significant differences in the outcome of complex forming resolutions. Three model compounds (26, 28, 37) among the previously investigated chiral alcohols were selected for test reactions with DPTTA. Optical resolutions of these compounds served the best results with DBTA. The results of the comparative resolution experiments with DPTTA and DBTA are collected in Table 13. [49]... 

Tanaka, K., Honke, S., Urbanczyk-Lipkowska, Z., and Toda, F. New chiral hosts derived from dimeric tartaric acid efficient optical resolution of aliphatic alcohols by inclusion complexation, J. Org. Chem. 2000,(55,3171-3176. 

Kozma, D., Bocskei, Zs., Kassai, Cs., Simon, K., and Fogassy, E. Optical resolution of racemic alcohols by diastereoisomeric complex formation with 0,0 -dibenzoyl-(2R,3R)-tartaric acid, the crystal structure of the (-)-lR,2 S, 5R-menthol.O,0,-dibenzoyl-(2R,3R)-tartaric acid complex. J. Chem. Soc. Chem. Commun. 1996, 753-754. 

The most popular methods of preparing optically active l-octyn-3-ol involve asymmetric reduction of l-octyn-3-one with optlcally-active alcohol complexes of lithium aluminum hydride or aluminum hydride. These methods give optical purities and chemical yields similar to the method reported above. A disadvantage of these metal-hydride methods is that some require exotic chiral alcohols that are not readily available in both enantiomeric forms. Other methods include optical resolution of the racemic propargyl alcohol (100 ee) (and Note 11) and microbial asymmetric hydrolysis of the propargyl acetates (-15% ee for l-heptyn-3-ol)... 

M.-J. Brienne, A. Collet, J. Jacques, A convenient optical resolution of sec-phenethyl alcohol by preferential crystallization of its 3,5-dinitrobenzoate, Synthesis (1983) 704—705. 

Resolution of Alcohols. Although not a well exploited use of brucine, a variety of secondary benzylic alcohols have been resolved by complexation and crystallization with brucine (eq 5). About a dozen alcohols were obtained in close to enantiomeric purity by this procedure. Also resolved by crystallization of their brucine inclusion complexes were a series of tertiary propargylic alcohols (eq 6). In this case, the enantiomer that does not crystallize with brucine can be obtained in almost complete optical purity from the mother liquors. 

Resolution of alcohols can be achieved following derivatization with phthalic anhydride. Racemic l-undecyn-3-ol was converted into a phthalic monoester derivative and resolved with (R)-(+)-NEA (eq 2). Liberation of the resolved phthalic ester and saponification yielded (R)-(+)-alcohol in 92% optical purity (eq 2). Similarly, the (S)-(-) alcohol is obtained upon resolution with (S)-(-)-NEA (eq 2). 

Alcohol 470 was also converted to 3-deoxy-D-araZ m6>-heptulosonic acid [213b] and to enantio pure 2-deoxyhexoses [213c]. Cycloheptatrienone (tropone) has been converted into heptitol derivatives via the optical resolution of the (tropone)Fe(CO)3 complex [213d]. 

Resolution of organic bases is carried out by reversing the process just described using naturally occurring optically active acids, (—)-malic acid, for example. Resolution of alcohols, which we shall find to be of special importance in synthesis, poses a special problem since alcohols are neither appreciably basic nor acidic, they cannot be resolved by direct formation of salts. Yet they can be resolved by a rather ingenious adaptation of the method we have just described one attaches to them an acidic handle, which permits the formation of salts, and then when it is no longer needed can be removed. 

Uses. The optically active form is useful for the resolution of ( )-alcohols and amines. The crude d/-form (m.p. 81-83°) is suitable for oxidation to ( )-ketopinic... 

Fig. 1. Optical resolution of partly decomposed 1-methyl-l-phenylpropyl hydroperoxide. Eluent water-saturated hexane/2-propanol, 98/2, v/v upper optical rotation lower UV 1 unknown, 2 (-l-)-enantiomer and 3 (—)-enantiomer of the related alcohol, 4 (+)-enantiomer and 5 (—/-enantiomer of the hydroperoxide...

This molecule (6) was needed for the resolution of alcohol <7) into optical isomers, a derivative with an ionisable group (here CO2H) being required. 

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