Alcohols optical resolution

Industrial Synthetic Improvements. One significant modification of the Stembach process is the result of work by Sumitomo chemists in 1975, in which the optical resolution—reduction sequence is replaced with a more efficient asymmetric conversion of the meso-cyc. 02Lcid (13) to the optically pure i7-lactone (17) (Fig. 3) (25). The cycloacid is reacted with the optically active dihydroxyamine [2964-48-9] (23) to quantitatively yield the chiral imide [85317-83-5] (24). Diastereoselective reduction of the pro-R-carbonyl using sodium borohydride affords the optically pure hydroxyamide [85317-84-6] (25) after recrystaUization. Acid hydrolysis of the amide then yields the desired i7-lactone (17). A similar approach uses chiral alcohols to form diastereomic half-esters stereoselectivity. These are reduced and direedy converted to i7-lactone (26). In both approaches, the desired diastereomeric half-amide or half-ester is formed in excess, thus avoiding the cosdy resolution step required in the Stembach synthesis. 

From intermediate 28, the construction of aldehyde 8 only requires a few straightforward steps. Thus, alkylation of the newly introduced C-3 secondary hydroxyl with methyl iodide, followed by hydrogenolysis of the C-5 benzyl ether, furnishes primary alcohol ( )-29. With a free primary hydroxyl group, compound ( )-29 provides a convenient opportunity for optical resolution at this stage. Indeed, separation of the equimolar mixture of diastereo-meric urethanes (carbamates) resulting from the action of (S)-(-)-a-methylbenzylisocyanate on ( )-29, followed by lithium aluminum hydride reduction of the separated urethanes, provides both enantiomers of 29 in optically active form. Oxidation of the levorotatory alcohol (-)-29 with PCC furnishes enantiomerically pure aldehyde 8 (88 % yield). 

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). 

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). 

In certain cases, especially for neutral substrates, the formation of covalent p,n-pairs, instead of salts, may be necessary to achieve optical resolution by crystallization. Suitable derivatives are esters of camphanic acid (1) or chrysanthemic acid (2) with racemic alcohols, or esters of menthol (3) and 1-phenylethanol (5) with racemic acids, or hydrazones of menthylhydrazine (4) with racemic aldehydes and ketones. 

Contrary to the optical resolutions described in Sections 2.1.1.-2.1.3., which depend on the solubility or chromatographic properties ( Thermodynamic resolution ), the kinetic resolution rests on rate differences shown by the enantiomers when reacted with an optically active reagent. In the ideal case, only one enantiomer is converted into the envisaged product and the other enantiomer is unchanged. In this way, optical resolution is reduced to the more simple separation of two different reaction products. In practice, only two methods of kinetic resolution are reasonably general and reliable the Sharpless epoxidation of allylic alcohols and the enzymatic transesterification of racemic alcohols or carboxylic acids. 

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. 

Yeast-mediated reductions predominantly form a single enantiomer and it is often difficult to find conditions which produce the opposite stereoisomer selectively. It has, however, been possible to obtain both enantiomers in 50% yield in 100% via enzymatic optical resolution. Chiral fluorinated secondary alcohols possessing the mono-, di- and/or trifluoromethyl group have been prepared by enzyme-catalyzed kinetic resolutions [27]. 

In this type of study, the terminally-CF3 propargylic alcohol (S)- derived from the enzymatic resolution is also a useful intermediate. This material is transformed into the corresponding E- and Z-allylic alcohols after successful enzymatic optical resolution. Os04-catalyzed oxidation eventually led to the formation of the desired triols 30 in a diastereoselective manner. 

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 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... 

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

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. 

Toda, F., and Tanaka, K. (1981) ANew Optical Resolution Method of Tertiary Acetylenic Alcohol Utilizing Complexation with Brucine, Tetrahedron Lett., 22, 4669-4672. 

Key words optical resolution, diastereoisomeric complexes, 0,0 -dibenzoyltartaric acid, hydroxycarboxylic acid esters, hydroxycarboxylic acids, chiral phosphine oxides, racemic alcohols. 

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. 

Recovery of the resolved alcohols was achieved by extraction or distillation. In special cases ligand exchange (similar to the before mentioned workup procedures of the calcium compounds) was used to liberate the previously complexed alcohol enantiomer. Results of the optical resolutions made by DBTAZn are summarized in Table 3 where the overall numbers of the coordinated auxiliary ligands (nAi and mA2) are also given on the basis of X-ray analysis data. [25]... 

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. 

Newman, P. Optical Resolution Procedures for Chemical Compounds, (1978) Vol. 1, Amines and Related Compounds, (1981) Vol. 2, Acid, (1984) Vol. 3, Alcohols, Phenols, Thiols, Aldehydes and Ketones, Optical Resolution Information Center, New York. 

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