Optically active alcohols

Properties White or yellowish crystals slight camphor odor. Mp 137C. Slightly soluble in water and ether soluble in acetone and hot alcohol. Optically active. Combustible. 

Properties White, crystalline plates. Soluble in water insoluble in alcohol. Optically active. DL-cys-tine, mp 260C. D(+)-cystine, mp 247-249C. l(—)-cystine, mp 258-261C with decomposition. 

The silicon-carbon bonds having at least one hetero-atom substituent on the silicon atom are oxidized by H202 with a fluoride source to give the corresponding alcohols with retention of the configuration at the carbon atoms [103,104]. The Si-C oxidation is successfully combined with bis-silylation reactions, providing new access to stereo-defined alcohols. Optically active (3-hydroxy ketones 108 are synthesized by enantioselective 1,4-bis-silylation of a,(3-unsaturated ketones followed by transformations including the Si-C oxidation (Scheme 9) [64]. 

When simple aldehydes were converted to allylic alcohols, they could be transformed to the corresponding trichloroacetimidates and subjected to thermal rearrangement to provide aUyl amines. The aUyl amine functionality was also accessible from enantio-selective reduction of propargyl ketones followed by conversion to the phthalamide derivative and reduction of the triple bond. Ozonolysis of these substrates provided the corresponding a-amino methyl esters in good yield (eq 48). As with the allyl alcohols, optically active substrates were treated with ozone without loss of enantiopurity of the chiral center. 

Meerwein-Ponndorf-Verley type asymmetric reduction has also been accomplished with alkyloxy magnesium halides prepared from optically active alcohols. Optically active 2-octyloxy-2-d magnesium bromide reduced butyraldehyde to optically active n-butyl-1-d alcohol (Streitwieser, 1953). Reduction of benzaldehyde with 1-deuteroisobornyloxy magnesium halide produced optically active benzyl-l-d alcohol (Streitwieser and Wolfe, 1957 Streitwieser et al, 1959). 

Borneol and isoboineol are respectively the endo and exo forms of the alcohol. Borneol can be prepared by reduction of camphor inactive borneol is also obtained by the acid hydration of pinene or camphene. Borneol has a smell like camphor. The m.p. of the optically active forms is 208-5 C but the racemic form has m.p. 210-5 C. Oxidized to camphor, dehydrated to camphene. 

An optically active, secondary terpene alcohol. ( —)-Piperilol is found in various eucalyptus oils and (-l-) piperitol in the oil from a species of Andropogon. A somewhat viscous oil of pleasant smell. It yields piperitone on oxidation with chromic acid. 

Isovaleric acid, Me2CHCH2COOH, is a colourless liquid with the unpleasant odour of valerian, b.p. 177 "C. Occurs in the roots of valerian and angelica together with an optically active form of methylethylethanoic acid. Prepared by oxidation of isoamyl alcohol. A mixture of acids similar to that obtained from valerian roots is prepared by oxidation of fusel oil. 

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

The 7, i5-unsaturated alcohol 99 is cyclized to 2-vinyl-5-phenyltetrahydro-furan (100) by exo cyclization in aqueous alcohol[124]. On the other hand, the dihydropyran 101 is formed by endo cyclization from a 7, (5-unsaturated alcohol substituted by two methyl groups at the i5-position. The direction of elimination of /3-hydrogen to give either enol ethers or allylic ethers can be controlled by using DMSO as a solvent and utilized in the synthesis of the tetronomycin precursor 102[125], The oxidation of the optically active 3-alkene-l,2-diol 103 affords the 2,5-dihydrofuran 104 in high ee. It should be noted that /3-OH is eliminated rather than /3-H at the end of the reac-tion[126]. 

The carbonyiation of o-diiodobenzene with a primary amine affords the phthalimide 501 [355,356]. Carbonyiation of iodobenzene in the presence of (9-diaminobenzene (502) and DBU or 2,6-lutidine affords 2-phenylbenzimida-zole (503)[357, The carbonyiation of aryl iodides in the presence of pentaflnor-oaniline affords 2-arylbenzoxazoles directly, 2-Arylbenzoxazole is prepared indirectly by the carbonyiation of (9-aminophenol[358j. The optically active aryl or alkenyl oxazolinc 505 is prepared by the carbonyiation of the aryl or enol triflates in the presence of the opticaly active amino alcohol 504, followed by treatment with thionyl chloride[359]. 

An advantage that sulfonate esters have over alkyl halides is that their prepara tion from alcohols does not involve any of the bonds to carbon The alcohol oxygen becomes the oxygen that connects the alkyl group to the sulfonyl group Thus the configuration of a sulfonate ester is exactly the same as that of the alcohol from which It was prepared If we wish to study the stereochemistry of nucleophilic substitution m an optically active substrate for example we know that a tosylate ester will have the same configuration and the same optical purity as the alcohol from which it was prepared... 

The few studies that have been carried out with optically active tertiary alcohols indicate that almost complete racemization accompanies the preparation of tertiary alkyl halides by this method... 

Suggest a reasonable mechanism for this reaction based on the observation that the ether produced from optically active alcohol is racemic and that alkenes can be shown not to be intermediates in the reaction... 

Identical conclusions come from stereochemical studies 8aponification of esters of optically active alcohols proceeds with retention of configuration... 

Other uses of Snp2 are in the synthesis of fluorophosphate glasses having low melting temperatures (13—15), in formation of transparent film (16), and in the preparation of optically active alcohols (17). 

Sulfonic acids are prone to reduction with iodine [7553-56-2] in the presence of triphenylphosphine [603-35-0] to produce the corresponding iodides. This type of reduction is also facile with alkyl sulfonates (16). Aromatic sulfonic acids may also be reduced electrochemicaHy to give the parent arene. However, sulfonic acids, when reduced with iodine and phosphoms [7723-14-0] produce thiols (qv). Amination of sulfonates has also been reported, in which the carbon—sulfur bond is cleaved (17). Ortho-Hthiation of sulfonic acid lithium salts has proven to be a useful technique for organic syntheses, but has Httie commercial importance. Optically active sulfonates have been used in asymmetric syntheses to selectively O-alkylate alcohols and phenols, typically on a laboratory scale. Aromatic sulfonates are cleaved, ie, desulfonated, by uv radiation to give the parent aromatic compound and a coupling product of the aromatic compound, as shown, where Ar represents an aryl group (18). 

The chemistry of complexes having achiral ligands is based solely on the geometrical arrangement on titanium. Optically active alcohols are the most favored monodentate ligands. Cyclopentadienyl is also well suited for chiral modification of titanium complexes. 

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. 

Butyl alcohols encompass the four stmcturaHy isomeric 4-carbon alcohols of empirical formula C H qO. One of these, 2-butanol, can exist in either the optically active R — ) or configuration or as a racemic ( ) mixture [15892-23-6]. 

Optically Active Acids and Esters. Enantioselective hydrolysis of esters of simple alcohols is a common method for the production of pure enantiomers of esters or the corresponding acids. Several representative examples are summarized ia Table 4. Lipases, esterases, and proteases accept a wide variety of esters and convert them to the corresponding acids, often ia a highly enantioselective manner. For example, the hydrolysis of (R)-methyl hydratropate [34083-55-1] (40) catalyzed by Hpase P from Amano results ia the corresponding acid ia 50% yield and 95% ee (56). Various substituents on the a-carbon (41—44) are readily tolerated by both Upases and proteases without reduction ia selectivity (57—60). The enantioselectivity of many Upases is not significantly affected by changes ia the alcohol component. As a result, activated esters may be used as a means of enhancing the reaction rate. 

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. 

Table 5. Optically Active Alcohols and Esters Produced by Hydrolysis...

Hydroboration - regloseiective and stereoselective (syn) addition of BH3 (RBH2, R2BH) to olefins. Synthesis of alcohol including optically active alcohols from olefins. Also useful In synthesis of ketones by stitching ot olefins and CO... 

Chirazymes. These are commercially available enzymes e.g. lipases, esterases, that can be used for the preparation of a variety of optically active carboxylic acids, alcohols and amines. They can cause regio and stereospecific hydrolysis and do not require cofactors. Some can be used also for esterification or transesterification in neat organic solvents. The proteases, amidases and oxidases are obtained from bacteria or fungi, whereas esterases are from pig liver and thermophilic bacteria. For preparative work the enzymes are covalently bound to a carrier and do not therefore contaminate the reaction products. Chirazymes are available form Roche Molecular Biochemicals and are used without further purification. 

Compound A can be resolved to given an enantiomerically pure substance, [a]p = —124°. Oxidation gives the pure ketone B, which is optically active, [aJo — —439°. Heating the alcohol A gives partial conversion (an equilibrium is established) to an isomer with [a]p = +22°. Oxidation of this isomer gives the enantiomer of the ketone B. Heating either enantiomer of the. ketone leads to the racemic mixture. Explain the stereochemical relationships between these compounds. 

---