The optical resolution is the method of separating enantiomers from racemates. There are currently many methods to obtain optically active compounds. These methods include asymmetric synthesis, use of chiral building blocks, and optical resolution. In recent years, there has been rapid improvements in asymmetric synthesis, with many reports of success.
Optical resolution is widely used, as it is an easy and practical method. One of the most common optical resolution methods utilizes diastereomer which are obtained from the reaction of racemic compounds and an optical resolving agents. The differences of physical properties between diastereomers are utilized in this method. The optical resolving agents are often easily obtained from natural products. For example, alkaloids are used for the optical resolution of racemic acids and tartaric acid is used for the optical resolution of racemic bases. In both cases, diastereomeric salts are formed. When alcohols are to be resolved, the alcohols are reacted with phthalic anhydride to form half ester. The resulting carboxylic acid (half ester) is often then reacted with alkaloids to form diastereomeric salts, which are then resolved.
Recently, Ikegami and co-workers have reported a new resolution method for alcohols using amino acid derivatives.1) According to their report, racemic 1-octyn-3-ol is reacted with (S)-N-p-toluenesulfonylphenylalanyl chloride, to produce diastereomeric ester. This diastereomeric ester is recrystallized four times from mixed solution of ethanol and hexane, giving the resolved ester with
a theoretical yield of 64% (>99% de). Finally, (S)-1-octyn-3-ol is obtained by hydrolysis of pure diastereomeric ester (>99% ee). This method is drawing attention as an easy and accurate way to optically resolve alcohols.
On the other hand, it has been reported that optical resolution is achieved by catalytic amount of chiral source. Ishihara and co-workers have studied minimal artificial enzymes to overcome various problems of enzymatic reactions and to use optical resolution. One reagent that has been developed is Nα-(2,4,6-triisopropylbenzenesulfonyl)-O-(tert-butyldimethylsilyl)-π-methyl-L-histidinol. They reported that this reagent was a very effective catalyst for kinetic resolution of racemic alcohols by selective acylation2). This reagent can also be used as catalyst for the kinetic resolution of 1,2-diols, β-hydroxycarboxylic acids, and 2-amino alcohols after the suitable derivatization.
Shiina and co-workers developed the kinetic resolution of racemic alcohols and racemic carboxylic acids using 4-methoxybenzoic anhydride (PMBA) and a Birman-type asymmetric catalyst3) [(+)-benzotetramisole, (+)-BTM].4) For example, in the reaction of racemic alcohols with achiral carboxylic acids, first the mixed anhydrides are formed from PMBA and the carboxylic acids. Subsequently the mixed anhydrides and one enantiomer of racemic alcohol react preferentially to form optically active esters and optically active alcohols using catalyst (+)-BTM. If this reaction is performed replacing the reactive substrates with racemic carboxylic acids and achiral alcohols, the kinetic resolution proceeds efficiently and optically active esters and optically active carboxylic acids can be obtained. The optical resolution of an anti-inflammatory agent, ibuprofen, has been achieved as an example of this reaction.
for Resolution of Acids
for Resolution of Bases
for Resolution of Alcohols & Thiols
for Resolution of Acids
for Resolution of Bases
for Resolution of Alcohols & Thiols
C0998
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B3296
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M1221
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A1454
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C1417
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B1508
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C1308
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B3549
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C1022
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M0573
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M0571
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M0990
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A1453
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C1418
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I0334
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I0336
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A2128
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I0398
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I0335
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A1984
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B1219
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B1220
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N0581
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N0582
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T1444
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T2223
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Literature
2) K. Ishihara, Y. Kosugi, M. Akakura, J. Am. Chem. Soc., 2004, 126, 12212 [DOI].
3) V. B. Birman, X. Li, Org. Lett., 2006, 8, 1351 [DOI].
4) I. Shiina, K. Nakata, Tetrahedron Lett., 2007, 48, 8314 [DOI]; I. Shiina, K. Nakata, Y. Onda, Eur. J. Org. Chem., 2008, 5887 [DOI].
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