Tartaric acid, derivs optical resolution with

Miyamoto, FL, Sakamoto, M., Yoshioka, K., Takaoka. R., and Toda, F. Resolution of hydrocarbons by inclusion complexation with a chiral host compound Tetrahedron Asymmetry 2000, 11, 3045-3048 Tanaka, K., Honke, S., Urbanczyk-Lipowska, Z., and Toda, F. New chiral hosts derived from dimeric tartaric acid Efficient optical resolution of aliphatic alcohols by inclusion complexation, Ear. J. Org. Chem. 2000,3171-3176. 

Some amide derivatives have been reported to form inclusion complex with a wide variety of organic compounds.9 Optically active amide derivatives are expected to include one enantiomer of a racemic guest selectively. According to this idea, some amide derivatives of tartaric acid (11-13) were designed as chiral hosts.10 As will be described in the following section, these amide hosts were found to be useful for resolution of binaphthol (BNO) (14) and related compounds (15,16). 

Optical resolution of some hydrocarbonds and halogeno compounds by inclusion complexation with the chiral host (9a) has been accomplished.11,12 Preparation of optically active hydrocarbons is not easy and only a few example of the preparation of optically active hydrocarbons have been reported. For example, optically active 3-phenylcyclohexene has been derived from tartaric acid through eight synthetic steps.11 Although one-step synthesis of optically active 3-methylcyclohexene from 2-cyclo- hexanol by the Grignard reaction using chiral nickel complex as a catalyst has been reported, the enantiomeric purity of the product is low, 15.9%.11 In this section, much more fruitful results by our inclusion method are shown. 

Toda, F., Miyamoto, H., and Ohta, H. (1994) Efficient Optical Resolution of c7.s -4-Methylcyclohex-4-enc-l, 2-dicarboxylic Anhydride, c/.v-4-Methylcyclohex-4-ene-1,2-dicarboximide, and Their Derivatives by Complexaion with Optically Active Host Compounds Derived from Tartaric Acid, J. Chem. Soc., Perkin Trans 1. 1601-1604. 

Toda, F., Tanaka, K., and Okuda, T. (1995) Optical resolution of methyl phenyl and benzyl methyl sulfoxides and alkyl phenylsulfinates by complexation with chiral host compounds derived from tartaric acid, J. Chem. Soc., Chem. Commun. 1995, 639-640. 

Recently, a number of ferrocenylphosphines have been developed for asymmetric hydrogenation and C—C bond formation. A breakthrough in the chemistry of ferrocenylphosphines was the optical resolution of ferrocenylamines with tartaric acid [60]. Many optically active ferrocenylphosphines are derived as outlined in Scheme 10.12 [61]. 

A chemical reaction is carried out between the racemate and an optically active form (either laevo-or dextro-) of a substance capable of reacting with the racemate. This other optically active compound is usually derived from a natural source. To resolve the racemates of amines (or other bases) and alcohols, for example, use may be made of the naturally occurring d-tartaric acid (from wine tartar). The reaction with amines gives salts and esters are formed with alcohols. For the resolution of racemates of acids, use is frequently made of alkaloids such as quinine or stiychnine extracted from plants in which each of these alkaloids is present in an optically active form. The racemate mixture forms two diastereoisomers (compounds that are stereoisomers of each other, but are not enantiomers) of a derivative, with the optically active reagent used. If the... 

The monoaminomonophosphonic acids, either in the free state or, very often, as their diethyl esters, have been resolved by the usual techniques of repeated crystallization of appropriate salts those of L-(+)-tartaric acid (2,3-dihydroxybutanedioic acid) or its mono-or di-benzoyl derivativesor of D-(-)-mandelic acid, have been widely employed the use of di-O-benzoylated L-tartaric anhydride, which is based on the separation of diastereoisomeric amides (111), has also been employed to a limited extent. In selected cases, such as the monoaminomonophosphonocarboxylic acids or A -acylated (aminoalkyl)phosphonic acids, resolution following salt formation with organic bases has also been carried out ephedrine, quinine and both enantiomers of l-phenylethylamine have all been used. In many cases, only one enantiomer of the (aminoalkyl)phosphonic acid (or diester) has been isolated in optically pure form. Sometimes, the acidity of the substrate, and hence choice of base for resolution, can be modified by using a mono- (as opposed to di-) ester or (or even in addition to) protection of the amino group as, for example, the phthalimido, benzyloxycarbonyl (cbz) or r r -butyloxycarbonyl (boc) derivative. Resolved di- and mono-esters can be hydrolysed to the free acids under acidic conditions, and A -protection can also be removed through the customary procedures. 

The antihistamine dmg cetirizine, which is a piperazine derivative, is a racemic mixture, and has been used in the treatment of rhinitis and hay fever. It is available over the counter as the well-known ZYRTEC (McNeil-PPC, Inc). However the levo-rotatory R-enantiomer (10.29) was later found to be the more active form and is now on the market as the prescription dmg XYZAL (Sanofi-Aventis U.S. LLC). An approach for the synthesis of the enantiomers of cetirizine is expressed by Scheme 10.11, wherein chiralty in the dmg is introduced at an early stage in the synthesis. Thus, compound 10.28 was synthesized in racemic form then converted into diastereoisomeric salts with an optically active tartaric acid. To procure the (—)-enantiomer of 10.28, the resolution was performed with (-l-)-tartaric acid for the (-l-)-enantiomer, the resolution employed (—)-tartaric acid. After separation of the salts by crystallization, the 10.28 enantiomers were released by treatment with base and each then converted to optically active cetirizine enantiomers or related compounds by use of the general reaction suggested by Scheme 10.11 for the synthesis of the (R)-isomer of cetirizine. 

The epimerization and analysis of the reaction mixture were conducted in a manner similar to that described in a previous section, except for the reaction temperature and time. In this study, different kinds of optically active chiral diamines were used as ligands. Diamines considered as ethylenediamine derivatives were chosen as ligands because of their structural similarity to ethylenediamine (en) that had shown the highest epimerizing ability in previous studies. The optically active cyclohexanediamine was obtained by resolution of the di-astereomers obtained by the reaction of L-tartaric acid and the primary cyclohexanediamine (chxn) [51]. 2,2 -Chxn was prepared by the N-acetylation of the optically resolved chxn, followed by reduction of the acetyl group. Three other types of ethylenediamine derivatives, 2,2 -Me-en, 2,2 -Bn-en and 2,2 -Ph-en, were synthesized from the amino acids, alanine, phenylalanine and phenylgly-cine, respectively. The optical purity of the chxn was confirmed by comparison of specific rotations with published values [52]. The results of the epimerization are summarized in Table 6 and Figs. 8 and 9. 

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