Dicarboxylic esters chiral—

The oxidation of chiral imines with peracids and the oxidation of achiral imines with chiral peracids to give optically active A-alkyl oxaziridines has been reviewed <84MI 112-01 >. The resolution of chiral A-alkyloxaziridine-3,3-dicarboxylic esters through the enzymatic hydrolysis of the racemic diesters, in moderate ees, has been reported <88CC1614>. 

The second method of determining tacticities is essentially an extension of the first, the only difference being that the chiral centre is placed in the side chain(s) of a monomer that would otherwise be prochiral. The adjacent olefinic protons in the polymer may be equivalent and uncoupled (HH or TT), or non-equivalent and coupled (HT). The application of this method to the case of 5,6-dicarboxylic esters of norbomadienes is described in Section 13.4.1.4. It turns out that an all-/rans polymer is syndiotactic and an all-cw polymer is isotactic, which is the opposite way round to what was found for 5,5-dimethylnorbomene (see above). 

Acyclic weso-dicarboxylic esters with a succinic and glutaric acid backbone were also good substrates for PLE [224] and a-chymotrypsin (Scheme 2.28) [225]. Interestingly, an additional hydroxy group in the substrate led to an enhancement of the chiral recognition process in both cases. 

Triflates of phenols are carbonylated to form aromatic esters by using PhjP[328]. The reaction is 500 times faster if dppp is used[329]. This reaction is a good preparative method for benzoates from phenols and naphthoates (473) from naphthols. Carbonylation of the bis-triflate of axially chiral 1,1 -binaphthyl-2,2 -diol (474) using dppp was claimed to give the monocarboxy-late 475(330]. However, the optically pure dicarboxylate 476 is obtained under similar conditions[331]. The use of 4.4 equiv. of a hindered amine (ethyldiisopropylamine) is crucial for the dicarbonylation. The use of more or less than 4.4 equiv. of the amine gives the monoester 475. 

The kinetic resolution using a chiral zirconocene-imido complex 286 took place with high enantioselectivity to result in chiral allenes 287 (up to 98% ee) (Scheme 4.74) [116]. However, a potential drawback of these methods is irreversible consumption of half of the allene even if complete recovery of the desired enantiomer is possible. Dynamic kinetic resolutions avoid this disadvantage in the enantiomer-differentiating reactions. Node et al. transformed a di-(-)-L-menthyl ester of racemic allene-l,3-dicarboxylate [(S)- and (RJ-288] to the corresponding chiral allene dicarbox-ylate (R)-288 by an epimerization-crystallization method with the assistance of a catalytic amount of Et3N (Scheme 4.75) [117]. 

In a recent study, chiral separations for pyrethroic acids, which are the chiral building blocks of synthetic pyrethroids and the primary metabolites of the acid part of these potent ester insecticides, have been developed [62], For example, a polar-organic mobile phase allowed the complete baseline resolution of all four stereoisomers of chrysanthemic acid (2,2-dimethyl-3-(2-methylprop-l-enyl)-cyclopropanecarboxylic acid) on a 0-9-(tcrt-butylcarbamoyl)quinine-based CSP(acjj = 1.20, oLtrans = 1-35, critical Rs = 3.03) (Figure 1,32a). This chiral acid is the precursor of pyrethroids like allethrin, phenothrin, resmethrin, and tetramethrin but not excreted as metabolite. The primary acid metabolite of these pyrethroids is chrysanthemum dicarboxylic acid (3-[(l )-2-carboxyprop-l-enyl]-2,2-dimethylcyclopropanecarboxylic acid) the stereoisomers of which could also be resolved with a reversed-phase eluent (acetonitrile— 30-mM ammonium acetate buffer 90 10, v/v pHa = 6.0) and employing an O-9-(2,6-diisopropylphenylcarbamoyl)quinine-based CSP ads = 1-09, atrans = 1-50,... 

The most common method of resolving an alcohol is to convert it to a half-ester of a dicarboxylic acid, such as butanedioic (succinic) or 1,2-benzene-dicarboxylic (phthalic) acid, with the corresponding anhydride. The resulting half-ester has a free carboxyl function and may then be resolvable with a chiral base, usually brucine ... 

The 5,6-dicarboxylic chiral esters (71, 72) have already been mentioned in connection with the determination of tacticity see Section VIIIA.5. Other polysubstituted norboma-dienes, not containing fused aromatic rings, which undergo ROMP are 21510,126,325,550, 217551, 218551, 21910 325 552 - 555, 220539, 221551, 222121,550,551 but not 21610. 

In 1988 Koizumi et al. reported the first sulfoxide used as a chiral synthetic equivalent of dimethyl acetylene dicarboxylate [86a]. The synthesis of dimethyl (R)s-2-(10-isobornylsulfmyl) maleate (88), its reaction with cyclopentadiene catalyzed by ZnCl2, and the further transformation of the major adduct 89 into a half-ester 90 (which had been used as the starting material for the synthesis of carbocyclic nucleosides (-)-aristeromycin and (-)-neplanomicin) are described (Scheme 46). 

Azo compounds like esters or imides of azo dicarboxylic acid act as reactive dienophiles in normal electron demand hetero Diels-Alder reactions due to the strong activation caused by two electron-withdrawing moieties. In the last years, considerable attention has focused on alkyl and phenyl derivatives of 1,2,4-tria-zoline-3,5-diones since their cycloadditions to chiral dienes proceed with often excellent facial selectivities. Thus, when reacting an oxapropellane derived diene with N -methyltriazolinedione, Paquette et al. obtained the cycloadduct as single diastereomer, but both maleic anhydride and N-phenyl maleimide were distinctly less reactive and turned out to undergo cycloadditions with poor selectivities [289]. 

The asymmetric hydrolysis of several cyclic meso-diesters has been accomplished and optically pure monoesters have been obtained. A classical example is the hydrolysis of dimethyl cis-4-cyclohexene-1,2-dicarboxylate, which affords the corresponding nearly optically pure half ester, a versatile synthon for various chiral cyclohexane derivatives (eq 3). ... 

Both monocarboxylates, e.g., Hg(OCCOCl3)2 and HgfOAclj, where OAc is —0C(0)CH3, and dicarboxylates, e.g., Hg succinate can be used. Chiral carboxylates also are employed. Diastereoisomers are isolated from the reaction of s-Bu2Hg and the Hg salt of the monoethyl ester of (d)-tartaric acid . 

Enantiomer-differentiating hydrolysis with pig liver esterase has, as with other hydrolases, become an important method for resolution (Table 11.1-5). Kinetic resolution of oxirane mono- and dicarboxylic acid esters with pig liver esterase proceeds effeciently with good selectivities, as demonstrated in the cases 14 and 15. Resolution is of course not restricted to enantiomers with central chirality. Axial and planar chiral racemic ester have been resolved with moderate to good results with pig liver esterase (33-36). 

Asymmetric hydrocarboxylation has also been applied to heterofunctionalized alkenes, such as vinyl imides, giving chiral amino acids. Similarly, methacrylic esters give chiral dicarboxylic acids and allylic alcohols give chiral y-butyrolactones. The results of these conversions are compiled in Tabic 12. 

S)-a-Amino acids (47) were prepared in high enantiomeric purity via addition of the anion of the chiral ester (46) to di(t-butyl)azo-dicarboxylate (Scheme 77) the chiral auxiliary (X) can be recovered efficiently. A very promising asymmetric... 

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