Carbohydrate ester enolate

Ester enolates formed from carbohydrate esters, e.g. 2, display peculiar properties. Thus, the ester enolate 3 of the 3-0-propionyl-diisopylidene-glucofuranose 2 slowly decomposes even at -70 C to give the ketene 4 and the alcoholate 5. This effect obviously arises from the intramolecular complexation of the lithium ion in the carbohydrate ester enolate which renders the carbohydrate a good leaving group. 

The interpretation of the observed stereochemistry in reactions of carbohydrate ester enolates 3,7 and 12 in terms of a guidance of the electrophile by the lithium ion is also supported by results obtained in... 

The synthesis in Scheme 13.44 is also based on a carbohydrate-derived starting material. It controlled the stereochemistry at C(2) by means of the stereoselectivity of the Ireland-Claisen rearrangement in Step A (see Section 6.4.2.3). The ester enolate was formed under conditions in which the T -enolate is expected to predominate. Heating the resulting silyl enol ether gave a 9 1 preference for the expected stereoisomer. The... 

The alkylation of enolates constitutes a very powerful method for the formation of C-C bonds. Several methods have been developed in order to control the stereoselectivity of this process. First applications of carbohydrate auxiliaries in stereoselective alkylations of ester enolates were described by Heathcock et al. [152] in 1981. 

Kunz, H, Mohr, J, Carbohydrates as chiral templates reactivity and stereoselectivity of carboxylic ester enolates, 7. Chem. Soc. Chem. Commun., 1315-1317, 1988. 

The potential of the ester enolate Claisen rearrangement for the stereocontrolled synthesis of highly functionalized, complex systems has been demonstrated in numerous applications in natural product synthesis. Utilizing the 1,3-chirality transfer Ireland has synthesized oxygen heterocycles with chiral side chains, such as are found as units in polyether antibiotics and macrolides, starting from enantiomerically pure furanoid or pyranoid glycal systems of type (41), which are easily accessible from carbohydrates (Scheme 65). ... 

Carbohydrate-derived titanium cnolates also provide yvn-x-amino-/l-hydroxy esters of high diastcrcomeric and enantiomeric purity. For this purpose, the lithium enolate derived from ethyl (2,2,5,5-tetramcthyl-2,5-disilapyrrolidin-l-yl)acetate is first transmctalated with chloro(cy-clopentadienyl)bis(1,2 5,6-di-0-isopropylidene-a-D-glucofuranos-3-0-yl)titanium and subsequently reacted with aldehydes.. vj-n-a-Amino-/ -hydroxy esters are almost exclusively obtained via a predominant /te-side attack (synjanti 92 8 to 96 4 87-98% ee for the xvn-adducts)623-b. 

Reetz and Goossen et al. reported recently the asymmetric hydrogenation of a series of enol esters using monodentate phosphite ligands 17 and 24 based on a combination of BINOL and carbohydrates or simple alcohols the results of these studies are shown in Table 28.6. 

Covalently bonded chiral auxiliaries readily induce high stereoselectivity for propionate enolates, while the case of acetate enolates has proved to be difficult. Alkylation of carbonyl compound with a novel cyclopentadienyl titanium carbohydrate complex has been found to give high stereoselectivity,44 and a variety of ft-hydroxyl carboxylic acids are accessible with 90-95% optical yields. This compound was also tested in enantioselective aldol reactions. Transmetalation of the relatively stable lithium enolate of t-butyl acetate with chloro(cyclopentadienyl)-bis(l,2 5,6-di-<9-isopropylidene-a-D-glucofuranose-3-0-yl)titanate provided the titanium enolate 66. Reaction of 66 with aldehydes gave -hydroxy esters in high ee (Scheme 3-23). 

Another interesting variant of Claisen rearrangement has been introduced by Ireland [149], and used by his group in carbohydrate chemistry. The starting compound is again an allylic alcohol that is esterified by a suitable carboxylic acid. This ester is enolized in basic medium, and quenching of the intermediate enolate at low temperature gives a ketene silyl... 

The chemistry of enolates has provided excellent routes to highly complex structures, in particular in the total synthesis of natural products. Because of the highly oxygenated structures of carbohydrates, enolate formation could easily result in p-elimination of a suitably located oxygenated group (ethers, esters, and such) to provide enone. For these reasons, the chemistry of carbohydrate enolates has been poorly documented. 

Addition to (l-acyloxy enol esters. Addition of lithium dimethylcuprate to chiral enol esters derived from carbohydrates provides access to C6 chiral synthons with four alternating and/or consecutive methyl and hydroxyl groups.21 Example ... 

Carbohydrates easily complex oxygenophilic electrophiles, e.g., lithium cations and zinc(II) chloride. The coordination between the carbohydrate moiety and the Lewis acids is an important factor which orients the auxiliary-bound substrate. The com-plexation of lithium cations through the carbohydrate moiety influences the reactivity and stereodifferentiation in carbohydrate-derived esters and their enolates [16]. 

Separation of MDA on an amino-bonded silica phase Separation and measurement of MDA in the enolate anionic form can be achieved using a Waters carbohydrate analysis column (3.5 mm x 30 cm) eluted with acetonitrile/water (Esterbauer and Slater, 1981 Ester-bauer et al., 1984). The method is particularly suited to the analysis... 

The capability of the highly oxygenated carbohydrate auxiliaries to coordinate the counter-ion of the enolate allows the formation of chiral chelate complexes with a restricted flexibility of the enolate moiety. The cation complexation also increases the tendency of the carbohydrate to react as a leaving group. It has been found [153] that the enolate 204 generated by deprotonation of the carbohydrate linked ester 203 with LDA underwent an elimination of the carbohydrate moiety generating the alcohol chelate complex 205 and the ketene 206 (Scheme 10.67). 

Regioselective acylations of polyhydroxylated compounds such as carbohydrates, glycerols, steroids, or alkaloids have been carried out with lipases, esterases, and proteases [13, 20]. One example is the Candida antartica lipase (immobilized on acrylic resin) catalyzed monoacylation of the signalling steroid ectysone (1) giving selectively the 2-C)-acetate 2 (eq. (1)). Using vinyl acetate for this transesterification the reaction was irreversibly pushed to the product side, since the liberated enol instantaneously isomerizes to acetaldehyde [21]. The sometimes unfavorable aldehyde is avoided when 1-ethoxyvinyl acetates [22], trichloro- or -fluoroethyl esters [23 a, b], oxime esters [23 c] or thioesters [23 d] are employed for the quasi-irreversible reaction courses. 

Certain anomalous optical and reducing properties of the compound X find a ready explanation in the fact that it possesses two five-membered rings in the molecule, for Smith has shown that such dicyclic systems in the carbohydrate group readily enolize in the presence of alkali. Treatment of X with hot acidic methyl alcohol brings about a ring change from furanose to pyranose and there is produced the methyl ester of methyl n-glucopyruronoside (XV) identified by methylation and conversion to the amide (XII). 

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