Chiral auxiliary carbohydrate

Asymmetric syntheses of heterocycles using carbohydrates as chiral auxiliaries 97T14823. 

Hultin P. G., Earle M. A. and Sudharshan M. Synthetic Studies with Carbohydrate-Derived Chiral Auxiliaries Tetrahedron 1997 53 14823-14870 Keywords sugar-linked dienes, sugar-linked dienophiles... 

Nitroalkenes with Chiral Auxiliaries The use of carbohydrates as chiral auxiliary in Diels-Alder reactions for the stereoselective preparation of carbocyclic and heterocyclic chiral rings is well documented.48 For example, D-manno-nitroalkene reacts with 2,3-dimethyl-1,3-butadiene to give a 65 35 mixture of adducts, as shown in Eq. 8.29. The configurations at C-4 and C-5 have been determined to be (4R,5R) and (45,55), respectively. Hydrolysis of the product followed by degradative oxidation of the sugar side chains leads to enantiomerically... 

A nice and convergent approach to both compounds makes use of RCM to form the 5-membered building block 71, which mimics the carbohydrate part of the nucleosides. The necessary diene precursor 69 is readily assembled via Evans aldol chemistry. RCM then affords the ring in almost quantitative yield (69->70), leaving the chiral centers and the free hydroxyl group intact. Removal of the chiral auxiliary by reductive cleavage, attachment of the base by means of jt-allylpalladium chemistry, and a final deprotection step complete these highly efficient syntheses [46]. 

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). 

For acrylates, or type I reagents, applied in asymmetric Diels-Alder reactions, several chiral auxiliaries such as menthol derivatives, camphor derivatives,16,3 and oxazolidinones4 are available. Carbohydrate compounds have also been reported as chiral auxiliaries in a recent publication, although the stereoselectivity was not good.5 Here are examples in which asymmetric Diels-... 

Carbohydrates have found widespread use as chiral auxiliaries in asymmetric Diels-Al-der reactions156. A recent example is a study conducted by Ferreira and colleagues157 who used carbohydrate based chiral auxiliaries in the Lewis acid catalyzed Diels-Alder reactions of their acrylate esters 235 with cyclopentadiene (equation 66). Some representative results of their findings, including the ratios of products 236 and 237, have been summarized in Table 9. The formation of 236 as the main product when diethylaluminum chloride was used in dichloromethane (entry 3) was considered to be the result of an equilibrium between a bidentate and monodentate catalyst-dienophile complex. The bidentate complex would, upon attack by the diene, lead to 236, whereas the monodentate complex would afford 236 and 237 in approximately equal amounts. The reversal of selectivity on changing the solvent from dichloromethane to toluene (entry 2 vs 3) remained unexplained by the authors. 

A review of Diels-Alder reactions of fullerenes with acyclic and cyclic dienes has been presented. The addition of substituted pyrimidine o-quinodimethanes (75) to [60]fullerenes yields novel organofullerenes (76) bearing a pyrimidine nucleus covalently attached to the Ceo cage (Scheme 26). The Diels-Alder dimerization of cyclopenta[/]phenanthrene (77) with isobenzindene (78) yields the dimer (79) in 85% yield (Scheme 27). Further evidence has been supplied to support an early reorganization of the r-network in the dimerization of 2-methoxycarbonylbuta-1,3-diene. The Lewis acid-catalysed Diels-Alder reactions of acrylate derivatives of new carbohydrate-based chiral auxiliaries with cyclohexadiene show excellent endo. exo... 

Cycloaddition of enantiomerically pure a-chloro nitroso compounds derived from steroids and carbohydrates (e.g. 158, equation 102) proceeds with considerable stereoselectivity. Final removal of the chiral auxiliary results in Af-unsubstituted cyclic hydroxylamines of high ee. 

Carbohydrates are configurationally stable, easily available in enantiopure forms from the chiral pool, and they show a high density of chiral information per molecular unit. Their polyfunctionality and structural diversity fadhtate their tailor-made modification, derivatization, and structural optimization for a broad spectrum of synthetic applications. While derivatives of various saccharides have already been utilized as versatile starting materials and building blocks for chiral auxiliaries, ligands, and reagents [330] their obvious role as precursors for the... 

The most widely applicable method of optical resolution utilizes a chiral auxiliary, which is taken from either the chiral pool 14 (carbohydrates, terpenes, amino acids etc.) or obtained by previous optical resolution. The auxiliary A, in an optically pure form, combines with the racemic substrate S to form two diastereomers p and n, respectively. 

Mur 207), has received renewed interest in recent years. A fine review covering the intermolecular asymmetric Diels-Alder reaction was compiled by Mori 208>. In this article the use of terpenes and carbohydrates as chiral auxiliaries is discussed no amino acid derivatives are mentioned in this context. A chiral a-hydroxycarboxylic acid derivative was also used to achieve an asymmetric Diels-Alder reaction 209). High asymmetric induction could be detected in the intramolecular Diels-Alder reaction of chiral molecules. 

FIGURE 6. Carbohydrate derived chiral auxiliaries for the cyclopropanation of aUylic alcohols... 

A survey of the literature reports regarding the synthesis of (3-lactam using carbohydrate precursors has recently been published by Furman et al. [215]. They have shown that the carbohydrates were used either as chiral tools or chiral auxiliaries. A few solid phase approaches have been outlined in the survey using the vinyl ether bound to the polymeric support through a sulfonyl linker. Two alternative modes of attachment of the vinyl ethers to the resin have been reported. 

H. Kunz Stereoselective syntheses using carbohydrates as chiral auxiliaries G. W. Hart Ubiquitous and temporal glycosylation of nuclear and cytoplasmic proteins... 

S. G. Davies, H. M. Kellie, and R. Polywka, Opening of carbohydrate 5,6-epoxides with chiral acetate and propionate enolate equivalents attached to the iron chiral auxiliary [(C5H5)Fe(CO)P(Ph)3], Tetrahedron Asymmetry, 5 (1994) 2563-2570. 

General Three Carbon Chiral Synthons from Carbohydrates Chiral Pool and Chiral Auxiliary Approaches... 

The development of chiral Diels-Alder reactions to form enantiomerically enriched isoquinuclidines has been of considerable interest. Older examples focused on the use of chiral auxiliaries, generally attached to the nitrogen of the 1,2-dihydropyridine, the best of which were carbohydrate based <1990TL1995>. Recently, amidines have been shown to be very efficient chiral auxiliaries with l-A-amidine-l,2-dihydropyridine 96 undergoing [4+2] cycloaddition with maleic anhydride to give only the endo-product 97 with >95% diastereomeric excess (Equation 4) <2005OL5773>. 

Initially, the de novo synthesis of enantiomerically pure carbohydrates [110] and glycolipids [111] using transition metal complexes and chiral auxiliaries afforded only modest success. Ultimately, it was the use of enantiomerically pure aldehydes, such as the R and S enantiomers of 2-(phenylseleno)propionaldehyde, to convey facial selectivity upon the LACDAC reaction that enabled the synthesis of optically pure glycals. Syntheses of several complex monosaccharides such as the main sialic acid-type N-acetylneuraminic acid (Neu5Ac) and rac-3-deoxy-ma o-2-octulosonic acid (KDO) were accomplished with this technology [112, 113], The LACDAC... 

Although carbohydrates are cheap and readily available chiral compounds, their application in stereoselective synthesis was for a long time limited to ex-chiral-pool syntheses [3]. They have been considered too complex compared to other chiral auxiliaries, for example a-pinene in borane-chemistry [4] or BINAP-derivatives in reduction chemistry [5]. However, it has been shown during the past few years that carbohydrates can be successfully applied as stereodifferentiating tools in many different reaction types such as aldol- [6], hydrogenation- [7], carbonyl addition- [8], Michael- [9], Diels-Alder- [10], hetero-Diels-Alder [11], and rearrangement reactions [12]. 

Heterocycles are very important in pharmaceutical research [49,50] and the stereo-controlled synthesis of chiral heterocyclic compounds is therefore a major task in modem organic chemistry. Besides catalytic methods, auxiliaries are valuable for asymmetric syntheses of chiral heterocycles. Carbohydrates have been used as auxiliaries in the stereoselective formation of heterocycles, as well as in the stereoselective introduction of functionalities into the heterocyclic framework. 

R)-a-Amino acids.1 This carbohydrate has been used as the chiral auxiliary as well as the amine in the Ugi four-component condensation for synthesis of a-amino acids (7, 366).2... 

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