Chiral carbohydrate-based

Asymmetric epoxidation is another important area of activity, initially pioneered by Sharpless, using catalysts based on titanium tetraisoprop-oxide and either (+) or (—) dialkyl tartrate. The enantiomer formed depends on the tartrate used. Whilst this process has been widely used for the synthesis of complex carbohydrates it is limited to allylic alcohols, the hydroxyl group bonding the substrate to the catalyst. Jacobson catalysts (Formula 4.3) based on manganese complexes with chiral Shiff bases have been shown to be efficient in epoxidation of a wide range of alkenes. 

When comparing these results with those previously obtained using carbohydrate-based vinyl ethers as chiral dienophiles, this improved facial diastereoselectivity to heterodienes under similar conditions is noteworthy.81 The efficient chiral transfer in the second example might mostly be attributed to the specific architecture of the l,2 5,6-di-0-isopropylidene-a-D-glucofuranose moiety.Those findings open the way to develop well-defined spiro-carbohydrate templates towards improved auxiliaries for chirality transfer in a wide range of syntheses. 

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... 

Suven Life Sciences Synthon Chiragenics (Monmouth Junction, NJ, USA) Carbohydrate-based chiral technology N/A... 

Besides a considerable number of chiral Wilkinson-catalysts prepared from chiral a-hydroxy acids 33), carbohydrates 34), stereoids 35), and ferrocenylphosphines 36), many functionalized chiral hiphosphanes based on amino acids have also been developed. The first optically active tertiary phosphane was synthesized in 1961 by Horner et al.37). 

The Staudinger [2+2] cycloaddition of chiral carbohydrate Schiff base with phthalimidoacetyl chloride has yielded the sugar-based monocyclic (3-lactam as a single isomer [88]. This latter could be transformed in several (3-lactams variously functionalized through ozonolysis, reduction, hydrolysis, and acetylation reactions, (Scheme 26). 

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>. 

An alternative stereoselective synthesis of chiral heterocycles based on carbohydrate-induced stereodifferentiation includes nucleophilic addition reactions on heterocyclic systems already bound to the carbohydrate auxiliary. An example of this strategy has been shown by stereoselective addition of Grignard reagents to carbohydrate-linked 4-pyridones [61]. For this purpose, trimethylsiloxypyridine was glycosylated regioselectively using pivaloyl-protected glycosyl fluorides. 

Hollingsworth, R. I. Wang, G. Toward a Carbohydrate-Based Chemistry Progress in the Development of General-Purpose Chiral Synthons from Carbohydrates, Chem. Rev. 2000, 100, 4267 282. 

Hollingsworth, R I, Wang, G, Towards a carbohydrate-based chemistry progress in the development of general-purpose chiral synthons from carbohydrates, Chem. Rev., 100, 4267-4282, 2000. 

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