Carbohydrates chiral auxiliaries derived from

In the past Lewis acid-catalyzed [4+2] cycloaddition reactions of chiral alkyl acrylates have been systematically studied. Chiral auxiliaries derived from camphor, menthol and amino acids or from carbohydrates have been developed. Stereochemical and theoretical aspects of these chiral inductors have been intensively reviewed (see. Chapter 6). Asymmetric Diels-Alder reactions of chiral acrylamides derived from Ca-symmetrical secondary amines lead selectively to the cycloadducts in the presence of Lewis acids such as AICI3. In reactions of chiral auxiliaries derived from (iS)-proline and (iS)-prolinol excellent endo/exo selectivities and diastereoselectivities were obtained in the presence of catalytic amounts of Et2AlCl or TiCL. Cycloadducts of chiral crotonoyl derivatives derived from oxazolidinones 62, sultam 63 or for example (S)-lactate IS were obtained with high selectivities in the presence of Lewis acids such as Et2AICl. 

In Sj reactions, substrate and reagent combine to form a diastereomeric transition state. In the case of auxiliary-controlled reactions, the asymmetric induction is promoted by a chiral element temporarily linked to the arene or the nucleophile. The ideal chiral auxiliary has to fulfill several requirements (i) it must be easily available in both enantiomeric forms to permit selective synthesis of both enantiomers, (ii) it must induce good stereoselectivity, (iii) the diastereomeric products must be easily separated, and (iv) cleavage of the chiral auxiliary must provide the requisite enantiomer in high yield without racanization. Additionally, an efficient work-up to allow easy recovay of expensive chiral auxiliaries is highly desirable. Most chiral auxiliaries are either natural products (alcohols, amino acids, carbohydrates, etc.) or derived from natural products. 

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... 

Considerable work was done to induce chirality via chiral auxiliaries. Reac tions with aromatic a-ketoesters like phenylglyoxylates 21 and electron-rich al kenes like dioxoles 22 and furan 23 were particularly efficient (Scheme 6). Yield up to 99% and diastereoselectivities higher than 96% have been observed whet 8-phenylmenthol 21a or 2-r-butylcyclohexanol 21b were used as chiral auxiliarie [14-18]. It should be noted that only the exoisomers 24 and 25 were obtained from the reaction of dioxoles 22. Furthermore, the reaction with furan 23 wa regioselective. 24 were suitable intermediates in the synthesis of rare carbohydrate derivatives like branched chain sugars [16], Other heterocyclic compounds liki oxazole 28 [19] and imidazole 29 [20] derivatives as well as acyclic alkenes 3fl 31, and 32 [14,15,21,22] were used as olefinic partners. Numerous cyclohexane derived alcohols [18,21-24] and carbohydrate derivatives [25] were used as chiri... 

Enholm [12] has also prepared an enantiomerically pure soluble polymer support 82 by couphng xylose-derived chiral auxiliary 81 with 77 (Scheme 18). The chiral support was then treated with bromopropionic acid 83 to give substrate 84. Eree radical allyl transfer from allyltributyltin imder thermal conditions provided 85 in 93% yield, and basic cleavage from the resin gave (R)-(-)-2-methylpent-4-enoic acid 86 in 80% yield and 97% ee, with a 92% yield of recovered 82. Previous studies of the same process in solution had found the addition of Lewis acids to be crucial for high selectivities to be obtained. Interestingly, the addition of Lewis acids to the reaction on polymer support led to cleavage of the carbohydrate from the polymer backbone. En-... 

Bicyclic oxazolidinones derived from carbohydrates have been used as chiral auxiliaries in conjugate addition reactions [147]. After deprotonation with MeMgBr, the D-galacto-oxazolidin-2-one 178 and the D-g/wc6>-oxazolidin-2-one 179 (Figure 10.17) were A-acylated with... 

A diastereoselective cyclization of a 5-hexenyl radical linked to a carbohydrate scaffold was reported by Enholm et al. [171]. The authors used (+ )-isosorbit and ( —)-D-xylose as the chiral auxiliaries. The a,p-unsaturated bromo ester 262 derived from (-h )-isosorbit was reacted with tributyltinhydride and Lewis acids. The influence of the reaction temperature and of the solvent on the yield and stereoselectivity of the cyclization were also examined. Best results were obtained when ZnCl2 was used as Lewis acid at — 78°C (Scheme 10.85). The cyclization furnished the ester... 

The examples outlined in this chapter show that carbohydrates are efficient stereodifferentiating auxiliaries, which offer possibilities for stereochemical discrimination in a wide variety of chemical reactions. Interesting chiral products are accessible, including chiral carbo- and heterocycles, a- and 3-amino acid derivatives, 3-lactams, branched carbonyl compounds and amines. Owing to the immense material published since the time of the earlier review articles on carbohydrates in asymmetric synthesis [9,10], the examples discussed in this chapter necessarily focused on the use of carbohydrates as auxiliaries covalently linked to and cleavable from the substrate. Given the scope of this chapter, a discussion of other interesting asymmetric reactions has not been permitted — for example, reactions in which carbohydrate-derived Lewis acids, such as cyclopentadienyl titanium carbohydrate complexes, exhibit stereocontrol in aldol reactions [180]. Similarly, processes in which in situ glycosylation induces reactivity and stereodifferentiation — for example, in Mannich reactions of imines [181] — have also been excluded from this discussion. 

Besides monoallylethers of chiral alcohols, allylglycosides bearing a free alcohol functionality have been applied in asymmetric syntheses of enantiomerically pure cyclopropanemethanols with success." The cleavage of the chiral carbohydrate-derived auxiliary was achieved by treatment of the cycloadducts with a. Tf20, pyridine b. DMF/H2O, pyridine, whereas for the compounds derived from 57 a. Tf20, BU4NI and b. nBuLi were applied. 

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