Auxiliaries glycosylations using chiral

SCHEME 3.2 Stereoselective glycosylation by using chiral auxiliaries. 

Chiacchio et al. (43,44) investigated the synthesis of isoxazolidinylthymines by the use of various C-functionalized chiral nitrones in order to enforce enantioselec-tion in their cycloaddition reactions with vinyl acetate (Scheme 1.3). They found, as in the work of Merino et al. (40), that asymmetric induction is at best partial with dipoles whose chiral auxiliary does not maintain a fixed geometry and so cannot completely direct the addition to the nitrone. After poor results with menthol ester-and methyl lactate-based nitrones, they were able to prepare and separate isoxazo-lidine 8a and its diastereomer 8b in near quantitative yield using the A-glycosyl... 

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

New strategies for preparing either 1,2-cis- or 1,2-trans-glycosides stereoselectively have been reported.61 A chiral auxiliary containing a nucleophile is used to control the anomeric selectivity of the glycosylation. A sample reaction is shown in Scheme 8. 

A novel strategy for stereoselective glycosylations has been reported in which a chiral auxiliary at the 2-position of a glycosyl donor is used (Scheme 126).189 Upon formation of an oxonium ion, participation of the nucleophilic moiety of the auxiliary is (g) selective and depedent on the chirality. 

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. 

Carbohydrate-derived auxiliaries exhibit an efficient stereoselective potential in a number of nucleophilic addition reactions on prochiral imines. a-Amino acids, P amino acids and their derivatives can be synthesized in few synthetic steps, and with high enantiomeric purity. A variety of chiral heterocycles can readily be obtained from glycosyl imines by stereoselective transformations, providing evidence that carbohydrates have now been established as useful auxiliaries in stereoselective syntheses of various interesting classes of chiral compounds. 

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. 

FIG. 12. The / -mandelic acid (in gold)-based chiral auxiliary at 0-2 can form a more-stable 6-membered dioxolenium ion, frans-decalm-like (32.9 kJ mol-1 relative to its BO), whereas its epimer can lead to a cw-decalin type of dioxolenium ion (72.8 kJ mol-1), ADF-DFT (DPZ frozen core). The trans-decalin leads to a glycosides, whereas the cw-decalin leads to / glycosides. Both 6-membered-ring dioxolenium ions are more stable then any dioxolenium ion based on participation from 0-3 (R 43.9 kJ mol-1 and 5 46.7 kJ mol-1). If R = allyl, then it is hypothesized that non-facially selective glycosylation takes place through the oxacarbenium ion (BO or Bl). Note that the experiment used O-benzyl and not the O-methyl, which was used for the calculation to avoid complications of multiple minima. 

N-Glycosylnitrones have received considerable attention as chiral equivalents in enantioselective synthesis because the glycosyl moiety acts as an auxiliary, which can be easily removed by acid treatment at an advanced stage of a synthetic sequence. Concerning cycloadditions, it has mainly been AT-glycosylnitrones derived from formaldehyde (C-unsubstituted) [43-45], from glyoxylates (C-alkoxycarbonyl) [46-51], or from aromatic aldehydes (C-aryl) [52,53] that have been used, and these compounds usually showed very interesting stereoselectivities. 

Carbohydrates are inexpensive and renewable natural products which contain numerous functional groups and chiral centers. Utilizing their pronounced complexing abilities and their content of chiral information, carbohydrates are applied as chiral auxiliaries in Diels-Alder and aza-Diels-Alder reactions. The method involves the use of Lewis acid catalysts with different complexing properties. Thus, dienes of low reactivity can be transformed to their cycloadducts with high asymmetric induction. The use of N-glycosyl imines as the dienophiles offers stereoselective access to enantiomerically pure piperidine derivatives, e.g. the alkaloids coniin and anabasin. 

Boons explored the application of ethyl mandelate as first-generation chiral auxiliary in 1,2-ds glycosylation reaction. However, it was shown that the desired 1,2-ds glycoside was accorr5)aniedby a small amount of the undesired anomer. The use of an auxiliary based on the 1-phenyl-2-phenylthioethyl group, however, resulted in excellent selectivities for the desired 1,2-ds glycosides. ... 

A review examines the use of carbohydrates as versatile starting materials for chiral auxiliaries in glycosylation, Mannich-type, stereoselective Strecker condensation and Ugi reactions. ... 

In Scheme 4.11, the use of the chiral auxiliary is illustrated in the solid-phase assembly of an a-glucan pentasaccharide repeating unit found in Aconitum carmichadi [34]. The synthesis commenced with the TMSOTf-catalyzed union of polystyrene resin-bound alcohol 85 and donor 86. The glycosylation was carried out... 

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