Glycosylations chiral auxiliary

A glycosyl chiral auxiliary can be easily removed from cycloadducts of A -glycosylnitrones such as 330 by acidic treatment or with hydroxylamine, to afford N-unsubstituted isoxazolidines <2003EJ04152, 2004T9997>. 

Scheme 5 Stereoselective 1,2-cis-glycosylations with chiral auxiliaries at C-2 of glycopyranosyl donors.

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... 

In order to have a milder cleavage of the chiral auxiliary, various other glycosyl-amines have been introduced, such as 2-acetamido-3,4,6-tri-0-acetyl-l-amino-2-deoxy-/i-D-glucopyranose 30 [38], 2,3,4,6-tetra-0-alkyl-/i-D-glucopyranosylamines 31 [39] and l-amino-5-desoxy-5-thio-2,3,4-tri-0-isobutanoyl-/ -D-xylopyranose 32 [40] (Scheme 1.14). 

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. 

SCHEME 3.2 Stereoselective glycosylation by using chiral auxiliaries. 

SPOS also benefited from other technical improvements such as the on-resin analytical methods [112], the capture-release purification technique [113], and hydrophobically assisted switching phase [114], Recently, chiral auxiliary-mediated 1,2-n.v-glycosylations were introduced to SPOS, allowing for the efficient and stereoselective assembly of oligosaccharides [115] (see Chapter 7). 

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. 

Kim J-H, Yang H, Boons G-J (2005) Stereoselective glycosylation reactions with chiral auxiliaries. Angew Chem hit Ed Engl 44 947-949... 

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