P-C-glycosides

An attractive flexibility in using anomeric phenyl sulfones is that a stereodivergent synthesis of C-glycosides is available by alkylation before the reductive desulfonylation event. Thus, a one-pot four-step sequence of sulfone deprotonation-electrophile quenching-reductive lithiation-methanol quenching on sulfone 14 provides stereoselectively P-C-glycosides 19 as shown with aldehyde 16 (Fig. 

Narasaka, K, Ichikawa, Y I, Kubota, H, Stereoselective preparation of p-C-glycosides from 2-deoxyribose utilizing neighboring participation by 3-O-methylsulfinylethyl group, Chem. Lett., 2139-2142, 1987. 

Molina, A, Czernecki, S, Xie, J, StereocontroUed s3mthesis of (i-C-glycosides and amino p-C-glycosides by Wittig olefination of perbenzylated glyconolactones derivatives. Tetrahedron Lett., 39, 7507-7510, 1998. 

In both reactions the intermediate glycosyl radicals are trapped from the a-face by hydrogen atom donors. Thus, by taking advantage of the stereoelectronic and conformational effects of hexopyranosyl radicals, these strategies enable the production of p-C-glycosides. 

Jeanneret, V., Meerpoel, L., Vogel, P. C-Glycosides and C-disaccharide precursors through carbonylative Stille coupling reactions. Tetrahedron Lett. 1997, 38, 543-546. 

The addition of allylstannanes to glycal a-oxides provides an entry to P-C-glycosides. The reaction is catalyzed by BUjSnOTf. 

Although the above results appear useful for the preparation of C-furanosides, these reactions are not always this specific. As shown in Scheme 2.3.31, Martin, et al.,60 attempted a similar reaction with the simpler furanose shown. Although a good yield was achieved for this reaction, the stereochemical outcome presented a 1 1 mixture of anomers. However, as shown in Scheme 2.3.32, when intramolecular delivery of the allyl group was effected, the reaction yielded a 5 1 mixture favoring the p anomer. Thus, this approach is a potentially useful route to p-C-glycosides. 

Pyranose-derived glycals are also useful as substrates in C-glycosidations with pyrimidinyl mercuric acetates. As shown in Scheme 4.1.8, Farr, eta/.,7 carried out such reactions utilizing 3-O-silyl protected glycals. Palladium acetate was used as the catalyst and no salt additives were used. Compared to the results presented in the previous four schemes, the illustrated coupling proceeded cleanly with the formation of an 84% yield of a p-C-glycoside. 

Similar acid mediated cyclizations have been reported on a variety of substrates. For example, as shown in Scheme 7.3.2, Casiraghi, etal.,14 treated 2,3,4,6-tetra-O-benzyl-D-glucopyranose with a pyrrole-derived Grignard reagent and a titanium based Lewis acid. As shown, the addition proceeded in 64% yield with the formation of a single diasteriomer. Subsequent exposure to an acidic DOWEX resin provided a 50% yield of the p-C-glycoside and an additional 21% isolated as the corresponding a anomer. 

Scheme 10-73 Intramolecular radical cyclization provides a stereospecific route to a- and P-C-glycosides. Reagents and conditions i) Bu3SnH, AIBN, PhH, reflux, 0.01 M, (syringe pump used in 6-exo cyclization) ii) TBAF, THF.

A sulfoxide derived from phenyl 3,4-0-isopropylidene-l-thio-P-L-fucoside, on treatment with MeLi followed by fcrt-BuLi, gave the glycosyl carbanion which added to iso-butanal to give p-C-glycosides as an epimeric pair, and the a-thioglycoside led to the a-C-glycosides. ... 

Smoliakova IP, Caple R, Gregory D, Smit WA, Shashkov AS (1995) Highly selective formation of a p-C-glycosidic bond in the reactions of ArSCl-glucal adducts with sihcon-containing nucleophiles. J Org Chem 60 1221-1227... 

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