Glycosyl phenyl sulfones

Both glycosyl phenyl sulfones and glycosyl 2-pyridyl sulfones have been employed as donors in glycosylation reactions. The phenyl sulfones are activated with MgBr2 etherate in THF at room temperature (Schemes 4.54 and 4.55) [307,309], Considerable rate enhancement has been reported either by heating at reflux or by the use of ultrasonication. 

Our strategy for the Smij-promoted synthesis of l,2-cis-C-glycosides is illustrated in Figure 3. It was assumed that one-electron transfer to the LUMO of the aryl sulfone group in A would result in concomitant cleavage of the C1 -S bond liberating an anomeric radical intermediate, as previously observed in the reductive lithiation of glycosyl phenyl sulfones." If 5-exo cyclization onto the silicon-tethered alkene/alkyne is substantially favored over a second electron transfer from Smij, then the exocyclic carbon radical B would ultimately be formed. On the other hand, reduction of the Cl-radical by... 

De Pouilly P, Chenede A, Mallet JM, Sinay P. Reductive elimination of glycosyl phenyl sulfones by Sml2-HMPA-a convenient synthesis of substituted pyranoid glycals. Tetrahedron Lett. 1992 33(52) 8065-8068. 

The favored formation of acetylated l-a-deuterio-l,5-anhydro-D-glucitol 78 in labeling experiments has been put forward to support the occurrence of carbohydrate radicals as intermediates in the photolytic decomposition of glucopyranosyl phenyl sulfone acetates104 as well as the Cp2TiBD4193 and zinc-silver/graphite-197 mediated reduction of glycosyl halides. Cationic intermediates would have favored the opposite stereochemistry 26... 

Next, the scope of this C-glycosylation reaction was investigated. The NeuSAc chloride was found to serve as a donor in samarium mediated C-glycosylation, unfortunately, purification of C-glycoside from excess chloride donor is often problematic, making the NeuSAc phenyl sulfone the donor of choice. A variety of acceptors were also evaluated including alkenes, epoxides, vinyl esters, aldehydes and ketones. Only the aldehydes and ketones afforded the desired C-glycoside products. 

Retrosynthetic analysis (Scheme 5) suggested that samarium mediated C-glycosylation of aldehyde acceptor 36 with NeuSAc phenyl sulfone donor 7 would afford the nor-C-disaccharide target 35 (44). The success of this synthetic route relies on the design of aldehyde acceptor 36, which we envision could be synthesized using the previously reported sialic acid thiophenyi glycoside 39 (62). 

The ring size of glycosyl alkyl sulfones can be determined by periodate oxidation. It has been shown that oxidation of /3-o-glucopyranosyl phenyl sultone (26) and related analogs proceeds by stoichiometric, Malaprade-... 

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