Pyridyl sulfone

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. 

The 2-pyridyl sulfones have been activated with Sm(OTf)3 in toluene at 70 °C. The reaction also proceeds in refluxing methylene chloride, albeit with slightly diminished yields (Scheme 4.56) [308]. The mechanism has not been studied in either case, but activation has been suggested to involve the complexation of the metal ion with the pyridyl nitrogen and one of the sulfur oxygens, followed by the cleavage of the Cl—S bond leading to an oxacarbenium ion, for the pyridyl sulfones. 

Skrydstrup, Beau and co-workers122 have adapted Stork s method to the SmI2-reduction of glycosyl pyridyl sulfones bearing a silicon-tethered unsaturated group at HO-C(2). An example is shown with the synthesis of methyl a-C-zso-maltoside 172 from alkyne 170 via the 5-exo-dig radical cyclization of 171 (Scheme 56).144... 

Another interesting reaction of sulfonylpyridines is with f-BuOK in CH2CI2, in which even a bulky alkoxide such as f-BuOK substitutes the sulfonyl group to give 2-r-butoxypyridine in substantial yield together with (6 -chloro-2 -pyridylmethyl)-6-chloro-2-pyridyl sulfone. The formation of this sulfone is accounted for by the initial formation of the sulfonyl carbanion which reacts further with the starting sulfone to afford the product [reaction (27)] (82UP2). This reaction also demonstrates that even a... 

Furukawa et al.281 have compared the activity of pyridyl sulfones and sulfoxides with that of sulfides. 

In conclusion, neuraminic acid 2-pyridyl sulfone, 2-phenyl sulfone or 2-chloro derivatives react with ketones or aldehydes in THF in the presence or absence of HMPA resulting in the near instantaneous and stereospecific formation of Neu5Ac a-C-glycosides. 

Some indication that such a mechanism is occurring with Smij was made evident while examining the reduction rates of the 4-pyridyl sulfone and the 2-pyridyl sulfide derivatives. The former was also... 

An interesting observation was made in the case of the 5-exo dig radical cyclization of the glucosyl pyridyl sulfone derivative 6 (Fig. 9b). An ( ) (Z)-stereoselectivity of greater than 50 1 was observed in the product, which was a fourfold increase in selectivity, compared with the previously reported tin hydride method. Closer examination of this reaction revealed that the stabilized vinylic radical was reduced to an alkenyl organosamarium species, as shown by a remarkably high incorporation of deuterium at this position (91%) when the reaction was performed in the presence of MeOD (Fig. 12). Compared with other studies on similar reductions of stabilized alkenyl radicals, this... 

Coupling of the mannosyl pyridyl sulfone 37 with aldehydes 36a and 36b in the presence of Smij was remarkably efficient leading to only one diastereomer 38a and 38b in each case, as shown in Figure 23 That indeed no epimerization of the aldehyde had occurred under the reaction conditions was confirmed by comparing the coupling product with that obtained from the same C-glycosyl donor and the aldehyde earlier prepared by Jung and Choe (Fig. 17). ... 

We have noted exceptional behavior of this type with anomeric pyridyl sulfone 46 and similar mannosyl and galactosyl sulfones (Fig. 27). ... 

A) the suhbne in THF, at - 78 °C, was treated with LDA (in the case of pyridyl sulfones n-butylHthium could also be used) and then (usually after 0.5 to 1 h) an aldehyde (a sHght excess) was added the mixture was kept for a certain time at - 78 °C and then it was allowed to warm to room temperature and... 

Juha and coworkers conducted extensive studies [7-9] of the reaction of benzothiazolyl and pyridyl sulfones, with emphasis given to the former, and selected carbonyl compounds, mainly aldehydes. Some pyrimidyl sulfones were also examined. A large number of experiments were siunmarized in ta-... 

Representative results for the reaction of benzothiazolyl and pyridyl sulfones with unbranched aliphatic and benzyhc aldehydes are shown in Table 12. Anions were generated in situ with LDA (BT sulfones) or separately using n-butyllithium (Pyr sulfones). The yields vary between low and 95%. High stereoselectivities with -isomers favored were recorded for aromatic aldehydes. 

Table 12 Reaction of benzothiazolyl and pyridyl sulfones with unbranched aliphatic and benzylic aldehydes according to Scheme 73 (BT sulfones—under Barbier conditions, Pyr—sulfones with premetalation)...

Chang, G X, Lowary, T L, A glycosylation protocol based on activation of glycosyl 2-pyridyl sulfones with samarium triflate, Org. Lett., 2, 1505-1508, 2000. 

For the assembly of the C-linked disaccharide Q -D-Man-(1—>4)-D-Man, Mikkelsen andSkryd-strap followed the same route using this Sml2-mediated coupling of pyridyl sulfone 156 with... 

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