Sulfones 2-pyridyl

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. 

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... 

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. 

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. 

This Sml2-induced C-glycosylation was extended to the s)mthesis of C-linked glycosides of 2-acetamido-2-deoxy sugars [88,89,90]. Reductive samariation of the 2-pyridyl sulfone of A-acetylglucosamine 184 in the presence of aldehyde 167 leads selectively to the a-C-gly-cosyl dimer 185 [90] (O Scheme 38). 

Another intramolecular approach to C-linked disaccharides has been described by Skrydstrup and Beau [116] using 2-pyridyl sulfones to generate anomeric radicals. Tethering sulfone 280 with chlorosilane 279 provides silyl ether 281 (O Scheme 60). 

Reaction of p-hydroxy or p-acetoxy sulfones with Sml2 in the presence of HMPA caused effective reductive elimination to provide olefins [66]. In contrast, Kende recorded a poor result in the reductive elimination of the P-hydroxy phenyl sulfones with Sml2 without HMPA [67]. Finally, it has been reported that contrary to phenyl sulfones, 2-pyridyl sulfones are instantaneously reduced in the presence of Sml2 without additives [68]. 

Glycosylation. Samarium(III) triflate catalyzes the reaction of glycosyl 2-pyridyl sulfones with alcohols. This method is applicable to the preparation of di- and trisaccharides containing both furanose and pyranose residues. The difference in reactivity from... 

Scheme 10-76 A 5-exo-dig cyclization initiated by the action of SmU on 2-pyridyl sulfone 241 allowed the preparation of a-C-isomaltoside 240.

It was shown that f ,Z-dienes could be synthesized from a,p-unsaturated aldehydes and 2-pyridyl sulfones with good yields and selectivities. NaHMDS and KHMDS were equally effective in promoting this condensation (eq 43). 

Methyl 2-deoxy-2-C-formyl-3,4,6-tri-0-benzoyl-a-D-mannopyranoside reacted with a protected glycosyl 2-pyridyl sulfone in the presence of samarium diiodide and produced the disaccharide 26. (See Vol. 29, p. 197, ref. 32 for an analogous... 

The benzyl-protected mannosyl a-trichloroacetimidate has been used for the gly-cosylation of 2-mercaptopyridine (Scheme 50) [207], but the stereoselectivity was low. The P-glycoside was separated and oxidized to Ae 2-pyridyl sulfone which was employed as glycosyl donor for the synthesis of C-glycosides. The corresponding azidogalactose and 7V-acetylgalactosamine derivatives have also been prepared [208],... 

The standard tin hydride conditions for generating an anomeric radical can be replaced by the divalent samarium-induced reductions of glycosyl aryl sulfones [59, 60]. In one instance the Sinay group employed the 2-pyridyl sulfone group, introduced by Skrydstrup and Beau in 1994 [30, 31], which was rapidly reduced by Sml2 at room temperature (Scheme 31). In this way, a significant increase in the cyclization yield of 118 was achieved [60]. 

Prakash and co-workers have prepared monofluoro-methyl 3,5-bis(trifluoromethyl)phenyl sulfone and have used it in the fluoroalkenylation of aldehydes and ketones.They employ KOH or CsF as base in DMSO at 20°C. On their side, Hu and co-workers have developed TBTSO2CH2F as a versatile fluoromethylidene synthon. Difluoromethyl 2-pyridyl sulfone has been used for the gem-difluoromethylenation of aldehydes and ketones and was found to be a more efficient difluoromethyfidene synthon than BTSO2CF2H, PTSO2CF2H and TBTS02CF2H. ... 

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