Use of Lactones with Organometallic Based Nucleophiles

Dondoni and Scherrmann published a full account of their thiazole-based approach to formyl C-glycosides. Addition of the thiazololithio species to lactone 371 gave

Scheme 65

the a-C-glycoside 372 as the major product. Reduction under standard conditions followed reduction-epimerization, and demasking of the protected aldehyde group then gave 373 (Scheme 66) [108]. Genet et al. used a similar protocol to access C-glycosyl aldehydes. Both the dithiane group (375 ^ 377) and an acetylene (378 ^ 377) served well as masked aldehyde equivalents (Scheme 66) [109].

Heterocyclic nucleophiles have also been utilized with pyranose sugars to prepare potential glucosidase inhibitors. In the case shown in Scheme 67, Lewis acid mediated silane reduction did not work owing to chelation of the Lewis acid with the imidazole group, and a slightly longer route was required to effect the reduction [110]. Epoxide alkyl ¡-C-glycosides, potential inhibitors of ¡-glucan hydrolases, have also been prepared from sugar lactones (374 ^ 377) [111].

The reaction of 2-deoxy-2-azido sugar lactones seems to parallel the reactivity of the corresponding 2-oxygenated lactones as shown for the conversion of 389 to 392 (Scheme 68) [112]. Martin and Saavedra utilized a conceptually related approach, the reduction of hemiacetals to give ¡-alkyl products, in the preparation of aza sugar analogs. Addition of (methoxymethoxy)methyllithium to lactone 374 gave 394, and this was followed by conversion to diketone 395. Reductive amination then furnished the protected C-aza sugar 396 (Scheme 68) [113].

Wightman et al. showed that in furanose sugars, reduction of C-glycoside lac-tols gives 1,2-anti products predominantly. It seems that silane reduction occurs preferentially from the same face as the vicinal oxygen substituent (Scheme 69) [114].

The reaction of enolates with lactones has also been carried out to give chain-extended sugars. Three approaches have been published, two on samarium diiodide mediated chemistry [115,116] and one on classical Claisen-type chemistry [117]. Representative examples are shown in Scheme 70.

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