Condensation of pentane-2,4-dione with different unprotected sugars in alkaline aqueous media gave quantitatively in one step b-C-glycosidic ketones.C-Glycosides are becoming useful as building blocks for the synthesis of various types of natural products and as potential enzyme inhibitors. 1 In addition, they are used as a model in enzymatic and metabolic studies, indeed it has been shown that the conformational differences between the O-(or N-) glycosides and the C-linked analogue are minimal. 2 Moreover, Cglycosides are essentially inert to degradation because the natural anomeric centre has been transformed from a hydrolytically labile O or N acetal link to an ether. As a result, significant attention has been focused in the last decade on the development of new routes for their syntheses.The most common method for C-C bond formation at the anomeric centre involves nucleophilic attack on this naturally electrophilic carbon atom. 3 A wide variety of electrophilic sugars have been employed such as reducing sugars, alkyl glycosides, anomeric esters, anomeric trichloroacetimidates, or glycosyl halides. The carbon nucleophiles that have been used include cyanides, allyl-and propargylsilanes, silyl enol ethers, silyl ketenes, enamines and organometallics such as Grignard reagents, organolithiums, cuprates, or aluminates. 4 In most cases, these procedures require specific, awkward reaction conditions and generally suffer from low yields.Recently, there have been several advances in C-C bond formation in aqueous media. These milder methods include the coupling of unprotected sugars with malonate-derived nucleophiles such as barbituric derivatives 5 or Meldrum acid, 6 with Wittig-type reagents, 7 or with allyl bromides promoted by tin or indium in Barbier-type reactions. 8 In fact, water is now recognised as an attractive medium for many organic reactions 9 but curiously, for the most part, sugar chemistry stays away from this development of organic synthesis in water. Yet, the use of water-soluble unprotected reducing carbohydrates would allow syntheses without the tedious protection-deprotection protocol.The Knoevenagel condensation, 10 a century-old reaction, consists of the condensation of aldehydes with active methylene-containing derivatives such as malonic acid or its ester. Despite the Knoevenagel reaction being a net dehydration, this reaction was surprisingly in some cases favoured in aqueous media. 11 In this communication, we describe the very efficient onestep synthesis of b-C-glycosidic ketones in alkaline aqueous media from unprotected carbohydrates via the Knoevenagel condensation.C-Glycosidic ketones are normally prepared in anhydrous conditions from an activated protected sugar by addition of a suitable nucleophile such as silyl enol ether 12 or enamines 13 to give generally the a-C-glycoside anomers as the major stereoisomer. Alternatively they can be obtained through multistep chemical transformations of allyl C-glycosides or using Wittig-type reaction on reducing sugars. 14 We describe here the r...
