C-alkyl glycoside

Grignard reagents react with alkyl halides453 and have been used to form alkyl C-glycosides, in good yields, by reaction with glycosyl halides454. 

Aglycons . Reaction of 2-C-formylglycals with organocopper reagents can occur in different ways to give saturated or unsaturated alkyl C-glycosides as shown in Scheme... 

Beau and Sinay described a method which laid the groundwork for cyanohydrin acetonide alkylations [1]. Their strategy involved alkylation and reductive desulfonylation of glucopyranosyl sulfones 4. In this one-pot procedure, low temperature alkylation and subsequent reductive desulfonylation with lithium naphthalenide generated -C-glycosides with good selectivity >10 1 j3 a) and in moderate to good yield (Eq. 1). 

The enolic double bond of a difluorovinyl group in the anomeric position is able to add a radical. It can thus afford a difluoro-C-glycoside, either directly or indirectly. When the alkylating radical is generated from a 6-halogenopyranoside, the reaction can lead to difluoro-C-disaccharide. These reactions are even more efficient if the radical has an electrophilic character (e.g., with an a-halogenoester instead of an alkyl radical). 

The anomeric proton in phenylthio 2,3-dideoxy-hex-2-enopyranosides is sufficiently acidic to enable deprotonation and, for example, reaction of S-glyco-side 68 with BuLi leads to dianion 69 which alkylates or acylates at C (1) from the a-face to give C-glycosides 70 (Scheme 17) [24]. Similarly, deprotonation of hex-2-enopyranoside 71 and coupling with cyclic sulfate 72 provides alkylated product 73 which, upon hydrolysis at pH > 3.5, undergoes a loss of sulfate and a... 

Although ethers have been used less frequently than alcohols, it has recently been reported that tetrahydrofuran (THF) is photocatalytically activated by TBADT, and the alkylation of unsaturated nitriles is obtained in good yield [15]. As an alternative, the C—Br bond in various glycosyl bromides has been homolytically cleaved, and the resulting radical trapped by acrylonitrile to form the corresponding C-glycosides. The halogen abstraction step is initiated by a photolabile iron-based dimeric metal complex [16]. 

Friedel-Crafts alkylation has been used in an important synthesis of aryl C-glycosides, which are potent anti-tumor agents, from glycosyl fluorides (equation 99)65 661. The reaction takes place rapidly in dichloromethane, at room temperature using a novel zirconium complex and silver perchlorate combination catalyst. A similar alkylation has been performed by replacing the aromatic compound with either a silyl enol ether or an allylic compound using silver triflate as the catalyst662,663. 

The synthesis of a variety of stable carbohydrate mimetics using a RCM approach is discussed. An esterification-ring-closing metathesis (RCM) approach has been utilized for the preparation of a variety of alkyl and aryl C-glycosides. The synthesis of a number of C-saccharides will also be addressed. Yield optimization studies and the synthesis of the substrates will also be discussed. 

Figure 2. Structure of a- C -glycosides of ulosonic acids, R =H or OH R2 - H or alkyl/aryl R = alkyl/aryl/C-linked saccharide.

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