Synthesis of C-glycosides and C-disaccharides using Mukaiyama aldol reaction in aqueous media

We describe here a new strategy for the preparation of C-glycosides and C-disaccharides in the aqueous phase using the Mukaiyama aldol reaction. We first studied the reaction between formyl-2,3,4,6-tetra-O-benzyl-beta-D-glucopyranoside 1 and the trimethylsilyl enol ether 2 derived from acetophenone. Using Yb(OTf)(3) (10 mol%) as catalyst in a mixture of THF/water at room temperature, the enol adducts were isolated in a high (90%) yield but with a moderate diastereoselectivity. The reaction can also be performed in pure THF leading to a single diastereoisomer but in a much lower yield (56%). The aldol reaction was then applied to the synthesis of C-disaccharides using the trimethylsilyl enol ether 10 derived from the functionalized ketone 9. In both the aqueous phase and in anhydrous THF, the reaction can be achieved in high yields giving in each case only two aldol products out of the four possible diastereoisomers.