Synthesis of C-glycosides and C-linked disaccharides through carbonylative Stille coupling reactions

• Lausanne: EPFL, 2005

In the first part, we described the synthesis of C-(1'→1) and C-(1'→4) disaccharide precursors, which are readily obtained via the carbonylative Stille coupling of glucal and isolevoglucosenone derivatives. Tin glycals and triflates, derived from isolevoglucosenone, undergo the carbonylative Stille condensation under special conditions requiring AsPh3, LiCl and powdered charcoal as co-catalysts to give the corresponding cross-conjugated dienones, in which the bicyclic alkene moiety is more reactive than the glucal alkene moiety. The bicyclic part of the formed disaccharides precursors undergo selective nucleophilic additions with hydrogen, methoxybenzylamine and thiophenol. The other alkene moiety can undergo a selective epoxidation. The reactivity of the bicyclic part permitted a regio- and stereoselective hydrogenation of the bicyclic enone, that was then reduced with K-Selectride with high diastereoselectivity. The allylic alcohols so-obtained can undergo hydroboration giving a diol protected as an acetonide. The anhydro-moiety is then opened by a thioglycosidation reaction to form a partially protected glycoside-donor which can be used, in principle, for O-glycosidation. The C(1'→4) linked disaccharide so-obtained consists of a protected form of β-D-glucopyranose, attached at position C(4) of a α-D-3-deoxy-lyxo-hexopyranoside derivative via a (R)-hydroxymethanol linker. Another methodology based on 1,4-addition of thiophenol, allow one to form of several C-(1'→4) linked disaccharide precursors. Simple C-(1'→1)-disaccharides could also be prepared in similar fashion. In a second part the palladium-catalyzed cross-coupling reaction of tinglucal and tingalactal derivatives with arenesulfonyl chlorides provide aryl C-glycosides precursors. Desulfitative carbonylative Stille cross-coupling between 1-naphthalenesulfonyl chloride and a tinglucal derivative gives, after stereoselective reduction of the keto moiety and stereoselective oxidative hydroboration, C-glycosides consisting of a β-C-glucopyranoside and (R)-(naphtha-1-yl)methanol. Benzyl C-glycoside precursors are obtained by desulfitative Stille coupling of phenylmethanesulfonyl chloride with the corresponding protected tinglycals. In a third part we discussed the synthesis of carbohydrate based scaffolds for the deprotection of allylic alcohols by polysulfones. In this part we successfully applied the cleavage of allyl-protected carbohydrate derivatives by polysulfones, solid catalysts for the chemoselective cleavage of methyl substituted allyl ethers, such as prenyl, methylallyl and methylprenyl, developed by Markovic in our group. Allyl ethers are not cleaved under these conditions. This establishes a new method of selective polyol semi-protection in which a neutral, solid catalyst induces cleavage of ethers with the following reactivity sequence: 2-methylprenyl > prenyl > methallyl >> allyl.

Thèse École polytechnique fédérale de Lausanne EPFL, n° 3233 (2005)
Section de chimie et génie chimique
Faculté des sciences de base
Institut des sciences et ingénierie chimiques
Jury: Bruno Botta, Peter Goekjian, Manfred Mutter, Raymond Roulet

Public defense: 2005-6-10

Reference

• doi:10.5075/epfl-thesis-3233
• Print copy in library catalog

Record created on 2005-03-16, modified on 2016-08-08