Alcohol acceptor

Kusumoto and coworkers have found that the treatment of hemiacetal 1 with trifluoro- or trichloroacetic anhydride 94 (1 equiv) and trimethylsilyl perchlorate (0.2 equiv) selectively provides the corresponding anomeric ester intermediate 91 [152], Hemiacetal acylation occurs even in the presence of the alcohol acceptor. With Lewis acid assistance, the glycosyl ester intermediate is displaced to provide disaccharide products in good yields. This transformation allowed the synthesis of disaccharides 98 (81%) and 99 (91%). In some cases, acetic anhydride has been used as the electrophilic activator of hemiacetal donors and the reaction with thiol acceptors yields S-linked glycosides [153,154],... 

Despite the high utility of glycosyl fluorides as stand-alone glycosyl donors, there has been only one example of a direct dehydrative glycosylation whereby hemiacetal activation proceeds through a glycosyl fluoride intermediate. Hirooka and Koto have detailed the use of diethylaminosulfur trifluoride (DAST) for dehydrative glycosylations with hemiacetal donors (Scheme 3.16) [160]. Treatment of a mixture of hemiacetal 1 and alcohol acceptor (R OH) with DAST 108 (2 equiv) at 0°C provides the... 

Further development of this idea led to the proposal (56) that reactive B=C groups, for instance carbonyl systems, would be able to activate alcohol acceptors AH by generating a related A—B—C—H intermediate (Scheme 8, path I). It seemed that chloral might act as a catalyst along these lines. However, it turned out that the rate of decay in the transition state is too low in all systems tested thus far. Therefore, the carbonyl compound is more or less a substitute for a Lewis acid catalyst, as indicated in Scheme 8, path II. The high reactivity and diastereoselectivity in chloral-catalyzed reactions is attributable to the nitriles used as solvents in these reactions [see Section III.3.b and Ref. (62)]. 

These factors arc mostly concerned with the so-called glycosyl donor molecule. Additional parameters to be considered in the formation of 0-glycosides involve the nature of the alcohol acceptor, the polarity of the solvent, and the type of catalyst or promoter needed to activate the leaving group at the anomeric carbon of the donor molecule. 

The glycosylation reaction should be fairly general for a variety of alcohol acceptors. 

Franck and Marzabadi755 have developed the heterocyclic donor 180 and used it in coupling with a variety of alcohol acceptors to obtain /8-glycosides in good yields with excellent stereoselectivities using equimolar amount of triflic acid [Eq. (5.286)]. 

Fig. 5. Comparison of supernatant liquids and residues. Catalyst 2 mg. Pd in 40 cc. of 50% alcohol. Acceptor 0.5 oc. CaHsNOj. A, supernatant liquid of sample centrifuged at 500 r.p.s. B, supernatant liquid of sample centrifuged at 200 r.p.s. C, residue of catalyst centrifuged at 200 r.p.s. D, residue of catalyst centrifuged at 500 r.p.s. E, normal Hz-reduced PVA-Pd. All measurements are converted to 25°C. and 760 mm.

Glycosylation of Supported Alcohol Acceptors with NPG Donors. 611... 

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