Dehydrative glycosylation

Scheme 3.1 Electrophilic activation of hemiacetals for dehydrative glycosylation.

Scheme 3.3 Bransted acid promoted dehydrative glycosylations.

In addition to Bronsted acid promoted Fischer-type glycosylations, Lewis acids have been investigated (Scheme 3.4). A variety of Lewis acids promote glycosylation under mild conditions, often in substoichiometric amounts. The earliest examples include ZnCl2 [18] and FeCl3 [19], although these readions were demonstrated only for preparation of trehalose-type disaccharides. Mukaiyama et al. have very recently developed metal triflate catalysts for the dehydrative glycosylation with... 

One of the earliest reports of silicon-based eledrophilic adivation comes from the Koto laboratory on the use of silyl halide eledrophiles to promote the dehydrative glycosylation with hemiacetal donors [40,41]. In the readion (Scheme 3.5),... 

Scheme 3.7 Dehydrative glycosylation with [R3P0]2 Tf20.

In 1980, Gross and coworkers first applied this concept to a direct dehydrative glycosylation using tris(dimethylamino)phosphine and carbon tetrachloride [99]. 

The first direct dehydrative glycosylation promoted by sulfur electrophiles was reported by Leroux and Perlin [105]. In this reaction (Scheme 3.9), activation of... 

Scheme 3.10 Dehydrative glycosylation with sulfonyl halides.

Scheme 3.12 Dehydrative glycosylation with heta7l onium salts.

Scheme 3.14 Dehydrative glycosylation with carbonyl activators.

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... 

Dehydrativeglycosylation of 1-hydroxy donors with Ph2S0/Tf20 in conjunction with thioglycoside acceptors opens the way for sequential double glycosylation, one-pot procedures for trisaccharide synthesis, as exemplified by the efficient one-pot synthesis of the a-Gal epitope and a hyaluronan trisaccharide [566]. This study also shows the potential of selenoglycoside as acceptors in dehydrative glycosylation (Scheme 4.112). 

An interesting approach towards the formation of glycosyl 1-phosphates by dehydrative glycosylation of nucleophilic dialkyl phosphate acceptors with... 

SCHEME 3.24 Dehydrative glycosylation promoted by Tf20/Ph2S0. 

Seeberger PH, Bilodeau MT, Danishefsky SJ. Synthesis of biologically important oligosaccharides and other glycoconjugates by the glycal assembly method. Aldrichim. Acta. 1997 30 75-92. Gin D. Dehydrative glycosylation with 1-hydroxy donors. J. Carb. Chem. 2002 21 33-52. 

Catalysis with protic acids has traditionally been used in Fischer glycosylations. As with the recent variations of the above procedure, Lewis acid catalysis is also valuable for dehydrative glycosylations with protected derivatives (Scheme 4.40). Trimethylsilyl triflate has been shown to promote reactions of glucuronic acid hemiacetals [420], and pyridine and TMSOTf was used for the synthesis of cw-glucosides [421]. Pyridinium / -toluenesulfonate (PPTS) was used for the synthesis of glycosides of the biologically important Kdo [422]. 

Garcia, B A, Gin, D Y, Dehydrative glycosylation with activated diphenyl sulfonium reagents. Scope, mode of C(l)-hemiacetal activation, and detection of reactive glycosyl intermediates, J. Am. Chem. Soc., 122, 4269-4279, 2000. 

Nguyen, Ft M, Chen, Y, Duron, S G, Gin, D Y, Sulfide-mediated dehydrative glycosylation,... 

Suzuki, T, Watanabe, S, Yatnada, T, Hiroi, K, Dehydrative glycosylation of tri-O-benzylated 1-hydroxyribofuranose catalyzed by a copper(II) complex. Tetrahedron Lett., 44, 2561-2563, 2003. 

Gin, D, Dehydrative glycosylation with 1-hydroxy donors, J. Carbohydr. Chem., 21, 645-665, 2002. 

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