Glycosyl Sulfonates

The first reported preparation of a glycosyl sulfonate, in 1929, involved the heating of acetobromoglucose with silver toluenesulfonate in diethyl ether; Helferich and Gootz noted that the product was white and crystalline but decomposed in a matter of hours in chloroform solution at room temperature [1]. Many years after this inauspicious start, Schuerch and his coworkers turned their attention to an exploration of the uses of glycosyl sulfonates as glycosyl donors. Thus, in a 1973 paper that presaged many of the later developments, Kronzer and Schuerch suggested that the treatment of 2,3,4,6-tetra-O-benzyl-a-d-glucopyranosyl chloride (1) or bromide with silver triflate at —78°C in dichloromethane or diethyl ether provided the anomeric triflate 2 (Scheme 1) [2]. They opined that, owing to the strongly electron-withdrawing nature of the triflate group, this substance probably had the a configuration. It was also noted that subsequent couplings with methanol, conducted at —78°C, were ^-selective in dichloromethane but unselective in diethyl ether, and the difference was attributed to the superior shielding of the a face provided by the tighter ion pair in dichloromethane [2]. The rapidity of the reactions, both the initial formation of the triflate and its subsequent reaction with methanol at —78°C, were also noted at this time [2].

Prompted by the extreme reactivity of the triflates and the desire to work with isolable, characterized intermediates, Schuerch and Eby subsequently turned their attention to the use of toluenesulfonates and mesylates [3]. Thus, 2,3,4,6-tetra-O-benzyl-a-d-glucopyranosyl chloride, or bromide, was allowed to react with silver toluenesulfonate in acetonitrile at room temperature. The authors were able to use standard vacuum line techniques to remove the silver halide by filtration and obtain an 1H NMR spectrum of the product in deuteriochloroform: the characteristics of the anomeric proton (8 6.1,3J12 = 3.5 Hz) led to the attribution of the a stereochemistry. In the case of the analogous 2,3,4-tri-O-benzyl-6-O-(N-phenylcarbamoyl) series, signals attributed to the ^-toluenesulfonate (8 5.5, 3J12 = 8.0 Hz) accounted for approximately 15% of the reaction mixture [3]. In agreement with the earlier report of Helferich and Gootz, complete decomposition was noted after several hours at room temperature. Coupling reactions of the so-formed 2,3,4,6-tetra-O-benzyl-1-O-tosyl-a-d-glucopyranose, conducted with methyl 2,3,4,-tri-O-benzyl-a-d-glucopyranoside in a range of solvents, gave moderate yields but little selectivity. Kinetic measurements, carried out polarimetrically, revealed no clear dependence of reaction rate on alcohol structure or concentration and suggested to the authors that the couplings were SN1 in character and involved a series of interchanging tight ion pairs [3]. Eby and Schuerch also noted that the anomeric toluenesulfonates formed from silver toluenesulfonate and peracylated (acetyl, benzoyl) glucosyl halides were considerably more stable, and less reactive, and upon exposure to methanol led to mixtures of a- and ^-glucosides as well as to orthoesters. These latter results prompted them to suggest that the esterified toluenesulfonates would probably be of little use in glycosylation [3]. Schuerch and his coworkers also investigated the galactopyranosyl toluenesulfonates and triflates. As in the glucose series, these were formed from the corresponding bromides by metathesis reactions with the appropriate silver sulfonates [4,5]. With a series of differentially 6-O-protected 2,3,4-tri-O-benzylgalactopyranosyl

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