Glycosylation with Sulfoxides and Sulfinates as Donors or Promoters

Crich, David; Lim, Linda B. L.


The efficient, stereocontrolled formation of glycosidic bonds is arguably the most fundamental reaction in glycoscience. This chapter surveys four recent distinct glycosylation methods united by the common theme of employing sulfoxides, or closely related sulfinates, either in the glycosyl donor itself or as an integral part of the promoter. In the first method (the sulfoxide method), a glycosyl sulfoxide, the donor, is coupled to an acceptor alcohol by means of an activating agent to give the glycosidic bond. The activating agent is typically triflic anhydride, but other compounds have been used.

In the second method (the thiogylcoside method) the donor is thioglycoside. It is activated by means of a promoter derived from the reaction of trifluoromethanesulfonic anhydride and thiosulfinate, a sulfinaminde, or diphenylsulfoxide before coupling to an acceptor alcohol. The third method is dehydrative coupling. This chapter is concerned only with the recent variations in which dehydration is achieved by means of a combination of diaryl sulfoxides and trifluoromethanesulfonic acid. The last method (the oxidative method), involves the direct oxidative glycosylation of glycals. This method differs significantly from the other methods since it does not employ a traditional anomeric derivative as glycosly donor, but derives one from the formal oxidation of glycal.

At some time in the activation process, all four methods typically involve the reaction of a sulfoxide, or sulfinate with trifluoromethanesulfonic anhydride. All four methods possess the distinct advantage of using readily prepared, stable gylcosyl donors. Three of them are metal-free and two of them are capable of coupling to enable the most hindered unreactive alcohols in a matter of minutes at low temperature. These methods are some of the most powerful available for the formation of glycosidic linkages.