| The sulfoxide glycosylation reaction has emerged as an important method for the construction of glycosidic linkages. It is especially useful for glycosylating very unreactive alcohols and for solid phase synthesis of carbohydrates. However, the factors that influence stereoselectivity and efficiency in the reaction are not well understood due to the complex nature of the mechanism of the sulfoxide reaction.;In this thesis, new mechanistic studies on the intermediates and byproducts that form in the reaction are described. One of the intermediates that forms in the reaction, an anomeric sulfenate, has been identified. Mechanisms for sulfenate formation and the energetics of sulfenate formation are discussed. Based on the studies, a new activation procedure has been developed which can be used to improve the efficiency of a glycosylation reaction. In addition to studying the intermediates, new studies on the byproducts are reported. We find that the byproducts produced in the sulfoxide reaction can cause a number of side reactions and that methods to prevent byproduct mediated side reactions significantly improve the yield of a glycosylation reaction.;By studying the intermediates and byproducts in detail, we now have a better understanding of the factors that affect stereoselectivity and efficiency in the sulfoxide reaction as well as new methods to improve the outcome of a glycosylation reaction. To illustrate how the mechanistic studies have had an impact, the synthesis of ciclamycin 0 is discussed. The synthesis of this anthracycline antibiotic provides a good example of how the mechanistic information can be used to analyze and improve difficult glycosylation reactions. The mechanistic studies described in this thesis will allow the sulfoxide glycosylation reaction to be used more effectively for the synthesis of carbohydrates. |
