| Gaining access to stereodefined deoxy-sugar containing oligosaccharides, such as those containing 2,6-dideoxy and 2,3,6-trideoxy motifs, remains a formidable challenge. This is largely due to the difficulties associated with controlling the selectivity of glycosylations using deoxy-sugar donors. Herein, the development of three generations of reagent-controlled approaches utilizing cyclopropenium cations are described. Chapter 2 describes our first-generation approach which utilized a 3,3-dichloro-1,2-diphenylcyclopropene/tetrabutylammonium iodide (TBAI) promoter system for alpha-selective glycosylations. These substrates reacted with a range of glycosyl acceptors to afford products in 55 to 99% yield, with selectivities ranging from 3:1 alpha:beta to all alpha, determined by NMR. In chapter 3 we describe how we improved upon the method by utilizing a 3,3-dibromo-1,2-diphenylcyclopropenone/TBAI system. This latter system activated deoxy-sugar donors to react with a range of glycosyl acceptors to afford products within 50 to 98% yield, with selectivities ranging from 8:1 alpha:beta to all alpha. Chapter 4 describes our studies to improve the synthetic utility and substrate scope of the reaction and eliminate the need for TBAI. In these studies we found that activating 2-deoxy-hemiacetal donors with 2,3-bis(2,3,4-trimethoxyphenyl)cyclopropenone/oxalyl bromide or 2,3-bis(2,3,4-trimethoxyphenyl)cyclopropene-1-thione/oxalyl bromide can also induce alpha-selective glycosylations without the need for TBAI. These latter activating agents are much faster and higher yielding then our initial approaches, reacting with a range of glycosyl donors and acceptors to afford products within 53 to 74% yield, with selectivities ranging from 6:1 alpha:beta to all alpha. Most importantly, it allows for the glycosylations for the highly reactive and acid sensitive 2,3,6-trideoxy sugar L-rhodinose, an important structural motif in various carbohydrate based natural products. |
