Palladium (II)-catalyzed stereoselective formation of [alpha]-O-glycosides

by Schuff, Brandon Patrick.

The development of new methods for stereoselective formation of ?- or ?-Oglycosides has been extensively investigated due to the critical roles carbohydrates play in a variety of biological systems. To date, many efforts have focused on developing new methods and reagents for the generation of isolated glycosyl donors which subsequently undergo glycosidic bond formation with nucleophilic glycosyl acceptors. Despite their potential applications to complex carbohydrate synthesis, each of these methods relies on the nature of the substrates to stereoselectively control the formation of glycosidic bonds. Recently, the use of glycal derivatives as glycosyl donors has been utilized in ?- allylpalladium strategies for the stereoselective synthesis of O-glycosides. However, due to the poor reactivity of the glycal donors as well as the alcohol nucleophiles, these groups utilized the more activated pyranone donors. Lee, who recognized the challenge in this approach, utilized Zn(II) ion to activate both the alcohol acceptors for the nucleophilic addition and the glycal donors for the ionization. My research focuses on the development of a novel method for the stereoselective construction of ?-O-glycosides directly from glycals. In this reaction, the Pd(II)/L catalyst is believed to activate the glycal ?-system for stereoselective attack by the oxygen nucleophile, and the C(3)-trichloroacetimidate group serves as the leaving group as well as directs Pd(II) to the double bond of the glycal. This strategy relies on palladium-ligand catalyst-donor complexation to control the anomeric selectivity rather than the nature of the protecting groups on the substrates, thus eliminating the need for cumbersome protecting group manipulations that are often employed in glycosylation. The ?- selectivity relies on the reagent rather than on the nature of the substrates, which is often employed in traditional glycosylation. This mild method is applicable to an array of glycal donors and aliphatic and aryl alcohol acceptors. The advantages of this methodology are the mild conditions, low reaction temperatures, short reaction times, scope of glycosyl acceptors and donors it applies to, and minimal catalytic loading. Furthermore these reactions are generally express high yield and selectivity. 1