Access Type

Open Access Dissertation

Date of Award

January 2018

Degree Type


Degree Name




First Advisor

David Crich


This dissertation presents the development of cyclization reactions as clocks for the determination of the molecularity of glycosylation reactions in individual pyranoside systems and extends it to the arabinofuranoside systems. It also describes the development of selective hydrogenolytic cleavage of naphthylmethyl ethers in the presence of sulfides.

The first part of chapter one gives an overview of the significance of glycochemistry and the challenges involved. The second part describes some selected glycosylation methods and extends this to the general mechanistic studies of glycosylation. This is followed by the discussion of the general clock reactions in literature which initiates a further discussion of the concept of cyclization as a clock for probing reaction mechanism and providing specific previous studies as well as the limitations involved and finally proposes the possible solution.

The second chapter discusses the cation clock method based on the intramolecular Sakurai reaction to probe the concentration dependence of representative O- and C-glycosylation reactions from glycosyl trichloroacetimidate donors on activation by trimethylsilyl triflate. The 4,6-O-benzylidene-directed β-mannosylation, and both α and β-glucosylation demonstrated to proceed with a strong dependence on the concentration of the acceptor alcohol, whereas the α-mannosylation is much less concentration dependent.

In the third chapter, the further development of the concept cation clock reactions for the determination of relative reaction kinetics in arabinofuranosylation is discussed. The use of intramolecular hydroxyl groups as candidates for clock reactions has been shown, leading to the formation of cyclic clock products in both 3,5-O-di-tert-butylsilylene and 3,5-di-O-benzyl arabinofuranoside series. In the study, formation of the β-arabinofuranoside is more concentration dependent than the α-isomers in the 3,5-O-di-tert-butylsilylene protected donor. The unselective formation of both, β and α-O-glycosides in the 3,5-di-O-benzyl protected arabinofuranosides is also understood in terms of a more of SN1-like mechanism with a strong nucleophile.

Chapter four discusses the use of the cation clock method to determine the influence of acceptor nucleophilicity on the arabinofuranosylation mechanism. The use of acceptors of varying nucleophilicity, revealed that 3,5-di-tert-butylsilylene protected arabinofuranosylation is likely to occur vial a loose SN2 mechanism from each of the two rapidly equilibrating glycosyl triflate.

In chapter five, hydrogenolytic cleavage of naphthylmethyl ethers in the presence of sulfides is described. The series of model thioethers or thioglycosides protected with combinations of benzyl ethers and 2-naphthylmethyl ethers, that the latter are readily cleaved selectively under hydrogenolytic conditions in the presence of the frequently catalyst-poisoning sulfides.

Finally, chapter six documents the experimental procedures and characterization data for the synthesized compounds