Document Type

Dissertation

Degree

Doctor of Philosophy

Major

Chemistry, Organic

Date of Defense

4-5-2019

Graduate Advisor

Alexei V. Demchenko

Committee

Alexei V. Demchenko

Cynthia M. Dupureur

Christopher D. Spilling

Michael R. Nichols

Abstract

Stereocontrol of glycosylation reactions is a constant struggle in the field of synthetic carbohydrate chemistry. The application of the picoloyl (Pico) substituent can offer numerous stereocontrolling avenues. The most popular application is the Hydrogen-bond-mediated Aglycone Delivery (HAD) method that provides excellent selectivity in the glycosylation of a variety of sugar substrates. The HAD method relies on the formation of an intermolecular hydrogen bond between the nitrogen atom of the Pico substituent on the glycosyl donor with the hydroxyl group of the glycosyl acceptor. This interaction provides a facial preference for the nucleophilic attack and hence provides powerful stereocontrol for the glycosidic bond formation. A significant utility of the HAD method has been previously demonstrated in the stereocontrolled α-glycosylation and multi-step synthesis of α-linked oligosaccharides. Described herein is the application of the Pico group to β-stereoselective synthesis of carbohydrates. Upon introducing new reaction conditions, we uncovered a new mechanistic pathway by which the Pico-substituted substrates may react. The in-depth mechanistic studies were designed to uncover the details of the new mechanistic iii pathway. Investigation of the reaction intermediates by high-field NMR led to the identification of a quasi-stable glycosyl triflate that was deemed to be the key intermediate of the reaction. This study demonstrates a novel method for glycosyl triflate formation that may have broad applications in the field of organic chemistry. In the application to the β-stereoselective synthesis of glycans, the glycosyl triflate intermediate was credited for excellent stereoselectivity achieved.

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