Sulfoxide Catalyzed Dehydrative Glycosylation. Reaction Development and Mechanistic Analysis

A sulfoxide-catalyzed dehydrative glycosylation for the coupling of carbohydrate hemiacetals and nucleophilic alcohols has been developed. In this procedure, a glycosyl hemiacetal is treated with the reagent combination of benzenesulfonic anhydride and a substoichiometric amount of n-butyl sulfoxide, followed by the addition of an appropriate nucleophilic acceptor to provide for the formation of new anomeric linkages. Mechanistic studies focused on the hemiacetal activation process show that this transformation proceeds through the intermediacy of a glycosyl sulfonate species, which serves as resting state prior to the addition of an external nucleophile and glycosidic bond formation. Successful determination of the proportion of 18O-incorporation in the glycosyl sulfonate as a function of its formation, via the technique of dynamic monitoring of 13C-16/18O isotopic chemical shift perturbations, provides strong evidence that hemiacetal activation proceeds through initial nucleophilic addition of the hemiacetal hydroxyl to the S(IV)-center of a putative sulfonium sulfonate intermediate. Further confirmation for this mechanistic pathway was obtained through the independent synthesis, structure verification, and 1H NMR detection of a glycosyl oxosulfonium species during the sulfoxide-catalyzed conversion of a glycosyl hemiacetal to a glycosyl sulfonate.

Name thesis:degree_name

Ph.D.

Level thesis:degree_level

Dissertation

Discipline thesis:degree_discipline

Chemistry

Grantor

University of Illinois at Urbana-Champaign

Year dc:date

2015

Author dc:creator

• Boebel, Timothy A.

Contributors dc:contributor

• Gin, David Y.

• Chemistry, Biochemistry

Language dc:language

eng

Identifier

(MiAaPQ)AAI3198929

OAI identifier oai:identifier

oai:www.ideals.illinois.edu:2142/84181