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Structural, Mechanistic, and Computational Analysis of the Effects of Anomeric Fluorines on Anomeric Fluoride Departure in 5-Fluoroxylosyl Fluorides

TitleStructural, Mechanistic, and Computational Analysis of the Effects of Anomeric Fluorines on Anomeric Fluoride Departure in 5-Fluoroxylosyl Fluorides
Publication TypeJournal Article
Year of Publication2011
AuthorsLee, SSeo, Greig, IR, Vocadlo, DJ, McCarter, JD, Patrick, BO, Withers, SG
JournalJOURNAL OF THE AMERICAN CHEMICAL SOCIETY
Volume133
Pagination15826-15829
Date PublishedOCT 12
ISSN0002-7863
Abstract

The effects of fluorine substitution at the C-5 center of pyranosyl fluorides on the reactivity at the C-1 anomeric center was probed by studying a series of 5-fluoroxylosyl fluoride derivatives. X-ray structures of their per-O-acetates detailed the effects on the ground-state structures. First-order rate constants for spontaneous hydrolysis, in conjunction with computational studies, revealed that changes in the stereochemistry of the 5-fluorine had minimal effects on the solvolysis rate constants and that the observed rate reductions were broadly similar to those caused by additional fluorine substitution at C-1 but significantly less than those due to substitution at C-2. Differences in the trapping behavior of 5- versus 2-fluoro-substituted glycosyl fluorides with alpha- and beta-glycosidases arise more from differences in steric effects and hydrogen-bonding interactions than from intrinsic reactivity differences.

DOI10.1021/ja204829r