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Furanosyl Oxocarbenium Ion Conformational Energy Landscape Maps as a Tool to Study the Glycosylation Stereoselectivity of 2‐Azidofuranoses, 2‐Fluorofuranoses and Methyl Furanosyl Uronates
Author(s) -
van der Vorm Stefan,
Hansen Thomas,
van Rijssel Erwin R.,
Dekkers Rolf,
Madern Jerre M.,
Overkleeft Herman S.,
Filippov Dmitri V.,
van der Marel Gijsbert A.,
Codée Jeroen D. C.
Publication year - 2019
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.201900651
Subject(s) - oxocarbenium , chemistry , stereoselectivity , glycosyl , reactivity (psychology) , conformational isomerism , stereochemistry , computational chemistry , substituent , molecule , organic chemistry , catalysis , medicine , alternative medicine , pathology , nucleophile
The 3D shape of glycosyl oxocarbenium ions determines their stability and reactivity and the stereochemical course of S N 1 reactions taking place on these reactive intermediates is dictated by the conformation of these species. The nature and configuration of functional groups on the carbohydrate ring affect the stability of glycosyl oxocarbenium ions and control the overall shape of the cations. We herein map the stereoelectronic substituent effects of the C2‐azide, C2‐fluoride and C4‐carboxylic acid ester on the stability and reactivity of the complete suite of diastereoisomeric furanoses by using a combined computational and experimental approach. Surprisingly, all furanosyl donors studied react in a highly stereoselective manner to provide the 1,2‐ cis products, except for the reactions in the xylose series. The 1,2‐ cis selectivity for the ribo ‐, arabino ‐ and lyxo ‐configured furanosides can be traced back to the lowest‐energy 3 E or E 3 conformers of the intermediate oxocarbenium ions. The lack of selectivity for the xylosyl donors is related to the occurrence of oxocarbenium ions adopting other conformations.