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Do Glycosyl Sulfonium Ions Engage in Neighbouring‐Group Participation? A Study of Oxathiane Glycosyl Donors and the Basis for their Stereoselectivity
Author(s) -
Fascione Martin A.,
Kilner Colin A.,
Leach Andrew G.,
Turnbull W. Bruce
Publication year - 2012
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.201101889
Subject(s) - sulfonium , stereoselectivity , chemistry , glycosyl , stereochemistry , organic chemistry , catalysis , salt (chemistry)
Abstract Neighbouring‐group participation has long been used to control the synthesis of 1,2‐ trans ‐glycosides. More recently there has been a growing interest in the development of similar strategies for the synthesis of 1,2‐ cis ‐glycosides, in particular the use of auxiliary groups that generate sulfonium ion intermediates. However, there has been some debate over the role of sulfonium ion intermediates in these reactions: do sulfonium ions actually engage in neighbouring‐group participation, or are they a resting state of the system prior to reaction through an oxacarbenium ion intermediate? Herein, we describe the reactivities and stereoselectivities of a family of bicyclic thioglycosides in which an oxathiane ring is fused to the sugar to form a trans ‐decalin‐like structure. A methyl sulfonium ion derived from one such glycosyl donor is so stable that it can be crystallised from ethanol, yet it reacts with complete stereoselectivity at high temperature. The importance of a ketal group in the oxathiane ring for maintaining this high stereoselectivity is investigated using a combination of experiment and ab initio calculations. The data are discussed in terms of S N 1 and S N 2 type mechanisms. Trends in stereoselectivity across a series of compounds are more consistent with selective addition to oxacarbenium ions rather than a shift between S N 1 and S N 2 mechanisms.