TY - JOUR
T1 - Revised mechanistic explanation for the alcohol-promoted amination of benzylic fluorides under highly concentrated conditions
T2 - Computational and experimental evidence on a model substrate
AU - Champagne, Pier Alexandre
AU - Drouin, Mélina
AU - Legault, Claude Y.
AU - Audubert, Clément
AU - Paquin, Jean François
N1 - Publisher Copyright:
© 2014 Elsevier B.V. All rights reserved.
PY - 2015/3
Y1 - 2015/3
N2 - The nucleophilic substitution of a benzylic fluoride by morpholine promoted by alcohols in neutral conditions has been studied extensively by DFT calculations and structure-activity analysis. This CF activation strategy is possible through hydrogen-bond donation from the alcohol. The experiments demonstrate that this reaction is very tolerant of variations on the promoting alcohol, yet some activators are significantly weaker. These results were supported by DFT calculations, which indicate that three OH groups around the fluorine atom at the transition-state are better to activate the CF bond, but only two of them can originate from a single triol molecule, at least for the triol under study. A revised mechanistic explanation has been proposed and provides a better understanding of experimental results. Finally, the use of a catalytic amount of triol was also investigated.
AB - The nucleophilic substitution of a benzylic fluoride by morpholine promoted by alcohols in neutral conditions has been studied extensively by DFT calculations and structure-activity analysis. This CF activation strategy is possible through hydrogen-bond donation from the alcohol. The experiments demonstrate that this reaction is very tolerant of variations on the promoting alcohol, yet some activators are significantly weaker. These results were supported by DFT calculations, which indicate that three OH groups around the fluorine atom at the transition-state are better to activate the CF bond, but only two of them can originate from a single triol molecule, at least for the triol under study. A revised mechanistic explanation has been proposed and provides a better understanding of experimental results. Finally, the use of a catalytic amount of triol was also investigated.
KW - Benzyl fluoride
KW - CF bond activation
KW - Hydrogen-bonding
KW - Nucleophilic substitution
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U2 - 10.1016/j.jfluchem.2014.08.018
DO - 10.1016/j.jfluchem.2014.08.018
M3 - Article
AN - SCOPUS:84923106894
SN - 0022-1139
VL - 171
SP - 113
EP - 119
JO - Journal of Fluorine Chemistry
JF - Journal of Fluorine Chemistry
ER -