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Positioning a Carbon–Fluorine Bond over the π Cloud of an Aromatic Ring: A Different Type of Arene Activation
Author(s) -
Holl Maxwell Gargiulo,
Struble Mark D.,
Singal Prakhar,
Siegler Maxime A.,
Lectka Thomas
Publication year - 2016
Publication title -
angewandte chemie international edition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.831
H-Index - 550
eISSN - 1521-3773
pISSN - 1433-7851
DOI - 10.1002/anie.201601989
Subject(s) - chemistry , substituent , electrophilic aromatic substitution , electrophile , fluorine , nitration , aryl , ring (chemistry) , nucleophilic aromatic substitution , electrophilic substitution , aromaticity , medicinal chemistry , photochemistry , molecule , stereochemistry , organic chemistry , nucleophilic substitution , alkyl , catalysis
It is known that the fluoro group has only a small effect on the rates of electrophilic aromatic substitutions. Imagine instead a carbon–fluorine (C−F) bond positioned tightly over the π cloud of an aryl ring—such an orthogonal, noncovalent arrangement could instead stabilize a positively charged arene intermediate or transition state, giving rise to novel electrophilic aromatic substitution chemistry. Herein, we report the synthesis and study of molecule 1 , containing a rigid C−F⋅⋅⋅Ar interaction that plays a prominent role in both its reaction chemistry and spectroscopy. For example, we established that the C−F⋅⋅⋅Ar interaction can bring about a >1500 fold increase in the relative rate of an aromatic nitration reaction, affording functionalization on the activated ring exclusively. Overall, these results establish fluoro as a through‐space directing/activating group that complements the traditional role of fluorine as a slightly deactivating aryl substituent in nitrations.