Positioning A Carbon-Fluorine Bond Over The Pi Cloud Of An Aromatic Ring: A Different Type Of Arene Activation

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 pi 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 center dot center dot center dot Ar interaction that plays a prominent role in both its reaction chemistry and spectroscopy. For example, we established that the C-F center dot center dot center dot 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.