Ru-Catalyzed C–H Arylation of Fluoroarenes with Aryl Halides

Although
the ruthenium-catalyzed C–H arylation of arenes
bearing directing groups with haloarenes is well-known, this process
has never been achieved in the absence of directing groups. We report
the first example of such a process and show that unexpectedly the
reaction only takes place in the presence of catalytic amounts of
a benzoic acid. Furthermore, contrary to other transition metals,
the arylation site selectivity is governed by both electronic and
steric factors. Stoichiometric and NMR mechanistic studies support
a catalytic cycle that involves a well-defined η6-arene-ligand-free Ru­(II) catalyst. Indeed, upon initial pivalate-assisted
C–H activation, the aryl-Ru­(II) intermediate generated is able
to react with an aryl bromide coupling partner only in the presence
of a benzoate additive. In contrast, directing-group-containing substrates
(such as 2-phenylpyridine) do not require a benzoate additive. Deuterium
labeling and kinetic isotope effect experiments indicate that C–H
activation is both reversible and kinetically significant. Computational
studies support a concerted metalation–deprotonation (CMD)-type
ruthenation mode and shed light on the unusual arylation regioselectivity.