methodology have been reported. Both unfunctionalized and
directing-group-containing substrates can be arylated by aryl
halides, stannanes, boronates, or aryliodonium salts under
palladium, rhodium, and ruthenium catalysis.5 Our group has
previously developed a general method for coupling directing-
group-containing substrates with aryl iodides.6 Anilides, ben-
zamides, benzylamines, 2-arylpyridines, and benzoic acids can
be efficiently arylated by employing this methodology.7 Good
functional group tolerance is usually observed.
Unfortunately, this method cannot be employed for benzoni-
trile ortho-arylation. Nitriles are known to slow down or even
stop catalytic cycles as a result of strong binding of cyano group
to transition metals.8 An alternative is to use another directing
group that can be transformed into cyano group after the
arylation step.9
Carbon-Hydrogen Bond Functionalization
Approach for the Synthesis of Fluorenones and
ortho-Arylated Benzonitriles
Dmitry Shabashov, Jesu´s R. Molina Maldonado, and
Olafs Daugulis*
Department of Chemistry, UniVersity of Houston, Houston,
Texas 77204-5003
ReceiVed June 17, 2008
It is known that amides can be converted to nitriles by using
strong dehydrating agents, for example, phosphorus oxychloride
or thionyl chloride.10 Catalytic dehydration of primary amides
is known.11 Mild conditions (trifluoroacetic anhydride, room
temperature) can be employed to obtain a benzonitrile from a
primary benzamide.12
We have shown that arylated anilides can be dehydrated to
form phenanthridines by using trifluoroacetic anhydride
reagent.7f We decided to apply this approach to the synthesis
of ortho-arylated benzonitriles. In preliminary experiments,
isopropyl benzamides were subjected to the standard arylation
conditions7c followed by reaction mixture treatment with
A sequence consisting of palladium-catalyzed benzamide
ortho-arylation/reaction with (CF3CO)2O was developed
allowing a convenient one-pot synthesis of ortho-arylated
benzonitriles and fluorenone derivatives. The outcome of this
transformation is dependent on the amide N-alkyl substituent.
Dehydration of ortho-arylated N-cyclohexyl-benzamides by
(CF3CO)2O results in efficient production of benzonitriles.
In contrast, o-arylated N-propylbenzamides are converted to
fluorenone derivatives.
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methods.2 However, this requires both coupling partners to be
functionalized. Often, starting materials for these coupling
reactions need to be synthesized, lengthening the synthetic
schemes. Coupling of a C-H bond with a carbon-leaving group
bond would allow the use of simple starting materials.3
The first transition-metal-catalyzed C-H/C-halogen bond
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in the 1980s.4 Recently many other examples utilizing this
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10.1021/jo801300y CCC: $40.75 2008 American Chemical Society
Published on Web 09/03/2008