Angewandte
Chemie
À
C H Activation
Iridium-Catalyzed ortho-Arylation of Benzoic Acids with
Arenediazonium Salts
Liangbin Huang, Dagmar Hackenberger, and Lukas J. Gooßen*
Abstract: In the presence of catalytic [{IrCp*Cl2}2] and
Ag2CO3, Li2CO3 as the base, and acetone as the solvent,
benzoic acids react with arenediazonium salts to give the
corresponding diaryl-2-carboxylates under mild conditions.
We believe that this field could benefit significantly from
the use of arenediazonium salts as aryl electrophiles, because
these are readily available from low-cost anilines in great
structural diversity, and their intrinsic reactivity is high even
This C H arylation process is generally applicable to diversely
at low temperatures.[12] The use of diazonium salts in C H
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substituted substrates, ranging from extremely electron-rich to
electron-poor derivatives. The carboxylate directing group is
widely available and can be removed tracelessly or employed
for further derivatization. Orthogonality to halide-based cross-
couplings is achieved by the use of diazonium salts, which can
be coupled even in the presence of iodo substituents.
arylating reactions was pioneered by Pschorr[13] and Gomberg
and Bachmann.[14] Modern versions of such nondirected
(hetero)arylations were reported by the groups of Heinrich,
Kçnig, Felpin, and Martín, respectively (Scheme 1a).[15] The
T
he design of efficient synthetic routes to construct biaryls is
of great importance due the prevalence of this structural unit
in pharmaceuticals, agrochemicals, and functional materials.[1]
Established methods to access this substructure include the
Ullmann reaction, catalytic cross-couplings of preformed
organometallic reagents, and decarboxylative couplings.[2,3]
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C H Arylating reactions have been studied extensively as
an alternative to these intrinsically regioselective couplings
since in principle, they do not require prefunctionalization
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steps. The regioselectivity of the C H arylation can be
controlled by various directing groups.[4] However, these
often need to be introduced and later removed in additional
reaction steps, increasing the complexity of the overall
synthetic sequence.
The use of carboxylates as directing groups represents
a tremendous advance in this area.[5] Benzoic acids are widely
available in great structural diversity, and after ortho-aryla-
tion, the carboxylate group can be removed tracelessly,[6] or
converted into other functionalities via decarboxylative cross-
couplings.[7] However, the low coordinating ability of this
group poses substantial challenges with regard to the
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Scheme 1. Direct C H arylation of (hetero)arenes with arenediazonium
salts.
only ortho-directed arylations were disclosed by Sanford, who
used pyridine and other nitrogen-based directing groups in
a photoredox/palladium-catalyzed reaction (Scheme 1b),[16]
and Chang and co-workers, who employed tert-butyl amides
to arylate electron-poor arenediazonium salts.[17]
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reactivity and selectivity of the C H activating step. Sub-
stantial progress in this field has been made by the groups of
Yu,[8] Daugulis,[9] Larrosa,[6d,f,10] Su,[6g] and others,[6h,11] who
developed transformations based on aryl halides, arylboronic
acids, and (hetero)arenes as the aryl sources. The limitations
of these approaches are the high reaction temperatures, the
cost of the substrates, the restriction to specific substrates and
substitution patterns, and the use of stoichiometric silver salts
as halide scavengers and/or oxidants.
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In order to probe whether a C H arylation of benzoic
acids with arenediazonium salts could be directed into the
ortho position of the weakly coordinating carboxylate group,
we treated 2-methylbenzoic acid (1a) with 4-methoxybenz-
enediazonium tetrafluoroborate (2a) (Table 1).[18] At the
desired low reaction temperature of 608C, many state-of-
the-art catalysts widely employed in ortho-arylations, includ-
ing [{RhCp*Cl2}2],[19] Pd(OAc)2,[8,9] and [{Ru(p-cym)Cl2}2],[20]
were inactive in this challenging transformation (entries 1–
[*] Dr. L. Huang, D. Hackenberger, Prof. Dr. L. J. Gooßen
FB Chemie-Organische Chemie
3).[4] [{IrCp*Cl2}2]/Ag2CO3, a system similar to that employed
in C H aminations, alkenylation, and alkynylations, was
the only catalyst to give the desired 2-arylbenzoic acid 3.
After some optimization, we managed to achieve high yields
even with the ecofriendly solvent acetone (entry 4), which
[21]
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Technische Universität Kaiserslautern
Erwin-Schrçdinger-Strasse Geb. 54, 67663 Kaiserslautern (Germany)
E-mail: goossen@chemie.uni-kl.de
Supporting information for this article is available on the WWW
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sets this apart from many other C H activating reactions that
Angew. Chem. Int. Ed. 2015, 54, 12607 –12611
ꢀ 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
12607