Angewandte
Chemie
DOI: 10.1002/anie.201203792
À
C H Activation
Selective Rhodium(III)-Catalyzed Cross-Dehydrogenative Coupling of
Furan and Thiophene Derivatives**
Nadine Kuhl, Matthew N. Hopkinson, and Frank Glorius*
The cross-dehydrogenative coupling (CDC) of two
unfunctionalized arenes is one of the most attractive
transformations to build up the ubiquitous biaryl
motif.[1,2] In comparison to established cross-cou-
pling reactions between aryl halides and organome-
tallic reagents,[3] CDC is considered a more efficient
and environmentally friendly approach since it
circumvents the often tedious and wasteful pre-
functionalization of starting materials. However, the
À
use of C H bonds as functional groups in these
reactions raises substantial challenges. Besides reac-
tivity and regioselectivity, a major challenge is to
control the reaction pathway such that the cross-
coupling product is favored over undesired homo-
coupling pathways.[4]
In the last few years, several studies describing
the CDC of, for example, one arene decorated with a directing
group and one simple arene,[5] the coupling between two
simple arenes,[6] and the arylation of heterocycles[7] have been
reported. In comparison, the cross-dehydrogenative coupling
of two heteroarenes is surprisingly under-represented despite
the high value of the resulting bi(heteroarene) products in
medicinal chemistry and materials science.[8,9] First reports on
palladium-catalyzed couplings between electron-rich hetero-
arenes and electron-deficient N-containing heterocycles, such
as azoles and pyridine N-oxides, were disclosed by You
et al.[10] and Itami et al.[11] [Eq. (1)]. Concurrently, Ofial and
co-workers also demonstrated that very similar azole hetero-
particular of furans, thiophenes, and pyrroles, has not been
accomplished to date.[14,15]
Rhodium(III)-catalyzed reactions[16] of arenes with ole-
fins,[17] alkynes,[18] allenes,[19] carbon monoxide,[20] chloro-
amines,[21] or carbonyl compounds[22] have been studied over
the last few years. However, the Rhodium(III)-catalyzed
À
À
formation of biaryls by C H/C H coupling has remained
unprecedented.[23,24] Recently it was demonstrated that
[{RhCp*Cl2}2] (Cp* = C5Me5) is also a suitable catalyst for
the intermolecular CDC of benzamides and haloarenes to
afford halogenated biaryl compounds with high levels of
chemo- and regioselectivity.[25]
cycles undergo efficient C H/C H bond coupling.[12] Several
oxazoles, thiazoles, and imidazoles were shown to selectively
cross-couple at their C2-positions with various benzannulated
azoles.[12] Similarly, You et al. revealed that this transforma-
tion is even feasible for two structurally similar azoles.[13]
However, a chemo- and regioselective transition-metal-cata-
lyzed CDC of two similar heterocycles other than azoles, in
Herein, we report the successful application of
[{RhCp*Cl2}2] to the dehydrogenative coupling of structurally
similar furan and thiophene heterocycles, affording coupled
products featuring the 2,2’-bi(heteroaryl) motif which is
prominent in semiconducting materials[26] and biologically
active compounds.[27] These reactions proceed with excellent
regiocontrol whilst high selectivity for the cross-coupled
products was generally observed [Eq. (2)]. Furthermore, the
methodology could also be extended to sensitive indole and
pyrrole coupling partners.[28]
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[*] N. Kuhl, Dr. M. N. Hopkinson, Prof. Dr. F. Glorius
Organisch-Chemisches Institut
The CDC of 2-n-butylfuran (1a) and benzothiophene (2a)
was selected as the model transformation as this system allows
Westfꢀlische Wilhelms-Universitꢀt Mꢁnster
Corrensstrasse 40, 48149 Mꢁnster (Germany)
E-mail: glorius@uni-muenster.de
1
for facile analysis of the reaction by H NMR spectroscopy.
Starting from our previously reported conditions,
[{RhCp*Cl2}2] (2.5 mol%), AgSbF6 (10 mol%), CsOPiv
[**] We thank A. Rꢁhling and C. Weitkamp for great experimental
support. Generous financial support by the European Research
Council under the European Community’s Seventh Framework
Program (FP7 2007–2013)/ERC Grant agreement no. 25936, the
Alfried Krupp von Bohlen and Halbach Foundation, and the Fonds
der Chemischen Industrie (N.K.) is gratefully acknowledged.
(20 mol%),
PivOH
(1.1 equiv),
and
Cu(OAc)2
(2.2 equiv),[25] an initial solvent screen revealed tert-
AmylOH to be superior, delivering the desired cross-coupled
product 3a in 47% NMR yield along with 18% of 2,2’-
bi(furan) 4a resulting from homocoupling of 1a (Table 1,
entry 1). Interestingly, no homocoupling of 2a was observed
even though this component was used in slight excess
Supporting information for this article is available on the WWW
Angew. Chem. Int. Ed. 2012, 51, 1 – 6
ꢀ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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