Communications
DOI: 10.1002/anie.201006222
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C H Activation
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Rhodium-Catalyzed Oxidative Olefination of C H Bonds in
Acetophenones and Benzamides**
Frederic W. Patureau, Tatiana Besset, and Frank Glorius*
In memory of Keith Fagnou
The oxidative Heck-type reaction, as pioneered by Fujiwara
and Moritani,[1] has emerged as an attractive method for the
coupling of arenes and olefins, because in contrast to the
traditional Heck reaction,[2] it obviates prior activation of
either reaction partner. For this transformation, palladium is
process is not oxidative, rendering stilbene derivatives out
of reach. Herein we report on the oxidative olefination of
acetophenones and electronically related benzamides[9] with a
broad range of olefins.
the established catalyst,[3–5] for example in the C H oxidative
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olefination of acetanilides with acrylate derivatives reported
by van Leeuwen et al.[4] and in the use of remote carboxylic
acids as efficient directing groups described by Yu et al.[5]
Miura and Satoh et al.,[6] we,[7] and others have looked at
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other transition metals for these C H activation processes,
specifically rhodium, which often allows lower catalytic
loadings, higher selectivities, and broader olefin scope.
Recently we have had some success with the rhodium-
catalyzed coupling of unactivated acetanilides (electron-rich
arenes) with styrenes and even ethylene [Eq. (1); the atoms in
bold are part of the directing group (DG), the bond in bold is
Understanding and utilizing the characteristics of these
commonly occurring directing groups, on their own, or in
concert, should have a strong impact on synthetic organic
chemistry. For some time, we believed that the electron-
the coupling site].[7a] In contrast, the C H activation process-
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richness of the C H-activated arenes was critical to the high
conversions in the rhodium-catalyzed oxidative olefination,[10]
as the most electron-rich acetanilide substrates afforded the
highest yields in couplings with electron-neutral styrenes.[7a]
We were therefore surprised to find that the significantly less
nucleophilic ketone moiety of acetophenones is also a
suitable directing group for this rhodium-catalyzed oxidative
Heck-type reaction.[11] Acetophenone coupled with styrene
selectively to furnish stilbene 2a in 57% yield (Scheme 1).[12]
In contrast to acetanilides and benzamides (see below),
electron-poor 3-trifluoromethylacetophenone did not react.
In reactions of activated n-butyl acrylate, lower catalyst
loadings could be used (0.5 mol% of Rh dimer), affording
slightly higher yields with both substituted and unsubstituted
acetophenones (2e and 2 f, Scheme 1). Interestingly, the
coupling of a polycyclic 2-acetophenone derivative with
styrene furnished the corresponding product 2h in an
improved yield of 72% and required only 0.5 mol% catalyst
precursor. The polycyclic character of the substrate seems to
es of many difficult-to-activate, electron-poor substrates such
as common carbonylated arenes remain underdeveloped.[8]
Acetophenones, for example, were found by Murai et al. to
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undergo ortho C H activation with ruthenium catalysts but
reacted with only a limited scope of very electron-rich,
generally silylated olefins [Eq. (2)].[8d] Furthermore, the
[*] Dr. F. W. Patureau, Dr. T. Besset, Prof. Dr. F. Glorius
Organisch-Chemisches Institut
der Westfꢀlischen Wilhelms-Universitꢀt Mꢁnster
Corrensstrasse 40, 48149 Mꢁnster (Germany)
Fax: (+49)251-83-33202
E-mail: glorius@uni-muenster.de
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be beneficial for the efficiency of the C H functionalization,
an effect that we speculate could be attributed to the
extended aromatic conjugation. Interestingly, even challeng-
ing 2-vinyl-5-trifluoromethylacetanilide (1a), which itself was
prepared from ethylene and the corresponding acetanilide in
65% yield by rhodium catalysis under standard conditions
[Eq. (1)],[13] could be coupled with a polycyclic 2-acetophe-
none derivative with high selectivity although in moderate
yield and only under harsher conditions (2.5 mol% rhodium
precursor, 1408C, product 2i, 44% yield; Scheme 1). This
reactivity trend was confirmed when acetyl indole substrates
[**] We thank Christoph Grohmann and Nadine Kuhl for their
contributions as well as the Alexander von <Humboldt Foundation
(F.W.P.) and the DFG (SFB 858) for generous support. The research
of F.G. has been supported by the Alfried Krupp Prize for Young
University Teachers from the Alfried Krupp von Bohlen und Halbach
Foundation.
Supporting information for this article is available on the WWW
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ꢀ 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Angew. Chem. Int. Ed. 2011, 50, 1064 –1067