Oxidative coupling of arylboronic acids with arenes via Rh-catalyzed direct C-H arylation

Article abstract of DOI:10.1021/ol702659a

Oxidative coupling of three different arenes and a thiophene derivative with various arylboronic acids was achieved with a [RhCl(C₂H ₄)₂]₂/P[p-(CF₃)C₆H ₄]₃ catalyst sy

Full text of DOI:10.1021/ol702659a

ORGANIC
LETTERS
2008
Vol. 10, No. 1
129-131
Oxidative Coupling of Arylboronic Acids
with Arenes via Rh-Catalyzed Direct
C−H Arylation
Thomas Vogler and Armido Studer*
Fachbereich Chemie, Organisch-Chemisches Institut, Westfa¨lische
Wilhelms-UniVersita¨t, Corrensstrasse 40, 48149 Mu¨nster, Germany
studer@uni-muenster.de
Received November 5, 2007
ABSTRACT
Oxidative coupling of three different arenes and a thiophene derivative with various arylboronic acids was achieved with a [RhCl(C2H4)2]2/
P[p-(CF3)C6H4]3 catalyst system. Commercially available 2,2,6,6-tetramethylpiperidine-N-oxyl radical (TEMPO) was used as a stoichiometric
oxidant. A 2-pyridyl group and an imine functional group served as ortho-directing groups to mediate the direct C
complex. Moderate to excellent yields were obtained for the coupling reactions.
−H arylation by a Rh
Biaryls are an important class of compounds which have
found widespread application as ligands in asymmetric
synthesis.1 Moreover, they occur in many natural products2
and are interesting building blocks for the construction of
new organic materials.3,4 Biaryls have been predominantly
prepared by metal-catalyzed cross-coupling reactions of aryl
halides and aryl metal compounds.1 More recently, many
research groups have focused on the direct arylation of arenes
and heteroarenes without preactivation of one of the coupling
partners.5,6 Mostly, Pd catalysis has been used for arene
activation,5 but also Rh-mediated reactions are known.7 Only
a few examples of the direct transition-metal-catalyzed
coupling of boronic acid derivatives with arenes or hetero-
arenes have been published to date.8,9 Pd and Ru catalysts
were applied in these studies. Herein, we present, for the
first time, oxidative Rh-catalyzed coupling reactions of
various arylboronic acids with four different arenes.10
As an oxidant, we selected the commercially available
2,2,6,6-tetramethylpiperidine-N-oxyl radical (TEMPO). Op-
(7) (a) Oguma, K.; Miura, M.; Satoh, T.; Nomura, M. J. Am. Chem.
Soc. 2000, 122, 10464. (b) Bedford, R. B.; Coles, S. J.; Hursthouse, M. B.;
Limmert, M. E. Angew. Chem., Int. Ed. 2003, 42, 112. (c) Oi, S.; Watanabe,
S.-i.; Fukita, S.; Inoue, Y. Tetrahedron Lett. 2003, 44, 8665. (d) Lewis, J.
C.; Wiedemann, S. H.; Bergman, R. G.; Ellman, J. A, Org. Lett. 2004, 6,
35. (e) Wang, X.; Lane, B. S.; Sames, D. J. Am. Chem. Soc. 2005, 127,
4996. (f) Lewis, J. C.; Wu, J. Y.; Bergman, R. G.; Ellman, J. A. Angew.
Chem., Int. Ed. 2006, 45, 1589. (g) Yanagisawa, S.; Sudo, T.; Noyori, R.;
Itami, K. J. Am. Chem. Soc. 2006, 128, 11748. (h) Lewis, J. C.; Bergman,
R. G.; Ellman, J. A. J. Am. Chem. Soc. 2007, 129, 5332. (i) Proch, S.;
Kempe, R. Angew. Chem., Int. Ed. 2007, 46, 3135.
(8) (a) Kakiuchi, F.; Kan, S.; Igi, K.; Chatani, N.; Murai, S. J. Am. Chem.
Soc. 2003, 125, 1698. (b) Giri, R.; Maugel, N.; Li, J.-J.; Wang, D.-H.;
Breazzano, S. P.; Saunders, L. B.; Yu, J.-Q. J. Am. Chem. Soc. 2007, 129,
3510. (c) Shi, Z.; Li, B.; Wan, X.; Cheng, J.; Fang, Z.; Cao, B.; Qin, C.;
Wang, Y. Angew. Chem., Int. Ed. 2007, 46, 5554.
(1) (a) Pu, L. Chem. ReV. 1998, 98, 2405. (b) Hassan, J.; Se´vignon, M.;
Gozzi, C.; Schulz, E.; Lemaire, M. Chem. ReV. 2002, 102, 1359.
(2) Bringmann, G.; Price Mortimer, A. J.; Keller, P. A.; Gresser, M. J.;
Garner, J.; Breuning, M. Angew. Chem., Int. Ed. 2005, 44, 5384.
(3) Kraft, A.; Grimsdale, A. C.; Holmes, A. B. Angew. Chem., Int. Ed.
1998, 37, 402.
(4) Roncali, J. Chem. ReV. 1992, 92, 711.
(5) (a) Alberico, D.; Scott, M. E.; Lautens, M. Chem. ReV. 2007, 107,
174. (b) Satoh, T.; Miura, M. Chem. Lett. 2007, 36, 200. (c) Seregin, I. V.;
Gevorgyan, V. Chem. Soc. ReV. 2007, 36, 1173.
(9) Alkyl-aryl coupling: (a) Chen, X.; Goodhue, C. E.; Yu, J.-Q. J.
Am. Chem. Soc. 2006, 128, 12634. (b) Pastine, S. J.; Gribkov, D. V.; Sames,
D. J. Am. Chem. Soc. 2006, 128, 14220.
(6) C-H activation of both coupling partners: Stuart, D. R.; Fagnou,
K. Science 2007, 316, 1172.
10.1021/ol702659a CCC: $40.75
© 2008 American Chemical Society
Published on Web 12/12/2007

timization studies were conducted with thiophene 1, bearing
the ortho-directing 2-pyridyl group,10b,11 and phenylboronic
acid using various Rh catalysts in the presence of excess
TEMPO in dioxane/t-BuOH at 130 °C in sealed tubes for 8
h (Table 1).
10). The coupling with 20 mol % of TEMPO and oxygen or
air as co-oxidants at 90 °C (13 h) provided lower yields
(entries 11 and 12). The lowest yield in the series was
achieved in the absence of TEMPO with oxygen as the only
oxidant (entry 13). The directing 2-pyridyl group is essential
since C-H arylation did not occur on 3-methoxythiophene.7g
It is important to note that no additional base was required
for the coupling reaction.
Table 1. Rh-Catalyzed C-H Phenylation Using Various
To study the scope and limitations of the oxidative Rh-
catalyzed coupling reaction, the arylboronic acid component
was systematically varied (9 h reaction time). As expected,
an alkyl group at the para position did not influence the
reaction outcome to a large extent (2b). Interestingly, a vinyl
group was inert under the applied conditions (2c). Electronic
effects at the boronic acid moiety did not play a significant
role since similar yields were obtained for electron-rich (2d)
and for electron-poor arenes (2e,f). However, steric effects
influenced the reactivity. Slightly lower but acceptable yields
were achieved for the coupling reaction with ortho-
substituted arylboronic acids (2g,h).
Catalysts
entry
Rh(I) source
phosphine
PPh3
P[p-(MeO)C6H4]3
P[p-(CF3)C6H4]3
dppbb
P[p-(CF3)C6H4]3
P[p-(CF3)C6H4]3
P[p-(CF3)C6H4]3
P[p-(CF3)C6H4]3
P[p-(CF3)C6H4]3
P[p-(CF3)C6H4]3
P[p-(CF3)C6H4]3
P[p-(CF3)C6H4]3
P[p-(CF3)C6H4]3
yielda (%)
1
2
3
4
5
6
7
8c
9d
10e
11e,f
12e,g
13e,h
[RhCl(cod)]2
[RhCl(cod)]2
[RhCl(cod)]2
[RhCl(cod)]2
[RhCl(coe)2]2
[Rh(OH)(cod)]2
[RhCl(C2H4)2]2
[RhCl(C2H4)2]2
[RhCl(C2H4)2]2
[RhCl(C2H4)2]2
[RhCl(C2H4)2]2
[RhCl(C2H4)2]2
[RhCl(C2H4)2]2
22
27
72
34
91
99
99
91
78
88
46
51
29
a Isolated yield. b 10 mol % of dppb was used. c 2.0 equiv of TEMPO
was used. d 2 equiv of PhB(OH)2 was used. e Reaction conducted at 90 °C
for 13 h. f With 20 mol % of TEMPO and oxygen. g With 20 mol % of
TEMPO and air. h With oxygen in the absence of TEMPO.
Next, we tested whether C-H activation also works
on benzene derivatives. We selected 2-(2-ethoxyphenyl)-
pyridine (3) as a test substrate. Coupling reactions were
conducted under the conditions optimized for thiophene
derivative 1.
Combination of [RhCl(cod)]2 with PPh3 provided 2a in
22% yield (cod ) 1,5-cyclooctadiene, entry 1). The electron-
rich phosphine ligand P[p-(MeO)C6H4]3 afforded a slightly
higher yield, whereas a satisfactory result (72%) was obtained
with P[p-(CF3)C6H4]3 (entries 2 and 3). The bidentate ligand
bis(diphenylphosphino)butane (dppb) afforded a lower yield
(34%, entry 4). Further improvement was achieved with the
use of [RhCl(coe)2]2 as a precatalyst (91%, coe ) cyclo-
octene, entry 5). With [Rh(OH)(cod)]2 and [RhCl(C2H4)2]2,
biaryl 2a was formed in quantitative yield (99%, entries 6
and 7). Since [RhCl(C2H4)2]2 is cheaper than [Rh(OH)(cod)]2,
all subsequent studies were performed with the ethene-ligated
precatalyst. The use of 2 equiv of TEMPO (entry 8) or 2
equiv of phenylboronic acid led to a slightly reduced yield
(entry 9). A lower yield was obtained at 90 °C for 13 h (entry
Slightly lower yields were obtained for the reactions of 3
with arylboronic acids as compared to the couplings with 1.
Coupling of 3 with para-substituted arylboronic acids af-
forded the biphenyl derivatives 4a-e in 65-75% yield. As
above, electronic effects at the boronic acid moiety did not
play an important role. Similar yields were obtained for the
coupling of 3 with meta-substituted arylboronic acids (4f,g).
We were also able to show that sluggish coupling with an
alkenylboronic acid was possible under the applied condi-
tions. Hence, stilbene derivative 4h was isolated in 32% yield
along with 56% of unreacted substrate 3.
(10) Oxidative C-H activation using Pd: (a) ref 6. (b) Kalyani, D.;
Deprez, N. R.; Desai, L. V.; Sanford, M. S. J. Am. Chem. Soc. 2005, 127,
7330. (c) Deprez, N. R.; Kalyani, D.; Krause, A.; Sanford, M. S. J. Am.
Chem. Soc. 2006, 128, 4972. (d) Yang, S.; Li, B.; Wan, X.; Shi, Z. J. Am.
Chem. Soc. 2007, 129, 6066. Oxidative coupling of phenols using Rh:
Barrett, A. G. M.; Itoh, T.; Wallace, E. M. Tetrahedron Lett. 1993, 34,
2233.
(11) (a) Oi, S.; Fukita, S.; Inoue, Y. Chem. Commun. 1998, 2439. (b)
Oi, S.; Fukita, S.; Hirata, N.; Watanuki, N.; Miyano, S.; Inoue, Y. Org.
Lett. 2001, 3, 2579. (c) Shabashov, D.; Daugulis, O. Org. Lett. 2005, 7,
3657. (d) Ackermann, L.; Althammer, A.; Born, R. Angew. Chem., Int. Ed.
2006, 45, 2619. (e) Ackermann, L.; Born, R.; AÄ lvarez-Bercedo, P. Angew.
Chem., Int. Ed. 2007, 46, 6364.
130
Org. Lett., Vol. 10, No. 1, 2008

Scheme 1. Proposed Mechanism (L ) P[p-(CF3)C6H4]3)
We found that the activating ethoxy group in 3 was not
necessary for successful direct C-H arylation. Thus, treat-
ment of pyridine 5 with PhB(OH)2 gave biphenyl derivative
6 in 50% yield along with 18% of the double-arylated
compound 7 (eq 1). To broaden the scope of the reaction,
we tested whether the 2-pyridyl group could be replaced by
another ortho-directing group. Imines have been successfully
used in that regard.12 Therefore, we tested imine 8 in the
Rh-catalyzed coupling reaction with PhB(OH)2 and achieved
biaryl formation under slightly modified conditions (lower
temperature and longer reaction time). The crude product
was hydrolyzed to give aldehyde 9a in 51% yield (eq 2).
Similarly, the fluorinated analogue 9b was prepared in 49%
yield.
generate the Rh(III) complex 13 and TEMPOH.7b,c,e The
TEMPO anion probably acts as base under these conditions.
As shown in the experiment, the activation works better when
using the electron-poor P[p-(CF3)C6H4]3 ligand as compared
to PPh3. Therefore, we assume that at least one phosphine
ligand is bound to the Rh atom during the direct C-H
arylation. Reductive elimination and ligand exchange eventu-
ally provide the coupling product and Rh(I) complex 14.
In conclusion, we developed an oxidative Rh-catalyzed
coupling reaction of arenes and heteroarenes with arylboronic
acids via direct C-H arylation. Two different ortho-directing
groups can be used to mediate the direct C-H arylation step.
TEMPO used as an oxidant is commercially available and
no additional base is required for the coupling reaction. To
the best of our knowledge, Rh-catalyzed biaryl formation
via direct C-H arylation with an external oxidant is
unprecedented.15 We believe that oxidative transformation
of readily available Rh(I) complexes using an external
stoichiometric oxidant is a highly efficient approach for the
generation of the corresponding Rh(III) complexes.16
The proposed mechanism is depicted in Scheme 1. The
Rh(I) intermediate 10 is generated via transmetalation of
Rh(I) aminoalkoxide 14 with arylboronic acid.13 Complex
10 is assumed to be oxidized by 2 equiv of TEMPO to give
the Rh(III) complex 11.14-16 Ligand exchange of a phosphine
with the arene bearing the ortho-directing group should then
lead to 12, which eventually undergoes C-H arylation to
(12) (a) Oi, S.; Ogino, Y.; Fukita, S.; Inoue, Y. Org. Lett. 2002, 4, 1783.
(b) Ackermann, L. Org. Lett. 2005, 7, 3123. (c) Ueura, K.; Satoh, T.; Miura,
M. Org. Lett. 2005, 7, 2229.
Acknowledgment. We thank Novartis Pharma AG (Young
Investigator Award to A.S.), the Fonds der Chemischen
Industrie (stipend to T.V.), Dr. Jeffrey R. Simard (Chemical
Genomics Centre, Dortmund) for polishing the English, and
Ciba Specialty Chemicals for donation of chemicals.
(13) Zhao, P.; Incarvito, C. D.; Hartwig, J. F. J. Am. Chem. Soc. 2007,
129, 1876.
(14) (a) Chan, K. S.; Leung, Y.-B. Inorg. Chem. 1994, 33, 3187. (b)
Feng, M.; Chan, K. S. Organometallics 2002, 21, 2743.
(15) Direct C-H arylations with Ph4Sn and tetraphenylborates have been
reported; see refs 12c and 11a. However, in these reactions, no oxidant
was used. As suggested, insertion of a Rh(I) complex into a C-H aryl
bond (aryl-H activation) leads to a HRh(III)aryl species which undergoes
further reaction. Our process is different since an external oxidant is
necessary and the “C-H-activation” probably occurs via electrophilic
aromatic substitution. In fact, without oxidant our reactions did not proceed.
(16) Rh(I) carboxylates can be oxidized with Cu(OAc)2 to the corre-
sponding Rh(III) complexes, which subsequently undergo directed C-H
arylation: Ueura, K.; Satoh, T.; Miura, M. Org. Lett. 2007, 9, 1407.
Supporting Information Available: Experimental details
and characterization data for the products. This material is
available free of charge via the Internet at http://pubs.acs.org.
OL702659A
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