Direct C-H arylation of (hetero)arenes with aryl iodides via rhodium catalysis

Article abstract of DOI:10.1021/ja064500p

A new method for the catalytic C-H arylation of heteroarenes and arenes that manifests high activity paired with reasonably broad scope was developed. Under the catalytic influence of RhCl(CO){P[OCH(CF₃)₂]₃}₂ an

Full text of DOI:10.1021/ja064500p

Published on Web 08/17/2006
Direct C-H Arylation of (Hetero)arenes with Aryl Iodides via Rhodium
Catalysis
†
†
†
,†,‡
Shuichi Yanagisawa, Tomoko Sudo, Ryoji Noyori, and Kenichiro Itami*
Department of Chemistry and Research Center for Materials Science, Nagoya UniVersity, Nagoya 464-8602, Japan,
and PRESTO, Japan Science and Technology Agency (JST), Japan
Received June 26, 2006; E-mail: itami@chem.nagoya-u.ac.jp
Organic molecules having (hetero)aryl-(hetero)aryl bonds rep-
resent privileged structural motifs frequently found in natural
products or used in pharmaceuticals and functional organic materi-
als. Therefore, the development of efficient methods for biaryl
formation has been a topic of unparalleled importance in all aspects
1
of pure and applied chemistry. Although metal-catalyzed cross-
coupling reactions of organometallics and organic halides have
1
enjoyed widespread applications, the direct C-H arylation of
heteroarenes and arenes holds significant synthetic potential as it
2
eliminates preactivation of coupling components. During the last
several years, impressive progress has been made for the direct
C-H arylation methodology (mainly Pd catalysis),3 but there still
-5
A preliminary survey of substrates revealed that a range of five-
exists considerable room for further development. For example, a
membered heteroarenes, such as thiophenes, furans, pyrroles, and
universal catalyst that can directly arylate all heteroarenes as well
indoles, could be arylated through the present catalysis (Table 1).
as simple arenes has not been forthcoming.
Although aryl bromides and triflates possessed poor reactivity,
As a part of our program aimed at establishing programmable
synthesis of (hetero)arene core functional molecules, we developed
7
arylation proceeded efficiently with aryl and heteroaryl iodides.
While thiophenes (2a,b), bithiophene (2c), and 2,3-dimethylfuran
a rhodium complex 1 bearing a strongly π-accepting ligand,
(2d) were arylated selectively at carbons next to sulfur or oxygen,
3 2 3
P[OCH(CF ) ] , as an efficient catalyst precursor for C-H arylation
1-phenylpyrrole (2e) was selectively arylated at the 3-position. The
of (hetero)arenes with aryl iodides (Figure 1). The complex 1 can
Table 1. Direct C-H Arylation of Heteroarenes Catalyzed by 1a
Figure 1. Rhodium complex 1 for catalytic direct C-H arylation.
be prepared quantitatively by mixing [RhCl(CO)
2 2
] and P[OCH-
(
CF in toluene. A notable feature of this complex is its
3 2 3
) ]
outstanding stability in air and moisture in the solid state. Virtually
no decomposition of 1 has been detected after extended (>8
months) exposure to air. The X-ray crystal structure of 1 indicates
that this may be due to the effective shielding of the rhodium atom
by two bulky phosphite ligands (Figure 1).
The following examples are typical (eqs 1 and 2). A mixture of
3
-methoxythiophene (2a) and iodobenzene (3a) in m-xylene was
stirred at 150 °C for 12 h in the presence of 1, Ag CO , and 1,2-
dimethoxyethane (DME) (1:2a:3a:Ag CO :DME ) 0.03:1.5:1.0:
.0:1.0 molar ratio). A direct C-H arylation took place at the
-position of 2a to afford 4aa in 75% yield with virtually complete
2
3
2
3
1
2
regioselectivity (eq 1). When the reaction was conducted at 200
4c
°
C under microwave irradiation, the reaction was complete within
0
.5 h to furnish 4aa in 73% yield. The addition of DME suppressed
6
the formation of diarylated product 5aaa. Selective double C-H
arylation also was possible when an excess amount of 3a (2.2 equiv
to 2a) was employed, yielding an interesting thiophene core
π-system 5aaa in 79% yield (eq 2).
a
Molar ratio: 1:2:3:Ag2CO3:DME ) 0.03:1.5:1.0:1.0:1.0. Conditions:
b
1
50-200 °C, 0.5 h (microwave) in m-xylene. 3-Methoxythiophene (2a),
2-ethylthiophene (2b), 2,2′-bithiophene (2c), 2,3-dimethylfuran (2d), 1-phen-
ylpyrrole (2e), 1-methylindole (2f). c Iodobenzene (3a), 4-iodoacetophenone
(3b), 3-iodothiophene (3c), 4-iodotoluene (3d), 4-iodobenzonitrile (3e).
†
‡
Nagoya University.
PRESTO, JST.
d
Isolated yield. The yield in parentheses is determined by NMR.
11748
9
J. AM. CHEM. SOC. 2006, 128, 11748-11749
10.1021/ja064500p CCC: $33.50 © 2006 American Chemical Society

C O M M U N I C A T I O N S
Table 2. Effect of Ligand in Rh-Catalyzed C-H Arylation
the reaction mechanism, development of more active catalysts, and
applications of the direct arylation technology for materials science
and pharmaceutical chemistry are currently underway.
Acknowledgment. This work was supported in part by PRESTO,
Japan Science and Technology Agency (JST). We thank Dr. Atsushi
Wakamiya for assistance in X-ray analysis.
ligand (L)
yield of 4ab (%)
ν
CO in RhCl(CO)L
2
(cm-1)
P[OCH(CF3)2]3
P(C6H5)[OCH(CF3)2]2
P(OC6H5)3
P[OCH(CH3)2]3
P(C6H5)3
94
31
6
9
0
2070
2038
2018
2002
1983
Supporting Information Available: Experimental procedures and
characterization data for all new compounds. This material is available
free of charge via the Internet at http://pubs.acs.org.
References
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8
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(
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2
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9
plexes. Although the mechanism remains unknown, a possible
I
III
mechanism could be a Rh /Rh cycle with (i) oxidative addition
I
10
of aryl iodides to Rh , (ii) electrophilic metalation of heteroarenes,
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(
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alkoxybenzenes is consistent with an electrophilic metalation
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and/or C-H oxidative addition.2 A preliminary examination
(
2
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128, 8754.
in low efficiency. Nevertheless, the successful arylation of arenes
(
6) 5aaa was obtained in 17% yield together with 4aa (66%) when the reaction
was conducted without DME under microwave irradiation.
5
without catalyst directing groups is noteworthy.
(
7) Although arylation proceeded well with electron-deficient and -neutral
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(
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(
11) During the course of this study, we became aware of Rh-catalyzed arylation
of indoles and pyrroles reported by Sames (ref 4b). Although they also
proposed a mechanism based on electrophilic metalation, the regioselec-
tivities were somewhat different with our catalysis. In addition, the
arylation of thiophenes, furans, and simple arenes was not mentioned.
12) The yield of arylation products (7 and 8) gradually decreased by decreasing
the amount of anisole (6) employed: 51% (3f:6 ) 1:27), 48% (3f:6 )
1:10), 42% (3f:6:n-octane ) 1:5:6; n-octane was added as cosolvent),
In summary, a new method for the catalytic C-H arylation of
heteroarenes that manifests high activity paired with reasonably
broad scope was developed. The successful C-H arylation of
simple arenes speaks well for the potential of the present Rh
catalysis for further development and applications. Elucidation of
(
25% (3f:6:n-octane ) 1:2:6; n-octane was added as cosolvent).
JA064500P
J. AM. CHEM. SOC.
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VOL. 128, NO. 36, 2006 11749