Communications
DOI: 10.1002/anie.200806358
Synthetic Methods
ꢀ
Iridium Catalysis for C H Bond Arylation of Heteroarenes with
Iodoarenes**
Benoꢀt Join, Takuya Yamamoto, and Kenichiro Itami*
Arylated heteroarenes (heterobiaryls) are ubiquitous in
natural products and pharmaceuticals, and are frequently
used in organic materials or as ligands for metals.[1] Con-
sequently, the development of efficient methods for making
heterobiaryl motifs has been a topic of immense importance
in chemical synthesis.[2] Typically, heterobiaryls have been
constructed by means of Pd-catalyzed cross-coupling reac-
tions of metalated (hetero)arenes and halogenated (hetero)-
investigated, by using [Ir(cod)2]BF4 (cod = 1,5-cycloocta-
diene) as the source of IrI. Screening of ligands indicated
that PCy3 was by far the most effective ligand, producing the
arenes.[2] More recently, the direct C H bond arylation of
ꢀ
ꢀ
ꢀ
ꢀ
heteroarenes with haloarenes (Het H + Ar X!Het Ar)
has emerged as an area of extensive research because it can
streamline the synthesis by skipping the premetalation step in
the cross-coupling strategy.[3,4] Although a number of useful
catalytic systems incorporating Pd,[5] Rh,[6] Ru,[7] and Cu[8]
heterobiaryl 3Aa in 88% yield (Table 1, entry 6).[14]
A
dramatic difference between PCy3 and other closely related
alkylphosphanes, such as PCyp3 (Cyp = cyclopentyl), is nota-
ble and intriguing. In developing a stable Ir+/PCy3 pre-
catalyst, we identified [Ir(cod)(py)PCy3]PF6 (Crabtreeꢀs cata-
lyst;[15,16] py = pyridine) to be very convenient (Table 1,
entry 11). A quantitative coupling using an equimolar quan-
tity of each coupling partner was possible at 1608C with this
catalyst (Table 1, entry 12). Interestingly, the corresponding
rhodium complex [Rh(cod)(py)PCy3]PF6 was totally ineffec-
tive under otherwise identical conditions (Table 1, entry 13).
The importance of Ag2CO3 was also recognized, as other
additives, such as AgOTf, AgOAc, AgSbF6, Na2CO3, K2CO3,
ꢀ
have been developed for the C H bond arylation of hetero-
arenes with haloarenes,[9] the repertoire of applicable cata-
lysts still remains rather limited. Fujita and Yamaguchi have
reported an interesting [(Cp*IrHCl)2]/KOtBu (Cp* = pen-
ꢀ
tamethylcyclopentadienyl) system that promotes the C H
bond arylation of unactivated arenes (benzene, toluene, and
anisole) with iodoarenes.[10,11] However, this Ir-based catalytic
system employs the arene substrate as a solvent (40 equiv-
alents), and cannot be applied to heteroaromatic sub-
strates.[10]
As an initial foray into this area,[12] we recently reported
Table 1: Effect of ligands in Ir-catalyzed coupling of 1A and 2a.[a]
that the system [RhCl(CO)(P{OCH(CF3)2}3)2]/Ag2CO3 pro-
[12a]
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moted the C H bond arylation of arenes with iodoarenes.
To develop a new metal catalyst based on this lead, we set out
I
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to explore the Ir /Ag2CO3 system as a platform for C H bond
arylation. We report herein our finding that an Ir+/PCy3/
ꢀ
Ag2CO3 (Cy = cyclohexyl) system catalyzes the C H bond
Entry
Ligand[b]
Yield [%][c]
arylation of electron-rich heteroarenes with iodoarenes.
We began our study by applying various iridium com-
plexes with Ag2CO3 to the reaction of 2-methylthiophene
(1A, one equivalent) and iodobenzene (2a, one equivalent)
1
2
3
4
5
6
7
8
P[OCH(CF3)2]3
PPh3
P(C6H4OMe-p)3
PCy2(o-biphenyl)
PCy2Ph
PCy3
PCyp3
PAd2(nBu)
<1
2
2
in m-xylene (1408C, 12 h).[13] In contrast to Rh catalysis, a
proved ineffec-
tive (Table 1, entry 1). Thus, the effect of the ligand was
4
29
88
16
9
cationic IrI complex with P[OCH(CF3)2]3
[12a]
9
P(nBu)3
P(tBu)3
[Ir(cod)(py)PCy3]PF6
[Ir(cod)(py)PCy3]PF6
[Rh(cod)(py)PCy3]PF6
5
2
85
>99
<1
[*] Dr. B. Join, T. Yamamoto, Prof. Dr. K. Itami
Department of Chemistry, Graduate School of Science
Nagoya University, and PRESTO Science and Technology Agency
Chikusa, Nagoya 464-8602 (Japan)
10
11[d]
12[d,e]
13[d]
Fax: (+81)52-788-6098
E-mail: itami@chem.nagoya-u.ac.jp
[a] Conditions: 1 A (0.40 mmol), 2a (0.40 mmol), [Ir(cod)2]BF4
(0.02 mmol), ligand (0.02 mmol), Ag2CO3 (0.42 mmol), m-xylene
(2 mL), 1408C, 12 h. [b] Cy=cyclohexyl, Cyp=cyclopentyl, Ad=1-ada-
mantyl, nBu=n-butyl, tBu=tert-butyl, cod=1,5-cyclooctadiene, py=
pyridine. [c] Determined by GC analysis using n-decane as an internal
standard. [d] Isolated complex was employed as a catalyst. [e] Reaction
was conducted at 1608C for 18 h.
[**] This work was supported by the PRESTO program of JST, and a
Grant-in-Aid for Scientific Research from MEXT and JSPS. B.J. is a
recipient of a JSPS Postdoctoral Fellowship.
Supporting information for this article is available on the WWW
3644
ꢀ 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Angew. Chem. Int. Ed. 2009, 48, 3644 –3647