Development of recyclable iridium catalyst for C-H borylation

Article abstract of DOI:10.1016/j.tetlet.2009.08.080

Aromatic C-H borylation using [IrCl(COD)]₂ and 2,2′-bipyridinedicarboxylic acids was studied. 2,2′-Bipyridine-4,4′-dicarboxylic acid was complexed with [IrCl(COD)]₂ in the presence of bis(pinacolato)diboron. The resulting iridium catalyst could be readily separated from the reaction mixture by simple filtration, and the recovered catalyst under a nitrogen atmosphere was still active and could be reused more than 10 times.

Full text of DOI:10.1016/j.tetlet.2009.08.080

Tetrahedron Letters 50 (2009) 6176–6179
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Tetrahedron Letters
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Development of recyclable iridium catalyst for C–H borylation
Tsuyoshi Tagata a,b, Mayumi Nishida b, Atsushi Nishida a,
*
a Graduate School of Pharmaceutical Sciences, Chiba University, 1-33 Yayoi-cho, Inage-ku, Chiba 263-8522, Japan
b Koei Chemical Company, Ltd., 25, Kitasode, Sodegaura, Chiba 299-0266, Japan
a r t i c l e i n f o
a b s t r a c t
Aromatic C–H borylation using [IrCl(COD)]2 and 2,20-bipyridinedicarboxylic acids was studied. 2,20-Bipyr-
idine-4,40-dicarboxylic acid was complexed with [IrCl(COD)]2 in the presence of bis(pinacolato)diboron.
The resulting iridium catalyst could be readily separated from the reaction mixture by simple filtration,
and the recovered catalyst under a nitrogen atmosphere was still active and could be reused more than
10 times.
Article history:
Received 29 June 2009
Revised 24 August 2009
Accepted 25 August 2009
Available online 27 August 2009
Ó 2009 Elsevier Ltd. All rights reserved.
Arylboronic acids and their derivatives have been prepared by
reacting arylmetal compounds and boronic acid esters.1 However,
these processes involve highly reactive organolithium or organo-
magnesium reagents. Recently, iridium-catalyzed aromatic C–H
borylation has been developed2a–i and the conditions are much
safer and milder than the traditional methods. The most effective
catalyst developed by Miyaura and Hartwig3a–f was generated from
4,40-di-tert-butyl-2,20-bipyridine, an iridium complex such as
[IrCl(COD)]2 or [IrOMe(COD)]2, and a boron reagent such as
bis(pinacolato)diboron (Pin2B2, 1) or pinacolborane (PinBH, 2). A
trisboryl iridium complex, which was the active species in this cat-
alyst system, was isolated and well characterized.4 Although a high
turnover number was observed for the catalysts in this reaction, it
was difficult to recover and reuse the catalysts because they were
unstable and highly soluble in organic media. It is highly desirable
for industrial-scale processes to develop a new catalyst system that
allows easy recovery and reuse of precious iridium catalysts.
In 2007, Zhu et al. reported that iridium(I) salicylaldiminato-
cyclooctadiene complexes could be used for aromatic C–H boryla-
tion in the presence of tetra-2-pyridylpyrazine and an ionic liquid.
These catalytic systems could be reused at least six times.5 However,
before the catalyst could be reused, the products first had to be
Table 1
Substitution effect of 2,20-bipyridinedicarboxylic acidsa
(1.5 mol%)
[IrCl(COD)]2
O
O
O
O
/ Ligand (3 mol%)
B
B
B
80 oC, 12 h
O
O
1
Ligand
CO2H
N
CO2H
HO2C
CO2Na
N
CO2Na
CO2H
N
CO2H
N
N
N
N
N
HO2C
5
4
6
3
Yieldb
77%
86%
78%
79%
a
All reactions were performed at 80 °C for 12 h with benzene (60 mmol), 1 (1.0 mmol), and [IrCl(COD)]2 (1.5 mol %), ligand (3 mol %).
Yield was determined by GC using 4-ethylbiphenyl as an internal standard.
b
* Corresponding author. Tel.: +81 43 290 2907; fax: +81 43 290 2909.
E-mail address: nishida@p.chiba-u.ac.jp (A. Nishida).
0040-4039/$ - see front matter Ó 2009 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2009.08.080

T. Tagata et al. / Tetrahedron Letters 50 (2009) 6176–6179
6177
Table 2
Conditions for the iridium-catalyzed C–H borylation of benzene by bis(pinacolato)diboron and pinacolborane
Ir precursor
(1.5 mol%)
4
O
(3 mol%)
O
O
O
O
O
B
or
B
B
BH
O
O
12 h
1
2
60 mmol
1.0 mmol
2.0 mmol
Entry
Ir precursors
Boranes
Temp
Yielda
1
2
3
4
5
6
[IrCl(COD)]2
[IrOMe(COD)]2
[IrCl(COD)]2
[IrOMe(COD)]2
[IrCl(COD)]2
[IrOMe(COD)]2
1
1
1
1
2
2
80 °C
80 °C
25 °C
25 °C
80 °C
80 °C
86%
76%
trace
trace
78%
80%
a
Yields based on borylating reagent in 1 or 2 were determined by GC analysis using 4-ethylbiphenyl as an internal standard.
Table 3
Use of other arenes and heteroarenes in an [IrCl(COD)]2 and 4 systema
R
X
[IrCl(COD)]2
(0.75 mol%)
4
R
BPin
(1.5 mol%)
X
or
O
O
or
B
B
O
O
Methylcyclohexane
80 oC, 12 h
BPin
Y
2.0 mmol
Arene
1
Y
1.2 mmol
Entry
1
Product
Yieldb (%)
20c,d
OMe
OMe
BPin
CO2Me
CO2Me
2
76c,e
BPin
CF3
CF3
Cl
3
4
64c,f
BPin
PinB
Cl
83
Cl
Cl
CF3
PinB
PinB
CF3
5
95
CF3
CF3
Cl
Cl
6
7
8
84
86
78
N
N
Cl
Cl
BPin
BPin
S
S
O
O
a
A mixture of [IrCl(COD)]2, 4, and 1 in methylcyclohexane was heated at 80 °C for 5 min. A solution of an arene in methylcyclohexane was added to the mixture and the
whole was heated at 80 °C for 12 h.
b
Yield was determined by GC using 4-ethylbiphenyl as an internal standard and the isomer ratio was determined by 1H NMR.
Isolated yield.
o:m:p = 6:76:18.
m:p = 50:50.
c
d
e
f
m:p = 58:42.3,5-Diborylated compound was obtained in 13% yield based on trifluoromethylbenzene.

6178
T. Tagata et al. / Tetrahedron Letters 50 (2009) 6176–6179
Table 4
C–H borylation of benzene catalyzed by recyclable iridium catalysta,b
[IrCl(COD)]2
4
(1.5 mol%) (3 mol%)
O
O
O
O
B
B
B
80 oC, 12 h
O
O
1
Iridium Complex (reusable)
60 mmol
1.0 mmol
Cycle
Yieldc (%)
Ir leachingd (ppm)
Cycle
Yieldc (%)
Ir leachingd (ppm)
1
2
3
4
5
98
98
98
99
99
<0.1
<0.1
<0.1
<0.1
<0.1
6
7
8
9
10
99
99
96
99
99
<0.1
<0.1
<0.1
<0.1
<0.1
a
b
c
Iridium complex was prepared under standard C–H borylation conditions and isolated by filtration in a glove box.
All reactions were performed at 80 °C for 12 h with benzene (240 mmol), 1 (4.0 mmol), and recycled catalyst.
Yield was determined by GC using 4-ethylbiphenyl as an internal standard.
d
Ir leaching into filtrate was checked by ICP analysis.
separated from the reaction mixture by distillation. Thus, a more
convenient catalyst that is easier to recover and reuse is still needed.
To develop a new recyclable catalyst, we focused on the feasibil-
ity of 2,20-bipyridinedicarboxylic acids (BPDCAs),6a–d such as
2,20-bipyridine-3,30-dicarboxylicacid(3), 2,20-bipyridine-4,40-dicar-
boxylic acid (4)7, and 2,20-bipyridine-5,50-dicarboxylic acid (5), as
ligands. Since 3, 4, and 5 are less soluble in most organic media than
their parent compound, we expect that they might be useful for
separating the catalyst from the reaction mixture. Here, we report
aromatic C–H borylation using BPDCA as a functional ligand.
We first examined the effect of the positions of carboxyl groups
on the 2,20-bipyridine ring for the C–H borylation of benzene with
bis(pinacolato)diboron (1) using [IrCl(COD)]2 as an iridium precur-
sor. The results are shown in Table 1. Borylations were typically
carried out in benzene (60 mmol) with bis(pinacolato)diboron 1
(1.0 mmol) in the presence of [Ir(COD)Cl]2 (0.015 mmol) and BPD-
CAs (0.03 mmol) at 80 °C for 12 h under a nitrogen atmosphere. All
reactions with BPDCA, or even its sodium salt, as a ligand pro-
ceeded smoothly and gave phenylpinacolborane in good yield.
Among the ligands we examined, 4 was most effective and was se-
lected for further survey.
In these reactions, the yellow reaction mixture turned black at
around 70 °C. After the reactions were completed, the black irid-
ium complex could be separated by filtration, and evaporation of
the colorless filtrate gave the product with high purity (GC
>98%). In the filtrates of the reactions using 4 and 5 (entries 2
and 3), iridium metal was not detected by ICP analysis (less than
0.1 ppm). However, 1.0 ppm of iridium metal was observed in
the filtrate of the reaction using 3 (entry 1). It seemed that iridium
complex prepared from 3 was not sufficiently stable under these
reaction conditions.8
4, and 1 which were heated at 80 °C for 5 min. In the reaction of
anisole, the borylated product was obtained in low yield. The
methoxy group may coordinate with the iridium catalyst because
10 ppm iridium was detected in the filtrate. On the other hand,
reactions using other substrates proceeded smoothly and could
be tolerated by a wide variety of functionalities, such as Cl, CO2Me,
and CF3 groups, as with Miyaura’s catalyst.3b
Since the iridium complex could be removed from the reaction
mixture by filtration, we turned our attention to recycling the cat-
alyst. When the reaction mixture was filtered under air, the iridium
complex did not show any catalytic activity. On the other hand,
when the iridium complex was filtered under nitrogen in a glove
box, the isolated iridium complex could be reused more than 10
times for one week. No iridium was leached into the filtrates.
The results are shown in Table 4.9
Although we were interested in the structure of this iridium
complex, it was difficult to analyze because of its instability under
air and its insolubility in organic solvents. At the beginning of the
reaction, cyclooctane was observed in the reaction mixture by GC
analysis, which indicated the dissociation of cyclooctadiene
(COD) from [IrCl(COD)]2 and hydrogenation to cyclooctane due to
the generated hydrogen. On the other hand, cyclooctane was not
observed in the reaction using the recycled iridium complex. ICP
analysis of the complex showed that it contained both iridium
and boron atoms in a molar ratio of 1:2.3–2.5. Based on these
results, this complex may have a structure similar to that of
the tris(boryl)iridium complex reported by Miyaura and co-
workers.3b
In conclusion, we have developed a new recyclable iridium cat-
alyst for C–H borylation. The iridium catalyst was readily separated
from the reaction mixture by filtration and the recovered catalyst
could be reused more than 10 times. This catalyst system could
be applied to an industrial process for C–H borylation.
Next, we surveyed combinations of iridium complex and boron
reagents. As shown in Table 2, [IrOMe(COD)]2 and pinacolborane
could be used in the C–H borylation of benzene with 4 as a ligand.
In contrast to Miyaura’s catalyst system,3d the reaction using 4
as a ligand did not proceed at room temperature. The active species
might not be produced because 2,20-bipyridine-4,40-dicarboxylic
acid shows very low solubility in benzene at room temperature.
We also used other substrates with the new catalyst system
(Table 3). Methylcyclohexane was used as a solvent. To avoid the
deactivation caused by coordination of the substrate to the catalyst
precursor, substrates were added into the mixture of [Ir(COD)Cl]2,
A more detailed mechanistic study and a structural investiga-
tion of the insoluble iridium complex are underway.
Acknowledgments
We thank Mr. Matsuo (Koei Chemical Company, Ltd.) for the ICP
analysis and Mr. Ishikawa (Koei Chemical Company, Ltd.) for the
GC–MS analysis. Financial support from Koei Chemical Company,
Ltd. is gratefully acknowledged.

T. Tagata et al. / Tetrahedron Letters 50 (2009) 6176–6179
6179
6. BPDCAs are commercially available and are used as ligands for dye-sensitized
solar cells, as electro-luminescent materials, and as catalysts for polymers. see:
(a) Wei, H.; Du, Y.; Kang, J. Z.; Xu, G. B.; Wang, E. K. Chin. J. Chem. 2007, 25, 159–
163; (b) Chen, C. Y.; Wu, S. J.; Wu, C. G.; Chen, J. G.; Ho, K. C. Angew. Chem., Int. Ed.
2006, 45, 5822–5825; (c) Kuang, D.; Klein, C.; Snaith, H. J.; Moser, J. E.;
Humphry-Baker, R.; Comte, P.; Zakeeruddin, S. M.; Graetzel, M. Nano Lett. 2006,
6, 769–773; (d) Min, D.; Yoon, S. S.; Lee, S. W. Inorg. Chem. Commun. 2002, 5,
143–146.
7. Compound 4 is available from Koei Chemical Co, Ltd. in industrial quantities.
It is prepared by the coupling reaction of 2-chloropyridine-4-carboxylic acid
in the presence of Pd/C, hydrazine, and base. see; Shimada, M., JP
2006240997.
References and notes
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9. Representative procedure for Table 4; A 50 mL test tube equipped with a
magnetic stirring bar and a three-way cock with a septum inlet was charged
with [IrCl(COD)]2 (40.4 mg, 0.06 mmol), 2,20-bipyridine-4,40-dicarboxylic acid
(29.2 mg, 0.12 mmol), and bis(pinacolato)diboron (1.02 g, 4.0 mmol) and then
flushed with nitrogen. Benzene (240 mmol) was added and the mixture was
stirred at 80 °C for 12 h in a glove box. The reaction mixture was filtered and the
residue was washed twice with 10 mL benzene to give a black powder (89 mg).
Combined filtrate and washings were analyzed by GC and GC mass spectroscopy
to determine the yield using 4-ethylbiphenyl as an internal standard. The black
powder was used for a second run under the same conditions. Leaching of
iridium metal was determined by ICP analysis.
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