Iridium-catalyzed selective C-C bond cleavage of nitriles and ketones

Article abstract of DOI:10.1055/s-2004-831333

Selective and catalytic C-C bond cleavage of pentanedinitriles and 5-oxohexanenitriles can be performed in the presence of iridium hydride complex IrH₅(Pi-Pr₃)₂ (1). The key steps of this reaction are α-C-H activation of t

Full text of DOI:10.1055/s-2004-831333

LETTER
2185
Iridium-Catalyzed Selective C-C Bond Cleavage of Nitriles and Ketones
Selective C-C
B
on
i
dClea
v
r
age of
N
o
itriles and
K
k
etones i Terai,a Hikaru Takaya,*a Shun-Ichi Murahashi*b
a
Department of Chemistry, Graduate School of Engineering Science, Osaka University, 1-3 Machikaneyama, Toyonaka, Osaka 560-8531,
Japan
Fax +81(6)68506222; E-mail: takaya@chem.es.osaka-u.ac.jp
b
Department of Applied Chemistry, Faculty of Engineering, Okayama University of Science, 1-1 Ridai-cho, Okayama 700-0005, Japan
Received 3 June 2004
Abstract: Selective and catalytic C-C bond cleavage of pentane-
dinitriles and 5-oxohexanenitriles can be performed in the presence
of iridium hydride complex IrH5(Pi-Pr3)2 (1). The key steps of this
reaction are a-C-H activation of the cyano or carbonyl group and
subsequent b-carbon elimination.
C
R
CH2X
Ir
C
R
CHX
Ir
H
2
3
C
CHX
H
Key words: iridium hydride complex, C-H activation, b-carbon
elimination, nitrile, ketone
Ir
R
H
+
C
CHX
R
Ir
X = CN, COR
4
Scheme 1
The selective catalytic cleavage of C-C single bond by
transition metals under homogeneous conditions has re-
ceived much interest in recent years, because this type of
reaction enables us to perform a novel one-step transfor-
mation of molecular skeleton1,2 which cannot be achieved
by conventional organic synthesis. Furthermore, this type
of C-C bond cleavage could form a key part of environ-
mentally friendly processes for recycling polymer to the
corresponding monomer.3,4
fin-coordinated iridium intermediate 4. Reductive elimi-
nation of iridium from 4 would produce R-H and olefin
with regeneration of the iridium catalyst.
In order to assess the catalytic activity of various iridium
complexes, a series of C-C bond cleavage reactions was
carried out by adding iridium catalysts to a solution of 2-
methyl-2-phenyl-pentanedinitrile (5) in toluene at 150 °C
(Scheme 2).15
Recent studies on transition-metal-catalyzed C-C single
bond cleavage5 are roughly classified into two categories:
i) oxidative addition, and ii) b-carbon elimination. Direct
oxidative addition of transition metals into the C-C bonds
is generally driven by release of ring strain6 or by chela-
tion assistance.7 Transition metal-mediated b-carbon
elimination, well recognized as an important mechanism
for chain scission of polymer,8 has a potent ability to
cleave unstrained inactive C-C single bonds. However,
except for a few examples,9 strain release strategy has
been widely used for most b-carbon eliminations.10,11
Ir–cat.
CN
CN
(10 mol%)
Ph
CN
Ph
toluene
5
6
150 °C, 5 h
: 32%
IrH (Pi-Pr3)2 (1)
5
Ir–cat. =
IrH5(PCy3)2
IrH5(PPh3)2
: 23%
: 4%
Scheme 2 Catalytic activities of various iridium complexes for the
C-C bond cleavage of 1,3-dicyano-3-phenylbutane (5)
Currently, we are investigating catalytic C-C single bond
cleavage of non-strained compounds via b-carbon elimi-
nation. In this report, we describe iridium-catalyzed C-C
single bond cleavage of nitriles and ketones via b-carbon
elimination. Our investigation was based on the following
concept (Scheme 1).
Heating the solution for five hours in the presence of 10
mol% of iridium complex catalysts gave the correspond-
ing 2-phenylpropionitrile (6). In this trial, the reaction
time was shortened in order to estimate the initial reaction
rate. The iridium-pentahydride complex, IrH5(Pi-Pr3)2 (1)
has proven to be the best catalyst. The hydride ligands
easily leave as molecular hydrogen from pentahydride iri-
dium complexes to form coordinatively unsaturated ac-
tive species.16 The strong electron donating triisopropyl
phosphine ligand would also facilitate C-H activation.
Complexes such as IrH(CO)(PPh3)2, IrCl(CO)(PPh3)2,
Both nitriles (X = -CN) and ketones (X = -COR) readily
react with metals to give nitrile- or ketone-coordinated
complex 2. Iridium hydride complexes have proven to be
effective catalysts for C-H bond activation of nitriles.12
The activation of C-H bond adjacent to X would give an
alkyliridium intermediate 3.13,14 The C-C bond b- to X
could be cleaved by b-carbon elimination to yield an ole-
Ir(CO)2(acac),
IrHCl2(PCy3)2,
Ir(acac)3,
IrCl3,
SYNLETT 2004, No. 12, pp 2185–2187
Advanced online publication: 01.09.2004
DOI: 10.1055/s-2004-831333; Art ID: U15804ST
© Georg Thieme Verlag Stuttgart · New York
0
1
.1
0
.2
0
0
4
[IrCl2Cp*]2, [IrCl(coe)2]2, Na3IrCl6 were not effective as
catalysts. Phosphine ligands such as Pi-Pr3, PCy3, and
PPh3 also showed no catalytic activity.

2186
H. Terai et al.
LETTER
Table 1 C-C Bond Cleavage Reactions Catalyzed by IrH5(Pi-Pr3)2
(1)
CN
R2
CN
R2
H
IrH5(Pi-Pr3)2 (1)
R1
X
R1
H
Entry Substrate
Product
Yield (%)
49
11
IrLn
1
CN
CN
NC
H
Ph
Ph
CN
CN
R2
H
R1
IrLn
6
R2
5
R1
X
IrLn
10
2
98
CN
CN
7
Ph
CN
Ph
Ph
Ph
H
NC
H
X
3
4
82
32
CN
CN
CN
NC
IrLn
R1
IrLn
γ
R2
Ph
Ph
CN
R1
X
Ph
Ph
R2
β
9
X
8
CN
CN
X = CN or COR
Scheme 3
O
O
O
5
6
50
38
CN
CN
mediate 8.18 Subsequent b-carbon elimination from 8
would proceed to afford olefin-coordinated intermediate
9. Dissociation of the olefin (X = -CN; acrylonitrile, X =
-COR; methylvinylketone) from 9 would lead to alkyliri-
dium intermediate 10. Reductive elimination of iridium in
10 would yield product 11 with regeneration of the cata-
lyst. During this catalytic cycle, thermodynamic stability
of Ir-C bond20 might contribute to generation of interme-
diates 8–10.
Ph
Ph
Ph
Ph
Ph
Ph
Ph
CN
Ph
Representative results of this reaction are shown in
Table 1.
Acknowledgment
In the presence of catalytic amounts of IrH5(Pi-Pr3)2 (0.10
mmol) (1), the b-selective C-C bond cleavage of nitriles
or ketones (1.0 mmol) proceeds to give the corresponding
product in good yields.17 The reaction of nitriles having
two phenyl groups at 2-position proceeds more effectively
than that of the nitrile with one phenyl group. For exam-
ple, 2,2-diphenyl-pentanedinitrile could react to produce
diphenylacetonitrile almost quantitatively (entry 2). Phe-
nyl group at 2-position is essential for this reaction. It is
noteworthy that the iridium-catalyzed C-H activation
tolerates bulky substituents at a-position of the nitriles.
Typically, the reaction of 2,4-dimethyl-2- phenypentane-
dinitrile gave better yield than the reaction of 5 (entry 3).
Generally, ketones are less reactive than nitriles toward
a-C-H activation because of their poor coordination abil-
ity to metals. However, in the presence of catalyst 1, the
C-C bond cleavage of ketones can be performed as shown
in entries 4–6. A similar rate enhancement due to two
phenyl groups was also observed in the reaction of ketone
(entry 5).
This work was supported by the Research for the Future Program
from the Japan Society for the Promotion of Science, and a Grant-
in-Aid for Scientific Research, the Ministry of Education, Science,
Sports, and Culture, Japan. This work was also supported by
Sasagawa Scientific Research Grant from The Japan Science Socie-
ty and Kansai Research Foundation for Technology Promotion
(KRF). The authors express special thanks to the center of ex-
cellence (21COE) program ‘Creation of Integrated EcoChemistry
of Osaka University’. The authors thank Professor Takeshi Naota of
Osaka University for his helpful discussion and generous support.
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A plausible mechanism of this reaction is shown in
Scheme 3. The catalytically active species seems to be un-
saturated iridium complexes IrLn (L = Pi-Pr3 and H)
which would be formed by dissociation of molecular hy-
drogen from 1.16 Nitriles or ketones would coordinate to
the iridium active catalyst IrLn to give intermediate 7. The
activation of C-H bond adjacent to X would provide inter-
Synlett 2004, No. 12, 2185–2187 © Thieme Stuttgart · New York

LETTER
Selective C-C Bond Cleavage of Nitriles and Ketones
2187
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(17) General Procedure for the Iridium-Catalyzed C-C Bond
Cleavage of Nitriles and Ketones.
In a 25mL of sealed tube, IrH5 (Pi-Pr3)2 (1, 0.2 mmol),
nitriles or ketones (1 mmol), and toluene (0.5 mL) were
placed and stirred for 12 h at 150 °C under argon
atmosphere. The yields of products were determined by
NMR using dibenzyl as an internal standard. All the
products were confirmed by 1H NMR, 13C NMR, and
HRMS.
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dinitrile (12), the formation of 2-amino-1-cyano-3-methyl-
3-phenylcyclopentene (13) was observed.19 The cyclization
would proceed via nucleophilic addition of alkyliridium
intermediate to the CN triple bond of nitriles (Scheme 4).
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8 (Scheme 4).
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CN
H2N
Ph
CN
1 (10 mol%)
CN
Ph
toluene
150 °C
24 h
12
13
24%
1
C-H
activation
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–IrLn
+
N
C
H
nucleophilic
addition
IrLn
CN
N
CN
IrLn
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Ph
C
δ-
δ+
Ph
H
Scheme 4
(19) In a 25mL of sealed tube, 2-methyl-2- phenylhexanedinitrile
(12, 200 mg, 1.0 mmol), IrH5 (Pi-Pr3)2 (1, 52 mg, 0.1 mmol),
and toluene (0.5 mL) were placed and stirred for 24 h at
150 °C under argon atmosphere. After removal of the
solvent, the mixture was purified by silica gel column
chromatography and by Kugelrohr distillation to give 2-
amino-1-cyano-3-methyl-3-phenylcyclopentene (13, 1:0.8
diastereomer mixture) as a colorless oil (47 mg, 24%). 1H
NMR (270 MHz, CDCl3): d = 1.54 (s, 3 H, -CH3), 1.95–2.15
[m, 2 H, -CH2-C(Me)(Ph)-], 2.48–2.53 [m, 2 H, -CH2-
C(CN)-], 4.25 (br, 2 H, -NH2), 7.22–7.40 (m, 5 H, -C6H5).
13C NMR (68 MHz, CDCl3): d = 167.2 (C-NH2), 144.1
(-C6H5), 128.4 (-C6H5), 126.7 (-C6H5), 126.2 (-C6H5), 118.8
(-CN), 74.2 (C-CN), 53.0 (C-CH3), 41.5 [-CH2-C(Me)(Ph)-],
28.1 [-CH2-C(CN)-], 22.9 (-CH3). MS (EI, 70 eV):
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(1 mmol), and toluene (0.5 mL) were placed and stirred for
12 h at 150 °C under argon atmosphere. The yield of
2-phenylpropionitrile 6 was determined by NMR using
dibenzyl as an internal standard.
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Synlett 2004, No. 12, 2185–2187 © Thieme Stuttgart · New York