Cationic iridium-BINAP complex-catalyzed addition of aryl ketones to alkynes and alkenes via directed C-H bond cleavage

Article abstract of DOI:10.1016/j.jorganchem.2008.09.065

Cationic Ir complex ([Ir(cod)₂]BF₄ + BINAP) catalyzed the addition of ortho-C-H bonds in aryl ketones to alkynes, which gave alkenylated products in good to high yield. Styrene derivatives were good substrates, and the enantioselecti

Full text of DOI:10.1016/j.jorganchem.2008.09.065

Journal of Organometallic Chemistry 693 (2008) 3939–3942
Contents lists available at ScienceDirect
Journal of Organometallic Chemistry
journal homepage: www.elsevier.com/locate/jorganchem
Note
Cationic iridium–BINAP complex-catalyzed addition of aryl ketones to alkynes
and alkenes via directed C–H bond cleavage
*
Kyoji Tsuchikama, Mitsugu Kasagawa, Yu-Ki Hashimoto, Kohei Endo, Takanori Shibata
Department of Chemistry and Biochemistry, School of Advanced Science and Engineering, Waseda University, Okubo, Shinjuku, Tokyo 169-8555, Japan
a r t i c l e i n f o
a b s t r a c t
Article history:
Cationic Ir complex ([Ir(cod)2]BF4 + BINAP) catalyzed the addition of ortho-C–H bonds in aryl ketones to
alkynes, which gave alkenylated products in good to high yield. Styrene derivatives were good substrates,
and the enantioselective addition to norbornene was also described.
Received 4 August 2008
Received in revised form 22 September
2008
Accepted 25 September 2008
Available online 8 October 2008
Ó 2008 Elsevier B.V. All rights reserved.
Keywords:
Iridium
C–H bond cleavage
Ketone
Alkyne
Alkene
1. Introduction
the high catalytic activity in the addition of aryl ketones to alkynes
[6]. The additions to several alkenes are also reported.
The transition metal-catalyzed inactive C–H bond functionaliza-
tion is an attractive process from both synthetic and atom-eco-
nomical points of view, because it can eliminate the pre-
activation step of substrates and reduce waste by-products [1].
Especially, Murai’s report [2a], where ortho-C–H bonds in aryl ke-
tones were added to olefins catalyzed by a ruthenium complex,
opened a new frontier in highly selective C–H bond activation
using directing groups such as carbonyl and imine [2]. In most of
these examples, transition metal complexes with monodentate li-
gands were used and the examples of catalysts with bidentate li-
gands were few [3].
2. Results and discussion
2.1. Optimization of the reaction conditions
We chose diphenylacetylene (1a) and acetophenone (2a) as
model substrates, and examined several Rh and Ir catalysts in re-
fluxed 1,2-dichloroethane (DCE) for 20 h (Table 1). [Rh(bip-
hep)]BF4, which was prepared in situ from [Rh(cod)2]BF4 and
BIPHEP, and pre-treated with hydrogen gas to exclude 1,5-cyclo-
octadiene (COD), gave a low conversion (entry 1). Notably, the
replacement of Rh with Ir dramatically increased the conversion
ratio and yield (entry 2). Moreover, the exclusion of COD was found
to be unnecessary: [Ir(cod)2]BF4 and BIPHEP gave hydroarylative
product 3aa with high yield along with a small amount of dialke-
nylated product 4aa (entry 3). rac-BINAP was more effective and
product 3aa was afforded in high yield as a sole stereoisomer
(entry 4). In the case of monodentate ligands such as triphenyl
and tricyclohexyl phosphines, and other bidentate ones such as
1,2-bis(2,5-dimethylphospholano)benzene (MeDUPHOS), most
substrates were recovered and the adducts could not be detected
under the same reaction conditions. These results mean that
Ir–bidentate biaryl phosphine complex possesses high catalytic
activity for the present reaction. Actually, the catalyst loading
could be lowered to 1 mol%, which also achieved the high yield
(entry 5). We decided to apply the reaction conditions of Entry 4
for further investigation.
We previously reported that the cationic Rh-BIPHEP (BIPHEP:
2,20-bis(diphenylphosphino)-1,10-biphenyl)
complex-catalyzed
hydroarylative cyclization of diynes and enynes with aryl ketones
[4]. We assumed that the bond cleavage of the ortho-C–H bonds
in aryl ketones is an initial step of the cyclization [5]. In the course
of our mechanistic studies, Rh-BIPHEP was also found to be an ac-
tive catalyst in the addition of benzophenone to diphenylacetylene,
which encouraged us to consider that cationic transition metal–
diphosphine complex could catalyze directed C–H bond function-
alization. We here disclose that cationic Ir–BINAP complex exhibits
* Corresponding author. Tel./fax: +81 3 5286 8098.
E-mail address: tshibata@waseda.jp (T. Shibata).
0022-328X/$ - see front matter Ó 2008 Elsevier B.V. All rights reserved.
doi:10.1016/j.jorganchem.2008.09.065

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K. Tsuchikama et al. / Journal of Organometallic Chemistry 693 (2008) 3939–3942
Table 1
Screening of reaction conditions.
Ph
Ph
Ph
O
O
[M(cod)2]BF4 (5 mol%)
Ligand (5 mol%)
Ph
O
Me
Ph
Ph
Ph
Me
DCE, reflux, 20 h
Me
1a
2a
(2 equiv)
Ph
3aa
4aa
Entry
M
Ligand
Yield of 3aa/%a (E/Z)b
Yield of 4aa/%a
1c
2c
3
Rh
Ir
Ir
Ir
Ir
BIPHEP
BIPHEP
BIPHEP
rac-BINAP
rac-BINAP
22 (15/1)
63 (1/1.8)
NDd
NDd
6
15
16
74 (7.4/1)
4
83 (75)e (>20/1)
80 (13/1)
5f
a
Yield was determined by 1H NMR integration relative to 1,1,2,2-tetrachloroethane as an internal standard.
b
c
d
e
f
The stereochemistry of 3aa was determined by the comparison of 1H NMR analysis of that of 3ai in Table 2.
1,5-Cyclooctadiene (cod) in the metal catalyst was excluded prior to the reaction.
Not detected.
Isolated yield.
The catalyst (1 mol%) was loaded.
2.2. Examination of several aryl ketones with alkynes
amount of the corresponding adduct (entries 4–6). Benzophenone
(2h) and tert-butyl phenyl ketone (2i) were submitted to the reac-
tion and the sole stereoisomers were obtained with high to quan-
titative yield (entries 7 and 8). The stereochemistry of adducts 3ah
and 3ai was determined to be E by X-ray crystallography [7], which
supports that the present reaction would involve carbonyl-directed
ortho-C-H bond cleavage of aryl ketones and syn-addition to
diphenylacetylene.
We examined the addition of several aryl ketones to alkyne 1a
(Table 2). Various substituents at the para position of acetophe-
none were tolerable in the present reaction: p-methyl, p-methoxy,
and p-trifluoromethyl groups did not retard the reaction and good
conversions to mono and dialkenylated products were achieved
(entries 1–3). However, substituents at the ortho position signifi-
cantly affected the reactivity: tetralone (2e) and o-methoxyaceto-
phenone (2f) provided the hydroarylative products in high yields
but o-trifluoromethylacetophenone (2g) did not give detectable
1-Phenyl-2-(trimethylsilyl)acetylene (1b) also reacted with ke-
tone 2f: adduct 3bf was obtained in moderate yield along with an
inseparable isomer Eq. (1) [8,9].
Table 2
Direct addition of ortho-C–H bonds of aryl ketones 2 to diphenylacetylene (1a).
Ph
Ph
Ph
R1
O
Ph
O
[Ir(cod)2]BF4 (5 mol%)
rac-BINAP (5 mol%)
O
Me
Ph
R2
1a
R2
DCE, reflux, 20 h
R1
R1
2
Ph
3
(2 equiv)
4
Entry
R1
R2
2
Yield of 3/%a (E/Z)b
Yield of 4/%c
1
2
3
4
5
6
7e
8
p-Me
p-OMe
p- CF3
H
o-OMe
o-CF3
H
Me
Me
Me
2b
2c
2d
2e
2f
2g
2h
2i
67 (3ab) (5.8/1)
72 (3ac) (>20/1)
59 (3ad) (>20/1)
26 (4ab)
20 (4ac)
10 (4ad)
–
ꢀ(CH2)3ꢀ
Quant. (3ae) (5.4/1)
Quant. (3af) (>20/1)
NDd
Me
–
–
Me
Ph
t-Bu
Quant. (3ah) (>20/1)f
84 (3ai) (>20/1)f
NDd
NDd
H
a
Isolated yield.
b
c
d
e
f
The stereochemistry of adduct 3 was determined by the comparison of 1H NMR analysis of that of 3ai in Entry 8.
Yield was determined by 1H NMR integration relative to 1,1,2,2-tetrachloroethane as an internal standard.
Not detected.
The reaction time is 6 h.
The stereochemistry was determined to be E by X-ray crystallography.

K. Tsuchikama et al. / Journal of Organometallic Chemistry 693 (2008) 3939–3942
3941
TMS
Ph
[Ir(cod)2]BF4 (5 mol%)
rac-BINAP (5 mol%)
O
inseparable isomer
(18%)
TMS
Ph
2f
ð1Þ
DCE, reflux, 20 h
Me
(2 equiv)
1b
OMe
3bf: 66%
2.3. The hydroarylation to alkenes including an enantioselective
reaction
ined under an argon atmosphere. IR spectra were recorded with
a JASCO FT/IR-4100 spectrometer. NMR spectra were recorded
with a JEOL AL-400 and Lambda 500 spectrometer using tetra-
methylsilane as an internal standard and CDCl3 as a solvent.
High-resolution mass spectra were measured on a JEOL JMS-
SX102A with FAB (Fast atomic bombardment) method.
Alkenes were also applicable to the present reactions using the
cationic Ir–diphosphine complex. Styrene derivatives gave corre-
sponding adducts with moderate regioselectivity, where tetra-
kis[3,5-bis(trifluoromethyl)phenyl]borate (BARF) as
a counter
anion of iridium complex and higher temperature were required
to achieve good yields Eq. (2) [10]. Norbornene (8) was also found
to be a good substrate: the enantioselective addition of o-methyl-
acetophenone (2i) to norbornene was achieved using (R)-MeO-BIP-
HEP (2,20-bis(diphenylphosphino)-6,60-dimethoxy-1,10-biphenyl)
as a chiral ligand Eq. (3) [3a].
4.2. Typical experimental procedure
Entry 4 in Table 1: Under an atmosphere of argon, [Ir(cod)2]BF4
(2.5 mg, 5 lmol) and rac-BINAP (3.1 mg, 5 lmol) were placed in a
Schlenk tube. After addition of alkyne 1a (18.0 mg, 0.1 mmol), aryl
ketone 2a (23 mL, 0.2 mmol), and degassed DCE (0.2 mL), the solu-
Ar
Ar
O
O
[Ir(cod)2]BARF (5 mol%)
rac-BINAP (5 mol%)
Me
OMe
Me
2f
ð2Þ
Ar
toluene, reflux, 40 h
5a-c
OMe
(5 equiv)
6
7
5a (Ar = Ph)
6fa/7fa: 75% (5/1)
6fb/7fb: 86% (3/1)
6fc/7fc: 70% (7/1)
p
H4)
5b (Ar = -Me-C6
p
5c (Ar = -F-C6H4)
O
[Ir(cod)2]BF4 (5 mol%)
(R)-MeO-BIPHEP (5 mol%)
Me
DCE, reflux, 20 h
Ar
ð3Þ
9
Me
8
58%, 70% ee
(Ar = 2-acetyl-
3-methylphenyl)
2j
(2 equiv)
tion was heated at reflux temperature for 20 h. The resultant mix-
ture was filtered through a silica pad, and dried in vacuo. The crude
products were purified by thin-layer chromatography (hexane/
AcOEt = 10/1) to give analytically pure 3aa (75%, E/Z = >20/1).
1-(2-(1,2-diphenylvinyl)phenyl)ethanone (3aa): 1H NMR
(400 MHz) d = 2.36 (s, 3H), 6.58 (s, 1H), 7.08–7.49 (m, 14H); 13C
NMR (125 MHz) d = 30.0, 127.2, 127.5, 127.7, 127.7, 128.1, 128.3,
129.4, 130.2, 130.7, 130.7, 131.8, 137.0, 139.7, 141.3, 141.7,
143.1, 204.2; IR (acetone) 1689, 762, 708 cmꢀ1; HRMS (FAB+) for
M+1 found m/z 299.1436, Calc. for C22H19O: 299.1436.
3. Conclusion
In summary, we have demonstrated the catalytic activity of cat-
ionic iridium–bidentate phosphine complex in carbonyl-directed
C–H bond cleavage. Alkenes could be also used and the enantiose-
lective reaction was accomplished in the reaction with norbornene.
Further studies on the applications of this catalytic system are in
progress.
4. Experimental
4.1. General
Acknowledgements
Anhydrous 1,2-dichloroethane and toluene are commercially
available. They were dried over molecular sieves 4A (MS 4A) and
degassed by argon bubbling before use. All reactions were exam-
This research was supported by a Waseda University Grant for
Special Research Projects. We also thank the Japan Society for the
Promotion of Science for the fellowship support to K.T.

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K. Tsuchikama et al. / Journal of Organometallic Chemistry 693 (2008) 3939–3942
(n) K. Ueura, T. Satoh, M. Miura, Org. Lett. 9 (2007) 1407;
Appendix A. Supplementary material
(o) K. Ueura, T. Satoh, M. Miura, J. Org. Chem. 72 (2007) 5362.
[3] The examples using diphosphine ligands: (a) R. Aufdenblatten, S. Diezi, A.
Togni, Monatsh. Chem. 131 (2000) 1345;
Supplementary material associated with this article can be
found, in the online version, at doi:10.1016/j.jorganchem.2008.
09.065.
(b) R. Dorta, A. Togni, Chem. Commun. (2003) 760;
The examples using phosphine–olefin ligands: (c) J.C. Lewis, A.M. Berman, R.G.
Bergman, J.A. Ellman, J. Am. Chem. Soc. 130 (2008) 2493.
[4] K. Tsuchikama, Y. Kuwata, Y.-K. Tahara, Y. Yoshinami, T. Shibata, Org. Lett. 9
(2007) 3097.
[5] The same type reaction was independently reported and the authors proposed
the mechanism containing a metallacycle intermediate: (a) K. Tanaka, Y. Otake,
A. Wada, K. Noguchi, M. Hirano, Org. Lett. 9 (2007) 2203;
(b) K. Tanaka, Y. Otake, H. Sagae, K. Noguchi, M. Hirano, Angew. Chem., Int. Ed.
120 (2008) 1332.
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