The synthesis and catalytic activity of the iridium(I) hydroquinone complex [(H2Q)Ir(COD)]+

Article abstract of DOI:10.1016/j.jorganchem.2008.09.066

The η⁶-hydroquinone iridium complex [(η⁶-H₂Q)Ir(COD)]BF₄ undergoes facile double deprotonation to the η⁴-quinone anionic analogue. The latter has been shown to be the first example of an iridium compl

Full text of DOI:10.1016/j.jorganchem.2008.09.066

Journal of Organometallic Chemistry 694 (2009) 52–56
Contents lists available at ScienceDirect
Journal of Organometallic Chemistry
journal homepage: www.elsevier.com/locate/jorganchem
The synthesis and catalytic activity of the iridium(I) hydroquinone
complex [(H2Q)Ir(COD)]+
Sang Bok Kim a, Chen Cai a, Marcus D. Faust a, William C. Trenkle b, Dwight A. Sweigart a,
*
a Department of Chemistry, Brown University, Providence, RI 02912, United States
b NIDDK, National Institutes of Health, DHHS, 9000 Rockville Pike, Bethesda, MD 20892, United States
a r t i c l e i n f o
a b s t r a c t
Article history:
The
the
g g
6-hydroquinone iridium complex [( 6-H2Q)Ir(COD)]BF4 undergoes facile double deprotonation to
g
4-quinone anionic analogue. The latter has been shown to be the first example of an iridium com-
Received 11 September 2008
Received in revised form 30 September
2008
Accepted 30 September 2008
Available online 8 October 2008
plex that catalyzes 1,4 conjugate addition reactions of aryl boronic acids to electron deficient olefins.
Ó 2008 Elsevier B.V. All rights reserved.
Keywords:
Iridium
Hydroquinone
Conjugate addition
1. Introduction
tion to enones (e.g., Eq. (1)) or of 1,4-addition to di-enones were
found with [Ir(COD)(OH)]2. In striking contrast to this behavior,
We have recently shown that the rhodium(I) hydroquinone
complex [(
6-H2Q)Rh(COD)]+ (1) serves as an excellent catalyst
the rhodium analogue [Rh(COD)(OH)]2 was shown to catalyze
addition to both enones and di-enones, with a preference for the
former electrophiles. Rhodium-catalyzed addition to di-enones
was found to be poorly regioselective, yielding a mixture of 1,4-
and 1,6-adducts [6]
g
precursor for the 1,2-addition of aryl boronic acids to aldehydes
and the 1,4 conjugate addition to electron deficient alkenes [1,2].
The active catalyst in these reactions, which can be conducted in
an aqueous medium, is believed to be the anionic
g
4-quinonoid
O
complex [(
g
4-Q)Rh(COD)]ꢀ (2 in Scheme 1). Complex 2 is readily
O
B(OH)2
1 (0.5 mol %)
LiOH (2 mol %)
formed from 1 by deprotonation and has been structurally charac-
terized with the cationic counterions Li+, K+, and Bu4N+ [1,3]. The
conjugate additions, typified by the reaction of 2-cyclohexen-1-
one shown in Eq. (1), generally give high yields, even with very
electron deficient aryl boronic acids, and occur with minimal pro-
to-deborylation and without formation of any Heck products.
The impressive results found with 1 as a catalyst precursor
prompted us to examine the chemistry of the iridium analogue,
+
(1)
DME/H2O (1:2)
50oC (1-3 h)
X
1.2 eq
1 eq
X
ð1Þ
Herein we report the synthesis of [(
g
6-H2Q)Ir(COD)]+ (3) and
[(g
6-H2Q)Ir(COD)]+ (3). The more than tenfold lower cost of irid-
demonstrate that it can indeed function as a catalyst precursor
for the 1,4-addition of aryl boronic acids to the electron deficient
olefin 2-cyclohexen-1-one, in analogy to the reaction shown in
Eq. (1). It is also disclosed that facile deprotonation of the hydro-
quinone ligand in 3 with a metal alkoxide allows the formation
of heterogeneous self-supporting quinonoid coordination net-
works and allows the covalent attachment of the iridium quino-
noid complex to silica surfaces. It should be noted that the
synthesis of iridium quinonoid complexes based on the fragment
Ir(Cp*)2+ has been reported previously, but without any applica-
tions [7].
ium in comparison to rhodium provides strong motivation for this
work. Iridium complexes are perhaps best known in catalytic
hydrogenations [4], can also be useful in catalytic C–C and C–X
(X = N, O, B) bond formation in allylic alkylation, cycloaddition,
and alkyne trimerization reactions, etc. [5]. Iridium-catalyzed con-
jugate addition of aryl boronic acids has been shown to occur with
electron deficient di-enones to give 1,6-adducts regiospecifically in
the presence of [Ir(COD)(OH)]2 [6]. However, no products of addi-
* Corresponding author. Tel.: +1 401 863 2767; fax: +1 401 863 9046.
E-mail address: Dwight_Sweigart@Brown.edu (D.A. Sweigart).
0022-328X/$ - see front matter Ó 2008 Elsevier B.V. All rights reserved.
doi:10.1016/j.jorganchem.2008.09.066

S.B. Kim et al. / Journal of Organometallic Chemistry 694 (2009) 52–56
53
- 2 H+
DME/D2O (1:8)
LiOH, 75 o
HO
OH
+
O
O
O
O
[(COD)IrCl]2
+
OH
HO
C
(ppt
)
>
t1/2 24 h
-
-
Rh(COD)
1
Rh(COD)
Ir(COD)
2
4
Scheme 3.
Scheme 1.
2. Results and discussion
Table 1
Solvent study of 1,4 conjugate additions catalyzed by 4.
The iridium hydroquinone complex [3]BF4 was easily synthe-
sized as an air-stable solid by reaction of commercially available
[Ir(COD)Cl]2 with AgBF4 and subsequent treatment with hydroqui-
none. 1H NMR spectra show that 3 is rapidly and reversibly depro-
tonated by two equivalents of LiOH in D2O to afford the anionic
quinone complex 4, which was found to be unchanged in this sol-
vent after 20 h at 75 °C. While stable indefinitely in CH2Cl2, com-
plex 3 in D2O at 50 °C is slowly attacked by the solvent to
liberate hydroquinone and generate the insoluble [(COD)Ir(-
D2O)2]BF4 according to Scheme 2. Interestingly, subsequent addi-
tion of LiOH to the reaction mixture was found to result in the
slow recoordination of the hydroquinone dianion to the iridium
to generate the quinone complex 4. In related experiments, the for-
mation of 4 from the reaction of hydroquinone with insoluble
[(COD)IrCl]2 in a basic aqueous medium according to Scheme 3
was attempted, but only small amounts of product were generated
after 20 h at 75 °C.
Our initial catalysis work focused substituting the iridium
hydroquinone complex 3 for the rhodium complex 1 in 1,4 conju-
gate addition to 2-cyclohexen-1-one using reaction conditions out-
lined in a previous publication, which consisted of 0.5 mol% of the
catalyst, 1.2 equivalents of boronic acid in DME and water [1,2].
While these conditions yielded no measurable product at 50 °C,
when the temperature was increased to 75 °C the desired product
was isolated in 29% yield. Although this discovery is noteworthy in
that it is the first example of an iridium catalyzed 1,4 conjugate
addition reaction, the isolated yield is well below practical limits
for the reaction. By comparison, rhodium(I) species catalyze the
reaction with the same starting materials in over 95% yield in less
than 3 h, leaving a great deal of improvement for the iridium cat-
alyst system.
O
O
0.5 mol % 3 , LiOH
(HO)2B
75 0C, 18 hr
Me
Me
Entry
Solvent system
% Yield
Entry
Solvent system
% Yield
1
2
3
4
DME/water (l:2)
THF/water (l:2)
Dioxane/water (l:2)
Water
29
18
0
5
6
7
8
EtOH
MeOH
0
0
10
36
MeOH/water (l:2)
Toluene/water (1:2)
26
did not work well for the iridium complex 3, which never produced
yields higher than 30%, even when 5 mol% of catalyst was used.
Although water was determined to be one of the better co-sol-
vents, reactions carried out in pure water with no organic co-sol-
vent gave only 26% yield.
With low catalyst loading, water and toluene appeared to offer
the best chance at improving the yield of reactions catalyzed by the
iridium complex based on its ability to solubilize the boronic acid
and maintain catalytic activity, in relation to the other solvents.
Conditions used were similar to the DME/water reaction, and the
desired product was isolated in 36% yield. A number of variables
were altered in an attempt to increase the isolated yield to levels
obtained using the rhodium catalyst system. First, the catalyst
loading was increased to 1 mol% and the amount of base was var-
ied to measure its effects on the reaction (Table 2). It was found
that small changes in the amount of base added, varying from 4
to 10 equivalents, had no visible effect on the catalyst or the reac-
tion in general, but when 200-fold excess base was used the yield
dropped by two thirds to 11%.
After the original DME/water solvent system failed to produce
reasonable yields,
a number of solvent combinations were
screened to find the best conditions for the iridium complex 3 (Ta-
ble 1). During this process several key differences between the irid-
ium 3 and rhodium 1 were observed. First of all, if the proton
source of the reaction was changed from water to an alcohol, such
as methanol or ethanol, the reactivity of the iridium complex de-
creased significantly. When rhodium (1) was used as the catalyst,
these changes had little to no effect on the overall yield of the reac-
tion. Second, ethereal solvents, which were the standard organic
co-solvents used for the rhodium catalyzed 1,4-addition reactions,
Since the concentration of base seemed to play a limited role in
determining the catalytic ability of the iridium catalyst 3, other
possible factors were examined, including catalyst loading, equiv-
alents of boronic acid and temperature (Table 3). Results showed
Table 2
Effect of base on the 1,4 conjugate addition reactions.
O
O
3, LiOH, 18 hr, 75oC
(HO)2B
D2O/LiOH
Toluene/H2O (1:2)
Me
HO
OH
+
O
O
-
HCl
Me
Ir(COD)
3
Ir(COD)
4
D2O
Entry
Mol% catalyst
Mol% base
% Yield
50o
t1/2 2 h
C
LiOH
50o
≅
C
≅
1
2
3
4
5
0.5
1
1
1
1
2
4
6
10
200
36
35
31
33
11
H2Q
+
[(COD)Ir(D2O)2]BF4
(ppt)
Scheme 2.

54
S.B. Kim et al. / Journal of Organometallic Chemistry 694 (2009) 52–56
Table 3
catalyst loading might have an advantageous effect, but even at
80 °C no appreciable improvements were observed.
Effect of several variables on the catalytic ability of 4.
To conclude our study of the iridium hydroquinone catalyst sys-
tem a number of different substrates were tried in an attempt to
establish the generality of the catalyst. A variety of different boro-
nic acids were subjected to the reaction conditions, and while it
was found that o-tolylboronic acid reacted in similar yield to p-tol-
ylboronic acid, while the other boronic acids either gave extremely
poor yields, or did not react at all (Table 4). When different conju-
gate acceptors were tested similar results were obtained, with
most not reacting at all (Table 5). The lone exception, ethylcinna-
mate, gave only 18% yield. All in all, it appears that the reaction
conditions developed above are quite specialized for the substrates
with which they were developed. The poor yields for the other sub-
strates also demonstrate the poor catalytic ability of the iridium in
relation to rhodium, which gives excellent yields with the majority
of the substrates tested in this study (with the m-nitrophenyl and
the olefinic boronic acid being the sole exceptions).
The most important information to come out of this research, is
the fact that iridium has been shown for the first time to be a cat-
alyst for 1,4 conjugate addition reactions. To date there have been
no other reports of iridium complexes being used in this fashion.
However, the poor reactivity of the iridium hydroquinone catalyst
may mean that further development in this area of catalysis will be
limited. Even though the iridium system may be far cheaper than
rhodium, the inability of the iridium benzoquinone to react with
abroad range of substrates gives the catalyst system a limited ap-
peal. While it may be possible under some conditions to obtain
high yields for 1,4 conjugate addition reactions catalyzed by irid-
ium, in all likelihood these conditions will not be as efficient as
those with rhodium, thus negating any cost benefit that might be
gained by choosing former.
O
O
3, LiOH, 18 hr
(HO)2B
Toluene/ H2O (1:2)
Me
Me
Entry
Mol% catalyst
Boronic acid (Eq)
Temperature (°C)
Yield
1
2
3
4
5
6
7
8
9
1
1
1
1
1
2
3
4
5
5
5
5
2
2
2
2.5
3
3
3
3
2
75
60
90
90
75
75
75
75
75
75
90
80
36
17
48
53
50
66
69
62
55
66
53
53
10
11
12
3
3
3
that lower temperatures hindered the catalyst’s ability to promote
the conjugate addition reaction, while increasing the temperature
to 90 °C improved the overall yield to 48% (Table 3, entry 3). With
the addition of greater amounts of boronic acid came further
improvements in yield, including 50% at 75 °C and 1 mol% catalyst
(entry 5). While all these results demonstrated significant
improvements, the iridium complex 3 was unable to produce re-
sults similar to those obtained using the rhodium catalyst. Finally,
the catalyst loading was varied between 1 mol% and 5 mol%, but
yields failed to increase appreciably with the amount of catalyst
added. Although no significant variation was observed between
2 mol% and 5 mol% catalyst loading, 3 mol% was selected as the
‘‘optimal” conditions as it gave the desired product in 69% yield
(entry 7). Further attempts to improve yield by increasing the reac-
tion temperature to 90 °C failed to produce useful results, and, in
fact, the yield decreased compared to reactions run at 75 °C. We at-
tempted to find a slightly higher temperature where the increased
3. Experimental
All reactions were carried out under N2 in flame-dried glass-
ware. [Ir(COD)Cl]2 was purchased from Strem Chemical Co. The
1H NMR spectra were recorded by Bruker (300 MHz) spectrometer.
Elemental analyses were performed by Quantitative Technologies
Inc.
Table 4
Iridium catalyzed 1,4 conjugate addition reactions with various boronic acids.
O
O
3, LiOH, 18 hr, 75oC
R
B(OH)2
Toluene/H2O (1:2)
R
Entry
1
Boronic acid
% Yield
57
Entry
3
Boronic acid
% Yield
18
B(OH)2
B(OH)2
Me
F
2
0
4
0
B(OH)2
B(OH)2
Cl
NO2

S.B. Kim et al. / Journal of Organometallic Chemistry 694 (2009) 52–56
55
Table 5
Iridium catalyzed 1,4 conjugate addition reactions with various electron deficient olefins.
Me
3, LiOH, 18 hr, 75oC
O
(HO)2B
R3
R
Toluene/H2O (1:2)
O
Me
R2
R3
R
R2
Entry
1
Substrate
% Yield
14
Entry
3
Substrate
% Yield
0
O
O
Ph
NHBn
Ph
OEt
2
0
4
0
O
O
Ph
H
Me
6-hydroquinoneÞIrðCODÞþBF4ꢀð3þBFꢀ4 Þ
genated H2O and was flushed with nitrogen and sealed. The result-
ing mixture was stirred at 75 °C for 18 h. Following this period of
time the reaction mixture was diluted in 4 ml of a 1:1 mixture of
ethyl acetate and hexanes, and washed sequentially with saturated
solution of NH4Cl (5 mL), 1 N NaOH and brine. The organic layers
were combined, dried over sodium sulfate, filtered through a silica
plug, and concentrated under reduced pressure to afford pure
product as a clear oil in 60% yield (56 mg).
-
3.1. Synthesis of +BF4 )ð
g
[Ir(COD)Cl]2 (0.20 g, 0.30 mmol) and AgBF4 (0.14 g, 0.71 mmol)
were dissolved in methylene chloride (5 mL) and acetone (1 ml),
respectively, and combined in a flame-dried one neck schlenk tube.
While stirring, a white precipitate of AgCl formed on the bottom of
the glassware. After 1 h, 1,4-hydroquinone (0.13 g, 1.2 mmol), dis-
solved in 2 mL of acetone, was added to the reaction mixture. After
stirring for 4 h at room temperature, the solvent was removed via a
rotary evaporator. The residue was dissolved in methylene chloride
(3 mL) and then filtered slowly (dropwise) through a celite plug
into 100 mL of diethyl ether. The resulting white precipitate was
filtered and washed three times with 10 mL aliquots of diethyl
ether. The product was recrystallized from methylene chloride by
cooling a solution in a freezer at ꢀ30 °C. The recrystallized product
was filtered through a fritted glass filter and dried under vacuum.
The isolated yield was 88% (0.25 g, 0.52 mmol). 1H NMR (CD2Cl2): d
8.40 (br.s, 2H), d 6.27 (s, hydroquinone ring, 4H), d 4.37 (br.s, ole-
finic COD protons, 4H), d 2.25 (m, aliphatic COD protons, 4H), d
2.12 (m, aliphatic COD protons, 4H).). 1H NMR (CD3OD): d 6.25
(s, 4H), d 4.30 (m, 4H), d 2.25(m, 4H), d 2.19 (m, 4H). Elemental
Anal. Calc.: C, 33.81; H, 3.65. Found: C, 33.78; H, 3.35%.
Acknowledgment
We are pleased to acknowledge the donors of the Petroleum Re-
search Fund, administered by the American Chemical Society, for
support of this research. This research was supported in part by
the Intramural Research Program of the NIH, National Institute of
Diabetes and Digestive and Kidney Disease (WCT).
Appendix A. Supplementary material
NMR of the products of the catalytic reactions. Supplementary
data associated with this article can be found, in the online version,
at doi:10.1016/j.jorganchem.2008.09.066.
6-hydroquinoneÞIrðCODÞþBF4ꢀð3þBFꢀ4 Þ
-
3.2. Deprotonation of +BF4 )ð
g
References
A solution of 3þBF4ꢀ in D2O was rapidly deprotonated by LiOH to
afford a stable solution of (
4-quinone)Ir(COD)ꢀ. 1H NMR (D2O): d
6.25 (s, 4H), d 4.38 (m, 4H), d 2.32(m, 4H), d 2.24 (m, 4H) after the
addition of LiOH changed to. d 5.38 (s, 4H), d 3.85 (m, 4H), d2.16 (m,
4H), d 2.04 (m, 4H). These changes are analogous to those seen
with the rhodium analogues, which have been fully characterized
[1,2].
[1] S.U. Son, S.B. Kim, J.A. Reingold, G.B. Carpenter, D.A. Sweigart, J. Am. Chem. Soc.
127 (2005) 12238.
[2] W.C. Trenkle, J.L. Barkin, S.U. Son, D.A. Sweigart, Organometallics 25 (2006)
3548.
[3] S.U. Son, J.A. Reingold, S.B. Kim, G.B. Carpenter, D.A. Sweigart, Angew. Chem., Int.
Ed 44 (2005) 7710.
[4] (a) R. Crabtree, Acc. Chem. Res. 12 (1979) 331;
(b) S. Bell, B. Wüstenberg, S. Kaiser, F. Menges, T. Netscher, A. Pfaltz, Science
311 (2006) 132–642;
g
(c) G. Stork, D.E. Kahne, J. Am. Chem. Soc. 105 (1983) 1072;
(d) K. Kallstrom, I. Munslow, P.G. Andersson, Chem. Eur. J. 12 (2006) 3194.
[5] (a) R. Takeuchi, S. Kezuka, Synthesis (2006) 3349;
(b) K. Fujita, K. Yamamoto, R. Yamaguchi, Org. Lett. 4 (2002) 2691;
(c) K. Taguchi, H. Nakagawa, T. Hirabayashi, S. Sakaguchi, Y. Ishii, J. Am. Chem.
Soc. 126 (2004) 72;
3.3. Typical catalytic procedure
A 1 dram vial fitted with a Teflon cap was charged with p-tolyl-
boronic acid (205 mg, 1.5 mmol, 3 equiv.), 2-cyclohexen-1-one
(48 mg, 0.5 mmol, 1.0 equiv.), and toluene (1.0 mL). To this mixture
was added the iridium catalyst 3 (7.5 mg, 0.015 mmol, 3 mol%) fol-
lowed by an aqueous LiOH solution (1.0 M, 0.090 mL, 0.090 mmol,
18 mol%). The headspace of the vial was filled with 2 mL of deoxy-
(d) J.-Y. Cho, M.K. Tse, D. Holmes, R.E. Maleczka Jr., M.R. Smith, Science 11
(2002) 305;
(e) R. Takeuchi, M. Kasho, Angew. Chem., Int. Ed. 36 (1997) 263;
(f) I. Matsuda, Y. Hasegawa, T. Makino, K. Itoh, Tetrahedron Lett. 41 (2000)
1405;
(g) I. Matsuda, Y. Hasegawa, T. Makino, K. Itoh, Tetrahedron Lett. 41 (2000) 1409;

56
S.B. Kim et al. / Journal of Organometallic Chemistry 694 (2009) 52–56
(h) D. Carmona, J. Ferrer, M. Lorenzo, F.J. Lahoz, I.T. Dobrinovich, L.A. Oro, Eur. J.
Inorg. Chem. (2005) 1657;
(i) T. Nishimura, Y. Yauhara, T. Hayashi, J. Am. Chem. Soc. 129 (2007) 7506.
[6] T. Nishimura, Y. Yasuhara, T. Hayashi, Angew. Chem., Int. Ed. 45 (2006) 5164.
[7] (a) J.L. Bras, H. Amouri, J. Vaissermann, J. Organomet. Chem. 553 (1998) 483;
(b) J.L. Bras, H. Amouri, J. Vaissermann, J. Organometallics 17 (1998) 1116.