Isolation and crystal structures of both enol and keto tautomer intermediates in a hydration of an alkyne-carboxylic acid ester catalyzed by iridium complexes in water

Article abstract of DOI:10.1021/ja807254d

Hydration of tetrolic acid ethyl ester as an alkyne-carboxylic acid ester catalyzed by an Ir-aqua complex [Ir^IIICp*(bpy)(OH ₂)]²⁺ (1, Cp* = η⁵-C ₅Me₅, bpy = 2,2′-bipyridine) in water provides ethyl acetoacetate as a β-keto acid ester. We report the successful isolation of both an Ir-enol tautomer intermediate [Ir^IIICp*(bpy){CH ₃C(OH)=CC(O)OC₂H₅}]⁺ (2) and an Ir-keto tautomer intermediate [Ir^IIICp*(bpy){CH ₃C(O)-CHC(O)OC₂H₅}]⁺ (3) in the catalytic hydration by optimizing the conditions of the isolation, such as pH of the solution, reaction time, and selection of counteranions. The structures of the enol and keto complexes with characteristic Ir-(sp²carbon) bond and Ir-(sp³ carbon) bond, respectively, were unequivocally determined by X-ray analysis, IR, electrospray ionization mass spectrometry (ESI-MS), and NMR studies including ¹H, ¹³C, distortionless enhancement by polarization transfer (DEPT) and correlation spectroscopy (COSY) experiments. It was confirmed that the hydration of tetrolic acid ethyl ester catalyzed by 2 or 3 as initial catalysts provides ethyl acetoacetate. Mechanism of the catalytic hydration of tetrolic acid ethyl ester as an alkyne-carboxylic acid ester is discussed based on isotopic labeling experiments with the Ir-enol and Ir-keto tautomers.

Full text of DOI:10.1021/ja807254d

Published on Web 11/14/2008
Isolation and Crystal Structures of Both Enol and Keto
Tautomer Intermediates in a Hydration of an
Alkyne-Carboxylic Acid Ester Catalyzed by Iridium
Complexes in Water
Hironobu Kanemitsu,† Keiji Uehara,‡ Shunichi Fukuzumi,‡ and Seiji Ogo*,†
Center for Future Chemistry, Kyushu UniVersity, 744 Moto-oka, Nishi-ku,
Fukuoka 819-0395, Japan, Core Research for EVolutional Science and Technology (CREST),
Japan Science and Technology Agency (JST), Kawaguchi Center Building, 4-1-8, Honcho,
Kawaguchi-shi, Saitama 332-0012, Japan, and Department of Material and Life Science,
DiVision of AdVanced Science and Biotechnology, Graduate School of Engineering, Osaka
UniVersity, Suita, Osaka 565-0871, Japan
Received September 22, 2008; E-mail: ogo-tcm@mbox.nc.kyushu-u.ac.jp
Abstract: Hydration of tetrolic acid ethyl ester as an alkyne-carboxylic acid ester catalyzed by an Ir-aqua
complex [IrIIICp*(bpy)(OH2)]2+ (1, Cp* ) η5-C5Me5, bpy ) 2,2′-bipyridine) in water provides ethyl acetoacetate
as a ꢀ-keto acid ester. We report the successful isolation of both an Ir-enol tautomer intermediate
[IrIIICp*(bpy){CH3C(OH)dCC(O)OC2H5}]+ (2) and an Ir-keto tautomer intermediate [IrIIICp*(bpy){CH3C(O)-
CHC(O)OC2H5}]+ (3) in the catalytic hydration by optimizing the conditions of the isolation, such as pH of
the solution, reaction time, and selection of counteranions. The structures of the enol and keto complexes
with characteristic Ir-(sp2carbon) bond and Ir-(sp3 carbon) bond, respectively, were unequivocally
determined by X-ray analysis, IR, electrospray ionization mass spectrometry (ESI-MS), and NMR studies
including 1H, 13C, distortionless enhancement by polarization transfer (DEPT) and correlation spectroscopy
(COSY) experiments. It was confirmed that the hydration of tetrolic acid ethyl ester catalyzed by 2 or 3 as
initial catalysts provides ethyl acetoacetate. Mechanism of the catalytic hydration of tetrolic acid ethyl ester
as an alkyne-carboxylic acid ester is discussed based on isotopic labeling experiments with the Ir-enol
and Ir-keto tautomers.
Introduction
Catalytic hydration of alkynes is an atom-economically useful
reaction to synthesize valuable carbonyl compounds such as
ketones (eq 1).1-4 A variety of transition metal catalysts have
so far been developed for regioselective hydration of alkynes
into ketones.5-17 It has been proposed that the hydration
proceeds through enol and keto tautomers of organometallic
intermediates with metal-carbon (M-C) bonds (eq 2).18 It is
well-known that the enol intermediate immediately rearranged
to the corresponding keto tautomers.18
† Kyushu University, CREST, JST.
‡ Osaka University.
Frontier works on observation and isolation of such enol and
keto complexes have been performed so far.19-24 There are a
(1) (a) Torst, B. M. Science 1991, 254, 1471–1477. (b) Torst, B. M.
Angew. Chem., Int. Ed. Engl. 1995, 34, 259–281. (c) Torst, B. M.
Acc. Chem. Res. 2002, 35, 695–705.
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3159.
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Countryman, R. M. J. Chem. Soc., Dalton Trans. 1983, 1619–1624.
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2008 American Chemical Society
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A R T I C L E S
Kanemitsu et al.
quadrupole mass spectrometer (PE-Sciex) in positive detection
mode, equipped with an ion spray interface. The sprayer was held
at a potential of +5.0 kV, and compressed N2 was employed to
assist liquid nebulization. The orifice potential was maintained at
+20 V. A Nissin magnetic stirrer (Model SW-R800) was used.
pH Adjustment. In a pH range of 1-8, pH values of the
solutions were determined by a pH meter (TOA, HM-18E) equipped
with a pH combination electrode (TOA, GC-5015C). The pH of
the solution was adjusted by using 1 M H2SO4/H2O (pH 1-3), 0.1
M CH3COOH/CH3COONa (pH 4-5), and 0.2 M Na2HPO4/
NaH2PO4 (pH 6-8) solutions. Below pH 1, the pH of the solution
was estimated by the concentration of the solution; for example,
pH values of 0.1 and 1.0 M H2SO4/H2O were estimated to be 1.3
and 0.3, respectively. Values of pD were corrected by adding 0.4
to the observed values (pD ) pH meter reading + 0.4).26
few examples of isolation of keto complexes as intermediates
in catalytic hydration of alkynes.19,21 On the other hand,
however, there is no example of isolation of enol complexes as
intermediates in catalytic hydration of alkynes as follows. Taube
and co-workers22 and Bergman and co-worker23 have isolated
enol complexes from a stoichiometric reaction with water and
2-butyne and a stoichiometric insertion of dimetyl acetylene-
dicarboxylate, respectively, but not from catalytic hydration of
alkynes. Recently, Laguna and co-workers reported a direct
observation of a Au-enol complex as an intermediate in
catalytic hydration of phenylacetylene by NMR at low temper-
ature.24 Thus, the isolation and crystallization of enol intermedi-
ates in catalytic hydration of alkynes has yet to be achieved.
Here, we report the successful isolation and crystallization
of [IrIIICp*(bpy){CH3C(OH)dCC(O)OC2H5}]+ (2, Cp* ) η5-
C5Me5, bpy ) 2,2′-bipyridine) and [IrIIICp*(bpy){CH3C(O)-
CHC(O)OC2H5}]+ (3), which are enol and keto tautomer
intermediates (eq 3) in a hydration of tetrolic acid ethyl ester
as an alkyne-carboxylic acid ester catalyzed by an Ir-aqua
complex [IrIIICp*(bpy)(OH2)]2+ (1). The structures of 2 and 3
with characteristic Ir-C bonds were unequivocally determined
by X-ray analysis. We also report the catalytic hydration of
tetrolic acid ethyl ester into a ketone (ethyl acetoacetate as a
ꢀ-keto acid ester) with not only the Ir-aqua complex 1 but
also the Ir-enol complex 2 or the Ir-keto complex 3 as initial
catalysts (eq 4).
[IrIIICp*(bpy){CH3C(OH)dCC(O)OC2H5}]CF3SO3
(2·CF3SO3). A reaction of [IrIIICp*(bpy)(OH2)](SO4) (1·SO4, 100
mg, 168 µmol) with tetrolic acid ethyl ester (30 µL, 260 µmol) in
H2O (9 mL) at pH 6.5 (0.2 M Na2HPO4/NaH2PO4 buffer) at 25 °C
for 1 min provided an orange solution of [2]2 ·SO4. To the solution
was added CF3SO3Na (103 mg, 600 µmol) at pH 6.5 in H2O (300
µL), and the mixture was stirred for 10 s to afford an orange powder
of 2·CF3SO3, which was collected by filtration, washed with H2O,
1
and dried in vacuo (yield 37.4% based on 1·SO4): H NMR of
2·CF3SO3 (300 MHz, in DMSO-d6, reference to TMS, 25 °C) δ
3
0.86 (t, JH,H ) 6.9 Hz, 3H), 1.65 {s, 15H}, 1.69 (s, 3H), 3.41 (q,
3JH,H ) 6.9 Hz, 2H), 7.41 {br s, 1H}, 7.70 (t, 3JH,H ) 6.3 Hz, 2H),
8.17 (t, 3JH,H ) 7.8 Hz, 2H), 8.66 (d, 3JH,H ) 7.5 Hz, 2H), 8.78 (d,
3JH,H ) 5.7 Hz, 2H); 13C{1H} NMR of 2·CF3SO3 (in DMSO-d6,
reference to TMS, 25 °C) δ 7.382 {s; η5-C5(CH3)5}, 14.05 {s;
CH3CH2}, 29.64 {s; C(OH)CH3}, 58.19 {s; CH3CH2}, 90.57 {s;
η5-C5(CH3)5}, 124.18 {s; CH of bpy}, 128.66 {s; CH of bpy},
139.44 {s; CH of bpy}, 151.93 {s; CH of bpy}, 155.22 {s; C of
bpy}. Anal. Calcd for C27H32N2F3IrO6S: C, 42.57; H, 4.23; N, 3.67.
Found: C, 42.74; H, 4.43; N, 3.72.
[IrIIICp*(bpy){CH3C(O)CHC(O)OC2H5}]PF6 (3·PF6). A reac-
tion of 1·SO4 (100 mg, 168 µmol) with tetrolic acid ethyl ester
(30 µL, 260 µmol) in H2O (9 mL) at pH 6.5 (0.2 M Na2HPO4/
NaH2PO4 buffer) at 25 °C for 15 min gave a yellow solution of
[3]2 ·SO4. To the solution was added NH4PF6 (48.9 mg, 300 µmol)
in H2O (300 µL) at pH 6.5 to form a yellow powder of 3·PF6,
which was collected by filtration (yield 52% based on 1·SO4): 1H
NMR of 3·PF6 (300 MHz, in CDCl3, reference to TMS, 25 °C) δ
1.12 (t, 3JH,H ) 3.9 Hz, 3H), 1.25 {s, 3H}, 1.61 {s, 15H}, 3.55 (m,
2H), 4.55 (s, 1H), 7.70 (m, 2H), 8.14 (m, 2H), 8.33 (d, 3JH,H ) 6.3
3
3
Hz, 1H), 8.43 (d, JH,H ) 6.3 Hz, 1H), 8.47 (d, JH,H ) 8.1 Hz,
2H); 13C{1H} NMR of 3·PF6 (300 MHz, in acetone-d6, reference
to TMS, 25 °C) δ 7.925 {s; η5-C5(CH3)5}, 14.53 {s; CH3CH2},
30.32 {s; C(O)CH3}, 36.28 {s; CH}, 51.19 {s; CH3CH2}, 91.92
{s; η5-C5(CH3)5}, 124.89 {s; CH of bpy}, 129.25 {s; CH of bpy},
Experimental Section
Materials and Methods. All experiments were carried out under
an air atmosphere. The aqua complex [IrIIICp*(bpy)(OH2)](SO4)
(1·SO4) was prepared by the method described in the literature.25
Tetrolic acid ethyl ester was purchased from Tokyo Kasei Kogyo
Co. Ltd. and was used as received. Ammonium hexafluorophosphate
(NH4PF6) and sodium trifluoromethanesulfonate (NaCF3SO3) were
purchased from Wako Pure Chemical Industries, Ltd. without
further purification. The manipulations in the acidic media were
carried out with plastic and glass apparatus (without metals). The
spectra of 1H and 13C{1H} NMR, DEPT-135, and H-H and C-H
COSY (HETCOR) were recorded on JEOL-JNM-AL300 spectrom-
eter at 25 °C. IR spectra were recorded on a Thermo Nicolet 8700
FT-IR instrument using 2 cm-1 standard resolution at ambient
temperature. ESI-MS data were collected on an API 365 triple
(19) (a) Matsumoto, K.; Nagai, Y.; Matsunami, J.; Mizuno, K.; Abe, T.;
Somazawa, R.; Kinoshita, J.; Shimura, H. J. Am. Chem. Soc. 1998,
120, 2900–2907. (b) Ochiai, M.; Lin, Y. S.; Yamada, J.; Misawa, H.;
Arai, S.; Matsumoto, K. J. Am. Chem. Soc. 2004, 126, 2536–2545.
(20) (a) Arikawa, Y.; Nishimura, Y.; Kawano, H.; Onishi, M. Organome-
tallics 2003, 22, 3354–3356. (b) Arikawa, Y.; Nishimura, Y.; Ikeda,
K.; Onishi, M. J. Am. Chem. Soc. 2004, 126, 3706–3707. (c)
Nishimura, Y.; Ikeda, K.; Inoue, T.; Onishi, M. Dalton Trans. 2005,
5, 930–937.
(21) Ogo, S.; Uehara, K.; Abura, T.; Watanabe, Y.; Fukuzumi, S. J. Am.
Chem. Soc. 2004, 126, 16520–16527.
(22) Harman, W. D.; Dobson, J. C.; Taube, H. J. Am. Chem. Soc. 1989,
111, 3061–3062.
(23) Woerpel, K. A.; Bergman, R. G. J. Am. Chem. Soc. 1993, 115, 7888–
7889.
(15) Mizushima, E.; Sato, K.; Hayashi, T.; Tanaka, M. Angew. Chem., Int.
Ed. 2002, 41, 4563–4565.
(24) Casado, R.; Contel, M.; Laguna, M.; Romero, P.; Snaz, S. J. Am. Chem.
Soc. 2003, 125, 11925–11935.
(16) Easton, N. R.; Cassady, D. R.; Dillard, R. D. J. Org. Chem. 1965, 30,
3084–3088.
(25) Ogo, S.; Makihara, N.; Kaneko, Y.; Watanabe, Y. Organometallics
2001, 20, 4903–4910.
(17) Damiano, J. P.; Postel, M. J. Organomet. Chem. 1996, 522, 303–305.
(18) March, J. AdVanced Organic Chemistry: Reactions, Mechanisms, and
Structures, 4th ed.; John Wiley & Sons: New York, 1992; p 762.
(26) (a) Glasoe, P. K.; Long, F. A. J. Phys. Chem. 1960, 64, 188–190. (b)
Mikkelsen, K.; Nielsen, S. O. J. Phys. Chem. 1960, 64, 632–637.
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Hydration of an Alkyne-Carboxylic Acid Ester
A R T I C L E S
Figure 1. 1H NMR spectrum of 2·CF3SO3 in DMSO-d6 at 25 °C. TMS,
reference with the methyl proton resonance set at 0.00 ppm.
140.32 {s; CH of bpy}, 153.04 {s; CH of bpy}, 156.86 {s; C of
bpy}. Anal. Calcd for C26H32N2O3IrPF6: C, 41.13; H, 4.26; N, 3.75.
Found: C, 41.21; H, 4.25; N, 3.69.
Figure 2. (a) Positive-ion ESI mass spectrum of 2·CF3SO3 in MeOH. (b)
Signal at m/z 613.2 for [2]+. Red circles, calculated isotopic distribution
[2]+. (c) Signal at m/z 614.2 for D-labeled [2]+. Red circles, calculated
isotopic distribution [D-labeled 2]+.
Typical Procedure for the pH-Dependent Hydration of
Tetrolic Acid Ethyl Ester with the Ir Complexes 1, 2, or 3. The
pH-dependent hydration of tetrolic acid ethyl ester catalyzed by
1·SO4 in water was investigated at 25 °C. The pH of the solution
of 1·SO4 (0.12 mg, 0.2 µmol) in H2O (2 mL) was adjusted by
using 0.1 M H2SO4/H2O, 0.1 M CH3COOH/CH3COONa and 0.2
M Na2HPO4/NaH2PO4. Five hundred equivalents of tetrolic acid
ethyl ester (11.5 µL, 0.1 mmol) was added to the solution. The
mixture was stirred for 1 h. It was extracted by CDCl3 with 1,4-
dioxane as the internal standard. The hydration of tetrolic acid ethyl
ester (11.5 µL, 0.1 mmol) with 2·CF3SO3 (0.15 mg, 0.2 µmol) or
3·PF6 (0.15 mg, 0.2 µmol) in H2O (2 mL) was investigated at pH
1.3 at 25 °C. The turnover numbers (TONs ) the number of moles
of ethyl acetoacetate as the product of the hydration formed per
moles of 1, 2, or 3) were determined by 1H NMR. It was confirmed
that no reaction occurred in the absence of complexes 1, 2, or 3.
X-ray Crystallographic Analysis. Crystallographic data for
2·CF3SO3 and 3·PF6 have been deposited with the Cambridge
Crystallographic Data Center as Supplementary Publication Nos.
CCDC-688408 and 688409, respectively. Copies of the data can
be obtained free of charge on application to CCDC, 12 Union Road,
Cambridge CB2 1EZ, UK {fax: (+44) 1223-336-033; e-mail:
deposit@ccdc.cam.ac.uk}. Measurements were made on Rigaku/
MSC Mercury CCD diffractometer with graphite monochromated
Mo KR radiation (λ ) 0.7107 Å) and Rigaku/MSC Saturn CCD
diffractometer with confocal monochromated Mo KR radiation (λ
) 0.7107 Å). Data were collected and processed using the
CrystalClear program (Rigaku). All calculations were performed
using the teXsan crystallographic software package of Molecular
Structure Corporation.
Figure 3. (a) IR spectrum of 2·CF3SO3 as a KBr disk. (b) IR spectrum of
D-labeled 2·CF3SO3 as a KBr disk. (c) IR spectrum of 3·CF3SO3 as a KBr
disk. A broad peak at around 3500 cm-1 was derived from water.
NMR spectrum of D-labeled 2·CF3SO3 (Figure S1), 13C{1H}
NMR (Figure S2), DEPT-135 (Figure S3), H-H COSY (Figure
S4), and C-H COSY (HETCOR) (Figure S5) spectra of
2·CF3SO3 are shown in the Supporting Information. A positive-
ion ESI mass spectrum of 2 · CF3SO3 in MeOH is shown in
Figure 2a. The prominent signal m/z 613.2 {relative intensity
(I) ) 100% in the range of m/z 200-1000} has a characteristic
distribution of isotopomers (Figure 2b) that matches well with
the calculated isotopic distribution (red circles) for [2]+. In an
IR spectrum in the 650-3800 cm-1 region as a KBr disk of
2 · CF3SO3 (Figure 3a), a prominent peak at 3339 cm-1 was
assigned to ν(O-H) that shifted to 2489 cm-1 by isotopic
substitution of H for D in the O-H group of the enol ligand
{CH3C(OH)dCC(O)OC2H5, Figure 3b}. The shift value (850
Results and Discussion
Isolation and Structure of the Enol Complex 2. The transient
Ir-enol intermediate 2 was successfully isolated as an orange
powder of 2·CF3SO3 by addition of CF3SO3Na to the solution
of the hydration of tetrolic acid ethyl ester with 1·SO4 in H2O
at pH 6.5 in a short time (1 × 103 s; see the section of
observation of keto-enol tautomerism by using 1H NMR). The
structure of 2·CF3SO3 was determined by NMR {1H and
13C{1H} NMR, DEPT-135, and H-H and C-H COSY (HET-
COR)}, ESI-MS, and IR. Figure 1 shows the 1H NMR spectrum
of 2·CF3SO3 in DMSO-d6. The signal at 1.65 ppm corresponds
1
to the Cp* protons {C5(CH3)5} of 2 · CF3SO3. The H NMR
spectrum of 2·CF3SO3 indicates the existence of a sp2 carbon
in 2, which agrees with the result of the X-ray analysis of 2. 1H
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A R T I C L E S
Kanemitsu et al.
Figure 5. (a) Positive-ion ESI mass spectrum of 3·PF6 in MeOH. (b) Signal
at m/z 613.2 for [3]+. Red circles, calculated isotopic distribution [3]+. (c)
Signal at m/z 614.2 for D-labeled [3]+. Red circles, calculated isotopic
distribution [D-labeled 3]+.
Figure 4. 1H NMR spectra of 3·PF6 (a) and D-labeled 3·PF6 (b) in CDCl3
at 25 °C. TMS, reference with the methyl proton resonance set at 0.00
ppm.
cm-1) agrees well with that expected by Hooke’s law calculation
for a pure OH stretching mode.27
Isolation and Structure of the Keto Complex 3. The water-
soluble aqua complex 1·SO4 reacts with tetrolic acid ethyl ester
in H2O, pH 6.5, at 25 °C for 15 min to give the water-soluble
keto complex [3]2 ·SO4. The stable keto complex 3 was isolated
as a yellow powder of 3 · PF6 by addition of NH4PF6 to the
solution of [3]2 ·SO4. The structure of 3·PF6 was established
by NMR {1H and 13C{1H} NMR, DEPT-135, and H-H and
C-H COSY (HETCOR)}, ESI-MS, and IR. Figure 4 shows
1H NMR spectra of 3·PF6 in CDCl3. The signal of the Cp*
protons of 3 was observed at 1.61 ppm. The Ir-keto complex
1
3 shows characteristic H NMR spectrum indicating the exist-
ence of a sp3 carbon in 3. 13C{1H} NMR (Figure S6), DEPT-
135 (Figure S7), H-H COSY (Figure S8), and C-H COSY
(HETCOR) (Figure S9) spectra of 3·PF6 are shown in the
Supporting Information. A positive-ion ESI mass spectrum of
3·PF6 in MeOH shows a prominent signal at m/z 613.2 (I )
100% in the range of m/z 200-1000, Figure 5a), which has a
characteristic distribution of isotopomers (Figure 5b) that
matches well with the calculated isotopic distribution (red
circles) for [3]+. An Ir-keto complex 3·CF3SO3 was prepared
by dissolving isolated 2·CF3SO3 in H2O. The solution was
evaporated and dried in vacuo to give 3·CF3SO3 as a hydro-
scopic powder, which was used for IR. The IR spectrum of
3·CF3SO3 (Figure 3c) showed no peak derived from ν(O-H),
which was observed at 3339 cm-1 in the IR spectrum of
2·CF3SO3 (Figure 3a). A prominent peak was observed at 1649
cm-1 in the IR spectrum of 3·CF3SO3 (Figure 3c), which was
Figure 6. ORTEP drawing of 2 with ellipsoids at 50% probability. The
counteranion (CF3SO3) is omitted for clarity.
assigned to ν(CdO). The IR spectrum of hydroscopic 3·CF3SO3
showed a broad peak at around 3500 cm-1 derived from water.
Crystal Structure of the Enol Complex 2. To a solution of
1·SO4 (10 mg, 16.8 µmol) was added CF3SO3Na (10.3 mg, 60
µmol) at pH 6.5 in H2O (0.9 mL). After the solution was added
to tetrolic acid ethyl ester (3 µL, 26 µmol) and left at rest,
complex 2·CF3SO3 was quickly crystallized in a few minutes.
ORTEP drawing of 2 is shown in Figure 6. Complex 2 adopts
distorted octahedral coordination that is surrounded by one Cp*,
one bpy, and one enol ligand. Complex 2 has the sp2 carbon
(C3 in Figure 6), as NMR studies imply the existence of sp2
carbon. The characteristic Ir1-C3 bond length is 2.100(4) Å.
The C2-C3 double bond length is 1.327(6) Å. They are close
to the Ir-C bond length and C-C double bond length observed
in IrCp*(PMe3)(Ph)[C(CO2Me)C(OH)(CO2Me)] {2.04(2),
(27) Nakamoto, K. Infrared and Raman Spectra of Inorganic and Coor-
dination Compounds, 5th ed.; Wiley: New York, 1997, and references
therein.
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Hydration of an Alkyne-Carboxylic Acid Ester
A R T I C L E S
Figure 9. The pH-dependent TONs of the formation of ethyl acetoacetate
in the reaction of 1·SO4 (0.2 µmol) with tetrolic acid ethyl ester (0.1 mmol)
in H2O (2.0 mL) at 25 °C for 1 h.
Figure 7. ORTEP drawing of 3 with ellipsoids at 50% probability. The
counteranion (PF6) and MeOH are omitted for clarity.
Table 1. Hydration of Alkyne-Carboxylic Acid Ethyl Esters to the
Corresponding ꢀ-Keto Acid Esters Catalyzed by Water-Soluble
Complexes 1·SO4, 2·CF3SO3, or 3·PF6 in Watera
Figure 8. Time-course of conversion from 2 (b) to 3 (O) in the reaction
of 1 with tetrolic acid ethyl ester in D2O at pD 6.5 at 25 °C monitored by
1H NMR. The red dotted line shows a limited period of time (1 × 103 s)
for the isolation of 2.
a The reaction was carried out pH 1.3 at 25 °C with alkyne
and 1.35(3) Å, respectively}.23 The angles of Ir1-C3-C2,
Ir1-C3-C4, and C2-C3-C4 are 114.7(3), 126.7(3), and
118.5(4)°, respectively. These results clearly indicate that C3
in 2 is sp2 carbon. The torsion angle between the least-squares
plane of bpy and that of an ester of the enol ligand is 164.1(1)°.
The distances of N1-O1, N2-O2, and N2-O3 (i.e., the
distance between the bpy ligand and the enol ligand of 2) are
3.244(5), 3.147(5), and 3.455(4) Å, respectively. The coordina-
tion geometry of 2 shows that the addition of water to the
carbon-carbon triple bond with 1 proceeds through a syn
addition (see the section of Mechanism of the Hydration of
Alkyne-Carboxylic Acid Esters).
Crystal Structure of the Keto Complex 3. A yellow crystal
of 3·PF6 used for X-ray analysis was obtained from MeOH/
diethyl ether. ORTEP drawing of 3 is shown in Figure 7.
Complex 3 adopts a distorted octahedral coordination that is
surrounded by one Cp*, one bpy, and one keto ligand. Complex
3 has the sp3 carbon (C3 in Figure 7), as shown in NMR spectra.
The characteristic Ir1-C3 (sp3 carbon) bond length of 3 is
2.211(3) Å, which is longer than the Ir1-C3 (sp2 carbon) bond
length of 2 {2.110(4) Å}. The C2-C3 bond length of 3 is
carboxylic acid esters in H2O.
1.469(5) Å, which is longer than that of 2 {1.327(6) Å}. The
Ir1-C3 length is close to the M-C bond length observed in
[Pt2(NH3)4{(CH3)3CCONH}2{CH(CH3)COCH3}](NO3)3 {2.146
(13) Å}19 and TpRuCl{CH2C(O)(p-CH3C6H4)}(NO) {Tp )
BH(prazol-1-yl)3} {2.151(2) Å}.20 The angles of Ir1-C3-C2,
Ir1-C3-C4, and C2-C3-C4 are 111.4(2), 108.6(2), and
116.8(3)°, respectively. C3 in 3 is sp3 carbon as described above.
The torsion angle between the least-squares plane of the bpy
ligand and that of carbonyl groups of the keto ligand is 15.4(2)°.
The distances of N1-O1, N2-O2, and N2-O3 (i.e., the
distance between the bpy ligand and the keto ligand of 3) are
2.985(3), 3.045(3), and 3.416(3) Å, respectively.
Observation of Keto-Enol Tautomerism by Using 1H
NMR. The reaction of 1·SO4 (10 mg, 16.8 µmol) with tetrolic
acid ethyl ester (3 µL, 26 µmol) in D2O (0.9 mL) at pD 6.5
(0.2 M Na2HPO4/NaH2PO4 buffer) at 25 °C was monitored by
1H NMR. The Ir-enol intermediate 2 was initially observed in
the reaction, and the subsequent keto-enol equilibrium (eq 3)
immediately afforded the Ir-keto intermediate 3 whose yields
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A R T I C L E S
Kanemitsu et al.
were determined by 1H NMR with 3-(trimethylsilyl)propionic-
2,2,3,3-d4 acid sodium salt (TSP) as the internal standard. Figure
8 shows the time course of conversion from the Ir-enol complex
2 to the Ir-keto complex 3 in the hydration of tetrolic acid
ethyl ester with 1. The red dotted line shows a limited period
time (1 × 103 s) for the isolation of 2. The keto-enol
tautmerization rate obeys first-order kinetics, and the rate
constant of conversion from 2 to 3 was determined to be 6.04
× 10-4 s-1 at 25 °C (Figures S10 and S11 in Supporting
Information).
Catalytic Hydration of Alkyne-Carboxylic Acid Esters
with 1, 2, or 3. Hydration of tetrolic acid ethyl ester as an
alkyne-carboxylic acid ester catalyzed by 1·SO4 provides ethyl
acetoacetate as a ꢀ-keto acid ester regioselectively (see the
section of Mechanism of the Hydration of Alkyne-Carboxylic
Acid Esters). The pH-dependent turnover numbers (TONs )
the number of moles of ethyl acetoacetate as the product of the
hydration formed per moles of 1) of the formation of ethyl
acetoacetate from the hydration of tetrolic acid ethyl ester with
1·SO4 shows a maximum around pH -1 (TON ) 382, Figure
9). In a pH range of -1 to 8, the lower is pH of the solution,
the faster is the rate of the hydration; that is the rate of the
hydration is dependent on H+ concentration. This is the reason
why the protonation of 3 gives ethyl acetoacetate to regenerate
the aqua complex 1.
Mechanism of the Hydration of Alkyne-Carboxylic Acid
Esters. The isolation and crystal structures of 2 and 3 and the
isotopic labeling experiments provide excellent opportunity to
elucidate the mechanism of the hydration of alkyne-carboxylic
acid esters catalyzed by 1 in water. Judging from the obtained
crystal structure of 2, whose stereochemistry was determined
(Z) by X-ray analysis (i.e., The Ir-C and O-C bonds exist in
the same direction of the C-C double bonds), we propose that
a syn addition of the H2O ligand of 1 into the carbon-carbon
triple bond of tetrolic acid ethyl ester proceeds to give
π-complexes A or B (eq 7). It can be assumed that the
π-complex A is formed selectively between the two possibilities
because the product of the hydration is ethyl acetoacetate but
not ethyl 2-oxobutanoate. The attack of the coordinated water
molecule in A on coordinated tetrolic acid ethyl ester results in
the formation of the Ir-enol complex 2 with the liberation of
a proton. The subsequent keto-enol tautomerism affords the
Ir-keto complex 3. The protonation of 3 gives ethyl acetoacetate
and regenerates 1. Scheme 1 shows the mechanism of the
hydration of tetrolic acid ethyl ester catalyzed by the Ir-aqua
complex 1 via the π-complex A, the Ir-enol complex 2, and
the Ir-keto complex 3.
Hydration of alkyne-carboxylic acid esters (R1CtCCO2-
C2H5, R1 ) CH3, C4H9, C5H11, and C6H13) catalyzed by the aqua
complex 1·SO4 at pH 1.3 in H2O at 25 °C gave the correspond-
ing ꢀ-keto acid esters (entries 1-5 in Table 1). The larger are
the alkyl groups (R1), the lower the TONs are. The isolated
enol complex 2 and keto complex 3 also catalyzed the hydration
of tetrolic acid ethyl ester at TONs of 55 (entry 6) and 57 (entry
7), respectively, in Table 1. It was confirmed that the isolated
enol complex 2 and keto complex 3 individually reacted with
H+ to provide the product of ethyl acetoacetate quantitatively.
As controlled experiments, we confirmed that no reaction
occurred in the absence of 1, 2, or 3, and that the bpy ligands
of 1, 2, and 3 were neither entirely nor partially dissociating
under the catalytic conditions even with the excess of bpy.
Isotopic Labeling Experiments. To establish the origin of the
enol ligand in 2·CF3SO3, the reaction of 1·SO4 with tetrolic
acid ethyl ester was carried out at pD 6.5 in D2O at 25 °C. The
Scheme 1
1
results of H NMR showed that the signal (observed at 7.41
ppm in Figure 1) of the OH proton of 2·CF3SO3 disappeared
in the 1H NMR spectrum (Figure S1 in Supporting Information);
that is, the D atoms derived from D2O were incorporated into
the enol ligand of 2·CF3SO3. Deuterium-labeled 3 was prepared
by a reaction of 1·SO4 with tetrolic acid ethyl ester in D2O at
pD 6.5 at 25 °C. The results of 1H NMR showed that the signal
(observed at 4.55 ppm in Figure 4a) of the methine proton of
1
3·PF6 disappeared in the H NMR spectrum (Figure 4b); that
is, the D atoms derived from D2O were incorporated into the
keto ligand of 3·PF6. Deuterium-labeled 3 was also prepared
by dissolving isolated deuterium-labeled 2 in D2O (eq 5). The
reaction of isolated D-labeled keto complex 3·PF6 quantitatively
reacted with H+ at pH 1.3 in H2O at 25 °C to provide
monodeutero ethyl acetoacetate {CH3C(O)CHDC(O)OC2H5}
(yield 99% based on 3·PF6) and Ir-aqua complex 1 (eq 6),
1
which was determined by H NMR (Figure S12 in Supporting
Information). Dideutero ethyl acetoacete {CH3C(O)CD2C(O)-
OC2H5} or ethyl acetoacetate {CH3C(O)CH2C(O)OC2H5} was
not obtained by the hydration, which indicated that the back
reaction from 3 to 2 was negligible.
In summary, we have succeeded in the isolation of both enol
tautomer intermediate 2 and keto tautomer intermediate 3 with
the characteristic Ir-C bonds in the catalytic hydration of tetrolic
acid ethyl ester in water by optimizing the conditions of the
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Hydration of an Alkyne-Carboxylic Acid Ester
A R T I C L E S
act as the active catalysts for the hydration of tetrolic acid ethyl
ester into ethyl acetoacetate.
Acknowledgment. This work was supported by Grants in aid
17350027, 17655027, 18033041, and 18065017 (Chemistry of
Concerto Catalysis), the Global COE Program, “Science for Future
Molecular Systems” from the Ministry of Education, Culture,
Sports, Science and Technology, Japan, and the Basic Research
Programs CREST Type, “Development of the Foundation for Nano-
Interface Technology” from JST, Japan.
Supporting Information Available: Figures S1-S12 and
crystallographic data (CIF) for 2·CF3SO3 and 3·PF6. This
material is available free of charge via the Internet at http://
pubs.acs.org.
isolation, such as pH of the solution, reaction time, and selection
of counteranions, as well as the combination of the IrCp*(bpy)
complexes and tetrolic acid ethyl ester for the first time. The
structures of 2 and 3 were unequivocally determined by X-ray
analysis. We have shown that the isolated complexes 2 and 3
JA807254D
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