Cyclopalladation of the indole ring in palladium(II) complexes of 2N1O-donor ligands and its dependence on the O-donor properties.

Article abstract of DOI:10.1021/ic0504801

Synthetic, structural, spectroscopic, and kinetic studies have been carried out on the Pd(II) complexes of new 2N1O-donor ligands containing a pendent indole, 3-(N-2-pyridylmethyl-N-2-hydroxy-5-methoxybenzylamino)ethylindole (HMeO-iepp), 3-(N-2-pyridylmethyl-N-2-hydroxy-5-nitrobenzylamino)ethylindole (HNO2-iepp), and (N-2-pyridylmethyl-3-indolylethylamino)acetic acid (Hiepc) (H denotes a dissociable proton). [Pd(MeO-iepp)Cl] (2), [Pd(NO2-iepp)Cl] (3), and [Pd(iepc)Cl] (4) were prepared and revealed by X-ray analysis to have a pyridine nitrogen, an amine nitrogen, a phenolate or carboxylate oxygen, and a chloride ion in the coordination plane. UV absorption and 1H NMR spectral changes indicated that all the complexes could be converted to the indole-binding complexes where the O donor was replaced by the indole C2 atom by cyclopalladation in DMSO or DMF in the temperature range of 40-60 degrees C. Formation of the indole-binding complex species obeyed the first-order kinetics, from which the activation parameters were estimated. The formation rate was dependent on the properties of the O-donor group, a lower pKa value of its conjugate acid causing faster conversion to the indole-binding species in the order 2 (methoxyphenolate) < 3 (nitrophenolate) < 4 (carboxylate). On the other hand, the ratio of the indole-binding complex to the O-donor complex as a result of the conversion was greater for the complexes with a higher pKa value of the ligand OH group, the order being 2 > 3 > 4.

Full text of DOI:10.1021/ic0504801

Inorg. Chem. 2005, 44, 6044−6051
Cyclopalladation of the Indole Ring in Palladium(II) Complexes of
2N1O-Donor Ligands and Its Dependence on the O-Donor Properties
Yuichi Shimazaki,*,† Minoru Tashiro,‡ Takeshi Motoyama,‡ Satoshi Iwatsuki,§ Tatsuo Yajima,‡
Yasuo Nakabayashi,‡ Yoshinori Naruta,† and Osamu Yamauchi*,‡
Institute for Materials Chemistry and Engineering, Kyushu UniVersity, Higashi-ku,
Fukuoka 812-8581, Japan, Unit of Chemistry, Faculty of Engineering, Kansai UniVersity,
Suita, Osaka 564-8680, Japan, and Department of Chemistry, Graduate School of Science and
Engineering, Waseda UniVersity, Okubo, Shinjuku-ku, Tokyo 169-8555, Japan
Received April 1, 2005
Synthetic, structural, spectroscopic, and kinetic studies have been carried out on the Pd(II) complexes of new
2N1O-donor ligands containing a pendent indole, 3-(N-2-pyridylmethyl-N-2-hydroxy-5-methoxybenzylamino)ethylin-
dole (HMeO-iepp), 3-(N-2-pyridylmethyl-N-2-hydroxy-5-nitrobenzylamino)ethylindole (HNO2-iepp), and (N-2-pyridyl-
methyl-3-indolylethylamino)acetic acid (Hiepc) (H denotes a dissociable proton). [Pd(MeO-iepp)Cl] (2), [Pd(NO2-
iepp)Cl] (3), and [Pd(iepc)Cl] (4) were prepared and revealed by X-ray analysis to have a pyridine nitrogen, an
amine nitrogen, a phenolate or carboxylate oxygen, and a chloride ion in the coordination plane. UV absorption
1
and H NMR spectral changes indicated that all the complexes could be converted to the indole-binding complexes
where the O donor was replaced by the indole C2 atom by cyclopalladation in DMSO or DMF in the temperature
range of 40−60 °C. Formation of the indole-binding complex species obeyed the first-order kinetics, from which the
activation parameters were estimated. The formation rate was dependent on the properties of the O-donor group,
a lower pKa value of its conjugate acid causing faster conversion to the indole-binding species in the order 2
(methoxyphenolate) < 3 (nitrophenolate) < 4 (carboxylate). On the other hand, the ratio of the indole-binding complex
to the O-donor complex as a result of the conversion was greater for the complexes with a higher pKa value of the
ligand OH group, the order being 2 > 3 > 4.
Introduction
side chains of tyrosine and phenylalanine and is reported to
be involved in electron tunneling pathways in electron
carriers and redox enzymes.5,6 Formation of the indolyl
radical in proteins has been established for the intermediate,
compound I, formed in the course of the catalytic reaction
of cytochrome c peroxidase (CcP).7-11 Indolyl radical forma-
tion is possible with systems such as modified azurins, where
the photogenerated tryptophan radical has been observed by
Gray et al.12
Tryptophan plays important roles in proteins and chemical
systems, because of the unique properties of the indole
ring.1-3 As the most hydrophobic amino acid among the
amino acids from protein sources,4 tryptophan is often found
at or near catalytic and molecular recognition sites. The
indole ring of tryptophan sometimes forms stacks with the
* To whom correspondence should be addressed. E-mail: yshima@
ms.ifoc.kyushu-u.ac.jp (Y.S.); osamuy@ipcku.kansai-u.ac.jp (O.Y.).
† Kyushu University.
‡ Kansai University.
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N.; Onuchic, J. N.; Hoffman, B. M. Chem. ReV. 1996, 86, 2359-
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M. M.; Carlos, R. M.; Richards, J. H.; Winkler, J. R.; Gray, H. B. J.
Am. Chem. Soc. 2001, 123, 3181-3182.
§ Waseda University.
(1) (a) Burley, S. K.; Petsko, G. A. Science 1985, 229, 23-28. (b) Burley,
S. K.; Petsko, G. A. AdV. Protein Chem. 1988, 39, 125-189. (c)
Burley, S. K.; Petsko, G. A. J. Am. Chem. Soc. 1986, 108, 7995-
8001. (d) Serrano, L.; Bycroft, M.; Fersht, A. R. J. Mol. Biol. 1991,
218, 465-475. (e) Hunter, C. A.; Singh, J.; Thornton, J. M. J. Mol.
Biol. 1991, 218, 837-846.
(2) Branden, C.; Tooze, J. Introduction to Protein Structure, 2nd ed.;
Garland Publishing: New York, 1998.
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Ed. 2003, 42, 1210-1250.
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6044 Inorganic Chemistry, Vol. 44, No. 17, 2005
10.1021/ic0504801 CCC: $30.25
© 2005 American Chemical Society
Published on Web 07/21/2005

Cyclopalladation of Indole Ring in Pd(II) Complexes
Scheme 1. Interconversion between [Pd(tbu-iepp)Cl] Isomers 1a and
1b and Indole Ring Deuteration18
Although no metal-indole nitrogen bonds are known for
biological systems, various modes of indole coordination in
transition-metal complexes13-18 and π-π interaction with a
metal-coordinated aromatic nitrogen ligand19-21 have been
reported for chemical systems. The Cu(I) complexes of
tripodal ligands having an indole moiety in place of one
of the coordinating groups were found to have a Cu(I)-
(C2dC3) η2 bond to form a tetrahedral structure.13 The indole
nitrogen atom of alkylindoles coordinates to Pd(II) as an
imine nitrogen of tautomeric 3H-indole where the pyrrole
hydrogen atom is bound at the C3 atom.14 Indole-3-acetate
(IA) reacts with Pd(II) in the 3H-indole form in the presence
of pyridine (py) to give a dimeric complex, [Pd2(IA)2(py)2],
where Pd(II) binds with the deprotonated C3 and carboxylate
oxygen atoms of IA in addition to the imine nitrogen to form
a spiro ring.15 Pd(II)-indole C2 bonding was also reported
to occur as a result of cyclopalladation.17 On the other hand,
the Pd(II) and Pt(II) complexes as artificial peptidases
developed by Kostic´ et al. recognize the indole moiety by
their high affinity for the indole ring and cleave the adjacent
amide or peptide bond specifically.16 Very recently, we
reported some Pd(II) complexes of 2N1O-donor ligands with
a pendent indole moiety (Scheme 1), which were found to
be interconvertible between the Pd(II)-phenolato(O) and
Pd(II)-indole(C2) complexes with a 2N1O1Cl and a
2N1C1Cl donor set, respectively. One-electron oxidation of
the Pd(II)-indole(C2) complex yielded the corresponding
Pd(II)-indole π-cation radical species.18 The Pd(II)-indole
bonding was formed under thermodynamically controlled
conditions in CH3CN and CH2Cl2/CH3CN. However, the
interconversion or formation of the Pd(II)-indole σ bonding
was found to be limited by factors such as the distance
Figure 1. Structures of ligands.
between the indole ring and the Pd center, the existence of
the phenol moiety, and the unsubstituted indole NH moiety.
We carried out crystallographic, spectroscopic, kinetic, and
mechanistic studies on the interconversion of the Pd(II) coor-
dination structures of various 2N1O donor ligands containing
an indole ring (Figure 1), to gain further insight into the
formation of the Pd(II)-indole bond. Especially, we focused
on the function of the phenol moiety and prepared a series
of the indole-containing ligands with a substituted phenol
moiety or a carboxylic acid. Our findings indicate a versatile
nature of the indole ring, which may suggest possibilities of
tryptophan as a functional unit in biological systems.
Experimental Section
Materials. Sodium cyanoborohydride was obtained from Tokyo
Kasei, triethylamine was from Wako, and PdCl2 was from Aldrich.
All the chemicals used were of the highest grade available and were
further purified whenever necessary.22 Solvents were purified be-
fore use by standard methods.22 DMSO-d6 was purchased from
Cambridge Isotope Laboratory. The synthesis of [N-2-pyridyl-
methyl-N-2-hydroxy-3,5-di(tert-butyl)benzylamino]methylindole
(Htbu-iepp) has been reported previously.18
3-(N-2-Pyridylmethyl-N-2-hydroxy-5-methoxybenzylamino)-
ethylindole (HMeO-iepp). To a solution of 2-hydroxy-5-meth-
oxybenzaldehyde (1.52 g, 10 mmol) and 3-(N-2-pyridylmethylamino)-
ethylindole23,24 (2.6 g, 10 mmol) in methanol (50 mL) was carefully
added sodium cyanoborohydride (0.63 g, 10 mmol). The reaction
mixture was then stirred for 24 h at room temperature, acidified
by addition of concentrated HCl, and evaporated almost to dryness
under a reduced pressure. The residue was dissolved in saturated
aqueous Na2CO3 (50 mL) and extracted with CHCl3. The combined
extracts were dried over Na2SO4 and evaporated almost to dryness
under reduced pressure to give a white powder. Yield: 2.44 g
(13) Shimazaki, Y.; Yokoyama, H.; Yamauchi, O. Angew. Chem., Int. Ed.
1999, 38, 2401-2403.
(14) Yamauchi, O.; Takani, M.; Toyoda, K.; Masuda, H. Inorg. Chem. 1990,
29, 1856-1860.
(15) Takani, M.; Masuda, H.; Yamauchi, O. Inorg. Chim. Acta 1995, 235,
367-374.
(16) (a) Kaminskaia, N. V.; Johnson, T. W.; Kostic´, N. M. J. Am. Chem.
Soc. 1999, 121, 8663-8664. (b) Kaminskaia, N. V.; Ullmann, G. M.;
Fulton, D. B.; Kostic´, N. M. Inorg. Chem. 2000, 39, 5004-5013. (c)
Kaminskaia, N. V.; Kostic´, N. M. Inorg. Chem. 2001, 40, 2368-
2377. (d) Milovic´, N. M.; Kostic´, N. M. Met. Ions Biol. Syst. 2001,
38, 145-186.
1
(63%). H NMR (400 MHz, CDCl3): δ (vs TMS) 8.52 (d, 1H),
7.94 (s, 1H), 7.51 (t, 1H), 7.34 (d, 1H), 7.30 (d, 1H), 7.13 (m, 3H),
6.99 (t, 1H), 6.94 (d, 1H), 6.73 (m, 2H), 6.59 (d, 1H), 3.87 (s, 2H),
3.85 (s, 2H), 3.72 (s, 3H), 3.01 (m, 2H), 2.92 (m, 2H).
(17) Robson, R. Inorg. Chim. Acta 1982, 57, 71-77.
(18) Motoyama, T.; Shimazaki, Y.; Yajima, T.; Nakabayashi, Y.; Naruta,
Y.; Yamauchi, O. J. Am. Chem. Soc. 2004, 126, 7378-7385.
(19) (a) Fischer, B. E.; Sigel, H. J. Am. Chem. Soc. 1980, 102, 2998-
3008. (b) Guogang, L.; Sigel, H. Z. Naturforsch. 1989, 44b, 1555-
1566.
(20) Yamauchi, O.; Odani, A.; Hirota, S. Bull. Chem. Soc. Jpn. 2001, 74,
1525-1545.
(21) Yamauchi, O.; Odani, A.; Takani, M. J. Chem. Soc., Dalton, Trans.
2002, 3411-3421 and references therein.
(22) Perrin, D. D.; Armarego, W. L. F.; Perrin, D. R. Purification of
Laboratory Chemicals; Pergamon Press: Elmsford, NY, 1966.
(23) Yajima, T.; Shimazaki, Y.; Ishigami, N.; Odani, A.; Yamauchi, O.
Inorg. Chim. Acta 2002, 337, 193-202.
(24) Shimazaki, Y.; Nogami, T.; Tani, F.; Odani, A.; Yamauchi, O. Angew.
Chem., Int. Ed. 2001, 40, 3859-3862.
Inorganic Chemistry, Vol. 44, No. 17, 2005 6045

Shimazaki et al.
Table 1. Crystallographic Data
2
3
4
formula
fw
cryst. color, habit
cryst. dimensions (mm)
cryst syst
a (Å)
PdC24H24N3O2Cl
528.33
orange, prism
0.15 × 0.12 × 0.11
orthorhombic
22.613(5)
PdC23H21N4O3Cl
543.30
yellow, prism
0.12 × 0.23 × 0.21
monoclinic
21.143(10)
14.237(10)
17.331(9)
PdC18H18N3O2Cl
450.21
orange, prism
0.18 × 0.13 × 0.05
triclinic
8.611(1)
7.983(1)
13.890(3)
87.206(9)
77.22(1)
117.437(9)
844.3(3)
P1h
b (Å)
c (Å)
5.311(1)
18.137(5)
R (deg)
â (deg)
99.18(3)
γ (deg)
V (Å3)
2178.1(9)
Pca21
4
1.611
1072.00
10.02
54.9
20 852
19 528
19 528
281
0.053
0.115
5150(5)
C2/c
8
1.401
2432.00
8.53
space group
Z value
2
D
calc (g/cm3)
1.771
452.00
12.75
55.0
8164
3764
3764
226
0.035
F(000)
µ (Mo KR)/ cm-1
2θmax/°
55.0
observed reflns
independent reflns
reflns used
18 822
5844
5844
334
0.091
0.206
number of variables
R1 [I > 2σ(I)]a
R
w (all data)b
0.089
2
2
a R1 ) ∑||Fo| - |Fc||/∑|Fo| for I > 2σ(I) data. b Rw ) {∑ω(|Fo| - |Fc|)2/∑ωFo }1/2; ω ) 1/σ2(Fo) ) {σ2 (Fo) + p2/4Fo }-1
.
c
1
3-(N-2-Pyridylmethyl-N-2-hydroxy-5-nitrobenzylamino)eth-
ylindole (HNO2-iepp). To a solution of 2-hydroxy-5-nitrobenzyl-
bromide (2.3 g, 10 mmol) and 3-(N-2-pyridylmethylamino)-
ethylindole23,24 (2.6 g, 10 mmol) in THF (50 mL) was carefully
added triethylamine (1.0 g, 10 mmol). The resulting solution was
stirred for 3 days at room temperature and evaporated almost to
dryness under a reduced pressure. The residue was purified by silica
gel column chromatography to give a yellow powder. Yield: 1.95
g (48%). 1H NMR (400 MHz, CDCl3): δ (vs TMS) 11.04 (br, 1H),
8.59 (d, 1H), 8.04 (q, 1H), 7.93 (s, 1H), 7.63 (t, 1H), 7.33 (m, 2H),
7.20 (m, 3H), 6.94 (d, 1H), 6.80 (d, 1H), 3.99 (s, 2H), 3.90 (s,
2H), 2.98 (m, 4H).
H, 4.22; N, 9.70. Found: C, 50.02; H, 4.01; N, 10.14. H NMR
(400 MHz, DMSO-d6): δ (vs TMS) 10.84 (s, 1H), 8.73 (d, 1H),
8.30 (d, 1H), 8.15 (t, 1H), 7.95 (q, 1H), 7.80 (d, 1H), 7.55 (t, 1H),
7.25 (d, 1H), 7.04 (t, 1H), 6.99 (d, 1H), 6.81 (d, 1H), 6.74 (d, 1H),
4.78 (d, 1H), 4.57 (d, 1H), 4.00 (d, 1H), 3.20 (m, 1H), 2.88 (m,
2H), 2.76 (m, 1H).
[Pd(iepc)Cl] (4). To a solution of Hiepc (0.31 g, 1.0 mmol) in
1:1 (v/v) EtOH/CH3CN (20 mL) was added PdCl2 (0.18 g, 1.0
mmol). Triethylamine (0.1 g, 1.0 mmol) was added to the resulting
solution, which was refluxed for 30 min to give yellow crystals.
Anal. Calcd for 4 (C18H18N3O2ClPd): C, 48.02; H, 4.03; N, 9.33.
1
Found: C, 48.09; H, 3.77; N, 9.32. H NMR (400 MHz, DMSO-
d6): δ (vs TMS) 10.91 (br, 1H), 8.42 (d, 1H), 8.07 (t, 1H), 7.63
(d, 1H), 7.50 (t, 1H), 7.41 (d, 1H), 7.26 (d, 1H), 7.22 (d, 1H), 7.05
(t, 1H), 6.93 (t, 1H), 5.23 (d, 1H), 4.58 (d, 1H), 4.34 (d, 1H), 3.67
(d, 1H), 3.33 (m, 2H), 3.03 (m, 2H).
(N-2-Pyridylmethyl-3-indolylethylamino)acetic Acid (Hiepc).
To a solution of bromoacetic acid (2.3 g, 10 mmol) and 3-(N-2-
pyridylmethylamino)ethylindole23,24 (2.6 g, 10 mmol) in ethanol
(25 mL) was carefully added triethylamine (1.0 g, 10 mmol). The
resulting solution was refluxed for 12 h and then evaporated almost
to dryness under a reduced pressure. The residue was purified by
silica gel column chromatography to give a pale-yellow powder.
Yield: 2.4 g (77%). H NMR (400 MHz, D2O): δ (vs TSP) 7.98
(d, 1H), 7.50 (d, 1H), 7.25 (m, 2H), 7.17 (t, 1H), 4.44 (s, 2H), 3.94
(s, 2H), 3.52 (t, 2H), 3.21 (t, 2H).
X-ray Structure Determination. The X-ray experiments were
carried out on a Rigaku RAXIS imaging plate area detector with
graphite monochromated Mo KR radiation (λ ) 0.710 73 Å). The
crystal was mounted on a glass fiber. To determine the cell constants
and orientation matrix, three oscillation photographs were taken
for each frame with an oscillation angle of 3° and an exposure
time of 3 min. Intensity data were collected by taking oscillation
photographs. Refraction data were corrected for both Lorentz and
polarization effects. The structures were solved by the direct method
and refined anisotropically for non-hydrogen atoms by full-matrix
least-squares calculations. Refinement was continued until all shifts
were smaller than one-third of the standard deviations of the
parameters involved. Atomic scattering factors were taken from
the literature.25 All hydrogen atoms were located at the calculated
positions, assigned a fixed displacement, and constrained to ideal
geometry with C-H ) 0.95 Å and N-H ) 0.90 Å. The thermal
parameters of calculated hydrogen atoms were related to those of
their parent atoms by U(H) ) 1.2Ueq(C,N). All the calculations
were performed by using the TEXSAN crystallographic software
program package from Molecular Structure Corporation.26 Sum-
1
[Pd(tbu-iepp)Cl] (1). Preparation of this complex has been
reported previously.18
[Pd(MeO-iepp)Cl] (2). To a solution of HMeO-iepp (0.38 g,
1.0 mmol) in 1:1 (v/v) CH2Cl2/CH3CN (20 mL) was added
PdCl2 (0.18 g, 1.0 mmol). A few drops of triethylamine were
added to the resulting solution, which was stirred overnight at
room temperature to give orange crystals. Anal. Calcd for 2
(C24H24N3O2ClPd): C, 54.56; H, 4.58; N, 7.95. Found: C, 54.68;
1
H, 4.41; N, 7.89. H NMR (400 MHz, DMSO-d6): δ (vs TMS)
10.77 (s, 1H), 8.69 (d, 1H), 8.08 (t, 1H), 7.73 (d, 1H), 7.52 (t, 1H),
7.25 (d, 1H), 7.05 (d, 1H), 7.00 (d, 1H), 6.97 (s, 1H), 6.81 (m,
2H), 6.64 (m, 2H), 5.06 (d, 1H), 4.63 (d, 1H), 4.47 (d, 1H), 3.72
(d, 1H), 3.61 (s, 3H), 3.09 (m, 1H), 2.86 (m, 1H), 2.77 (m, 2H).
[Pd(NO2-iepp)Cl]‚0.5H2O (3). This complex was prepared in
a manner similar to that described for 2 and was given as yellow
crystals. Anal. Calcd for 3 (C23H21N4O3ClPd‚0.5H2O): C, 50.16;
(25) Ibers, J. A.; Hamilton, W. C. International Tables for X-ray Crystal-
lography; Kynoch: Birmingham, U. K., 1974; Vol. IV.
6046 Inorganic Chemistry, Vol. 44, No. 17, 2005

Cyclopalladation of Indole Ring in Pd(II) Complexes
Figure 2. ORTEP view of [Pd(MeO-iepp)Cl] (2) drawn with the thermal
ellipsoids at the 50% probability level and the atomic labeling scheme.
Figure 3. ORTEP view of [Pd(NO2-iepp)Cl] (3) drawn with the thermal
ellipsoids at the 50% probability level and the atomic labeling scheme.
maries of the fundamental crystal data and experimental parameters
for the structure determinations of complexes 2-4 are given in
Table 1.
Spectroscopies and Kinetic Measurements. Electronic spectra
were measured with a Shimadzu UV-3101PC spectrophotometer,
equipped with a temperature-controlled apparatus. The temperature
of the reaction solution was held constant to within (0.1 °C. The
rate constants were determined by a least-squares analysis for
complexes 1-4. The NMR measurements were performed with a
JEOL JNM-GSX-400 (400 MHz) NMR spectrometer.
Results and Discussion
Preparations and Structures of Pd(II) Complexes.
HMeO-iepp and HNO2-iepp, where H denotes a dissociable
proton, reacted with PdCl2 and triethylamine in CH2Cl2/
CH3CN at room temperature to give [Pd(MeO-iepp)Cl] (2)
and [Pd(NO2-iepp)Cl] (3) as red and yellow crystals,
respectively. [Pd(iepc)Cl] (4), having a carboxylate donor,
was obtained as orange crystals by the reaction in 1:1 (v/v)
C2H5OH/CH3CN at 80 °C. Complexes 2, 3, and 4 were
revealed to have a mononuclear square-planar structure with
a phenolate or carboxylate oxygen, an amine nitrogen, a
pyridine nitrogen, and a chloride ion, as shown in Figures
2, 3, and 4, respectively. The side chain indole ring is not
coordinated and is without any interactions within the
complex molecules. These structures are very similar to
that of complex 1.18 The Pd-N and Pd-O bond lengths
(Pd-N ) 2.00-2.05; Pd-O ) 1.98-2.03 Å) (Table 2)
correspond well with those reported for Pd(II) complexes.23,27
The Pd-O bond length increased in the order 2 [1.989(2)
Å] < 3 [2.006(7) Å] < 4 [2.026(2) Å] (Table 2), which is
in agreement with the order of the pKa values of the
substituted phenol of the carboxylic acid of these ligands.28,29
Figure 4. ORTEP view of [Pd(iepc)Cl] (4) drawn with the thermal
ellipsoids at the 50% probability level and the atomic labeling scheme.
Table 2. Selected Bond Lengths (Å) and Angles (deg) for 2, 3, and 4
2
3
4
Bond Length (Å)
Pd-Cl(1)
Pd-O(1)
Pd-N(1)
Pd-N(2)
2.317(1)
1.989(2)
2.019(2)
2.052(3)
2.296(3)
2.006(7)
1.999(9)
2.042(7)
2.3254(6)
2.026(2)
2.005(2)
2.020(2)
Bond Angle (deg)
Cl(1)-Pd-O(1)
Cl(1)-Pd-N(1)
Cl(1)-Pd-N(2)
O(1)-Pd-N(1)
O(1)-Pd-N(2)
N(1)-Pd-N(2)
88.81(8)
95.16(7)
174.09(7)
175.93(9)
93.7(1)
86.8(2)
94.73(6)
97.63(7)
175.18(7)
167.31(8)
83.60(9)
84.29(9)
94.3(2)
176.7(3)
178.0(3)
96.0(3)
82.40(9)
82.9(3)
In this connection, the Pd-N(amine) bond length decreased
in the order 2 [2.052(3) Å] > 3 [2.042(7) Å] > 4 [2.020(2)
Å], but the trans effect in these complexes has not been
observed explicitly.
Characterization of the Pd(II) Complexes. The absorp-
tion spectrum of 2 in DMF in the range 250-1000 nm
exhibited peaks at 340 (ꢀ ) 4000) and 457 nm (ꢀ ) 950),
the latter of which has been assigned to the phenolate-to-
Pd(II) charge-transfer band (LMCT).18,23 While complex 3
(26) TEXSAN, Crystal Structure Analysis Package; Molecular Structure
Corporation: The Woodlands, TX, 1985 and 1999.
(27) Barnard, C. T. J.; Russel, M. J. H. In ComprehensiVe Coordination
Chemistry; Wilkinson, G., Gillard, R. D., McCleverty J. A., Eds.;
Pergamon: Oxford, 1987; Vol. 5, Chapter 53.
(28) Gross, K. C.; Seybold, R. G. Int. J. Quantum Chem. 2001, 85, 569-
579.
(29) Martell, A. E.; Smith, R. M. Critical Stability Constants; Plenum
Press: New York, 1977; Vol. 3.
Inorganic Chemistry, Vol. 44, No. 17, 2005 6047

Shimazaki et al.
Figure 5. Absorption spectral changes of 2 with time in DMSO at 60 °C
(1.0 × 10-3 M). The spectra were recorded at 30 min intervals.
Figure 6. 1H NMR spectra of 2 (a) in DMSO-d6 and (b) heated for 24 h
at 60 °C in DMSO-d6; concentration, 1.0 × 10-3 M.
with a coordinated p-nitrophenolate showed a strong absorp-
tion peak at 389 nm (ꢀ ) 1900) that is assigned to the
p-nitrophenolate π-π* transition band, the phenolate-to-
Pd(II) LMCT band that was observed at 450 nm for 118 was
not detected for 3. The absorption spectrum of the carboxy-
late complex 4 showed one peak at 314 nm (ꢀ ) 2500). The
1H NMR chemical shifts of the indole and pyridine rings
for all the complexes were very similar, and this supports
that conformations of these complexes, including the side
chain indole ring, are similar in solution. Since 1 had already
been reported to be without stacking interactions in solu-
tion,18,23 the environment of the indole ring in all of the
complexes is probably free from constraint and allows free
rotation. These observations indicate that the side chain
conformations as well as the coordination structures are
maintained both in the solid state and in solution.
of 2b. The first-order rate constant of the conversion reaction,
k
obs, was estimated to be 1.22 × 10-5 s-1 at 60 °C in DMF
for both 1 and 2. The reaction rate was substantially
dependent on the solvents, the order being DMF > DMSO,
for example, kobs ) 3.63 × 10-6 s-1 at 60 °C for 1 in DMSO.
This tendency has been observed for the formation of other
cyclopalladation complexes of our ligand series,18 but the
solvent dependence of the reaction rate of cyclopalladation
in general has been reported to be in the reverse order.30,31
During this conversion reaction, no intermediate was de-
tected. Whereas the conversion between 1 and 1b was
reversible, 2b in solution was not convertible and was very
stable at room temperature, and after a few weeks at room
temperature, it finally gave some decomposition products,
which could not be isolated and characterized. On the other
hand, 3 in DMF kept at 50 °C for 1 day exhibited a small
color change; the p-nitrophenolate π-π* transition band
gradually decreased, and a shoulder peak appeared at around
400 nm with isosbestic points. The kobs value for the
conversion of 3 to 3b was estimated to be 3.64 × 10-4 s-1
at 60 °C, which is greater than that for 2, although the final
Formation of the Indole-Binding Pd(II) Complexes.
When the solution of 1 and 2 in DMSO or DMF was kept
at 50 °C for a few days, a color change from orange to yellow
was observed.18 When a solution of 2 in DMF was left to
stand at 50 °C for 1 day, the LMCT band at 457 nm and the
π-π* band at 340 nm gradually disappeared with the
appearance of a 294 nm band (ꢀ ) 10 000), indicating the
formation of a different complex (2b) containing a protonated
phenol moiety18 (Figure 5), and similar spectral changes were
also observed for 3 and 4, showing that the corresponding
indole-binding species were formed from these complexes.
The 1H NMR spectra of 2 in DMSO measured under different
conditions indicated the conversion of 2 to 2b at 60 °C
(Figure 6); the signals of the indole C4 through C7 protons
(in4-in7) shifted upfield in 2b relative to those of 2 with
chemical shift differences, ∆δ ) -(δ2b - δ2), of 0.02-0.67
1
ratio of 3 to 3b was 1:0.1 in DMF or DMSO from the H
NMR measurement. The carboxylato complex 4 showed the
fastest rate of conversion with the estimated kobs value of
1.07 × 10-2 s-1 at 60 °C in DMF (vide infra). The final
ratio of 4 to 4b was found to be 1:0.2 in DMF. These kinetic
results may suggest that dissociation of the Pd-O bond is
included in the rate-determining step. Complexes 3b and 4b
were also stable, undergoing a slow decomposition over the
course of a few months at room temperature.
The specific point on the conversion of 4 was shown by
the NMR experiment. The chemical shifts of indole and
pyridine protons for 4 were very different from those of 1-3.
For example, while the py6 proton signal of 1b-3b exhibited
an upfield shift relative to that of 1-3,18 4b exhibited a
downfield shift of the signal, which may suggest that 4b has
a different structure, such as a carboxylate-bridged dinuclear
complex. In this connection, the kinetic studies indicated the
1
ppm (Table 3), and the H-1H COSY spectrum revealed
that 2b lacks the indole C2 proton signal. These results
indicate that the phenolato complex 2 was converted to the
indole-binding complex species where Pd(II) binds with the
C2 atom of the indole ring with deprotonation. Although
the crystal structure of the indole-binding complex 1b has
been successfully determined,18 we could not isolate and
structurally characterize the indole-binding complexes 2b,
3b, and 4b. The ratio of 1 to 1b was 1:0.3 in DMSO after
24 h at room temperature and 1:1 at 60 °C,18 while more
than 90% of 2 could be converted to 2b at 60 °C in DMSO
or DMF. Complete conversion of 2 was not possible at 100
°C and higher temperatures because of the decomposition
(30) (a) Yagyu, T.; Aizawa, S.; Hatano, K.; Funahashi, S. Chem. Lett. 1996,
1107-1108. (b) Yagyu, T.; Aizawa, S.; Funahashi, S. Bull. Chem.
Soc. Jpn. 1998, 71, 619-629. (c) Yagyu, T.; Iwatsuki, S.; Aizawa,
S.; Funahashi, S. Bull. Chem. Soc. Jpn. 1998, 71, 1857-1862.
(31) Ryabov, A. D.; Sakodinskaya, I. K.; Yatsimirsky, A. K. J. Chem. Soc.,
Dalton Trans. 1985, 2629-2638.
6048 Inorganic Chemistry, Vol. 44, No. 17, 2005

Cyclopalladation of Indole Ring in Pd(II) Complexes
Table 3. 1H NMR Chemical Shifts (δ/ppm) and Upfield Shifts (∆δ)a of Pyridine and Indole Proton Signals for Pd(II) Complexes in DMSO-d6
δ (∆δ)/ppm
tbu-iepp (1)
1b
MeO-iepp (2)
2b
NO2-iepp (3)
3b
iepc (4)
4b
py3
py4
py5
py6
in1
in2
in4
in5
in6
in7
7.77
8.11
7.52
8.69
10.74
6.88
7.22
6.72
6.96
6.72
7.16 (+0.61)
7.65 (+0.46)
7.15 (+0.37)
8.44 (+0.25)
8.34 (+2.40)
7.73
8.08
7.52
8.69
10.77
6.81
7.25
6.66
6.81
6.61
7.26 (+0.37)
7.72 (+0.36)
7.21 (+0.31)
8.47 (+0.22)
9.34 (+1.43)
7.76
8.13
7.53
8.73
10.82
7.03
7.20
6.79
6.98
6.74
7.26 (+0.50)
7.75 (+0.38)
7.20 (+0.33)
8.40 (+0.33)
9.50 (+1.32)
7.64
8.08
7.51
8.43
10.92
7.26
7.42
6.94
7.05
7.32
7.69 (-0.05)
8.05 (+0.03)
7.58 (-0.07)
8.79 (-0.26)
9.36 (+1.43)
7.36 (-0.14)
6.83 (-0.11)
6.83 (+0.13)
7.29 (-0.57)
7.34 (-0.09)
6.83 (-0.17)
6.83 (-0.02)
7.28 (-0.67)
7.34 (-0.14)
6.83 (-0.04)
6.83 (+0.15)
7.30 (-0.56)
7.28 (+0.14)
6.80 (+0.14)
6.80 (+0.15)
7.24 (+0.08)
a ∆δ ) -(δb - ∆δa), where δa and δb refer to the shifts for the O-donor complex and the corresponding indole-binding complex, respectively.
Table 4. Activation Parameters and Rate Constants at 60 °C, k333, for
Conversion between the O-Donor Complexes and Indole-Binding
Complexes in DMFa
∆H‡/kJ mol-1
∆S‡/J K-1 mol-1
104 k333/s-1
tbu-iepp(1)
MeO-iepp(2)
NO2-iepp(3)
iepc (4)
92 ( 4
96 ( 2
72 ( 1
38 ( 2
-64 ( 10
-51 ( 6
0.122
0.122
3.64
-94 ( 3
-170 ( 6
107
a Determined by the dependence of kobs on temperature (see ref 33).
presence of two components, the first one showing the first-
order reaction and the second one showing the reaction of
an unidentified order. From these results, the first component
of the reaction of 4 was assigned to the formation of the
mononuclear indole-binding species and the second one to
the conversion to a dinuclear complex or an intermolecularly
interacting species. We, therefore, adopted the first compo-
nent value as the rate constant for the formation of 4b.
Relation between Activation Energy and Oxygen Donor
Properties in the Structural Conversion. The kobs values
of the above conversion reaction followed the order of the
acidity of the oxygen donor, p-methoxyphenol < p-nitro-
phenol < carboxylic acid.28,29 The values for all the
complexes were dependent on the reaction temperature and
increased with the temperature. The activation parameters
for the conversion were determined, as listed in Table 4,
according to the theory of transition state by linear least-
squares fitting (see Supporting Information).33 The plot of
the activation energy E versus the pKa value of the ligand
OH group (Figure 7) clearly indicates that the energy barrier
of the conversion is correlated with the oxygen donor ability
and, hence, with the Pd-O bond strength, the order being
MeO-phenolate > NO2-phenolate > COO-. It is generally
agreed that cyclopalladation reactions of aryl compounds
Figure 7. Activation energies as a function of the pKa values of the ligand
OH groups.
proceed by an electrophilic substitution mechanism involving
the rate-determining step in such processes as C-H bond
cleavage, which is normally regarded as an irreversible
process.32,34 The rate-determining step of our conversion may
involve Pd-O bond cleavage in addition to the C-H bond
cleavage process. On the other hand, while the activation
parameters for 1 and 2 were comparable with and those for
3 were slightly smaller than the other values reported for
cyclopalladation,30 complex 4 exhibited a small activation
enthalpy (∆H‡) and a large negative entropy (∆S‡) value.
However, the activation parameters in Table 4 are correlated
with each other, suggesting a similar mechanism of cyclo-
palladation in our series of Pd(II) complexes.
Effect of Addition of Acids and Bases. The rates of
conversion from the phenolato complexes 2, 3, and 4 to the
indole-binding ones were temperature-dependent, whereas
the ratio of the phenolato complex to the indole-binding
complex was temperature-independent in the range 40-80
°C. For example, the ratio of 4 to 4b was estimated to be
1:0.2 from the 1H NMR experiment in this temperature range.
The addition of a few equivalents of benzoic acid to the
solutions of 3 and 4 in DMSO or DMF did not affect the
ratio, and the addition of 1 equiv of CF3SO3H to the solutions
of the phenolato complexes in DMSO gave some decom-
position products. On the other hand, the addition of
triethylamine changed the ratio: 4 equiv of triethylamine
(32) (a) Parshall, G. W. Acc. Chem. Res. 1970, 3, 139-144. (b) Ryabov,
A. D. Chem. ReV. 1990, 90, 403-424. (c) Beller, M.; Riermeier, T.
H.; Haber, S.; Kleiner, H.-J.; Herrmann, W. A. Chem. Ber. 1996, 129,
1259-1264.
(33) If the reactions in this study proceed via an intramolecular reversible
process, kobs should be expressed by the rate constants for the formation
of the indole-binding complex (kf) and the phenolato complex (kb) as
follows: kobs ) kf + kb. The equilibrium constant (K) for each system
can be estimated from the final ratio of the indole-binding complex
to the phenolato complex, K ) kf/kb. However, the subsequent side
(decomposition) reactions in the present systems gave rise to large
errors in the estimation of kf and kb and prevented the determination
of the detailed final ratios (see text). Therefore, only the temperature
dependence of kobs was measured and used for the calculation of the
activation parameters.
(34) Go´mez, M.; Granell, J.; Martinez, M. Eur. J. Inorg. Chem. 2000, 217-
224.
Inorganic Chemistry, Vol. 44, No. 17, 2005 6049

Shimazaki et al.
the cyclopalladation reaction is inhibited by excessive
amounts of additional ligands such as triphenylphosphine
(PPh3).34 According to the other mechanism (Scheme 2b),
cyclopalladation proceeds by the concerted mechanism via
a five-coordinate intermediate.30 If the former mechanism
is applied to our system, Pd-O bond cleavage as the first
step may be favored by the existence of protons. In the
present systems, however, the addition of benzoic acid to
the phenolato complexes in DMSO or DMF had only a slight
effect on the conversion, and an excess of PPh3 did not
replace the coordinated phenolate moiety; the indole-binding
species was formed irrespective of these conditions. On the
basis of this observation and considering that the reaction
was accompanied by a large negative entropy change as
compared with the other cyclopalladation,30 we may exclude
the three-coordinate 14-electron intermediate. Since the rate-
determining step of both mechanisms has been proposed to
be the C-H bond cleavage,30-32,34-36 the existence of protons
is considered to be unfavorable for the cyclopalladation.
It is generally agreed that cyclopalladation reactions of
aryl compounds proceed by an electrophilic substitution by
Pd(II) ions. The electrophilicity of the Pd(II) center to the
indole moiety should increase with the decreasing pKa
values of the ligand OH group, and our experiments have
shown that the reaction rates are in the order 2 < 1 < 3 <
4, which is in agreement with the decreasing order of the
pKa values of the corresponding ligands. Despite the lack of
further experimental results on the activated intermediate,
we may suggest that the intermediate of the conversion
reaction is associated with the O-donor properties of the
ligands, and all of our results are consistent with those
hitherto reported.30-32,34-36
Figure 8. 1H NMR spectral changes of 4 in DMSO-d6 with the addition
of triethylamine at 60 °C; concentration, 1.0 × 10-3 M.
Scheme 2. Proposed Mechanisms of Formation of the Indole-Binding
Complex: (a) Mechanism via 14-Electron Three-Coordinate
Intermediate and (b) Mechanism via Five-Coordinate Intermediate
Conclusion. We prepared and characterized the Pd(II)
complexes of a series of new tripod-like 2N1O-donor ligands
containing an oxygen donor with various substituents and a
pendent indolylethyl moiety. In the temperature range of
40-80 °C, all the Pd(II) complexes yielded the correspond-
ing indole-binding Pd(II) species, whose formation rate
constants and activation parameters have been determined.
The relationship between the structures of the complexes and
the activation parameters indicated that the formation rate
of the indole-binding Pd(II) species depends on the O-donor
properties, the complexes of the ligands with a lower ligand
OH pKa value exhibiting a faster conversion to the indole-
binding species in the order 2 < 3 < 4. On the other hand,
the formation ratio of the indole-binding complex to the
O-donor complex was higher for the complexes of the ligands
with a higher pKa value in the order 2 > 3 > 4. The addition
of a base enhanced the formation of the indole-binding
complex, which indicates that basic conditions are favorable
for the present cyclopalladation. Although no reaction
intermediate was detected in the present study, the O-donor
to C-donor conversion reaction may be explained by a
mechanism involving a five-coordinate intermediate, which
is not in conflict with the proposals that have been
reported.30-32,34-36 The present findings may add to our
knowledge of the properties of the indole ring under various
conditions.
added to the solution of 4 in DMSO at 70 °C gave 4b in
more than 90% yield, as seen from the H NMR spectral
1
changes (Figure 8). A similar tendency was also observed
for 3 in DMSO, where the yield of the indole-binding
complex 3b was increased 2 times by 5 equiv of triethyl-
amine at 70 °C. Accordingly, a more basic condition is more
favorable for the formation of the indole-binding complex30
and, thus, the cyclopalladation.
Conversion Mechanism. Recently, we reported that the
phenol OH group takes part in the process of the structural
conversion between 1 and 1b, where the phenolate oxygen
abstracts the indole C2 proton to form 1b.18 This result is in
agreement with the present result on the ratio of the phenolato
complex to the indole-binding complex, the conversion ratio
being lower for 3 and 4 containing a weak proton accep-
tor.28,29 In contrast, the reaction rates for 3 and 4 were greater
than those for 1 and 2 because of facile Pd-O bond cleavage.
The observed conversion may be interpreted by the proposed
cyclopalladation mechanisms shown in Scheme 2. One of
them involves a three-coordinate 14-electron intermediate
(Scheme 2a),31,32,34-36 which explains the observation that
(35) Deeming, A. J.; Rothwell, I. P. Pure. Appl. Chem. 1980, 52, 649-
655.
(36) (a) Thummel, R. P.; Jahng. Y. J. Org. Chem. 1987, 52, 73-78. (b)
Go´mez, M.; Granell, J.; Martinez, M. Organometallics 1997, 16,
2539-2546.
6050 Inorganic Chemistry, Vol. 44, No. 17, 2005

Cyclopalladation of Indole Ring in Pd(II) Complexes
Supporting Information Available: The X-ray crystallographic
data (CIF) for complexes 2, 3, and 4 and H NMR spectra (PDF)
showing the interconversion. This material is available free of
charge via the Internet at http://pubs.acs.org.
Acknowledgment. We gratefully acknowledge the sup-
port of this work by a Grant-in-Aid for Scientific Research
(Grant 17750055 to Y.S. and Grant 16350036 to O.Y.) and
the “Nanotechnology Support Project” of the Ministry of
Education, Culture, Sports, Science and Technology of
Japan.
1
IC0504801
Inorganic Chemistry, Vol. 44, No. 17, 2005 6051