The NCN-type pincer complex of palladium(II) with a 2,6-bis(2-pyridyl)-4-tert-butylbenzene tridentate ligand: synthesis, structure and catalytic activity in the mizoroki-heck reaction

Article abstract of DOI:10.3987/COM-08-S(N)125

The reaction of 1-bromo-4-tert-butyl-2,6-diiodobenzene with 2-pyridylzinc chloride in the presence of catalytic Pd(PPh₃)₄ afforded an NCN-type pincer palladium(II) complex with two pyridine donors. The structure of the complex was determined by X-ray crystallography. The complex was found to catalyze the Mizoroki-Heck reaction at 250 °C under aerobic conditions.

Full text of DOI:10.3987/COM-08-S(N)125

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HETEROCYCLES, Vol. 76, No. 2, 2008, pp. 1585 - 1592. © The Japan Institute of Heterocyclic Chemistry
Received, 3rd June, 2008, Accepted, 30th June, 2008, Published online, 7th July, 2008. COM-08-S(N)125
THE NCN-TYPE PINCER COMPLEX OF PALLADIUM(II) WITH A
2,6-BIS(2-PYRIDYL)-4-tert-BUTYLBENZENE TRIDENTATE LIGAND:
SYNTHESIS, STRUCTURE AND CATALYTIC ACTIVITY IN THE
MIZOROKI-HECK REACTION
Yuichi Hirano, Yuji Saiki, Hideki Taji, Shiro Matsukawa, and Yohsuke
Yamamoto*
Department of Chemistry, Graduate School of Science, Hiroshima University,
1-3-1 Kagamiyama, Higashi-Hiroshima 739-8526, Japan
Fax: +81-82-424-0723, Email: yyama@sci.hiroshima-u.ac.jp
Abstract – The reaction of 1-bromo-4-tert-butyl-2,6-diiodobenzene with
2-pyridylzinc chloride in the presence of catalytic Pd(PPh3)4 afforded an
NCN-type pincer palladium(II) complex with two pyridine donors. The structure
of the complex was determined by X-ray crystallography. The complex was
found to catalyze the Mizoroki-Heck reaction at 250 °C under aerobic conditions.
INTRODUCTION
Pincer complexes1 of transition metals are well-known to function as catalysts in a variety of useful
organic transformation reactions such as the Mizoroki-Heck reaction,2 allylation of aldehydes,3 and
dehydrogenation of alkanes.4 Pincer ligands are generally composed of an anionic benzene ring with two
substituents at the 2,6-positions which bear donor (P, N, S, Se, etc.) groups, and phosphorus donors
(PCP-type) are widely applied to the above-described catalytic reactions.
R2N
NR2
N
N
N
N
O
O
amine-type
oxazoline-type
t-Bu
tridentate ligand A
Figure 1

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As for pincer ligands with two nitrogen donors (NCN-type), amine- and oxazoline-types are well-known
(Figure 1).5 However, for the pyridine-type, only a few examples have been reported.6-9 During the course
of our study to isolate hypervalent compounds of main group elements such as carbon10,11 and boron,11,12
we designed a novel tridentate ligand with a 2,6-bis(2-pyridyl)-4-tert-butylbenzene skeleton (Figure 1, A).
In our several attempts to prepare a ligand precursor, 2,6-bis(2-pyridyl)-1-bromo-4-tert-butylbenzene,
using a Pd(II)-catalyzed cross-coupling reaction, we accidentally found that an NCN-type Pd(II) pincer
complex with two pyridine donors was formed. In this article, the synthesis, structure, and catalytic
activity of the NCN-type Pd(II) complex will be described.
RESULTS AND DISCUSSION
At first, 1-bromo-4-tert-butyl-2,6-diiodobenzene (2) was prepared from 4-tert-butyl-1-bromobenzene (1)
in 71% yield using the literature method (Scheme 1).13 The cross-coupling of 2 with 2-pyridylzinc
chloride was then performed in refluxing THF to give a monopyridylated compound (3) in low yield
(36%), but the desired compound (4) was not observed at all. Thus, when the reaction was performed at
125 °C in a pressure-resistant vessel using 25 mol% of catalyst, the formation of an NCN pincer
palladium complex (5) was observed. This clearly indicates that compound 4 which is formed by the
coupling reaction immediately reacts with the catalyst Pd(PPh3)4, followed by an exchange of the halogen
atom attached to Pd (Br to I) to afford 5. Complex 5 was isolated by silica-gel column chromatography,
and the isolated yield was 78% based upon the amount of Pd(PPh3)4 used.
ZnCl
Br
Br
N
Br
N
Br
N
N
I
I
I
H5IO6/KI
7.5 mol% Pd(PPh3)4
H2SO4
–30 ~ –20 ˚C, 24 h
71%
THF
reflux, 16 h
t-Bu
t-Bu
t-Bu
t-Bu
1
2
3 (36%)
4 (0%)
I
ZnCl
N
N
Pd
N
25 mol% Pd(PPh3)4
THF
125 ˚C, 60 h
t-Bu
5 (78% based on Pd)
in a pressure-resistant vessel
Scheme 1
The reported methods for the synthesis of NCN pincer Pd(II) complexes with pyridine donors involved
stepwise reactions, i.e., the 1,3-bis(2-pyridyl)benzene derivative was prepared, then the palladium atom
was introduced.7-9 At the step for introducing the palladium atom, Soro et al. used

HETEROCYCLES, Vol. 76, No. 2, 2008
1587
2,6-bis(2-pyridyl)phenylmercury chloride (6) as the synthetic intermediate to prepare complex 7 (Scheme
2).7 Later, Soro et al.8 and Ahn et al.9 independently developed the direct insertion of palladium by C-H
activation using a tetrachloropalladate salt to afford 8. However, our method can incorporate both the two
donor ligands and the palladium atom in a one-pot reaction.
X
Cl
N
Pd
N
N
Hg
N
1) Pd(OAc)2
2) LiX
N
N
1) Hg(OAc)2
2) LiCl
X = Cl, Br, I
6
7
Cl
Na2PdCl4
or K2PdCl4
N
N
N
Pd
N
AcOH
reflux
8
Scheme 2
Single crystals of 5 were grown by slow evaporation of a dichloromethane solution at room temperature.
The crystal structure of 5 was determined by X-ray crystallography (Figure 2). The three aromatic rings,
and the palladium and iodine atoms are on the same plane, and the palladium atom takes on a distorted
square planar geometry with an N1—Pd—N2 angle of 159.5(3)°. The overall structure is quite similar to
that of Soro's compound 7 (X = Cl).7
Figure 2. The ORTEP drawing of palladium complex 5 with the thermal ellipsoids shown at the 30%
probability level. The hydrogen atoms and the solvent (dichloromethane) were omitted for clarity.
Selected bond lengths (Å) and angles (°) for 5: Pd—I, 2.7351(8); Pd—N1, 2.073(7); Pd—N2, 2.073(7);
Pd—C1, 1.944(7); I—Pd—N1, 101.83(17); I—Pd—N2, 98.68(19); I—Pd—C1, 178.6(2); N1—Pd—N2,
159.5(3); N1—Pd—C1, 79.6(3); N2—Pd—C1, 79.9(3).

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Because complex 5 was stable even at 300 °C under air, we examined the catalytic activity of 5 in the
Mizoroki-Heck reaction14 under aerobic conditions. The results are summarized in Table 1. At the
reaction temperature of 120 °C (entries 1 and 3), catalytic activities were little observed. However, when
a higher reaction temperature (250 °C) was employed (entries 2, 4 and 5), the reactions proceeded to
afford the corresponding olefins with high trans selectivities. It should be noted that complex 5 still
remains after these reactions. The turnover numbers of 5 (~2,000) are two orders of magnitude lower than
the Soro's results (~100,000).7 This may be due to the choice of the base (NEt3 or Na2CO3) and the
gradual decomposition of complex 5 under our aerobic conditions.
Table 1. The catalytic activity of 5 in the Mizoroki-Heck reaction under aira
5, Na2CO3
R
R
+
ArX
Ar
DMF
entry ArX
R
5 (mol%) temp (°C) time (h)
product
trans (1.3%)
TONb
1.3
1
2
3
4
5
PhI
PhI
Ph
Ph
Ph
Ph
1.0
0.04
1.0
120
250
120
250
250
5
25
5
trans (82%), cis (trace) 2140
PhBr
PhBr
—
—
0.04
0.04
25
25
trans (50%), cis (trace) 1300
trans (74%) 1930
PhI CO2Bu
[a] Reaction conditions: ArX (5 mmol), olefin (6 mmol), Na2CO3 (6 mmol), DMF (3
mL). [b] TON = turnover number (= mol of product/mol of catalyst).
In summary, we demonstrated the novel synthesis of the NCN pincer palladium(II) complex (5) using the
one-pot introduction of two pyridine donors and a palladium atom into 1-bromo-4-tert-butyl-
2,6-diiodobenzene (2). The solid state structure of 5 was unambiguously determined by the single-crystal
X-ray crystallography. In the Mizoroki-Heck reaction, complex 5 showed the catalytic activity even under
aerobic conditions, showing the high robustness of 5 to air. Further investigations on the application of 5
as catalyst, involving oxidation of alkanes with molecular oxygen, are now in progress.
EXPERIMENTAL
General
1
The melting points were measured using a Yanaco micro melting point apparatus. The H NMR (400
MHz) and 13C NMR (100 MHz) spectra were recorded using a JEOL EX-400 or a JEOL AL-400
1
spectrometer. The H NMR chemical shifts (δ) are given in ppm downfield from Me4Si, determined by
13
residual CHCl3 (δ 7.26). The C NMR chemical shifts (δ) are given in ppm downfield from Me4Si,

HETEROCYCLES, Vol. 76, No. 2, 2008
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determined by CDCl3 (δ 77.0). Elemental analyses were performed using a Perkin-Elmer 2400 CHN
elemental analyzer. Tetrahydrofuran (THF) was freshly distilled from Na-benzophenone. Merck silica gel
60 was used for the column chromatography.
1-Bromo-4-tert-butyl-2,6-diiodobenzene (2)
To a 1000 mL flask equipped with a mechanical stirrer were added conc. H2SO4 (500 mL) and periodic
acid (22.8 g, 100 mmol). After the dissolution of periodic acid, KI (49.8 g, 300 mmol) was added in small
portions to produce
a
deep purple solution. To the solution was added dropwise
4-bromo-1-tert-butylbenzene (42.6 g, 200 mmol) at –30 °C. The mixture was stirred for 24 h while
maintaining the temperature between –30 and –20 °C. The mixture was then poured onto ice and filtered.
The residue was taken up in CH2Cl2, washed with 5% NaOH aq. (200 mL x 3) and H2O (200 mL x 2), and
dried over anhydrous MgSO4. After filtration, ethanol (100 mL) was added to the filtrate, CH2Cl2 was
evaporated and the resulting white precipitate was collected by filtration. The filtrate was concentrated to
give another crop of crystals. The combined solids were purified by column chromatography on silica gel
using hexane as eluent to give 1-bromo-4-tert-butyl-2,6-diiodobenzene (66.0 g, 142 mmol, 71%) as a
1
13
white solid. H NMR (CDCl3) δ 7.82 (s, 2H), 1.27 (s, 9H). C NMR (CDCl3) δ 153.6 (C), 137.1 (CH),
132.6 (C), 99.8 (C), 34.3 (C), 30.9 (CH3). mp 67-69 °C. Anal. Calcd for C10H11BrI2 (464.91): C 25.83, H
2.38. Found: C 25.94, H 2.33.
Attempted synthesis of 4 in refluxing THF ~ Isolation of 3 ~
Under Ar, to a solution of 2-bromopyridine (0.97 mL, 10 mmol) in THF (20 mL) under Ar at –78 °C was
added dropwise n-BuLi in n-hexane solution (7.6 mL, 1.57 M, 12 mmol) with vigorous stirring, and the
stirring was continued for 1.5 h at –78 °C. A 1 M ZnCl2 solution in ether (12 mL, 12 mmol) was added
dropwise, and the mixture was stirred for 10 min at the same temperature, then allowed to warm up to
room temperature and stirred for 1.5 h. The resulting solution was then concentrated to ca. 10 mL in
vacuo. The solution was added to a mixture of 1-bromo-4-tert-butyl-2,6-diiodobenzene (1.39 g, 4.00
mmol) and Pd(PPh3)4 (350 mg, 0.300 mmol) under Ar atmosphere. The mixture was concentrated to ca. 5
mL, then refluxed for 16 h. The resulting mixture was allowed to cool to rt, then diluted with CH2Cl2 and
filtered. The filtrate was evaporated to dryness. The residue was purified by column chromatography on
silica gel using CH2Cl2 as eluent to afford 1-bromo-2-iodo-6-(2-pyridyl)- 4-tert-butylbenzene (3) (453 mg,
1.09 mmol, 36%), but the desired 4 was not detected. 3: 1H NMR (CDCl3) δ 1.31 (s, 9H), 7.32 (t, J = 5 Hz,
1H), 7.40 (d, J = 2 Hz, 1H), 7.50 (d, J = 8 Hz, 1H), 7.78 (t, J = 8 Hz, 1H), 7.92 (d, J = 2 Hz, 1H), 8.70 (d,
J = 5 Hz, 1H).

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Attempted synthesis of 4 at 125 °C ~ Isolation of palladium complex 5 ~
Under Ar, to a solution of 2-bromopyridine (1.9 mL, 20 mmol) in THF (100 mL) at –78 °C was added
dropwise n-BuLi in n-hexane solution (14 mL, 1.60 M, 22 mmol) with vigorous stirring, and the stirring
was continued for 1 h at –78 °C. A 1 M ZnCl2 solution in ether (22 mL, 22 mmol) was added dropwise,
and the mixture was stirred for 10 min at the same temperature, then allowed to warm up to rt and stirred
for 3.5 h. The resulting solution was then concentrated to ca. 30 mL in vacuo. The solution was added to a
mixture of 1-bromo-4-tert-butyl-2,6-diiodobenzene (1.86 g, 4.00 mmol) and Pd(PPh3)4 (1.16 g, 1.00
mmol) in a pressure-resistant vessel. The mixture was heated for 60 h at 125 °C. The resulting mixture
was allowed to cool to rt, then poured into saturated aqueous EDTA disodium salt. To the mixture was
added aqueous NaHCO3 until the pH = ca. 8. The mixture was extracted with CH2Cl2 (250 mL) and
washed with H2O (50 mL x 2). The organic layer was dried over Na2SO4 and evaporated to dryness. The
crude product was purified by column chromatography (CH2Cl2) to give 2,6-bis(2-pyridyl)-4-tert-
butylphenylpalladium(II) iodide (5) (406 mg, 0.780 mmol, 78% based on Pd) as yellow needles. Single
crystals of 5 suitable for X-ray crystallography were obtained by slow evaporation of a CH2Cl2 solution.
5: 1H NMR (CDCl3) δ 9.49 (d, J = 6 Hz, 2H), 7.79 (t, J = 8 Hz, 2H), 7.63 (d, J = 8 Hz, 2H), 7.37 (s, 2H),
13
7.14 (dd, J = 8 Hz, J = 6 Hz, 2H), 1.34 (s, 9H). C NMR (CDCl3) δ 168.9 (C), 164.7 (C), 156.9 (CH),
148.0 (C), 143.0 (C), 138.5 (CH), 123.5 (CH), 121. 1 (CH), 118.9 (CH), 35.1 (C), 31.6 (CH3). mp
>300 °C. Anal. Calcd for C20H19IN2Pd (520.70): C 46.13, H 3.68, N 5.38. Found C 46.62, H 3.85, N 5.18.
General procedure for the Mizoroki-Heck reaction
DMF (3 mL) was added to a mixture of aryl halide (5.00 mmol), olefin (6.00 mmol), 5 (50.0 or 1.92
µmol), and Na2CO3 (645 mg, 6.00 mmol) in a pressure-resistant vessel. The mixture was heated for 5 h
(or 25 h) at 120 °C (or 250 °C). The mixture was allowed to cool to rt, then extracted with Et2O (100 mL)
and washed with H2O (100 mL x 2). The organic layer was dried over Na2SO4 and evaporated to dryness.
The residue was subjected to column chromatography to give the corresponding olefinic product.
Single crystal X-ray analysis of 5.
A single crystal suitable for the X-ray structural determination was mounted on a Mac Science DIP2030
imaging plate diffractometer and irradiated with graphite monochromated Mo-Kα radiation (λ = 0.71073
Å) at 293 K for data collection. The unit cell parameters were determined by separately autoindexing
several images in each data set using the DENZO program (MAC Science).15 For each data set, the
rotation images were collected in 3 degree increments with a total rotation of 180 deg about the φ axis.
The data were processed using SCALEPACK. The structure was solved by a direct method with the
SHELXS-97 program.16 Refinement on F2 was carried out using the full-matrix least-squares by the

HETEROCYCLES, Vol. 76, No. 2, 2008
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SHELXL-97 program.16 All non-hydrogen atoms were refined using the anisotropic thermal parameters.
The hydrogen atoms were included in the refinement along with the isotropic thermal parameters.
Crystallographic data for 5: orthorhombic system, space group Pnma (no. 62), a = 13.8010(6) Å, b =
6.87300(10) Å, c = 23.6280(9) Å, V = 2241.22(13) Å3, Z = 4, Dcalc = 1.795 g cm–3, data/param = 2619/162,
R1 (I > 2σ(I)) = 0.0637, wR2 (all data) = 0.2017, GOF = 1.233.
ACKNOWLEDGEMENTS
This work was supported by Grants-in-Aid for Scientific Research (Nos. 17550048, 19350024) from the
Ministry of Education, Culture, Sports, Science and Technology, Japan.
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