An efficient catalyst for Suzuki-Miyaura coupling reaction in aqueous medium under aerobic conditions

Article abstract of DOI:10.1016/j.tetlet.2004.10.177

A cylcopalladated complex, [Pd(Cl)(k²N,C-CH₂C ₆H₂(Me)₂CHNC₆H₃(Pr ⁱ)₂]₂ was found to be an excellent catalyst for Suzuki-Miyaura coupling of aryl halides with arylboronic acid in aqueous medium under aerobic conditions.

Full text of DOI:10.1016/j.tetlet.2004.10.177

Tetrahedron
Letters
Tetrahedron Letters 46 (2005) 521–523
An efficient catalyst for Suzuki–Miyaura coupling reaction
in aqueous medium under aerobic conditions
Chuan-Lin Chen, Yi-Hung Liu, Shie-Ming Peng and Shiuh-Tzung Liu*
Department of Chemistry, National Taiwan University, Taipei 106, Taiwan
Received 13 August 2004; revised 22 October 2004; accepted 26 October 2004
Available online 7 December 2004
Abstract—A cylcopalladated complex, [Pd(Cl)(k2N,C–CH2C6H2(Me)2CH@NC6H3(Pri)2]2 was found to be an excellent catalyst for
Suzuki–Miyaura coupling of aryl halides with arylboronic acid in aqueous medium under aerobic conditions.
ꢀ 2004 Elsevier Ltd. All rights reserved.
Among various palladium-catalyzed carbon–carbon
Pr-i
Cl
formation reactions, the Suzuki–Miyaura coupling pro-
vides a powerful tool for preparation of unsymmetrical
biaryls.1–5 In recent years, developments in this catalysis
have been focused on the syntheses of new transition
metal complexes as catalysts for the use of aryl chlo-
rides,1,4,5 under aerobic conditions2,4,5 or even in aque-
ous solutions.3,5 Accordingly, palladacycles were found
to the most promising catalysts in this regard. Recently,
i-Pr
Pr-i
(ACN) PdCl
i-Pr
N
N
2
2
Pd
ð1Þ
2
NaOAc
1
4
5
X-ray diffraction study on the single crystal confirmed
the detail of the structure proposed. Figure 1 displays
the ORTEP plot of the palladacycle. The palladium
metal displays a slightly distorted square-planar geome-
try with nitrogen and carbon donors in cis-fashion. All
bond distances and bond angles lie within normal
´
Bedford et al. and Najera and co-workers have dem-
onstrated that the coupling reaction of aryl chlorides
can be achieved efficiently by using the cyclopalladated
imino-complexes. Here, we would like to report the
preparation of benzylic palladacyles and its catalytic
activity toward Suzuki–Miyaura coupling in aqueous
solution under aerobic atmosphere.
8
˚
ranges for 1. The length of C(8)–N(1) [1.280(5) A] is
Condensation of 2,4,6-trimethylbenzaldehyde with the
2,6-diisopropylaniline yielded the desired imine ligand,
which was subsequently reacted with (CH3CN)2PdCl2
in the presence of sodium acetate in tetrahydrofuran at
ambient temperature for 38 h to give the palladacycle
product 17 (Eq. 1). This complex was isolated as air sta-
ble solid upon crystallization. The C–H activation at
1
benzylic position6 was established by its H NMR and
X-ray single-crystal determination. The appearance of
signal at 3.24 ppm with the integration of 2H in the
1H NMR spectra was assigned to the methylene protons
of Pd–CH2—resulted from the C–H activation with the
palladium complex.
Figure 1. ORTEP drawing of
ellipsoids); Pd(1)–N(1) 2.043(3) A, Pd(1)–C(1) 2.003(4) A, N(1)–
1 (drawn with 30% probability
˚
˚
*
Corresponding author. Tel.: +886 2 2366 0352; fax: +886 2 2363
6359; e-mail addresses: stliu@ntu.edu.tw; stliu@ccms.ntu.edu.tw
Pd(1)–C(1) 86.2(1)ꢁ.
0040-4039/$ - see front matter ꢀ 2004 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2004.10.177

522
C.-L. Chen et al. / Tetrahedron Letters 46 (2005) 521–523
characteristic for C@N double bond. The small bite
angle N(1)–Pd(1)–C(1) [86.1ꢁ] is similar to those benzylic
type palladacycles reported by Sales and coworkers.9 It
is noticed that the angle of Pd(1)–C(1)–C(2) [116.0(3)ꢁ]
deviating from the angle for a tetrahedral geometry is
presumably due to the constraints imposed by the che-
lating rings. The distances of Pd–C(l) trans to the carbon
that the coupling reaction was inhibited in the aceto-
nitrile solution, presumably due to the coordinating
nature of this solvent (entry 1).
It was found that the palladacycle 1 remained its cata-
lytic activity in the presence of air (entry 3), indicating
that this catalytic precursor is quite stable in air. There-
fore, the activities of the catalyst toward various of aryl
halides in the Suzuki–Miyaura reaction was screened
using water or ethanol as the solvents under aerobic
conditions (entries 5–20).
˚
donor are slightly longer (ca. 0.17 A) than those trans to
the imine donor, as expected, because of the trans influ-
ence. Examination of those dihedral angles along Pd(1)–
N(1)–C(8)–C(7)–C(2)–C(1) of 1 reveals this chelate ring
adopting to a twist half-chair conformation, which is
due to the presence of two double bonds of N(1)–C(8)
and C(2)–C(7) in the ring. The isopropyl groups on
the aromatic ring readily force that phenyl ring perpen-
dicular to the coordination plane.
As expected, the catalyst behaves better activity toward
the aryl bromides than the chlorides, which is essentially
similar to those for such coupling reactions. For the
chloride substrates, the addition of tetrabutylammo-
nium bromide (TBAB) in water was required for the bet-
ter conversion (entry 10), which is consistent with the
observation by Bedford et al.4 Palladacycle 1 shows an
excellent catalytic activity for p-acetylphenyl bromide
and the catalytic turnover number can reach up to 106
(entry 9). Complex 1 also catalyzed the coupling of a ste-
ric bulky aryl bromide with phenylboronic acid in good
conversion by increasing the concentration of the cata-
lyst (entry 6).
To illustrate the catalytic activity, complex 1 was used as
the catalyst for the Suzuki–Miyaura coupling reaction.
In a typical experiment for the reaction, aryl halide,
phenylboronic acid and K2CO3 in a ratio of 1:1.5:2 were
placed in the flask, followed by the addition of the sol-
vent and the catalyst. In all instances the solvent was
used as obtained commercially without further purifica-
tion, while the deionized water was used for aqueous
systems. The organic product was isolated by extraction
1
and then analyzed by the H NMR spectroscopy. All
results are summarized in Table 1.
For the activated chloride susbtrates, the palladium
complex 1 catalyzed the coupling reactions in good
yields. An excellent TON of 103 is seen at 0.1 mol %
of Pd (entry 15), suggesting that the conversion is influ-
enced by the lifetime of the catalyst. As can be seen, the
coupling of phenylboronic acid with either p-acetylphe-
nyl chloride or p-nitrophenyl chloride catalyzed by 1
also gave excellent results. However, a poor conversion
for the deactivated substrates and phenyl chloride was
observed (entries 16–18). For the other arylboronic
acids, the palladacyle showed a similar activity on the
In this catalysis, the initial reactions were performed
using 1 as the catalyst to study the solvent effect (Table
1, entries 1–5). It appeared that the protic solvents
including water gave much better results than any other
organic solvents. DMF and toluene are common sol-
vents for the coupling reactions, but providing moderate
conversion as compared with alcoholic solvents with
palladacycle 1 as the catalyst. It is interesting to note
Table 1. Coupling reaction of aryl halides with phenylboronic acid catalyzed by palladacycle 1a
Entry
ArX
Pd (mmol)
[ArX]/[Pd]
Additive
Solvent
Atm
t (h)
Conv.b
Yield (%)
TON
—
1
p-MeOC6H4Br
p-MeOC6H4Br
p-MeOC6H4Br
p-MeOC6H4Br
p-MeOC6H4Br
2,4,6-Me3C6H2Br
p-MeOC6H4Br
p-MeCOC6H4Br
p-MeCOC6H4Cl
p-MeCOC6H4Cl
p-NO2C6H4Cl
o-NO2C6H4Cl
o-NO2C6H4Cl
2,4-(NO2)2C6H3Cl
2,4-(NO2)2C6H3Cl
C6H5Cl
1 · 10ꢀ4
1 · 10ꢀ4
1 · 10ꢀ4
1 · 10ꢀ4
1 · 10ꢀ4
1 · 103ꢀ6
2 · 10ꢀ6
2 · 10ꢀ4
2 · 10ꢀ4
2 · 10ꢀ4
2 · 10
20,000
20,000
20,000
20,000
20,000
2000
—
—
CH3CN
Toluene
DMF
EtOH
H2O
Ar
Ar
3
3
Trace
70%
64%
—
65
60
99
99
72
55
97
—
83
87
90
47
40
100
22
24
8
2
14,000
3
—
—
Air
Air
Air
Air
Air
Air
Air
Air
Air
Air
Air
Air
Air
Air
Air
Air
Air
Air
3
12,800
20,000
20,000
1480
4
3
100%
100%
74%
5
—
—
3
6
EtOH
EtOH
EtOH
H2O
3
7
1,000,000
1,000,000
10,000
10,000
10,000
1000
—
—
20
20
1
57%
600,000
1,000,000
—
8
100%
Trace
87%
9
—
10
11
12
13
14
15
16
17
18
19c
20
TBAB
TBAB
TBAB
TBAB
TBAB
TBAB
TBAB
TBAB
TBAB
—
H2O
H2O
1
8700
8800
1
88%
91%
2 · 10ꢀ3
2 · 10ꢀ4
2 · 10ꢀ4
2 · 10ꢀ3
2 · 10ꢀ4
2 · 10ꢀ3
2 · 10ꢀ4
1 · 10ꢀ4
2 · 10ꢀ4
H2O
H2O
2.5
4
910
5200
10,000
10,000
1000
52%
43%
H2O
H2O
4
4300
1000
3
100%
22%c
24%
10,000
1000
H2O
H2O
2
2200
240
C6H5Cl
2
p-MeOC6H4Cl
p-MeOC6H4Br
p-MeCOC6H4Cl
10,000
20,000
10,000
H2O
EtOH
H2O
16
2
10%
100%
85%
1000
20,000
8500
100
82
TBAB
1
a Reaction conditions: ArX (2 mmol), PhB(OH)2 (3 mmol), K2CO3 (4 mmol), solvent (5 mL), at refluxing temperature.
b Determined by 1H NMR.
c p-MeOC6H4B(OH)2 was used instead of phenylboronic acid.

C.-L. Chen et al. / Tetrahedron Letters 46 (2005) 521–523
523
4. (a) Bedford, R. B.; Cazin, C. S. J.; Coles, S. J.; Gelbrich, T.;
Horton, P. N.; Hursthouse, M. B.; Light, M. E. Organo-
metallics 2003, 22, 987–999; (b) Bedford, R. B.; Blake, M.
E.; Butts, C. P.; Holder, D. Chem. Commun. 2003, 466–467;
Bedford, R. B.; Cazin, C. S. J.; Coles, S. J.; Gelbrich, T.;
Hursthouse, M. B.; Scordia, V. J. M. Dalton Trans. 2003,
3350–3356; (c) Bedford, R. B.; Cazin, C. S. J. Chem.
Commun. 2001, 1540–1541; (d) Bedford, R. B.; Cazin, C. S.
J.; Hursthouse, M. B.; Light, M. E.; Pike, K. J.; Wimperis,
S. J. Organomet. Chem. 2001, 633, 171–181.
coupling reaction (entries 19–20). Thus, complex 1 cata-
lyzed the reaction of p-methoxyphenyl bromide with
p-methoxyphenylboronic acid quantitatively.
In summary, cyclopalladated complex 1 has been
successfully prepared in a stable form. This catalyst
proves to be an excellent catalyst for Suzuki–Miyaura
coupling reaction, which can be carried out in air and
in aqueous or protic organic solutions. This result read-
ily offers an environmentally benign preparation of
diaryl compounds. Further studies on the reaction
mechanism and other applications are currently under
investigation.
´
5. (a) Alonso, D. A.; Najera, C.; Pacheco, M. C. J. Org.
Chem. 2002, 67, 5588–5594; (b) Botella, L.; Najera, C.
´
´
Angew. Chem., Int. Ed. 2002, 41, 179–181; (c) Najera, C.;
Gil-Molto, J.; Karlstroem, S.; Falvello, L. R. Org. Lett.
2003, 5, 1451–1454.
6. (a) Albert, J.; Ceder, R. M.; Gomez, M.; Granell, J.; Sales,
J. Organometallics 1992, 11, 1536–1541; (b) Albert, J.;
Granell, J. Trends Organomet. Chem. 1999, 3, 99–112.
7. Complex 1: 75%, orange solid, mp: 270 ꢁC (dec); IR (KBr):
Acknowledgements
1
1599 cmꢀ1 (mC@N); H NMR (CDCl3, 400 MHz): d 7.81 (s,
This research was supported by the National Science
Council (NSC92-2113-M002-037), Taiwan.
1H, –HC@N), 7.23 (t, J = 7.3 Hz, 1H, Ar H), 7.14 (d,
J = 7.3 Hz, 2H, Ar H), 6.98 (s, 1H, Ar H), 6.82 (s, 1H, Ar
H), 3.48–3.39 (m, 2H, –CH), 3.24 (s, 2H, –H2C–Pd), 2.30 (s,
3H, –Me), 2.29 (s, 3H, –Me), 1.47 (d, J = 6.7 Hz, 6H, –Me),
1.11 (d, J = 6.8 Hz, 6H, –Me); 13C NMR: d 162.7, 148.0,
146.5, 143.7, 140.7, 139.8, 130.6, 127.6, 126.8, 125.4, 123.3,
28.2, 24.8, 23.2, 22.5, 21.4, 19.1; FAB m/e: 861 (M+ꢀClꢀ);
Anal. Calcd for C44H56Cl2N2Pd2: C, 58.94; H, 6.29; N,
3.12; Found: C, 58.89, H, 6.35, N, 3.08.
References and notes
1. (a) Suzuki, A. J. Organomet. Chem. 1999, 576, 147–168; (b)
Bedford, R. B. Chem. Commun. 2003, 1787–1796; (c)
Stanforth, S. P. Tetrahedron 1998, 54, 263–303; (d) Hassan,
J.; Sevignon, M.; Gozzi, C.; Schulz, E.; Lemaire, M. Chem.
Rev. 2002, 102, 1359–1469; (e) Tucker, C. E.; De Vries, J.
G. Top. Catal. 2002, 19, 111–118; (f) Singleton, J. T.
Tetrahedron 2003, 59, 1837–1857; (g) Kotha, S.; Lahiri, K.;
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Kocovsky, P.; Malkov, A. V.; Vyskocil, S.; Lloyd-Jones,
G. C. Pure Appl. Chem. 1999, 71, 1425–1433; (i) Herrmann,
W. A. In Applied Homogeneous Catalysis with Organome-
tallic Compounds, 2nd ed.; Wiley–VCH: Weinheim, 2002;
Vol. 1, p 591.
2. (a) Venkatraman, S.; Li, C.-J. Org. Lett. 1999, 1, 1133–
1135; (b) Jensen, J. F.; Johannsen, M. Org. Lett. 2003, 5,
3025–3028.
3. (a) Badone, D.; Baroni, M.; Cardamone, R.; Ielmini, A.;
Guzzi, U. J. Org. Chem. 1997, 62, 7170–7173; (b) Oehme,
G.; Grassert, I.; Paetzold, E.; Meisel, R.; Drexler, K.;
Fuhrmann, H. Coord. Chem. Rev. 1999, 185–186, 585–600.
8. Crystal data for Complex 1: C44H56Cl2N2Pd2, Fw 896.61,
˚
Monoclinic, space group P21/c, a = 16.7242(2) A,
˚
b = 14.6933(2) A,
˚
c = 18.1016(2) A,
a = 90ꢁ,
b =
3
˚
108.931(1)ꢁ, g = 90ꢁ, V = 4207.57(9) A , Z = 4, Dcalcd
,
1.415 mg/m3, F(000) = 1840, 0.25 · 0.20 · 0.20 mm, 31,332
refln collected with 9636 (Rint = 0.0567), For [I > 2 (I)],
R1 = 0.0395, wR2 = 0.0896, Goodness-of-fit on F2: 1.082.
Crystallographic data (excluding structure factors) for 1
have been deposited with the Cambridge Crystallographic
Data Centre as supplementary publication numbers CCDC
240355. Copies of the data can be obtained, free of charge,
on application to CCDC, 12 Union Road, Cambridge CB2
1EZ, UK [fax: +44(0) 1223 336033 or e-mail: deposit@
ccdc.cam.ac.uk].
9. Barro, J.; Granell, J.; Sainz, D.; Sales, J.; Font-Bardia, M.;
Solans, X. J. Organomet. Chem. 1993, 456, 147.