First use of a palladium complex with a thiosemicarbazone ligand as catalyst precursor for the Heck reaction

Article abstract of DOI:10.1016/j.tetlet.2004.02.062

A novel palladium complex with salicylaldehyde N(4)-ethylthiosemicarbazone has been synthesized and according to its crystal structure the ligand is bound to the metal in an O, N, S-terdentate coordination mode. This phosphorus-free system efficiently catalyzes the Heck reaction of aryl bromides (from electron-rich to electron-poor) with styrene under argon, with turnover numbers of up to 43,000, at 150°C after 24h, and with a selectivity toward trans-stilbenes ranging from 92 to 96%. In air, for activated aryl bromides and for a palladium concentration of 1mM, the yields are essentially the same as those obtained when the reaction was performed under argon.

Full text of DOI:10.1016/j.tetlet.2004.02.062

Tetrahedron
Letters
Tetrahedron Letters 45 (2004) 2923–2926
First use of a palladium complex with a thiosemicarbazone ligand as
catalyst precursor for the Heck reaction
a,
Dimitra Kovala-Demertzi, Paras N. Yadav, Mavroudis A. Demertzis, Jerry P. Jasiski,
a
a
b
*
c
Fotini J. Andreadaki and Ioannis D. Kostas
c,
*
a
University of Ioannina, Department of Chemistry, Sector of Inorganic and Analytical Chemistry, 45110 Ioannina, Greece
b
Department of Chemistry, Keene State College, 229 Main Street, Keene, NH 03435-2110, USA
National Hellenic Research Foundation, Institute of Organic and Pharmaceutical Chemistry, Vas. Constantinou 48,
c
1
16 35 Athens, Greece
Received 9 December 2003; revised 4 February 2004; accepted 13 February 2004
Abstract—A novel palladium complex with salicylaldehyde N(4)-ethylthiosemicarbazone has been synthesized and according to its
crystal structure the ligand is bound to the metal in an O, N, S-terdentate coordination mode. This phosphorus-free system effi-
ciently catalyzes the Heck reaction of aryl bromides (from electron-rich to electron-poor) with styrene under argon, with turnover
numbers of up to 43,000, at 150 ꢀC after 24 h, and with a selectivity toward trans-stilbenes ranging from 92 to 96%. In air, for
activated aryl bromides and for a palladium concentration of 1 mM, the yields are essentially the same as those obtained when the
reaction was performed under argon.
ꢁ
2004 Elsevier Ltd. All rights reserved.
The palladium-catalyzed arylation of alkenes, known as
the Heck reaction, represents one of the most powerful
tools in organic synthesis for carbon–carbon bond for-
could play a constructive role for specific purposes, for
example, the construction of heteropolynuclear com-
plexes. This phosphine-free system attracted our
7
1
mation. The complexes used as catalysts are usually
2
attention due to the presence of additional potential
N-donors, since it is known that an additional coordi-
nation site as a stabilizing group during the course of a
metal-mediated reaction could improve the catalytic
based on phosphorus ligands. These catalysts are often
3
water- and air-sensitive. Therefore, catalysis under
phosphine-free conditions is a challenge of high impor-
4
2l;4e;8
tance, and a number of phosphine-free ligands as well
5
as ligand-free palladium catalysts for the Heck reaction
efficiency of the complex.
have been reported. In our attempts to evaluate phos-
phine-free systems in the Heck reaction, a substituted
salicylaldehyde thiosemicarbazone was chosen for this
purpose. The chemistry of thiosemicarbazones has been
an extremely active area of research primarily because of
the beneficial biological (viz. antiviral and antitumor)
Recently, our groups have published several papers
concerning the coordination chemistry of thiosemicar-
bazones and transition-metal homogeneous catalysis
9
employing phosphorus ligands with additional potential
donors, such as N, O, S, the constructive role of which
in catalysis is decisive, even though the additional donor
6
2l;10
activities of their transition-metal complexes. Salicyl-
is not bound to the metal.
In the present work, we
aldehyde thiosemicarbazone is a multidentate ligand
with five potential coordination sites: three N, one O,
and one S atoms. Usually, it is bonded to a transition-
metal leaving some potential donor sites unused, and it
report the synthesis and crystal structure of a palladium
complex with salicylaldehyde N(4)-ethylthiosemicar-
bazone. This phosphine-free system was applied to the
Heck reaction of aryl bromides with styrene. To our
knowledge, this paper represents the first study con-
cerning the evaluation of a thiosemicarbazone ligand in
the Heck reaction.
Keywords: Thiosemicarbazone; O, N, S-ligand; Phosphine-free ligand;
Palladium complex; Heck reaction; Homogeneous catalysis.
The synthesis of the palladium complex 3 is outlined in
Scheme 1. Salicylaldehyde N(4)-ethylthiosemicarbaz-
one (H Sal4Et) 2 was prepared by treatment of
2
*
Corresponding authors. Tel.: +30-26510-98425; fax: +30-26510-44-
31(D.K.-D); tel.: +30-210-7273878; fax: +30-210-7273877 (I.D.K);
e-mail addresses: dkovala@cc.uoi.gr; ikostas@eie.gr
11
8
12
0
040-4039/$ - see front matter ꢁ 2004 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2004.02.062

2924
D. Kovala-Demertzi et al. / Tetrahedron Letters 45 (2004) 2923–2926
15
protonated on N(2). The displacement from coplana-
rity is indicated by the dihedral angle between the phe-
nol ring and the plane defined by the five-membered
chelate ring Pd–S–C(9)–N(2)–N(1) being 3.45(12)ꢀ, and
the dihedral angle between the phenol ring and the plane
defined by the six-membered chelate ring Pd–N(1)–
C(8)–C(7)–C(2)–O(1) being 2.21(13)ꢀ.
Complex 3 was applied to the Heck reaction of styrene
with some representative 4-substituted aryl bromides
(
from electron-rich to electron-poor) in DMF at 150 ꢀC
for 24 h, using AcONa as base, and in the absence of any
16
promoting additive (Scheme 2, Table 1). Although the
reaction can be performed at lower temperatures, 150 ꢀC
is the best reaction temperature for synthetic purposes.
Catalysis was performed under an inert atmosphere as
well as in air. The reaction was first performed using a
Scheme 1.
1
:1000 catalyst:aryl bromide molar ratio to ensure a
higher yield process, and then by decreasing the ratio to
:100,000. There was good selectivity for formation of
salicylaldehyde 1 with N-ethylthiosemicarbazide in eth-
anol. The synthesis of complex 3 was achieved by the
1
trans-stilbenes 6, ranging from 92% to 96%, and it is
noteworthy that side-products, other than cis-stilbenes 7
and 1,1-diphenylethylenes 8, were absent or present only
in traces. As expected, the catalytic activity depended on
the halide, while electron-withdrawing groups on the
aryl ring increased the reaction rate. The activity follows
reaction of ligand 2 with Li
PdCl and LiCl. The microanalytical data are consistent
2 4
PdCl , prepared in situ from
2
with the formula C10
structure [Pd(HSal4Et)Cl] Æ H
water is suggested by the IR spectrum, which revealed
the appearance of a strong band at 3494 cm consistent
with a stretching m(H–O–H) bond. Also, the low value of
H
14ClN
3
O
2
PdS, which indicates the
2
O. The presence of lattice
ꢀ
1
in the order NO >CHO>H>OMe, suggesting that the
2
rate-determining step in the Heck reaction is the oxi-
ꢀ
1
m(Pd–Cl) at 291 cm suggests the presence of an inter-
or intramolecular halogen hydrogen bond.
dative addition of the aryl bromide to the palladium
catalyst. Under argon, the catalyst is thermally stable
and the reaction mixture remains yellow or colorless,
depending on the palladium concentration. A cata-
lyst:substrate ratio of 1:1000 leads to total yields of 46%
and 54% for the very inactive 4-bromoanisole and the
relatively inactive bromobenzene, respectively. At lower
conversions, for these substrates the reaction proceeds
with TONs of up to 17,000 and 18,000, respectively.
High activity was observed for the activated 4-bromo-
benzaldehyde and 1-bromo-4-nitrobenzene. A cata-
lyst:substrate ratio of 1:1000 led to high conversion
(95%) of the aryl bromide, and with a ratio of 1:100,000,
the reaction proceeded with TONs of up to 43,000. At
lower ratios, even higher TONs were possible but these
were not optimized. In spite of the thermal stability of
the complex under argon, unfortunately, at high tem-
peratures in air, partial decomposition took place, and
the reaction mixture turned to dark brown. In air, a
catalyst:substrate ratio of 1:1000 led to total yields of
13
Recrystallization of complex 3 from CH
(
3 3
CN/CH OH
1:1) yielded orange prisms suitable for single crystal X-
14
ray analysis. The structure is shown in Figure 1. The
presence of lattice water in the complex is obvious as
shown in its crystal structure. The monoanionic
HSal4Et ligand is coordinated to palladium in a tri-
dentate fashion via the phenoxy oxygen, the azomethine
nitrogen N(1), and the sulfur atom, forming one six- and
one five-membered chelate ring. The ligand shows a Z,
E, Z configuration for the donor centers oxygen, nitro-
gen, and sulfur, respectively. The S–C(9) bond distance
ꢀ
of 1.713(3) A is consistent with a double-bond character,
while both thioamide C–N distances (N(2)–C(9),
ꢀ ꢀ
.338(4) A; N(3)–C(9), 1.331(4) A) indicate an increased
1
single bond character, in accordance with a molecule
1
2% and 18% for 4-bromoanisole and bromobenzene,
respectively. These yields are significantly lower com-
pared to those obtained under argon. It is obvious,
however, that the catalyst remains active in air even for
the nonactivated aryl bromides. On the other hand, with
a catalyst:substrate ratio of 1:1000, and for the activated
aryl bromides, it is noteworthy that the yields were
found to be essentially the same as those obtained when
the reaction was performed under argon. However, in
air and at a very low palladium concentration, for a
catalyst:4-bromobenzaldehyde ratio of 1:100,000, the
yield was diminished.
In summary, we have synthesized and characterized a
chelate palladium complex with salicylaldehyde N(4)-
Figure 1. ORTEP drawing of palladium complex 3.

D. Kovala-Demertzi et al. / Tetrahedron Letters 45 (2004) 2923–2926
2925
Scheme 2.
Table 1. Heck reaction of aryl bromides with styrene catalyzed by palladium complex 3
a
b
Entry
R
Atmosphere
ArBr/Pd ratio
GC Yield (%)
TON
Selectivity 6:7:8
1
2
3
4
5
6
7
8
9
OMe
OMe
OMe
H
Argon
Air
1000
1000
46
12
17
54
18
18
95
94
30
14
95
94
43
460
120
95.4:0.5:4.1
94.1:––:5.9
92.0:0.2:7.8
96.4:0.7:2.9
95.0:––:5.0
95.3:––:4.7
95.1:0.1:4.8
96.4:0.3:3.3
95.1:––:4.9
95.7:0.7:3.6
95.1:0.7:4.2
96.1:0.7:3.2
94.8:0.5:4.7
Argon
Argon
Air
100,000
1000
1000
17,000
540
180
H
H
Argon
Argon
Air
100,000
1000
1000
18,000
950
940
CHO
CHO
CHO
CHO
Argon
Air
100,000
100,000
1000
30,000
14,000
950
1
1
1
1
0
1
2
3
NO
NO
NO
2
2
2
Argon
Air
Argon
1000
100,000
940
43,000
Reaction conditions: ArBr (1.0 mmol), styrene (1.5 mmol), AcONa (2.0 mmol), Pd complex 3 in DMF (1 mL), 150 ꢀC, 24 h.
Total GC yield of all isomers, based on the aryl bromide using decane as internal standard.
a
b
Turnover no (TON) ¼ fraction of products (6 þ 7 þ 8) · substrate/Pd ratio.
ethylthiosemicarbazone, in which, according to its
crystal structure, deprotonation from the alcohol func-
tion takes place, and the ligand is bound to the metal in
an O, N, S-terdentate coordination mode, forming one
six- and one five-membered chelate ring. This phos-
phorus-free complex with additional potential N-donors
is thermally stable under argon, and efficiently catalyses
the Heck reaction of aryl bromides with styrene, with
good turnover numbers, and good selectivity toward
trans-stilbenes. The catalyst is also active in air, in par-
ticular for the activated substrates. This first study of the
application of thiosemicarbazone ligands to the Heck
reaction provides important information on the catalytic
activity of these systems. The development of analogous
ligands for the Heck as well as other palladium-cata-
lyzed reactions is currently in progress.
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Acknowledgements
This investigation was supported in part by the Re-
search Committee of the University of Ioannina, Project
S. Dakaris, and in part by the General Secretariat of
Research and Technology of Greece. P.N.Y. thanks
IKY for a scholarship.
4
490–4499; (j) Imbos, R.; Minnaard, A. J.; Feringa, B. L.
J. Chem. Soc., Dalton Trans. 2003, 2017–2023; (k)
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2
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3. For air-stable phosphine catalysts, see for example Refs.
c,f.
References and notes
2
1
. Recent leading monographs and reviews: (a) Tsuji, J.
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D. Kovala-Demertzi et al. / Tetrahedron Letters 45 (2004) 2923–2926
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90–98; (e) Kostas, I. D. Inorg. Chim. Acta 2003, 355, 424–
427.
2
11. Analytical data. H
2
Sal4Et 2: mp 150 ꢀC. IR (KBr): m 3355
(OH), 3252 (NH), 3179 (NH), 1618, 1602 (C@N), 958 (N–
ꢀ1
1
N), 870 cm (C@S); H NMR (DMSO-d ): d 11.39 (s,
6
2
003, 5, 983–986; (h) N ꢁa jera, C.; Gil-Molt oꢁ , J.; Karlstr o€ m,
S.; Falvello, L. R. Org. Lett. 2003, 5, 1451–1454;
i) Masllorens, J.; Moreno-Ma n~ as, M.; Pla-Quintana,
1H), 9.90 (s, 1H), 8.48 (m, 2H), 7.95 (d, J ¼ 8:0 Hz, 1H),
7.27 (t, J ¼ 11:2 Hz, 1H), 6.89 (m, 2H), 3.66 (m, 2H), 1.18
(
(t, J ¼ 9:2 Hz, 3H). Anal. Calcd for C10
13 3
H N OS: C, 53.8;
A.; Roglans, A. Org. Lett. 2003, 5, 1559–1561; (j) Park,
S. B.; Alper, H. Org. Lett. 2003, 5, 3209–3212; (k)
Mazet, C.; Gade, L. H. Eur. J. Inorg. Chem. 2003, 1161–
H, 5.9; N, 18.8; S, 14.4. Found: C, 53.6; H, 6.1; N, 18.6; S,
14.2. [Pd(HSal4Et)Cl] Æ H O: mp 279 ꢀC. IR (KBr): m
3494 (OH ), 3279 (NH), 1600 (C@N), 817 cm (C@S);
FAR-IR (PE): m 424 (Pd–N), 392 (Pd–O), 343 (Pd–S),
2
ꢀ1
2
1168.
ꢀ1
1
5
. Recent selected papers: (a) Reetz, M. T.; Westermann, E.
Angew. Chem. Int. Ed. 2000, 39, 165–168; (b) Gruber,
A. S.; Pozebon, D.; Monteiro, A. L.; Dupont, J. Tetra-
hedron Lett. 2001, 42, 7345–7348; (c) Yao, Q.; Kinney,
E. P.; Yang, Z. J. Org. Chem. 2003, 68, 7528–7531;
291 cm (Pd–Cl); H NMR (DMSO-d ): d 8.46 (m, 2H),
6
7.95 (d, J ¼ 8:0 Hz, 1H), 7.24 (t, J ¼ 11:2 Hz, 1H), 6.86
(m, 2H), 3.35 (m, 2H), 1.17 (t, J ¼ 11:2 Hz, 3H). Anal.
3 2
Calcd for C10H14ClN O PdS: C, 31.4; H, 3.7; Cl, 9.5; N,
11.0; Pd, 27.9; S, 8.4. Found: C, 31.5; H, 3.7; Cl, 9.3; N,
11.2; Pd, 27.8; S, 8.3.
(
2
d) Schmidt, A. F.; Smirnov, V. V. J. Mol. Catal. A: Chem.
003, 203, 75–78; (e) de Vries, A. H. M.; Mulders,
12. Known compound: (a) Mishra, P.; Chowdhari, D.;
Katrolia, S. P.; Agrawal, R. K. Hind. Antibiot. Bull.
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C. E.; Mulders, J. M. C. A.; de Vries, J. G.; de
Vries, A. H. M. J. Organomet. Chem. 2003, 687, 494–
4
97.
13. Kovala-Demertzi, D.; Domopoulou, A.; Demertzis, M. A.;
Raptopoulou, C. P.; Terzis, A. Polyhedron 1994, 13,
1917–1925.
6
. Recent selected papers: (a) Quiroga, A. G.; Perez, J. M.;
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14. Crystallographic data for the structure of 3 has been
deposited with the Cambridge Crystallographic Data
Centre as supplementary publication number CCDC
225257. Crystal data for 3: Intensity data were collected
on a Rigaku AFC6S diffractometer with graphite mono-
ꢀ
chromated Mo-Ka radiation (k ¼ 0:71069 A) at 296 K,
using the x ꢀ 2h technique to a maximum 2h of
54.9ꢀ. C10
H
12ClN
3
OPdS Æ H
2
O, M ¼ 382:12, triclinic, a ¼
ꢀ
ꢀ ꢀ
8:9232ð7Þ A, b ¼ 9:522 (1) A, c ¼ 8:061 (2) A, a ¼ 103:56
ꢀ
3
(1)ꢀ, b ¼ 91:99 (1)ꢀ, c ¼ 92:55 (1)ꢀ, V ¼ 664:5 (2) A , space
3
group P-1 (no 2), Z ¼ 2, dcalcd ¼ 1.751 g/cm , 3245 reflec-
tions measured, 3049 reflections [I>2r(I)] were used in all
7
. (a) Pal, I.; Basuli, F.; Mak, T. C. W.; Bhattacharya, S.
Angew. Chem. Int. Ed. 2001, 40, 2923–2925; (b) Dutta, S.;
Basuli, F.; Peng, S.-M.; Lee, G.-H.; Bhattacharya, S. New
J. Chem. 2002, 26, 1607–1612.
calculations, R ¼ 0:0635, R ¼ 0:0262.
w
15. Kovala-Demertzi, D.; Miller, J. R.; Kourkoumelis, N.;
Hadjikakou, S. K.; Demertzis, M. A. Polyhedron 1999, 18,
1005–1013.
8
9
. Reetz, M. T.; Waldvogel, S. R.; Goddard, R. Tetrahedron
Lett. 1997, 38, 5967–5970.
16. General experimental procedure for the Heck reaction: A
Schlenk flask equipped with a reflux condenser, was
charged under argon or in air with aryl bromide
(1.0 mmol), styrene (0.17 mL, 1.5 mmol), AcONa
(0.164 g, 2.0 mmol), a stock solution of complex 3 in
DMF (1 or 0.01 mM, 1 mL, 0.001 or 0.00001 mmol,
respectively), and decane (0.08 mL, 0.4 mmol) as internal
standard, stirred in a preheated 150 ꢀC oil bath for 24 h,
and then allowed to cool to rt. After addition of aqueous
NaOH and extraction with dichloromethane, the organic
. (a) Kovala-Demertzi, D.; Kourkoumelis, N.; Demertzis,
M. A.; Miller, J. R.; Frampton, C. S.; Swearingen, J. K.;
West, D. X. Eur. J. Inorg. Chem. 2000, 727–734; (b)
Kovala-Demertzi, D.; Demertzis, M. A.; Miller, J. R.;
Papadopoulou, C.; Dodorou, C.; Filousis, G. J. Inorg.
Biochem. 2001, 86, 555–563; (c) Yadav, P. N.; Demertzis,
M. A.; Kovala-Demertzi, D.; Castineiras, A.; West, D. X.
Inorg. Chim. Acta 2002, 332, 204–209; (d) Kovala-
Demertzi, D.; Demertzis, M. A.; Filiou, E.; Pantazaki,
A. A.; Yadav, P. N.; Miller, J. R.; Zheng, Y. F.;
Kyriakidis, D. A. Biometals 2003, 16, 411–418.
phase was washed with brine, dried over Na
passed through Celite, and analyzed by GC and GC–MS.
2 4
SO , filtered,
2l
All the Heck products are known compounds.