1,3-Phenylene-bis-(1H)-tetrazole pincer ligand for palladium-catalyzed Suzuki cross-coupling reactions of arylhalides with arylboronic acids

Article abstract of DOI:10.1055/s-2004-831303

1,3-Phenylene-bis-(1H)-tetrazole pincer ligand was synthesized by the reaction of 1,3-phenylenediamine, sodium azide and triethyl orthoformate in acetic acid and successfully used in Suzuki cross coupling reactions of aryl halides with aryl boronic acids.

Full text of DOI:10.1055/s-2004-831303

LETTER
2227
1
,3-Phenylene-bis-(1H)-tetrazole Pincer Ligand for Palladium-Catalyzed
Suzuki Cross-Coupling Reactions of Arylhalides with Arylboronic Acids
1
A
, 3-Phenylene-bis-
r
(1
H
)-tet
u
r
azole Pincer
n
Ligand Kumar Gupta, Chul Yun Rim, Chang Ho Oh*
GOS Lab, Department of Chemistry, Hanyang University, Sungdong-Gu, Seoul 133-791, Korea
Fax +82(2)22990762; E-mail: changho@hanyang.ac.kr
Received 30 May 2004
Abstract: 1,3-Phenylene-bis-(1H)-tetrazole pincer ligand was
synthesized by the reaction of 1, 3-phenylenediamine, sodium azide
and triethyl orthoformate in acetic acid and successfully used in
Suzuki cross coupling reactions of aryl halides with aryl boronic
acids.
Key words: 1,3-phenylene-bis-(1H)-tetrazole pincer ligand, Suzu-
Equation 1
ki cross-coupling reactions, aryl halides
the tetrazole pincer complexes, the ligand, in combination
with palladium acetate, has been shown to catalyze the
coupling reactions of aryl halides with arylboronic acids
efficiently. A characteristic feature of our palladacycle is
the thermal stability, which makes it possible to perform
the reactions even at a temperature above 100 °C, which
is necessary for less reactive substrates such as aryl chlo-
rides and aryl bromides.
The tetrazole functionality plays an important role in me-
dicinal chemistry as a pharmacophore due to its ability to
serve as a bioequivalent (bioisostere) of the carboxylic
group, as well as in synthetic organic chemistry as a syn-
1
thon. There are few examples in which tetrazoles were
2
used as ligands with Ni or Ru. To our knowledge, how-
ever, reports on usage of tetrazole in palladium- or plati-
3
num-catalyzed reactions are scarce. Transition metal A preliminary screening of this ligand 2 for Suzuki cou-
pincer complexes using phosphorus as the donor atom pling of a chemically inert, cheap and readily accessible 4-
(
PCP pincer complex) were reported in the early 1970’s.4 chlorotoluene (3a) with 4-methoxyphenylboronic acid
Since then, many research groups have developed a vari- (4c) revealed that the coupling proceeds smoothly in
ety of pincer ligands; they offer a unique and highly pro- DMF solvent in the presence of Pd(OAc) metal catalyst,
2
tective environment for the resident metal. Opportunities t-BuOK as a base and tetrabutylammonium bromide
12
to fine-tune the metal properties have spawned extensive (TBAB) as an additive (Equation 2). In order to compare
research into the use of these complexes as catalysts. the reactivity of the ligand and to optimize the reaction
These complexes are used in a variety of reactions, includ- conditions, we have screened various solvents (THF,
5
ing the Heck reaction. Recently, new types of non-phos- toluene, etc.), bases (Cs CO , K CO , etc.), and different
2
3
2
3
phine ligands, such as heterocyclic carbenes, imines, catalysts (PdCl , PtCl , etc.). The results are summarized
2
2
imidazoles, and 1,2,4-triazoles, have emerged as alterna- in Table 1, Table 2, and Table 3, respectively.
tives for the carbon-carbon bond forming reactions.6
There is a continuing need for simple and versatile syn-
thetic ligands and catalysts for this type of reaction. In
continuation of our research interest in the development of
7
,8
new and novel synthetic methodologies, here we wish to
report a new and novel ligand, 1,3-phenylene-bis-(1H)-
tetrazole (2), which worked efficiently in Suzuki reaction.
Ligand 2 was readily prepared in one step from 1,3-phe-
Equation 2
nylene-diamine (1), sodium azide and triethyl orthofor-
mate in acetic acid (Equation 1).9
Table 1 Reaction of 4-Chlorotoluene 3a with 4-Methoxy Phenyl-
boronicacid 4c in Various Solvents
We believe that this tetrazole ligand 2 can have ability to
Entry
Solvent
Temp (°C),
time (h)
Yield
(%, conversion)
coordinate with palladium either through nitrogen as in
the case of 1,2,3-triazole pincer ligand (NCN),10 or by
C-H activation as in the case of imidazolyl pincer ligand
1
2
3
4
THF
60, 24
115, 12
60, 24
Trace
1
1
(
NHC). Although we have not yet fully characterized
Toluene
CHCl3
DMF
18 (40)
Trace
SYNLETT 2004, No. 12, pp 2227–2229
0
1
.1
0
.2
0
0
4
Advanced online publication: 31.08.2004
DOI: 10.1055/s-2004-831303; Art ID: U15304ST
100, 12
88 (100)
©
Georg Thieme Verlag Stuttgart · New York

2
228
A. K. Gupta et al.
LETTER
Table 1 Reaction of 4-Chlorotoluene 3a with 4-Methoxy Phenyl-
boronicacid 4c in Various Solvents
as products in good to excellent yields. As we have ex-
pected, the reaction of 4-cholorotoluene (3a) with 2,6-
dimethoxy phenylboronic acid (4f) afforded only 10%
yield. The similar reactivity was observed with 4-chloro-
anisole (3b) with five different arylboronic acids 4a–f.
Entry
5
Solvent
Temp (°C),
time (h)
Yield
(%, conversion)
1,4-Dioxane
100, 24
34 (56)
Table 2 Reaction of 4-Chlorotoluene 3a with 4-Methoxy Phenyl-
boronic Acid 4c with Different Bases
Entry
Base
Temp (°C),
Time (h)
Yield
(%, conversion)
Equation 3
1
2
3
4
5
6
7
Cs CO3
100, 12
100, 12
100, 12
100, 12
100, 12
100, 12
100, 12
Trace
2
Table 4 Reactions of Arylhalides 3a–i with Arylboronic Acids 4a–
K CO3
9 (21)
2
1
Temp (°C), time (h) Yield (%)a
Aryl R B- Base
halides (OH)2
K CO , TBAB
22 (65)
56 (60)
88 (100)
20 (53)
18 (40)
2
3
t-BuOK
3
3
3
a
4a
t-BuOK, TBAB
t-BuOK, TBAB
K CO , TBAB
100, 12
100, 12
100, 12
100, 12
100, 48
77
88
79
72
10
4
4
4
4
c
d
e
f
t-BuOK, TBAB
Sodium methoxide
KF·2H O
2
b
4a
100, 12
100, 12
100, 12
100, 12
100, 18
81
83
76
78
18
4
b
Table 3 Reaction of 4-Chlorotoluene 3a with 4-Methoxy Phenyl-
boronic Acid 4c with Different Catalysts
4d
4e
4
f
Entry
Catalyst
Temp (°C),
time (h)
Yield
(%, conversion)
ca
4b
100, 10
100, 10
81
82
2
3
4
c
K CO , TBAB
2 3
1
2
3
4
5
6
7
8
Pd(OAc)2
PdCl2
100,12
100, 12
100, 12
100, 12
100, 12
100, 12
100, 12
100, 12
88 (100)
12 (15)
13 (15)
Trace
3
3
3
3
3
da
ea
fa
4b
4b
4b
4b
K CO , TBAB
100,10
100, 10
100, 10
100, 10
65
69
62
58
2
3
K CO , TBAB
2
3
PtCl2
K CO , TBAB
2
3
Pd(Ph P)
3
4
4
ga
ha
K CO , TBAB
2 3
Pd(Ph P)
Trace
3
4a
4b
K CO , TBAB
100, 12
100, 12
100, 12
100, 12
100, 12
86
81
88
84
59
2
3
(CH CN) PdCl
31 (45)
37 (40)
23 (25)
3
2
2
4
d
Pd dba3
4e
2
4
f
NiCl2
3
ib
4a
Cs CO
80, 8
80, 8
80, 8
80, 8
80, 10
90
95
89
83
85
2
3
4
4
c
d
From these experimental results, a combination of
Pd(OAc) and ligand 2 in DMF as solvent were found to
4e
4f
2
be the most suitable conditions. We believe that ligand 2
plays an effective role in the present reaction, because
Pd(II) acetate itself can not catalyze Suzuki cross-cou-
pling reaction, when aryl chlorides are used. Although
low turn-over-number (TON, about 20–100) in the
present reaction is one major disadvantage, the reactivity
of ligand 2 was checked with various types of arylhalides
a
3
1
mol% catalyst was used.
mol% catalyst was used.
b
3
a–i
4a–f
1
2
X = Cl R = 4-CH (3a)
R = H (4a)
3
1
R = 4-OCH (3b)
3
3
4
a–i vs. arylboronic acids 4a–f (Equation 3 and Table 4).
-Chlorotoluene (3a) treated with five different aryl-
1
2
R = 4-NO (3c)
R = 4-CH (4b)
2
3
1
R = 2-NO
(3d)
2
1
2
boronic acids 4a–f from phenyl boronic acid (4a), p-tolyl-
boronic acid (4b), p-methoxyphenylboronic acid (4c),
3
boronic acid (4e) to a sterically hindered 2,6-dimethoxy- X = Br R = 4-OCH (3h)
phenyl boronic acid (4f). In all these cases except 4f, we
have obtained cross-coupled biphenyl compounds 5aa–ae
R = 4-CHO (3e)
R = 4-OCH (4c)
3
1
R = 4-COCH (3f)
3
1
2
,5-dimethylphenylboronic acid (4d), and 4-cyanophenyl
R = 3-NO
2
-pyridyl (3g)
R = 3,5-(CH
3
)
2
(4d)
1
2
R = 4-CN (4e)
3
1
2
X = I R = 4-CH (3i)
R = 2,6-(OCH ) (4f)
3
3 2
Synlett 2004, No. 12, 2227–2229 © Thieme Stuttgart · New York

LETTER
1,3-Phenylene-bis-(1H)-tetrazole Pincer Ligand
2229
Next, we took more reactive aryl halides like 4-nitrochlo-
robenzene (3c), 2-nitrochloro benzene (3d), 4-chloro-
benzaldehyde (3e), 4-chloro-acetophenone (3f) and 2-
chloro-3-nitro pyridine (3g) in the presence of K CO as a
(3) Kim, Y.-J.; Joo, Y.-S.; Han, J.-T.; Won, S. H.; Soon, W. L.
J. Chem. Soc., Dalton Trans. 2002, 18, 3611.
(
4) (a) Moulton, C. J.; Shaw, B. L. J. Chem. Soc., Dalton Trans.
976, 102. (b) Van Koten, G.; Timmer, K.; Noltes, J. G. J.
1
2
3
Chem. Soc., Chem. Commun. 1978, 250.
base and TBAB. The reactions underwent very smoothly
(
5) (a) Cabri, W. Acc. Chem. Res. 1995, 28, 2. (b) Suzuki, A.
Chem. Rev. 1995, 95, 2457. (c) Gupta, M.; Hagen, C.;
Kaska, W. C.; Crammer, R. E.; Jenson, C. M. J. Am. Chem.
Soc. 1997, 119, 840. (d) Dani, P.; Karlen, T.; Gossage, R.
A.; Gladiali, S.; Van Koten, G. Angew. Chem. Int. Ed. 2000,
even in 3 mol% usage of ligand 2 and Pd(OAc) and gave
2
the corresponding coupling products 5 in very good
yields. In order to extend the scope of the present ligand
2
, we tested an aryl bromide and an aryl iodide. 4-Bro-
39, 743. (e) Gorla, F.; Togni, A.; Venanzi, L.
moanisole (3h) as a representative aryl bromide was treat-
ed with aryl boronic acids 4a–e. Here we have taken a
Organometallics 1994, 13, 1607. (f) Stark, M. A.; Richards,
C. J. Tetrahedron Lett. 1997, 38, 5881. (g) Denmark, S.;
Stavenger, R. A.; Faucher, A. M.; Edwards, J. P. J. Org.
Chem. 1997, 62, 3375. (h) Hoveyda, A. H.; Morken, J. P.
Angew. Chem., Int. Ed. Engl. 1996, 35, 1262. (i) Longmire,
J. M.; Zhang, X. Tetrahedron Lett. 1997, 38, 1725.
mixture of ligand (3 mol%), Pd(OAc) (3 mol%), potassi-
2
um carbonate (2 equiv), TBAB, and heated for 10–12
hours in DMF. All arylboronic acids 4a–f including steri-
cally hindered arylboronic acid 4f gave the coupling prod-
ucts in excellent yields. The same methodology was also
successfully applied to 4-iodotoluene (3i) with only 1
mol% of the catalyst. In summary, we have synthesized
the new ligand 1,3-phenylene-bis-(1H)-tetrazole ligand
(
6) (a) Bourissou, D.; Guerret, O.; Gabbai, F. P.; Betrand, G.
Chem. Rev. 2000, 100, 39. (b) Vincent, C.; Bellemin-
Laponnaz, S.; Gade, L. H. Organometallics 2002, 21, 5204.
(
4
c) Tao, B.; Boykin, D. W. Tetrahedron Lett. 2002, 43,
955. (d) Yang, C.; Nolan, S. P. Synlett 2001, 10, 1539.
(
2) and have shown to be an effective catalyst for the
(7) (a) Oh, C. H.; Park, S. J. Tetrahedron Lett. 2003, 44, 3785.
(b) Oh, C. H.; Sung, H.; Park, S. J.; Ahn, K. H. J. Org. Chem.
Suzuki cross-coupling reactions of various aryl chlorides,
2002, 67, 7155. (c) Oh, C. H.; Lim, Y. M. Bull. Korean
bromides and iodides in combination with Pd(OAc) . We
2
Chem. Soc. 2002, 23, 663. (d) Oh, C. H.; Jung, H. H.; Kim,
K. S. Angew. Chem. Int. Ed. 2003, 42, 805. (e) Oh, C. H.;
Gupta, A. K.; Kim, K. S. Chem.Comm. 2004, 618. (f) Oh,
C. H.; Ahn, T. W.; Reddy, V. R. Chem. Commun. 2003,
believe that tetrazole-related ligands can offer promising
features for a number of other important palladium-cata-
lyzed reactions.
2
622.
8) Oh, C. H.; Gupta, A. K.; Song, C. Y. Tetrahedron Lett. 2004,
5, 4113.
(
Acknowledgment
4
We thank the Center of Molecular Design and Synthesis (CMDS)
and BK21for financial support of this research.
(9) Satoh, Y.; Marcopulos, N. Tetrahedron Lett. 1995, 36, 1759.
(10) (a) Diez-Barra, E.; Guerra, J.; Lopez-Solera, I.; Marino, S.;
Rodriguez-Lopez, J.; Sanchez-Verdu, P.; Tejeda, J.
Organometallics 2003, 22, 541. (b) Diez-Barra, E.; Guerra,
J.; Hornillos, V.; Merino, S.; Tejeda, J. Organometallics
References
2003, 22, 4610.
(
1) (a) Burger, A. Prog. Drug. Res. 1991, 37, 287. (b)Setsu,F.;
Umemura, E.; Sasaki, K.; Tadauchi, K.; Okutomi, T.;
Ohtsuka, K.; Takahata, S. PCT Int. Appl. WO 03042188,
(
(
11) (a) Grundemann, S.; Albrecht, M.; Loch, J. A.; Faller, J. W.;
Crabtree, R. H. Organometallics 2001, 20, 5485.
(b) Danopoulos, A. A.; Tsoureas, N.; Green, J. C.;
2003. (c) Schelenz, T.; Schäfer, W. J. Prakt. Chem. 2000,
Hurstouse, M. L. Chem. Commun. 2003, 756.
342, 91. (d) Aurer, F.; Kido, K.; Kurahashi, Y.; Sawada, H.;
12) General Procedure: Palldium acetate (5 mol%), ligand 2 (5
mol%), and appropriate base (2 equiv) and additive TBAB
Tanaka, K.; Otsu, Y.; Hattori, Y.; Shibuya, K.; Abe, T.;
Goto, T.; Ito, S. Eur. Pat. Appl. EP 855394, 1998.
(10 mol%) were taken in DMF (10 mL) and the mixture was
(
e) Ruelke, H.; Friedel, A.; Martin, E.; Kottke, K.; Graefe, I.;
stirred at r.t. for 1 h. Appropriate aryl halides 3a–i (0.1 mol)
and arylboronic acids 4a–f (0.11 mmol, 1.1 equiv) were
added followed by additional portion of DMF (1.0 mL). The
mixture was then stirred at 80–120 °C. The reaction was
monitored by TLC. The reaction mixture was cooled, diluted
with 20 mL of H O and extracted with Et O (2 × 20mL). The
Kuehmstedt, H. Pharmazie 1991, 46, 456.
(2) (a) Van den Heuvel, E. J. P.; Franke, L.; Verschoor, G. C.;
Zuur, A. P. Acta Cryst., Sect. C: Cryst. Struct. Commun.
1989, 39(3), 337. (b) Peter, P. L.; Haasnoot, G. J.; Zuur, P.
A. Inorg. Chim. Acta 1982, 59, 5. (c) Franke, P. L.;
Groeneveld, W. L. Transition Met. Chem. 1981, 6, 54.
2
2
combined organic portion was washed with brine solution,
(
1
d) Franke, P. L.; Groeneveld, W. L. Transition Met. Chem.
980, 5, 240. (e) Franke, P. L.; Groeneveld, L. W. Inorg.
Chim. Acta 1980, 40, 111.
dried over anhyd MgSO , and finally filtered. Evaporatation
4
of the volatiles under reduced pressure to get the
corresponding biphenyl products 5.
Synlett 2004, No. 12, 2227–2229 © Thieme Stuttgart · New York