1-(2-Iodophenyl)-1H-tetrazole as a ligand for Pd(II) catalyzed Heck reaction

Article abstract of DOI:10.1016/j.tetlet.2004.03.162

1-(2-Iodophenyl)-1H-tetrazole 2 was synthesized by the reaction of 2-iodoaniline, sodium azide and triethyl orthoformate in acetic acid. The newly synthesized ligand 2 was successfully used in Heck reaction to give the cross-coupled products in excellent yields.

Full text of DOI:10.1016/j.tetlet.2004.03.162

Tetrahedron
Letters
Tetrahedron Letters 45 (2004) 4113–4116
1-(2-Iodophenyl)-1H-tetrazole as a ligand for
Pd(II) catalyzed Heck reaction
Arun Kumar Gupta, Chung Hyun Song and Chang Ho Oh*
Green Organic Synthesis Lab, Department of Chemistry, Hanyang University, Seoul 133 791, South Korea
Received 21 February 2004; revised 23 March 2004; accepted 24 March 2004
Abstract—1-(2-Iodophenyl)-1H-tetrazole 2 was synthesized by the reaction of 2-iodoaniline, sodium azide and triethyl orthoformate
in acetic acid. The newly synthesized ligand 2 was successfully used in Heck reaction to give the cross-coupled products in excellent
yields.
ꢀ 2004 Elsevier Ltd. All rights reserved.
For the construction of carbon–carbon single bond,
Heck reaction has become one of the standard protocols
in the organic synthesis1 and also it became a bench
mark to estimate the efficiency of a catalytic system. In
general, phosphine palladium complexes are employed
for Heck reactions under inert atmosphere to minimize
the deleterious effect of oxygen in the air. Therefore,
many research groups have been seriously involved in
the development of easy-handling catalysts, which have
highly efficient catalytic activity and are stable towards
oxidants and moisture variations.2 Recently new types
of nonphosphine ligands such as heterocyclic carbenes,
imines, imidazoles and 1,2,3-triazoles have emerged as
an alternative for the Heck reaction.3 Though hetero-
cyclic carbenes show good to excellent catalytic activities
with palladium, they easily undergo decomposition
pathways at higher temperature.4 Also nitrogen-based
ligands are sensitive towards acidic conditions. There
are very few examples that tetrazoles were used as
ligands5 with Ni or Ru. To our knowledge, reports on
usage of tetrazole in palladium- or platinum-catalyzed
reactions are scarce.6 Literature reveals that tetrazole
functionality survives as one of the important pharma-
cophore in medicinal chemistry as well as synthon in
synthetic organic chemistry.7 In continuation of our
research interest in the development of new and novel
synthetic methodologies and catalysts,8 here we wish to
report synthesis of 1-(2-iodo-phenyl)-1H-tetrazole (2), a
new and novel ligand, which worked efficiently in Heck
reaction with good TON and TOF. Ligand 2 was readily
prepared in one step from 2-iodo aniline, triethyl
orthoformate and sodium azide in acetic acid at 6 h
reflux condition (Eq. 1).9
N
N
N
HC(OEt)3
NaN3
NH2
I
N
I
ð1Þ
AcOH, reflux, 6h
1
2
It should be noted that catalyst in this study was neither
preformed nor preactivated by any agents. The palla-
dacycle can be easily formed by simply mixing Pd(OAc)2
and base (2 equiv) together under reaction conditions. A
characteristic feature of our palladacycle is the thermal
stability, which makes it possible to perform the reac-
tions even at temperature above 100 ꢁC, which is nec-
essary for less reactive substrates such as aryl bromides.
We assume that ligand 2 can 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 1,2,4-triazole pincer ligand (NHC).11
O
I
O
OCH3
Pd(OAc)2 (1.0 mol%)
Ligand 2 (1.0 mol%)
NaOAc (1.5 eq)
+
OCH3
Keywords: 1H-Tetrazole; Aryl halides; Arylboronic acids; Heck
reaction.
H3C
5ia
3i
4a
H3C
* Corresponding author. Tel.: +82-222900963; fax: +82-222990762;
e-mail: akg1966@yahoo.com
ð2Þ
0040-4039/$ - see front matter ꢀ 2004 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2004.03.162

4114
A. K. Gupta et al. / Tetrahedron Letters 45 (2004) 4113–4116
Table 1. Heck arylation of methyl acrylate 4a with 4-iodotoulene 3i in
various solvents
Table 3. Reactions of 4-iodotoulene 3i with various a,b-unsaturated
carbonyl compounds (4a–j)
Entry
Solvent
Temp
(ꢁC)
Time
(h)
% Yield
(conversion)
Entry
4
Temp
(ꢁC)/
Time (h)
Products % Yield
1
2
3
4
5
THF
60
120
60
48
48
48
6
30 (70)
45 (50)
35 (70)
98 (100)
75 (80)
Toluene
Chlorofom
DMF
1
80, 6
5ia
99
COOCH3
COCH3
4a
80
1,4-Dioxane 100
12
2
3
100, 12
80, 10
5ib
5ic
93
96
4b
4c
4d
CHO
CN
In view of the optimization of the reaction conditions,
we have performed the reaction of 4-iodotoulene 3i with
methyl acrylate 4a in various solvents (Eq. 2). Table 1
showed that DMF was the suitable solvent for our
study. These reactions are highly selective and proceed
without formatting biphenyl. We found that ligand 2 is
more effective than classical Pd(II) salts, because
Pd(II)acetate itself catalyzes the Heck reaction a little,
when aryl iodides are used. Although we have not
attempted to search for lowest possible loads of the
precatalyst in the reactions with arylhalides, we have
tested the higher limits of activity of the palladacycle
(0.01 mol %), in the reaction of 4-iodotoulene 3i with
methyl acrylate 4a with very low load of ligand and
catalyst (Table 2). The use of 1.0 mol % catalyst was
turned out to be optimal condition to yield the Heck
reaction product 5ia.
4
5
100, 10
120, 15
5id
5ie
96
79
COOCH
3 4e
COOCH3
6
7
120, 12
80, 12
5if
5ij
82
78
4f
CONH2
4g
COOCH3
COOCH3
8
80, 10
5ih
72
4h
4i
O
O
O
9
100, 12
120, 12
5ii
5ij
65
68
In order to check the activity of ligand 2, we have per-
formed the reaction with various types of a,b-unsatu-
rated carbonyl compounds 4a-j, that is highly reactive
substances like methyl vinylketone 4b, acrolien 4c and
acrylonitrile 4d, substituted a,b-unsaturated carbonyl
compounds such as a-methyl methacarylate 4e and
methyl crotonate 4f, and very less reactive substance
such as acryl amide 4g (Eq. 3). Reactions of all a,b-
unsaturated carbonyl compounds 4b–g gave the corre-
sponding Heck products in good to excellent yields
(Table 3). But reactions with diethyl maleate 4h, maleic
anhydride 4i and cyclohexenone 4j were ended up to the
products in 72%, 65% and 68% yields, respectively. It is
surprising that acrylamide 4g, the least reactive substrate
among a,b-unsaturated carbonyl compounds 4a–j, gave
5id in almost quantitative yield. To our delight, further
data indicated that these Heck reactions catalyzed by
the tetrazole–Pd complex afforded to the products 5
stereoselectively in good to excellent yields. Next, we
have tested various aryl halides 3a–p with methyl acryl-
ate (4a) (Eq. 4) and the results thus obtained are sum-
marized in Table 4.12
10
O
4j
I
R2
R3
R4
Pd(OAc)2 (1.0 mol%)
Ligand 2 (1.0 mol%)
NaOAc (1.5 eq), DMF
R2
R3
+
R4
Me
3i
Me
4a-j
5ia-ij
ð3Þ
X
+
COOCH3
Pd(OAc)2 (1.0 mol%)
COOCH3
Z
Z
Ligand 2 (1.0 mol%)
base, DMF
5aa-pa
3a-p
4a
ð4Þ
It is remarkable that our ligand 2 exhibited good cata-
lytic activity in the Heck reaction even for arylbromides
Table 2. Heck reaction of methyl acrylate 4a with 4-iodotoluene 3i at various catalyst concentrationa
Entry
Catalyst (mol %)
Temp (ꢁC)
Time (h)
Yield (%)b
TONc
TOFd (hꢀ1
)
1
2
3
4
10
80
80
80
80
6
6
100
99
100
988
16.6
164
879
1. 0
0.1
10
24
87
56
8793
5600
0.01
233
a Reaction condition: 4-CH3–PhI (0.01 mol) methyl acrylate (0.02 mol), DMF solvent (25 mL), 80–100 ꢁC, NaOAc (2.0 equiv).
b Isolated yield.
c TON: turnover number (mol product per mol catalyst).
d TOF: TON per hour.

A. K. Gupta et al. / Tetrahedron Letters 45 (2004) 4113–4116
4115
Table 4. Reactions of aryl halides with methyl acrylate
Substrates
Base
Temp (ꢁC)/Time (h)
% Yield
No
Z
X
3a
3b
3c
3d
3e
3f
H
4-Me
2-Me
Br
Br
Br
Br
Br
Br
Br
I
K2CO3, TBAB
K2CO3, TBAB
K2CO3, TBAB
K2CO3, TBAB
K2CO3, TBAB
K2CO3, TBAB
K2CO3, TBAB
NaOAc
120, 24
120, 14
120, 32
120, 12
120, 14
120, 12
120, 48
80, 14
80, 6
65
76
57
67
76
47
15
86
99
94
95
91
78
69
79
81
39
4-CHO
4-OMe
2-CHO
2,6-(CH3)2
H
3g
3h
3i
4-Me
I
NaOAc
NaOAc
3j
4-OMe
4-NO2
4-COCH3
4-CHO
3-CHO
4-CN
I
80, 12
100, 12
80, 12
80, 12
80, 15
80, 15
80, 6
3k
3l
I
NaOAc
NaOAc
I
3m
3n
3o
3p
3q
I
NaOAc
NaOAc
I
I
NaOAc
NaOAc
K2CO3, TBAB
4-Br
4-Me
I
Cl
120, 48
3a–g. As Hermann et al. has reported, we have added an
additive, tetrabutylammoniumbromide (TBAB), to
increase the reactivity (substrates 3a–f).13 To check the
reactivity of the ligand on sterically hindered aryl
halides, we have taken 2,6-dimethylbromobenzene 3g,
but it gave the product 5ga only in 15% yield even after
refluxing conditions. All type of aryl iodides 3h–p gave
the products 4ha–pa in good to excellent yields with our
ligand at 80–100 ꢁC. It is interesting that we have
observed a high chemoselectivity when we used 4-bro-
moiodobenzene 3p, where only the iodo group was
involved in the reaction under these conditions. As
expected, the low relativity was observed when we used
4-chlorotoluene 3q.
In conclusion, we have synthesised the new ligand 1-(2-
iodophenyl)-1H-tetrazole 2 and demonstrated that
combination of the ligand 2 with Pd(OAc)2 could be an
effective catalyst for Heck reactions. Also an excellent
chemoselectivity in case of 4-bromoiodobenzene 3p was
observed. The new ligand is air, water and heat sta-
ble. Further studies aimed at the improvement of the
catalytic activity of our nitrogen catalysts are in pro-
gress.
Acknowledgements
This work was supported by research fund (HY-2001-
78) of Hanyang University, Korea. C. H. Song is
grateful for a graduate fellowship supported by the
BK21 project.
Since the report on Heck reactions of arylboronic acids
with a,b-unsaturated carbonyl compounds under ligand
support is scarce,14 we extended our work to arylboronic
acids. Ligand 2 has showed moderate activity for the
reaction of arylboronic acids 6a–f with methyl acrylate
4a in the presence of Mn(OAc)2 as an additive (Eq. 5).
The results thus obtained were described in Table 5.
References and notes
B(OH)2
1. (a) Mizoroki, T.; Mori, K.; Ozaki, A. Bull. Chem. Soc.
Jpn. 1971, 44, 581; (b) Amatore, C.; Jutand, A. Acc. Chem.
Res. 2000, 33, 314; (c) Heck, R. F. Palladium Reagents in
Organic Synthesis; Academic: London, 1990.
2. Whitcombe, N. J.; Hii, K. K.; Gibson, S. E. Tetrahedron
2001, 57, 7449.
3. (a) Bourissou, D.; Guerret, O.; Gabbai, F. P.; Betrand, G.
Chem. Rev. 2000, 100, 39; (b) Ten Brink, G.-J.; Arend, I.
W. C. E.; Sheldon, R. A. Science 2000, 287, 1636; (c)
Bianchi, D.; Bortolo, R.; D’Aloisio, R.; Ricci, M. K.
Angew. Chem., Int. Ed. 1999, 38, 706; (d) Yang, C.; Nolan,
S. P. Synlett 2001, 10, 1539.
COOCH3
Pd(OAc)2 (1.0 mol%)
Ligand 2 (1.0 mol%)
base, DMF
+
Z
4a
Z
6a-f
7aa-fa
ð5Þ
Table 5. Reactions of arylboronic acids with methyl acrylate
Arylboronic acid
Reaction condition
Yield (%)
No
Z
Temp (ꢁC) Time (h)
4. McGuiness, D. S.; Saendig, N.; Yates, B. F.; Carvell, K. J.
J. Am. Chem. Soc. 2001, 123, 4029.
6a
6b
6c
6d
6e
H
4-Me
110
110
110
110
110
12
12
12
12
12
75
62
67
61
33
5. (a) Van den Heuvel, E. J.; Franke, P. L.; Verschoor, G. C.;
Zuur, A. P. Acta Crystallogr. Sect. C: Cryst. Struct.
Commun. C 1983, 39(3), 337; (b) Franke, P. L.; Haasnoot,
J. G.; Zuur, A. P. Inorg. Chim. Acta 1982, 59, 5; (c)
Franke, P. L.; Groeneveld, W. L. Trans. Metal Chem.
1981, 6(1), 54; (d) Franke, P. L.; Groeneveld, W. L. Trans.
3,5-(Me)2
4-OMe
2,6-
(OCH3)2
3,5-F2
6f
100
12
58

4116
A. K. Gupta et al. / Tetrahedron Letters 45 (2004) 4113–4116
Metal Chem. (Dordrecht, Netherlands) 1980, 5, 240; 9. Satoh, Y.; Marcopulos, N. Tetrahedron Lett. 1995, 36,
(e) Franke, P. L.; Groeneveld, W. L. Inorg. Chim. Acta
1980, 40, 111.
6. Kim, Y.-J.; Joo, Y.-S.; Han, J.-T.; Won, S. H.; Soon, W.
L. J. Chem. Soc., Dalton Trans. 2002, 18, 3611.
1759.
10. Jung, I. G.; Son, S. U.; Park, K. H.; Chung, K.-C.; Lee, J.
W.; Chung, Y. K. Organometallics 2003, 22, 4715.
11. Stephan, G.; Martin, A.; Jennifer, A. L.; Jack, W. F.;
Robert, H. C. Organometallics 2001, 20, 5485.
7. (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. WO03042188,
2003; (c) Schelenz, T.; Schafer, W. J. Fuel Prakt. Chem.
2000, 342(1), 91; (d) Aurer, F.; Kido, K.; Kurahashi, Y.;
Sawada, H.; Tanaka, K.; Otsu, Y.; Hattori, Y.; Shibuya,
K.; Abe, T.; Goto, T.; Ito, S. Eur. Pat. Appl. EP 855394,
1998; (e) Ruelke, H.; Friedel, A.; Martin, E.; Kottke, K.;
Graefe, I.; Kuehmstedt, H. Pharmazie 1991, 46,
456.
8. (a) Oh, C. H.; Park, S. J. Tetrahedron Lett. 2003, 44, 3785;
(b) Oh, C. H.; Sung, H. R.; Park, S. J.; Ahn, K. H. J. Org.
Chem. 2002, 67, 7155; (c) Oh, C. H.; Lim, Y. M. Bull.
Korean 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. Commun.
2004, 618; (f) Oh, C. H.; Ahn, T. W.; Reddy, V. R. Chem.
Commun. 2003, 2622.
12. Palladium acetate (2.24 mg, 0.01 mmol), ligand 2 (2.72 mg,
0.01 mmol) and base (2 equiv) were taken in DMF
(10.0 mL) and the mixture was stirred at room temperature
for 1 h. Appropriate aryl halide 3 or aryl boronic acid 6
(1 mmol) and acrylates 4 (2 mmol) were added followed by
another additional portion of DMF (1.0 mL). The mixture
was then stirred at 80–120 ꢁC. The reaction completion was
monitored by TLC. The reaction mixture was cooled,
diluted with 50 mL of water and extracted with ether
(2 · 50 mL). The combined organic portion was washed
with brine solution, dried over anhydrous magnesium
sulfate and finally filtered. Evaporatation of the volatiles
under reduced pressure to get the corresponding product.
13. Hermann, W. A.; Bohm, V. P. W.; Reisinger, C. P.
J. Organomet. Chem. 1999, 576, 23.
14. Murugaiah, M. S. A.; Peter, N.; Mats, L. Chem. Commun.
2004, 218.