Palladium- and copper-catalyzed selective arylation of 5-aryltetrazoles by diaryliodonium salts

Article abstract of DOI:10.1016/S0040-4039(02)01325-4

Palladium(0)-catalyzed arylation of 5-aryltetrazoles in t-BuOH at 80°C with diaryliodonium salts proceeds in the presence of copper(II) phenylcyclopropyl carboxylate regioselectively at the N2 position.

Full text of DOI:10.1016/S0040-4039(02)01325-4

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 43 (2002) 6221–6223
Palladium- and copper-catalyzed selective arylation of
5-aryltetrazoles by diaryliodonium salts†
Irina P. Beletskaya, Dmitri V. Davydov* and Matvey S. Gorovoy
Chemical Department of Lomonosov Moscow State University, Leninsky Gory, Moscow 119899, Russia
Received 30 April 2002; revised 18 June 2002; accepted 28 June 2002
Abstract—Palladium(0)-catalyzed arylation of 5-aryltetrazoles in t-BuOH at 80°C with diaryliodonium salts proceeds in the
presence of copper(II) phenylcyclopropyl carboxylate regioselectively at the N2 position. © 2002 Elsevier Science Ltd. All rights
reserved.
the presence of the palladium catalyst, Pd(dba)2/rac-
BINAP, and a Cu(II) carboxylate salt in t-BuOH as
shown below (Scheme 2).
2,5-Diaryltetrazoles are used as convenient precursors
to a variety of nitrogen containing heterocycles2 and for
the preparation of tetrazolium salts possessing well-
known biological activity.3 Common methods for the
synthesis of 2,5-diaryltetrazoles involve multistep proce-
dures based on various cyclization protocols.4–7 Thus,
the development of a direct regioselective arylation of
easily available 5-aryltetrazoles8 at the N2 position of
the tetrazole ring would be a desirable alternative.
Generally, arylation can proceed forming two iso-
mers—a 1,5-diaryltetrazole (N1) and a 2,5-diaryltetra-
zole (N2) (Scheme 1).
The optimization of reaction conditions has been per-
formed using 5-phenyltetrazole and Ph2I+BF4 . The
−
data obtained are presented in Table 1.
Though the arylation of the Na-salt of 5-phenyltetra-
zole by Ar2I+BF4 takes place in the absence of a
−
catalyst,13 the reaction is slow and non-selective (Table
1, entry 1). The use of stoichiometric amounts of the
Cu(II)-salt (copper(II) phenylcyclopropyl carboxylate)
leads to a dramatic increase of selectivity but the yields
remain low (Table 1, entry 2). The use of Cu(OAc)2 was
unsuccessful.
Recently, two methods for regioselective N2-arylation
9
10
of 5-aryltetrazoles by ArB(OH)2 or by Ar3Bi(OAc)2
in the presence of Cu(OAc)2 were published. However
the first method gives modest yields of 2,5-diaryltetra-
zoles, while in the second two aryl groups of the
arylation agent are wasted.
On the other hand the addition of a Pd-catalyst
(Pd(dba)2/bidentate ligand) gave acceleration of reac-
tion and an increase in yields to nearly quantitative,
with rac-BINAP being particularly affective, although
the product contains the minor N1-arylation isomer
(Table 1, entries 3–6) Thus, it seemed sensible to
explore the synergistic effect of Cu(II) on selectivity and
Continuing our research on the Pd-catalyzed regioselec-
tive arylation of azoles,11,12 we have discovered that
sodium salts of 5-aryltetrazoles undergo regioselective
arylation at the N2 position by diaryliodonium salts in
Scheme 1.
Keywords: 5-aryltetrazoles; arylation; Pd-catalysis; regioselectivity; iodonium salts; Cu(II).
* Corresponding author. E-mail: dvdav@elorg.chem.msu.ru
† Preliminary communication. See Ref. 1.
0040-4039/02/$ - see front matter © 2002 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(02)01325-4

6222
I. P. Beletskaya et al. / Tetrahedron Letters 43 (2002) 6221–6223
Scheme 2.
−
Table 1. Arylation of the Na-salt of 5-phenyltetrazole by Ar2I+BF4 at 80°C in t-BuOH
N
Catalyst (mol%)
Ligand
Time (h)
Ratio of N2:N1 isomersa
Yield of N2+N1 isomers (%)a,b
1
2
3
4
5
6
7
8
–
–
–
18
18
6
6
6
6
6
18
ꢀ50:50
100:0
50:10
60:10
85:10
90:10
100:0
–
42
35
92
94
95
98
98
Cu(II) (100)
Pd(dba)2 (5)
Pd(dba)2 (5)
Pd(dba)2 (5)
Pd(dba)2 (5)
Pd(DBA)2 (5), Cu(II) (5)
Pd(DBA)2 (5)
DPPE
DPPB
DPPF
rac-BINAP
rac-BINAP
L2
No product
a N2:N1 ratio and yields of the products were measured by spectrophotometry after separation of reaction mixture aliquots by TLC.
b All products were characterized by NMR and MS spectra in good accordance with literature data.4–7
Table 2. Regioselective arylation of Na-salts of some 5-
aryltetrazoles by various diaryliodonium salts catalyzed by
Pd(dba)2/rac-BINAP (5 mol%) and Cu(II)-salt (5 mol%)
in t-BuOH at 80°C
Pd on the yield. Indeed the combination of Pd and Cu
complexes in catalytic amounts has resulted in the
development of a high-yielding regiospecific procedure
(Table 1, entry 7). We used the same copper salt (the
easy available Cu(II) phenylcyclopropyl carboxylate)
which already had proven its effectiveness in the early
developed procedures for regioselective arylation of
benzotriazole.11,12 However, while in the latter case
both Ar-groups of iodonium salts were incorporated
the product, in the arylation of 5-aryltetrazoles only
one residue is transferred. We were not able to perform
the arylation of 5-phenyltetrazole by ArI or ArBr as all
catalyst systems tried proved ineffective (Table 1, entry
8).
−
N
5-Aryltetrazole
Ar2I+BF4
Yield
of
N2 (%)a,b
1
5-(C6H5)-Tetrazole
Ph2I+BF4
98
97
94
97
93
−
(p-CH3C6H4)2I+BF4
−
(p-CH3OC6H4)2I+BF4
−
(p-ClC6H4)2I+BF4
−
−
2
3
4
5
5-(p-CH3C6H4)-
Tetrazole
Ph2I+BF4
(p-CH3C6H4)2I+BF4
(p-CH3OC6H4)2I+BF4
94
90
92
94
(p-ClC6H4)2I+BF4
−
5-(p-CH3OC6H4)-
Tetrazole
Ph2I+BF4
−
This procedure has been applied successfully for aryla-
tion of a series of 5-aryltetrazoles bearing both elec-
tron-donating or electron-withdrawing substituents.14
The data are gathered in Table 2.
(p-CH3C6H4)2I+BF4
93
93
97
97
−
(p-CH3OC6H4)2I+BF4
(p-ClC6H4)2I+BF4
−
−
5-(p-BrC6H4)-
Tetrazole
Ph2I+BF4
(p-CH3C6H4)2I+BF4
(p-CH3OC6H4)2I+BF4
96
94
97
95
96
93
97
References
−
−
−
(p-ClC6H4)2I+BF4
1. Davydov, D. V.; Gorovoy, M. S.; Beletskaya, I. P. Theses
of 10th Symposium on Organo-Metallic Chemistry; Ver-
sailles, France, July 1999; P-534.
2. Moderhack, D. J. J. Pract. Chem. 1998, 340, 687–709.
3. Zivich, A. B.; Koldobski, G. I.; Ostrovski, V. A. Chem.
Heterocyclic Comp. (English Trans.) 1990, 26, 1587–1598.
4. Ito, S.; Tanaka, Y.; Kakehi, A.; Kondo, K.-I. Bull. Chem.
Soc. Jpn. 1976, 49, 1920–1923.
5-(4-Py)-Tetrazole
Ph2IBF4
(p-CH3C6H4)2I+BF4
(p-CH3OC6H4)2I+BF4
(p-ClC6H4)2I+BF4
−
a Yields of the products isolated by preparative TLC.
b All products were characterized by NMR, MS and elemental analy-
sis and are in a good agreement with the published data.

I. P. Beletskaya et al. / Tetrahedron Letters 43 (2002) 6221–6223
6223
5. Shawali, A. S.; Fahmi, A. A.; Eweiss, N. F. J. Hetero-
cyclic Chem. 1979, 16, 123–126.
Tetrahedron Lett. 1998, 39, 5617–5620.
12. Beletskaya, I. P.; Davydov, D. V.; Moreno-Man˜as, M.
Tetrahedron Lett. 1998, 39, 5621–5622.
6. Ito, S.; Tanaka, Y.; Kakehi, A. Bull. Chem. Soc. Jpn.
13. Akiyama, T.; Imasaki, Y.; Kawanisi, M. Chem. Lett.
1974, 229–230.
1976, 49, 762–766.
7. Hassaneen, H. M.; Fahmi, A. A.; Abdelhamid, H.;
Yassin, A. A.; Shawali, A. S. J. Heterocyclic Chem. 1984,
21, 797–800.
14. Synthetic procedure: A mixture of the Na-salt of 5-aryltet-
razole obtained from 0.001 mol of 5-aryltetrazole and
0.001 mol of t-BuONa, 2 mol% of Pd(dba)2, 4 mol% of
rac-BINAP, 2 mol% of the Cu(II)-salt and 0.001 mol of
8. Koldobskii, G. I.; Ostrovskii, V. A. Russian Chem. Rev.
1994, 63, 797–865.
Ar2I+BF4 was heated under reflux in 20 ml. of t-BuOH
−
9. Lam, P. Y. S.; Clark, C. G.; Saubern, S.; Adams, J.;
Winters, M. P.; Chan, D. M. T.; Combs, A. Tetrahedron
Lett. 1998, 39, 2941–2944.
10. Fedorov, A. Yu.; Finet, J.-P. Tetrahedron Lett. 1999, 40,
2947–2948.
under N2 for 8 h (TLC control). The reaction mixture
was evaporated and residue was extracted by CH2Cl2.
The extract was passed through a layer of silica and
evaporated. The residue was recrystallized from an
appropriate solvent.
11. Beletskaya, I. P.; Davydov, D. V.; Moreno-Man˜as, M.