Tetrahedron Letters 48 (2007) 1099–1103
Synthesis of heteroarylazulenes: transition metal free
coupling strategy of azulene with heterocycles
a,
a
b
c
*
Taku Shoji, Ryuji Yokoyama, Shunji Ito, Masataka Watanabe,
a
d
a,
*
Kozo Toyota, Masafumi Yasunami and Noboru Morita
a
Department of Chemistry, Graduate School of Science, Tohoku University, Sendai 980-8578, Japan
Department of Materials Science and Technology, Faculty of Science and Technology, Hirosaki University, Hirosaki 036-8561, Japan
b
c
Institute of Multidisciplinary Research for Advanced Materials, Tohoku University, Sendai 980-8577, Japan
Department of Materials Chemistry and Engineering, College of Engineering, Nihon University, Koriyama 963-8642, Japan
d
Received 8 November 2006; revised 12 December 2006; accepted 14 December 2006
Available online 8 January 2007
Abstract—Azulene reacts with highly electrophilic trifluoromethanesulfonates of N-containing heterocycles to give 1-dihydrohetero-
aryl and 1,3-bis(dihydroheteroaryl)azulene derivatives in a good yield. Treatment of the dihydroheteroarylazulene derivatives with
KOH or tert-BuOK afforded 1-heteroaryl and 1,3-bis(heteroaryl)azulenes in a good yield.
Ó 2006 Elsevier Ltd. All rights reserved.
Heterocycles containing a nitrogen atom are found in
numerous natural products and many biologically active
pharmaceuticals comprise such heterocycles. Therefore,
romethanesulfonic anhydride (Tf O) with pyridine (2),
2
gave 6-(1-azulenyl)-1-trifluoromethanesulfonyl-1-aza-
hexa-1,3,5-triene as the main product, which comes
from an attack of 1 to the 2-position of TPT. However,
the reaction of 1 with TPT in the presence of a large
amount of 2 gave 1,3-bis(4-dihydropyridyl)azulene
derivatives (10b), which comes from an attack of 1 to
1
it is important to develop general methods to synthesize
or modify such compounds. Recently, many transition
metal-catalyzed aryl–aryl cross-coupling reactions such
2
3
4
as the Stille-, Suzuki-, and Ullmann-type reactions,
6
which require a relatively high temperature, are reported
in the literature. Previously, we have reported a
palladium-catalyzed synthesis of 2- and 6-heteroaryl-
the 4-position of TPT. Therefore, excess pyridine is
needed to obtain the dihydropyridylazulene derivatives
in a good yield. Actually, the selective synthesis of 1-
(4-dihydropyridyl)azulene (10a) and 1,3-bis(4-dihydro-
pyridyl)azulene derivative (10b) was easily controlled
5
azulenes. However, palladium-catalyzed aryl–azulenyl
coupling is not effective at the 1- or 1,3-positions of azu-
lene rings, because these positions have highly electron-
donating properties. Therefore, we report herein a facile
azulenyl–heteroaryl coupling reaction of heterocycles
containing a nitrogen atom at the 1 or 1,3-positions of
azulene via dihydroheteroarylazulene derivatives under
mild conditions without a transition metal catalyst.
by the amount of Tf O under excess 2. We extended this
2
procedure to several N-containing heterocycles such as
isoquinoline (3), acridine (4), 1,10-phenanthroline (5),
benzothiazole (6), benzoxazole (7), benzimidazole (8),
and quinoline (9). The general procedure is shown in
Refs. 15 and 16. The proportion of the amounts of
azulene, Tf O, and heterocycles is very important to
2
We have recently demonstrated a reaction of azulene (1)
with trifluoromethanesulfonylpyridinium trifluorome-
thanesulfonate (TPT). In this case, the reaction of 1 with
TPT, which is prepared from an equivalent of trifluo-
determine the products distribution. The results are
summarized in Table 1. Similarly to the reaction of pyr-
idine (2), nitrogen-containing heterocycles 3–8 reacted
with azulene (1) at room temperature in the presence
of Tf O to give the corresponding 1-dihydroheteroaryl-
2
azulene derivatives 10a–16a and 1,3-bis(dihydrohetero-
aryl)azulene derivatives 10b–16b in a good yield. In the
case of the reaction of acridine (4), Corey and Tian have
Keywords: Azulene; Heterocycle; Electrophilic substitution.
*
reported that electron-rich aniline derivatives do not re-
7
act with 4 in the presence of Tf O, whereas azulene (1),
2
0040-4039/$ - see front matter Ó 2006 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2006.12.083