Coupling reaction of azulenyl-4,4,5,5-tetramethyl-1,3,2-dioxaborolanes with haloazulenes

Article abstract of DOI:10.1055/s-2002-31947

In order to study the physicochemical properties of azulene oligomers, the synthesis and a coupling reaction of 2-(2-amino-1,3-bisethoxycarbonyl-6-azulenyl)-4,4,5,5-tetramethyl-1,3,2- dioxaborolane (1) and 2-(2-azulenyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (2) were examined.

Full text of DOI:10.1055/s-2002-31947

PAPER
1013
Coupling Reaction of Azulenyl-4,4,5,5-tetramethyl-1,3,2-dioxaborolanes with
Haloazulenes
C
K
oupling
R
eaction
e
of
A
zule
n
i
yl-4,4,5,5-tetr
K
a
methyl-1,3,2-dio
u
r
H
al
o
oazulenes tobi, Hiroshi Tabata, Masato Miyauchi, Toshihiro Murafuji,* Yoshikazu Sugihara*
Department of Chemistry, Faculty of Science, Yamaguchi University, Yamaguchi City 753-8512, Japan
Fax +81839335768; E-mail: murafuji@po.cc.yamaguchi-u.ac.jp; sugihara@po.cc.yamaguchi-u.ac.jp
Received 21 January 2002; revised 28 March 2002
bromine atom to give 2-amino-1,3-bisethoxycarbonylazu-
lene (4) in 53% yield (Scheme 1). Less polarized 2-ami-
no-6-bromoazulene (5) was likewise transformed into 2-
Abstract: In order to study the physicochemical properties of azu-
lene oligomers, the synthesis and a coupling reaction of 2-(2-amino-
1
,3-bisethoxycarbonyl-6-azulenyl)-4,4,5,5-tetramethyl-1,3,2-diox-
aborolane (1) and 2-(2-azulenyl)-4,4,5,5-tetramethyl-1,3,2-diox- aminoazulene (6) in 26% yield. In contrast, 2-iodoazulene
aborolane (2) were examined.
(7) was transformed into 2,2 -biazulene (8) in 42% yield,
although the formation of azulene (28%) was observed.
The reaction using 2-chloroazulene (9) also gave 8 in 60%
yield together with a small amount of azulene. Compari-
son of the results for 3, 5, 7 and 9 is indicative of the dif-
ference between the reactivities at the 2- and 6-position,
which could be definitely ascribed to the polarized struc-
ture of the azulene nucleus.
Key words: arenes, azulene, boron, borylazulene, cross-coupling
Azulene oligomers and polymers are considered to be in-
triguing molecules from the viewpoint of the construction
of functional substances, since azulene exhibits high re-
dox potential, together with a moderate dipole moment
vector. As for the dimers of azulene, some synthetic stud-
ies and physicochemical behavior have been reported,1
and some novel functionalities of azulene oligomers seem
to have been indicated. The synthetic methods, however,
were considered to restrict the development of further
studies. Thus, the Ullman coupling reactions at high
EtO2C
EtO2C
H N
a)
H2N
Br
2
EtO2C
2
EtO C
2
temperature or more sophisticated reactions that are
3
4
6
based on Hafner’s azulene synthesis, starting from bipy-
3
ridyls, were used. Though the coupling reaction cata-
a)
lyzed with nickel dihalides was reported, it was
H2N
Br
H2N
4
a
effectively applied only to 1-bromoazulene. The excel-
5
lent Suzuki coupling using boryl-aromatic compounds
which are derived from metalated aromatic compounds
has been excluded, since the metalated azulene, such as
5
6
azulenyl lithium and azulenyl magnesium halide, has not
been reported in synthetic chemistry.
Recently, Miyaura has reported replacement of the halo-
gen atom bonded to an aromatic ring by the pinacolatobo-
ryl group with use of bis(pinacolato)diboron and
dichloro[1,1 -bis(diphenylphosphino)ferrocene]palladi-
a)
X
8
X = I (7)
X = Cl (9)
7
a
um. This method was considered not to involve free met-
alated aromatic compounds. Hence, we decided to apply
this reaction to the introduction of a boryl group to the
azulene nucleus. It is important to study how the polarized
electronic structure of azulene affects the introduction of
the pinacolatoboryl group as well as the subsequent
coupling reaction.
Scheme 1 Reagents and conditions: a) (Ph P) NiCl , tris(2-furyl)-
3
2
2
phosphine, Zn, Et NI, THF
4
With the difference between the reactivities due to the po-
sitions of the azulene nucleus known, 2-(2-amino-1,3-
The nickel-catalyzed coupling reaction has been shown to bisethoxycarbonyl-6-azulenyl)-4,4,5,5-tetramethyl-1,3,2-
4
a
be applicable to the synthesis of 1,1 -biazulene. Applica- dioxaborolane (1) and 2-(2-azulenyl)-4,4,5,5-tetramethyl-
tion of this reaction to 2-amino-6-bromo-1,3-bisethoxy- 1,3,2-dioxaborolane (2) were examined in the coupling
carbonylazulene (3), however, resulted in the loss of the reactions (Scheme 2). Application of the Miyaura
7a
method to the compounds 3 and 7 effectively yielded 1
and 2, respectively. The success of this simple application
of the Miyaura method is considered to be a fair contribu-
tion in azulene chemistry.
Synthesis 2002, No. 8, 04 06 2002. Article Identifier:
437-210X,E;2002,0,08,1013,1016,ftx,en;F00902SS.pdf.
Georg Thieme Verlag Stuttgart · New York
ISSN 0039-7881
1
©

1
014
K Kurotobi et al.
PAPER
EtO2C
EtO2C
O
O
a)
a)
3
H2N
B
2
H2N
EtO2C
EtO2C
EtO2C
10 (71%)
1
(73%)
CO2Et
a)
O
O
1
H N
NH2
a)
2
7
B
EtO2C
CO2Et
11 (24%)
2
(42%)
Scheme 3 Reagents and conditions: a) 3, (Ph P) PdCl , Ba(OH) ,
3
2
2
2
Scheme 2 Reagents and conditions: a) bis(pinacolato)diboron,
DME–H O (50:1), reflux
2
Pd(dppf)Cl , KOAc, DMSO, 80 °C
2
Treatment of 1 with iodobenzene in the presence of sesses an electron-withdrawing butoxycarbonyl group on
dichlorobis(triphenylphosphine)palladium and barium the nitrogen atom likewise reacted with 1 to afford N-Boc-
8
hydroxide gave 2-amino-1,3-bisethoxycarbonyl-6-phe- 2,5-bis(2-amino-1,3-bisethoxycarbonyl-6-azulenyl)pyr-
nylazulene in 91% yield. 2-Amino-1,3-bisethoxycarbon- role (14) in 41% yield. The reaction of 1 with 2,5-dibro-
yl-6,2 -biazulene (10) was obtained by the treatment of 2 mothiophene, however, resulted in recovery of the
and 3 under the same conditions. Compound 10 was also starting materials. Using the same method, an azulene tri-
formed by the coupling reaction of 1 with 7; however, the mer, that is, 2,2 -diamino-1,1 ,3,3 -tetrakisethoxycar-
yield was very low (28%). 2,2 -Diamino-1,1 ,3,3 -tet- bonyl-6,1 :3 ,6 -terazulene (15), was, for the first time,
rakisethoxycarbonyl-6,6 -biazulene (11) was synthesized synthesized in 46% yield.
in the same manner using 1 and 3 (Scheme 3). The
coupling reaction of 1 with 2,6-dibromopyridine (12)
In conclusion, we feel azulene oligomers with the desired
structures in arrangement and length can be synthesized
which consists of an electron-withdrawing pyridine nu-
with the use of the Miyaura method, together with control
cleus and the bromine atoms effectively gave 2,6-bis(2-
of the reactivities of the substituents based on the polarity
amino-1,3-bisethoxycarbonyl-6-azulenyl)pyridine (13) in
of the azulene nucleus.
8
5% yield (Scheme 4). A pyrrole derivative which pos-
EtO2C
a)
N
CO2Et
NH2
Br
N
Br
H2N
12
EtO2C
CO2Et
13 (85%)
CO2Et
NH2
EtO2C
H2N
a)
N
Br
Br
N
Boc
Boc
EtO2C
CO2Et
14 (41%)
EtO2C
2
CO Et
Br
H2N
NH2
a)
EtO2C
CO2Et
Br
15 (46%)
Scheme 4 Reagents and conditions: a) 1, (Ph P) PdCl , Ba(OH) , DME–H O (50:1), reflux
3
2
2
2
2
Synthesis 2002, No. 8, 1013–1016 ISSN 0039-7881 © Thieme Stuttgart · New York

PAPER
Coupling Reaction of Azulenyl-4,4,5,5-tetramethyl-1,3,2-dioxaborolanes with Haloazulenes
1015
Cross-Coupling Reaction; Typical Procedure
All reactions were carried out under argon. THF, DME and DMSO
To a suspension of (Ph P) PdCl (0.014 mmol), 1 (0.1 mmol) and
3 2 2
1
13
were distilled from CaH under nitrogen before use. H and
C
Ba(OH) 8H O (0.2 mmol) in DME–H O (50:1) (2 mL) was added
2 2 2
iodobenzene (0.15 mmol), and the mixture was refluxed for 24 h.
The reaction was quenched with water and the resulting mixture
2
NMR spectra were recorded in CDCl on a BRUKER AVANCE
3
4
00S (400 MHz) spectrometer with tetramethylsilane as an internal
standard. IR spectra were obtained as KBr pellets on a Nicolet Im-
pact 410 spectrophotometer. Mass spectra (EI) were determined on
a Waters LC–MS Integrity System at an ionization potential 70 eV.
UV/VIS spectra were measured by means of a Shimadzu UV-
was extracted with CHCl (3 5 mL). The combined extracts were
3
dried (Na SO ) and concentrated to leave a residue, which was
2
4
chromatographed (silica gel; hexane–EtOAc, 2:1) to give 2-amino-
1,3-bisethoxycarbonyl-6-phenylazulene.
1
600PC spectrophotometer.
Yield: 91%; yellow powder; mp 142–150 °C.
–
1
Nickel-Catalyzed Reaction; General Procedure
To a flask charged with (Ph P) NiCl (0.1 mmol), Zn (1.4 mmol),
IR: 1655 (CO) cm .
1H NMR: = 1.49 (6 H, t, J = 7.1 Hz), 4.48 (4 H, q, J = 7.1 Hz), 7.42
(1 H, t, J = 7.3 Hz), 7.49 (2 H, t, J = 7.4 Hz), 7.63 (2 H, d, J = 7.1
Hz), 7.79 (2 H, d, J = 11.4 Hz), 7.81 (2 H, s), 9.19 (2 H, d, J = 11.4
Hz).
3
2
2
Et NI (1.0 mmol) and tris(2-furyl)phosphine (0.2 mmol) was added
4
THF (6 mL) and then haloazulene (1.0 mmol). The suspension was
stirred at 50 °C for 12 h (for 3 and 5), at r.t. for 4 h (for 7) and 24 h
(
for 9), the reaction was quenched with brine, and the resulting mix-
13C NMR:
1
= 14.69, 59.86, 99.97, 127.92, 128.28, 128.86, 130.89,
32.82, 143.86, 144.86, 146.42, 162.42, 166.58.
ture was extracted with Et O (3 5 mL). The combined extracts
2
were dried (Na SO ) and concentrated to leave a residue, which was
2
4
chromatographed (silica gel; hexane–EtOAc, 5:1) to give the deha-
logenated and/or coupling product.
UV/VIS (dioxane):
(11720), 461 (sh) (2390).
( ) = 247 (31250), 338 (52030), 423
max
+
+
MS: m/z (%) = 245 (M – CO Et – OEt, 100), 317 (M – OEt – 1,
2
2
Preparation of Azulenyl-4,4,5,5-tetramethyl-1,3,2-dioxaborol-
anes; General Procedure
+
8), 363 (M , 70).
Anal. Calcd for C22
2.12; H, 5.80; N, 3.94.
To a flask charged with Pd(dppf)Cl2 (0.03 mmol), KOAc (3.0
mmol) and bis(pinacolato)diboron (1.1 mmol) was added DMSO (6
H21NO : C, 72.71; H, 5.82; N, 3.85. Found: C,
4
7
9
mL) and then haloazulene (3 or 7) (1.0 mmol). The mixture was
stirred at 80 °C for 5 h, the reaction was quenched with H O (20
2-Amino-1,3-bisethoxycarbonyl-6,2 -biazulene (10)
Yield: 71%; brown powder; mp 172–173 °C.
IR: 1682 (CO) cm–1.
2
mL), and the resulting mixture was extracted with benzene (3
5
mL). The combined extracts were dried (MgSO ) and concentrated
4
to leave a residue, which was chromatographed (silica gel; hexane–
EtOAc, 5:1) to give the product.
1H NMR: = 1.51 (6 H, t, J = 7.1 Hz), 4.49 (4 H, q, J = 7.1 Hz), 7.19
(
2 H, t, J = 9.8 Hz), 7.55 (1 H, t, J = 9.9 Hz), 7.74 (2 H, s), 7.84 (2
H, s), 8.25 (2 H, d, J = 11.5 Hz), 8.31 (2 H, d, J = 9.4 Hz), 9.18 (2
H, d, J = 11.5 Hz).
13C NMR: = 15.10, 60.26, 100.56, 116.01, 124.67, 131.08, 133.03,
137.28, 137.75, 141.43, 141.86, 145.55, 152.03, 163.05, 166.96.
2
-(2-Amino-1,3-bisethoxycarbonyl-6-azulenyl)-4,4,5,5-tetrame-
thyl-1,3,2-dioxaborolane (1)
Yield: 73%; orange solid; mp 167–170 °C.
–
1
IR: 1670 (CO) cm .
1H NMR: = 1.38 (12 H, s), 1.47 (6 H, t, J = 7.1 Hz), 4.43 (4 H, q,
J = 7.1 Hz), 7.93 (2 H, s), 8.05 (2H, d, J = 10.6 Hz), 9.08 (2 H, d,
J = 10.6 Hz).
UV/VIS (dioxane): max ( ) = 251 (71300), 295 (23960), 334
(
(
94700), 358 (sh) (58530), 467 (54170), 576 (sh) (1180), 623 (sh)
830), 681 (sh) (320).
+
+
13C NMR:
MS: m/z (%) = 295 (M – CO Et – OEt, 100), 367 (M – OEt + 1,
2
= 14.55, 24.89, 59.82, 84.52, 99.69, 130.26, 138.63,
+
2
0), 413 (M , 67).
1
47.33, 144.86, 163.50, 166.60.
Anal. Calcd for C H NO : C, 75.53; H, 5.61; N, 3.39. Found: C,
2
6
23
4
UV/VIS (cyclohexane):
( ) = 249 (33910), 319 (52820), 329
max
7
5.93; H, 5.81; N, 3.79.
(65570), 374 (sh) (8080), 414 (11970), 454 (sh) (1660) nm.
+
+
MS: m/z (%) = 295 (M – CO Et – OEt, 100), 367 (M – OEt – 1,
2
2,2 -Diamino-1,1 ,3,3 -tetrakisethoxycarbonyl-6,6 -biazulene
11)
+
2
1), 413 (M , 56).
(
Anal. Calcd for C H BNO : C, 63.94; H, 6.83; N, 3.39. Found: C,
Yield: 24%; orange powder; mp 298 °C (decomp.).
2
2
28
6
6
4.21; H, 7.01; N, 3.41.
IR: 1674 (CO) cm–1.
1H NMR: = 1.50 (12 H, t, J = 7.1 Hz), 4.48 (8 H, q, J = 7.1 Hz),
2
-(2-Azulenyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (2)
7
.77 (4 H, d, J = 11.3 Hz), 7.86 (4 H, s), 9.16 (4 H, d, J = 11.3 Hz).
13C NMR: = 14.67, 59.97, 100.34, 130.46, 133.34, 144.87, 148.33,
62.73, 166.47.
UV/VIS (dioxane):
39420).
Yield: 42%; blue solid; mp 99–101 °C.
–
1
IR: 2980, 1510, 1340, 1240, 1140 cm .
1H NMR: = 1.40 (12 H, s), 7.12 (2 H, t, J = 9.8 Hz), 7.58 (1 H, dd,
J = 10.0, 9.8 Hz), 7.76 (2 H, s), 8.35 (2 H, d, J = 10.0 Hz).
13C NMR:
One carbon signal due to the azulene skeleton was not observed.
1
( ) = 249 (57650), 357 (72470), 463
max
(
= 24.93, 83.72, 122.72, 125.07, 138.17, 138.74, 140.68.
+
MS: m/z (%) = 149 (100), 167 (C H CONH, 41), 279 (M – 4
1
0
4
+
CO Et – 1, 12), 572 (M , 3).
2
UV/VIS (cyclohexane): ( ) = 203 (37240), 244 (34270), 284
max
Anal. Calcd for C H N O : C, 67.12; H, 5.63; N, 4.89. Found: C,
3
2
32
2
8
(
(
114360), 332 (9010), 347 (11300), 360 (4260), 434 (1530), 665
1460).
6
7.50; H, 5.28; N, 5.13.
MS: m/z (%) = 128 (C H , 29), 154 (C H BO, 99), 169 (19), 181
1
0
8
10
7
2,6-Bis(2-amino-1,3-bisethoxycarbonyl-6-azulenyl)pyridine
13)
+
(
84), 254 (M , 100).
(
Yield: 85%; brown powder; mp 223–225 °C.
Anal. Calcd for C H BO : C, 75.62; H, 7.54. Found: C, 75.22; H,
16
19
2
7
.55.
IR: (CO) 1670 cm–1.
Synthesis 2002, No. 8, 1013–1016 ISSN 0039-7881 © Thieme Stuttgart · New York

1
016
K Kurotobi et al.
PAPER
1H NMR: = 1.49 (12 H, t, J = 7.1 Hz), 4.47 (8 H, q, J = 7.1 Hz),
.73 (2 H, d, J = 7.9 Hz), 7.81 (1 H, t, J = 7.9 Hz), 7.85 (4 H, s), 8.27
4 H, d, J = 11.3 Hz), 9.14 (4 H, d, J = 11.3 Hz).
UV/VIS (dioxane):
(67410), 469 (49510), 620 (sh) (500).
( ) = 249 (66160), 280 (31010), 345
max
7
(
Anal. Calcd for C H N O : C, 72.19; H, 5.48; N, 4.01. Found: C,
4
2
38
2
8
13C NMR:
= 15.10, 60.32, 100.52, 120.77, 130.75, 132.31, 138.20,
42.96, 145.99, 158.83, 163.30, 166.89.
72.43; H, 5.64; N, 3.40.
1
UV/VIS (dioxane):
( ) = 249 (78600), 344 (99770), 440
max
Acknowledgment
(
51330).
+
+
We appreciate the financial support of Grants-in-Aid for Scientific
Research on Priority Area (A) (Nos. 12020239, 11133241 and
MS: m/z (%) = 295 (M – 4 CO Et – 2 NH – 1, 82), 412 (M – 2
2
2
+
CO Et– 1, 100), 649 (M , 71).
2
1
0146235) from the Ministry of Education, Science, Sports, and
Anal. Calcd for C H N O : C, 68.40; H, 5.43; N, 6.47. Found: C,
8.65; H, 5.30; N, 6.67.
3
7
35
3
8
Culture, Japan.
6
N-Boc-2,5-Bis(2-amino-1,3-bisethoxycarbonyl-6-azulenyl)pyr-
role (14)
Yield: 41%; red powder; mp 205–207 °C.
References
(
1) Gerson, F.; Lopez, J.; Metzger, A. Helv. Chim. Acta 1980,
3, 2135.
2) Morita, T.; Takase, K. Bull. Chem. Soc. Jpn. 1982, 55, 1144.
6
–
1
IR: 1746, 1674 (CO) cm .
(
1H NMR: = 1.13 (9 H, s), 1.48 (12 H, t, J = 6.8 Hz), 4.47 (8 H, q,
J = 6.8 Hz), 6.43 (2 H, s), 7.67 (4 H, d, J = 11.8 Hz), 7.79 (4 H, s),
(3) (a) Hanke, M.; Jutz, C. Angew. Chem. Int. Ed. Engl. 1979,
18, 214. (b) Hanke, M.; Jutz, C. Synthesis 1980, 31.
9
.10 (4 H, d, J = 11.8 Hz).
13C NMR:
= 14.59, 27.19, 59.83, 85.08, 100.08, 114.58, 128.25,
29.90, 133.21, 138.17, 139.69, 144.93, 162.36, 166.42.
(4) (a) Iyoda, M.; Sato, K.; Oda, M. Tetrahedron Lett. 1985, 26,
3
828. (b) For the coupling reaction of azulenes, see:
Okujima, T.; Ito, N.; Morita, N. Tetrahedron Lett. 2002, 43,
261. (c) See also: Dyker, G.; Borowski, S.; Heierrmann, J.;
1
1
UV/VIS (dioxane):
( ) = 248 (74410), 322 (54240), 364
max
Körning, J.; Opwis, K.; Henkel, G.; Köckerling, M. J.
Organomet. Chem. 2000, 606, 108. (d) See also:
Balschukat, D.; Dehmlow, C. V. Chem. Ber. 1986, 119,
2272.
(
47660), 457 (45100).
+
MS: m/z (%) = 108 (100), 149 (71), 184 (56), 571 (M – 2 CO Et –
2
2
+
+
OEt + 1, 24), 590 (M – CO t-Bu –OEt – 1, 20), 737 (M , 3).
2
(
(
5) Miyaura, N.; Suzuki, A. Chem. Rev. 1995, 95, 2457.
6) For generation of 2-azulenyllithium from 2-iodoazulene,
see: Shimoyama, H.; Ito, A.; Takeda, K.; Hamazaki, H.; Ota,
A.; Fujimori, K. In The Abstracts of the 29th Symposium on
Structural Organic Chemistry; Saitama: Japan, September
Anal. Calcd for C H N O : C, 66.74; H, 5.87; N, 5.70. Found: C,
6
41
43
3
10
7.10; H, 5.57; N, 5.45.
2
,2 -Diamino-1,1 ,3,3 -tetrakisethoxycarbonyl-6,1 :3 ,6 -ter-
azulene (15)
20-22: 1999, 310.
Yield: 46%; reddish brown powder; mp 235–238 °C.
(
7) (a) Ishiyama, T.; Murata, M.; Miyaura, N. J. Org. Chem.
1995, 60, 7508. (b) For a recent paper for palladium-
catalyzed borylation with aryl halides, see: Murata, M.;
Oyama, T.; Watanabe, S.; Masuda, Y. J. Org. Chem. 2000,
–
1
IR: 1673 (CO) cm .
1H NMR: = 1.51 (12 H, t, J = 7.1 Hz), 4.50 (8 H, q, J = 7.1 Hz),
7
7
9
.29 (2 H, t, J = 10.0 Hz), 7.72 (1 H, t, J = 8.8 Hz), 7.80 (4 H, s),
.92 (4 H, d, J = 11.4 Hz), 8.29 (1 H, s), 8.62 (2 H, d, J = 9.6 Hz),
.24 (4 H, d, J = 11.4 Hz).
65, 164.
(
(
8) Hyslop, A. G.; Kellett, M. A.; Iovine, P. M.; Therien, M. J.
J. Am. Chem. Soc. 1998, 120, 12676.
9) Nozoe, T.; Seto, S.; Matsumura, S. Bull. Chem. Soc. Jpn.
13C NMR:
36.80, 137.87, 138.25, 140.10, 142.04, 144.55, 162.23, 166.61.
= 14.73, 59.86, 100.02, 125.46, 130.77, 133.11, 134.93,
1
1962, 35, 1990.
Synthesis 2002, No. 8, 1013–1016 ISSN 0039-7881 © Thieme Stuttgart · New York