LETTER
Synthesis of Carbazole
379
Table 3 Effects of the Substituentsa
References and Notes
R4
ligand 1
Pd2(dba)3
Cs2CO3
R4
(1) For recent review on carbazole derivatives, see:
(a) Knölker, H.-J. Top. Curr. Chem. 2005, 244, 115.
(b) Knölker, H.-J.; Reddy, K. R. Chem. Rev. 2002, 102,
4303. (c) Kirsch, G. H. Curr. Org. Chem. 2001, 5, 507.
(d) Knölker, H.-J. Chem. Soc. Rev. 1999, 28, 151.
(2) Chakraborty, D. P. The Alkaloids 1993, 44, 257.
R3
R2
I
R3
R2
2
+
toluene
then NaOt-Bu
N
H2N
H
R1
R1
8
9
(3) Kuwahara, A.; Nakano, K.; Nozaki, K. J. Org. Chem. 2005,
70, 413.
(4) Kitawaki, T.; Hayashi, Y.; Ueno, A.; Chida, N. Tetrahedron
2006, 62, 6792.
Entry Substrate
Product Yield (%)
1
2
8a: R1 = R2 = R4 = H, R3 = NO2
8b: R1 = R2 = R4 = H, R3 = CF3
8c: R1 = R2 = R4 = H, R3 = F
8d: R2 = R3 = R4 = H, R1 = OMe
8e: R1 = R2 = R4 = H, R3 = OMe
8f: R1 = R2 = R3 = H, R4 = OMe
8g: R1 = R4 = H, R2 = R3 = OMe
8h: R2 = R3 = R4 = H, R1 = Me
8i: R1 = R3 = R4 = H, R2 = Me
8j: R1 = R2 = R4 = H, R3 = Me
8k: R1 = R2 = R3 = H, R4 = Me
9a
9b
9c
9d
9e
9f
4
13
60
64
47
32
42
63
51
54
42
(5) (a) Miyaura, N.; Yanagi, T.; Suzuki, A. Synth. Commun.
1981, 11, 513. For reviews, see: (b) Miyaura, N.; Suzuki, A.
Chem. Rev. 1995, 95, 2457. (c) Suzuki, A. J. Organomet.
Chem. 1999, 576, 147.
(6) (a) Watanabe, T.; Ueda, S.; Inuki, S.; Oishi, S.; Fujii, N.;
Ohno, H. Chem. Commun. 2007, 4516. (b) Ackermann, L.;
Althammer, A. Angew. Chem., Int. Ed. 2007, 46, 1627.
(c) Bedford, R. B.; Betham, M. J. Org. Chem. 2006, 71,
9403.
(7) (a) Yoshikawa, S.; Odaira, J.; Kitamura, Y.; Bedekar, A. V.;
Furuta, T.; Tanaka, K. Tetrahedron 2004, 60, 2225.
(b) Kitamura, Y.; Hashimoto, A.; Yoshikawa, S.; Odaira, J.;
Furuta, T.; Kan, T.; Tanaka, K. Synlett 2006, 115.
(8) Furuta, T.; Kitamura, Y.; Hashimoto, A.; Fujii, S.; Tanaka,
K.; Kan, T. Org. Lett. 2007, 9, 183.
(9) We have found that a Suzuki–Miyaura reaction of 12 and 13
mediated by ligand 1 provides biaryl product 14 even with
the chloride, which is known as a low reactive halide
(Scheme 2).
3
4
5
6
7
9g
9h
9i
8
9
10
11
9j
9k
a The reaction was conducted with Pd2(dba)3 (10 mol%), ligand 1 (12
mol%), Cs2CO3 (3.0 equiv), and NaOt-Bu (1.2 equiv).
Me
ligand 1 (5.0 mol%)
Cl
Me
Pd2(dba)3 (3.0 mol%)
+
Cs2CO3 (1.5 equiv)
1,4-dioxane
100 °C, 2.8 h
Table 4 Carbazole Synthesis with an Alternative Substrate Combi-
CN
B(OH)2
nationa
CN
12
13
14 (99%)
ligand 1, Pd(0)
Cs2CO3, solvent
B(OH)2
NH2
I
I
Scheme 2
+
5
then NaOt-Bu
(10) Experimental Procedure for the Synthesis of Carbazole
5 (Table 1, Entry 6)
10
11
To a solution of 2-bromophenylboronic acid (2, 30 mg, 0.15
mmol) and 2-iodoaniline (3, 30 mg, 0.14 mmol) in toluene
(0.5 mL) was added Pd2 (dba)3 (13 mg, 0.01 mmol), ligand 1
(6.9 mg, 0.02 mmol), and Cs2CO3 (134 mg, 0.41 mmol) at
r.t. under an argon atmosphere, then the mixture was stirred
at 100 °C for 2 h. The mixture was cooled to r.t., and then
NaOt-Bu (16 mg, 0.17 mmol) was added and stirred at
100 °C for 19 h. After stirring, H2O was added, and extracted
with EtOAc. The organic layer was washed with H2O, brine,
dried over MgSO4 and evaporated. The residue was purified
by column chromatography on silica gel (benzene–EtOAc,
99:1) to afford the 9H-carbazole (5, 16 mg, 71%) as a
colorless solid; Rf = 0.82 (benzene–EtOAc, 99:1). 1H NMR
(500 MHz, CDCl3): d = 8.08 (d, J = 7.9 Hz, 2 H), 8.03 (br s,
1 H), 7.50–7.40 (m, 4 H), 7.30–7.20 (m, 2 H). 13C NMR (68
MHz, CDCl3): d = 139.5, 125.8, 123.4, 120.3, 119.4, 110.6.
MS–FAB: m/z = 168 [M + H]+. HRMS–FAB: m/z calcd for
C12H10N [M + H]+: 168.0814; found: 168.0809.
Entry Catalyst
Solvent
Temp (°C) Yield (%)
1
2
3
4
Pd(OAc)2
Pd(OAc)2
Pd2(dba)3
Pd2(dba)3
1,4-dioxane
1,4-dioxane
toluene
100
80
67
76
25
30
100
100
1,4-dioxane
a The same amounts of Pd catalyst, ligand 1, Cs2CO3, and NaOt-Bu as
those in Table 3 were used.
this catalytic system are currently under way in our labo-
ratory.
Acknowledgment
(11) An isolation and structure determination of complex 4¢ was
This work was financially supported by SUNBOR Foundation, Ue-
hara Memorial Foundation, and a Grant-in-Aid for Scientific Rese-
arch on Priority Areas 17025011 from The Ministry of Education,
Culture, Sports, Science and Technology (MEXT) of Japan.
not tested.
(12) Addition of Cs2CO3 (1.2 equiv) instead of NaOt-Bu gave no
improvement of chemical yields to give 5 and 4 in 26% and
31%, respectively. This result also supports that the complex
4¢ plays a role in preventing the ring closure to 5.
Synlett 2008, No. 3, 377–380 © Thieme Stuttgart · New York