˚
5 B. Akermark, L. Eberson, E. Jonsson and E. Pettersson, J. Org. Chem.,
1975, 40, 1365.
activation exclusively proceeded at the sterically less-hindered
aromatic carbon of the triflate to afford carbazoles as the single
isomer. In many cases, N-arylation proceeded almost quantita-
tively, so the yield of carbazoles was mainly dependent on the
reactivity of the resulting diarylamines in the C–H activation step.
In conclusion, we have developed an efficient atom-economic
synthetic route from aryl triflates and anilines to functionalized
carbazoles in a one-flask reaction. This study first demonstrated
that a common palladium catalyst with different additives
promotes sequential N-arylation and oxidative C–H activation,
besides careful examination of interesting substituent effects on the
reactivity. Application of this method to the total synthesis of
biologically-active natural products and an investigation of the
reaction mechanism of C–H activation are now in progress.
This work was supported in part by a Grant-in-Aid for
Encouragement of Young Scientists (A) from the Ministry of
Education, Culture, Sports, Science and Technology of Japan, 21st
Century COE Program ‘Knowledge Information Infrastructure
for Genome Science’, National Institute of Biomedical Innovation,
Japan, and Meiji Seika, which are gratefully acknowledged.
6 See also: H.-J. Kno¨lker and N. O’Sullivan, Tetrahedron Lett., 1994, 35,
1695.
7 For applications of this process to total synthesis of alkaloids, see: (a)
R. B. Miller and T. Moock, Tetrahedron Lett., 1980, 21, 3319; (b)
M. Yogo, C. Ito and H. Furukawa, Chem. Pharm. Bull., 1991, 39, 328;
(c) H.-J. Kno¨lker and J. Kno¨ll, Chem. Commun., 2003, 1170; (d)
A. Benavides, J. Peralta, F. Delgado and J. Tamariz, Synthesis, 2004,
2299; (e) J. Kno¨ll and H.-J. Kno¨lker, Synlett, 2006, 651.
8 (a) H.-J. Kno¨lker and N. O’Sullivan, Tetrahedron, 1994, 50, 10893; (b)
H.-J. Kno¨lker and W. Fro¨hner, J. Chem. Soc., Perkin Trans. 1, 1998,
173; (c) H.-J. Kno¨lker, K. R. Reddy and A. Wagner, Tetrahedron Lett.,
1998, 39, 8267; (d) I. C. F. R. Ferreira, M.-J. R. P. Queiroz and
G. Kirsch, Tetrahedron, 2002, 58, 7943.
˚
9 B. Akermark, J. D. Oslob and U. Heuschert, Tetrahedron Lett., 1995,
36, 1325.
˚
10 (a) H. Hagelin, J. D. Oslob and B. Akermark, Chem.–Eur. J., 1999, 5,
2413; see also (b) T. Ohishi, J. Yamada, Y. Inui, T. Sakaguchi and
M. Yamashita, J. Org. Chem., 1994, 59, 7521.
11 (a) F. Paul, J. Patt and J. F. Hartwig, J. Am. Chem. Soc., 1994, 116,
5969; (b) A. S. Guram and S. L. Buchwald, J. Am. Chem. Soc., 1994,
116, 7901; (c) J. F. Hartwig, Angew. Chem., Int. Ed., 1998, 37, 2046; (d)
J. F. Hartwig, Pure Appl. Chem., 1999, 71, 1417; (e) B. H. Yang and
S. L. Buchwald, J. Organomet. Chem., 1999, 576, 125; (f) J. P. Wolfe,
H. Tomori, J. P. Sadighi, J. Yin and S. L. Buchwald, J. Org. Chem.,
2000, 65, 1158.
12 (a) J. P. Wolfe and S. L. Buchwald, J. Org. Chem., 1997, 62, 1264; (b)
˚
J. Ahman and S. L. Buchwald, Tetrahedron Lett., 1997, 38, 6363; (c)
Notes and references
J. Louie, M. S. Driver, B. C. Hamann and J. F. Hartwig, J. Org. Chem.,
1997, 62, 1268.
1 For pioneering work, see: (a) D. E. Ames and D. Bull, Tetrahedron,
1982, 38, 383; (b) D. E. Ames and A. Opalko, Tetrahedron, 1984, 40,
1919.
13 For recent examples of tandem multifunctional catalysis, see: (a)
P. A. Evans and J. E. Robinson, J. Am. Chem. Soc., 2001, 123, 4609; (b)
J. Louie, C. W. Bielawski and R. H. Grubbs, J. Am. Chem. Soc., 2001,
123, 11312; (c) E. Teoh, E. M. Campi, W. R. Jackson and
A. J. Robinson, Chem. Commun., 2002, 978; (d) A. N. Thadani and
V. H. Rawal, Org. Lett., 2002, 4, 4317; (e) J. Tian, N. Yamagiwa,
S. Matsunaga and M. Shibasaki, Angew. Chem., Int. Ed., 2002, 41, 3636;
for review, see: (f) A. Ajamian and J. L. Gleason, Angew. Chem., Int.
Ed., 2004, 43, 3754.
2 For some recent examples, see: (a) R. Grigg, V. Savic and
V. Tambyrajah, Tetrahedron Lett., 2000, 41, 3003; (b) C. C. Hughes
and D. Trauner, Angew. Chem., Int. Ed., 2002, 41, 1569; (c)
M. A. Campo and R. C. Larock, J. Am. Chem. Soc., 2002, 124,
14326; (d) E. J. Hennessy and S. L. Buchwald, J. Am. Chem. Soc., 2003,
125, 12084; (e) L.-C. Campeau, M. Parisien, M. Leblanc and K. Fagnou,
J. Am. Chem. Soc., 2004, 126, 9186; (f) G. Cuny, M. Bois-Choussy and
J. Zhu, J. Am. Chem. Soc., 2004, 126, 14475; (g) R. Ferraccioli,
D. Carenzi, O. Rombola` and M. Catellani, Org. Lett., 2004, 6, 4759; (h)
L.-C. Campeau, P. Thansandote and K. Fagnou, Org. Lett.,
2005, 7, 1857; (i) H. Abe, K. Nishioka, S. Takeda, M. Arai,
Y. Takeuchi and T. Harayama, Tetrahedron Lett., 2005, 46, 3197; (j)
J. Zhao and R. C. Larock, Org. Lett., 2005, 7, 701; (k) M. Parisien,
D. Valette and K. Fagnou, J. Org. Chem., 2005, 70, 7578; (l)
L.-C. Campeau, M. Parisien, A. Jean and K. Fagnou, J. Am. Chem.
Soc., 2006, 128, 581; (m) D. Garc´ıa-Cuadrado, A. A. C. Braga,
F. Maseras and A. M. Echavarren, J. Am. Chem. Soc., 2006, 128, 1066.
3 For our related work, see: (a) H. Ohno, K. Miyamura, Y. Takeoka and
T. Tanaka, Angew. Chem., Int. Ed., 2003, 42, 2647; (b) H. Ohno,
K. Miyamura, T. Mizutani, Y. Kadoh, Y. Takeoka, H. Hamaguchi and
T. Tanaka, Chem.–Eur. J., 2005, 11, 3728; (c) H. Ohno, M. Yamamoto,
M. Iuchi and T. Tanaka, Angew. Chem., Int. Ed., 2005, 44, 5103.
4 H. Yoshimoto and H. Itatani, Bull. Chem. Soc. Jpn., 1973, 46, 2490.
14 For recent reviews, see: H.-J. Kno¨lker and K. R. Reddy, Chem. Rev.,
2002, 102, 4303.
15 For recent synthesis of carbazoles, see: (a) Y. Kikugawa,
Y. Aoki and T. Sakamoto, J. Org. Chem., 2001, 66, 8612; (b)
B. Witulski and C. Alayrac, Angew. Chem., Int. Ed., 2002, 41, 3281; (c)
Z. Liu and R. C. Larock, Org. Lett., 2004, 6, 3739; (d) M. F. Mart´ınez-
Espero´n, D. Rodr´ıguez, L. Castedo and C. Saa´, Org. Lett., 2005, 7,
2213; (e) A. Kuwahara, K. Nakano and K. Nozaki, J. Org. Chem.,
2005, 70, 413.
16 R. B. Bedford and C. S. J. Cazin, Chem. Commun., 2002, 2310.
17 Phosphine ligand 3 was oxidized under the oxidative coupling conditions
(see ESI{).
18 Indeed, the treatment of diarylamine 4 in AcOH under oxygen
atmosphere with palladium dichloride or palladium acetate–tetrabutyl-
ammonium bromide led to recovery of the starting material.
4518 | Chem. Commun., 2007, 4516–4518
This journal is ß The Royal Society of Chemistry 2007