Communication
Organic & Biomolecular Chemistry
Y. Xue, Y. Li, F. D. Horgen, G. Yao and Y. Zhang, J. Nat.
Prod., 2012, 75, 2113; (f) S. A. Baecher, M. Fehr,
M. Habermeyer, A. Hofmann, K.-H. Merz, H.-H. Fiebig,
D. Marko and G. Eisenbrand, Bioorg. Med. Chem., 2013, 21,
814; (g) I. Slaninová, J. Slanina and E. Táborská, Cytometry,
Part A, 2007, 71, 700.
2 (a) A. Pictet and A. Hubert, Ber. Dtsch. Chem. Ges., 1896, 29,
1182; (b) G. T. Morgan and P. C. Walls, J. Chem. Soc., 1931,
2447; (c) L. Zhang, G. Y. Ang and S. Chiba, Org. Lett., 2013,
15, 3682; (d) M. Tobisu, K. Koh, T. Furukawa and
N. Chatani, Angew. Chem., Int. Ed., 2012, 51, 11363;
(e) D. Leifert, C. G. Daniliuc and A. Studer, Org. Lett., 2013,
15, 6286; (f) B. Zhang, C. G. Daniliuc and A. Studer, Org.
Lett., 2014, 16, 250; (g) I. Deb and N. Yoshikai, Org. Lett.,
2013, 15, 4254; (h) M. Ghosh, A. Ahmed, S. Dhara and
J. K. Ray, Tetrahedron Lett., 2013, 54, 4837; (i) R. Pearson,
S. Zhang, G. He, N. Ed-wards and G. Chen, Beilstein J. Org.
Chem., 2013, 9, 891; ( j) K. Beydoun and H. Doucet,
Eur. J. Org. Chem., 2012, 6745; (k) Y. Y. Liu, R.-J. Son,
C.-Y. Wu, L.-B. Gong, M. Hu, Z.-Q. Wang, Y.-X. Xie and
J.-H. Li, Adv. Synth. Catal., 2012, 354, 347; (l) J. Peng,
T. Chen, C. Chen and B. Li, J. Org. Chem., 2011, 76, 9507;
(m) T. Gerfaud, L. Neuville and J. Zhu, Angew. Chem., Int.
Ed., 2009, 48, 572.
Scheme 4 Proposed reaction mechanism for 2j–A and 2j–B.
these conditions (2n). To show the generality of our synthetic
procedure, we applied this method to synthesize the polycyclic
hetero-aromatic compounds using ring B as a hetero-aromatic
moiety. We could obtain products in good to excellent yields
(2p–2r) except for the pyridine ring moiety where no corres-
ponding phenanthridine product (2o) was observed.
Conclusions
In conclusion, we have demonstrated a simple and metal-free
2-step protocol for 6-unsubstituted phenanthridine and
phenanthridine-like synthesis involving a cascade TfOH-pro-
moted aryl migration and intramolecular annulation in the
first step to form dihydrophenanthridine, followed by I2 oxi-
dation. This highlights our strategy as a novel approach to con-
struct the 6-unsubstituted phenanthridine ring system via
tandem C–C and C–N bond formation. The reactions pro-
ceeded at room temperature and the conditions are applicable
to a wide range of substrates. This strategy obviates the use of
transition metal reagents rendering metal contamination-free
products, and solves decomposition problems, especially in
multiply-oxygenated compounds.
3 H. Jiang, Y. Cheng, R. Wang, M. Zheng, Y. Zhang and S. Yu,
Angew. Chem., Int. Ed., 2013, 52, 13289.
4 (a) F. Portela-Cubillo, E. M. Scanlan, J. S. Scott and
J. C. Walton, Chem. Commun., 2008, 4189; (b) R. Alonso,
A. Caballero, P. J. Campos and M. A. Rodrıguez, Tetra-
hedron, 2010, 66, 8828; (c) A. M. Linsenmeier,
C. M. Williams and S. Bräse, J. Org. Chem., 2011, 76,
9127.
5 F. Portela-Cubillo, J. S. Scott and J. C. Walton, J. Org. Chem.,
2008, 73, 5558.
6 B. Zhang, C. Mück-Lichtenfeld, C. G. Daniliuc and
A. Studer, Angew. Chem., Int. Ed., 2013, 52, 10792.
7 (a) Y. Wu, S. M. Wong, F. Mao, T. L. Chan and F. Y. Kwong,
Org. Lett., 2012, 14, 5306; (b) S. De, S. Mishra, B. N. Kakde,
D. Dey and A. Bisai, J. Org. Chem., 2013, 78, 7823.
8 B. K. Mehta, K. Yanagisawa, M. Shiro and H. Kotsuki, Org.
Lett., 2003, 5, 1605.
9 A. K. Mandadapu, M. Saifuddin, P. K. Agarwal and
B. Kundu, Org. Biomol. Chem., 2009, 7, 2796.
10 (a) J. Tummatorn, C. Thongsornkleeb and S. Ruchirawat,
Tetrahedron, 2012, 68, 4732; (b) J. Tummatorn,
C. Thongsornkleeb, S. Ruchirawat and T. Gettongsong, Org.
Biomol. Chem., 2013, 11, 1463.
Acknowledgements
This research work was supported in part by grants from the
Center of Excellence on Environmental Health and Toxicology,
Science & Technology Postgraduate Education and Research
Development Office (PERDO), the Ministry of Education,
Chulabhorn Research Institute and Thailand Toray Science
Foundation.
11 T.
Linnanen,
M.
Brisander,
N.
Mohell
and
Notes and references
A. M. Johansson, Bioorg. Med. Chem. Lett., 2001, 11, 367.
1 (a) S. D. Phillips and R. N. J. Castle, Heterocyclic Chem., 12 D. Intrieri, M. Mariani, A. Caselli, F. Ragaini and E. Gallo,
1981, 18, 232; (b) S. Frick, R. Kramell, J. Schmidt, A. J. Fist Chem. – Eur. J., 2012, 18, 10487.
and T. M. Kutchan, J. Nat. Prod., 2005, 68, 666; 13 H. Ishii, T. Ishikawa, Y.-I. Ichikawa, M. Sakamoto,
(c) T. Nakanishi, M. Suzuki, A. Saimoto and T. Kabasawa,
J. Nat. Prod., 1999, 62, 864; (d) I. Kock, D. Heber, M. Weide,
M. Ishi-kawa and T. Takahashi, Chem. Pharm. Bull., 1984,
32, 2984.
U. Wolschendorf and B. Clement, J. Med. Chem., 2005, 48, 14 (a) S. V. Kessar, Y. P. Gupta, P. Balakrishnan, K. K. Sawal,
2772; (e) Z. Luo, F. Wang, J. Zhang, X. Li, M. Zhang, X. Hao,
T. Mohammad and M. Dutt, J. Org. Chem., 1988, 53, 1708;
5080 | Org. Biomol. Chem., 2014, 12, 5077–5081
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