Organic Letters
Letter
(4) (a) Prelog, V.; Szpilfogel, S. Helv. Chim. Acta 1945, 28, 1684.
(b) Ishiguro, T.; Morita, Y.; Ikushima, K. Yakugaku Zasshi 1958, 78,
268. (c) Breitmaier, E.; Bayer, E. Tetrahedron Lett. 1970, 11, 3291.
(d) Kusumi, T.; Yoneda, K.; Kakisawa, H. Synthesis 1979, 1979, 221.
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(b) Boger, D. L. Chem. Rev. 1986, 86, 781. (c) Boger, D. L.
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substituted pyridine is readily available and allows construction
of the adjoining cycloheptane,19 most approaches rely on
building the pyridine ring starting from a cycloheptanone.20
We uncovered one limitation to cyclohepta[c]pyiridines
when we attempted to close adduct 40 derived from addition of
xanthate 19i to N-phenylmaleimide. A complex mixture was
obtained, caused apparently by a competing 1,5-hydrogen atom
translocation converting intermediate radical 41 into useless
radical 42, in preference to the desired cyclization to tricyclic
product 43. This internal abstraction of a benzylic-type
hydrogen is geometrically disfavored in the case of xanthate
37 because of the trans disposition of the two chains across the
rigid five-membered ring platform.
In summary, we have described an expedient, modular
approach to azaindanes that complements more traditional
routes. Many functional groups are tolerated, especially polar
functional motifs generally incompatible with ionic or organo-
metallic methods. The strategic ability of the xanthate transfer
process to mediate the successive formation of more than one
carbon−carbon bonds is indeed unique and allows easy access
to richly decorated azaindanes and, in some cases, cyclohepta-
[b]pyridines, that should be of interest to medicinal chemists.
(6) Beschke, H. Aldrichimica Acta 1978, 11, 13.
(7) For reviews on the xanthate transfer, see: (a) Quiclet-Sire, B.;
Zard, S. Z. Pure Appl. Chem. 2011, 83, 519. (b) Quiclet-Sire, B.; Zard,
S. Top. Curr. Chem. 2006, 264, 201.
(8) While the synthesis of 16 could, in principle, be accomplished in
one pot, isolation of intermediate xanthate 13 simplifies the analysis of
the reaction mixtures.
(9) For a review of applications to the synthesis of heteroaromatics,
see: El Qacemi, M.; Petit, L.; Quiclet-Sire, B.; Zard, S. Z. Org. Biomol.
Chem. 2012, 10, 5707.
(10) (a) Ly, T.-M.; Quiclet-Sire, B.; Sortais, B.; Zard, S. Z.
Tetrahedron Lett. 1999, 40, 2533. For a Mn(III)-based radical route
to indanes, see: (b) Citterio, A.; Fancelli, D.; Finzi, C.; Pesce, L.; Santi,
R. J. Org. Chem. 1989, 54, 2713. For a discussion of the Mn(III)
oxidation mechanism and the slowness of the ring-closure step to the
aromatic ring, see: (c) Snider, B. B. Tetrahedron 2009, 65, 10738. For
a recent general review on the synthesis of indanes and indenes, see:
(d) Gabriele, B.; Mancuso, R.; Veltri, L. Chem. - Eur. J. 2016, 22, 5056.
(11) Verevkin, S. P.; Emel’yanenko, V. N. J. Phys. Chem. A 2011, 115,
1992.
ASSOCIATED CONTENT
* Supporting Information
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S
(12) (a) Punta, C.; Minisci, F. Trends Het. Chem. 2008, 13, 1.
(b) Minisci, F.; Fontana, F.; Vismara, E. J. Heterocycl. Chem. 1990, 27,
79. (c) Minisci, F.; Vismara, E.; Fontana, F. Heterocycles 1989, 28, 489.
(13) Ferjancic, Z.; Quiclet-Sire, B.; Zard, S. Z. Synthesis 2008, 2008,
2996.
The Supporting Information is available free of charge on the
Experimental procedures, full spectroscopic data, and
1
copies of H and 13C NMR for all new compounds
(14) Han, S.; Zard, S. Z. Org. Lett. 2014, 16, 5386.
(15) We thank Dr S. Han for performing a preliminary experiment.
(16) For examples of radical ipso attacks on fluorinated pyridines, see:
(a) Laot, Y.; Petit, L.; Zard, S. Z. Org. Lett. 2010, 12, 3426. (b) Laot,
Y.; Petit, L.; Tran, N. D. M.; Zard, S. Z. Aust. J. Chem. 2011, 64, 416.
(c) Liu, Z.; Qin, L.; Zard, S. Z. Org. Lett. 2014, 16, 2704.
(17) Blackmond and Baran have found that, for radical attacks on
pyridines, an alkoxy group deactivates the meta position and an
electron-withdrawing group at C2 deactivates position C6: O’hara, F.;
Blackmond, D. G.; Baran, P. S. J. Am. Chem. Soc. 2013, 135, 12122.
(18) Luo, G.; Chen, L.; Conway, C. M.; Denton, R.; Keavy, D.;
Gulianello, M.; Huang, Y.; Kostich, W.; Lentz, K. A.; Mercer, S. E.;
Schartman, R.; Signor, L.; Browning, M.; Macor, J. E.; Dubowchik, G.
M. ACS Med. Chem. Lett. 2012, 3, 337.
AUTHOR INFORMATION
Corresponding Authors
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ORCID
Notes
The authors declare no competing financial interest.
(19) For recent examples, see: (a) Desai, L. V.; Hay, M. B.; Leahy, D.
K.; Wei, C.; Fanfair, D.; Rosner, T.; Hsiao, Y. Tetrahedron 2013, 69,
5677. (b) Leahy, D. K.; Fan, Y.; Desai, L. V.; Chan, C.; Zhu, J.; Luo,
G.; Chen, L.; Hanson, R. L.; Sugiyama, M.; Rosner, T.; Cuniere, N.;
Guo, Z.; Hsiao, Y.; Gao, Q. Org. Lett. 2012, 14, 4938. (c) Yoshizumi,
T.; Ohno, A.; Tsujita, T.; Takahashi, H.; Okamoto, O.; Hayakawa, I.;
Kigoshi, H. Synthesis 2009, 2009, 1153.
(20) For recent examples, see: (a) Pan, B.; Liu, B.; Yue, E.; Liu, Q.;
Yang, X.; Wang, Z.; Sun, W.-H. ACS Catal. 2016, 6, 1247. (b) Wu, K.;
Huang, Z.; Liu, C.; Zhang, H.; Lei, A. Chem. Commun. 2015, 51, 2286.
(c) Srimani, D.; Ben-David, Y.; Milstein, D. Chem. Commun. 2013, 49,
6632.
ACKNOWLEDGMENTS
We thank Ecole Polytechnique for a scholarship to Q.H. and
Mr. Shiwei Ren (Ecole Polytechnique) for technical assistance.
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DEDICATION
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This article is affectionately dedicated to Dr. Tarek S. Mansour,
formerly of Wyeth-Ayerst.
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