C O M M U N I C A T I O N S
Table 2. Synthesis of Pyridines, Isoquinolines and γ-Carbolinea b
,
azido-substituted carbon was observed to afford 2-phenylpyrrole
(8) in 62% yield, while a sterically less hindered ꢀ-carbon in the
substituted tert-cyclobutanol ring is normally eliminated2c-e (eq
4). Along with pyrrole 8, 19% yield of γ-keto nitrile 9 was formed
presumably via ꢀ-H elimination from an iminyl palladium(II)
intermediate,2g,9 although such nitriles were not obtained in the
other systems.
Further studies on the scope, mechanistic evaluation, and
synthetic applications of this intriguing Pd(II)-catalyzed ring
expansion of cyclic 2-azidoalcohol derivatives are in progress.
Acknowledgment. This work was supported by funding from
Nanyang Technological University, Singapore Ministry of Educa-
tion, and Science & Engineering Research Council (A*STAR Grant
No. 082 101 0019).
Supporting Information Available: Experimental procedures,
characterization of new compounds. This material is available free of
a Unless otherwise noted, the reactions were carried out using 0.3
mmol of azidoalcohols 1 or 3 in the presence of 15 mol % of
PdCl2(dppf) and 1 equiv of K2CO3 in ClCH2CH2Cl (2 mL) under N2.
b Isolated yields are recorded above. c The reaction was run using 10
mol % of Pd(OAc)2 and 2,2′-bipyridine as a catalyst. d 20 mol % of
PdCl2(dppf) was used. e The reaction was carried out using 10 mol % of
Pd(OAc)2 and 10 mol % of dppf at room temperature.
References
(1) For recent reviews, see: (a) Satoh, T.; Miura, M. Top. Organomet. Chem.
2005, 14, 1. (b) Jun, C.-H. Chem. Soc. ReV. 2004, 33, 610. (c) Rybtchinski,
B.; Milstein, D. Angew. Chem., Int. Ed. 1999, 38, 870. (d) Murakami, M.;
Ito, Y. In ActiVation of UnreactiVe Bonds and Organic Synthesis; Murai,
S., Ed.; Springer: New York, 1999; pp 97-129.
2). The reaction allowed installing not only aryl substituents but
also methyl and allyl moieties at C-3 on the pyridine ring (2b-2g).
3,4-Dialkylsubstituted pyridines 2h could also be synthesized in
good yield. Importantly, 3-chloro- and 3-bromopyridines 2i and 2j
were successfully formed with keeping the C-Cl or C-Br bond
intact. 3-Arylpyridines with some substituents were prepared using
this method (2k-2p). In addition to pyridines, this catalytic ring
expansion provided substituted isoquinoline derivatives. It is noted
that the reactions of both trans-1-azido-2-indanol 3 and 2-azido-
1-indanol 3′ proceeded to afford the same isoquinolines using a 10
mol % catalyst (4a and 4b). Interestingly, the reactions of 2-azido-
1-indanols 3a′-c′ proceeded at room temperature using a
Pd(OAc)2-dppf system in excellent yields. Both electron-with-
drawing (4a) and electron-donating groups (4b-d) were incorpo-
rated on the isoquinoline ring. Chloride substituents on the benzene
ring were tolerated (4c and 4e). Azidoalcohols bearing a phenyl
group at C-3 (3f) and C-2 (tertiary alcohol 3g) were converted into
corresponding isoquinolines in good yields. Moreover, this method
afforded γ-carboline 4h from 3h′.
Next, we envisioned applying this method to the other ring
systems (eqs 2-4). Although no C-C bond fission was observed
from six-membered ring azidoalcohol 5 (eq 2), formations of
pyridine and pyrrole occurred from 2-azidocyclopentanol 6 bearing
a saturated five-membered ring and strained 2-azidocyclobutanol
7, respectively (eqs 3 and 4). The reaction of 2-azidocyclopentanol
6 provided pyridine 2k in moderate yield after treatment with AcOH
under an oxygen atmosphere for further oxidation of a formed
dihydropyridine intermediate (eq 3). In the case of the reaction of
2-azidocyclobutanol 7, selective C-C bond fission involving the
(2) (a) Terao, Y.; Wakui, H.; Nomoto, M.; Satoh, T.; Miura, M.; Nomura, M.
J. Org. Chem. 2003, 68, 5236. (b) Wakui, H.; Kawasaki, S.; Satoh, T.; Miura,
M.; Nomura, M. J. Am. Chem. Soc. 2004, 126, 8658. (c) Nishimura, T.;
Ohe, K.; Uemura, S. J. Org. Chem. 2001, 66, 1455. (d) Nishimura, T.;
Uemura, S. J. Am. Chem. Soc. 1999, 121, 11010. (e) Nishimura, T.; Ohe,
K.; Uemura, S. J. Am. Chem. Soc. 1999, 121, 2645. (f) Matsumura, S.;
Maeda, Y.; Nishimura, T.; Uemura, S. J. Am. Chem. Soc. 2003, 125, 8862.
(g) Nishimura, T.; Uemura, S. J. Am. Chem. Soc. 2000, 122, 12049. (h)
Harayama, H.; Kuroki, T.; Kimura, M.; Tanaka, S.; Tamaru, Y. Angew.
Chem., Int. Ed. 1997, 36, 2352. (i) Necas, D.; Tursky, M.; Kotora, M. J. Am.
Chem. Soc. 2004, 126, 10222. (j) Terai, H.; Takaya, H.; Murahashi, S.-I.
Synlett 2004, 2185.
(3) For transition metal catalyzed retroallylation reactions of homoallyl alcohols,
see: (a) Hayashi, S.; Hirano, K.; Yorimitsu, H.; Oshima, K. J. Am. Chem.
Soc. 2006, 128, 2210. (b) Kondo, T.; Kodoi, K.; Nishinaga, E.; Okada, T.;
Morisaki, Y.; Watanabe, Y.; Mitsudo, T. J. Am. Chem. Soc. 1998, 120, 5587.
(4) Generation of alkylideneaminolithium species from Li enolates of R-azido
carbonyl compounds has been observed; see: (a) Manis, P. A.; Rathke, M. W.
J. Org. Chem. 1980, 45, 4952. (b) Edwards, O. E.; Purushothaman, K. K.
Can. J. Chem. 1964, 42, 712.
(5) (a) Gerfaund, T.; Neuville, L.; Zhu, J. Angew. Chem., Int. Ed. 2009, 48,
572. (b) Liu, S.; Liebeskind, L. S. J. Am. Chem. Soc. 2008, 130, 6918. (c)
Wang, Y.-F.; Toh, K. K.; Chiba, S.; Narasaka, K. Org. Lett. 2008, 10, 5019.
(d) Narasaka, K.; Kitamura, M. Eur. J. Org. Chem. 2005, 4505. (e) Sakoda,
K.; Mihara, J.; Ichikawa, J. Chem. Commun. 2005, 4684.
(6) For a report on the coordination of the internal nitrogen of azido moiety
with a Pd(II) complex, see: (a) Barz, M.; Herdweck, E.; Thiel, W. R. Angew.
Chem., Int. Ed. 1998, 37, 2262. (b) For a review on the coordination of
organic azides with transition metals, see: Cenini, S.; Gallo, E.; Caselli, A.;
Ragaini, F.; Fantauzzi, S.; Piangiolino, C. Coord. Chem. ReV. 2006, 250,
1234.
(7) A concerted pathway from B to D could also be proposed.
(8) Nitrile formation by radical fragmentation of 2-azidoalcohols with cleavage
of the C-C bond has been reported; see: (a) Herna´ndez, R.; Leo´n, E. I.;
Moreno, P.; Sua´rez, E. J. Org. Chem. 1997, 62, 8974. (b) Shimizu, I.; Fujita,
M.; Nakajima, T.; Sato, T. Synlett 1997, 887.
(9) (a) Zhao, P.; Hartwig, J. F. J. Am. Chem. Soc. 2005, 127, 11618. (b) Chiba,
S.; Kitamura, M.; Saku, O.; Narasaka, K. Bull. Chem. Soc. Jpn. 2004, 77,
785.
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