Organic Letters
Letter
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Scheme 3. DBU-Catalyzed Skeletal Rearrangement
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Unlike its N-linkage isomer H, species J is chemically reactive
to undergo a 3,3-sigmatropic shift,16 yielding 3-oxo-2-arylamides
K and L and ultimately providing desired product 5a.
[3 + 2]-Annulation reactions of N-hydroxy allenylamines with
nitrosoarenes to form isoxazolidin-5-ols are described; herein,
IPrCuCl/O2 functions as a radical initiator to generate key
nitroxyl radicals.17 In the presence of DBU, these isoxazolidin-5-
ols undergo skeletal rearrangement to form indole products. A
direct synthesis of such useful indole derivatives is developed to
manifest the practicality. The structural rearrangement of
isoxazolidin-5-ols (3) and indoles (5) can be satisfactorily
assessed, as their mechanisms are postulated to comprise nitroso-
ene reactions and ketenimine intermediates. Finally, we
demonstrate the utility of this indole synthesis18 with the short
synthesis of three commercial drug molecules based on the
derivatives of pravadolines.15
ASSOCIATED CONTENT
* Supporting Information
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S
The Supporting Information is available free of charge on the
Experimental details and spectral data of all compounds
(10) Lutz, R. E.; Lytton, M. R. J. Org. Chem. 1937, 2, 68.
(11) Kang, J. Y.; Bugarin, A.; Connell, B. T. Chem. Commun. 2008,
3522.
(12) Crystallographic data for compounds 3h and 5e were deposited at
Cambridge Crystallographic Center (3h, CCDC 1418733; 5e, CCDC
1423186).
(13) Adam, W.; Krebs, O. Chem. Rev. 2003, 103, 4131.
(14) Fisher, D. J.; Burnett, L. G.; Velasco, R.; de Alaniz, J. R. J. Am.
Chem. Soc. 2015, 137, 11614.
AUTHOR INFORMATION
Corresponding Author
■
Notes
The authors declare no competing financial interest.
(15) Pravadoline 7a (WIN 48098) is commercially sold at Abmole
Bioscience Inc., Adooq Biosciences, and Axon Medchem (>USD 170/
50 mg). Compound 7c (JWH-015) is currently available at Enzo Life
Science and Sigma (>USD 328/25 mg).
(16) (a) Kawade, R. K.; Huang, P.-H.; Karad, S. N.; Liu, R.-S. Org.
Biomol. Chem. 2014, 12, 737. (b) Wang, Y.; Ye, L.; Zhang, L. Chem.
Commun. 2011, 47, 7815.
(17) Under IPrCuCl/O2, the reaction of N-hydroxy allylamine with
nitrosoarene gave [3 + 2]-annulation products through vinyl nitrone
intermediates; one example is provided in the SI (see Scheme s1).
(18) For indole synthesis see: (a) Porcheddu, A.; Mura, M. G.; De
Luca, L.; Pizzetti, M.; Taddei, M. Org. Lett. 2012, 14, 6112. (b) Larock,
R. C.; Yum, E. K. J. Am. Chem. Soc. 1991, 113, 6689. (c) Bartoli, G.;
Palmieri, G. Tetrahedron Lett. 1989, 30, 2129. (d) Allen, G. R.; Pidacks,
C., Jr.; Weiss, M. J. J. Am. Chem. Soc. 1966, 88, 2536. (e) Chen, Y.; Xie,
X.; Ma, D. J. Org. Chem. 2007, 72, 9329.
ACKNOWLEDGMENTS
The authors thank the National Science Council and the
Ministry of Education, Taiwan, for supporting this work.
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