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Organic & Biomolecular Chemistry
Page 4 of 5
DOI: 10.1039/C5OB01519G
COMMUNICATION
Organic & Biomolecular Chemistry
7
For selected reviews, see: (a) C. J. Li, Acc. Chem. Res., 2009,
42, 335; (b) E. A. Mitchell, A. Peschiulli, N. Lefevre, L.
Meerpoel and B. U. W. Maes, Chem. Eur. J., 2012, 18, 10092.
For a selected review, see: S. A. Girard, T. Knauber and C. J.
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nitro- and 3-methyl-substituted indoles were not suitable
reaction partners, presumably as a result of their reduced
nucleophilicity.
8
9
In conclusion, we have developed the first oxidation of
unactivated aliphatic amines with IBX to give 1-pyrrolines.
Moreover, an efficient one-pot protocol for diastereoselective
α-functionalization of meso-pyrrolidines in oxidative Ugi-type
and aza-Friedel-Crafts reactions is presented.
P. Fontaine, A. Chiaroni, G. Masson and J. Zhu, Org. Lett.,
2008, 10, 1509.
10 (a) T. Ngouansavanh and J. P. Zhu, Angew. Chem. Int. Ed.,
2006, 45, 3495; (b) F. De Moliner, S. Crosignani, A. Galatini,
R. Riva and A. Basso, ACS Comb. Sci., 2011, 13, 453.
11 For an IBX-mediated oxidative Ugi four-component reaction,
see: (a) F. Drouet, G. Masson and J. P. Zhu, Org. Lett., 2013,
15, 2854; For IBX-mediated oxidative Ugi-type three-
Acknowledgements
component reactions, see: (b) T. Ngouansavanh and J. Zhu,
Angew. Chem. Int. Ed., 2007, 46, 5775; (c) D. Zhu, L. Xia, L.
Pan, S. Li, R. Chen, Y. Mou and X. Chen, J. Org. Chem., 2012,
77, 1386.
The Netherlands Organization of Scientific Research (NWO) is
gratefully acknowledged for financial support by means of a
TOP grant. The authors thank Christophe Vande Velde
(University of Antwerp, Belgium) for the X-ray structure
determination, and Matthias Zeller (Youngstown State
University, USA) for the collection of the X-ray diffraction data.
The diffractometer was funded by NSF Grant 1337296. We
thank Elwin Janssen for technical assistance, Sanne Bouwman
for HRMS measurements, and Dr. Andreas W. Ehlers for NMR
maintenance.
12 (a) A. Znabet, E. Ruijter, F. J. J. de Kanter, V. Kohler, M.
Helliwell, N. J. Turner and R. V. A. Orru, Angew. Chem. Int.
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J. J. de Kanter, N. J. Turner, R. V. A. Orru and E. Ruijter, Chem.
Commun., 2010, 46, 7918; (c) A. Znabet, J. Zonneveld, E.
Janssen, F. J. J. De Kanter, M. Helliwell, N. J. Turner, E. Ruijter
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Znabet, S. Blanken, E. Janssen, F. J. J. de Kanter, M. Helliwell,
N. J. Turner, E. Ruijter and R. V. A. Orru, Org. Biomol. Chem.,
2012, 10, 941.
13 Standard procedures for the oxidation of aliphatic amines to
imines are performed using a two-step protocol of N-
halogenation followed by base-mediated elimination.
Unfortunately, we experienced these procedures to be
highly dependent on concentration and batch of
halogenation reagent and therefore difficult to reproduce.
14 The oxidation was amenable to scale up (4 mmol) with minor
changes to the general procedure (0.4 M, 2 h), affording
imine 2a in 76% yield.
15 T. M. Chapman, S. Courtney, P. Hay and B. G. Davis, Chem.
Eur. J., 2003, 9, 3397.
16 Piperidine derivatives and acyclic secondary amines were not
converted under these conditions.
Notes and references
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19 For the corresponding diastereoselective Ugi-type reaction
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A single case of oxidation at a nonactivated position was
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21 The oxidation of dihydroindoline and tetrahydroquinoline
was only selective when using an excess of IBX (2 eq) and a
stoichiometric amount of radical inhibitor TEMPO (1 – 1.5
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4 | Org. Biomol. Chem., 2015, 00, 1-3
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