Journal of the American Chemical Society
Communication
(7) For oxidative dehydrogenation methods that use cyclohexanones
and cyclohexenones as precursors to other aromatic compounds, such as
aryl sulfides, coumarins, and aryl indoles, see: (a) Kim, D.; Min, M.;
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(8) This reaction could occur via a traditional β-hydride elimination
pathway or via an anti-elimination process, which has been observed
previously: Takacs, J. M.; Lawson, E. C.; Clement, F. J. Am. Chem. Soc.
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dehydrogenation of cyclohexenes, like the previous dehydrogen-
ation of cyclohexanones and related derivatives,3−7 offers
complementary appeal or significant advantages relative to
cross-coupling reactions in the preparation of substituted
aromatics. The dehydrogenation methods exploit classical
organic transformations, such as Diels−Alder cycloadditions
(to access cyclohexenes) and Robinson annulations (to access
cyclohexenones3a), as versatile and efficient routes to core
structures that are excellent precursors to selectively substituted
aromatic compounds.
In conclusion, we have identified new Pd catalyst systems for
the oxidative dehydrogenation of cyclohexenes. The method
enables efficient synthesis of substituted arene derivatives and
shows good functional group tolerance. Use of this method in the
preparation of a substituted phthalimide showcases the strategic
opportunity to use this transformation in the synthesis of
biologically active compounds.
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̌
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J. E.; Kocovsky, P. Tetrahedron Lett. 1984, 25, 4187. (b) Hansson, S.;
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̈
ASSOCIATED CONTENT
* Supporting Information
Additional catalyst screening data, experimental procedures,
compound characterization data. This material is available free of
(h) Grennberg, H.; Backvall, J.-E. Chem.Eur. J. 1998, 4, 1083.
̈
■
(i) Pilarski, L. T.; Selander, N.; Bose, D.; Szabo,
5518.
́
K. J. Org. Lett. 2009, 11,
̈
S
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(b) Sheldon, R. A.; Sobczak, J. M. J. Mol. Catal. 1991, 68, 1.
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(d) Williams, T. J.; Caffyn, A. J. M.; Hazari, N.; Oblad, P. F.; Labinger, J.
A.; Bercaw, J. E. J. Am. Chem. Soc. 2008, 130, 2418. (e) Bercaw, J. E.;
Hazary, N.; Labinger, J. A.; Oblad, P. F. Angew. Chem., Int. Ed. 2008, 47,
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ChemCatChem 2010, 2, 175.
AUTHOR INFORMATION
Corresponding Author
Notes
■
The authors declare no competing financial interest.
(12) Kandukuri, S. R.; Oestreich, M. J. Org. Chem. 2012, 77, 8750.
(13) A PdII catalyst system for dehydrogenation of terminal alkenes to
1,3-dienes, with a stoichiometric quinone oxidant, was reported
recently: Stang, E. M.; White, M. C. J. Am. Chem. Soc. 2011, 133, 14892.
(14) (a) Fu, P. P.; Harvey, R. G. Chem. Rev. 1978, 78, 317. (b) Buckle,
D. R. Encyclopedia of Reagents for Organic Synthesis; John Wiley & Sons,
Inc.: New York, 2010.
(15) Cahiez, G.; Alami, M.; Taylor, R. J. K.; Reid, M.; Foot, J. S.; Fader,
L. Encyclopedia of Reagents for Organic Synthesis; John Wiley & Sons,
Ltd.: 2001.
ACKNOWLEDGMENTS
■
We thank Yusuke Izawa for conducting preliminary research in
the area. We thank Drs. Jack W. Kruper and Anna Davis for useful
discussions. This work was supported by the NIH (R01-
GM100143) and The Dow Chemical Company. NMR spec-
troscopy facilities were partially supported by the NSF (CHE-
0342998, CHE-1048642) and NIH (S10 RR08389). Mass
spectrometry instrumentation was partially supported by the
NIH (S10 RR024601).
(16) For the 1-mmol-scale reactions, use of MgSO4 was found to
enhance the yields by 5−10%, presumably by serving as a drying agent.
See Supporting Information for the experimental procedure.
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