Organic Letters
Letter
(7) Denmark, S. E.; Forbes, D. C.; Hays, D. S.; DePue, J. S.; Wilde, R.
G. J. Org. Chem. 1995, 60, 1391.
(8) Yang, D.; Wong, M.-K.; Wang, X.-C.; Tang, Y.-C. J. Am. Chem. Soc.
use of a combination of H2O2 and acetic acid to generate
dioxiranes in situ.
In summary, this new organocatalytic method for C−H
oxidation enables for the first time the use of ketones as catalysts
for C−H hydroxylation. This method is applicable to the
hydroxylation of unactivated C−H bonds and is highly
chemoselective. Aqueous hydrogen peroxide serves as an
inexpensive and readily available terminal oxidant. To our
knowledge, the trifluoroacetophenones reported here are only
the second nonmetal catalysts shown to promote C−H
hydroxylation. We expect that this method will provide entry
to a much more thorough inquiry into dioxirane-mediated
catalytic C−H hydroxylation with the goal of improving
substrate scope, increasing catalyst turnover, and developing
asymmetric methods.
1998, 120, 6611.
(9) Shu, L.; Shi, Y. J. Org. Chem. 2000, 65, 8807.
(10) Fung, Y.-S.; Yan, S.-C.; Wong, M.-K. Org. Biomol. Chem. 2012, 10,
3122.
(11) Li, W.; Fuchs, P. L. Org. Lett. 2003, 5, 2853.
(12) This background reaction is likely mediated by peracetic acid
generated in situ, proceeding through either a concerted mechanism or a
mechanism involving free radicals: (a) Schleyer, P. v. R.; Nicholas, R. D.
J. Am. Chem. Soc. 1961, 83, 182. (b) Heywood, D.; Phillips, B.;
Stansbury, H., Jr. J. Org. Chem. 1961, 26, 281. (c) Moody, C. L.;
O’Connell, J. L. Chem. Commun. 2000, 1311.
(13) Only trace amounts of oxidation products (<5% conversion) were
observed in the absence of catalyst.
(14) Du, X.; Houk, K. N. J. Org. Chem. 1998, 63, 6480.
(15) See the Supporting Information for details.
(16) Hydroxylation does not occur in the absence of acetic acid.
(17) Peroxyhydrates are capable of transferring oxygen to olefins in
ketone-catalyzed epoxidations: (a) Van Vliet, M. C. A.; Arends, I. W. C.
E.; Sheldon, R. Synlett 2001, 1305. (b) Van Vliet, M. C. A.; Arends, I. W.
C. E; Sheldon, R. A. Chem. Commun. 1999, 263.
ASSOCIATED CONTENT
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S
* Supporting Information
Experimental details and analytical data for hydroxylation
products, as well as details for additional experiments. This
material is available free of charge via the Internet at http://pubs.
(18) See the Supporting Information for details.
(19) Yield of 1-adamantanol from adamantane in the presence of of 1.0
equiv of BHT: 75%. A simultaneous control experiment run in the
absence of BHT gave 77% yield of 1-adamantanol. See the Supporting
Information for details.
AUTHOR INFORMATION
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Corresponding Author
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
We thank the University of Virginia for financial support.
REFERENCES
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