tions of alcohols in water have been reported to date.6c,e,i
A crucial reason is that water can easily deactivate the
catalyst by competing with the substrates and/or inter-
mediates for vacant coordination sites on active metal
catalysts.10 Recently, we reported a transition-metal-free
aerobic oxidation system, where a wide range of alcohols
can be converted into their corresponding aldehydes or
ketones in high yields with a catalytic amount of TEMPO,
Highly Efficient Catalytic Aerobic
Oxidations of Benzylic Alcohols in Water
Renhua Liu, Chunyan Dong, Xinmiao Liang,
Xiujuan Wang, and Xinquan Hu*
11
Dalian Institute of Chemical Physics, the Chinese Academy
of Sciences, Dalian, 116023, People’s Republic of China
2 2
Br , and NaNO . As it did not involve transition metals
in the catalytic system, we envision that the newly
designed process could overcome the intrinsic disadvan-
tage that transition metal catalysts were often involved
in the aerobic alcohol oxidation with water as a solvent.
If we could replace bromine, which is undesirable due to
its hazardous nature albeit in catalytic amount, we could
then establish a green aerobic alcohol oxidation system.
In this communication, we report a TEMPO-catalyzed
aerobic alcohol oxidation in water, using 1,3-dibromo-5,5-
Received September 15, 2004
2
dimethylhydantoin and NaNO as cocatalysts (eq 1).
A highly efficient catalytic system without transition metals
in water has been developed for aerobic oxidations of
benzylic alcohols. The newly developed catalyst system could
oxidize benzylic alcohols and heteroaromatic analogues with
1
mol % TEMPO as a catalyst and with a catalytic amount
Our previous study demonstrated that the transition-
metal-free oxidation system was sequentially a cascade
of 1,3-dibromo-5,5-dimethylhydantoin and NaNO2 as cocata-
lysts. Under the optimal conditions, various alcohols could
be converted into their corresponding aldehydes or ketones
in high yields.
(
6) For palladium-catalyzed aerobic oxidation, see: (a) Peterson, K.
P.; Larock, R. C. J. Org. Chem. 1998, 63, 3185. (b) Nishimura, T.;
Onoue, T.; Ohe, K.; Uemura, S. J. Org. Chem. 1999, 64, 6750. (c) ten
Brink, G.-J.; Arends, I. W. C. E.; Sheldon, R. A. Science 2000, 287,
1636. (d) Stahl, S. S.; Thorman, J. L.; Nelson, R. C.; Kozee, M. A. J.
Am. Chem. Soc. 2001, 123, 7188. (e) ten Brink, G.-J.; Arends, I. W. C.
E.; Sheldon, R. A. Adv. Synth. Catal. 2002, 344, 355. (f) Steinhoff, B.
A.; Fix, S. R.; Stahl, S. S. J. Am. Chem. Soc. 2002, 124, 766. (g)
Steinhoff, B. A.; Stahl, S. S. Org. Lett. 2002, 4, 4179. (h) Schultz, M.
J.; Park, C. C.; Sigman, M. S. Chem. Commun. 2002, 3034. (i) Uozumi,
Y.; Nakao, R. Angew. Chem., Int. Ed. 2003, 42, 194. (j) Jensen, D. R.;
Schultz, M. J.; Mueller, J. A.; Sigman, M. S. Angew. Chem., Int. Ed.
2003, 42, 3810. (k) Iwasawa, T.; Tokunaga, M.; Obora, Y.; Tsuji, Y. J.
Am. Chem. Soc. 2004, 126, 6554.
The use of water as a reaction solvent has attracted
great attention and become an active area of research in
green chemistry because water is a cheap, safe, conve-
nient solvent and benign to the environment. Although
much progress has been made with water-based catalytic
systems in the past few years, there still remains a great
1
2
challenge for some reactions. Transition-metal-catalyzed
aerobic oxidation of alcohols3 is one of the typical
(
7) For ruthenium-catalyzed aerobic oxidation, see: (a) Marko, I.
examples. Although many highly efficient aerobic alcohol
oxidation systems either catalyzed by transition-metal
catalysts (mainly copper, palladium, or ruthenium )
alone or in combination with nitroxyl radical 2,2,6,6-
tetramethyl-piperidyl-1-oxy (TEMPO)8 have been de-
veloped, only a few examples of catalytic aerobic oxida-
E.; Giles, P. R.; Tsukazaki, M.; Chelle-Regnaut, I.; Urch, C. J.; Brown,
S. M. J. Am. Chem. Soc. 1997, 119, 12661. (b) Csjernyik, G.; Ell, A.
H.; Fadini, L.; Pugin, B.; Backvall, J.-E. J. Org. Chem. 2002, 67, 1657.
4
5,6
7
(
c) Yamaguchi, K.; Mizuno, N. Angew. Chem., Int. Ed. 2002, 41, 4538.
d) Musawir, M.; Davey, P. N.; Kelly, G.; Kozhevnikov, I. V. Chem.
(
,9
Commun. 2003, 1414. (e) Zhan, B.-Z.; White, M. A.; Sham, T.-K.;
Pincock, J. A.; Doucet, R. J.; Ramana, Rao K. V.; Robertson, K. N.;
Cameron, T. S. J. Am. Chem. Soc. 2003, 125, 2195.
(
8) For reviews of TEMPO-catalyzed alcohol oxidation, see: (a) de
(1) (a) Anastas, P. T.; Warner, J. C. Green Chemistry: Theory and
Nooy, A. E. J.; Besemer, A. C.; van Bekkum, H. Synthesis 1996, 1153.
(b) Adam, W.; Saha-Moller, C. R.; Ganeshpure, P. A. Chem. Rev. 2001,
101, 3499. (c) Sheldon, R. A.; Arends, I. W. C. E.; ten Brink, G.-J.;
Dijksman, A. Acc. Chem. Res. 2002, 35, 774.
Practice; Oxford University Press: New York, 1998. (b) Li, C.-J.; Chan,
T.-H. Organic Reactions in Aqueous Media; John Wiley & Sons: New
York, 1997. (c) Organic Synthesis in Water; Grieco, P. A., Ed.; Blackie
Academic and Professional: London, 1998.
(9) For transition metal-assisted TEMPO-catalyzed aerobic alcohol
oxidations, see: (a) Semmelhack, F. M.; Schmidt, C. R.; Cortes, D. A.;
Chou, C. S. J. Am. Chem. Soc. 1984, 106, 3374. (b) Betzemeier, B.;
Cavazzini, M.; Quici, S.; Knochel, P. Tetrahedron Lett. 2000, 41, 4343.
(c) Cecchetto, A.; Fontana, F.; Minisci, F.; Recupero, F. Tetrahedron
Lett. 2001, 42, 6651. (d) Dijksman, A.; Mmarino-Gonzalez, A.; i
Payeras, A. M.; Arends, I. W. C. E.; Sheldon, R. A. J. Am. Chem. Soc.
2001, 123, 6826. (e) Ben-Daniel, R.; Alsters, P.; Neumann, R. J. Org.
Chem. 2001, 66, 8650. (f) Ansari, I. A.; Gree, R. Org. Lett. 2002, 4,
1507. (g) Gamez, P.; Arends, I. W. C. E.; Reedijk, J.; Sheldon, R. A.
Chem. Commun. 2003, 2414. (h) Minisci, F.; Recupero, F.; Pedulli, G.
F.; Lucarini, M. J. Mol. Catal. A 2003, 204-205, 63. (i) Dijiksman, A.;
Arends, I. W. C. E.; Sheldon, R. A. Org. Biomol. Chem. 2003, 1, 3232.
(j) Minisci, F.; Recupero, F.; Cecchetto, A.; Gambarotti, C.; Punta, C.;
Faletti, R.; Paganelli, R.; Pedulli, G. F. Eur. J. Org. Chem. 2004, 109.
(10) Hill, C. L. Angew. Chem., Int. Ed. 2004, 43, 402.
(2) For reviews, see: (a) Kobayashi, S.; Manabe, K. Acc. Chem. Res.
2
002, 35, 209. (b) Anastas, P. T.; Kirchhoff, M. M. Acc. Chem. Res.
002, 35, 686.
2
(3) (a) Hudlicky, M. Oxidations in Organic Chemistry, American
Chemical Society: Washington, DC, 1990. (b) Larock, R. C. In
Comprehensive Organic Transformation, 2nd ed.; Wiley-VCH: New
York, 1999; p 1197.
(
4) For copper-catalyzed aerobic alcohol oxidation, see: (a) Marko,
I. E.; Giles, P. R.; Tsukazaki, M.; Brown, S. M.; Urch, C. J. Science
996, 274, 2044. (b) Marko, I. E.; Giles, P. R.; Tsukazaki, M.; Chelle-
Regnaut, I.; Gautier, A.; Brown, S. M.; Urch, C. J. J. Org. Chem. 1999,
4, 2433. (c) Marko, I. E.; Gautier, A.; Dumeunier, R.; Doda, K.;
Philippart, F.; Brown, S. M.; Urch, C. J. Angew. Chem., Int. Ed. 2004,
3, 1588.
1
6
4
(5) For palladium-catalyzed aerobic alcohol oxidation, see recent
review: Stahl, S. S. Angew. Chem., Int. Ed. 2004, 43, 3400 and
references cited therein.
(11) Liu, R.; Liang, X.; Dong, C.; Hu, X. J. Am. Chem. Soc. 2004,
126, 4112.
1
0.1021/jo048369k CCC: $30.25 © 2005 American Chemical Society
Published on Web 12/29/2004
J. Org. Chem. 2005, 70, 729-731
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