Selective alcohol oxidation is a fundamental transformation
for the production of a variety of important intermediates and
fine chemicals.7 Although numerous inorganic oxidants (i.e.,
CrO3, KMnO4, MnO2, SeO2, etc.) in a stoichiometric amount
have been traditionally used to accomplish this transformation,8
there are considerable drawbacks such as their high cost and
the production of environmental hazardous/toxic byproducts.
Clearly, the most promising protocol to address these issues is
the development of catalytic aerobic alcohol oxidation meth-
odologies. The use of molecular oxygen as the primary oxidant
has remarkable advantages, including abundance, low cost,
improved safety, and benign byproducts (H2O and/or H2O2).
Accordingly, many transitional metals (mainly copper,9 pal-
ladium,10 and ruthenium11) alone or in combination with the
nitroxy radical 2,2,6,6-tetramethyl-piperidyl-1-oxy (TEMPO)12,13
have been intensively studied for the aerobic catalytic oxidation
of alcohols. Of particular interest are the catalytic systems
consisting of an inexpensive transition-metal compound and
TEMPO for mild and selective aerobic alcohol oxidations.
However, TEMPO is a rather expensive chemical agent and
efficient recycling of TEMPO is highly desirable, especially
when the reactions are run on a large scale. Several groups have
Cu(II)-Catalyzed Selective Aerobic Oxidation of
Alcohols under Mild Conditions
Nan Jiang and Arthur J. Ragauskas*
Department of Chemistry, Georgia Institute of Technology,
Atlanta, Georgia 30332
ReceiVed April 20, 2006
Aerobic Alcohol Oxidation. An efficient four-component
system consisting of acetamido-TEMPO/Cu(ClO4)2/TMDP/
DABCO in DMSO has been developed for room-temperature
aerobic alcohol oxidation. Under the optimal conditions,
various alcohols could be converted into their corresponding
aldehydes or ketones in good to excellent yields. The newly
developed catalytic system could also be recycled and reused
for three runs without any significant loss of catalytic activity.
(7) Hudlick, M. Oxidations in Organic Chemistry; American Chemical
Society: Washington, DC, 1990.
(8) March, J. AdVanced Organic Chemistry: Reactions, Mechanisms,
and Structure, 4th ed.; John Wiley & Sons: New York, 1992.
(9) For copper-catalyzed aerobic alcohol oxidation, see: (a) Marko, I.
E.; Giles, P. R.; Tsukazaki, M.; Brown, S. M.; Urch, C. J. Science 1996,
274, 2044. (b) Saint-Aman, E.; Menage, S.; Pierre, J.-L.; Defrancq, E.;
Gellon, G. New J. Chem. 1998, 393. (c) Wang, Y.; DuBois, J. L.; Hedman,
B.; Hodgson, K. O.; Stack, T. D. P. Science 1998, 279, 5350. (d) Chaudhuri,
P.; Hess, M.; Mueller, J.; Hildenbrand, K.; Bill, E.; Weyhermueller, T.;
Wieghardt, K. J. Am. Chem. Soc. 1999, 121, 9599. (e) Marko, I. E.; Gautier,
A.; Dumeunier, R.; Doda, K.; Philippart, F.; Brown, S. M.; Urch, C. J.
Angew. Chem., Int. Ed. 2004, 43, 1588. (f) Zaccheria, F.; Ravasio, N.; Psaro,
R.; Fusi, A. Chem. Commun. 2005, 253.
(10) For palladium-catalyzed aerobic alcohol oxidation, see: (a) Black-
burn, T. F.; Schwartz, J. Chem. Commun. 1977, 157. (b) Kaneda, K.; Fujii,
M.; Morioka, K. J. Org. Chem. 1996, 61, 4502. (c) Nishimura, T.; Onoue,
T.; Ohe, K.; Uemura, S. Tetrahedron Lett. 1998, 39, 6011. (d) Peterson, K.
P.; Larock, R. C. J. Org. Chem. 1998, 63, 3185. (e) ten Brink, G.-J.; Arends,
I. W. C. E.; Sheldon, R. A. Science 2000, 287, 1636. (f) Steinhoff, B. A.;
Fix, S. A.; Stahl, S. S. J. Am. Chem. Soc. 2002, 124, 766. (g) ten Brink,
G.-J.; Arends, I. W. C. E.; Sheldon, R. A. AdV. Synth. Catal. 2002, 344,
355. (h) Steinhoff, B. A.; Stahl, S. S. Org. Lett. 2002, 4, 4179. (i) Schultz,
M. J.; Park, C. C.; Sigman, M. S. Chem. Commun. 2002, 3034. (j) Uozumi,
Y.; Nakao, R. Angew. Chem., Int. Ed. 2003, 42, 194. (k) Jensen, D. R.;
Schultz, M. J.; Mueller, J. A.; Sigman, M. S. Angew. Chem., Int. Ed. 2003,
42, 3810. (l) Iwasawa, T.; Tokunaga, M.; Obora, Y.; Tsuji, Y. J. Am. Chem.
Soc. 2004, 126, 6554. (m) Mueller, J. A.; Cowell, A.; Chandler, B. T.;
Sigman, M. S. J. Am. Chem. Soc. 2005, 127, 14817. (n) Hou, Z.; Theyssen,
N.; Brinkmann, A.; Leitner, W. Angew. Chem., Int. Ed. 2005, 44, 1346.
(o) Schultz, M. J.; Hamilton, S. S.; Jensen, D. R.; Sigman, M. S. J. Org.
Chem. 2005, 70, 3343. (p) Steinhoff, B. A.; King, A. E.; Stahl, S. S. J.
Org. Chem. 2006, 71, 1861.
The design of efficient catalytic systems that provide facile
recovery of catalysts and isolation of a catalyst-free product are
highly attractive due to practical economic and environmental
manufacturing considerations.1 To address this challenge, dif-
ferent strategies are being developed including the use of ionic
liquids,2 fluorous biphasic systems,3 soluble polymer-based
ligands,4 and aqueous biphasic systems.5 However, the use of
the polar aprotic solvent dimethyl sulfoxide (DMSO) to recycle
and reuse homogeneous transitional metal catalysts is less
developed.6 Nonetheless, considering its capacity to dissolve
various organic, inorganic, and organometallic compounds and
its immiscibility with many nonpolar organic solvents, it was
anticipated that these properties would facilitate catalyst-
product separation by simple extraction. Thus, the use of DMSO
as the reaction media should provide opportunities for facilitating
the recovery and recycling of catalysts.
(1) Cornils, B.; Herrmann, W. A. Applied Homogeneous Catalysis with
Organometallic Compounds, 2nd ed.; Wiley-VCH: New York, 2002.
(2) (a) Welton, T. Chem. ReV. 1999, 99, 2071. (b) Wassercheid, P.; Keim,
W. Angew. Chem., Int. Ed. 2000, 39, 3772. (c) Sheldon, R. A. Chem.
Commun. 2001, 2399. (d) Dupont, J.; de Souza, R. F.; Suares, P. A. Z.
Chem. ReV. 2002, 102, 3667.
(3) (a) Horva´th, I. T.; Rabai, J. Science 1994, 266, 72. (b) Cornils, B.
Angew. Chem., Int. Ed. Engl. 1997, 36, 2057. (c) Horva´th, I. T. Acc. Chem.
Res. 1998, 31, 641. (d) Cavazzini, M.; Montanari, F.; Pozzi, G.; Quici, S.
J. Fluorine Chem. 1999, 94, 183.
(4) (a) Bergbreiter, D. E. Catal. Today 1998, 42, 389. (b) Dickerson, T.
J.; Reed. N. N. Chem. ReV. 2002, 102, 3325.
(5) (a) Herrmann, W. A.; Kohlpaintner, C. W. Angew. Chem., Int. Ed.
Engl. 1993, 32, 1524. (b) Joo´, F.; Katho´, AÄ . J. Mol. Catal. A: Chem. 1997,
116, 3. (c) Joo´, F. Acc. Chem. Res. 2002, 35, 738. (d) Wilkes, J. S. J. Mol.
Catal. A: Chem. 2004, 214, 11.
(6) For using DMSO to immobilize the homogeneous catalyst, see: (a)
Kollhofer, A.; Plenio, H. Chem.-Eur. J. 2003, 9, 1416. (b) Remmele, H.;
Koellhofer, A.; Plenio, H. Organometallics 2003, 22, 4098. (c) an der,
Heiden, M.; Plenio, H. Chem.-Eur. J. 2004, 10, 1789.
(11) For ruthenium-catalyzed aerobic alcohol oxidation, see: (a) Matsu-
moto, M.; Watanabe, N. J. Org. Chem. 1984, 49, 3435. (b) Kaneda, K.;
Yamashita, T.; Matsushita, T.; Ebitani, K. J. Org. Chem. 1998, 63, 1750.
(c) Masutani, K.; Uchida, T.; Irie, R.; Katsuki, T. Tetrahedron Lett. 2000,
41, 5119. (d) Yamaguchi, K.; Mori, K.; Mizugaki, T.; Ebitani, K.; Kaneda,
K. J. Am. Chem. Soc. 2000, 122, 7144. (e) Pagliaro, M.; Ciriminna, R.
Tetrahedron Lett. 2001, 42, 4511. (f) Yamaguchi, K.; Mizuno, N. Angew.
Chem., Int. Ed. 2002, 41, 4538. (g) Musawir, M.; Davey, P. N.; Kelly, G.;
Kozhevnikov, I. V. Chem. Commun. 2003, 1414. (h) Zhan, B.-Z.; White,
M. A.; Sham, T.-K.; Pincock, J. A.; Doucet, R. J.; Ramama, R. K. V.;
Robertson, K. N.; Cameron, T. S. J. Am. Chem. Soc. 2003, 125, 1195. (i)
Shimizu, H.; Onitsuka, S.; Egami, H.; Katsuki, T. J. Am. Chem. Soc. 2005,
127, 5396. (j) Egami, H.; Onitsuka, S.; Katsuki, T. Tetrahedron Lett. 2005,
46, 6049.
10.1021/jo060837y CCC: $33.50 © 2006 American Chemical Society
Published on Web 07/29/2006
J. Org. Chem. 2006, 71, 7087-7090
7087