Aerobic Oxidation of Secondary Alcohols
taken every 10 min for the first 40 min. The aliquots were passed
through a pad of silica using EtOAc as eluent, which quenched the
reaction by removal of the catalyst. Reactions were run in a parallel
as well in a competitive manner. The resulting solutions were ana-
lyzed by GC (CP Chirasil DEXCB) in the case of the parallel ex-
periments. Samples from the competitive runs were analyzed by
GC/MS.
inactive ruthenium species. We could also see that the rate
of the reaction was heavily dependent on the solubility of
both catalysts. Control experiments further showed that no
aerobic oxidation took place according to GC within 24 h if
one of the components of the catalytic system was removed.
Supporting Information (see also the footnote on the first page of
this article): Kinetic plots and reaction profiles.
Conclusions
We have developed an efficient catalytic process for the
biomimetic aerobic oxidation of secondary alcohols that
tolerates a wide range of substrates. The oxidation of benz-
ylic alcohols as well as aliphatic alcohols can be performed.
Electron-rich, electron-deficient and sterically hindered
alcohols can be oxidized to the corresponding ketones
in high yield and selectivity by this methodology. The
deuterium isotope effect was determined by the use of
1-deuterio-1-phenylethanol. Due to the efficiency of intra-
molecular electron transfer, hybrid catalyst 1 allows for a
lower catalytic loading and milder reaction conditions com-
pared to the use of the separate quinone and Co(salmdpt)
triple catalytic system.
Acknowledgments
The Swedish Research Council and the K&A Wallenberg Founda-
tion are gratefully acknowledged for financial support.
[1] a) M. J. Schultz, M. S. Sigman, Tetrahedron 2006, 62, 8227; b)
I. W. C. E. Arends, R. A. Sheldon, Modern Oxidation of
Alcohols using Environmentally Benign Oxidants, in: Modern
Oxidation Methods (Ed.: J.-E. Bäckvall), Wiley-VCH,
Weinheim, Germany, 2004, pp. 83–118.
[2] a) F. Shi, M. K. Tse, Z. Li, M. Beller, Chem. Eur. J. 2008, 14,
8793; b) D. C. Ebner, R. M. Trend, C. Genet, M. J. McGrath,
P. O_Brien, B. M. Stoltz, Angew. Chem. Int. Ed. 2008, 47, 6367;
c) R. M. Trend, B. M. Stoltz, J. Am. Chem. Soc. 2008, 130,
15957; d) S. Arita, T. Koike, Y. Kayaki, T. Ikariya, Angew.
Chem. Int. Ed. 2008, 47, 2447; e) M. Wills, Angew. Chem. Int.
Ed. 2008, 47, 4264; f) E. T. T. Kumpulainen, A. M. P. Kos-
kinen, Chem. Eur. J. 2009, 15, 1090; E. Karlsson, T. Privalov,
Chem. Eur. J. 2009, 15, 1862.
Experimental Section
General: 1H NMR and 13C NMR spectra were obtained with a
400 MHz spectrometer using [D1]chloroform (δ = 7.26 ppm 1H,
77 ppm 13C) as internal standard and were in good agreement with
the data previously reported in the literature.[9d] Analytical gas
chromatography was performed with a Varian 3800 GC with a FID
detector, connected to a Varian computing integrator. A 30-m CP-
CHIRASIL-DEX CB fused silica column was used. Ruthenium
catalyst 2 was prepared according to a literature procedure.[17] The
hybrid catalysts 1 was prepared according to a new method devel-
oped in our laboratory.[13b] Compound 3a-d1 was prepared accord-
ing to a literature procedure.[18] All other reagents are commercially
available and were used without further purification. Column
chromatography was performed with DAVISIL LC60A silica gel
and analytical TLC was performed on Merck precoated silica 60-
F254 plates. Solvents for extraction and chromatography were of
analytical grade.
[3] J. Clayden, N. Greeves, S. Warren, P. Wolters, Organic Chemis-
try, Oxford Univ. Press, New York, 2001.
[4] a) J. Piera, J. E. Bäckvall, Angew. Chem. Int. Ed. 2008, 47,
3506–3523; b) F. G. Gelalcha, G. Anilkumar, M. K. Tse, A.
Brückner, M. Beller, Chem. Eur. J. 2008, 14, 7697; c) P. C. A.
Bruijnincx, I. L. C. Buurmans, S. Gosiewska, M. A. H. Moel-
ands, M. Lutz, A. L. Spek, G. van Koten, R. J. M. Klein Geb-
bink, Chem. Eur. J. 2008, 14, 1228.
[5] a) S. S. Stahl, Angew. Chem. Int. Ed. 2004, 43, 3400; b) B. V.
Popp, S. S. Stahl, Chem. Eur. J. 2009, 15, 2915.
[6] G. J. ten Brink, I. W. C. E. Arends, R. A. Sheldon, Science
2000, 287, 1636.
[7] J.-E. Bäckvall, R. B. Hopkins, H. Grennberg, M. Mader, A. K.
Awasthi, J. Am. Chem. Soc. 1990, 112, 5160.
[8] a) K. Bergstad, S. Y. Jonsson, J.-E. Bäckvall, J. Am. Chem. Soc.
1999, 121, 10424; b) S. Y. Jonsson, K. Färnegårdh, J.-E.
Bäckvall, J. Am. Chem. Soc. 2001, 123, 1365.
General Procedure for Ruthenium-Catalyzed Aerobic Oxidation of
Secondary Alcohols 3a–e. Oxidation of 3a to 4a: Ruthenium com-
[9] a) J. Piera, K. Närhi, J.-E. Bäckvall, Angew. Chem. Int. Ed.
2006, 45, 6914; b) J. Piera, A. Persson, X. Caldentey, J.-E.
Bäckvall, J. Am. Chem. Soc. 2007, 129, 14120.
plex
2 (11 mg, 0.01 mmol) and hybrid catalyst 1 (12.5 mg,
0.02 mmol) were mixed and stirred in acetonitrile (1 mL). Com-
pound 3a (244 mg, 2 mmol) was added to the resulting solution
whilst stirring at 75 °C in a closed vessel under air atmosphere with
an oxygen replacement balloon connected to the reaction vessel
via a 5 cm long syringe (diameter 1.2 mm). After the appropriate
reaction time, the mixture was cooled to room temperature, the
solvent was removed by rotary evaporation and then purified by
flash chromatography (pentane/diethyl ether, 9:1). All the products
obtained, shown in Table 2, are known compounds and were char-
acterized by comparison with spectroscopic data from the litera-
ture.
[10] J. Wöltinger, J.-E. Bäckvall, A. Zsigmond, Chem. Eur. J. 1999,
5, 1460.
[11] a) J.-E. Bäckvall, R. L. Chowdhury, U. Karlsson, J. Chem.
Soc., Chem. Commun. 1991, 473; b) G.-Z. Wang, U. Andreas-
son, J.-E. Bäckvall, J. Chem. Soc., Chem. Commun. 1994, 1037;
c) G. Csjernyik, A. H. Éll, L. Fadini, B. Pugin, J.-E. Bäckvall,
J. Org. Chem. 2002, 67, 1657.
[12] J. S. M. Samec, A. H. Éll, J.-E. Bäckvall, Chem. Eur. J. 2005,
11, 2327.
[13] a) W. Purse, L. H. Tran, J. Piera, B. Åkermark, J.-E. Bäckvall,
Chem. Eur. J. 2008, 14, 7500; b) E. V. Johnston, E. A. Karlsson,
L.-H. Tran, B. Åkermark, J.-E. Bäckvall, Eur. J. Org. Chem.
2009, 3973; c) E. Johnston, E. A. Karlsson, S. A. Lindberg, B.
Åkermark, J.-E. Bäckvall, Chem. Eur. J. 2009, 15, 6799.
[14] a) Y. Blum, D. Czarkie, Y. Rahamin, Y. Shvo, Organometallics
1985, 4, 1459; b) Y. Shvo, D. Czarkie, Y. Rahamin, J. Am.
Chem. Soc. 1986, 108, 7400; c) Y. Shvo, I. Goldberg, D. Czer-
kie, D. Reshef, Z. Stein, Organometallics 1997, 16, 133.
General Procedure for the Kinetic Experiments: Ruthenium complex
2 (11 mg, 0.01 mmol) and hybrid catalyst 1 (12.5 mg, 0.02 mmol)
were mixed and stirred in acetonitrile (1 mL). Compound 3a
(244 mg, 2 mmol) was added to the resulting solution whilst stirring
at 75 °C in air with an oxygen replacement balloon. Aliquots were
Eur. J. Org. Chem. 2010, 1971–1976
© 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
1975