Cesium hydroxide-promoted aerobic oxidation of sec-aromatic alcohols

Article abstract of DOI:10.1016/j.tetlet.2008.06.061

A CsOH-promoted aerobic oxidation of sec-aromatic alcohols has been developed, using air as a free and clean oxidant, and providing aryl ketones in good to excellent yields.

Full text of DOI:10.1016/j.tetlet.2008.06.061

Tetrahedron Letters 49 (2008) 5336–5338
Contents lists available at ScienceDirect
Tetrahedron Letters
journal homepage: www.elsevier.com/locate/tetlet
Cesium hydroxide-promoted aerobic oxidation of sec-aromatic alcohols
Weiwei Zhang, Miaochang Liu, Huayue Wu, Jinchang Ding, Jiang Cheng *
College of Chemistry and Materials Science, Wenzhou University, Wenzhou 325027, PR China
a r t i c l e i n f o
a b s t r a c t
Article history:
A CsOH-promoted aerobic oxidation of sec-aromatic alcohols has been developed, using air as a free and
clean oxidant, and providing aryl ketones in good to excellent yields.
Ó 2008 Published by Elsevier Ltd.
Received 13 February 2008
Revised 10 June 2008
Accepted 13 June 2008
Available online 18 June 2008
Keywords:
Diarylketone
Cesium hydroxide
Aerobic oxidation
sec-Aromatic alcohol
Aryl ketones
The oxidation of sec-alcohols into ketones is one of the most
important functional group transformation reactions in organic
chemistry. In the past decades, much attention has been paid to
develop efficient methods for this transformation.1 Many stoichi-
ometric oxidants, such as chromium(VI) and manganese reagents,
partly oxidized from the corresponding secondary alcohol, which
was formed in situ by the addition of organoboronic acids to alde-
hydes. Herein, we wish to explore the feasibility of catalytic
amount of base-promoted aerobic oxidation of sec-aryl alcohol.
Initially, we studied the aerobic oxidation of benzo[d][1,3]diox-
ol-5-yl(phenyl)methanol in the presence of a series of bases in the
common organic solvents. The results are summarized in Table 1.
2
were employed. Considering environmental and economic
demands, developing relative clean and efficient methods has been
a highly desired goal in organic synthesis. Molecular oxygen usu-
2 3 2 3
At first, weak bases such as CsF, K CO and Cs CO were tested in
the transformation. Much to our disappointment, these weak bases
3
ally plays an important role in the oxidation reaction. Lately,
4
5
6
many examples of using copper, palladium and ruthenium cat-
alysts for such kind of oxidation reactions using molecular oxygen
or air have been reported. Very recently, the efficient non-equiva-
lent for activation of molecular oxygen and its application in aero-
bic alcohol oxidation described by Hu is of great interest due to the
obviation of transition metal.7
Table 1
a
Screen of the base in aerobic oxidation of carbinol
OH
O
O
O
base, sol., air
O
O
O
PdCl , P(1-nap)3
K2CO3 (3 equiv)
OH
Ar'
2
+
Ar'B(OH)2
Ar'B(OH)2
Yieldb (%)
Ar
Entry
Base
Equiv
Solvent
Ar
Ar
H
ð1Þ
O
O
1
2
KOH
KOH
CsOH
NaOH
CsF
0.4
0.2
0.2
0.2
0.2
0.2
0.2
0.2
0.2
0.2
0.2
0.2
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
THF
84
26
82
77
<5
<5
<5
<5
10
11
<5
<5
Pd2(dba)3, P(1-nap)3
+
H
Cs CO3 (3 equiv)
Ar
Ar'
b
2
3
4
5
6
7
7
8
9
10
11
In our previous work, we found that the combination of K
2 3
CO ,
PdCl and P(1-nap) in THF could efficiently catalyze the reaction
2
3
K CO
2
3
of aryl aldehydes with aryl boronic acids, providing the carbinol
derivatives in good yield. During the researching process, we found
that aryl ketones were formed. Interestingly, the employment of
Cs
2
CO
3
K
3
PO
4
ꢀ3H
2
O
CsOH
CsOH
CsOH
CsOH
3
CH CN
Dioxane
EtOH
Cs
2
CO
3
instead of K
2
CO
3
provides the aryl ketones in moderate to
8
good yields under air (Eq. 1). The desired products were at least
a
All reactions were run under air in the presence of indicated amounts of base in
*
Corresponding author. Tel./fax: +86 577 88156826.
E-mail address: jiangcheng@wzu.edu.cn (J. Cheng).
indicated solvents under refluxing for 24 h.
b
Isolated yield.
0
040-4039/$ - see front matter Ó 2008 Published by Elsevier Ltd.
doi:10.1016/j.tetlet.2008.06.061

W. Zhang et al. / Tetrahedron Letters 49 (2008) 5336–5338
5337
were totally ineffective. So we employed several strong bases to
OH
Ar'
1
OH
test the activity. In the presence of 0.4 equiv KOH, 84% of the prod-
uct was isolated. However, the yield dramatically decreased to 26%
in the presence of 0.2 equiv of KOH. Surprisingly, 82% and 77%
products were formed in the presence of 0.2 equiv of CsOH and
NaOH, respectively. Solvents also played important roles in the oxi-
dation reaction. Among the tested common organic solvents, tolu-
ene was the best. At last, the optimal reaction condition was to use
Ar
1/2O2
2
H
1/2 O2
0
.2 equiv of CsOH in toluene under air.
O
With the optimized reaction conditions in hand, a series of sub-
Ar
Ar'
strates were subjected to broaden the substrates scope (Fig. 1). The
electronic effect of the substitution groups on the aryl ring was not
obvious in the reaction. The carbinol derivatives possessing both
electron-withdrawing groups and electron-donating groups ran
smoothly, and provided corresponding aryl ketones in good to
excellent yields. The hindrance in the ortho-position of the aryl
group had little effects on the yield such as 2j and 2k were isolated
in 97% and 82% yields, respectively. The hetero-carbinol derivatives
such as 1m, 1n, 1o were also good substrates in the reaction.
or
H
A
H O
2
H
O
Ar
Ar'
2
1
-(Naphthalen-1-yl)ethanol 1p and 1-(p-phenyl)phenylethanol
Figure 2. Plausible mechanism.
1
q also ran smoothly, and the products were isolated in moderate
yields. Interestingly, 1l could proceed smoothly to deliver the
product 2l in 70% isolated yield. 2-Hydroxy-1,2-di-tolylethanone
was also a good reaction partner and 2r was formed in 74% yield.
However, alkyl alcohols, such as cyclohexanol did not work under
A plausible mechanism was proposed, as shown in Figure 2.
The catalytic cycle might contain three steps: (1) carbinol could
undergo deprotonation to form intermediate A; (2) intermediate A
ꢁ
9
could extrude a H to form the oxidation product; (3) the formed
this condition. The reaction could run under N
2
, and 84% yield of
ꢁ
ꢁ
H
either could react with O
2
to form OH or could undergo direct
benzophenone was isolated in the presence of 1.0 equiv of CsOH.
ꢁ
hydrolysis to form OH and 2 mol of atomic hydrogens, which
2 2
could react with O to form H O. A radical pathway could not be
OH
0.2 equiv CsOH
O
ruled out either.
In conclusion, a CsOH-promoted aerobic oxidation of sec-
aromatic alcohols has been developed, providing corresponding
ketones in good to excellent yields. Both the use of air as a free
and environment-friendly oxidant and the obviation of transi-
tion-metal catalyst all consist of the charming characters in this
Ar
R
air,toluene, refluxing Ar
R
1
2
O
O
O
OMe
10
procedure.
2
a 96%
2b 92%
2c 88%
O
O
Acknowledgement
O
O
We thank the National Natural Science Foundation of China
(No. 20504023) for financial support.
O
MeO
OMe F
NO2
2d 82%
2e 96%
2f 57%
O
O
O
Supplementary data
Cl
Supplementary data associated with this article can be found, in
the online version, at doi:10.1016/j.tetlet.2008.06.061.
Br
Cl
2g 94%
2h 98%
2i 98%
O
O
OMe
O
References and notes
Ph
1.
(a) Hudlicky, M. Oxidation 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; (c) Sheldon, R.
A.; Arends, I. W. C. E. In Modern Oxidation Methods; Backvall, J.-E., Ed.; Wiley-
VCH: Weinheim, 2004; p 83; (d) Tojo, G.; Fernandez, M. In Oxidation of Alcohols
to Aldehyde and Ketones: A Guide to Current Common Practice; Tojo, G., Ed.;
Springer: New York, 2006.
2j 97%
2k 82%
2l 70%
O
O
O
N
S
N
O
2.
(a) Cainelli, G.; Cardillo, G. Chromium Oxidants in Organic Chemistry; Springer:
Berlin, 1984; (b) Ley, S. V.; Madin, A. In Comprehensive Organic Synthesis; Trost,
B. M., Fleming, I., Ley, S. V., Eds.; Pergamon: Oxford, UK, 1991; Vol. 7, pp 251–
2
m 99%
2n 93%
2o 92%
289.
O
O
3. (a) Trost, B. M. Science 1991, 254, 1471; (b) Kaneda, K. T.; Yamashita, T.;
Matsushita, K.; Ebitani, K. J. Org. Chem. 1998, 63, 1750; (c) Ishii, Y.; Iwahama, T.;
Sakaguchi, S.; Nakayama, K.; Nishiyama, Y. J. Org. Chem. 1996, 61, 4520; (d)
Sharma, V. B.; Jain, S. L.; Sain, B. Tetrahedron Lett. 2003, 44, 383.
Ph
O
4.
(a) Marko, E.; Gautier, A.; Dumeunier, R.; Doda, K.; Philippart, F.; Brown, S. M.;
Urch, C. J. Angew. Chem., Int. Ed. 2004, 43, 1588; (b) Marko, I. E.; Giles, P. R.;
Tsukazaki, M.; Brown, S. M.; Urch, C. J. Science 1996, 274, 2044; (c) Marko, I. E.;
Giles, P. R.; Tsukazaki, M.; Chelle-Regnaut, I.; Gautier, A.; Brown, S. M.; Urch, C.
J. J. Org. Chem. 1999, 64, 2433.
2
p 46%
2q 49%
2r 74%
Figure 1. Cesium hydroxide-promoted aerobic oxidation of sec-aromatic alcohols.
Reagents and conditions: carbinol (0.5 mmol), CsOH (15 mg, 0.1 mmol), toulene
5.
(a) Kaneda, K.; Fujii, M.; Morioka, K. J. Org. Chem. 1996, 61, 4503; (b) Kaneda, K.;
Fujie, Y.; Ebitani, K. Tetrahedron Lett. 1997, 38, 9023; (c) Nishimura, T.; Onoue,
(
3 mL), under air at 110 °C for 24 h. Isolated yield.

5
338
W. Zhang et al. / Tetrahedron Letters 49 (2008) 5336–5338
T.; Ohe, K.; Uemura, S. Tetrahedron Lett. 1998, 39, 6011; (d) Peterson, K. P.;
Kozhevnikov, I. V. Chem. Commun. 2003, 1414; (f) Zhan, B.-Z.; White, M. A.;
Sham, T.-K.; Pincock, J. A.; Doucet, R. J.; Ramana, R. K. V.; Robertson, K. N.;
Cameron, T. S. J. Am. Chem. Soc. 2003, 125, 2195; (g) Shimizu, H.; Onitsuka, S.;
Egami, H.; Katsuki, T. J. Am. Chem. Soc. 2005, 127, 5396.
Larock, R. C. J. Org. Chem. 1998, 63, 3185; (e) Nishimura, T.; Onoue, T.; Ohe, K.;
Uemura, S. J. Org. Chem. 1999, 64, 6750; (f) Stahl, S. S.; Thorman, J. L.; Nelson, R.
C.; Kozee, M. A. J. Am. Chem. Soc. 2001, 123, 7188; (g) ten Brink, G.-J.; Arends, I.
W. C. E.; Sheldon, R. A. Adv. Synth. Catal. 2002, 344, 355; (h) Steinhoff, B. A.; Fix,
S. R.; Stahl, S. S. J. Am. Chem. Soc. 2002, 124, 766; (i) Uozumi, Y.; Nakao, R.
Angew. Chem., Int. Ed. 2003, 42, 194; (j) Jensen, D. R.; Schultz, M. J.; Mueller, 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; (l) Mori, K.; Hara, T.;
Mizugaki, T.; Ebitani, K.; Kaneda, K. J. Am. Chem. Soc. 2004, 126, 10657; (m)
Kwon, M. S.; Kim, N.; Park, C. M.; Lee, J. S.; Kang, K. Y.; Park, J. Org. Lett. 2005, 7,
7. Xie, Y.; Mo, W.; Xu, D.; Shen, Z.; Sun, N.; Hu, B.; Hu, X. J. Org. Chem. 2007, 72,
4288.
8. (a) Qin, C.; Wu, H.; Cheng, J.; Chen, X.; Liu, M.; Zhang, W.; Su, W.; Ding, J. J. Org.
Chem. 2007, 72, 4102; (b) Qin, C.; Chen, J.; Wu, H.; Cheng, J.; Zhang, Q.; Zuo, B.;
Su, W.; Ding, J. Tetrahedron Lett. 2008, 49, 1884.
ꢁ
9. The extrusion of
H
under strong base is possible, see the Cannizzaro
reaction: (a) Cannizzaro, S. Justus Liebigs Ann. Chem. 1853, 88, 129; (b) Pfeil,
E. Chem. Ber. 1951, 84, 229; (c) Hazlet, S. E.; Stauffer, D. A. J. Org. Chem. 1962, 27,
2021.
1
077; (n) Hou, Z.; Theyssen, N.; Brinkmann, A.; Leitner, W. Angew. Chem., Int.
Ed. 2005, 44, 1346.
6
.
(a) Matsumoto, M.; Watanabe, N. J. Org. Chem. 1984, 49, 3435; (b) Murahashi,
S.-I.; Naota, T.; Hirai, N. J. Org. Chem. 1993, 58, 7318; (c) Markó, I. E.; Giles, P.;
Tsukazaki, R. M.; Chellé-Regnaut, I.; Urch, C. J.; Brown, S. M. J. Am. Chem. Soc.
10. General procedure: Under air, a reaction tube was charged with CsOH (14.9 mg,
20 mol %), sec-aromatic alcohol (0.5 mmol) and toluene (3 mL). The mixture
was heated under air at 110 °C for 24 h, then cooled to room temperature. The
mixture was concentrated in vacuo and the residue was purified by flash
column chromatography on a silica gel to give the desired product.
1
997, 119, 12661; (d) Csjernyik, G.; Ell, A. H.; Fadini, L.; Pugin, B.; Backvall, J.-E.
J. Org. Chem. 2002, 67, 1657; (e) Musawir, M.; Davey, P. N.; Kelly, G.;