View Article Online
Table 2 Substrate scopea
b
b
b
Entry
1
Substrate
Yield (%)
Entry
6
Substrate
Yield (%)
Entry
12
Substrate
Yield (%)
93
96
95
95
97
93
98
2
3
7
8
13
14
81
90e
4
85
9
0
15
93
5
50c
10
2-Decanol
1-Dodecanol
97
88
16
17
30f
39
d
g
11
a
All products have been previously reported in the literature. Average of two experiments. c 36 h. d 0.1 M alcohol. e Product is the corresponding lactone.
b
f
g
5
mol% Pd(OAc)
2
and 50 mol% TEA. 5 mol% Pd(OAc)
2
and 300 mol% TEA.
excess TEA, where A is the catalytically active species at room
temperature.
Since the reactivity of catalysts derived from pyridine and
the vessel and GC analysis performed. Upon completion of reaction, the
reaction mixture was loaded directly on a small pad of silica. The plug was
then flushed with hexanes to remove the toluene and the product eluted with
dichloromethane. The solvent was removed in vacuo to yield acetophenone
TEA are dramatically different at room temperature, we
1
(
137 mg, 95% yield). Purity confirmed by GC and H NMR.
3
examined Uemura’s catalyst using Pd(OAc)
2
and pyridine by
1
H NMR. In contrast to the use of TEA, the use of pyridine
results in a single Pd-species, C, at room temperature and 80 °C.
From these results, it is apparent that the nature and number of
1 Y. Tamaru, Y. Yamamoto, Y. Yamada and Z. Yoshida, Tetrahedron
Lett., 1979, 1401–1404; Y. Tamaru, K. Inoue, Y. Yamada and Z.
Yoshida, Tetrahedron Lett., 1981, 22,, 1801–1804; Y. Tamaru, Y.
Yamada, K. Inoue, Y. Yamamoto and Z. Yoshida, J. Org. Chem., 1983,
nitrogen-based ligands on Pd play a vital role in catalyst
activity.11
4
8, 1286–1292; B. M. Choudary, N. P. Reddy, M. L. Kantam and Z.
In conclusion, a convenient aerobic alcohol oxidation, which
is effective at room temperature, has been developed. To the
best of our knowledge, this is the first example of a Pd-catalyzed
aerobic oxidation of an alcohol at room temperature. All
reagents are commercially available. Using a catalyst loading of
Jamil, Tetrahedron Lett., 1985, 26, 6257–6258; S. Aït-Mohand, F.
Hénin and J. Muzart, Tetrahedron Lett., 1995, 36, 2473–2476.
T. F. Blackburn and J. Schwartz, J. Chem. Soc., Chem Commun., 1977,
2
1
57–158; E. Gomez-Bengoa, P. Noheda and A. M. Echavarren,
Tetrahedron Lett., 1994, 35, 7097–7098; K. Kaneda, M. Fujii and K.
Morioka, J. Org. Chem., 1996, 61, 4502–4503; K. Kaneda, Y. Fujie and
K. Ebitani, Tetrahedron Lett., 1997, 38, 9023–9026; K. P. Peterson and
R. C. Larock, J. Org. Chem., 1998, 62, 3185–3189; G.-J. ten Brink, I. W.
C. E. Arends and R. A. Sheldon, Science, 2000, 287, 1636–1639; K.
Hallman and C. Moberg, Adv. Synth. Catal., 2001, 343, 260–263.
T. Nishimura, T. Onoue, K. Ohe and S. Uemura, Tetrahedron Lett.,
3
2
mol% Pd(OAc) , both benzylic and aliphatic alcohols can be
oxidized. Initial mechanistic studies provide evidence that the
active catalyst may be a Pd-complex containing a single TEA
ligand. The development of more active catalysts, and elucidat-
ing the exact role of TEA are currently being investigated.
We acknowledge the NIH (NIGMS, GM63540) for support
of this research. We thank the University of Utah Research
Foundation, Merck Research, and Rohm and Haas Research,
and Invenux Inc. for partial support of this research. We thank
professor Gary Keck for chemicals and insightful discussions.
3
4
1
998, 39, 6011–6014; T. Nishimura, T. Onoue, K. Ohe and S. Uemura,
J. Org. Chem., 1999, 64, 6750–6755; N. Kakiuchi, Y. Maeda, T.
Nishimura and S. Uemura, J. Org. Chem., 2001, 66, 6620–6625.
P. Luhring and A. J. Schumpe, J. Chem. Eng. Data, 1989, 34, 250.
5 D. R. Jensen, J. S. Pugsley and M. S. Sigman, J. Am. Chem. Soc., 2001,
123, 7475–7476.
2
We thank Johnson Matthey for supplying Pd(OAc) .
6
For a related oxidative kinetic resolution, see: E. M. Ferreira and B. M.
Stoltz, J. Am. Chem. Soc., 2001, 123, 7725–7726.
The use of triethylamine with Pd(OAc) for oxidations at elevated
2
Notes and references
7
‡
Typical procedure for alcohol oxidation: Pd(OAc)
2
(8.1 mg, 0.036 mmol,
temperatures has been reported by Uemura. However, pyridine was a
better additive under the conditions reported, see ref. 3.
0.03 equiv., 3 mol%), toluene (3.4 ml), THF (0.6 ml), triethylamine (0.01
ml, 0.072 mmol, 0.06 equiv., 6 mol%), 3Å molecular sieves (200 mg), and
a magnetic stir bar were placed in a 25 ml schlenk flask. A balloon attached
to a three-way valve was placed on the flask and the vessel evacuated then
filled with oxygen. The purge was repeated three times using a water
aspirator. The mixture was allowed to stir at room temperature under an
oxygen atmosphere for 30 min. At this time, the sec-phenethyl alcohol
8 On small scale ( < 0.3 mmol), oxygen could be replaced with a balloon
of air and MS 3Å were not required. However, reactions on larger scale
required MS 3Å for reactions to proceed without decomposion of
palladium. For details on the use of MS 3Å, see ref. 3.
9 See ESI† for details.
10 For a mechanistic study of a Pd(II)–DMSO system, see: B. A. Steinhoff,
S. R. Fix and S. S. Stahl, J. Am. Chem. Soc., 2002, 124, 766–767.
11 For a mechanistic study of Uemura’s system, see: B. A. Steinhoff and
S. S. Stahl, Org. Lett., 2002, 4, 4179–4181.
(0.145 ml, 1.2 mmol, 1.0 equiv.) was syringed into the flask. Upon addition
of the alcohol, the mixture changed from yellow to orange. The reaction
mixture was allowed to stir for 12 h. A 0.03 ml aliquot was syringed out of
CHEM. COMMUN., 2002, 3034–3035
3035