Highly efficient aerobic oxidation of benzylic and allylic alcohols by a simple catalyst system of [RuCl2(p-cymene)]2/Cs2CO3

Article abstract of DOI:10.1016/S0040-4039(00)01284-3

A new catalyst system of [RuCl₂(p-cymene)]₂/Cs₂CO₃ has been disclosed for highly efficient aerobic oxidation of activated alcohols to the corresponding carbonyl compounds, which is characterized by its high selectivity and activity, operational simplicity, and low air and moisture sensitivity. (C) 2000 Elsevier Science Ltd.

Full text of DOI:10.1016/S0040-4039(00)01284-3

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 41 (2000) 7507–7510
Highly efficient aerobic oxidation of benzylic and allylic
alcohols by a simple catalyst system of
[RuCl2(p-cymene)]2/Cs2CO3
Myunghee Lee and Sukbok Chang*
Department of Chemistry, Ewha Womans University, Seoul 120-750, South Korea
Received 23 June 2000; revised 17 July 2000; accepted 24 July 2000
Abstract
A new catalyst system of [RuCl2(p-cymene)]2/Cs2CO3 has been disclosed for highly efficient aerobic
oxidation of activated alcohols to the corresponding carbonyl compounds, which is characterized by its
high selectivity and activity, operational simplicity, and low air and moisture sensitivity. © 2000 Elsevier
Science Ltd. All rights reserved.
From an economical and environmental point of view the use of molecular oxygen as a
stoichiometric reoxidant has attracted considerable attention, and recently there have been great
efforts in the development of efficient and selective aerobic oxidation protocols catalyzed by
transition metal complexes.1 Among the various complexes employed for the chemistry, and in
particular, some ruthenium catalysts such as RuCl2(PPh3)3 or Pr4N+·RuO4−3 in the presence of
2
other co-catalysts or additives, have appeared to be some of the promising candidates to meet
the facile green chemistry. However, despite some recent progress, there is still a need to develop
a new procedure for aerobic oxidation employing a more convenient catalyst system of high
activity, operational simplicity, and low air and moisture sensitivity. Here we describe our initial
efforts towards this goal.
Among a variety of easily available ruthenium complexes tested as oxidation catalysts, we
found that the use of [RuCl2(p-cymene)]2 (1)4 coupled with some additives displayed a high
catalytic activity on the oxidation under atmospheric oxygen.5
As shown in Table 1, whereas benzyl alcohol was oxidized very slowly under the oxygen
atmosphere by the ruthenium complex 1 alone, a significant rate enhancement was observed in
the presence of molecular sieves under the same conditions. After extensive experiments on the
effects of other additives, we discovered that cesium carbonate exhibited the most dramatic rate
* Corresponding author. Fax: (+82) 2-3277-2384; e-mail: sbchang@mm.ewha.ac.kr
0040-4039/00/$ - see front matter © 2000 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(00)01284-3

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enhancement of the aerobic oxidation in combination with the ruthenium complex 1 (entry 5).
We were finally pleased to observe that even a catalytic amount of the cesium salt was enough
to perform the aerobic oxidation with almost the same efficiency as in the stoichiometric
reaction (entry 7).6 Whereas the reaction was most efficiently carried out in the temperature
range of 90–110°C, conversion was slowed down upon reducing the temperatures. Other bases
such as K2CO3, t-BuOK, CsOH·H2O, or amines were less effective compared with cesium
carbonate (for example, entry 9). Cesium alkoxides are distinguished from other alkali metal
counterparts in view of nakedness, weak conjugation, high solubility, appropriate basicity, good
stability, and/or weak solvation.7 The metal-catalyzed aerobic oxidation is generally known to
proceed via the formation of an alkoxy metal intermediate, which subsequently undergoes
b-elimination to afford carbonyl compounds and a metal hydride.8 Although the exact role of
Cs2CO3 in the present oxidation system awaits further studies, the cesium salt possibly facilitates
the initial stage of the reaction: formation of the alkoxy ruthenium intermediate in the catalytic
cycle.
Table 1
Aerobic oxidation of benzyl alcohol to benzaldehyde catalyzed by 1a
Entry
1 (equiv.)
Additive (equiv.)
–
T/°C
t/h
Conversion (%)b
1
2
3
4
5
6
7
8
9
–
100
100
100
100
100
100
100
50
12
12
12
12
1.0
12
2.5
B5
25
80
B5
\99
B5
\99
77
0.2
0.2
–
0.2
–
0.03
0.03
0.03
–
c
,
,
MS 4 A
MS 4 A
c
Cs2CO3 (1.2)
Cs2CO3 (1.2)
Cs2CO3 (0.1)
Cs2CO3 (0.1)
K2CO3 (0.1)
12
12
100
68
a All reactions were performed under O2 atmosphere (using an O2 balloon) and in 0.6 M concentration.
1
b Conversion was determined by H NMR of the crude reaction mixture.
c Used in 0.4 g/mmol of the alcohol.
Under the explored standard conditions, a range of alcohols were evaluated as substrates for
the aerobic oxidation (Table 2).9 All the tested primary alcohols of benzylic and allylic position
were smoothly and quantitatively converted into the corresponding aldehydes in excellent yields
(entries 1–9). Electronic and/or steric variation of the alcohols has little effect on the efficiency
of the aerobic oxidation. Common protecting groups such as silylether or acetate were tolerant
under the present protocol (entries 3 and 4). It is especially noteworthy that a nearby diol such
as 1,2-benzenedimethanol was oxidized in excellent yield to afford the corresponding lactone
(entry 6). Allylic alcohols were also good substrates, and in this case no isomerization of the
conjugated double bonds was observed (entries 7 and 8). Heteroatoms such as sulfur did not
result in any notorious effects on the catalytic system (entry 9). Aromatic ketones were produced
in an equally efficient way by the aerobic oxidation from the corresponding secondary alcohols
(entries 10 and 11). Whereas benzylic and allylic alcohols were oxidized in a highly efficient way,
aliphatic alcohols were less reactive under the conditions established here and therefore higher
loading of the catalyst 1 and Cs2CO3 was required to obtain the aliphatic carbonyl compounds
in good yields (entry 12). It should also be noted that under the present catalytic oxidation

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Table 2
Aerobic oxidation of various alcohols by a catalyst system of [RuCl2(p-cymene)]2 (1, 5 mol%)/Cs2CO3 (10
mol%)a
Entry
1
Alcohol
t/h
Product
Isolated yield
91
1
2
3
1
1
1
1
2
1
3
2
3
5
5
94
99
87
98
95
85
95
94
81
94
83
4
5
6
7
8
9
10
11
12b
a All reactions were carried out at 100°C in toluene (0.6 M) under an oxygen atmosphere (using an O2 balloon).
b In this case, 15 mol% of 1 was used in combination with 1.0 equiv. of Cs2CO3.
system, selectivity for the corresponding aldehyde or ketones was >99% in all cases and no other
over-oxidized compounds were detected.
In summary, catalytic amounts of cesium carbonate have profound effects on the [RuCl2(p-
cymene)]2 catalyzed aerobic oxidation and a variety of benzylic and allylic alcohols were
aerobically oxidized in excellent yields using the catalyst system. Aliphatic substrates, however,
were less effective and further studies concerning this aspect is currently underway.
Acknowledgements
This research was supported by the Center for Molecular Design and Synthesis (CMDS) at
KAIST.

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References
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9. Representative experimental procedure: To a solution of 4-chlorobenzyl alcohol (285 mg, 2.0 mmol) in toluene (3.3
mL) was added Cs2CO3 (65 mg, 0.2 mmol), [RuCl2(p-cymene)]2 (61 mg, 0.1 mmol) and the reaction mixture was
stirred for 1 h at 100°C under an oxygen atmosphere (using an O2 balloon). After cooling to room temperature,
hexane (10 mL) was added and the mixture was filtered on celite, washing with hexane. Purity of the crude
reaction mixture was determined to be >95% by 1H NMR integration after removal of the solvent. Column
chromatography on silica gel (ethyl acetate/hexane=1/3) provided the analytically pure product, 4-chlorobenzalde-
hyde (264 mg, 94%).
.