Chemoselective aerobic oxidation of primary alcohols catalyzed by a ruthenium complex

Article abstract of DOI:10.1016/S0040-4039(01)01447-2

In the presence of secondary alcohols, primary alcohols are selectively oxidized to aldehydes under aerobic conditions by using a (nitrosyl)Ru(salen) complex as catalyst.

Full text of DOI:10.1016/S0040-4039(01)01447-2

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 42 (2001) 7067–7070
Chemoselective aerobic oxidation of primary alcohols catalyzed
by a ruthenium complex
Atsushi Miyata, Masakazu Murakami, Ryo Irie and Tsutomu Katsuki*
Department of Chemistry, Faculty of Science, Graduate School, Kyushu University 33, CREST,
JST (Japan Science and Technology), Hakozaki, Higashi-ku, Fukuoka 812-8581, Japan
Received 16 July 2001; revised 30 July 2001; accepted 3 August 2001
Abstract—In the presence of secondary alcohols, primary alcohols are selectively oxidized to aldehydes under aerobic conditions
by using a (nitrosyl)Ru(salen) complex as catalyst. © 2001 Elsevier Science Ltd. All rights reserved.
Oxidation of primary alcohols to aldehydes is transfor1-
mation of tremendous importance in organic synthesis
and many transition metal compounds have been used
for this purpose. Ruthenium compounds are intensively
studied transition metal compounds and many method-
aerobic oxidation of racemic secondary alcohols under
photo-irradiation with good enantiomer-differentiation
(Scheme 2). Since the ruthenium ion is directly oxi-
dized by oxygen through single electron-transfer, a
mediator such as hydroquinone is not necessary for this
reaction. To take advantage of this reaction, we exam-
ined (nitrosyl)Ru(salen)-catalyzed oxidation of primary
alcohols.
7
2
ologies have been developed with them. However,
stoichiometric chemical oxidants were needed in most
cases. Use of air or molecular oxygen as the terminal
oxidant is desirable from economical and environmen-
tal points of view. Recently, several aerobic oxidations
We first synthesized (nitrosyl)Ru(salen) 2 and 3 bearing
electron-withdrawing groups, expecting enhancement of
catalytic activity and catalyst stability by introducing
such groups. Contrary to our expectation, however,
complexes 2 and 3 showed poor catalytic activity. The
poor catalytic activity was partly attributed to the fact
that the single electron transfer is retarded by introduc-
tion of the electron-withdrawing group. Accordingly,
we next synthesized poly-alkylated (nitrosyl)Ru(salen)
4. It has been reported that a five-membered chelate
ring formed by the ruthenium ion and the ethylenedi-
amine unit in cationic (nitrosyl)Ru(salen) adopts a half-
3
,4
of alcohols have been reported. However, most of
them oxidize not only primary alcohols but also sec-
5
ondary alcohols. Oshima et al. reported that primary
alcohols are selectively oxidized to aldehydes in the
presence of secondary alcohols by using stoichiometric
Ru(PPh ) Cl or a Ru(PPh ) Cl and TMSOOTMS sys-
3
3
2
3 3
2
2
c,e
tem.
Ishii et al. successfully achieved aerobic oxida-
tion using Ru(PPh ) Cl as the catalyst in the presence
3
3
2
of hydroquinone without diminishing chemoselectivity
6
(
Scheme 1). Hydroquinone has been considered to be
oxidized in situ to benzoquinone, which participates in
the oxidative recycling of the ruthenium species.
8
chair conformation. Therefore, we expected that two
of the four methyl groups at the ethylenediamine unit
in 4 occupy pseudo-axial position.
We recently found that (nitrosyl)Ru(salen) 1-catalyzed
H
OH
O
83%
Ru(PPh ) Cl (10 mol %)
3
3
2
+
+
hydroquinone (10 mol %)
O , C H CF , K CO , 60 °C
2
6
5
3
2
3
OH
O
3%
Scheme 1.
Keywords: Ru(salen); oxidation; oxygen; primary alcohol; aldehyde; photo-irradiation.
*
Corresponding author.
0
040-4039/01/$ - see front matter © 2001 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(01)01447-2

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068
A. Miyata et al. / Tetrahedron Letters 42 (2001) 7067–7070
NO
NO
N
O
N
O
N
O
N
O
Ru
Cl
Ru
X
X
t-Bu
Bu-t
Cl
X
X
Bu-t
t-Bu
2
: X= F
4
3: X= Br
R1
R2
R1
R1
R2
1, hν, air, rt
R-OH
OH
+
O
OH
R2
N
kS / kR = 11-20
N
R
RuIV
racemic
O
O
Cl
R
NO
N
O
N
Ru
Figure 1.
O
Cl
Ph Ph
and benzyl/phenethyl alcohols. Even in the presence of
secondary benzylic alcohol, non-activated primary alco-
hol was oxidized much faster (relative rate >12), though
the amount of ketone was gradually increased as the
reaction time was prolonged.
R
1
Functionalized primary alcohols were also oxidized in
quantitative yields under the present reaction condi-
tions except for p-cyanobenzyl alcohol (Scheme 5). The
cyano group of the latter compound was considered to
strongly coordinate to the ruthenium ion of the cata-
lyst, poisoning the catalytic activity.
Scheme 2.
On the other hand, the above-described (ON)Ru(salen)-
catalyzed oxidation of secondary alcohols is considered
to follow the sequence: (i) dissociation of the nitrosyl
group by photo-irradiation, (ii) oxidation of the result-
ing Ru(III) complex 5 via single electron transfer, (iii)
coordination of alcohol to the Ru(IV) species and (iv)
oxidation of alcohol to ketone via hydrogen atom and
proton abstraction, regenerating complex 5 (Scheme
It is noteworthy that the resulting aldehyde was not
oxidized to the corresponding carboxylic acids, though
aldehydes served as co-reductants under Mukaiyama
10
7
,9
aerobic oxidations.
3
). We considered that the alcohols approaching the
Ru(IV) species derived from complex 4 should suffer
,3-diaxial repulsion (Fig. 1) and that primary alcohols
Typical experimental procedure was exemplified by the
oxidation of p-nitrobenzyl alcohol. p-Nitrobenzyl alco-
hol (15.3 mg, 0.1 mmol) and 4 (1.4 mg, 2 mmol) were
weighed into a round-bottomed flask (Pyrex) and dis-
solved in toluene (1 mL). The mixture was irradiated
with a halogen lamp (15 V, 150 W) through an infrared
1
should coordinate to the ruthenium(IV) ion in prefer-
ence to secondary alcohols and be selectively oxidized.
Based on this analysis, we studied the relative aerobic
oxidation rate between primary and secondary alcohols
by using complex 4 as the catalyst under photo-irradia-
tion (Scheme 4). As expected, primary alcohols were
selectively oxidized at room temperature under the
conditions. No oxidation of secondary alcohols was
observed in the competitive reactions of 1-/2-decanols
11
filter at room temperature for 24 h. The reaction
mixture was directly deposited on a silica gel column
and eluted with a 9:1 mixture of hexane and ethyl
acetate to give p-nitrobenzaldehyde (15.1 mg) in quan-
titative yield.
R2
R1
OH
R2
R1
R2
N
R1
N
O
O2
O2-
N
O
NO N
RuII
hν
OH
N
O
N
RuIII
N
O
N
RuIV
5
-
·NO
RuIV
O
Cl
O
O
O
Cl
Cl
5
O
Cl
1
Scheme 3.

A. Miyata et al. / Tetrahedron Letters 42 (2001) 7067–7070
7069
O
OH
4, hν, air
quantitative
H
O
OH
d6-benzene, rt, 12 h
0%
Ph
Ph
O
Ph
Ph
OH
quantitative
4
, hν, air
H
O
OH
d6-benzene, rt, 5 h
0%
O
OH
4
, hν, air
H
OH
O
quantitative
29%
d6-benzene, rt, 24 h
Ph
Ph
kdecanol/kphenethyl alcohol > 12/1
Scheme 4.
4
(2 mol %), hν, air
RCH OH
RCHO
2
toluene, rt, 24 h
MeO
O N
2
CHO CH O
CHO
O
CHO NC
CHO
3
quantitative
quantitative
15%
quantitative
Scheme 5.
Competitive oxidations of primary and secondary alco-
hols were examined typically as follows. Primary and
secondary alcohols (0.1 mmol) were weighed into a
round-bottomed flask (Pyrex) followed by addition of
pentamethylbenzene (0.1 mmol) as an internal standard
Acknowledgements
T.K. is grateful to Professor Victor S. Martin, Univer-
sida de La Laguna, Spain, who suggested to him the
importance of selective oxidation of primary alcohols.
and d -benzene (1 mL). An aliquot was taken out of the
6
1
flask and submitted to H NMR (400 MHz) analysis to
adjust the molar ratio of the components. To the
solution was added 4 (1.4 mg, 2 mmol) and the mixture
was irradiated for the specified period as shown in
Scheme 4 under the same conditions as described
above. The reaction mixture was analyzed by GC and
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reasonably designed (ON)Ru(salen) complex oxidized
primary alcohols selectively in the presence of sec-
ondary alcohols. Further study is under way in our
laboratory.

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stage of the reaction, though irradiation was continued
throughout the oxidation described in the text. Indeed,
the reaction irradiated for only 2 h gave the same result
as that described in the text.