A reasonable explanation for the mechanism of photo-promoted chemoselective aerobic oxidation of alcohols using (ON)Ru(salen) complex as catalyst

Article abstract of DOI:10.1016/j.tetlet.2005.07.005

The mechanism of aerobic oxidation of alcohols using (ON)Ru(salen) complex as catalyst under photo-irradiation was examined through studies of kinetics of the oxidation, kinetic isotope effect in the oxidation, and effect of the ligand structure on the chemoselectivity of the oxidation of primary and secondary alcohols. It was demonstrated that the aerobic oxidation includes an intramolecular hydrogen atom transfer process that is attributed to realization of efficient differentiation of primary and secondary alcohols in the oxidation.

Full text of DOI:10.1016/j.tetlet.2005.07.005

Tetrahedron
Letters
Tetrahedron Letters 46 (2005) 6049–6052
A reasonable explanation for the mechanism of photo-promoted
chemoselective aerobic oxidation of alcohols using
(ON)Ru(salen) complex as catalyst
Hiromichi Egami, Satoaki Onitsuka and Tsutomu Katsuki*
Department of Chemistry, Faculty of Science, Graduate School, Kyushu University 33, CREST,
Japan Science and Technology Agency (JST), 6-10-1 Hakozaki, Higashi-ku, Fukuoka 812-8581, Japan
Received 7 June 2005; revised 1July 2005; accepted 4 July 2005
Available online 18 July 2005
Abstract—The mechanism of aerobic oxidation of alcohols using (ON)Ru(salen) complex as catalyst under photo-irradiation was
examined through studies of kinetics of the oxidation, kinetic isotope effect in the oxidation, and effect of the ligand structure on the
chemoselectivity of the oxidation of primary and secondary alcohols. It was demonstrated that the aerobic oxidation includes an
intramolecular hydrogen atom transfer process that is attributed to realization of efficient differentiation of primary and secondary
alcohols in the oxidation.
Ó 2005 Elsevier Ltd. All rights reserved.
Oxidation of primary alcohols to aldehyde, especially in
the presence of secondary alcohols, is an important topic
in organic synthesis and many methodologies have been
developed.1,2 Of the various methods, aerobic oxidation
or oxidation using molecular oxygen as the stoichio-
metric oxidant has attracted the attention of chemists
due to its high atom efficiency and ecological benig-
nity.3,4 Some of the reported aerobic oxidations show
high chemoselectivity, but the addition of some media-
tor4a–c,p or forced conditions4e,f,n are required for such
reactions. We have recently found that (ON)Ru(salen)
complexes catalyze aerobic oxidation at room tempera-
ture under irradiation of visible light in the absence of
any additive.3e In the course of the study on this aerobic
oxidation, (ON)Ru(salen) complex 1 that bears the
1,1,2,2-tetramethylethylene-diamine unit was found to
catalyze selective aerobic oxidation of primary alcohols
in the presence of secondary alcohols (Scheme 1).5 Com-
plex 1 had been designed on the assumption that two of
the four methyl groups should adopt pseudo-axial orien-
tation and the alkyl part of the incoming alcohols would
be directed away from the axial methyl group and a
bulkier alkyl part should cause stronger steric interac-
O
OH
n-C H
8
17
n-C H
8
17
cat., hν, air
benzene-d
H
O
OH
6
R
R
R = n-C H
8
1, r.t. :decanal/2-decanone=100/ 0
17
1, r.t. : k
3, 10 C : k
/k
=15
decanol Phenylethanol
R = Ph
o
/k
>50
decanol Phenylethanol
NO
N
N
Ru
L
5'
5
2
2
R
O
O
R
3'
3
1
1
R
R
1
2
1
2
1: R =R = tert-Bu, L = Cl
2: R =R = 1-ethyl-1-methylpropyl,
L = Cl
1
2
1
2
3: R =R = 1-ethyl-1-methylpropyl,
4: R =R = tert-Bu, L = OH
L = OH
Scheme 1.
tion with the C3- or C30-tert-butyl group: oxidation of
secondary alcohols is slower than that of primary alco-
hols. Along this line, we further designed (ON)Ru(salen)
complexes (2 and 3) bearing a 1-ethyl-1-methylpropyl
group at C3, C30, C5, and C50, in which C3- and C30-
substituents were expected to adopt a C–Me in-plane
conformation and the two ethyl groups protrude above
and below the basal salen plane, increasing steric
Keywords: (ON)Ru(salen) complex; Aerobic oxidation; Intramolecular
hydrogen atom transfer.
*
Corresponding author. Fax: +8192 642 2607; e-mail: katsuscc@
mbox.nc.kyushu-u.ac.jp
0040-4039/$ - see front matter Ó 2005 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2005.07.005

6050
H. Egami et al. / Tetrahedron Letters 46 (2005) 6049–6052
Table 1. Kinetic isotope effect for (ON)Ru(salen)-catalyzed oxidation
of alcoholsa
R
Me
Me
N
Entry Substrate (R)
Catalyst KIE (kH/kD)b
NO
Ru
N
1Ph(CH
2)2CHDOH
1
4
1
4
1
4
9.8 0.3
7.9 0.4
8.8 0.4
5.05 0.06
1.5 0.2
2.6 0.3
O
O
L
2
Ph(CH2)2CHDOH
Ph Ph
3
4
5c
6c
Ph(CH2)3OH/Ph(CH2)2CD2OH
Ph(CH2)3OH/Ph(CH2)2CD2OH
Ph(CH2)3OH/Ph(CH2)2CD2OH
Ph(CH2)3OH/Ph(CH2)2CD2OH
aR
5: L= Cl
6: L= OH
a Reactions were carried out for 24 h in C6D6 at room temperature
under irradiation with a halogen lamp using 2 mol % of catalyst.
2-Bromonaphthalene was used as the internal standard.
b Average of four runs.
H
R
H
H
N
R
1
H
N
OP
III
OP
N
N
O•
c Independent measurement was examined under the same condition.
III
2
Ru
Ru
OP
O
O
O
O
OH
Cl
A: P1= H, P2= non or
P = H
P = non
B:
reaction rates (kH/kD) are summarized in Table 1. The
two kH/kD values obtained under competitive conditions
directly reflect KIE for HAT but the value obtained by
the third method depends not only on the KIE in RDS
but also on the reaction coordinate of the oxidation: if
the HAT is not the RDS of the oxidation, the kH/kD
value measured by the third method should be small.7c
The kH/kD values reported for HAT from a-methylene
of metal alkoxide in oxidation with galactose oxidase
or its model compounds, a Cu(II)-Schiff base catalyst,
and a Cu(I)-TEMPO system, range from 3 to 7.9,10
The kH/kD values measured under intra- and inter-
molecular competitive conditions with 1 and 4 were
9.8, 7.9, 8.8, and 5.05, respectively, and these values
indicated that the hydrogen atom was abstracted from
the a-methylene carbon and the oxygen radical was
generated on the phenol oxygen atom (entries 1–4).7c
Intermolecular KIEs determined by independent mea-
surement were found to be 1.5 and 2.6 for the oxidation
with 1 and 4, respectively (entries 5 and 6). These results
support the above-described kinetics: HAT is not RDS
for the oxidation with 1, while HAT is RDS for the oxi-
dation with 4. However, if only HAT step contributes to
the TS of the oxidation, the intermolecular KIE value
does not depend on its measurement method. Indeed,
the intermolecular KIEs observed for the oxidation of
Ph(CH2)3OH/Ph(CH2)2CD2OH using 6 as catalyst
under competitive and independent measurements
P1= non, P2= H
Figure 1.
effectiveness of the C3- and C30-groups remarkably.6 As
expected, primary alcohols were selectively oxidized
even in the presence of activated secondary alcohols
such as 1-phenylethanol, especially when complex 3
bearing an apical hydroxo ligand was used as catalyst.
On the other hand, our recent study on the mechanism
of aerobic oxidation of mono-ols using (ON)Ru(salen)
complexes (5 and 6) as catalyst disclosed that hydrogen
atom transfer (HAT) from their a-carbons occurs in an
intramolecular way via oxygen radical intermediates (A
and B), respectively (Fig. 1, vide infra).7c In contrast
to the above assumption, this mechanistic study means
that the alkyl part of the mono-ol is forced to come close
to the C3- and C30-substituent sites at the event of
hydrogen atom transfer not by the steric but by the
mechanistic reason. However, the oxygen radicals in
A and B are stabilized by the resonance with the naph-
thalene ring, but complexes 1 and 3 possess a benzene
ring in place of the naphthalene ring. Thus, we examined
if the proposed mechanism for the oxidation using 5
or 6 can be applied to the oxidation using usual
(ON)Ru(salen) complexes such as 1. We then examined
the kinetics and kinetic isotopic effect in the oxidation
using 1 and 4 as catalyst.
are similar values [3.42 and 2.51(KIE compet/KIEindep
=
1.36), respectively].7c On the other hand, the KIEcompet
/
KIEindep value observed for the oxidation using 4 was
1.94 (cf. entries 4 and 6).11 This indicated that the KIEs
for the latter oxidation might depend on measurement
method, though the kinetics and the kinetic isotope
effect of the oxidation unambiguously demonstrated
that the HAT was the RDS of the oxidation. These para-
doxical phenomena may be explained if the product
serves as a week catalytic poison. Thus, we examined
the oxidation of Ph(CH2)3OH by using 4 or 6 as catalyst
in the absence or the presence of an equimolar amount
of Ph(CH2)2CHO. Indeed, the oxidation rate of the
alcohol in the absence of the aldehyde was 2.3 times fas-
ter than that in the presence of the aldehyde, when the
catalyst was 4. On the other hand, the oxidation rate
of the alcohol did little depend on the presence or
absence of the aldehyde, when 6 was used as catalyst.
Since the selectivity of the oxidation using 4 or 6 is high
The kinetics of the oxidation using complexes 1 and 4 as
catalyst were determined by using 1-decanol as the test
material: the rate law for the oxidation with 1 was
rate = k[1-decanol][1][O2]0.1, while the rate law for the
oxidation with 4 was rate = k[4].8 The observed kinetics
with 1 and 4 were similar to those for the oxidation with
5 and 6 (rate = k[alcohol][5][O2] and rate = k[6][O2]0.42),
respectively, except that the influence of the oxygen
pressure to the rate was markedly reduced: the ligand
exchange exclusively contributed to the rate-determining
step (RDS) for the oxidation with 1, while HAT was the
RDS for the oxidation with 4. We also examined kinetic
isotopic effect (KIE) for the oxidation using complexes 1
and 4 under three different conditions (intra- and inter-
molecular competitive conditions and independent mea-
surement conditions) and the observed H/D relative

H. Egami et al. / Tetrahedron Letters 46 (2005) 6049–6052
6051
Table 2. IRR between 1-decanol and 1-phenylethanol observed with
complexes (1, 4, and 8–13)a
R
R
2
3'
R
Entry
Catalyst
IRR (1-decanol/1-phenylethanol)
O
2
H
R
1
O
O
1
2
3
4
5
6
7
8
1
15
18
9
14
6
5.5
4
13.5
R
3
III
Ru
4
N
N
Me
8
Me
L
1
9
R = Me or H
1
R
10
11
12
13
2
R = t-Bu or H
Figure 2.
a Reactions were carried out for 24 h in C6D6 at room temperature
under irradiation with a halogen lamp by using 2 mol % of catalyst,
unless otherwise mentioned. Pentamethylbenzene was used as the
internal standard.
•O H
R
2
or
R
–
•O
2
O
OP
5
or
6
hν, –NO
2
OH
N
O
N
N
O
N
IV
III
hν
SET
Ru
L
R CHOH
2
Ru
L
O
O
and formation of a product other than the aldehyde is
unlikely, these results support the assumption that the
aldehyde produced could be a week catalytic poison
for catalyst 4. However, it is unclear why the aldehyde
coordinates with complexes 4 and 6 differently.
P = H
P = non
RHC=O
RCH OH
Ligand exchange
2
H
R
H
R
H
N
HAT
OP
O
N
N
N
We further examined the oxidation of 1-decanol in the
presence of 1-phenylethanol using several (ON)Ru-
(salen) complexes (1, 4, and 8–13) (Table 2). Initial reac-
tion ratios (IRRs) between 1-decanol and 1-phenyletha-
nol were calculated from the following equation:
IRR = (% yield of decanal)/(% yield of acetophenone),
at ca. 20% conversion of 1-decanol. The IRRs of the oxi-
dation with 8 or 9, which has no pseudo-axial methyl
group at the diamine unit were 9 and 14, respectively
(entries 3 and 4). On the other hand, the IRRs of the
oxidation with 10 or 11, which has no substituent at
C3, C30 of the salen ligand were 6 and 5.5, respectively
(entries 5 and 6). These results suggested that the IRR
is primarily determined by steric repulsion between the
alkyl part of alcohols and the ligand substituents,
mainly the substituents at C3 and C30 (cf., entries 3, 5,
7, and 8) and the orientation of the alkyl part is not dic-
tated by the steric factor but is due to mechanistic rea-
son (Fig. 2). This agreed with the above discussions.
However, the presence of the pseudo-axial methyl group
increased the IRR to some extent, probably because
coordination of a bulkier alcohol becomes disfavored
by the presence of the axial methyl group (cf. entries
1–4). It is noteworthy that the effect of the pseudo-axial
methyl group was influenced by the location of RDS
(cf., entries 3 and 4, and entries 5 and 6).
III
III
Ru
Ru
•O H
H O
2
2
2
or
2
O
O
O
O
L
L
–
•O
P = H
P = non
Scheme 2.
Our previous study on the mechanism of aerobic oxida-
tion of alcohols and oxidative desymmetrization of
meso-diols using complexes (5 and 6) has disclosed that
the catalytic cycles of these oxidations include SET,
HAT, and ligand exchange steps (Scheme 2). The pres-
ent study supported that the oxidation of alcohols using
1 and 4 as catalyst also proceeds through the same cat-
alytic cycle (Fig. 2), though the influence of the oxygen
pressure to the rate was markedly reduced. Therefore,
high chemoselectivity observed in the oxidation using
complexes 1–4 is mainly attributed to steric repulsion
caused by the intramolecular HAT step; however, the
effect of the axial substituent on chemoselectivity can
not be completely ruled out, especially when ligand
exchange step is the RDS for oxidation (vide supra).
General procedure for the determination of IRR: pri-
mary and secondary alcohols (0.1mmol, each) were
weighed into a Schlenk tube (Pyrex) followed by addi-
tion of pentamethylbenzene (0.1mmol) as an internal
standard and benzene-d6 (1mL). An aliquot was taken
4
3
R
R
R
4
3
R
1
out of the tube and submitted to H NMR (400 MHz)
NO
N
O
N
analysis to adjust the molar ratio of the components.
Ru complex (2 lmol) was added to the solution and
the mixture was vigorously stirred with irradiation using
a halogen lamp (150 W) in air. The reaction mixture was
Ru
L
5'
2
5
2
2
R
O
R
3'
3
1
1
R
R
1
1
3
1
2
3
traced by H NMR analysis to calculate the ratio of
9: R =R = tert-Bu, R = -(CH ) -,
8: R =R = tert-Bu, R = -(CH ) -,
2 4
2 4
4
4
R = H, L = OH
unreacted alcohols, aldehyde, and ketone. In all the
reactions, the mass balances were excellent and no for-
mation of carboxylic acid was detected.
R = H, L = Cl
1
2
3
4
1
2
3
4
10: R = H, R = tert-Bu, R =R = Me,
11: R = H, R = tert-Bu, R =R = Me,
L = Cl
L = OH
1
2
3
4
1
2
3
4
12: R = H, R = H, R =R = Me, L = Cl 13: R = tert-Bu, R = H, R =R = Me,
In conclusion, based on the present study, we propose a
new mechanism for photo-promoted chemoselective
L = Cl

6052
H. Egami et al. / Tetrahedron Letters 46 (2005) 6049–6052
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and 4 as catalyst, in which the intramolecular HAT step
is responsible for chemoselection by the catalysts. Kinet-
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with complexes (1 and 4) and with complexes (5 and 6)
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