Efficient ruthenium-catalyzed aerobic oxidation of amines by using a biomimetic coupled catalytic system

Article abstract of DOI:10.1002/chem.200401082

Efficient aerobic oxidation of amines was developed by the use of a biomimetic coupled catalytic system involving a ruthenium-induced dehydrogenation. The principle for this aerobic oxidation is that the electron transfer from the amine to molecular oxygen occurs stepwise via coupled redox systems and this leads to a low-energy electron transfer. A substrate-selective ruthenium catalyst dehydrogenates the amine and the hydrogen atoms abstracted are transported to an electron-rich quinone (2a). The hydroquinone thus formed is subsequently reoxidized by air with the aid of an oxygen-activating [Co(salen)]-type complex (27). The reaction can be used for the preparation of ketimines and aldimines in good to high yields from the appropriate corresponding amines. The reaction proceeds with high selectivity, and the catalytic system tolerates air without being deactivated. The rate of the dehydrogenation was studied by using quinone 2a as the terminal oxidant. A catalytic cycle in which the amine promotes the dissociation of the dimeric catalyst 1 is presented.

Full text of DOI:10.1002/chem.200401082

FULL PAPER
Efficient Ruthenium-Catalyzed Aerobic Oxidation of Amines by Using a
Biomimetic Coupled Catalytic System
Joseph S. M. Samec, Alida H. ꢀll, and Jan-E. Bꢁckvall*[a]
Abstract: Efficient aerobic oxidation of
amines was developed by the use of a
biomimetic coupled catalytic system in-
volving a ruthenium-induced dehydro-
genation. The principle for this aerobic
oxidation is that the electron transfer
from the amine to molecular oxygen
occurs stepwise via coupled redox sys-
tems and this leads to a low-energy
electron transfer. A substrate-selective
ruthenium catalyst dehydrogenates the
amine and the hydrogen atoms ab-
stracted are transported to an electron-
rich quinone (2a). The hydroquinone
thus formed is subsequently reoxidized
by air with the aid of an oxygen-acti-
vating [Co(salen)]-type complex (27).
The reaction can be used for the prepa-
ration of ketimines and aldimines in
good to high yields from the appropri-
ate corresponding amines. The reaction
proceeds with high selectivity, and the
catalytic system tolerates air without
being deactivated. The rate of the de-
hydrogenation was studied by using
quinone 2a as the terminal oxidant. A
catalytic cycle in which the amine pro-
motes the dissociation of the dimeric
catalyst 1 is presented.
Keywords: homogeneous catalysis ·
imines · oxidation · ruthenium
Introduction
known.[4–11] In these so-called biomimetic oxidations the
electrons are smoothly transported from the reduced form
of the substrate-selective catalyst (often a transition metal)
to molecular oxygen or hydrogen peroxide (Figure 1).
Our group has recently designed and developed coupled
catalytic electron transfer systems for 1,4-oxidations of con-
jugated dienes,[4] allylic oxidations,[4a,5] oxidations of alco-
hols,[6] and dihydroxylations of olefins[7] for which either O2
or H2O2 are used as the oxidant.
Imines are useful intermediates in organic synthesis,
which act as electrophilic reagents in many different reac-
tions such as reductions, additions, condensations, and cyclo-
additions (see Scheme 1 for some examples). Many of these
transformations can be carried out with high enantioselectiv-
ity. Imines also occur as intermediates in the racemization
of chiral amines.[12] The standard protocol for their synthesis
involves condensation of an amine and a carbonyl com-
pound (aldehyde or ketone). Owing to their unstable and
reactive nature it would be desirable to obtain imines by
pathways other than those from an electrophilic carbonyl
compound. Amines are stable and easily accessible com-
pounds and would therefore be suitable precursors for
imines by dehydrogenation.
Oxidation reactions are of fundamental importance in or-
ganic chemistry.[1] Stoichiometric amounts of metal-based
oxidants such as dichromate ions, permanganate ions, man-
ganese dioxide, silver oxide, and lead tetraacetate are still
used in many oxidations.[2] The stoichiometric use of such
oxidants is undesirable from both an environmental and an
economic point of view. Therefore much attention has been
paid to the use of a transition-metal catalyst to achieve effi-
cient oxidations with molecular oxygen or hydrogen perox-
ide as terminal oxidants.[1,2] One challenge to overcome
when using a substrate-selective transition-metal catalyst is
the usually high energy barrier for the reoxidation of the re-
duced form of the metal by molecular oxygen. An efficient
and successful way to circumvent the high-energy pathway
for reoxidation of the metal is to mimic biological oxida-
tions, where large jumps in oxidation potentials are avoided
by the use of several coupled redox catalysts as electron-
transfer mediators (ETMs).[3] A number of such oxidation
systems that mimic biological electron transfer are
The biological oxidation of amines involves amine dehy-
drogenases/oxidases, which are important in a variety of
processes ranging from bacterial growth on amines to the
oxidation of neurotransmitters in animals.[20] The oxidation
is initiated by a condensation of the amine to a quinone,
[a] J. S. M. Samec, Dr. A. H. ꢀll, Prof. Dr. J.-E. Bꢁckvall
Department of Organic Chemistry, Arrhenius Laboratory
Stockholm University, 106 91 Stockholm (Sweden)
Fax : (+46)8-154-908
E-mail: jeb@organ.su.se
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DOI: 10.1002/chem.200401082
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2327

one (2a) as catalysts and
MnO2 as terminal oxidant effi-
ciently promoted the dehydro-
genation of aromatic amines to
their
corresponding
ket-
imines.[25] Jensen and co-work-
ers reported an iridium pincer
complex that catalyzed the de-
hydrogenation of amines to the
corresponding imines using an
olefin as terminal oxidant.[26]
However, very harsh reaction
conditions were required for
this transformation. Recently,
Figure 1. Dividing the oxidation potential using catalyst and ETM.
Mizuno and co-workers report-
ed a ruthenium-catalyzed het-
erogeneous aerobic oxidation of primary amines to ni-
triles.[27] This system also catalyzed the oxidation of secon-
dary amines to aldimines and two examples were given. A
Scheme 1. Imines as important intermediates: 1) hydrogenation;[13] 2)
Mannich;[14] 3) Strecker;[15] 4) imino—ene;[16] 5) addition; 6) [2 + 2] addi-
tion;[17] 7) aza-Baylis—Hillman;[18] 8) aza-Diels—Alder.[19]
Scheme 2. Biological oxidation of amines.
leading to the formation of an iminoquinone. Water hydro-
lysis of this intermediate releases the carbonyl compound.
The aminoquinol is subsequently oxidized back to quinone
by molecular oxygen, which releases ammonia (Scheme 2).
The problem with mimicking these systems is that the
amines are not dehydrogenated but rather react with a car-
bonyl group of a quinone, forming an imine intermediate
that is hydrolyzed to a ketone. Therefore this is not a suita-
ble path to mimic the generation of imines.
We therefore searched for alternative pathways for the
aerobic oxidation of amines to imines. A few methods for
the oxidation of amines to imine are known in the litera-
ture.[21] Murahashi et al.[22] reported a ruthenium-catalyzed
oxidation using tBuOOH as the oxidant, and James and
Bailey[23] described a porphyrin-catalyzed aerobic procedure
for the oxidation of amines to imines.[24] We recently found
that the coupled catalytic system involving the ruthenium
complex 1 (see [Eq. (1)]) and 2,6-dimethoxy-1,4-benzoquin-
problem with the latter reaction is that overoxidation to ni-
trile occurs and therefore the selectivity to imine is moder-
ate. The lack of mild catalytic procedures to obtain both ket-
imines and aldimines motivated further studies of the oxida-
tion of amines. Here we describe a mild and efficient aero-
bic catalytic system for the generation of aldimines and keti-
mines by ruthenium-catalyzed dehydrogenation of amines
involving a biomimetic coupled catalytic system. The design
of the system was inspired by the biological oxidation of sec-
ondary alcohols. Instead of NAD+ we employed a rutheni-
um complex as the substrate-selective catalyst, the ubiquin-
one (Q) was replaced by another electron-rich quinone
(2a), and in place of cytochrome c, a metal macrocycle
(MLm), a [Co(salen)]-type complex, was used for the O2 ac-
tivation (Scheme 3).
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Aerobic Oxidation of Amines
FULL PAPER
required CO dissociation
from ruthenium being slow
(entry 3,
Table 1).
Both
Noyoriꢃs catalyst (5) and
[RuCl2(PPh3)3] (6), which
have been successfully used
in the transfer hydrogenation
of imines,[13,30] showed very
low activity in the dehydro-
genation (entries 4 and 5,
Table 1).
Scheme 3.
Results and Discussion
Substrate effect on the rate: In the transfer hydrogenation
of imines, we found that the rate of the reaction was de-
pendent on the electronic properties of the substrate.[31]
Thus, electron-rich substrates gave a higher rate (measured
in TOF) than electron-deficient substrates. For example,
when N-phenyl-(1-phenylethylidene)amine was substituted
for N-phenyl-[1-(4-methoxyphenyl)ethylidene]amine the
rate was increased from 730 to 840 hÀ1, whereas a p-fluoro
substituent in the same position decreased the rate from 730
to 120 hÀ1.[31] Interestingly the same trend was found also for
the dehydrogenation reaction using catalyst 3, where the
Choice of catalyst: In a previous study we showed that cata-
lyst 1 is efficient in catalyzing the dehydrogenation of aro-
matic amines to ketimines.[25] The rate-limiting step of this
process is the transfer of the a-hydrogen atom from the sub-
strate to ruthenium.[28] In the dehydrogenation of N-phenyl-
1-phenylethylamine with the Shvo catalyst 1, where the 16-
electron complex A is the active catalyst, a deuterium iso-
tope effect kCHNH/kCDNH of 3.24 compared to kCHNH/kCDND of
3.26 was observed.[28] The active species A is continuously
regenerated from 1a by reaction with the quinone 2a
(Scheme 4).
Table 1. Catalyst screening.[a]
Entry
Catalyst
Yield [%]
after 2 h[b]
1
97
2
3
95
33
Scheme 4.
The active species A can be generated also from the di-
meric structure [{Ph4(h5-C4CO)Ru(CO)2}2] (3) as recently
reported by Casey and co-workers[29] or from [{Ph4(h4-
C4CO)}Ru(CO)3] (4) by loss of CO. We found that both
complexes 1 and 3 showed a high activity in the transfer de-
hydrogenation of N-(4-methoxyphenyl)-N-(1-phenylethyl)-
amine using 2,6-dimethoxy-1,4-benzoquinone (2a) as oxi-
dant (entries 1 and 2, Table 1). However, complex 4 showed
lower activity than catalysts 1 and 3 most likely due to the
4
5
10[c]
5[c]
[a] The reactions were carried out on a 0.125-mmol scale in toluene
(1 mL) at 1108C with 2 mol% of Ru catalyst and 1.5 equivalents of quin-
one 2a. [b] Determined by 1H NMR spectroscopy. [c] 4 mol% of K2CO3
was added.
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J.-E. Bꢁckvall et al.
rate of the reaction (calculated in TOF) was higher for elec-
tron-rich substrates. For example, substrates having a me-
thoxy or a methyl group on one of the aromatic rings dis-
played higher rates (entries 1–6, Table 2). An additive effect
was found when more than one methoxy group was intro-
duced (entry 1, Table 2). In the transfer hydrogenation of
imines, we observed that aldimines react slower than ket-
imines. We observe the same trend for the reversed reaction
studied here, dehydrogenation of amines, that is, aldimines
are generated slower than ketimines (entry 9, Table 2). In
contrast to the transfer hydrogenation of imines, an ethyl
group instead of a methyl group a to the amino function did
not increase the rate (entry 8, Table 2). A possible explana-
tion for the latter is that the dehydrogenation is more sensi-
tive towards steric effects than transfer hydrogenation. A p-
CN substituent on one of the phenyl rings made the amine
unreactive under the general conditions used. However, a
high TOF was obtained using microwave assistance
(entry 10, Table 2).
Aerobic oxidation of amines: To develop an aerobic process
for the oxidation of amines to imines it is necessary to reox-
idize the dimethoxyquinone 2 with molecular oxygen. For
the alcohol oxidation in biological systems, ubiquinol is re-
oxidized to ubiquinone with
molecular oxygen, which is ac-
Table 2. Ruthenium-catalyzed dehydrogenation of amines to imines by quinone 2a.[a]
tivated by an iron porphyrin in
cytochrome c.[32] Recently, we
reported a successful coupled
oxidation system of secondary
alcohols that mimics this bio-
logical system where hydroquin-
one 2b was reoxidized by O2
to generate 2a.[6c] In this
system the [Co(salen)]-type
complex 27 was found to be ef-
Entry
Substrate
Product
TOF[b] after
10 min
Yield [%]
after 1 h[c]
[hÀ1
]
1
2
3
4
71
>95
85
60
58
51
87
ficient for the activation of
molecular oxygen and cata-
lyzed the reoxidation of 2b to
2a. It was of interest to find
out if this artificial oxidation
system also could be applied
to the aerobic oxidation of
amines. One concern was that
the water formed may hydro-
lyze the imine to give a ketone
(aldehyde). Initial attempts to
use the coupled aerobic system
for oxidation of amines to
imines gave varying results,
and difficulties were encoun-
tered to obtain good yields.
After some variation of the re-
action conditions we found
that a moderate stream of air
through the reaction flask gave
the best results.
90
5
6
7
47
33
87
68
44
32[d]
8
31
24
38
30
–
9
10
<1
60[e]
Thus, the biomimetic system
used for alcohols[6c] works well
also for the dehydrogenation
of amines to imines in good to
[a] The reactions were carried out on a 0.125-mmol scale in toluene (1 mL) at 1108C with 2 mol% of 3 and
1.5 equivalents of quinone 2a. [b] TOF (turnover frequency) based on Ru. [c] Determined by 1H NMR spec-
troscopy. [d] 4 mol% of 3 and 1.5 equivalents of quinone 2a was used. [e] Run under microwave irradiation at
1808C for 5 min.
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Aerobic Oxidation of Amines
FULL PAPER
high yields with catalytic amounts of 3, 2a, and 27 under air
(Table 3).[33] Both ketimines (entries 1–7, 9, 10, Table 3) and
aldimines (entries 8, 11, 12, Table 3) can be prepared from
the corresponding amines. Amines with a secondary alkyl
group reacted faster (to give ketimines) than those with a
primary alkyl group (to give aldimines). Interestingly, also
nonbenzylic amines can be used as substrates with high se-
lectivity (entries 7 and 10, Table 3). Surprisingly, only traces
of the hydrolyzed product were detected in the 1H NMR
spectrum for the unstable imine in entry 10 even after 12 h.
A possible explanation why these rather unstable imines are
not hydrolyzed in the present system, is that the water
formed is continuously distil-
led off by the air stream used.
Table 3. Aerobic oxidation of amines using a biomimetic coupled catalytic system.[a]
Mechanistic
considerations:
Complex 1 is one of the resting
states with any of the catalysts
in the first three entries in
Table 1. To obtain catalysis
with complex 1 it has to break
up into 1a and A under ther-
mal conditions [Eq. (1)].[29,34]
Interestingly, neither 1a nor A
have been observed under
thermal conditions, which can
be explained by a very low dis-
Entry
1
Substrate
Product
Time
[h]
Yield
[%][b]
6
90
86
95
88
2
3
4
6
sociation
[Eq. (1)]. However attempts to
dissociate catalyst under
constant
Kdiss
1
12
6
thermal conditions failed with-
out nucleophiles such as alco-
hols and amines, or hydrogen
gas.
During a mechanistic study
of 1a with imines we found
that 1 together with N-methyl-
substituted amine 36 gave a
new complex 37 at low temper-
atures (Scheme 5).[35] This is
most likely the first step in the
dissociation of dimer 1.
5
6
6
88
90
12
With these results in hand,
we propose an alternative cat-
alytic cycle. Instead of thermal
dissociation of 1, the cycle
7
8
12
24
83[c]
99[c,e]
starts with abstraction of
a
proton of 1 by an amine and
replacement of the proton by
the protonated amine to form
complex 37 (Scheme 6).[36] This
complex decomposes to form
complexes 1a and amine com-
plex 38. b-Elimination from
the amine in 38 gives the cor-
responding imine and another
molecule of 1a. Quinone 2a
then oxidizes one of the two
molecules of 1a to A, which
combines with 1a to form the
dimer 1 and this completes the
catalytic cycle. When 3 is em-
ployed as the catalytic precur-
9
12
84
10
11
12
12
24
24
76[c,d]
99[c,e]
99[e,f]
[a] Unless otherwise stated, the reactions were carried out on a 0.125-mmol scale in toluene (1 mL) at 1108C
with 2 mol% of 3, 20 mol% of quinone 2a, and 2 mol% of 27 under a steady flow of air. Caution: Air with
toluene at 1008C produces explosive mixtures in the gas phase. [b] Determined by 1H NMR spectroscopy.
[c] 4 mol% of 3 was used. [d] Traces of hydrolyzed product were observed in the H NMR spectra. [e] The re-
actions were carried out on a 0.25-mmol scale in toluene (2 mL). [f] 8 mol% of 3 and 4 mol% of 27 were
1
used.
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J.-E. Bꢁckvall et al.
(Scheme 7),[37] we have demon-
strated that the imines generat-
ed from the aerobic oxidation
procedure can be conveniently
used in an organocatalytic re-
action without further purifica-
tion. Removal of the solvent
from the aerobic oxidation re-
action and replacement with
N-methylpyrrolidinone (NMP),
followed by addition of l-pro-
line and propionaldehyde gave
syn-Mannich products in high
yields and high ee.
Scheme 5.
Conclusion
We have developed an effi-
cient catalytic process for the
biomimetic aerobic oxidation
of secondary amines that toler-
ates
important
substrate
classes. Both aldimines and ket-
imines can be prepared by this
methodology. Generally, elec-
tron-rich substrates react faster
than electron-deficient sub-
strates. The catalytic cycle for
the transformation involves
ruthenium–amine complexes
as the key intermediates; it
was shown that an amine can
react with 1 to give complex
37. The hydroquinone 2b
formed in Scheme 6 is continu-
ously recycled to quinone 2a
in the aerobic process (cf.
Scheme 3).
Scheme 6. Proposed mechanism for the ruthenium-catalyzed dehydrogenation of secondary amines (Q+
=
[RR’CHNH2R’’]+.
sor the catalyst enters the catalytic cycle via complex 38,
which is formed from reaction of 3 with the amine.
Synthetic applications: As mentioned in the introduction,
imines participate in a large number of synthetic transfor-
mations. The usual way of preparing imines is from the cor-
responding carbonyl compound and the appropriate amine,
with removal of water under anhydrous conditions. The
imine usually has to be isolated from this mixture before
using it in the subsequent transformations. The biomimetic
catalytic aerobic oxidation of amines reported here gener-
ates the imine from the amine without any stoichiometric
reagents except molecular oxygen. These conditions are
very favorable for using the imine in situ for further reac-
tions. In a separate paper to be published elsewhere
Scheme 7.
Experimental Section
1H NMR spectra were recorded in CDCl3 with a Varian XL-400 spec-
trometer using the residual peak of CDCl3 (d=7.26 ppm for H) as inter-
nal standard. Ruthenium catalysts 1 and 3 were prepared according to
reference [29]. Quinone 2a was dried prior to use. Bis(salicylidenimina-
to-3-propyl)methylaminocobalt(ii) (27) was purchased from Aldrich and
used as received. All other reagents are commercially available and were
1
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Aerobic Oxidation of Amines
FULL PAPER
used without further purification. Solvents were technical grade and dis-
tilled before use. The amines used were either commercially available or
prepared by standard procedures. Spectral data for imines 17,[38] 20, 22,
23, 24, 25, 32, 33,[31] and 34, 35[39] were in accordance with those previous-
ly reported.
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[2] R. A. Sheldon, J. K. Kochi, Metal Catalyzed Oxidations of Organic
Compounds, Academic Press, New York, 1981.
Reference samples imines 18, 19, 21, and 26 were prepared according to
reference [31].
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N-(2,4,6-trimethylphenyl)-(1-phenylethylidene)amine
(18):
1H NMR
(400 Hz, CDCl3, 258C): d=8.02–8.05 (m, 2H), 7.45–7.50 (m, 3H), 6.89 (s,
2H), 2.30 (s, 3H), 2.08 (s, 3H), 2.00 ppm (s, 6H); 13C NMR (100 Hz,
CDCl3, 258C): d=165.6, 146.6, 139.5, 132.9, 130.3, 128.7, 128.5, 127.2,
125.7, 20.9, 18.1, 17.6 ppm.
N-(2-methylphenyl)-(1-phenylethylidene)amine (19): 1H NMR (400 Hz,
CDCl3, 258C): d=8.02–8.05 (m, 2H), 7.46–7.50 (m, 3H), 7.18–7.24 (m,
2H), 7.01–7.05 (m, 1H), 6.67–6.69 (m, 1H), 2.19 (s, 3H), 2.13 ppm (s,
3H); 13C NMR (100 Hz, CDCl3, 258C): d=165.1, 150.5, 139.6, 130.6,
130.5, 128.5, 127.3, 126.5, 123.4, 118.6 17.9, 17.6 ppm.
N-(4-methoxyphenyl)-(1-phenylethylidene)amine (21): 1H NMR (400 Hz,
CDCl3, 258C): d=7.95–7.97 (m, 2H), 7.43–7.45 (m, 3H), 6.90–6.92 (m,
2H), 6.74–6.77 (m, 2H), 3.82 (s, 3H), 2.25 ppm (s, 3H); 13C NMR
(100 Hz, CDCl3, 258C): d=165.1, 156.1, 152.1, 140.0, 130.5, 128.5, 127.3,
120.9, 114.4, 55.7, 17.5 ppm.
1
N-(4-methoxyphenyl)-[1-(4-cyanophenyl)ethylidene]amine (26): H NMR
(400 Hz, CDCl3, 258C): d=8.05–8.08 (m, 2H), 7.72–7.75 (m, 2H), 6.91–
6.94 (m, 2H), 6.74–6.77 (m, 2H), 3.83 (s, 3H), 2.28 ppm (s, 3H);
13C NMR (100 Hz, CDCl3, 258C): d 164.1, 156.7, 144.1, 143.8, 132.4,
127.9, 120.9, 118.8, 114.5, 113.9, 55.7, 17.5 ppm.
General procedure for ruthenium-catalyzed dehydrogenation of amines
with a stoichiometric amount of 2a: Ruthenium complex 3 (2.7 mg,
2.5 mmol, 2 mol%) and dry quinone 2a (31.5 mg, 0.2 mmol, 1.5 equiv)
were dissolved under an argon atmosphere in toluene (1 mL) in a round-
bottomed flask equipped with a condenser and a stirring bar. Amine
(0.125 mmol) was added and the reaction mixture was heated to 1108C.
The reaction course was monitored by 1H NMR spectroscopy. The prod-
uct was characterized by comparison with an authentic sample.
General procedure for the ruthenium-catalyzed aerobic oxidation of
amines: Ruthenium complex 3 (4.2 mg, 2.5 m mol, 2 mol%), quinone 2a
(4.2 mg, 25 m mol, 20 mol%), and cobalt complex 27 (1 mg, 2.5 mmol,
2 mol%) were charged into a 5-mL round-bottomed flask under an
argon atmosphere. The amine (1 mL, 0.125m in toluene, 0.125 mmol) was
added to this mixture followed by flushing with air for about 1 min. A
stream of air was allowed to pass through the system, and the mixture
was heated to 1108C in an oil bath (reaction times are given in
Table 3).[40] When the reaction was complete, the mixture was cooled to
room temperature and analyzed by 1H NMR spectroscopy. The product
was characterized by comparison with an authentic sample.
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[14] A. Cꢆrdova, Acc. Chem. Res. 2004, 37, 102.
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[2,3,4,5-Ph4(h5-C4CO)Ru(CO)2N(CH3)(CH(4-MeO-Ph)(CH3))][2,3,4,5-
Ph4(h5-C4COH)Ru(CO)2H] (37): Complex
1 (30 mg, 0.03 mmol) was
weighed into an NMR tube, and CD2Cl2 (0.5 mL) was added under an
argon atmosphere. The sample was cooled to À788C, 36 (0.03 mmol,
0.3m, 0.1 mL) was added, then the sample was shaken carefully and in-
serted into the NMR spectrometer pre-cooled to À208C. Full conversion
to 37 was observed. 1H NMR (400 Hz, CD2Cl2, À208C): d=À15.17 (s,
1H; RuH), 0.79 (s, 3H; NMe), 0.96 (brd, J=6.4 Hz, 3H; CCH3), 2.47
(br, 1H; CH), 3.78 (s, 3H; OCH3), 6.80–7.26 (m, 44H; Ar), 8.91 (brs,
1H; NH), 9.56 ppm (brs, 1H; NH); 1H NMR (400 Hz, CD2Cl2, 258C):
d=À16.27 (brs, 1H; RuH), 1.07 (brd, J=7.3 Hz, 3H; CCH3), 1.24 (s,
3H; NMe), 2.92 (brq, 1H; CH), 3.80 (s, 3H; OCH3), 6.85–7.26 ppm (m,
44H; Ar).
[17] J. S. Sandhu, B. Sain, Heterocycles 1987, 26, 777.
[18] a) M. Shi, Y.-M. Xu, Angew. Chem. 2002, 114, 4689; Angew. Chem.
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2002, 67, 2329; c) D. Balan, H. Adolfsson, J. Org. Chem. 2001, 66,
6498.
[19] K. Hattori, H. Yamamoto, J. Org. Chem. 1992, 57, 3264.
[20] C. Anthony, Biochem. J. 1996, 320, 697.
[21] Apart from those reported in references [22—27] a few noncatalytic
methods are known. See for example: K. C. Nicolaou, C. J. N. Ma-
thiason, T. Montagnon, Angew. Chem. 2003, 115, 4111; Angew.
Chem. Int. Ed. 2003, 42, 4077, and references therein.
[22] a) S.-I. Murahashi, T. Naota, H. Taki, J. Chem. Soc. Chem.
Commun. 1985, 613; b) S. -I. Murahashi in Transition Metals for Or-
ganic Synthesis, Vol. 2 (Eds.: M. Beller, C. Bolm), Wiley-VCH,
Weinheim, 2004, p. 497;
Acknowledgements
[23] A . J. Bailey, B. R. James, Chem. Commun. 1996, 2343.
[24] For an example of ruthenium-catalyzed aerobic oxidative cyanation
see reference [15b].
This work was supported by grants from the Swedish Research Council.
Professor Charles P. Casey is gratefully acknowledged for helping us with
the structure of compound 37.
Chem. Eur. J. 2005, 11, 2327 – 2334
www.chemeurj.org
ꢂ 2005 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
2333

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[26] X.-Q. Gu, W. Chen, D. Morales-Morales, C. M. Jensen, J. Mol.
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Am. Chem. Soc. 2001, 123, 1090.
conversion to imine was observed compared to >30% with the cou-
pled system. However no oxidation took place without 3 (reaction
checked after 4 h).
[34] a) N. Menashe, Y. Shvo, Organometallics 1991, 10, 3885; b) O.
Pamies, J.-E. Bꢁckvall, Chem. Eur. J. 2001, 7, 5052.
[35] J. S. M. Samec, A. H. ꢀll, J.-E. Bꢁckvall, unpublished results.
[36] Park and co-workers have reported a similar complex having Na+ at
the proton/ammonium position see: H. M. Jung, S. T. Shin, Y. H.
Kim, M.-J. Kim, J. Park, Organometallics 2001, 20, 3370.
[37] I. Ibrahem, J. S. M. Samec, J.-E. Bꢁckvall, A. Cꢆrdova, unpublished
results.
[38] N. De Kimpe, C. Stevens, Tetrahedron 1991, 47, 3407.
[39] I. Ojima, I. Habus, M. Zhao, M. Zucco, Y. H. Park, C. M. Sun, T.
Brigaud, Tetrahedron 1992, 48, 6985.
[40] Air with toluene at 1008C produces explosive mixtures in the gas
phase.
[30] G.-Z. Wang, J.-E. Bꢁckvall, J. Chem. Soc. Chem. Commun. 1992,
980.
[31] J. S. M. Samec, J.-E. Bꢁckvall, Chem. Eur. J. 2002, 8, 2955.
[32] This overall redox reaction involves more detailed steps where the
cytochrome first is reduced from FeIII to FeII followed by oxygen
À
À
binding and another single electron transfer to generate Fe OO .
This intermediate is then hydrolyzed to form water and the active
FeV=O that subsequently oxidizes the substrate.
[33] It was shown that 3 and 27 alone (without quinone 2a) slowly cata-
lyzed the aerobic oxidation of amines to imines. After 1 h, <10%
Received: October 25, 2004
Published online: February 10, 2005
2334
ꢂ 2005 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
Chem. Eur. J. 2005, 11, 2327 – 2334