Synthetic scope of alcohol transfer dehydrogenation catalyzed by Cu/Al 2O3: A new metallic catalyst with unusual selectivity

Article abstract of DOI:10.1002/chem.200501619

A method for the anaerobic oxidation of a wide series of alcohols including cyclohexanols and steroidal alcohols, has been set up. It relies on a transfer dehydrogenation reaction from the substrate alcohol to styrene catalyzed by a heterogeneous, reusable copper catalyst under very mild liquid phase experimental conditions (90°C, N₂) and shows unusual selectivity. Thus, the method is selective for the oxidation of secondary and allylic alcohols even in the presence of unprotected primary and benzylic alcohols. Electronic effects and the choice of the hydrogen acceptor account for the selectivity observed.

Full text of DOI:10.1002/chem.200501619

DOI: 10.1002/chem.200501619
Synthetic Scope of Alcohol Transfer Dehydrogenation Catalyzed by
Cu/Al2O3: A New Metallic Catalyst with Unusual Selectivity
Federica Zaccheria,[a] Nicoletta Ravasio,*[b] Rinaldo Psaro,[b] and Achille Fusi[a]
Abstract: A method for the anaerobic
oxidation of a wide series of alcohols
including cyclohexanols and steroidal
alcohols, has been set up. It relies on a
transfer dehydrogenation reaction from
the substrate alcohol to styrene cata-
phase experimental conditions (908C,
N2) and shows unusual selectivity.
Thus, the method is selective for the
oxidation of secondary and allylic alco-
hols even in the presence of unprotect-
ed primary and benzylic alcohols. Elec-
tronic effects and the choice of the hy-
drogen acceptor account for the selec-
tivity observed.
Keywords: alcohols · dehydrogena-
tion
· heterogeneous catalysis ·
lyzed by
a heterogeneous, reusable
hydrogen transfer · oxidation
copper catalyst under very mild liquid-
Introduction
plored by using a wide variety of metals. Very active copper
based homogeneous systems have been setup,[11] whereas
the heterogeneous systems mainly rely on the use of noble
metals.[12]
The oxidation of alcohols to carbonyl compounds is an es-
sential functional-group transformation in organic synthesis.
Countless methods have been developed to perform this re-
action, the most popular represented by the Collins,[1]
Jones,[2] pyridinium chlorochromate (PCC),[3] pyridinium di-
chromate,[4] and Swern[5] oxidations. Most of these methods
suffer from the use of stoichiometric toxic reagents, cryogen-
ic conditions, and/or the production of copious amounts of
waste.
An alternative approach is the use of a catalyst in combi-
nation with a stoichiometric oxidant, for example, tetrapro-
pylammonium perruthenate (TPAP) with stoichiometric N-
methylmorpholine (NMO),[6] while the use of supported[7,8]
or unsupported[9] stable nitroxyl free radical precursor
TEMPO (TEMPO=tetramethylpiperdinyloxy free radical)
and of hypervalent iodine reagents[10] are an alternative to
metal based oxidants.
An interesting alternative to aerobic conditions is repre-
sented by the use of a readily available organic molecule in-
stead of oxygen as the hydrogen acceptor, thus overcoming
safety concerns linked with the use of flammable solvents.
However, only few cases of alcohol transfer dehydrogena-
tion promoted by heterogeneous catalysts are known. Re-
cently three palladium-based systems have been reported by
Hayashi[13,14] and Baiker,[15] both active only in the oxidation
of aromatic or allylic alcohols and one based on Ru.[16]
We recently reported that a low loading supported copper
catalyst, 8% Cu/Al2O3, is very effective in selective oxida-
tion of nonactivated aliphatic secondary alcohols under hy-
drogen-transfer dehydrogenation conditions.[17] Here we
wish to report some additional results together with a mech-
anistical investigation on this catalytic system.
Much more attractive is the use of molecular oxygen or
air as the terminal oxidant, therefore the development of
catalysts for the aerobic oxidation of alcohols has been ex-
Results and Discussion
Copper catalysts prepared through a nonconventional chem-
isorption-hydrolysis technique have been shown to be active
and very selective in a wide range of reductions, not only
under catalytic hydrogenation conditions but also in hydro-
gen transfer reactions from secondary alcohols. In particular,
Cu/Al2O3 was shown to be the most active reagent in trans-
ferring hydrogen from 2-propanol to 4-tert-butylcyclohexa-
none (Scheme 1). A detailed study aimed to elucidate the
[a] Dr. F. Zaccheria, Prof. A. Fusi
Dip. CIMA, Università degli Studi di Milano
Via G. Venezian 21, 20133 Milano (Italy)
[b] Dr. N. Ravasio, Dr. R. Psaro
CNR-Istituto Scienze e Tecnologie Molecolari
Via C. Golgi 19, 20133 Milano (Italy)
Fax : (+39)02-5031-4405
E-mail: n.ravasio@istm.cnr.it
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FULL PAPER
times, particularly over Cu/Al2O3. The byproduct, ethylben-
zene, is easily removed from the reaction mixture together
with the solvent. The catalyst was pretreated in H2 at 543 K
before use to reduce all the copper to the metallic phase;
however, reduction at a much lower temperature (Table 2,
entry 1b) still resulted in a very active material . On the con-
trary a lower copper loading on the catalyst results in much
lower activity (entry 1a versus 1d and 21a versus 21b).
Three main features are apparent from the results report-
ed in Table 2: the uncomplete conversion of benzylic alcohol
(entry 5), the inactivity of primary alcohols (entries 3 and 7),
and the high activity for secondary unactivated alcohols.
This trend is very different from that observed over
almost all the oxidation catalytic systems reported so far,
both based on a metal and on a radical precursor, which
always convert benzylic alcohols faster than the other alco-
hols, thus suggesting that a different mechanism is operating
in the present case.
Scheme 1.
effect of the donor alcohol structure revealed the existence
of a two-step mechanism based on the dehydrogenation of
the donor followed by substrate reduction.[18]
In particular when (iPr)2CHOH and 3-octanol were used
as hydrogen donors, formation of the corresponding ketones
was observed also after complete conversion of 4-tert-butyl-
cyclohexanone. Moreover the stereochemistry observed in
diisopropylcarbinol was coincident with that obtained under
catalytic hydrogenation conditions, strongly suggesting that
hydrogen availability on the catalyst surface is comparable
both in the presence of molecular H2 and when using this
particular alcohol as a donor.
These results and the need for heterogeneous and simple
systems for the oxidation of hydroxyl groups under liquid-
phase conditions prompted us to investigate the activity of
these copper catalysts in alcohol dehydrogenation reactions.
From the results catalysts Cu/SiO2 and Cu/Al2O3 seemed
promising, although in the absence of an acceptor an equili-
brium situation between dehydrogenation and hydrogena-
tion was reached. On the other hand if hydrogen is spilled
off from the reactor (Table 1) it is apparent that the dehy-
However, in total analogy with the Ru/Al2O3 systems,[22]
the plot of log
(kX/kH) versus the Brown–Okamoto s+ for a
G
series of different benzylic alcohols was found to be linear
with a slope corresponding to a Hammett 1+ value of
À0.75 (r2 =0.97), while the correlation with the s+ is better
than that with s constants, particularly for electron donating
substituents (Figure 1, Table 3). This shows that the forma-
tion of a carbocation-type transition state is involved in the
oxidation path. Therefore benzylic alcohols should exhibit
the fastest reaction rates, owing to the higher stability of
their corresponding carbocations. The uncomplete conver-
sion observed under our experimental conditions can thus
be ascribed to the inadequacy of the hydrogen acceptor
used, which is unable to prevail over the aromatic aldehyde
formed.
This apparent drawback, however, also has a plus side as
it allows us to finely-tune the system selectivity. Thus, the
competitive dehydrogenation of cyclooctanol and benzyl al-
cohol shows a marked selectivity towards the oxidation of
the secondary alcohols (Figure 2), but in the absence of sty-
rene, benzaldehyde acts as the acceptor and oxidation of cy-
clooctanol becomes specific (Figure 3).
The large decrease in the rate of cyclooctanol disappear-
ance during competitive dehydrogenation and the small re-
duction in the rate of benzyl alcohol oxidation are strong
evidence that the latter compound displaces cyclooctanol
from the catalyst surface.[23] This is why benzaldehyde or
substituted benzaldehydes may well be used as the acceptor,
as shown by a test carried out on cyclooctanol (Table 2,
entry 21c), but with a dramatic decrease in reaction rate.
It is worth underlining that this is the only case in which
the product competes with the acceptor, as even secondary
benzylic alcohols can be readily oxidized notwithstanding
the high activity of Cu/Al2O3 in the hydrogenation of aro-
matic ketones[24] (entry 6). The effectiveness of styrene with
respect to aromatic ketones in trapping the hydrogen
formed is also shown by the dehydrogenation of optically
pure (R)-1-phenyl-ethanol which proceeds without racemi-
zation with up to 80% conversion.
Table 1. Oxidation of 3-octanol with different 8% Cu catalysts.[a]
Entry
Catalyst
t [h]
Conversion [%]
Selectivity [%]
1
2
3
Cu/SiO2
Cu/Al2O3
Cu/MgO
20
12
20
100
84
40
100
100
100
[a] Reaction carried out by spilling-off H2 from the reactor.
drogenation reaction can go to completion. No reaction oc-
curred in the presence of Al2O3 alone, although under these
conditions the support showed some activity in hydrogen-
transfer reactions from 2-propanol.[19]
However, Cu/MgO, which showed activity comparable
with that of Cu/SiO2 in the transfer hydrogenation of 4-tert-
butylcyclohexanone from 2-propanol, is scarcely active in 3-
octanol dehydrogenation (entry 3), thus confirming once
more that its activity in the former reaction is due mainly to
a
MPV-type mechanism (MPV=Meerwein–Ponndorf–
Verley) and not to its dehydrogenation ability.[18]
To improve the synthetic potential of this reaction it
seemed more effective to adopt transfer dehydrogenation
conditions by exploiting a pivotal feature of these catalytic
systems already expressed in other synthetic applica-
tions,[20,21] that is, their specificity towards hydrogenation of
a conjugated system in the presence of an isolated one.
Thus, by adding styrene in an equimolar ratio with respect
to the substrate as a hydrogen acceptor, complete oxidation
of the desired alcohol was obtained in very short reaction
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N. Ravasio et al.
Table 2. Transfer dehydrogenation of different alcohols over Cu/Al2O3.
Steric effects also play a sig-
nificant role. This is apparent in
the monosubstituted cyclohexa-
nols series (entries 9–12), in the
very low activity of isopinocam-
pheol (entry 15), and from the
comparison between linear and
branched substrates (entry 1
versus 4). This effect is so
strong that in disubstituted cy-
clohexanols the reaction takes
place at a reasonable rate only
when the OH group is in axial
conformation, as shown by the
comparison of (À)-menthol
Entry
Substrate
t [h]
Conversion [%]
Selectivity [%]
a
b
c
1.5
100
98
97
100
100
100
100
2.5[a]
1
2.5[b]
4[c]
d
96
2
3
4
100
4
100
100
24
4
5
6
100
100
100
20
51.5
6
0.75
100
100
with
neomenthol
(entry 13
versus 14).
7
8
24
3
1
100
98
For the same reason in 3-ster-
ols the oxidation is faster when
the OH group is in the 3b-posi-
tion both in the 5a (entry 24
99
9
10
11
12
R=2-Me
R=3-Me
R=4-Me
R=4-tBu
3.5
3
1.5
1.5
99
100
100
97
100
100
100
100
versus 25)
and
5b
series
(entry 26 versus 27). This shows
that the OH group has to be as
unhindered as possible to effec-
tively adsorb on the catalyst
surface.
13
14
48
50[d]
97[d]
40[d]
100
100
100
According to the relevant lit-
erature on the mechanism of
secondary alcohols dehydrogen-
ation over metallic copper cata-
lysts, a proper orientation of
the alcohol molecule on the sur-
face is required.[25–27] In particu-
lar, Rioux and Vannice suggest-
ed that formation of a hydrogen
molecule from isopropanol
occurs in two sequential ele-
mentary steps and that the first
hydrogen atom removed is the
hydroxyl one. Even though the
6
15
16
17
48
a
b
2.5
100
100
88
95
1.5[e]
30
95
93
91
84
18
19
2
À
O H bond is stronger than the
À
30
6
15
95
100
91
C H one, its cleavage prior to
the a hydrogen is attributed to
its orientation on the surface of
copper on carbon catalysts.[25]
We suggest that this also holds
for the Cu/Al2O3-catalyzed re-
action. After this step, the
richer the incipient carbenium
ion in the electrons the fastest
will be the remotion of the
second hydrogen atom from the
a carbon.
20
21
a
b
c
0.5
1[c]
9[f]
100
90
90
100
100
100
22
23
2
97
100
100
1.5
100
The understanding of the
strong electronic effects operat-
ing in this catalytic system and
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Heterogeneous Catalysis
FULL PAPER
though in this last case steric ef-
fects may also play a role. Se-
lectivity is not high when secon-
dary reactions can take place,
as in the case of geraniol, which
under these conditions gives cit-
ronellol and isopulegol,[28] but
anaerobic conditions avoid for-
mation of the corresponding
carboxylic acid which are often
observed when using gold cata-
lysts.[12a,29]
The oxidation of carveol re-
quires some more comments.
Thus, under catalytic dehydro-
genation conditions both nickel
and conventional copper-based
catalysts convert carveol into
carvacrol and tetrahydrocar-
vone, therefore methods pro-
posed for this transformation
on the industrial scale rely on
the use of Oppenauer oxidation
Table 2. (Continued)
Entry
Substrate
t [h]
Conversion [%]
100
Selectivity [%]
96
24
25
2.5
4
86
41
100
75
26
27
24
5
89
80
[a] Catalyst activated at 453 K. [b] Ethylbenzene as solvent. [c] Catalyst with 5% Cu loading. [d] Mixture of
ketone diastereoisomers. [e] Substrate/styrene=1:2. [f] Benzaldehyde as hydrogen acceptor.
Table 3. Oxidation of substituted benzylic alcohols.
0.7
0.6
0.5
0.4
0.3
0.2
0.1
0
Entry
Substrate
t [h]
Conversion [%]
80
p-OMe
1
20
2
20
57
p-Me
p-F
3
4
5
20
20
20
52
49
33
p-H
0.1
-0.9
-0.7
-0.5
-0.3
-0.1
0.3
0.5
+
σ
p-Cl
-0.1
-0.2
Figure 1. Hammett plot for competitive dehydrogenation of benzyl alco-
hol and p-substituted benzyl alcohols. Reaction conditions: benzyl alco-
hol (0.5 mmol), p-substituted benzyl alcohol (0.5 mmol), styrene
(1 mmol), 8% Cu/Al2O3 (100 mg), toluene (8 mL), 363 K, N2 atmosphere.
No suitable data are available for the reaction of p-NO2-benzyl alcohol
due to poisoning of the catalyst in the presence of the nitro group.[24]
systems[30,31] or homogeneous dehydrogenation systems.[32]
On the contrary, over Cu/Al2O3 carveol was oxidized with
88% selectivity under standard conditions and with 95% se-
lectivity by only using two equivalents of hydrogen acceptor,
giving carvone, one of the more sought after compounds in
the flavor and fragrances industry. On the other hand, in the
absence of styrene, dihydrocarvone could be obtained in
moderate yield directly from carveol, acting as both the hy-
drogen donor and acceptor (Scheme 2).
of the role played by the acceptor have significant conse-
quences from the synthetic point of view.
The formation of a carbocation-type transition state can
account for the inactivity of primary alcohols, such as 1-oc-
tanol. Indeed, competitive hydrogenation of 1-octanol and
cyclooctanol gave >97% cyclooctanone; 1-octanol was re-
covered unchanged (Figure 4).
On the contrary, allylic alcohols react very fast, much
faster than their saturated analogues, as shown by the com-
parison between mirtenol and mirtanol (entry 18 versus 19)
and of carveol and dihydrocarveol (entry 16 versus 17) al-
In addition, perillyl aldehyde is typically obtained from
perillyl alcohol through Oppenauer-type oxidation systems
in the presence of alkylboron compounds and six equiva-
lents of pivalaldehyde[33] or in the presence of aluminium
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N. Ravasio et al.
100
80
60
40
20
0
cyclooctanol
cyclooctanone
benzyl alcohol
benzaldehyde
0
1
2
3
4
5
Scheme 2.
t / h
Figure 2. Competitive dehydrogenation of cyclooctanol and benzyl alco-
hol in the presence of styrene. Reaction conditions: benzyl alcohol
(0.5 mmol), cyclooctanol (0.5 mmol), styrene (1 mmol), 8% Cu/Al2O3
(100 mg), toluene (8 mL), 363 K, N2 atmosphere.
nol and a series of substituted cyclohexanols (entries 8–12).
In the case of 4-tert-butylcyclohexanol, for example, the ac-
tivity based on the total metal content (TOF=3.5 hÀ1) is
comparable with that observed under aerobic conditions
both over 1% Pd/MgO (TOF=3.5 hÀ1)[12b] and 1% Ru/
Al2O3 (TOF=2.1 hÀ1),[22] whereas for cyclooctanol the activ-
ity (TOF=12.5 hÀ1) is higher than that observed for both
systems (TOF=3.2 hÀ1 for Pd/MgO and TOF=2.7 hÀ1 for
Ru/Al2O3). However, if we consider productivity expressed
as gproduct/gcatalyst ”h, Cu/Al2O3 turns out to be one order of
magnitude more active than the other two systems for the
dehydrogenation of 4-tert-butylcyclohexanol and two orders
of magnitude for the dehydrogenation of cyclooctanol.
The catalyst is efficient for at least six catalytic runs with-
out relevant loss in activity or in selectivity. The Cu content
before use and after six runs was found to be unchanged by
AAS analysis, while Cu in the filtrates was found to be
absent by GF-AAS. Moreover, TPR profiles before and
after six runs appeared to be identical, showing the high sta-
bility of the metallic phase (Figure 5).
100
80
60
40
cyclooctanol
cyclooctanone
benzyl alcohol
20
benzaldehyde
0
0
2
4
6
8
10
t / h
Figure 3. Competitive dehydrogenation of cyclooctanol and benzyl alco-
hol in the absence of styrene Reaction conditions: benzyl alcohol
(0.5 mmol), cyclooctanol (0.5 mmol), 8% Cu/Al2O3 (100 mg), toluene
(8 mL), 363 K, N2 atmosphere.
18
16
14
th
6
RUN
12
10
8
Fresh
6
4
2
Figure 4. Competitive dehydrogenation of cyclooctanol and 1-octanol.
Reaction conditions: 1-octanol (0.5 mmol), cyclooctanol (0.5 mmol), sty-
rene (1 mmol), 8% Cu/Al2O3 (100 mg), toluene (8 mL), 363 K, N2 atmos-
phere.
0
-50
0
50
100
150 200 250 300 350 400 450 500
-2
T / °C
Figure 5. TPR profiles of the fresh catalyst and of the catalyst used for
six catalytic runs.
isopropoxide and more than the stoichiometric amounts of
nitrobenzaldehyde,[30] whereas under the conditions required
by the present system it can be obtained in 86% yield with-
out formation of any waste but some ethylbenzene
(entry 20).
Remarkable activity is observed for nonactivated secon-
dary alcohols that are less easily oxidized by other systems.
In particular, a striking activity was observed for cyclohexa-
Experimental Section
Cu/Al2O3 was prepared as already reported[17] by chemisorption-hydroly-
sis using alumina from Grace Davison (BET=300 m2gÀ1, pore volume =
1.0 mLgÀ1). The powder was added to a [Cu(NH3)4]2+ solution prepared
R
by dropping aqueous NH3 to a Cu(NO3)2·3H2O solution until pH 9 had
U
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Heterogeneous Catalysis
FULL PAPER
been reached. After 20 min under stirring, the slurry, held in an ice bath
at 273 K, was diluted with water. The solid was separated by filtration,
washed with water, dried overnight at 383 K, and calcined in air at 673 K
for 4 h.
[4] E. J. Corey, G. Schmidt, Tetrahedron Lett. 1979, 20, 399–402.
[5] A. J. Mancuso, D. Swern, Synthesis 1981, 165–185.
[6] S. V. Ley, J. Norman, W. P. Griffith, S. P. Marsden, Synthesis 1994,
639–666.
[7] M. Gilhespy, M. Lok, X. Baucherel, Chem. Commun. 2005, 1085–
1086.
[8] G. Pozzi, M. Cavazzini, S. Quici, M. Tenaglia, G. Dell’Anna, Org.
Lett. 2004, 6, 441–443.
[9] R. A. Sheldon, I. W. C. E. Arends, Adv. Synth. Catal. 2004, 346,
1051–1071.
[10] H. Tohma, Y. Kita, Adv. Synth. Catal. 2004, 346, 111–124.
[11] a) I. E. Markꢁ, A. Gautier, R. Dumeunier, K. Doda, S. Philippart,
S. M. Brown, C. J. Urch, Angew. Chem. 2004, 116, 1614–1617;
Angew. Chem. Int. Ed. 2004, 43, 1588–1591, and references therein;
b) P. Gamez, I. W. C. E. Arends, R. A. Sheldon, J. Reedijk, Adv.
Synth. Catal. 2004, 346, 805–811.
Before reaction, the catalyst (100 mg) was treated in the reaction vessel
for 20 min in air at 543 K, for 20 min under reduced pressure, and then
reduced in hydrogen (1 atm) at the same temperature.
The substrates (100 mg, 200 mg for steroids) and styrene (1 equiv) were
dissolved in toluene (8 mL) and the solution transferred under nitrogen
into the reaction vessel containing the prereduced catalyst (100 mg). Cat-
alytic tests were carried out at 363 K under nitrogen and with magnetic
stirring (1000 rpm).
For the recycling test, the catalyst was separated by filtration after reac-
tion, washed with acetone, dried, and reactivated by hydrogenation
before recycling.
The reaction mixtures were analyzed by means of GC (nonbonded bis-
cyanopropyl-polysiloxane capillary column, 100 m), GCMS (HP-5 MS
cross-linked 5% phenyl methyl silicone, 30 m), and 1H NMR (Bruker,
300 MHz) spectroscopy.
[12] a) A. Abad, P. Conception, A. Corma, H. Garcia, Angew. Chem.
2005, 117, 4134–4137; Angew. Chem. Int. Ed. 2005, 44, 4066–4069;
b) U. R. Pillai, E. Sahle-Demessie, Green Chem. 2004, 6, 161–165;
c) for a review see T. Mallat, A. Baiker, Chem. Rev. 2004, 104,
3037–3058.
Competitive reactions, were carried out by preparing a solution of the
two substrates in an equimolar ratio and styrene (2 equiv) in toluene
(8 mL).
[13] M. Hayashi, K. Yamada, S. Nakayama, H. Hayashi, S. Yamazaki,
Green Chem. 2000, 2, 257–260.
[14] T. Tanaka, H. Kawabata, M. Hayashi, Tetrahedron Lett. 2005, 46,
4989–4991.
[15] C. Keresszegi, T. Mallat, A. Baiker, New J. Chem. 2001, 25, 1163–
1167.
[16] R. Karvembu, R. Prabhakaran, K. Senthilkumar, P. Viswanathamur-
ty, K. Natarajan, React. Kinet. Catal. Lett. 2005, 86, 211–216.
[17] F. Zaccheria, N. Ravasio, A. Fusi, R. Psaro, Chem. Commun. 2005,
253–255.
[18] F. Zaccheria, A. Fusi, R. Psaro, N. Ravasio in Catalysis of Organic
Reactions, Chem. Industry, Vol. 104 (Ed.: J. R. Sowa Jr.), Taylor &
Francis, Boca Raton, 2005, pp. 293–301.
TPR experiments were conducted on a Micromeritics Pulse Chemisorb
2700 apparatus. Samples were calcined in O2 flow (50 mLminÀ1) at 773 K
for 1 h, cooled down to 200 K in Ar flow (50 mLminÀ1), and then TPR
was performed in H2 (8%)/Ar flow (15 mLminÀ1, heating rate 88minÀ1
to 773 K).
The copper content analyses of the solutions were performed by graphite
furnace atomic absorption spectroscopy (GF-AAS) by using a GBC
908 AA instrument and the analysis of the catalysts by a Perkin–Elmer
400 atomic absorption spectrophotometer.
[19] N. Ravasio, F. Zaccheria, A. Fusi, R. Psaro, Recent. Res. Devel. Cat-
alysis 2005, 3, 1–15.
[20] N. Ravasio, M. Antenori, M. Gargano, P. Mastrorilli, Tetrahedron
Lett. 1996, 37, 3529–3532.
Conclusion
The Cu/Al2O3-catalyzed transfer dehydrogenation reaction
has been shown to be a versatile and powerful tool for the
oxidation of secondary and allylic alcohols under very mild
conditions. Electronic effects and the choice of the acceptor
make this catalytic system unique as it allows selective oxi-
dation of a secondary alcohol in the presence of an unpro-
tected primary alcohol and also of a benzylic alcohol. More-
over, the catalyst can also be used for hydrogenation and
cyclization reactions, always showing excellent selectivity,
good productivity, stability, and reusability, basic features
for the application of heterogeneous catalysts to fine-chemi-
cal synthesis.
[21] N. Ravasio, F. Zaccheria, M. Guidotti, R. Psaro, Top. Catal. 2004,
27, 157–168.
[22] a) K. Yamaguchi, N. Mizuno, Angew. Chem. 2002, 114, 4720–4724;
Angew. Chem. Int. Ed. 2002, 41, 4538–4542; b) K. Yamaguchi, N.
Mizuno, Chem. Eur. J. 2003, 9, 4353–4361.
[23] U. K. Singh, M. N. Sysak, M. A. Vannice, J. Catal. 2000, 191, 181–
191.
[24] F. Zaccheria, N. Ravasio, A. Fusi, R. Psaro, Tetrahedron Lett. 2005,
46, 3695–3697.
[25] R. M. Rioux, M. A. Vannice, J. Catal. 2003, 216, 362–376.
[26] V. Z. Fridman, A. A. Davydov, K. Titiesky, J. Catal. 2004, 222, 545–
557.
[27] V. Z. Fridman, A. A. Davydov, J. Catal. 2000, 195, 20–30.
[28] F. Zaccheria, N. Ravasio, A. Fusi, M. Rodondi, R. Psaro, Adv.
Synth. Catal. 2005, 347, 1267–1272.
[29] D. I. Enache, D. W. Knight, G. J. Hutchings, Catal. Lett. 2005, 103,
43–52.
[30] S. Tanikawa, S. Matsubayashi, M. Tanikawa, T. Komatsu (Nikken
Chem. Ltd., Japan) US-Pat. Appl. 2002198411, 2002 [Chem. Abstr.
2003, 138, 39431j].
[31] T. Ooi, H. Otsuka, T. Miura, H. Ichikawa, K. Maruoka, Org. Lett.
2002, 4, 2669–2672.
Acknowledgements
The authors wish to thank Dr. Angelamaria Maia, CNR-ISTM, Milano
(I) for helpful discussion on the kinetic data and Dr. Damiano Monticelli,
University of Insubria, Como (I) for trace analysis of Cu.
[32] G. Kolomeyer, J. S. Oyloe (Millenium Speciality Chem. USA), PCT
Int. Appl. WO 2004108646, 2004 [Chem. Abstr. 2005, 142, 56539a].
[33] K. Ishihara, H. Kurihara, H. Yamamoto, J. Org. Chem. 1997, 62,
5664–5665.
[1] J. C. Collins, W. W. Hess, F. J. Frank, Tetrahedron Lett. 1968, 9,
3363–3366.
[2] K. E. Harding, L. M. May, K. F. Dick, J. Org. Chem. 1975, 40, 1664–
1665.
[3] E. J. Corey, J. W. Suggs, Tetrahedron Lett. 1975, 16, 2647–2650.
Received: December 23, 2005
Published online: May 26, 2006
Chem. Eur. J. 2006, 12, 6426 – 6431
ꢀ 2006 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
6431