Chemoselective Oxidation of Alcohols to Aldehydes and Ketones by tert -Butyl Hydroperoxide Catalyzed by a Ruthenium Complex of N,N′,N″-Trimethyl-1,4,7-triazacyclononane

Article abstract of DOI:10.1021/jo971892x

An operationally simple method based on [Cn*Ru^III(CF₃CO₂) ₃·H₂O] (Cn* = N,N′,N″-trimethyl-1,4,7-triazacyclononane) catalyst and 1-1.2 equiv of tert-butyl hydroperoxide as terminal oxidant is effective for selective transformation of alcohols to aldehydes and ketones in methylene chloride. The reaction proceeds in high yield and selectivity. Preparation of benzaldehyde (98% yield) from benzyl alcohol on a 200 mmol scale can be performed without modification of the procedure such as slow addition of the oxidant or cooling to 0°C, and catalyst turnovers of 700 are achieved. Oxidation of geraniol which contains an isolated trisubstituted C=C bond leads to geranial selectively without oxidation of the C=C bond. Results from Hammett correlation studies (ρ = -0.47) and primary kinetic isotope effect (k_H/k_D = 4.8) for the catalytic benzyl alcohol oxidations are inconsistent with an oxoruthenium (O=Ru) based mechanism. A mechanism involving reactive tBuO·/tBuOO· radicals is also excluded based on results from previous works: Cheng, W.-C.; Fung, W.-H.; Che, C.-M. J. Mol. Catal. (A) 1996, 113, 311; absence of di-tert-butyl peroxide; and using cumyl hydroperoxide as a radical probe. A tert-butylperoxoruthenium complex is postulated to be the active intermediate.

Full text of DOI:10.1021/jo971892x

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J . Org. Chem. 1998, 63, 2873-2877
2873
Ch em oselective Oxid a tion of Alcoh ols to Ald eh yd es a n d Keton es
by ter t-Bu tyl Hyd r op er oxid e Ca ta lyzed by a Ru th en iu m Com p lex
of N,N′,N′′-Tr im eth yl-1,4,7-tr ia za cyclon on a n e
Wai-Hong Fung, Wing-Yiu Yu, and Chi-Ming Che*
Department of Chemistry, The University of Hong Kong, Pokfulam Road, Hong Kong
Received October 14, 1997
An operationally simple method based on [Cn*RuIII(CF3CO2)3‚H2O] (Cn* ) N,N′,N′′-trimethyl-1,4,7-
triazacyclononane) catalyst and 1-1.2 equiv of tert-butyl hydroperoxide as terminal oxidant is
effective for selective transformation of alcohols to aldehydes and ketones in methylene chloride.
The reaction proceeds in high yield and selectivity. Preparation of benzaldehyde (98% yield) from
benzyl alcohol on a 200 mmol scale can be performed without modification of the procedure such
as slow addition of the oxidant or cooling to 0 °C, and catalyst turnovers of 700 are achieved.
Oxidation of geraniol which contains an isolated trisubstituted CdC bond leads to geranial
selectively without oxidation of the CdC bond. Results from Hammett correlation studies (F )
-0.47) and primary kinetic isotope effect (kH/kD ) 4.8) for the catalytic benzyl alcohol oxidations
are inconsistent with an oxoruthenium (OdRu) based mechanism. A mechanism involving reactive
tBuO•/tBuOO• radicals is also excluded based on results from previous works: Cheng, W.-C.; Fung,
W.-H.; Che, C.-M. J . Mol. Catal. (A) 1996, 113, 311; absence of di-tert-butyl peroxide; and using
cumyl hydroperoxide as a radical probe. A tert-butylperoxoruthenium complex is postulated to be
the active intermediate.
S2O8 under mild conditions.8 A notable example is
tetra-n-propylammonium perruthenate(VII) which is an
effective catalyst for oxidation of alcohols to aldehydes
by methylmorpholine N-oxide.9 Despite its remarkable
selectivity, the reaction usually requires two to three
times excess of terminal oxidant and high catalyst
loading (5 mol %) with modest catalytic turnovers around
250.
Our interest in ruthenium-mediated alcohol oxidations
was initiated by our recent success to achieve highly
chemoselective epoxidation of unfunctionalized alkenes
using the “[Cn*RuIII(CF3CO2)3‚H2O] + tBuOOH” system
(Cn* ) N,N′,N′′-trimethyl-1,4,7-triazacyclononane).10 The
reaction exhibits good chemoselectivity toward epoxides
formation with retention of configuration of the starting
alkenes, i.e., trans-alkenes to trans-epoxides; cis-alkenes
to cis-epoxides. Herein is described that the same system
can bring about chemoselective oxidation of alcohols to
aldehydes/ketones with high turnovers (Scheme 1). Our
findings demonstrate the potential synthetic utilities of
this protocol and suggest a tert-butylperoxoruthenium
complex as a possible reactive intermediate.
2-
In tr od u ction
Oxidation of alcohols to carbonyl compounds is an
important transformation in synthetic organic chemistry.
Although several stoichiometric reagents based on acti-
vated dimethyl sulfoxide (Swern oxidation),1 hypervalent
iodine compounds (Dess-Martin),2 and reactive oxo-
metal compounds3 (MnO2 and pyridinium chlorochro-
mate) have been developed to display high degree of
selectivities, the search for new catalytic procedures for
selective alcohol oxidations using inexpensive oxidants
such as H2O2 and tert-butyl hydroperoxide (TBHP)6
4,5
remains an area of intensive interest. RuCl2(PPh3)3 and
some high valent oxoruthenium complexes are known to
mediate alcohol oxidations using a variety of oxidants
such as PhIO,7 methylmorpholine N-oxide, BrO3-, and
(1) Lee, T. V. In Comprehensive Organic Synthesis; Trost, B. M.,
Fleming, I., Eds.; Pergamon: Oxford, 1991; Vol. 7, p 291.
(2) Dess, D. B.; Martin, J . C. J . Org. Chem. 1983, 48, 4155.
(3) (a) Ley, S. V.; Madin, A. In Comprehensive Organic Synthesis;
Trost, B. M., Fleming, I., Eds.; Pergamon: Oxford, 1991; Vol. 7, p 251.
(b) Mijs, W. J .; DeJ onge, C. R. H. I. Organic Synthesis by Oxidation
with Metal Compounds; Plenum: New York, 1986.
(4) For some selected examples of Mo(VI) and W(VI) catalyzed
alcohol oxidations, see (a) Sato, K.; Aoki, M.; Takagi, J .; Noyori, R. J .
Am. Chem. Soc. 1997, 119, 12386 and references therein. (b) Bailey,
A. J .; Griffith, W. P.; Parkin, B. C. J . Chem. Soc., Dalton Trans. 1995,
1833. (c) Bortolini, O.; Conte, V.; Di Furia, F.; Modena, G. J . Org. Chem.
1986, 51, 2661.
(5) (a) Manganese-catalyzed benzyl alcohol oxidations, see: Zonder-
van, C.; Hage, R.; Feringa, B. L. J . Chem. Soc., Chem. Commun. 1997,
419. (b) CH3ReVIIO3-catalyzed alcohol oxidations, see: Murray, R. W.;
Iyanar, K.; Chen, J .-X.; Wearing, J . T. Tetrahedron Lett. 1995, 36(36),
6415 (c) For [Ru]: Goldstein, A. S.; Beer, R. H.; Drago, R. S. J . Am.
Chem. Soc. 1994, 116, 2424.
(6) Several metals have been reported to mediate TBHP oxidation
of alcohols: for [Cr], see: (a) Muzart, J . Chem. Rev. 1992, 92, 113. For
[Mo]: (b) Trost, B. M.; Masuyama, Y. Tetrahedron Lett. 1984, 25(2),
173. (c) Masuyama, Y.; Takahashi, M.; Kurusu, Y. Tetrahedron Lett.
1984, 25(39), 4417. For [Se]: (d) Kuwajima, I.; Shimizu, M.; Urabe,
H. J . Org. Chem. 1982, 47, 837. For [Ru]: (e) Tanaka, M.; Kobayashi,
T.; Sakakura, T. Angew. Chem., Intl. Ed. Engl. 1984, 23, 518. (f)
Murahashi, S. I.; Naota, T. Synthesis 1993, 433.
Resu lts a n d Discu ssion
Treatment of benzyl alcohol (1 mmol) with TBHP (1-
1.2 mmol, 3.33 M in 1,2-dichloroethane) in the presence
of catalytic quantity of [Cn*RuIII(CF3CO2)3‚H2O] complex
(1) (1 mol %) in methylene chloride (5 mL) afforded
(7) Mu¨ller, P.; Godoy, J . Tetrahedron Lett. 1981, 22(25), 2361.
(8) (a) Griffith, W. P. Chem. Soc. Rev. 1992, 21, 179. (b) Bailey, A.
J .; Cother, L. D.; Griffith, W. P.; Hankin, D. M. Transition Met. Chem.
1995, 20, 590.
(9) (a) Griffith, W. P.; Ley, S. V.; Whitcombe, G. P.; White, A. D. J .
Chem. Soc., Chem. Commun. 1987, 1625. (b) Ley, S. V.; Norman, J .;
Griffith, W. P.; Marsden, S. P. Synthesis 1994, 639.
(10) Cheng, W.-C.; Fung, W.-H.; Che, C.-M. J . Mol. Catal. (A) 1996,
113, 311.
S0022-3263(97)01892-6 CCC: $15.00 © 1998 American Chemical Society
Published on Web 04/04/1998

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2874 J . Org. Chem., Vol. 63, No. 9, 1998
Fung et al.
Ta ble 1. Ru th en iu m -Ca ta lyzed Oxid a tion of P r im a r y Ben zyl a n d Allyl Alcoh ols to Ald eh yd es Usin g TBHP
Sch em e 1
benzaldehyde in 88% yield after stirring for 12 h at room
temperature (Table 1). The production of di-tert-butyl
peroxide due to decomposition of TBHP is negligible.
When 2 equiv of TBHP was used, at full benzyl alcohol
conversion, benzoic acid was formed as the major product
(benzaldehyde-to-benzoic acid ratio ) 40:60). Methylene
chloride is the solvent of choice. Complex 1 in acetone
showed a much reduced catalytic activity toward benzyl
alcohol oxidation by TBHP, whereas the reaction was
inhibited when carried out in methanol. Irrespective of
this, the reaction is unretarded by atmospheric moisture
and, therefore, can be conducted without the need of inert
atmosphere. The ruthenium-catalyzed reaction can be
conveniently scaled-up to oxidize 200 mmol of benzyl
alcohol to benzaldehyde without modification of the
procedure, such as slow addition of the oxidant or cooling
to 0 °C. With the use of 200 mmol of TBHP and 0.1 mol
% of 1 in methylene chloride, benzaldehyde was isolated
in 97% yield,11 and up to 700 catalyst turnovers were
achieved.
tions, i.e., 1 equiv of TBHP and 1 mol % Ru in CH2Cl2.
Addition of another 1 equiv of THBP to the reaction
mixtures would produce R,â-unsaturated acids in 95%
isolated yield. As previously noted, electron deficient
alkenes are poor substrates for the “[Cn*Ru] + tBuOOH”
system;10 therefore, no effective epoxidation of the CdC
bond of the R,â-unsaturated acids was observed upon
addition of further quantity of TBHP. It is worthy to
mention that geraniol (entry 6), which contains an
isolated trisubstituted CdC bond, can be oxidized to
geranial in 84% yield; yet no epoxidation products were
detected if only 1 equiv of TBHP was used. Oxidation of
primary aliphatic alcohols such as n-octanol is ineffective
by this Ru-catalyzed reaction, and the starting alcohols
are recovered.
Likewise secondary alcohols are converted to ketones
(Table 2) when treated with 1.2 equiv of TBHP in the
presence of 1 mol % Ru catalyst at slightly elevated
temperature (40 °C). Under such conditions, 1-phenyl-
ethanol and benzhydrol were efficiently oxidized to
acetophenone (entry 1) and benzophenone (entry 2),
respectively, as well as some aliphatic secondary alcohols
to their ketones (entries 4-8). Oxidation of cyclohexenol
afforded cyclohexenone selectively (entry 3); again addi-
tion of further quantity of TBHP did not lead to CdC
oxidation. Cyclic aliphatic alcohols (C4, C6, and C8) were
Primary allyl alcohols (entries 4-6) were all selectively
oxidized to corresponding aldehydes without oxidation of
the CdC bond or overoxidation to carboxylic acids when
subjecting the alcohols to the standard reaction condi-
(11) Benzyl alcohol was consumed by 70%, and benzaldehyde was
isolated in 97% yield based on the amount of alcohol consumed.

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Chemoselective Oxidation of Alcohols to Aldehydes and Ketones
J . Org. Chem., Vol. 63, No. 9, 1998 2875
Ta ble 2. Ru th en iu m -Ca ta lyzed Oxid a tion of Secon d a r y Alcoh ols to Keton es Usin g TBHP
Ta ble 3. Listin g of kr el a n d σ Va lu es for th e
Ru -Ca ta lyzed Oxid a tion of P a r a -Su bstitu ted Ben zyl
Alcoh ols
tuted benzyl alcohols (p-Y-C6H4CH2OH, Y ) MeO, Me,
H, F, Cl, and CF3), krel, were evaluated by monitoring
the reactions with gas chromatography (see Experimental
Section). Figure 1 depicts a linear correlation (R ) 0.994)
of log krel [krel ) k(p-Y-C6H4CH2OH)/k(C6H5CH2OH)] vs
substituent constants σ. The slope of the plot (F ) -0.47)
is much smaller than those (F ) -1.2 to -1.9)13 observed
in the stoichiometric benzyl alcohol oxidations by the
cationic dioxoruthenium(VI), [(N4)RuVIO2]2+, complexes
(N4 ) tertiary tetraamine macrocycles). This reveals that
the electronic substituent effect exhibited by the “[Cn*Ru]
+ tBuOOH” system is considerably less pronounced. On
the other hand, the correlation between the log krel values
with substituent constants σ+ is less satisfactory (R )
-0.94). This finding together with the small negative F
value argue against the involvement of carbocation
intermediates. The primary kinetic isotope effect (kH/
kD) for the Ru-catalyzed oxidation of benzyl alcohol and
benzyl alcohol-d7 has been found to be 4.8 (see Experi-
mental Section). Although this value indicates substan-
tial C-H bond cleavage on progressing to the transition
entry
Y
krel
σ
1
2
3
4
5
6
MeO
Me
H
F
Cl
1.38
1.24
1.00
0.93
0.78
0.58
-0.28
-0.14
0.00
+0.15
+0.24
+0.53
CF3
all selectively oxidized to the corresponding ketones
without formation of the ring opening products (entries
4-6), in contrast to the oxidation of cyclobutanol by
RuVIIO4 in which case 1-butanal is produced.12
-
The effect of para-substituents on the catalytic benzyl
alcohol oxidations has been investigated. The relative
rates for the catalytic oxidation of several para-substi-
(12) Lee, D. G.; Congson, L. N. Can. J . Chem. 1990, 68, 1774.
(13) (a) Che, C.-M.; Tang, W.-T.; Lee, W.-O.; Wong, K.-Y.; Lau, T.-
C. J . Chem. Soc., Dalton Trans. 1992, 1551. (b) Cheng, W.-C.; Yu, W.-
Y.; Li, C.-K.; Che, C.-M. J . Org. Chem. 1995, 60, 6840.

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2876 J . Org. Chem., Vol. 63, No. 9, 1998
Fung et al.
studies (small F value) and primary kinetic isotope effect
(small kH/kD) for the catalytic benzyl alcohol oxidations
do not warrant an oxoruthenium (OdRu) based mecha-
nism.
The observed small kH/kD value could be a manifesta-
tion of a free radical chain mechanism where tBuO• and/
or tBuOO• species are the active agents. Yet the reactive
intermediate generated from the “[Cn*Ru] + tBuOOH”
system can effect stereoselective epoxidation of unfunc-
tionalized alkenes (cis-alkenes f cis-epoxides),10 which
is characteristic of an “oxene” (two-electron oxidant)
species.19 The absence of di-tert-butyl peroxide, formed
by the homocoupling of tBuO• radicals, has also dis-
counted the possibility of a free radical chain mechanism.
This notion is further scrutinized by employing cumyl
hydroperoxide as a mechanistic probe, because once the
hydroperoxide yields cumyloxy radicals, it will undergo
facile â-scission to form acetophenone and a methyl
radical (Scheme 2).20 Under typical reaction conditions,
alcohol (1 mmol), cumyl hydroperoxide (1 mmol), and 1
(1 mol %) in methylene chloride, benzyl alcohol was
effectively converted to benzaldehyde in 91% yield at 74%
substrate conversion without the formation of acetophe-
none. This strongly supports that the “[Cn*Ru] +
tBuOOH” system should not operate via reactive alkoxy
radicals resulting from ruthenium-catalyzed TBHP de-
composition analogous to Fenton-type chemistry.
Sch em e 2
F igu r e 1. Hammett correlation studies (log krel vs σ) for the
ruthenium-catalyzed oxidation of para-substituted benzyl al-
cohols by TBHP.
state, it is still far smaller than those found for the
stoichiometric benzyl alcohol oxidations by the cationic
cis-[Cn*RuVIO2(CF3CO2)]+ (kH/kD ) 17),14 [(N4)RuVIO2]2+
(kH/kD ) 15-21),13 and [(bpy)2(py)RuIVO]2+ (py ) pyridine)
complexes (kH/kD ) 50).15
The mechanistic findings have led us to propose a
reactive tert-butylperoxoruthenium species, Ru-OOt-
Bu,21 as the active intermediate for the ruthenium-
catalyzed TBHP oxidation of alcohols, although no de-
finitive structural assignment (e.g. monomeric vs bridging
dimer) can be made. Reports on peroxo complexes for
early transition metals are numerous,22 and the synthetic
values of some peroxo complexes of Ti(IV), V(V), and
Mo(VI) have been well documented in the literature.23
On the contrary, reactive peroxoruthenium complexes are
relatively sparse, and studies on their synthetic utilities
in organic oxidations24 are largely in its infancy. None-
The action of H2O2 on some [(N4)RuIII(H2O)2]3+ com-
plexes has afforded the dioxoruthenium(VI), [(N4)-
RuVIO2]2+, complexes16 some of which have been charac-
terized by X-ray crystallography.16c Their OdRuIV/RuV
derivatives can undertake electrocatalytic oxidation of
benzyl alcohols.17 cis-[Cn*RuVIO2(CF3CO2)]+ complex was
hitherto prepared by Ce(IV) oxidation of 1 in 0.1 M CF3-
CO2H, and its structure was established by X-ray crys-
tallography.18 However, the UV/vis spectra of 1 in the
presence of excess H2O2 or TBHP lack any distinctive
features in 300-700 nm range, as opposed to cis-
[Cn*RuVIO2(CF3CO2)]+ complex which shows intense
absorption at ca. 340 nm (ꢀ ) 2400) and a weak absorp-
tion at ca. 695 nm (ꢀ ) 50) in 1 M CF3CO2H. Apparently,
the dioxoruthenium(VI) complex is not generated on
treatment with excess peroxides under ambient condi-
tion. Furthermore, results from Hammett correlation
(19) Kamaraj, K.; Bandyopadhyay, D. J . Am. Chem. Soc. 1997, 119,
8099.
(20) Snelgrove, D. W.; MacFaul, P. A.; Ingold, K. U.; Wayner, D. D.
M. Tetrahedron Lett. 1996, 37(6), 823.
(21) A hydroperoxoiron(III) species has recently been demonstrated
as the active form of bleomycin which is an antitumor drug capable of
oxidizing DNA, see: (a) Sam, J . W.; Tang, X.-J .; Peisach, J . J . Am.
Chem. Soc. 1994, 116, 5250. (b) Sam, J . W.; Tang, X.-J .; Magliozzo, R.
S.; Peisach, J . J . Am. Chem. Soc. 1995, 117, 1012. (c) Westre, T. E.;
Loeb, K. E.; Zaleski, J . M.; Hedman, B.; Hodgson, K. O.; Solomon, E.
I. J . Am. Chem. Soc. 1995, 117, 1309.
(22) Conte, V.; Di Furia, F.; Modena, G. In Organic Peroxides; Ando,
W., Ed.; J ohn Wiley and Sons: New York, 1992; p 559 and references
therein.
(14) Fung, W.-H. Ph.D. Thesis, The University of Hong Kong, 1998.
(15) Roecker, L.; Meyer, T. J . J . Am. Chem. Soc. 1987, 109, 746.
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Synthesis; Ojima, I., Ed.; VCH: New York, 1993; p 103. (b) Mimoun,
H. In Comprehensive Coordination Chemistry; Wilkinson, G., Gillard,
R. D., McCleverty, J . A., Eds.; Pergamon: Oxford, 1987; Vol. 6, p 317.
(24) Murahashi, S.-I. Angew. Chem., Int. Ed. Engl. 1995, 34, 2443.
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M. C.; Valerga, P. J . Chem. Soc., Dalton Trans. 1996, 377. (c) Lindner,
E.; Haustein, M.; Fawzi, R.; Steinmann, M.; Wegner, P. Organome-
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