Regioselective alkene carbon-carbon bond cleavage to aldehydes and chemoselective alcohol oxidation of allylic alcohols with hydrogen peroxide catalyzed by [cis-Ru(II)(dmp)2(H2O)2] 2+ (dmp = 2,9-dimethylphenanthroline)

Article abstract of DOI:10.1021/ol052025e

(Chemical Equation Presented) [cis-Ru(II)(dmp)₂(H ₂O)₂]²⁺ (dmp = 2,9-dimethylphenanthroline) was found to be a selective oxidation catalyst using hydrogen peroxide as oxidant. Thus, primary alkenes were very efficiently oxidized via direct carbon-carbon bond cleavage to the corresponding aldehydes as an alternative to ozonolysis. Secondary alkenes were much less reactive, leading to regioselective oxidation of substrates such as 4-vinylcyclohexene and 7-methyl-1,6-octadiene at the terminal position. Primary allylic alcohols were chemoselectively oxidized to the corresponding allylic aldehydes, e.g., geraniol to citral.

Full text of DOI:10.1021/ol052025e

ORGANIC
LETTERS
2005
Vol. 7, No. 22
5039-5042
Regioselective Alkene Carbon−Carbon
Bond Cleavage to Aldehydes and
Chemoselective Alcohol Oxidation of
Allylic Alcohols with Hydrogen Peroxide
+
Catalyzed by [cis-Ru(II)(dmp)2(H2O)2]2
(dmp
) 2,9-dimethylphenanthroline)
Vladimir Kogan, Miriam M. Quintal, and Ronny Neumann*
Department of Organic Chemistry, Weizmann Institute of Science,
RehoVot, Israel, 76100
ronny.neumann@weizmann.ac.il
Received August 22, 2005
ABSTRACT
+
[cis-Ru(II)(dmp)2(H2O)2]2 (dmp
)
2,9-dimethylphenanthroline) was found to be a selective oxidation catalyst using hydrogen peroxide as
carbon bond cleavage to the corresponding aldehydes as an
oxidant. Thus, primary alkenes were very efficiently oxidized via direct carbon
−
alternative to ozonolysis. Secondary alkenes were much less reactive, leading to regioselective oxidation of substrates such as 4-vinylcyclohexene
and 7-methyl-1,6-octadiene at the terminal position. Primary allylic alcohols were chemoselectively oxidized to the corresponding allylic aldehydes,
e.g., geraniol to citral.
The use of hydrogen peroxide as an intrinsically environ-
mentally benign oxidant has in recent years attracted
considerable research attention in both the academic and
industrial communities. One way to characterize this flurry
of activity can be to differentiate between reactions by the
type of reactive intermediate species formed and the ensuing
mechanism of the oxygen transfer reaction. Probably the
largest body of research deals with catalysis by high-valent
metal compounds, predominantly Ti(IV), V(V), Mo(VI),
W(VI), and Re(VII), that have in common the formation of
reactive intermediate peroxo and/or hydroperoxo species.1
A smaller but still significant body of research deals with
the formation of high-valent metal-oxo species, mostly of
Fe, Mn, Os, and Ru, and their use as reactive oxygen transfer
agents.2 These metal-oxo species are accessible through a
variety of mono-oxygen donors including only in relatively
few cases hydrogen peroxide. Often these types of metal
complexes have relatively high redox potentials and so tend
to considerably dismutate hydrogen peroxide; hydroxy and
hydroperoxy radicals formed during the decomposition may
lead to nonselective transformations.
(1) (a) Ku¨hn, F. E.; Scherbaum, A.; Herrmann, W. A. J. Organomet.
Chem. 2004, 689, 4149. (b) Jost, C.; Wahl, G.; Kleinhenz, D.; Sundermeyer,
J. Peroxide Chem. 2000, 341. (c) Sanderson, W. R. Pure Appl. Chem. 2000,
72, 1289. (d) Conte, V.; di Furia, F.; Licini, G. Appl. Catal., A 1997, 157,
335. (e) Adam, W.; Mitchell, C. M.; Saha-Mu¨ller, C. R.; Weichold, O.
Struct. Bonding 2000, 97, 237.
10.1021/ol052025e CCC: $30.25
© 2005 American Chemical Society
Published on Web 09/28/2005

Oxidative alkene carbon-carbon bond cleavage reactions,
classically carried out by ozonolysis or with permanganate,
can be performed also catalytically with RuO4/NaOCl, RuO4/
Scheme 1. Formation of [cis-Ru(VI)(dmp)2(O)2]2+ from
[cis-Ru(II)(dmp)2(H2O)2]2+ with Hydrogen Peroxide
-
IO4 or with OsO4/oxone3 and using peroxotungstate com-
plexes with H2O2 under relatively strongly acidic conditions.4
Related cis-dihydroxylation of alkenes, usually performed
5
with OsO4 in the presence of various oxidants, has also been
observed with some Fe, Ru, Mn, and Re complexes.6 The
Os-, Ru-, Mn-, and Re-based complexes seem to have in
common the formation of reactive metal dioxo intermediates
and probably react via 3 + 2 addition of the dioxo species
to the alkene. Carbon-carbon bond cleavage with peroxo-
tungstates appears to occur sequentially: epoxidation, hy-
drolysis to the trans-diol, and oxidation of the vicinal alcohol
by the peroxotungstates.
To the best of our knowledge highly regioselective C-C
bond cleavage of alkenes favoring less nucleophilic double
bonds has never been reported, although such regioselective
epoxidation has been observed in few instances.7
reacted easily with 1-octene to yield n-heptanal. This unusual
reactivity profile of [cis-Ru(VI)(dmp)2(O)2]2+ led us to
explore the catalytic properties of [cis-Ru(II)(dmp)2(H2O)2]2+
with hydrogen peroxide as oxidant. In lieu of a crystal
structure of [cis-Ru(VI)(dmp)2(O)2]2+, a computer-generated
structure via DFT calculation, Figure 1 (see Supporting
About a decade ago Drago and co-workers8 reported on
the oxidation of [cis-Ru(II)(dmp)2(H2O)2]2+ (dmp ) 2,9-
dimethylphenanthroline)9 with hydrogen peroxide to the cis-
ruthenium(VI)dioxo species, [cis-Ru(VI)(dmp)2(O)2]2+, via
the intermediate [cis-Ru(IV)(dmp)2O(H2O)]2+ (Scheme 1).10,11
Our initial studies with [cis-Ru(VI)(dmp)2(O)2]2+ showed
that it reacted very poorly with cyclohexene but surprisingly
(2) (a) McLain, J. L.; Lee, J.; Groves, J. T. In Biomimetic Oxidations
Catalyzed by Transition Metal Complexes; Meunier, B., Ed.; Imperial
College Press: London, 2000; pp 91. (b) Meunier, B. Chem. ReV. 1992,
92, 1411. (c) Brinksma, J.; de Boer, J. W.; Hage, R.; Feringa, B. L. Modern
Oxidation Methods; Ba¨ckvall, J. E., Ed.; Wiley-VCH: Weinheim, Germany,
2004; p 295.
(3) (a) Sica, D. Recent Res. DeV. Org. Chem 2003, 7, 105. (b) Courtney,
J. L. Organic Synthesis and Oxidation with Metal Compounds; Mijs, W.
J., Cornelis, R. H. I., Eds.; Plenum: New York, 1986; p 445. (c) Travis, B.
R.; Narayan, R. S.; Borhan, B. J. Am. Chem. Soc. 2002, 124, 3824-3825.
(4) (a) Antonelli, E.; D’Aloisio, R.; Gambaro, M.; Fiorani, T.; Venurello,
C. J. Org. Chem. 1998, 63, 7190. (b) Haimov, A.; Cohen, H.; Neumann,
R. J. Am. Chem. Soc. 2004, 126, 11762.
(5) (a) Beller, M.; Sharpless, K. B. Applied Homogeneous Catalysis with
Organometallic Compounds, 2nd ed.; Cornils, B., Herrmann, W. A., Eds.;
Wiley-VCH: Weinheim, Germany, 2002; Vol. 3, p 1149. (b) Donohoe, T.
J. Synlettt 2002, 1223. (c) Severeyns, A.; de Vos, D. E.; Jacobs, P. A. Top.
Catal. 2002, 19, 125. (d) Sundermeier, U.; Do¨bler, C.; Beller, M. Modern
Oxidation Methods; Ba¨ckvall, J. E., Ed.; Wiley-VCH: Weinheim, Germany,
2004; p 1.
(6) (a) Brinksma, J.; Schmieder, L.; van Vleit, G.; Boaron, R.; Hage,
R.; de Vos, D. E.; Alsters, P. L.; Feringa, B. L. Tetrahedron Lett. 2002,
43, 2619. (b) de Vos, D. E.; de Wildeman, S.; Sels, B. F.; Grobet, P. J.;
Jacobs, P. A. Angew. Chem., Int. Ed. 1999, 38, 980. (c) Fujita, M.; Costas,
M.; Que, L. J. Am. Chem. Soc. 2003, 125, 9912. (d) Costas, M.; Que, L.
Angew. Chem., Int. Ed. 2002, 41, 2179. (e) Ryu, J. Y.; Kim, J.; Costas, M.;
Chen, K.; Nam, W.; Que, L. Chem. Commun. 2002, 1288. (f) Costas, M.;
Tipton, A. K.; Chen, K.; Jo, D. H.; Que, L. J. Am. Chem. Soc. 2001, 123,
6722. (g) Herrmann, W. A.; Marz, D.; Herdtweck, E.; Scha¨fer, A.; Wagner,
W.; Kneuper, H.-J. Angew. Chem., Int. Ed. Engl. 1987, 26, 462. (h) Shing,
T. K. M.; Tai, V. W.-F.; Tam, E. K. W. Angew. Chem., Int. Ed. Engl.
1994, 33, 2312. (i) Shing, T. K. M.; Tam, E. K. W.; Tai, V. W.-F.; Chung,
I. H. F.; Jiang, Q. Chem. Eur. J. 1996, 2, 50.
Figure 1. CPK representation of the computer-generated structure
of [cis-Ru(VI)(dmp)2(O)2]2+: Ru ) green, N ) blue, C ) black,
O ) red, H ) pink.
Information for computational details), showed that the
methyl substituents on phenanthroline highly masked the
oxygen ligands and lent credibility to a hypothesis that [cis-
Ru(VI)(dmp)2(O)2]2+ may, in fact, be a regioselective
oxidant.
The oxidation of a series of alkenes and dienes with
aqueous hydrogen peroxide catalyzed by [cis-Ru(II)(dmp)2-
(H2O)2]2+ is presented in Table 1.
As may be observed from Table 1, the [cis-Ru(II)(dmp)2-
(H2O)2]2+/H2O2 system is highly regioselective for the
oxidative cleavage of alkenes to aldehydes with a relative
reactivity of 1-octene > 2-methyl-1-heptene . trans-2-
octene . 2-methyl-2-heptene and styrene > â-methylstyrene.
Importantly, this relative reactivity leads to the highly
selective oxidation of 1,4-hexadiene, 7-methyl-1,6-octadiene,
4-vinylcyclohexene, and limonene at the terminal alkene
position. A very unusual phenomenon that was observed was
the reduced reactivity of 4-vinylcyclohexene and limonene
compared to vinylcyclohexane, which is as reactive as
(7) (a) Suslick, K. S.; Cook, B. R. J. Chem. Soc., Chem. Commun. 1987,
200. (b) Ahn, K. H.; Groves, J. T. Bull. Korean Chem. Soc. 1994, 15, 957.
(c) Lai, T.; Lee, S. K.; Yeung, L.; Liu, H.; Williams, I. D.; Chang, C. K.
Chem. Commun. 2003, 620. 7(d) Kamata, K.; Nakagawa, Y.; Yamaguchi,
K.; Mizuno, N. J. Catal. 2004, 224, 224. 7(e) Groves, J. T.; Neumann, R.
J. Am. Chem. Soc. 1987, 109, 5045.
(8) (a) Goldstein, A. S.; Beer, R. H.; Drago, R. S. J. Am. Chem. Soc.
1994, 116, 2424. (b) Goldstein, A. S.; Drago, R. S. J. Chem. Soc., Chem.
Commun. 1991, 218. (c) Bailey, C. L.; Drago, R. S. J. Chem. Soc., Chem.
Commun. 1987, 179.
(10) The [cis-Ru(II)(dmp)2(H2O)2]2+ compound was prepared with a PF6
counteranion.
(11) We were also able to confirm, by ESI-MS, the formation of [cis-
Ru(IV)(dmp)2(O)(Cl)]1+ and then [cis-Ru(VI)(dmp)2(O)2]2+ from the
dichloro precursor [cis-Ru(II)(dmp)2(Cl)2]. Peaks attributable to the mo-
lecular clusters were observed at m/z ) 559 and 550, respectively.
(9) Collin, J. P.; Sauvage, J. P. Inorg. Chem. 1986, 25, 135.
5040
Org. Lett., Vol. 7, No. 22, 2005

equiv of H2O2 are expended on a reaction that requires 3
equiv of H2O2); and (c) the only products observable in the
oxidation of cyclohexene as substrate are 2-cyclohexen-1-
ol (34%) and 2-cyclohexen-1-one (66%) at a ∼5 mol %
conversion under reaction conditions noted in Table 1. Such
allylic oxidation products are also observable as minor
byproducts in the oxidation of 4-vinylcyclohexene and
limonene.
Table 1. Oxidatione of Alkenes and Dienes with 30% H2O2
Catalyzed by [cis-Ru(II)(dmp)2(H2O)2]2+
conversion, selectivity,
substrate
1-octene
1-heptene
1-hexene
product
n-heptanal
n-hexanal
n-pentanal
n-hexanal
2-heptanone
no product
mol %
mol %
80
85
95
18
73
>99
>99
>99
>99
>99
It should be noted that trace amounts of epoxide formed
in most of the reactions are not intermediate products on
the way to the formation of the cleaved oxidation products;
both octene oxide and 1,2-octanediol are completely inert
under reaction conditions. It is likely that the additional
mono-oxo intermediate species, [cis-Ru(IV)(dmp)2(H2O)-
(O)]2+, also formed in the [cis-Ru(II)(dmp)2(H2O)2]2+/H2O2
system is the species responsible for epoxide formation.7 In
fact, when the reaction was carried out in methanol as a
coordinating solvent (1 M 1-octene, 0.01 M [cis-Ru(II)-
(dmp)2(H2O)2]2+ in methanol at 55 °C; 10 equiv of 30% H2O2
added in 10 portions over 8 h), the product ratio was 62
mol % 1-octene oxide and 38 mol % heptanal and its
hemiacetal. Notable also is the observation that when the
reaction is carried out in acetonitrile, no significant formation
of carboxylic acids was observed via further oxidation of
the aldehydes. However, if the reaction is carried out in
acetone, some acid is formed. For example, 1 M 1-octene
0.01 M [cis-Ru(II)(dmp)2(H2O)2]2+ in acetone at 55 °C with
addition of 10 equiv of 30% H2O2 in 10 portions over 8 h
yielded a product distribution of 78% heptanal and 22%
heptanoic acid at a 92% conversion. Finally, it is worth
pointing out that even electron-poor alkenes substituted with
electron-withdrawing groups at the allylic position (allyl
chloride, methylacrylate, and methyl methacrylate) were
moderately reactive and also yielded mostly products ema-
nating from C-C bond cleavage.
E-2-octene
2-Me-1-heptene
2-Me-2-heptene
1,4-hexadiene
7-Me-1,6-octadiene
vinylcyclohexane
3-pentenal
84
87
88
90a
85b
99
6-Me-5-heptenal
cyclohexane-
carboxaldehyde
cyclohexene-4-
carboxaldehyde
4-acetyl-1-Me-
cyclohexene
4-vinylcyclohexene
limonene
21
11
97c
95c
styrene
benzaldehyde
benzaldehyde
2-chloroethanal
methylglyoxylate
92
71
60
37
21
>99
>99
78d
97
â-methylstyrene
allyl chloride
methylacrylate
methyl methacrylate methylpyruvate
92
a 10% reaction at both double bonds. b 15% selectivity to 7-methyl-6,7-
epoxy-1-octene. c the remaining products were ene-ols and ene-ones formed
on the cyclohexyl ring. d 22% epichlorohydrin. e Reaction conditions: 1
M substrate, 0.01 M [cis-Ru(II)(dmp)2(H2O)2]2+ in acetonitrile at 55 °C;
10 equiv of 30% H2O2 added in 10 portions over 8 h. Analysis was by GC
and GC-MS including use of reference standards when available and using
chlorobenzene (0.1 M) as internal standard (mass balance was 100 ( 5%).
It should be noted that the cleavage reaction at the terminal alkene moiety
led also to formation of formaldehyde (GC and NMR) and traces of formic
acid (GC).
1-octene. One possible but unproven explanation is that the
more nucleophilic cyclohexenyl moiety may preferably
interact with the [cis-Ru(VI)(dmp)2(O)2]2+ intermediate,
which does not, however, lead to C-C bond cleavage for
steric reasons. Some support for this idea may be drawn from
the observations that (a) addition of nonreactive 2-methyl-
2-heptene as a competitive substrate to reactive 1-octene
leads to inhibition of the oxidation of 1-octene (∼2%
conversion versus 55% with 1-octene alone after 3 h; reaction
conditions as in Table 1); (b) the lifetime of the [cis-Ru-
(VI)(dmp)2(O)2]2+ is limited; that is, the catalytic system
shows relatively significant H2O2 dismutation activity (10
Since less accessible double bonds are not oxidized using
the [cis-Ru(II)(dmp)2(H2O)2]2+/H2O2 catalytic system and
aldehyde oxidation to carboxylic acids can be prevented by
choice of solvent, it was recognized that primary allylic
alcohols may be chemoselectively oxidized to the corre-
sponding allylic aldehydes. Usually oxidation of primary
allylic alcohols with hydrogen peroxide is chemoselective
to reaction at the double bond because oxidation of primary
alcohols are more difficult; catalytic oxidation reactions at
Table 2. Oxidationd of Primary Allylic Alcohols with 30% H2O2 Catalyzed by [cis-Ru(II)(dmp)2(H2O)2]2+
substrate
product
conversion, mol %
selectivity, mol %
3-Me-2-buten-1-ol
trans-2-hexen-1-ol
cis-2-hexen-1-ol
cis-3,7-diMe-2,6-octadien-1-ol (nerol)
trans-3,7-diMe-2,6-octadien-1-ol (geraniol)
farnesolb
3-Me-2-butenal
trans-2-hexenal
cis-2-hexenal
cis-3,7-diMe-2,6-octadienal (neral)
trans-3,7-diMe-2,6-octadienal (geranial)
farnesalc
90
82
87
83
85
86
95
88a
81a
>99
>99
>99
a The remaining observed product was butanal. b Mixture of isomers 95% trans,trans- and trans,cis-3,7,10-trimethyl-2,6,10-dodecatrien-1-ol. c Mixture
of isomers 95% trans,trans- and trans,cis-3,7,10-trimethyl-2,6,10-dodecatrienal. d Reaction conditions 1 M substrate, 0.01 M [cis-Ru(II)(dmp)2(H2O)2]2+ in
acetonitrile at 55 °C; 15 equiv of 30% H2O2 added in 10 portions over 12 h. Analysis was by GC and GC-MS including use of reference standards when
available and using chlorobenzene (0.1 M) as internal standard (mass balance was 100 ( 5%).
Org. Lett., Vol. 7, No. 22, 2005
5041

the alcohol position are usually effected by use of other
oxidants, e.g., hypochlorite or molecular oxygen.12 In Table
2 are presented the results for the oxidation of a series of
primary allylic alcohols with aqueous hydrogen peroxide
catalyzed by [cis-Ru(II)(dmp)2(H2O)2]2+.
In summary, it was found that the known [cis-Ru(II)-
(dmp)2(H2O)2]2+ compound appears to have a hindered active
site. This led to the use of [cis-Ru(II)(dmp)2(H2O)2]2+ as a
regioslective catalyst for alkene carbon-carbon bond cleav-
age with hydrogen peroxide to form aldehydes with signfi-
cant preference for primary alkenes. This regioselectivity
manifested itself also in the chemoselective oxidation of
primary allylic alcohols to the corresponding allylic alde-
hydes.
From the results shown it Table 2, one may observe that
high to very high chemoselectivity was obtained in the
oxidation of primary allylic alcohols to the correspondinding
allylic aldehydes without loss of stereoselectivity at the
double bond positions. For allylic alcohols with more
hindered alkene moieties such as in geraniol, nerol, and
farnesol and to a slightly lesser degree for 3-methyl-2-buten-
1-ol, there was practically no carbon-carbon bond cleavage
observed. For less hindered double bonds such as those in
cis- and trans-2-hexen-1-ol, chemoselectivity was slightly
reduced (80-90%) and some butanal was formed. In the
oxidation of 1-octen-3-ol, as expected, there was only 50%
chemoselectivity to the ketone product. Further, recalling that
the double bond of cyclohexene is resistant to oxidation, the
oxidation of 2-cyclohexen-1-ol in fact only yielded 2-cyclo-
hexen-1-one as the observed product (97% conversion,
>98% selectivity. The regioselectivity observed in the simple
alkene oxidations was indeed translated to chemoselectivity
in the oxidation of primary allylic alcohols.
Acknowledgment. This research was supported by the
German Federal Ministry of Education and Research (BMBF)
within the framework of the German-Israeli Project Coopera-
tion (DIP) and the Helen and Martin Kimmel Center for
Molecular Design. M.M.Q. thanks the U.S.-Israel Educa-
tional Foundation for a Fulbright Fellowship. Jan M. L.
Martin is thanked for his aid in the computational studies.
R.N. is the Rebecca and Israel Sieff Professor of Organic
Chemistry.
Supporting Information Available: Experimental details
on the oxidation reactions and computational studies. This
material is available free of charge via the Internet at
http://pubs.acs.org.
(12) Arends, I. W. C. E.; Sheldon, R. A. Modern Oxidation Methods;
Ba¨ckvall, J. E., Ed.; Wiley-VCH: Weinheim, Germany, 2004; p 83.
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