Ruthenium-catalyzed redox isomerization/transfer hydrogenation in organic and aqueous media: A one-pot tandem process for the reduction of allylic alcohols

Article abstract of DOI:10.1039/b916117a

The hexamethylbenzene-ruthenium(ii) dimer [{RuCl(μ-Cl) (η⁶-C₆Me₆)}₂] 1 and the mononuclear bis(allyl)-ruthenium(iv) complex [RuCl₂(η ³:η²:η³-C₁₂H ₁₈)]2, associated with base and a hydrogen donor, were found to be active catalysts for the selective reduction of the CC bond of allylic alcohols both in organic and aqueous media. The process, which proceeds in a one-pot manner, involves a sequence of two independent reactions: (i) the initial redox-isomerization of the allylic alcohol, and (ii) subsequent transfer hydrogenation of the resulting carbonyl compound. The highly efficient transformation reported herein represents, not only an illustrative example of auto-tandem catalysis, but also an appealing alternative to the classical transition-metal catalyzed CC hydrogenations of allylic alcohols. The process has been successfully applied to aromatic as well as aliphatic substrates affording the corresponding saturated alcohols in 45-100% yields after 1.5-24 h. The best performances were reached using (i) 1-5 mol% of 1 or 2, 2-10 mol% of Cs₂CO₃, and propan-2-ol or (ii) 1-5 mol% of 1 or 2, 10-15 equivalents of NaO₂CH, and water. The catalytic efficiency is strongly related to the structure of the allylic alcohol employed. Thus, in propan-2-ol, the reaction rate essentially depends on the steric requirement around the CC bond, therefore decreasing with the increasing number of substituents. On other hand, in water the transformation is favoured for primary allylic alcohols vs. secondary ones.

Full text of DOI:10.1039/b916117a

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PAPER
www.rsc.org/greenchem | Green Chemistry
Ruthenium-catalyzed redox isomerization/transfer hydrogenation in
organic and aqueous media: A one-pot tandem process for the reduction
of allylic alcohols
Victorio Cadierno,* Pascale Crochet, Javier Francos, Sergio E. Garc´ıa-Garrido, Jose´ Gimeno* and
Noel Nebra
Received 5th August 2009, Accepted 11th September 2009
First published as an Advance Article on the web 16th October 2009
DOI: 10.1039/b916117a
6
The hexamethylbenzene-ruthenium(II) dimer [{RuCl(m-Cl)(h -C6Me6)}2] 1 and the mononuclear
3
2
3
bis(allyl)-ruthenium(IV) complex [RuCl2(h :h :h -C12H18)] 2, associated with base and a hydrogen
=
donor, were found to be active catalysts for the selective reduction of the C C bond of allylic
alcohols both in organic and aqueous media. The process, which proceeds in a one-pot manner,
involves a sequence of two independent reactions: (i) the initial redox-isomerization of the allylic
alcohol, and (ii) subsequent transfer hydrogenation of the resulting carbonyl compound. The
highly efficient transformation reported herein represents, not only an illustrative example of
auto-tandem catalysis, but also an appealing alternative to the classical transition-metal catalyzed
=
C C hydrogenations of allylic alcohols. The process has been successfully applied to aromatic as
well as aliphatic substrates affording the corresponding saturated alcohols in 45–100% yields after
1.5–24 h. The best performances were reached using (i) 1–5 mol% of 1 or 2, 2–10 mol% of Cs2CO3,
and propan-2-ol or (ii) 1–5 mol% of 1 or 2, 10–15 equivalents of NaO2CH, and water. The
catalytic efficiency is strongly related to the structure of the allylic alcohol employed. Thus, in
=
propan-2-ol, the reaction rate essentially depends on the steric requirement around the C C
bond, therefore decreasing with the increasing number of substituents. On other hand, in water
the transformation is favoured for primary allylic alcohols vs. secondary ones.
on ruthenium, rhodium and iridium complexes,4,5 where the
Introduction
hydride-metal entity can be both preformed prior to the catalytic
event or generated in situ. TH reactions are usually performed in
propan-2-ol which acts both as solvent and the hydrogen source,
acetone being formed along with the desired alcohol.
On the other hand, it has also been demonstrated that
transition-metal hydrides are able to promote the redox-
isomerization of allylic alcohols into the corresponding satu-
rated ketones or aldehydes.6 For this particular process, the
highest activities are, in general, reached using iron-, ruthenium-
and rhodium-based precursors.6,7
The development of new methodologies aimed at improving
the efficiency in organic synthesis is an important goal of
contemporary chemistry. In particular, the replacement of
multistep transformations by more straightforward “one-pot”
processes has attracted considerable research efforts due to the
obvious advantages of the latter, i.e. they minimize the overall
reaction time, the generation of chemical waste and the energy
consumption, therefore limiting the global cost of the synthetic
pathway.1 In this context, metal-catalyzed tandem reactions
have attracted an increasing interest during the last decade.2,3
These processes, which provide operationally simple synthetic
procedures, are based on the ability of a unique organometallic
precursor to promote two or more successive transformations in
the same reaction medium.
With these precedents in mind, it is reasonable to assume that
a hydride-metal species associated with an appropriate hydrogen
=
source, such as propan-2-ol, could be able to reduce the C C
bond of allylic alcohols through a two-step tandem process
involving: (i) the initial redox-isomerization of the substrate, and
(ii) the subsequent TH of the resulting carbonyl intermediate
(Scheme 1). The overall transformation represents an appealing
It is well-established that transition-metal hydrides are the ac-
tive catalytic species in transfer hydrogenation (TH) reactions,4
being able to efficiently reduce carbonyl compounds into the
corresponding alcohols. The best results, in terms of activity
and selectivity, have been reported for catalytic systems based
=
alternative to the classical transition-metal catalyzed C C
hydrogenations (Ru, Rh and Ir catalysts)8 since it avoids the
use of hydrogen gas, a hazardous and flammable reactant.
During the last years, the increasing awareness of environmen-
tal concerns has stimulated the development of metal-catalyzed
reactions in aqueous media, since water represents the most
benign and inexpensive solvent known.9 In this context, it has
been largely demonstrated that the two individual processes
considered in Scheme 1, i.e. the redox-isomerization and the TH
Departamento de Qu´ımica Orga´nica e Inorga´nica, Instituto Universitario
de Qu´ımica Organometa´lica “Enrique Moles” (Unidad Asociada al
CSIC), Universidad de Oviedo, Julia´n Claver´ıa 8, 33006, Oviedo, Spain.
E-mail: vcm@uniovi.es, jgh@uniovi.es; Fax: +(34)985103446;
Tel: +(34)985102985
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Table 1 Metal catalyzed reduction of 1-octen-3-ol in propan-2-ol and
in the presence of Cs2CO3.a
Scheme 1 Reduction of allylic alcohols through an isomerization/TH
tandem process using propan-2-ol as solvent and hydrogen donor.
Entry Catalyst precursor
Time Conv.
Yieldb
6
1
2
3
4
[{RuCl(m-Cl)(h -C6Me6)}2] 1
3.5 h > 99%
99%
95%
91%
75%
92%
35%
26%
16%
1%
steps, can be efficiently performed under aqueous conditions.10,11
So, potentially, the planned tandem reduction of allylic alcohols
could also be operative in water.
6
[{RuCl(m-Cl)(h -mesitylene)}2]
6 h
9 h
9 h
9 h
9 h
9 h
9 h
9 h
9 h
9 h
9 h
9 h
9 h
9 h
9 h
9 h
9 h
9 h
9 h
9 h
9 h
9 h
9 h
9 h
9 h
9 h
> 99%
> 99%
> 99%
> 99%
> 99%
> 99%
> 99%
> 99%
> 99%
> 99%
98%
> 99%
> 99%
> 99%
> 99%
> 99%
> 99%
0%
> 99%
0%
96%
36%
29%
64%
1%
> 99%
6
[{RuCl(m-Cl)(h -p-cymene)}2]
6
[{RuCl(m-Cl)(h -C6H6)}2]
5
[RuCl2(PPh3)3]
In this article, full details of our search for efficient catalysts
for this tandem process are presented.12,13 In particular, among
the different metal precursors checked, excellent results in terms
of activity, selectivity and scope have been reached with the
6c
[Ru(h -2-C3H4Me)2(cod)]
3
7c
[{RuCl2(cod)}n]
8
9
[RuCl2(DMSO)4]
5
[RuCl(h -C5H5)(PPh3)2]
[RuCl(h -C9H7)(PPh3)2]
5
10
11
12
13d
14e
15
16c
17f
18g
19
20c
21
22h
23
24
25c
26
27
4%
3%
2%
6
dinuclear hexamethylbenzene-Ru(II) complex [{RuCl(m-Cl)(h -
RuCl3·nH2O
C6Me6)}2] 1 and the mononuclear bis(allyl)-Ru(IV) derivative
[Ru3(CO)12]
3
2
3
3
2
3
[RuCl2(h :h :h -C12H18)] 2 (see Fig. 1).
[RuCl2(h :h :h -C12H18)] 2
94%
86%
8%
21%
20%
18%
0%
15%
0%
6%
4%
2%
7%
0%
3
3
[{RuCl(m-Cl)(h :h -C10H16)}2]
RhCl3·nH2O
[{Rh(m-Cl)(cod)}2]
[{Rh(m-Cl)(nbd)}2]
[{Rh(m-Cl)(coe)2}2]
[NH4]2[IrCl6]
[{Ir(m-Cl)(cod)}2]
[Pd(PPh3)4]
[Pd2(dba)3]
PdCl2
Pd(OAc)2
[PdCl2(cod)]
[PdCl2(PPh3)2]
PtCl2
Fig. 1 Structure of the ruthenium catalysts 1 and 2.
10%
a Reactions performed under N2 atmosphere at 82 ◦C using 2 mmol of
1-octen-3-ol (0.1 M in propan-2-ol). [Substrate] : [M] : [Cs2CO3] ratio =
100 : 1 : 2. b Yield of octan-3-ol determined by GC. The differences
between conversion and octan-3-ol yield correspond to the intermediate
octan-3-one present in the reaction media. c cod = 1,5-cyclooctadiene.
d C12H18 = dodeca-2,6,10-triene-1,12-diyl. e C10H16 = 2,7-dimethylocta-
2,6-diene-1,8-diyl. f nbd = norbornadiene. g coe = cyclooctene. h dba =
dibenzylideneacetone.
Results and discussion
Reduction of allylic alcohols in organic medium: Catalyst
screening and scope
Firstly, using the reduction of 1-octen-3-ol into octan-3-ol
as a model reaction, the efficiency and selectivity of several
commercially available or readily accessible metallic precursors
was checked. Experiments were performed at 82 ◦C employing
2 mmol of substrate, 1 mol% of metal, 2 mol% of Cs2CO314 and
propan-2-ol (0.1 M solutions of the allylic alcohol) as solvent
and hydrogen source (see Table 1). Under these conditions, all
of the precursors tested, with the exception of [NH4]2[IrCl6]
(entry 19), [Pd(PPh3)4] (entry 21), PdCl2 (entry 23), Pd(OAc)2
(entry 24), [PdCl2(cod)] (entry 25) and [PdCl2(PPh3)2] (entry 26),
led to the almost total consumption of the substrate after 9 h
of heating (≥96% conversion; GC determined). However, the
selectivity of the process was found to be strongly dependent on
the nature of the catalyst employed. Thus, only the arene-Ru(II)
quantities of octan-3-ol being in these cases detected by GC
(≤ 35%).
From this general catalyst screening, ruthenium clearly
emerged as the metal of choice, with the hexamethylbenzene-
6
Ru(II) dimer [{RuCl(m-Cl)(h -C6Me6)}2] 1 leading to the best
results in terms of both activity and selectivity (99% GC yield
of octan-3-ol after only 3.5 h; entry 1).15 Although related
6
[{RuCl(m-Cl)(h -arene)}2] dimers were also active in the tandem
reduction process, their efficiency and selectivity were lower,
decreasing with the donor capacity of the arene ligand, i.e. in
the order C6Me6 > mesitylene, p-cymene > C6H6 (entries 1–4).
As far as Ru(IV) is concerned, the mononuclear deriva-
6
dimers [{RuCl(m-Cl)(h -arene)}2] (arene = C6Me6, mesitylene,
p-cymene, C6H6; entries 1–4), the mononuclear Ru(II) complex
[RuCl2(PPh3)3] (entry 5), and the bis(allyl)-Ru(IV) derivatives
3
2
3
3
3
3
2
3
[RuCl2(h :h :h -C12H18)] and [{RuCl(m-Cl)(h :h -C10H16)}2] (en-
tries 13–14), afforded the desired reduced alcohol as the major
product (≥75% GC yield). In contrast, the rest of ruthenium
precatalysts, as well as the rhodium, iridium, palladium and
platinum ones, gave rise preferentially to the intermediate
carbonyl compound octan-3-one, the formation of only small
tive [RuCl2(h :h :h -C12H18)] 2 was found to be more active
(94% GC yield after 9 h, entry 13) than the dimeric one
3
3
[{RuCl(m-Cl)(h :h -C10H16)}2] (86% GC yield after 9 h, entry
14). Remarkably, although these ruthenium(IV) complexes are
among the most active catalysts presently known for the redox-
isomerization of allylic alcohols,10f–h,16 they were less efficient
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6
Table 2 Reduction of monosubstituted allylic alcohols catalyzed by
than [{RuCl(m-Cl)(h -C6Me6)}2] 1 in the reduction of 1-octen-
6
3
2
3
complexes [{RuCl(m-Cl)(h -C6Me6)}2] 1 and [RuCl2(h :h :h -C12H18)] 2
3-ol (entries 13–14 vs. entry 1). This fact clearly indicates that
the TH of the intermediate carbonyl compound is the rate
limiting step of the tandem reduction process. In accord with
this, monitoring the reduction of 1-octen-3-ol catalyzed by
in propan-2-ol and in the presence of Cs2CO3.a
6
[{RuCl(m-Cl)(h -C6Me6)}2] 1 by GC (see Fig. 2) showed that
Entry
R
Cat.
% Ru
Time
Conv.
Yieldb
the initial isomerization step readily takes place (ca. 15 min).
In contrast, the evolution of the intermediate octan-3-one into
the final saturated alcohol is very slow (3.5 h are required to
obtain a quantitative yield of the desired octan-3-ol). A similar
tendency was also observed with the rest of the ruthenium
catalysts employed.17
1
2
3
4
5
6
7
8
H
1
2
1
2
1
2
1
2
1
2
1
2
1
2
1
2
1
2
1
2
1
2
1
2
1 mol%
1 mol%
1 mol%
1 mol%
1 mol%
1 mol%
1 mol%
1 mol%
1 mol%
1 mol%
1 mol%
1 mol%
1 mol%
1 mol%
1 mol%
1 mol%
2 mol%
2 mol%
2 mol%
2 mol%
2 mol%
5 mol%
5 mol%
5 mol%
5.5 h >99%
8 h >99%
5.5 h >99%
5.5 h >99%
99%
98%
98%
99%
97%
93%
99%
93%
97%
91%
98%
98%
97%
99%
90%
83%
99%
99%
99%
98%
99%
99%
98%
99%
Me
Et
3 h
>99%
8.5 h >99%
3.5 h >99%
8.5 h >99%
nPr
9
nBu
3 h
9 h
>99%
>99%
>99%
>99%
>99%
>99%
>99%
>99%
>99%
>99%
>99%
10
11
12
13
14
15c
16
17
18
19
20
21
22
23
24
Bn
22 h
24 h
10 h
23 h
22 h
24 h
15 h
6 h
Ph
4-C6H4OMe
3-C6H4OMe
4-C6H4F
4-C6H4Cl
2-Furanyl
24 h
8.5 h >99%
24 h
4 h
5 h
>99%
>99%
>99%
3.5 h >99%
a Reactions performed under N2 atmosphere at 82 ◦C using 2 mmol of
the corresponding allylic alcohol (0.1 M in propan-2-ol). [Ru] : [Cs2CO3]
ratio = 1 : 2. b Yield of the saturated alcohol determined by GC. The
differences between conversion and yield correspond to the intermediate
carbonyl compound present in the reaction media. c ca. 8% of 1-
methoxy-4-propylbenzene is also formed.
Fig. 2 Product distribution as a function of time for the reduction of
1-octen-3-ol catalyzed by complex 1 (1 mol% of Ru).
In order to investigate the scope of this new catalytic
transformation, the reduction of a broad array of allylic alcohols
was studied using the most active Ru(II) and Ru(IV) catalysts,
6
3
2
3
i.e. [{RuCl(m-Cl)(h -C6Me6)}2] 1 and [RuCl2(h :h :h -C12H18)] 2.
substrate is probably associated to the competitive coordination
of the furyl and olefin units onto the active ruthenium species.
Remarkably, catalysts 1 and 2 were also able to promote
the double reduction of the bis(allylic alcohol) 3, affording
1,3-bis(1-hydroxypropyl)benzene 4 in more than 72% GC-yield
(Scheme 2). Solvent removal and chromatographic work-up on
silica-gel allowed the isolation of pure samples of 4 (88% and
60% yield) whose identity was confirmed by NMR spectroscopy
and MS fragmentation.18
The results obtained are collected in Tables 2–3 and Scheme 2.
Scheme 2 Reduction of 3 catalyzed by complexes 1 and 2 in organic
medium.
Although disubstituted and trisubstituted allylic alcohols
could also be reduced efficiently by the action of complexes 1 and
2, in these cases longer reaction times and higher Ru loadings
(3–5 mol%) were required to generate the corresponding sat-
urated alcohols in good yields (see Table 3). In fact, only the
reduction of trans-3-penten-2-ol (entries 7–8) and 2-methyl-2-
propen-1-ol (entries 17–18), both containing the less sterically
Although all the substrates tested could be conveniently
transformed into the corresponding saturated alcohols (GC
yields ≥ 83%), the catalytic performances of compounds 1 and
2 were found to be strongly dependent on the substitution
degree of the carbon–carbon double bond of the allylic alcohol
employed. Thus, as a general trend, the efficiency of the
isomerization/TH tandem process decreased with the increase
=
demanding methyl group as substituent on the C C bond,
=
of the number of substituents on the C C unit, a tendency
could be conveniently performed using a ruthenium loading of
1 mol%. The lower reactivity of these di- and tri-substituted
substrates stems from a drastic rate decrease in the initial
isomerization step due to the sterically disfavoured coordination
commonly observed in catalytic redox-isomerization reactions.6
Concerning the monosubstituted allylic alcohols (Table 2), as
observed for 1-octen-3-ol, they were readily reduced in almost
quantitative yields using low ruthenium loadings (1–2 mol% of
Ru; entries 1–21 in Table 2). Only the reduction of 1-(furan-
2-yl)-2-propen-1-ol required a higher catalyst loading (5 mol%
of Ru; entries 23–24 in Table 2). The lower reactivity of this
of the C C bond to ruthenium.19 This situation is exemplified in
=
Fig. 3 which shows the reaction course (GC-monitoring) for the
reduction of 2-cyclohexen-1-ol into cyclohexanol promoted by
3
2
3
complex [RuCl2(h :h :h -C12H18)] 2 (5 mol%). In this case, the
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=
Table 3 Reduction of allylic alcohols containing substituted C
C
1 and
Table 3 (Contd.)
6
bonds catalyzed by complexes [{RuCl(m-Cl)(h -C6Me6)}2]
3
2
3
[RuCl2(h :h :h -C12H18)] 2 in propan-2-ol and in the presence of
Cs2CO3.a
Entry Substrate
29
Cat. % Ru
Time
24 h
Conv.
Yieldb
97%
1
5 mol%
>99%
Entry Substrate
1
Cat.
% Ru
Time
3.5 h
Conv.
Yieldb
99%
30
31
2
1
5 mol%
5 mol%
24 h
24 h
>99%
>99%
98%
90%
1
5 mol%
>99%
2
3
2
1
5 mol%
5 mol%
4 h
3 h
>99%
>99%
97%
99%
32
2
5 mol%
23 h
96%
95%
a Reactions performed under N2 atmosphere at 82 ◦C using 2 mmol of
the corresponding allylic alcohol (0.1 M in propan-2-ol). [Ru] : [Cs2CO3]
ratio = 1 : 2. b Yield of the saturated alcohol determined by GC. The
differences between conversion and yield correspond to the intermediate
carbonyl compound present in the reaction media.
4
5
2
1
5 mol%
5 mol%
2.5 h
5 h
>99%
>99%
99%
79%
6
7
2
1
5 mol%
1 mol%
5 h
9 h
>99%
>99%
83%
97%
8
9
2
1
1 mol%
3 mol%
7 h
7.5 h
>99%
>99%
97%
97%
10
11
2
1
3 mol%
5 mol%
24 h
9 h
>99%
>99%
90%
90%
12
13
2
1
5 mol%
5 mol%
9 h
22 h
>99%
>99%
98%
91%
14
15
2
1
5 mol%
3 mol%
4 h
24 h
>99%
>99%
96%
99%
Fig. 3 Product distribution as a function of time for the reduction of
2-cyclohexen-1-ol catalyzed by complex 2 (5 mol% of Ru).
16
17
2
1
3 mol%
1 mol%
24 h
9 h
94%
>99%
90%
92%
transfer hydrogenation step is clearly faster than the initial redox
isomerization of the substrate, the proportion of the carbonyl
intermediate, i.e. cyclohexanone, present in the reaction medium
never exceeding 10%.
18
19
2
1
1 mol%
5 mol%
9 h
9 h
>99%
>99%
98%
98%
The chemoselectivity shown by both complexes in the re-
duction of geraniol (entries 29–30, Table 3) and nerol (entries
31–32) merits to be highlighted. Thus, although these com-
pounds present two carbon–carbon double bonds, only the
20
21
2
1
5 mol%
5 mol%
1.5 h
6 h
>99%
>99%
99%
96%
=
reduction of the C C in the a-position with respect to the
alcohol group takes place, affording citronellol selectively. These
results compete favourably with the poor selectivity usually
observed in classical metal-catalyzed hydrogenations of this type
of terpenoid, which in most cases give rise to reaction mixtures
containing the unsaturated- and saturated-alcohol as well as
cyclization products.20
22
23
2
1
5 mol%
5 mol%
4.5 h
9.5 h
>99%
>99%
99%
93%
24
25
2
1
5 mol%
5 mol%
7 h
9 h
>99%
>99%
94%
93%
It is also interesting to note that, in contrast to the tendency
observed with monosubstituted allylic alcohols (Table 2), the
3
2
3
mononuclear bis(allyl)-Ru(IV) complex [RuCl2(h :h :h -C12H18)]
2 was found to be more efficient than the Ru(II) dimer
26
27
2
1
5 mol%
5 mol%
7 h
5 h
>99%
>99%
96%
90%
6
[{RuCl(m-Cl)(h -C6Me6)}2] 1 for the reduction of di- and
trisubstituted substrates (Table 3). In fact, only in a limited
28
2
5 mol%
22 h
>99%
91%
number of examples, such as trans-2-buten-1-ol (entries 1 vs. 2),
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Table 4 Influence of the NaO2CH/substrate ratio in the reduction
trans-3-phenyl-2-propen-1-ol (entries 9 vs. 10), 2-cyclohexen-
1-ol (entries 15 vs. 16), and 3-methyl-2-buten-1-ol (entries 27
vs. 28), the catalytic performance of complex 1 surpassed that
of 2. So, it can be concluded that when the TH is the rate-
determining step of the tandem process, i.e. for the reduction
6
of trans-3-phenyl-2-propen-1-ol catalyzed by complex [{RuCl(m-Cl)(h -
C6Me6)}2] 1 in water.a
6
of monosubstituted allylic alcohols, complex [{RuCl(m-Cl)(h -
3
2
3
Yieldb
C6Me6)}2] 1 is more efficient than [RuCl2(h :h :h -C12H18)] 2,
Entry
[Substrate]
NaO2CH/substrate ratio
Time
otherwise the efficiency of both catalysts is inverted.
1
2
3
4
5
6
1 M
1 M
1 M
1 M
1 M
1 M
1 : 1
5 : 1
10 : 1
15 : 1
20 : 1
25 : 1
20 h
20 h
20 h
7 h
20 h
20 h
70%
99%
98%
99%
63%
60%
Catalytic reduction of allylic alcohols using water as solvent
6
The high stability of complexes [{RuCl(m-Cl)(h -C6Me6)}2] 121
3
2
3
and [RuCl2(h :h :h -C12H18)] 210f,h in water prompted us to
explore the isomerization/TH tandem process in an aqueous
medium (Scheme 3). The replacement of propan-2-ol by water
makes necessary the introduction of an additive that could act as
a hydrogen source. In this sense, the most popular reagent used
in metal-catalyzed transfer hydrogenation processes to carbonyl
compounds performed in water is sodium formate, which reacts
with the metal precursor in this media to form the active hydride
species and carbon dioxide.11 As a consequence of the drastic
experimental changes associated with the use of this reagent, a
preliminary study to determine the optimal reaction conditions
in aqueous media was necessary. To this end, the reduction of
trans-3-phenyl-2-propen-1-ol (5 mmol) catalyzed by complex
a Reactions performed under N2 atmosphere at 100 ◦C using 5 mmol of
trans-3-phenyl-2-propen-1-ol (1 M in water). [Substrate] : [Ru] ratio =
100 : 1. b Yield of 3-phenyl-propan-1-ol determined by GC.
Table 5 Influence of the substrate molar concentration in the reduction
6
of trans-3-phenyl-2-propen-1-ol catalyzed by complex [{RuCl(m-Cl)(h -
C6Me6)}2] 1 in water.a
Entry
[substrate]
NaO2CH/substrate ratio
Time
Yieldb
6
[{RuCl(m-Cl)(h -C6Me6)}2] (1; 1 mol% of Ru) in presence of
1
2
3
4
0.25 M
0.33 M
0.5 M
1 M
15 : 1
15 : 1
15 : 1
15 : 1
23 h
6 h
5.5 h
7 h
99%
98%
99%
99%
sodium formate, in water at 100 ◦C, was chosen as the model
reaction.
a Reactions performed under N2 atmosphere at 100 ◦C using 5 mmol
of trans-3-phenyl-2-propen-1-ol. [Substrate] : [Ru] : [NaO2CH] ratio =
100 : 1 : 1500. b Yield of 3-phenyl-propan-1-ol determined by GC.
constant (15 : 1), we checked different concentrations of trans-
3-phenyl-2-propen-1-ol in water, ranging between 0.25 and
1 M. As shown in Table 5, the best results were achieved
using a 0.5 M solution. Thus, under these new conditions,
quantitative conversion of trans-3-phenyl-2-propen-1-ol into
3-phenyl-propan-1-ol could be reached after only 5.5 h of
heating (entry 3). Remarkably, this result using water as solvent
competes favourably with that previously observed in organic
medium (propan-2-ol) since a lower catalyst loading is required
(entry 3 in Table 5 vs. entry 3 in Table 3).
Scheme 3 Reduction of allylic alcohols through an isomerization/TH
tandem process in aqueous media.
Firstly, we screened the optimal NaO2CH/substrate ratio
performing experiments with 1 : 1 to 25 : 1 molar relations,
maintaining constant the concentration of trans-3-phenyl-2-
propen-1-ol (1 M solution in water). Thus, as shown in Table 4,
when only one equivalent of sodium formate per allylic alcohol
was used, complete reduction of the allylic alcohol could not
be reached even after 20 h of heating (entry 1). However,
the progressive increase of the NaCO2H/substrate ratio up to
15 : 1 improved notably both the reaction rate and the yield.
In particular, the use of a 15-fold excess of NaCO2H led to
the quantitative formation of the desired 3-phenyl-propan-1-
ol after only 7 h (entry 4, Table 4).22 In contrast, no further
enhancement of the catalytic activity of complex 1 could be
achieved by using supplementary amounts of sodium formate
(entries 5–6). This phenomena is not surprising, since previous
studies have evidenced that the formation of the active hydride-
species is strongly pH-dependent, being disfavoured at very high
or very low pH values.11e
In accord with all these observations, a substrate/Ru/
NaO2CH ratio of 100 : 1 : 1500 and a molar concentration
of 0.5 M of the substrate in water were considered as the
optimal reaction conditions for the rest of our catalytic studies
6
using [{RuCl(m-Cl)(h -C6Me6)}2] 1 as catalyst. We note that
a similar optimization process was also carried out using the
3
2
3
mononuclear Ru(IV) complex [RuCl2(h :h :h -C12H18)] 1, the
optimal experimental conditions found in this case being only
slightly different (a substrate/Ru/NaO2CH ratio of 100 : 1 : 1000
and a concentration 1.0 M of the substrate in water).
Using these optimal reaction conditions, the generality of this
aqueous transformation was then explored. Results obtained
for a family of monosubstituted allylic alcohols are collected in
Table 6 and Scheme 4, while those involving allylic alcohols
The influence exerted by the substrate concentration on
the rate of the reduction process was also investigated. Thus,
keeping the NaO2CH/trans-3-phenyl-2-propen-1-ol molar ratio
=
containing di- and trisubstituted C C bonds are shown in
Table 7. Surprisingly, in contrast with that observed using
1996 | Green Chem., 2009, 11, 1992–2000
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=
Table 6 Reduction of monosubstituted allylic alcohols catalyzed by
Table 7 Reduction of allylic alcohols containing substituted C
C
and
6
3
2
3
6
complexes [{RuCl(m-Cl)(h -C6Me6)}2] 1 and [RuCl2(h :h :h -C12H18)] 2
bonds catalyzed by complexes [{RuCl(m-Cl)(h -C6Me6)}2]
1
3
2
3
using water as solvent and NaO2CH as hydrogen source.
[RuCl2(h :h :h -C12H18)] 2 using water as solvent and NaO2CH as
hydrogen source.
Entry
R
Cat. % Ru
1 mol%
Time
Conv.
Yieldc
1a
H
1
2
1
2
1
2
1
2
1
2
1
2
1
2
1
2
1
2
1
2
1
2
1
2
1
2
6 h
2 h
9 h
>99% 99%
>99% 99%
98%
Entry Substrate
1a
Cat. % Ru
Time
9 h
Conv. Yieldb
2b
1 mol%
1 mol%
1 mol%
5 mol%
5 mol%
5 mol%
5 mol%
5 mol%
5 mol%
5 mol%
5 mol%
5 mol%
5 mol%
5 mol%
5 mol%
5 mol%
5 mol%
5 mol%
5 mol%
5 mol%
5 mol%
5 mol%
5 mol%
5 mol%
5 mol%
3a
Me
61%
1
1 mol%
>99% 96%
4b
24 h
24 h
24 h
24 h
24 h
24 h
24 h
24 h
24 h
24 h
20 h
24 h
24 h
24 h
24 h
24 h
20 h
24 h
24 h
24 h
19 h
24 h
6 h
>99% 93%
>99% 86%
>99% 98%
>99% 46%
>99% 45%
>99% 41%
>99% 61%
>99% 23%
>99% 67%
>99% 98%
>99% 82%
>99% 79%
>99% 82%
>99% 55%
5a
Et
6b
2b
3a
2
1
1 mol%
1 mol%
11 h
5.5 h
>99% 99%
>99% 99%
7a
nPr
8b
9a
nBu
10b
11a
12b
13a
14b
15a
16b
17a
18b
19a
20b
21a
22b
23a
24b
25a
26b
4b
5a
2
1
1 mol%
5 mol%
24 h
8.5 h
>99% 98%
>99% 79%
nPent
Bn
6b
7a
2
1
5 mol%
5 mol%
1 h
6.5 h
>99% 83%
Ph
98%
13%
4-C6H4OMe
3-C6H4OMe
4-C6H4F
4-C6H4Cl
2-Furanyl
68%
65%
8b
9a
2
1
5 mol%
5 mol%
9 h
24 h
>99% 93%
93% 93%
>99% 75%
>99% 80%
>99% 82%
>99% 65%
>99% 87%
>99% 92%
>99% 99%
>99% 94%
10b
11a
2
1
5 mol%
5 mol%
20 h
24 h
>99% 98%
>99% 87%
12b
13a
2
1
5 mol%
5 mol%
24 h
24 h
>99% 71%
>99% 83%
a Reactions performed in a sealed tube under N2 atmosphere at
100 ◦C using 5 mmol of the corresponding allylic alcohol (0.5 M in
H2O). [substrate] : [Ru] : [NaO2CH] ratio = 100 : 1 : 1500. b Reactions
performed in a sealed tube under N2 atmosphere at 100 ◦C using
5 mmol of the corresponding allylic alcohol (1.0 M in H2O). [sub-
strate] : [Ru] : [NaO2CH] ratio = 100 : 1 : 1000. c Yield of the saturated
alcohol determined by GC. The differences between conversion and
yield correspond to the intermediate carbonyl compound present in the
reaction media.
14b
15a
2
1
5 mol%
5 mol%
20 h
4 h
>99% 67%
>99% 99%
16b
17a
2
1
5 mol%
5 mol%
8 h
5 h
>99% 99%
>99% 99%
18b
19a
2
1
5 mol%
5 mol%
3 h
5 h
>99% 96%
>99% 99%
Scheme 4 Reduction of 3 catalyzed by complexes 1 and 2 in water.
20b
21a
2
1
5 mol%
5 mol%
2 h
24 h
>99% 99%
93%
73%
propan-2-ol as solvent, the rate of the global process does not
seem to be governed by the substitution degree of the carbon–
carbon double bond. Thus, for example, the reduction of a
monosubstituted substrate, such as 1-propen-3-ol, required 24 h
to generate pentan-3-ol in 86–98% yield (entries 5–6, Table 6),
while 2-methyl-3-phenyl-prop-2-en-1-ol, a trisubstituted allylic
alcohol, was quantitatively converted into 2-methyl-3-phenyl-
propan-1-ol in only 5 h (entries 19–20, Table 7) using the same
ruthenium loadings (5 mol%). Apparently, the overall reaction
is favoured when the carbonyl intermediate is an aldehyde, i.e.
those reactions involving primary alcohols.23 In these cases, the
reduction process could be efficiently performed with a low
catalyst loading (1 mol% of Ru; entries 1–2 in Table 6, and
entries 1–4 and 29–32 in Table 7) or in short reaction times
(entries 5–6, 17–20 and 27–28 in Table 7).
22b
23a
2
1
5 mol%
5 mol%
20 h
24 h
>99% 84%
>99% 69%
24b
25a
2
1
5 mol%
5 mol%
24 h
24 h
>99% 7%
>99% 36%
26b
27a
2
1
5 mol%
5 mol%
24 h
9 h
>99% 45%
>99% 99%
28b
2
5 mol%
9 h
>99% 87%
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Table 7 (Contd.)
ruthenium(IV) catalyst 2 provides the highest activities in these
cases.
Moreover, the reduction process can also be efficiently per-
formed in water. In this environmentally benign medium, the
TH of the intermediate carbonyl compound is the rate-limiting
step regardless of the nature of the allylic alcohol. Consequently,
the best performances are obtained starting from primary allylic
alcohols, since the TH of aldehydes vs. ketones proceeds faster.
Entry Substrate
29a
Cat. % Ru
Time
24 h
Conv. Yieldb
1
1 mol%
>99% 37%
=
In summary, the new methodology for the reduction of C C
bonds of allylic alcohols presented herein is believed to be
30b
31a
2
1
1 mol%
1 mol%
30 h
24 h
>99% 93%
>99% 43%
of interest for a wide range of synthetic chemists since: (i)
=
it represents an appealing alternative to the classical C C
hydrogenations with H2(g) avoiding the use of this hazardous
8
32b
2
1 mol%
23 h
>99% 99%
reactant, (ii) it provides an efficient synthetic approach which
a Reactions performed in a sealed tube under N2 atmosphere at
100 ◦C using 5 mmol of the corresponding allylic alcohol (0.5 M in
H2O). [substrate] : [Ru] : [NaO2CH] ratio = 100 : 1 : 1500. b Reactions
performed in a sealed tube under N2 atmosphere at 100 ◦C using
5 mmol of the corresponding allylic alcohol (1.0 M in H2O). [sub-
strate] : [Ru] : [NaO2CH] ratio = 100 : 1 : 1000. c Yield of the saturated
alcohol determined by GC. The differences between conversion and
yield correspond to the intermediate carbonyl compound present in the
reaction media.
allows the use of an aqueous reaction medium,25 (iii) it is selective
=
towards C C bonds in the a-position with respect to the alcohol
group and (iv) it can be conveniently performed on a preparative
scale (see details in the Experimental).
Experimental
General methods
In this sense, the bis(allyl)-Ru(IV) catalyst 2 was able to reduce
quantitatively and chemoselectively the terpenoids geraniol
(entry 30 in Table 7) and nerol (entry 32 in Table 7) into
citronellol employing only 1 mol% of Ru. These results contrast
favourably with those obtained in propan-2-ol where 5 mol%
of Ru was required to achieve similar conversions (entries 30
and 32 in Table 3). However, we must mention that when
the arene-Ru(II) dimer 1 was tested in the reduction of these
substrates (entries 29 and 31), low yields were observed due to
the competitive formation of several unidentified by-products.
It is important to note that, regardless of the substrate
employed, in all the catalytic reactions performed in water, the
rate limiting step is the transfer hydrogenation of the carbonyl
intermediate. The enhanced reactivity observed with primary
allylic alcohols could be therefore ascribed to the lower steric
The manipulations were performed under an atmosphere of
dry nitrogen using a vacuum-line and standard Schlenk or
sealed tube techniques. Solvents were dried by standard
methods and distilled under nitrogen before use. All
reagents were obtained from commercial suppliers and
used without further purification with the exception of
6
compounds [{RuCl(m-Cl)(h -arene)}2] (arene = C6Me6 1,
mesitylene, p-cymene, C6H6),26 [RuCl2(h :h :h -C12H18)] 2,27
3
2
3
3
3
3
[{RuCl(m-Cl)(h :h -C10H16)}2],28
[RuCl2(PPh3)3],29
[Ru(h -
2-C3H4Me)2(cod)],30 [{RuCl2(cod)}n],31 [RuCl2(DMSO)4],32
[RuCl(h -C5H5)(PPh3)2],33 [RuCl(h -C9H7)(PPh3)2],34 [{Rh(m-
Cl)(cod)}2],35 [{Rh(m-Cl)(nbd)}2],36 [{Rh(m-Cl)(coe)}2],37 [{Ir(m-
Cl)(cod)}2],38 1-phenyl-3-buten-2-ol,39 1-(4-methoxyphenyl)-
2-propen-1-ol,40 1-(3-methoxyphenyl)-2-propen-1-ol,41 1-(4-
chlorophenyl)-2-propen-1-ol,42 1-(4-fluorophenyl)-2-propen-1-
ol,43 1-(furan-2-yl)-2-propen-1-ol,44 1,1¢-(1,3-phenylene)-2-di-
propen-1-ol,45 trans-2-methyl-1-phenyl-1-hepten-3-ol,7f trans-
5
5
=
requirements of the C O bond of the transient aldehyde inter-
mediates. Indeed, the most common TH mechanisms involve
the coordination of the carbonyl function to the metal center,4
a process which would be sterically favoured for aldehydes vs.
ketones.
3-methyl-4-phenyl-3-buten-2-ol,46
trans-1-phenyl-1-hepten-
3-ol,47 and trans-2-methyl-1,3-diphenyl-2-propen-1-ol,48 which
were prepared by following the methods reported in the
literature. GC measurements were made on Hewlett-Packard
Conclusions
HP6890 equipment using
a HP-INNOWAX cross-linked
poly(ethyleneglycol) (30 m, 250 mm), a Supelco Beta-DexTM 120
(30 m, 250 mm), or a Supelco Gamma-DexTM (30 m, 250 mm)
column. GC-MS measurements were performed on Agilent
6890 N equipment coupled to a 5973 mass detector (70-eV
electron impact ionization) using a HP-1MS column.
In this work, an operationally simple and highly efficient
procedure for the selective reduction of the C C bond of allylic
alcohols has been developed. This one-pot catalytic transforma-
tion, involving the use of the commercially available ruthenium
complexes [{RuCl(m-Cl)(h -C6Me6)}2] 1 and [RuCl2(h :h :h -
C12H18)] 2,24 is based on a novel tandem process consisting
of the initial redox isomerization of the allylic alcohol into
the corresponding carbonyl compound and subsequent transfer
hydrogenation of the latter from propan-2-ol. For the less
sterically demanding substrates (monosubstituted C C bonds),
the TH is the rate determining step and the arene-ruthenium(II)
derivative 1 was found to be the catalyst of choice. In contrast, for
crowded allylic alcohols (di- and trisubstituted C C bonds), the
=
6
3
2
3
General procedure for the catalytic reduction of allylic alcohols
using propan-2-ol as solvent
In a Schlenk flask fitted with a condenser, the corresponding
allylic alcohol (2 mmol), the ruthenium catalyst 1 or 2 (0.01–
0.1 mmol; 1–5 mol% of metal) and Cs2CO3 (0.02-0.2 mmol;
2–10 mol%) were dissolved in propan-2-ol (20 cm3) under inert
atmosphere. The reaction mixture was then stirred at 82 ◦C for
the indicated time (see Tables 2–3 and Scheme 2), the course of
=
=
redox isomerization becomes the slowest step and the bis(allyl)-
1998 | Green Chem., 2009, 11, 1992–2000
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the reaction being monitored by regular sampling and analysis
by gas chromatography. The identity of the resulting saturated
alcohols, as well as the carbonyl intermediates, was assessed
by comparison with commercially available, or independently
synthesized (following reported procedures), pure samples and
by their fragmentation in GC-MS. Analytically pure samples of
the saturated alcohols can be obtained by solvent removal and
chromatographic work-up of the residue on silica-gel using a
mixture of EtOAc–hexane (1 : 10) as eluent (yields of isolated
product were usually 70–80%).
We note that all these reactions can be performed in a
preparative scale. Representative example: Under nitrogen at-
mosphere, 1-phenyl-2-propen-1-ol (2.68 g, 20 mmol), complex 1
(0.067 g, 0.1 mmol), Cs2CO3 (0.132 g, 0.4 mmol) and propan-2-
ol (200 cm3) were introduced in a Schlenk flask and the reaction
mixture stirred at 82 ◦C for 15 h (almost quantitative yield
by GC). After removal of the solvent under vacuum, flash
chromatography (silica-gel) of the residue using a mixture of
EtOAc–hexane (1 : 10) as eluent afforded 2.45 g (17.99 mmol) of
analytically pure 1-phenyl-propan-1-ol (90% yield).
Notes and references
1 See, for example: (a) L. F. Tietze, Chem. Rev., 1996, 96, 115; (b) S. F.
Mayer, W. Kroutil and K. Faber, Chem. Soc. Rev., 2001, 30, 332;
(c) J. M. Lee, Y. Na, H. Han and S. Chang, Chem. Soc. Rev., 2004,
33, 302.
2 Some examples of illustrative reviews on metal-catalyzed tandem
processes: (a) G. A. Molander and C. R. Harris, Chem. Rev., 1996,
96, 307; (b) P. Eilbracht, L. Ba¨rfacker, C. Buss, C. Hollmann, E.
Kitsos-Rzychon, C. L. Kranemann, T. Rische, R. Roggenbuck and
A. Schmidt, Chem. Rev., 1999, 99, 3329; (c) G. Poli, G. Giambastiani
and A. Heumann, Tetrahedron, 2000, 56, 5959; (d) S.-I. Ikeda, Acc.
Chem. Res., 2000, 33, 511; (e) S. F. Mayer, W. Kroutil and K. Faber,
Chem. Soc. Rev., 2001, 30, 332; (f) J.-C. Wasilke, S. J. Obrey, R. T.
Baker and G. C. Bazan, Chem. Rev., 2005, 105, 1001; (g) C. Bruneau,
S. De´rien and P. H. Dixneuf, Top. Organomet. Chem., 2006, 19, 295.
3 For a highly formative review on tandem catalysis see: D. E. Fogg
and E. N. dos Santos, Coord. Chem. Rev., 2004, 248, 2365.
4 For recent reviews, see: (a) S. E. Clapman, A. Hadzovic and R. H.
Morris, Coord. Chem. Rev., 2004, 248, 2201; (b) S. Gladiali and A.
Alberico, Chem. Soc. Rev., 2006, 35, 226; (c) J. S. M. Samec, J.-E.
Ba¨ckvall, P. G. Andersson and P. Brandt, Chem. Soc. Rev., 2006, 35,
237; (d) T. Ikariya and A. J. Blacker, Acc. Chem. Res., 2007, 40, 1300.
5 For recent examples of highly efficient catalysts, see: (a) W. Baratta,
G. Chelucci, S. Gladiali, K. Siega, M. Toniutti, M. Zanette, E.
Zangrando and P. Rigo, Angew. Chem., Int. Ed., 2005, 44, 6214;
(b) W. Baratta, K. Siega and P. Rigo, Adv. Synth. Catal., 2007, 349,
1633; (c) W. Baratta, M. Ballico, G. Esposito and P. Rigo, Chem.–
Eur. J., 2008, 14, 5588; (d) W. Baratta, G. Chelucci, S. Magnolia,
K. Siega and P. Rigo, Chem.–Eur. J., 2009, 15, 726.
6 For reviews, see: (a) R. C. van der Drift, E. Bouwman and E. Drent,
J. Organomet. Chem., 2002, 650, 1; (b) R. Uma, C. Cre´visy and R.
Gre´e, Chem. Rev., 2003, 103, 27; (c) V. Cadierno, P. Crochet and
J. Gimeno, Synlett, 2008, 1105.
7 For recent examples of highly efficient catalysts, see: (a) M. Ito, S.
Kitahara and T. Ikariya, J. Am. Chem. Soc., 2005, 127, 6172; (b) B.
Mart´ın-Matute, K. Boga´r, M. Edin, F. B. Kaynak and J.-E. Ba¨ckvall,
Chem.–Eur. J., 2005, 11, 5832; (c) P. Crochet, M. A. Ferna´ndez-
Zu´mel, J. Gimeno and M. Scheele, Organometallics, 2006, 25, 4846;
(d) L. Mantilli and C. Mazet, Tetrahedron Lett., 2009, 50, 4141; (e) L.
Mantilli, D. Ge´rard, S. Torche, C. Besnard and C. Mazet, Angew.
Chem., Int. Ed., 2009, 48, 5143.
General procedure for the catalytic reduction of allylic alcohols
using water as solvent and complex [{RuCl(l-Cl)(g6-C6Me6)}2] 1
as catalyst
In a sealed tube, the corresponding allylic alcohol (5 mmol),
complex 1 (0.025-0.125 mmol; 1–5 mol% of Ru) and NaO2CH
(5.15 g, 75 mmol) were mixed in water (10 cm3) under inert
atmosphere. The reaction mixture was then stirred at 100 ◦C for
the indicated time (see Tables 6–7 and Scheme 4), the course of
the reaction being monitored by regular sampling and analysis
by gas chromatography. The resulting saturated alcohols can
be isolated from the aqueous solution after saturation with
NaCl, extraction with diethyl ether (3 ¥ 10 cm3), drying with
anhydrous MgSO4, concentration to a small volume (ca. 5 cm3)
and subsequent chromatographic work-up on silica-gel using a
mixture of EtOAc–hexane (1 : 10) as eluent.
8 Examples of metal-catalyzed hydrogenation of allylic alcohols can
be found in: (a) H. Takaya, T. Ohta, S. Inoue, M. Katimura and
R. Noyori, Org. Synth., 1995, 72, 74; (b) Y. Sun, C. Le Blond, J.
Wang, D. G. Blackmond, J. Laquidara and J. R. Sowa Jr, J. Am.
Chem. Soc., 1995, 117, 12647; (c) D. G. Blackmond, A. Lightfoot, A.
Pfaltz, T. Rosner, P. Schnider and N. Zimmermann, Chirality, 2000,
12, 442; (d) Z. Yang, M. Ebihara and T. Kawamura, J. Mol. Catal.
A: Chem., 2000, 158, 509; (e) N. Makihara, S. Ogo and Y. Watanabe,
Organometallics, 2001, 20, 497; (f) S. Nanchen and A. Pfaltz, Helv.
Chim. Acta, 2006, 89, 1559; (g) Q. Chen and F.-L. Qing, Tetrahedron,
2007, 63, 11965.
General procedure for the catalytic reduction of allylic alcohols
using water as solvent and complex [RuCl2(g3:g2:g3-C12H18)] 2 as
catalyst
In a sealed tube, the corresponding allylic alcohol (5 mmol),
complex 2 (0.05-0.25 mmol; 1–5 mol% of Ru) and NaO2CH
(3.43 g, 50 mmol) were mixed in water (5 cm3) under inert
atmosphere. The reaction mixture was then stirred at 100 ◦C for
the indicated time (see Tables 6–7 and Scheme 4), the course of
the reaction being monitored by regular sampling and analysis
by gas chromatography. Purification of the saturated alcohols
can be performed as described in the precedent section.
9 See, for example: (a) J. C. Li and T. H. Chan, Organic Reactions in
Aqueous Media, John Willey & Sons, New York, 1997; (b) A. S.
Matlack, Introduction to Green Chemistry, Marcel Dekker, New
York, 2001; (c) U. M. Lindstro¨m, Chem. Rev., 2002, 102, 2751; (d) M.
Lancaster, Green Chemistry: An Introductory Text, RSC, Cambridge,
2002; (e) C.-J. Li, Chem. Rev., 2005, 105, 3095; (f) C.-J. Li and
L. Chen, Chem. Soc. Rev., 2006, 35, 68; (g) Organic Reactions in
Water: Principles, Strategies and Applications, ed. U. M. Lindstro¨m,
Blackwell, Oxford, 2007; (h) S. Y. Tang, R. A. Bourne, R. L. Smith
and M. Poliakoff, Green Chem., 2008, 10, 268.
10 Examples of redox-isomerizations of allylic alcohols in aqueous
media can be found in: (a) D. V. McGrath, R. H. Grubbs and
J. W. Ziller, J. Am. Chem. Soc., 1991, 113, 3611; (b) T. Karlen and
A. Ludi, Helv. Chim. Acta, 1992, 75, 1604; (c) D. V. McGrath and
R. H. Grubbs, Organometallics, 1994, 13, 224; (d) H. Schummann,
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Acknowledgements
This work was supported by the Ministerio de Educacio´n y
Ciencia (MEC) of Spain (Projects CTQ2006-08485/BQU and
Consolider Ingenio 2010 (CSD2007-00006)) and the Gobierno
del Principado de Asturias (FICYT Project IB08-036). J.F.,
N.N. and S.E.G.-G. thank MEC and the European Social Fund
for the award of Ph.D. grants and a Ramo´n y Cajal contract,
respectively.
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22 In spite of the insolubility of complex 1 in water, the reduction process
proceeded efficiently. A close examination of the reaction mixture
showed that it was an emulsion rather than a homogeneous solution,
the catalytic reaction probably taking place at the interface.
23 Aldehydes have previously proven to be especially reactive in metal-
catalyzed TH processes under NaO2CH/H2O conditions. See ref.
11.
24 Complexes 1 and 2 are commercialized by TCI Laboratory Chemicals
and Strem Chemicals Inc., respectively.
25 We note that a related Ru-catalyzed isomerization/hydrogenation
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12 Part of this work has been preliminary communicated: V. Cadierno,
J. Francos, J. Gimeno and N. Nebra, Chem. Commun., 2007, 2536.
13 After the publication of our seminal work, Mizuno and co-
workers have described that supported ruthenium hydroxides
(Ru(OH)x/Al2O3 or Ru(OH)x/TiO2) can also act as efficient het-
erogeneous catalysts for this transformation: (a) J. W. Kim, T. Koike,
M. Kotani, K. Yamaguchi and N. Mizuno, Chem.–Eur. J., 2008, 14,
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14 Both individual steps, i.e. the allylic alcohol isomerization and the
TH of the carbonyl intermediate, require the use of a base as co-
catalyst to promote the formation of the active metal-hydride species.
As expected, very low conversions (0–15%) of the substrate were
observed in the absence of base.
15 Further attempts to improve the activity by changing the reaction
conditions failed. In particular, other bases (Li2CO3, Na2CO3,
K2CO3, LiOH·H2O, NaOH, KOH, CsOH·H2O, NaOtBu, KOtBu)
and [Ru] : [base] ratios (from 1 : 1 to 1 : 24) were checked without
success.
3
2
3
3
3
16 Using [RuCl2(h :h :h -C12H18)] 2 and [{RuCl(m-Cl)(h :h -C10H16)}2]
as catalysts TOF values of 429 h-1 and 3000 h-1, respectively, were
attained in the isomerization of 1-octen-3-ol into octan-3-one in
refluxing THF (0.2 mol% Ru; 0.4 mol% of Cs2CO3), while, under
37 A. Van Der Ent and A. L. Onderdelinden, Inorg. Synth., 1973, 14,
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6
the same reaction conditions, the Ru(II) dimer [{RuCl(m-Cl)(h -
C6Me6)}2] led to a TOF value of only 125 h-1. See references 10f–g.
17 Remarkably, in the case of the bis(allyl)-ruthenium(IV) derivatives
3
2
3
3
3
[RuCl2(h :h :h -C12H18)] 2 and [{RuCl(m-Cl)(h :h -C10H16)}2] the
graphs obtained showed that the initial isomerization step is finished
after only 5–10 min of heating. This observation is in complete accord
6
with the higher performances of these complexes vs. [{RuCl(m-Cl)(h -
43 N. Marion, R. Gealageas and S. P. Nolan, Org. Lett., 2007, 9, 2653.
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C6Me6)}2] in redox isomerization processes (see ref. 16).
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2001, 66, 4333.
45 G. Dyker, D. Kadzimirsz and G. Henkel, Tetrahedron Lett., 2003, 44,
19 Coordination of the carbon–carbon double bond is a key step in
the different catalytic cycles proposed for the metal-catalyzed redox
isomerization of allylic alcohols. For mechanistic discussions see
ref. 6.
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46 T. N. Grant and F. G. West, J. Am. Chem. Soc., 2006, 128, 9348.
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20 See, for example: (a) U. K. Singh, M. N. Sysak and M. A. Vannice,
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J. Catal., 2000, 191, 181; (b) F. Zaccheria, N. Ravasio, A. Fusi, M.
2000 | Green Chem., 2009, 11, 1992–2000
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The Royal Society of Chemistry 2009
©