Ruthenium(IV)-catalyzed isomerization of the C=C bond of O-allylic substrates: A theoretical and experimental study

Article abstract of DOI:10.1002/chem.201101131

A general mechanism to rationalize Ru^IV-catalyzed isomerization of the C=C bond in O-allylic substrates is proposed. Calculations supporting the proposed mechanism were performed at the MPWB1K/6-311+G(d,p)+SDD level of theory. All experimental observations in different solvents (water and THF) and under different pH conditions (neutral and basic) can be interpreted in terms of the new mechanism. Theoretical analysis of the transformation from precatalyst to catalyst led to structural identification of the active species in different media. The experimentally observed induction period is related to the magnitudes of the energy barriers computed for that process. The theoretical energy profile for the catalytic cycle requires application of relatively high temperatures, as is experimentally observed. Participation of a water molecule in the reaction coordinate is mechanistically essential when the reaction is carried out in aqueous medium.

Full text of DOI:10.1002/chem.201101131

FULL PAPER
DOI: 10.1002/chem.201101131
Ruthenium(IV)-Catalyzed Isomerization of the C=C Bond of O-Allylic
Substrates: A Theoretical and Experimental Study
Adriꢀn Varela-ꢁlvarez,*[a] Josꢂ A. Sordo,[a] Estefanꢃa Piedra,[b] Noel Nebra,[b]
Victorio Cadierno,*[b] and Josꢂ Gimeno[b]
Abstract: A general mechanism to ra-
tionalize RuIV-catalyzed isomerization
of the C=C bond in O-allylic substrates
is proposed. Calculations supporting
the proposed mechanism were per-
formed at the MPWB1K/6-311+G-
cation of the active species in different
media. The experimentally observed
induction period is related to the mag-
nitudes of the energy barriers comput-
ed for that process. The theoretical
energy profile for the catalytic cycle re-
quires application of relatively high
temperatures, as is experimentally ob-
served. Participation of a water mole-
cule in the reaction coordinate is mech-
anistically essential when the reaction
is carried out in aqueous medium. The
new mechanistic proposal helped to de-
velop a new experimental procedure
for isomerization of allyl ethers to 1-
propenyl ethers under neutral aqueous
conditions. This process is an unique
example of efficient and selective cata-
lytic isomerization of allyl ethers in
aqueous medium.
ACHTUNGTRENNUNG(d,p)+SDD level of theory. All experi-
mental observations in different sol-
vents (water and THF) and under dif-
ferent pH conditions (neutral and
basic) can be interpreted in terms of
the new mechanism. Theoretical analy-
sis of the transformation from precata-
lyst to catalyst led to structural identifi-
Keywords: density functional calcu-
lations · isomerization · reaction
mechanisms · ruthenium · synthetic
methods
Introduction
oxidation of the alcohol unit and reduction of the alkene
moiety (path A in Scheme 1).[4] This catalytic transformation
is undoubtedly much more attractive than the classical two-
step approaches (paths B and C), which are rather ineffi-
cient considering that stoichiometric or even excess reduc-
tant and oxidant must be applied to effect reorganization of
the internal oxidation pattern. Several metal complexes,
mainly of Groups 8–10, that can promote this redox process
have been described to date,[4] and the most recent advances
are focused on the development of asymmetric versions,
tandem processes, and its application in total syntheses.[5] In
this sense, the metal-catalyzed isomerization of an allylic al-
cohol moiety, as a key step in the enantioselective synthesis
of the naturally occurring pheromones muscone[5a] and
(+)-iso-exo-brevicomin,[6a] and the marine alkaloid (ꢀ)-bre-
visamide,[6b] has already been reported in the literature.
From a mechanistic point of view, the catalytic isomeriza-
tion of allylic alcohols is based on the well-known ability of
transition-metal complexes to assist the migration of
carbon–carbon double bonds;[7] that is, the catalyst turns the
allylic alcohol into an enol which readily tautomerizes to the
corresponding carbonyl compound. Three general mecha-
nisms are usually invoked to explain this process.[4,8] In the
first one (path a in Scheme 2), the key intermediate is an
alkyl metal complex generated by insertion of the olefinic
The search for organic reactions proceeding with efficiency,
selectivity, and atom economy is a major goal in synthetic
chemistry.[1] For this purpose transition-metal complexes
have been extensively exploited since they are able to pro-
mote a huge number of chemo-, regio-, and stereoselective
transformations.[2] In particular, a variety of catalytic systems
which enable the introduction of the desired functionality
into organic molecules and selective transformation of many
functional groups has been designed and widely used in syn-
thesis.[3] Among the catalytic reactions that fulfill the pre-
cept of atom economy, considerable efforts have been de-
voted to the redox isomerization of allylic alcohols to car-
bonyl compounds, a one-step process involving simultaneous
[a] Dr. A. Varela-ꢀlvarez, Prof. Dr. J. A. Sordo
Laboratorio de Quꢁmica Computacional
Departamento de Quꢁmica Fꢁsica y Analꢁtica
Universidad de Oviedo
Juliꢂn Claveria 8, 33006 Oviedo (Spain)
Fax : (+34)985-103-125
E-mail: adrian.varela@emory.edu
[b] E. Piedra, N. Nebra, Dr. V. Cadierno, Prof. Dr. J. Gimeno
Departamento de Quꢁmica Orgꢂnica e Inorgꢂnica
IUQOEM (Unidad asociada al CSIC)
Universidad de Oviedo
ꢀ
unit of the allylic alcohol into the M H bond of a metal hy-
Juliꢂn Claveria 8, 33006 Oviedo (Spain)
Fax : (+34)985-103-446
dride catalyst (either isolated or generated in situ). Subse-
quent b-hydrogen elimination, followed by decomplexation,
liberates the enol and regenerates the catalytically active hy-
dride species.[9] In the second mechanism (path b in
E-mail: vcm@uniovi.es
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/chem.201101131.
Chem. Eur. J. 2011, 17, 10583 – 10599
ꢃ 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
10583

Scheme 2), the enol is generat-
ed via a p-allyl metal hydride
intermediate formed by oxida-
ꢀ
tive addition of the allylic C H
bond to the catalyst.[10] Finally,
in path c, the allylic alcohol co-
ordinates to the metal center to
form a metal alkoxide complex.
Following a b-hydrogen elimi-
Figure 1. Ruthenium(IV) catalysts active in the redox isomerization of allylic alcohols.
nation/insertion sequence, a key p-oxoallyl complex is then
produced which, after protonation, releases the enol and re-
generates the starting complex. Remarkably, only in the
last-named mechanism, initially proposed by Trost and Kula-
wiec for the redox isomerization of allylic alcohols catalyzed
allylic alcohols.[15] In particular, with dimeric complex 1, im-
pressive turnover frequencies (TOF) and turnover numbers
(TON) of up to 62500 hꢀ1 and 1500000, respectively, could
be reached by performing the catalytic reactions in refluxing
THF and in the presence of basic Cs2CO3 as cocatalyst.[16]
Introduction of Cs2CO3 was found to be imperative to attain
good conversions in this organic medium; the catalytic activ-
ity of complex 1 decreases drastically under neutral condi-
tions.
More importantly, by taking advantage of the known sta-
bility of bis-allyl ruthenium(IV) complexes towards water
and their ability to form aqua complexes,[14] we could also
demonstrate that dimer 1 behaves as a highly active and se-
lective catalyst in eco-friendly aqueous medium.[15,17,18] Inter-
estingly, at the same working temperature (758C), the iso-
merization process was found to proceed faster in water
than in THF.[19] In addition, in contrast to the behavior of 1
in THF, no remarkable differences in activity were observed
in aqueous medium when the
by [CpRuClACHTUNGTRENNUNG
(PPh3)2],[11] is a specific role assigned to the al-
cohol moiety; an important aspect is that in many cases al-
lylic alcohols are isomerized faster than unfunctionalized al-
kenes or even exclusively.[11,12] Experimental evidence, ob-
tained by using, for example, deuterium-labeled substrates,
has demonstrated that several ruthenium and rhodium cata-
lysts operate through this metal alkoxide mechanism.[13]
Recently, we reported on the outstanding catalytic activity
of bis-allyl ruthenium(IV) dimer [{Ru(h3:h3-C10H16)Cl
ACTHNUTRGNE(UNG m-
Cl)}2] (C10H16 =2,7-dimethylocta-2,6-diene-1,8-diyl) (1 in
Figure 1) and its mononuclear derivatives [Ru(h3:h3-
C10H16)Cl2(L)] (2; L=CO, PR3, CNR, NCR) and [Ru(h3:h3-
C10H16)ClACHTUNGTRENNUNG
(NCMe)2]SbF6 (3)[14] in the redox isomerization of
catalytic reactions were per-
formed in the presence or ab-
sence of Cs2CO3.
Our previous work also includ-
ed a theoretical discussion fo-
cused on the mechanism of the
reaction under basic condi-
tions.[15] The calculated reaction
pathway,
starting
from
A
(Figure 2) and closely related to
the metal alkoxide route pro-
posed by Trost and co-workers
(path c in Scheme 2),[11] ex-
Scheme 1. Transformation of allylic alcohols into carbonyl compounds.
Scheme 2. Simplified mechanism of catalytic isomerization of allylic alcohols via a) alkyl metal intermediates, b) p-allyl metal hydride intermediates, and
c) p-oxoallyl metal intermediates.
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C=C Isomerization of O-Allylic Substrates
FULL PAPER
Results and Discussion
Theoretical analysis of the isomerization of 2-propen-1-ol to
propanal: mononuclear precatalyst of type trans-
[Ru(h3:h3-C10H16)Cl
2A(H2O)] (2 in Figure 1) was chosen as
A
CTHUNGTRENNUNG
the starting point for our theoretical analysis. This species,
in which the water ligand occupies an equatorial position, is
Figure 2. Active species in the isomerization of 2-propen-1-ol catalyzed
by complex 1.
expected to be formed from [{Ru(h3:h3-C10H16)Cl
ACHTUNGTRENNUNG(m-Cl)}2]
(1; C10H16 =2,7-dimethylocta-2,6-diene-1,8-diyl) in the aque-
ous reaction medium through chloride bridge cleavage by
water molecules.[14] The 2,7-dimethylocta-2,6-diene-1,8-diyl
spectator ligand was modeled by means of the computation-
ally less expensive unsubstituted octa-2,6-diene-1,8-diyl
(C8H12). Among the different allylic alcohols used experi-
mentally, we chose for our calculations the simplest one,
that is, 2-propen-1-ol. Table 1 summarizes the results experi-
mentally observed in the isomerization of this substrate to
propanal using dimer 1 under different reaction conditions.
plained satisfactory the need for relatively high tempera-
tures (758C) to improve the catalytic efficiency, and also re-
vealed the key role played by the p-oxoallyl intermediate in
the catalytic cycle. In spite of these interesting results, some
fundamental questions still need to be addressed: 1) The
mechanism through which catalytically active Ru alkoxide
species A is formed was not studied. 2) The experimentally
observed induction period was not explained. 3) Our previ-
ous theoretical work was restricted to the catalytic cycle in
basic media. A reaction pathway operative under neutral
conditions needs to be considered. 4) Our previous work did
not analyze the intriguing experimental observation that,
while the catalytic reactions proceed efficiently in both neu-
tral and basic water, in organic medium a base is needed.
5) Our previous calculations predicted that, under basic con-
ditions, the catalytic reactions should be slightly more effi-
cient in THF than in water, but the experiments showed the
reverse pattern. 6) Explicit participation of water molecules
in the reaction coordinate associated to the catalytic cycle
was not considered.
Table 1. Isomerization of 2-propen-1-ol to propanal catalyzed by dimer
1.[a]
Entry
Solvent
Cocatalyst
Yield [%][c]
Time
1
2
3
4
5
6
THF[b]
none
Cs2CO3 (2 mol%)
none
Cs2CO3 (2 mol%)
none
Cs2CO3 (2 mol%)
69
24 h
1 h
20 min
20 min
11 h
THF[b]
100
100
100
100
100
H2O
H2O
THF/H2O (50/1)
THF/H2O (50/1)
30 min
In the present contribution, all of the above points are
properly addressed, and thus we obtain a global mechanistic
picture of the metal-catalyzed isomerization of the C=C
bond in O-allylic substrates under different experimental
conditions. In particular, a new reaction pathway for the
redox isomerization of allylic alcohols catalyzed by
[a] Reactions performed under N2 atmosphere at 758C with 4 mmol of 2-
propen-1-ol (0.2m in THF or water). [b] Small amounts of water impurity
may be present. [c] Yield of propanal determined by GC.
[{Ru(h3:h3-C10H16)Cl
N
Formation of the catalytically active species from the precata-
lyst: Scheme 4 shows the Gibbs free energy profile for the
transformation of precatalyst trans-[Ru(h3:h3-C8H12)Cl2-
conditions, is proposed. The main novel feature in this
mechanism arises from participation of the cationic alcohol
complex B, instead of A, as the catalytically active species
(see Figure 2). In this new mechanism the OH hydrogen
atom of the allylic alcohol remains as a mere spectator
during the whole cycle, which suggests that replacement of
the hydrogen atom by other groups should not affect the C=
C bond-migration process. Experimental confirmation of
this theoretical prediction was obtained by studying the iso-
merization of allyl ethers to 1-propenyl ethers
(Scheme 3),[20] a process of synthetic relevance in polymer
chemistry[21] and in the protection/deprotection of alco-
hols.[22]
AHCTUNGTREN(GUNN H2O)] (P0_H2O) into the corresponding catalytically active
species I0 and I0H in water and THF, and under neutral and
basic conditions. The detailed geometries of the species in-
volved in this process can be found in Figure S1 of the Sup-
porting Information.
This process starts with dissociation of the water ligand
from the precatalyst to generate 16-electron complex P1.
This step is endergonic (5.5 kcalmolꢀ1 in water and 7.2 kcal
molꢀ1 in THF) and the associated barrier heights
(TSP0_H2O-P1) are relatively low in both solvents
(14.5 kcalmolꢀ1 in water and 14.0 kcalmolꢀ1 in THF). Obvi-
ously, such a 16-electron species can react with the solvent
to produce a coordinatively saturated 18-electron complex.
In water, this process regenerates P0_H2O and consequently
it does not play any mechanistic role. In THF, the corre-
sponding complex (P0_THF) is even less stable (ꢀ15.7 kcal
molꢀ1) than the 16-electron complex P1 (ꢀ16.7 kcalmolꢀ1).
Consequently, solvent coordination has no effect on these
mechanisms.
Scheme 3. Ru-catalyzed isomerization of allyl ethers to 1-propenyl ethers.
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10585

V. Cadierno, A. Varela-ꢀlvarez et al.
Scheme 4. Gibbs free energy profile in solution (water in black and THF in gray ) for the studied reaction (a temperature of 758C and the standard state
1m were assumed). [Ru]=[Ru(h3:h3-C8H12)].
Next step is the coordination of the allylic alcohol to the
RuIV complex. It can take place through two different path-
ways:
molꢀ1 in THF) are lower than those of p-olefin coordina-
tion (P0_H2O!P2).
Both intermediates P2 and P2’ can evolve towards ionic
pair I0Hd+···Cldꢀ. The corresponding transition structures
(TSP2-I0H and TSP2’-I0H) involve breaking of one of the
1) Through h2-olefin coordination of the allylic alcohol: The
double bond of the allylic alcohol occupies the vacant
site of the Ru complex leading to corresponding p-olefin
complex P2 through transition structure TSP1-P2. In
water P2 is almost as stable as P0_H2O (ꢀ23.5 kcalmolꢀ1
versus ꢀ23.6 kcalmolꢀ1) and is even more stable than
P0_H2O in THF (ꢀ24.3 kcalmolꢀ1 for P2 versus
ꢀ23.9 kcalmolꢀ1 for P0_H2O). The global kinetic barri-
ers for the transformation from P0_H2O to P2 are
19.1 kcalmolꢀ1 in water and 17.7 kcalmolꢀ1 in THF. Bear-
ing in mind that the experimental temperature is 758C
(see Table 1), they can be considered to be relatively
low.
ꢀ
ꢀ
Ru Cl bonds. For TSP2-I0H, a new Ru O bond is formed
at the same time. In the case of TSP2’-I0H, h2-coordination
of the C=C bond occurs. For the first pathway (that which
evolves through P2), the kinetic barriers of the overall trans-
formation (P0_H2O!I0Hd+···Cldꢀ) are 28.4 kcalmolꢀ1 (in
water) and 28.7 kcalmolꢀ1 (in THF). For the second path-
way (that which evolves through P2’), the barriers in both
solvents are much higher (40.1 kcalmolꢀ1 in water and
38.7 kcalmolꢀ1 in THF). Consequently, the first pathway
should be the preferred mechanism. The above relatively
high kinetics barriers are consistent with the induction
period experimentally observed in both solvents.[15]
2) Through O coordination of the allylic alcohol: The O
atom of the allylic alcohol approaches (TSP1-P2’) 16-
The evolution of intermediate I0Hd+···Cldꢀ depends on
the reaction media. Thus, in neutral media, the following
equilibria should be considered [Reactions (R1) and (R2)].
ꢀ
electron species P1 to form a Ru O bond in the alcohol
complex P2’, which is notably less stable than P2 in both
water (ꢀ17.6 kcalmolꢀ1 versus ꢀ23.5 kcalmolꢀ1) and
THF (ꢀ19.8 kcalmolꢀ1 versus ꢀ24.3 kcalmolꢀ1), but the
barriers associated with the global transformation from
P0_H2O to P2’ (18.1 kcalmolꢀ1 in water and 16.9 kcal
I0Hdþ ꢁ ꢁ ꢁ Cldꢀ Ð I0 þ HCl
I0Hdþ ꢁ ꢁ ꢁ Cldꢀ Ð I0Hþ þ Clꢀ
ðR1Þ
ðR2Þ
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C=C Isomerization of O-Allylic Substrates
FULL PAPER
While in neutral aqueous solution R1 is endergonic
(Scheme 4), R2 is exergonic, and I0H is almost as stable as
P0_H2O (ꢀ22.5 kcalmolꢀ1 versus ꢀ23.6 kcalmolꢀ1). There-
fore, I0H should be the species responsible for catalysis in
neutral aqueous solution. In THF, under neutral conditions,
R1 and R2 are strongly endergonic (Scheme 4). Conse-
quently, in neutral THF medium, I0 and I0H will be present
at very low concentrations. Considering that the kinetic bar-
riers involved in the catalytic cycles are about 30 kcalmolꢀ1
(see below), the catalytic efficiency must be moderate.
In basic media, in addition to R1 and R2, equilibrium R3
should also be considered.
intermediate I1H, in which the allylic alcohol is coordinated
ꢀ
to the metal center through both a C H bond from the
CH2OH group and the allylic p bond. This process involves
moderate kinetic barriers (20 kcalmolꢀ1 in water and
18.3 kcalmolꢀ1 in THF) as a consequence of the stabilizing
ꢀ
effect of the agostic interaction and the fact that the Ru O
bond is activated (the alcoholic oxygen atom is protonated).
The next step is transformation of the allylic unit into an
ꢀ
enol (TSI1H-I2H). In this step the C H bond forming the
agostic interaction breaks and the hydrogen atom goes to
the CH2 group of the olefin fragment, thus creating a new
ꢀ
ꢀ
C H bond. This new C H bond participates in an agostic
interaction in I2H. As a consequence, the allylic p bond
shifts from an allylic to an enolic position. At the same time,
in order to make the hydrogen addition to the double bond
easier, the substrate rotates from a disposition with the alco-
holic group far away from the Cl ligand to one that keeps
the Cl ligand and the OH group close to each other.
I0Hdþ ꢁ ꢁ ꢁ Cldꢀ þ OHꢀ Ð I0 þ Clꢀ þ H2O
ðR3Þ
Scheme 4 shows that R3 is strongly exergonic both in
water and THF. Species I0 becomes the most stable in basic
aqueous medium and it is about 15 kcalmolꢀ1 more stable
than P0_H2O (Scheme 4). Hence, the precatalyst is fully
converted to I0, and this structure should be the starting
point for the catalytic cycle in basic aqueous solution. On
the other hand, in basic THF, R3 is strongly exergonic, and
thus catalytic species I0 is very stable (ꢀ47.4 kcalmolꢀ1 for
I0 versus ꢀ24.3 kcalmolꢀ1 for P2); that is, in basic THF the
precatalyst will be fully converted to catalytic species I0.
Transformation from I2H to I3H (through TSI2H-I3H) in-
volves rotation of the double bond which is coordinated to
the metal center. During this rotation, the agostic interac-
tion is broken and the enolic oxygen atom creates a new
ꢀ
Ru O bond. The global transformation from I0H to I3H
can be viewed as a hydrogen 1,3-shift that turns the allylic
substrate into an enol. Such a process is endergonic (9.8 kcal
molꢀ1 in water and 10.1 kcalmolꢀ1 in THF) and shows a
moderate kinetic barrier both in water (23.4 kcalmolꢀ1) and
THF (26.7 kcalmolꢀ1), bearing in mind that the experimen-
tal temperature is 758C.
The above theoretical predictions are consistent with the
experimental observation that the catalytic reaction is feasi-
ble in neutral and basic water (entries 3 and 4 in Table 1),
but in THF a base is needed for efficiently optimum cataly-
sis (entries 1 and 2 in Table 1).
The next steps of the mechanism involve decoordination
of the enol, which evolves towards the more stable aldehyde
species, and coordination of a new allylic substrate, regener-
ating I0H and closing the catalytic cycle. The transformation
from I3H to I4H through TSI3H-I4H corresponds to de-
coordination of the enolic C=C bond and simultaneous for-
Catalytic cycle under neutral conditions I: general mecha-
nism: The catalytic cycle in neutral solvent is depicted in
Scheme 5, and the corresponding profile in Scheme 6. The
structures involved in this cycle are collected in Figure S2 of
the Supporting Information.
ꢀ
mation of a new Ru O bond involving a new substrate mol-
The starting point of this cycle is complex I0H. Simultane-
ecule, which is taken from solution. The resulting I4H struc-
ture has an enol and an allylic alcohol as ligands, both coor-
dinated through their respective oxygen atoms. Species I4H
leads to the coordinatively unsa-
ꢀ
ous cleavage of the Ru O bond and creation of an agostic
interaction through transition structure TSI0H-I1H leads to
turated intermediate I5H by
ꢀ
cleavage of the Ru O bond in-
volving the enol. This transfor-
mation involves the highest-
energy transition structure in the
present mechanism (36.0 kcal
molꢀ1 in water and 27.7 kcal
molꢀ1 in THF). The free enol
tautomerizes to the correspond-
ing carbonyl compound in solu-
tion. Finally, I0H is regenerated
through p complexation of the
olefin fragment to the metal
center. Such
a transformation
(TSI5H-I0H) is associated with a
rather low energy barrier and is
strongly exergonic (Scheme 6).
Scheme 5. Catalytic cycle under neutral conditions. [Ru]=[Ru(h3:h3-C8H12)].
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V. Cadierno, A. Varela-ꢀlvarez et al.
Scheme 6. Gibbs free energy profile in solution (water in black and THF in gray) for the studied reaction under neutral conditions (a temperature of
758C and the standard state 1m were assumed). [Ru]=[Ru(h3:h3-C8H12)].
Scheme 7. Catalytic cycle involving one water molecule under neutral conditions. [Ru]=[Ru(h3:h3-C8H12)].
As expected for the energetic balance of an isomerization
process from an allylic alcohol to the corresponding alde-
hyde, the overall cycle is strongly exergonic (ꢀ14.7 kcal
molꢀ1 in water and ꢀ16.8 kcalmolꢀ1 in THF). From a kinet-
ics viewpoint, the rate-limiting step corresponds to decoordi-
nation of the enol ligand (TSI4H-I5H). The global free
energy barrier in water (36.0 kcalmolꢀ1) is higher than that
expected for an efficient catalytic reaction at 758C, but we
show below that explicit participation of a water molecule
in the reaction coordinate notably lowers the barrier in-
volved, and thus provides a picture fully consistent with the
experimental facts. In THF, the energy barrier is moderate
(27.7 kcalmolꢀ1), considering that the experimental temper-
ature is relatively high (758C). Thus, the low efficiency of
the catalytic process experimentally observed in neutral
THF (entry 1 in Table 1), must arise from the expected
rather small existing concentration of the catalyst (I0H)
mentioned above.
Catalytic cycle under neutral conditions II: water as a reac-
tive species: Scheme 7 shows the complete catalytic cycle in
neutral solvent with participation of water in the reaction
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C=C Isomerization of O-Allylic Substrates
FULL PAPER
through TSI7_H2O-I0H, involv-
ing both decoordination of the
water molecule and p complexa-
tion of the allylic carbon–carbon
double bond.
This new catalytic cycle exhib-
its exactly the same strongly ex-
ergonic thermodynamics as that
which does consider water as
part of the reaction coordinate
described above (ꢀ14.7 kcal
molꢀ1 in water and ꢀ16.8 kcal
molꢀ1 in THF). However, signifi-
cant changes are observed in the
kinetics. In neutral aqueous so-
lution the barrier height drops
by about 7 kcalmolꢀ1 on partici-
pation of a water molecule in
the
reaction
coordinate
(Schemes 6 and 8). Such an
energy barrier (29.2 kcalmolꢀ1)
is consistent with the experimen-
tally observed requirement for
high temperature (758C). The
kinetics law should now depend
on the water concentration
rather than on the allylic alcohol
Scheme 8. Gibbs free energy profile in solution (water in black and THF in gray) for the studied reaction
under neutral conditions when coordination of a water molecule is explicitly considered (a temperature of
758C and the standard state 1m were assumed). [Ru]=[Ru(h3:h3-C8H12)].
coordinate. Scheme 8 shows the Gibbs free energy profile
for the transformation from I3H to I0H, assisted by coordi-
nation of a water molecule. The detailed geometries of the
new structures involved are collected in Figure S3 of the
Supporting Information.
concentration, although, since the conversion I0H!I3H is
slightly endergonic (Schemes 5 and 6), a dependence on the
alcohol concentration will arise associated with the equilibri-
um between precatalyst and catalyst (the alcohol displaces
the equilibrium towards catalyst formation).
We showed above that decoordination of the enol from
I3H is assisted by coordination of a new substrate molecule.
Here we consider water instead of allylic alcohol (see
Scheme 5) as that new substrate. Species I3H can evolve to-
wards I4H_H2O by incorporating a water molecule as
ligand. This step (TSI3H-I4H_H2O) simultaneously involves
decoordination of the allylic double bond to generate the
necessary vacancy. Species I4H_H2O is rather similar to the
I4H (Scheme 5), with the only difference that a water mole-
cule takes the place of the allylic alcohol molecule in the
metal coordination sphere. The next step is decoordination
of the enol (which readily tautomerizes to the thermody-
namically more stable aldehyde) through TSI4H_H2O-
Interestingly, the calculations presented in this section
strongly suggest the important role played by a water mole-
cule coordinated to the metal center, notably lowering the
energy barrier. In the case of neutral THF, comparison of
Schemes 6 and 8 leads to the conclusion that the existence
of water impurities in this medium should lower the energy
barrier associated with the enol elimination step TSI4H-
I5H/TSI4H_H2O-I5H_H2O from 27.7 (pure THF;
Scheme 6) to 23.1 kcalmolꢀ1 (THF contaminated with
water; Scheme 8). Under such circumstances, the transfor-
mation I1H!I2H (1,3-hydrogen shift) would become the
rate-limiting step in the catalytic cycle (Scheme 6). Never-
theless, despite such a moderate energy barrier, the rather
small concentration of catalyst I0H and the extremely low
concentration of water present as an impurity will keep the
efficiency of this reaction pathway almost negligible. The re-
action will mainly proceed through the mechanism analyzed
in the preceding section (Scheme 6).
ꢀ
I5H_H2O. This step involves breaking of the Ru O bond
between the metal center and the allylic alcohol and its tran-
sition structure is the highest point along the Gibbs free
energy profile (29.2 kcalmolꢀ1) in neutral aqueous medium.
Importantly, this barrier is almost 7 kcalmolꢀ1 lower than
the corresponding one obtained when participation of water
in the reaction coordinate was not considered (see above).
Catalytic cycle under basic conditions I: general mechanism:
The catalytic cycle under basic conditions is shown in
Scheme 9, and the corresponding Gibbs free energy profile
in water and THF in Scheme 10. The structures involved in
this cycle are collected in Figure S4 of the Supporting Infor-
mation.
The 16-electron intermediate I5H_H2O undergoes a rotation
[23]
ꢀ
about the Ru O bond leading to I6H_H2O. Then, a new
molecule of allylic alcohol coordinates through its oxygen
atom to the metal center, leading to I7H_H2O. Finally, the
starting point of the catalytic cycle (I0_H2O) is regenerated
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10589

V. Cadierno, A. Varela-ꢀlvarez et al.
Scheme 9. Catalytic cycle under basic conditions. [Ru]=[Ru(h3:h3-C8H12)].
As expected, the cycle is qualitatively similar to that pre-
viously reported when employing the B3LYP functional.[15]
The Gibbs free energy barriers become higher when com-
puted with Truhlarꢄs new-generation MPWB1K functional
(B3LYP global highest energy barriers were 27.0 and
26.0 kcalmolꢀ1 for water and THF, respectively). The corre-
sponding MPWB1K values were 40.1 in THF and 33.6 kcal
molꢀ1 in H2O). We have showed above that the catalytically
active species in basic medium (I0; Scheme 4) is thermody-
namically favored in both water and THF, contrary to what
we have found for neutral conditions. This makes the energy
barrier associated with the rate-controlling step the main
factor responsible for the efficiency of the reaction when
carried out under basic conditions. In this regard, the above
energy barrier can be considered consistent with the experi-
mentally observed high efficiency when the reaction is car-
ried out in THF with Cs2CO3 as cocatalyst (entry 2 in
Table 1), bearing in mind the stabilizing action expected for
the existence of a number of TSI10-I11-like structures on
the potential-energy surface (PES).[24] Exploratory calcula-
tions showed the existence of a number of such structures
with energy barriers close to 30 kcalmolꢀ1. As demonstrated
in reference [24], where a quantitative discussion of the re-
markable mechanistic impact of this important point is pre-
sented, consideration of those transition structures does con-
tribute to a notable reduction in the actual barrier height.
However, the MPWB1K energy barrier, as computed under
basic aqueous conditions, is hardly compatible with the high
catalytic efficiency experimentally observed (entry 4 in
Table 1). We show below that consideration of a water mol-
ecule as part of the reaction coordinate does provide a pic-
ture in full agreement with the experimental facts.
The thermodynamics of the global process (exergonicities
of ꢀ14.7 and ꢀ16.8 kcalmolꢀ1 in water and THF, respective-
ly) is quite similar to that previously predicted with the
B3LYP functional (ꢀ15.9 kcalmolꢀ1 in both solvents).[15]
This observation fully supports the general belief that while
B3LYP does provide, in general, accurate thermodynamics,
more elaborate functionals like MPWB1K may be required
to provide satisfactory kinetics.[25]
Catalytic cycle under basic conditions II: water as a reactive
species: The complete catalytic cycle involving participation
of a water molecule in the reaction coordinate under basic
conditions is shown in Scheme 11. The corresponding Gibbs
free energy profile in solution is provided in Scheme 12 (to
be compared with the lower part of the Scheme 10, in which
no water molecule takes place in the reaction coordinate).
The upper part of Scheme 10 is common to both cases and
is not included in Scheme 12). The detailed geometries of
the species involved in this mechanism are collected in Fig-
ure S5 of the Supporting Information.
In the mechanism considered in the preceding section, the
ruthenium complex undergoes coordination of a new sub-
strate molecule (allylic alcohol) which acts as a proton
source and helps enol decoordination. A water molecule can
do both, and this option is studied in the present section.
Thus, under basic aqueous conditions, I7 can undergo coor-
dination of a water molecule to the metal center through a
process (TSI7-I8_H2O) in which a parallel breaking of the
p-coordinated enolate ligand takes place. The resulting in-
termediate (I8) exhibits hydrogen bonding between one of
the water OH groups and the oxygen atom in the enolate.
Hydrogen transfer from the water ligand to the enolate
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C=C Isomerization of O-Allylic Substrates
FULL PAPER
Scheme 10. Gibbs free energy profile in solution (water in black and THF in gray) for the studied reaction under basic conditions (a temperature of
758C and the standard state 1m were assumed). [Ru]=[Ru(h3:h3-C8H12)].
leads to I9_H2O, which generates in turn 16-electron species
I10_H2O through a process involving the highest Gibbs free
energy barrier for both water and THF. Coordination of a
new substrate molecule (allylic alcohol) to I10_H2O leads to
I11_H2O. Transfer of a hydrogen atom from the alcohol
group to the hydroxyl group (TSI11_H2O-I12_H2O) and fur-
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10591

V. Cadierno, A. Varela-ꢀlvarez et al.
Scheme 11. Catalytic cycle involving one water molecule under basic conditions. [Ru]=[Ru(h3:h3-C8H12)].
ther decoordination of a water molecule (TSI12_H2O-I11)
gives rise to 16-electron structure I11, which finally evolves
towards the starting point of the catalytic cycle (I0) through
p complexation of the allylic carbon–carbon double bond to
the metal center.
concentration of water (about 50m according to the experi-
mental conditions) is involved. Consequently, one might
expect that such concentration dependences should counter-
balance the effect of the slightly larger barrier computed for
the reaction in water, and thus make it a somewhat more ef-
ficient pathway, as experimentally observed (entries 2 and 4
in Table 1). Interestingly, when the reaction is carried out in
THF/H2O solution (entry 6 in Table 1), the process becomes
slightly slower than in water (entry 4 in Table 1), consistent
with the lower concentration of water present in the former
case.
Again, the thermodynamics of the cycle is governed by
the strongly exergonic reaction that converts 2-propen-1-ol
to propanal (ꢀ14.7 kcalmolꢀ1 in water and ꢀ16.8 kcalmolꢀ1
in THF). From a kinetics viewpoint, the global rate-limiting
transformation corresponds to the conversion I7!I10_H2O.
The Gibbs free energy barriers are 33.1 kcalmolꢀ1 in water
and 28.4 kcalmolꢀ1 in THF. An exploration of the PESs al-
lowed us to identify a number of different conformations for
the involved transition structures that will contribute to the
lowering of the above energy barriers in a similar way as
was reported in reference [24]. The resulting barriers (ca.
30 kcalmolꢀ1) are fully compatible with the experimental
observation that the reaction proceeds at 758C under basic
conditions with 100% yield and short reaction times (en-
tries 2 and 4 in Table 1).
Isomerization of allylic alcohols: the global picture: In the
preceding sections we have explored and analyzed in detail
the different plausible mechanisms through which the bis-
AHCTUNGERTG(NNUN allyl)-ruthenium(IV)-catalyzed isomerization of allylic alco-
hols to aldehydes should proceed under different conditions.
Calculations allowed us to rationalize, at the semiquantita-
tive level and for the first time, all experimental observa-
tions under different conditions (neutral and basic media)
and with different solvents (water and THF). Moreover, we
also provide a thorough mechanistic description of the pro-
cess in which the active catalyst is formed, fully consistent
with the experimental facts, thus offering a solid theoretical
support to the structural identification of such a species.
Although the energy barrier in THF is slightly lower than
that in water, the rate of reaction in the former (see
Scheme 10) does exhibit a dependence on the concentration
of alcohol (about 0.2m according to the experimental condi-
tions), while for the reaction in water (see Scheme 12), the
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C=C Isomerization of O-Allylic Substrates
FULL PAPER
Scheme 12. Gibbs free energy profile in solution (water in black and THF in gray) for the studied reaction under basic conditions when a water molecule
is explicitly considered (a temperature of 758C and the standard state 1m were assumed). [Ru]=[Ru(h3:h3-C8H12)].
At this point, we wanted to test the predictive ability of
our mechanistic proposal. According to Schemes 7 and 8
(neutral aqueous medium), the alcoholic hydrogen atom
does not play any relevant mechanistic role during the iso-
merization. This suggests that replacement of this hydrogen
atom by other groups should not interfere with the C=C mi-
gration process. To probe this theoretical prediction, the
75–1108C, and the course of the reaction was monitored by
gas chromatography. Selected results are summarized in
Table 2.
As shown in entries 1–5 of Table 2, regardless of the tem-
perature employed, almost quantitative conversion of 3a
(>98%) was in all cases observed within 1.75h of heating
with a ruthenium loading of 3 mol% (1.5 mol% of dimer 1).
However, at 90–1108C (Table 2, entries 1–3), significant dis-
crepancies were noted between the conversion of 3a and
ability of complex [{Ru(h3:h3-C10H16)Cl
ACTHNUTRGNE(NUG m-Cl)}2] (1) to pro-
mote the isomerization of allyl ethers to synthetically useful
1-propenyl ethers[26] in water at neutral pH was explored.
Despite the plethora of studies performed to date on this
catalytic transformation,[20] the search for active catalysts in
aqueous media still remains a challenge. Thus, to the best of
our knowledge, only the hexaaquo ruthenium(II) complex
Table 2. Isomerization of allyl phenyl ether in water catalyzed by com-
plex [{Ru(h3:h3-C10H16)Cl
ACTHNUGTRNE(NUG m-Cl)}2] (1): Optimization of the reaction con-
ditions.[a]
[RuACHTUNGTRENNUNG(H2O)6]Tos2 has been described, albeit with limited suc-
cess due to the competitive hydrolysis of the resulting 1-pro-
penyl ethers.[9,18a]
Entry
[Ru]
[mol%]
T
[8C]
t
Conv.[b]
[%]
Yield of
E/Z
G
[h]
4a[b] [%]
ratio[b]
Catalytic isomerization of allyl ethers to 1-propenyl ethers:
For the isomerization of commercially available allyl phenyl
ether (3a) to phenyl 1-propenyl ether (4a) as model reac-
tion, our theoretical predictions were completely confirmed,
1
2
3
4
5
6
3
3
3
3
3
5
110
100
90
85
75
1.75
1.75
1.75
1.75
1.75
1
99
99
99
99
98
99
75
81
94
97
98
99
6/1
6/1
9/1
11/1
19/1
5/1
since dimer [{Ru(h3:h3-C10H16)Cl
ACTHNUTRGEN(NUG m-Cl)}2] (1) was able to cat-
75
alyze efficiently this C=C migration process in water under
neutral conditions. In a typical experiment, ruthenium cata-
lyst precursor 1 (3–5 mol% of Ru) was added to a 0.2m
aqueous solution of 3a and the resulting mixture heated at
[a] Reactions performed under N2 atmosphere with 1 mmol of allyl
phenyl ether 3a (0.2m in water). [b] Determined by GC. The differences
between conversion and yield of 4a correspond to the phenol formed by
hydrolysis of 4a.
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V. Cadierno, A. Varela-ꢀlvarez et al.
Table 3. Isomerization of aromatic allyl ethers in water catalyzed by
the yield of desired 1-propenyl ether 4a due to formation of
phenol and propanal as byproducts, which results from the
competing hydrolysis of 4a. By lowering the temperature to
858C (Table 2, entry 4) this side reaction could be largely
minimized, and 3a was generated in 97% yield (GC). Only
2% of phenol was observed in this case in the crude reac-
tion mixture by GC. At this temperature, 4a is formed as a
mixture of E/Z stereoisomers in 11/1 ratio. The stereoselec-
tivity of the process could be improved by further reducing
the temperature (Table 2, entry 5). Thus, by carrying out the
reaction at 758C, a 19/1 ratio in favor of the thermodynami-
cally more stable E stereoisomer could be reached. This im-
provement in stereoselectivity was also accompanied by
complete suppression of the competing hydrolysis process,
and 4a was generated selectively in 98% yield (GC). As ex-
pected, an increase of the ruthenium loading from 3 to
5 mol% resulted in an increase of the reaction rate (Table 2,
entry 6 versus 5). However, this acceleration was accompa-
nied by a decrease in the stereoselectivity of the process (E/
Z ratio from 19/1 to 5/1). Based on these results, we decided
to adopt a working temperature of 758C and a ruthenium
loading of 3 mol% as the optimal conditions for the rest of
our catalytic tests.[27]
complex 1.[a]
Entry
Ar
t
Conv.[b]
[%]
Yield of
[c] [%]
E/Z
[h]
4
ratio[b]
1
2
3
4
5
6
7
8
Ph (3a)
1.75
2.5
5.5
4
1
8
6
3
2
6
98
98
99
99
96
74
95
98
99
98
98
4a; 98 (82)
4b; 98 (84)
4c; 99 (88)
4d; 96 (79)
4e; 96 (80)
4 f; 73 (60)
4g; 95 (83)
4h; 98 (85)
4i; 99 (86)
4j; 95 (81)
4k; 98 (88)
19/1
10/1
10/1
10/1
32/1
24/1
5/1
4/1
10/1
5/1
2-C6H4Cl (3b)
3-C6H4Cl (3c)
4-C6H4Cl (3d)
4-C6H4CHO (3e)
4-C6H4NHAc (3 f)
2-C6H4Me (3g)
4-C6H4Me (3h)
4-C6H4OMe (3i)
3-C6H4NEt2 (3j)
6-Quinolinyl (3k)
9
10
11
5
9/1
[a] Reactions performed under N2 atmosphere with 1 mmol of the corre-
sponding allyl ether (0.2m in water). [b] Conversion of 3 determined by
GC. [c] Yield of 4 determined by GC (yields of isolated compounds in
parentheses). The differences between conversion of 3 and GC yield of 4
are due to formation of minor amounts of the corresponding alcohol by
hydrolysis of 4.
Under these optimized reaction conditions the ability of 1
to promote the isomerization of a number of other allyl
ethers was explored. Thus, as observed for 3a, other aromat-
ic and heteroaromatic substrates 3b–k could be selectively
transformed into corresponding 1-propenyl ethers 4b–k
after only 1–8h of heating, regardless of their substitution
pattern and electronic nature (Table 3). Common functional
groups, such as chloride (Table 3, entries 2–4), aldehyde
(Table 3, entry 5), acetamide (Table 3, entry 6), methoxyl
(Table 3, entry 9), and diethylamino (Table 3, entry 10),
were compatible with this aqueous catalytic protocol. The
reactions led to the desired products in high yields (73–
99%) as mixtures of the E and Z stereoisomers (E/Z 4/1 to
32/1). Subsequent purification by column chromatography
on silica gel provided analytically pure samples of 4b–k,
which were isolated in 60–88% yield and spectroscopically
characterized.
groups of the molecule have either a E (major) or Z
(minor) stereochemistry (details are given in the Experi-
mental Section). Formation of the E/Z isomer mixture was
not detected, an unusual fact in metal-catalyzed isomeriza-
tions of bis(allyl ethers).[28]
However, despite the high generality of the process, com-
plex 1 was unable to promote isomerization of aromatic
allyl ethers 3m–o. In the case of 2-acetylphenyl allyl ether
Remarkably, complex 1 was also effective in the simulta-
neous isomerization of both carbon–carbon double bonds of
2,2ꢄ-bisACHTUNGTRENNUNG(allyloxy)-1,1ꢄ-binaphthalene (3l), generating the
bis(1-propenyl) derivative 4l in good yield (82%) as a mix-
ture of only two of the three possible isomers
(Scheme 13).[28] The NMR data of 4l confirmed the exclu-
sive presence in solution of species in which the CH=CH
(3m) and 2-allyloxy-benzophenone (3n), the relative dispo-
sition of the oxygen atoms of the carbonyl and ether groups
allows chelating coordination of these substrates to rutheni-
um forming a stable six-membered metallacycle. Such O,O
coordination could block the catalyst, thus preventing the
isomerization of the C=C bond. As demonstrated in our the-
oretical analysis (see Scheme 6), coordination of the olefinic
unit to ruthenium is essential
for migration of the C=C unit
to take place. The preferential
coordination of nitrile versus
olefin unit may also explain the
lack of reactivity observed
when 2-cyanophenyl allyl ether
(3o) was used as substrate.
As shown in Table 4, this
aqueous process is not restrict-
Scheme 13. RuIV-catalyzed isomerization of 2,2’-bis
G
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C=C Isomerization of O-Allylic Substrates
FULL PAPER
Table 4. Isomerization of alkyl allyl ethers in water catalyzed by complex
Conclusion
1.[a]
Isomerization of allylic alcohols by bis-allyl RuIV complexes
has been theoretically analyzed at the MPWB1K/6-311+
G**+SDD level. The thermodynamics of conversion from
Entry
Alk
t
Conv.[b]
[%]
Yield of
[c] [%]
E/Z
precatalyst [Ru(h3:h3-C8H12)Cl
2ACHTNUTRGENNG(U H2O)] to the catalytic spe-
[h]
4
ratio[b]
cies [Ru(h3:h3-C8H12)Cl(k1:h2-OCH2CH=CH2)] (I0) and
[Ru(h3:h3-C8H12)Cl(k1:h2-HOCH2CH=CH2)]+ (I0H) showed
that in aqueous media the species responsible for catalysis
are I0H and I0 under neutral and basic conditions, respec-
tively. In THF, generation of I0 and I0H is strongly ender-
gonic under neutral conditions. However, the precatalyst is
fully converted to I0 under basic conditions. These results
allow us to rationalize why catalysis is not so efficient in
neutral THF. The kinetics of transformation from precata-
lyst to catalyst involves barriers about 28–29 kcalmolꢀ1 in
both solvents. Such relatively high energy barriers are com-
patible with the induction period experimentally observed
for the studied reactions.
A general mechanism is proposed that rationalizes, for
the first time, all experimental observations made in differ-
ent media (water and THF) and under different conditions
(neutral and basic). Interestingly, participation of a water
molecule in the reaction coordinate proved to be mechanis-
tically essential in aqueous medium. For all the analyzed
cycles, the energy barriers predicted are about 30 kcalmolꢀ1.
This theoretical prediction is fully consistent with the need
for the relatively high temperatures (758C) experimentally
required to carry out the reactions.
1
2
3
4
5
Et (3p)
cyclooctyl (3q)
CH2Ph (3r)
CH2CH2CH2Ph (3s)
CHPh2 (3t)
2
2.8
1
2.8
1
99
99
93
99
99
4p; 99 (85)
4q; 99 (91)
4r; 93 (80)
4s; 99 (86)
4t; 97 (84)
4/1
1/2
4/1
1/2
2/1
[a] Reactions performed under N2 atmosphere with 1 mmol of the corre-
sponding allyl ether (0.2m in water). [b] Conversion of 3 determined by
GC. [c] Yield of 4 determined by GC (yields of isolated compounds in
parentheses). The differences between conversion of 3 and GC yield of 4
are due formation of minor amounts of the corresponding alcohol by hy-
drolysis of 4.
ed to aromatic allyl ethers; selective isomerization of sub-
strates containing alkyl–oxygen bonds is readily (1–2.8h)
and efficiently (93–99% GC yields) achieved under the
standard reaction conditions. This fact clearly confirms the
wide scope of this catalytic transformation. However, start-
ing from these allylic substrates, the C=C isomerization pro-
ceeds with a notably lower E/Z stereoselectivity compared
to their aromatic counterparts. Indeed, preferential forma-
tion of the Z isomer was even observed in some cases (en-
tries 2 and 4 in Table 4).
The allyl group is frequently used in organic synthesis as a
protecting group for alcohols.[22] Its removal usually requires
a two-step process involving initial metal-mediated isomeri-
zation of the allyl ether to the corresponding 1-propenyl
ether, followed by acidic or basic hydrolysis. Since extensive
phenol formation (ca. 24%) was observed when the isomeri-
zation of allyl phenyl ether (3a) was performed in water at
1108C (entry 1 in Table 3), we wondered about the possibili-
In neutral water, calculations predict that the hydroxylic
proton of the allylic alcohol does not play a key role during
the catalytic cycle, and this allowed us to develop an experi-
mental procedure for isomerization of allyl ethers to 1-pro-
penyl ethers under these particular conditions. Such a pro-
cess, which is promoted by the dimeric complex [{Ru(h3:h3-
C10H16)ClACHTNUGRTENUNG(m-Cl)}2] (1), is a unique example of efficient and
ty of using dimer [{Ru(h3:h3-C10H16)Cl
(m-Cl)}2] (1) as an effi-
selective catalytic isomerization of allyl ethers in aqueous
medium. Furthermore, simply by adjusting the working tem-
perature, a new method of deprotection of allyl ethers has
seen the light. Formation of the corresponding deprotected
alcohol involves hydrolytic cleavage of the initially formed
1-propenyl ether.
cient catalyst for these type of deprotection processes.[29] We
found that, simply by heating at 1108C for 8h, almost com-
plete deallylation of 3a occurs (94% GC yield of free
phenol) without the need of an external acid or base. Posi-
tive results were also obtained starting from 3i, 3q, and 3r
(Scheme 14). These preliminary results bring to light a new
catalytic method of deprotection of allyl ethers that, remark-
ably, proceeds efficiently in environmental benign aqueous
media under neutral conditions. All of these facts give the
synthetic methodology reported herein genuine potential for
practical application in organic chemistry.
Experimental Section
Theoretical methods: Isomerization of 2-propen-1-ol to propanal, cata-
lyzed by model complex [RuCl2(h3:h3-C8H12)
ACHTUNGTRNE(UNG H2O)] (C10H12 =octa-2,6-
diene-1,8-diyl), was studied by using the meta-GGA[30] MPWB1K func-
tional.[31] This functional is able to produce accurate predictions for both
kinetic and thermodynamic properties when applied to molecules con-
taining first- and second-row atoms.[32] In our own recent experience, it
also provided excellent results for gas-phase organometallic reactions.[25]
Pople 6-311+GACTHNUTRGNEUNG
(d,p) basis sets were chosen for the C, H, and O atoms,[33]
and the SDD basis set with effective core potential (ECP) was used for
the Ru atom.[34] Solvents effects were included by means of the polarized
continuum model (PCM).[35] Free energies in solution were computed
as[35b]
G
soln =Ggas +DGsolv +RTln
ACHTNUGERTN(NUNG RT/P), where DGsolv is the solvent con-
Scheme 14. RuIV-catalyzed deprotection of allyl ethers in water.
tribution to the free energy DGsolv =(Esoln +Gnes)ꢀEgas, where Esoln and
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10595

V. Cadierno, A. Varela-ꢀlvarez et al.
Egas are the electronic energies in presence or absence of the continuum
field, and Gnes is a term that includes nonelectrostatic contributions.[35b]
Water and THF were considered as solvents in this study. All theoretical
calculations were carried out with the Gaussian 03 packages of pro-
grams.[36] Very tight criteria for the SCF convergence and an ultrafine
grid numerical integrations were employed. Also, a tight criterion was re-
quested for all the optimizations.
tion was monitored by regular sampling and analysis by GC). Once fin-
ished, the reaction mixture was cooled to room temperature and extract-
ed with diethyl ether (3ꢅ5 mL). The combined organic phases were
washed with brine, dried over anhydrous MgSO4, filtered, and evaporat-
ed to give crude 1-propenyl ethers 4a–t, which were purified by flash
chromatography on silica gel with hexane/EtOAc (10/1) as eluent. The
identities of compounds 4a,[51] 4b–f,[52] 4g,[53] 4h and 4i,[54] 4p,[55] 4r,[56]
and 4s[57] were assessed by comparison of their 1H and 13C{1H} NMR
data with those previously described in the literature, and by their frag-
General experimental methods: Manipulations were performed under an
atmosphere of dry nitrogen by using vacuum-line and standard Schlenk
or sealed-tube techniques. Organic solvents were dried by standard meth-
ods and distilled under nitrogen before use. All reagents were obtained
from commercial suppliers and used without further purification with the
mentation in GC/MSD. 4j: Orange oil, yield: 0.332 g (81%). E/Z ratio=
ꢀ1
~
5:1 (GC determined). IR (Nujol): n=1674 cm (m, C=C); MS (EI,
70 eV): m/z 205 [M+] (30), 190 (100), 162 (10), 149 (10), 133 (10), 120
(10%); NMR data for the E isomer: 1H NMR (C6D6): d=0.97 (t, 6H,
J=7.0 Hz), 1.55 (dd, 3H, J=7.0 and 1.6 Hz), 3.05 (q, 4H, J=7.0 Hz),
5.45 (dq, 1H, J=12.0 and 7.0 Hz), 6.39 (m, 1H), 6.50–6.57 (m, 3H), 7.16–
7.21 ppm (m, 1H); 13C{1H} NMR (C6D6): d=12.1, 12.4, 44.2, 100.9, 103.4,
106.8, 130.1, 143.0, 149.3, 159.5 ppm; NMR data for the Z isomer:
1H NMR (C6D6): d=0.98 (t, 6H, J=7.0 Hz), 1.85 (dd, 3H, J=7.0 and
1.9 Hz), 3.05 (q, 4H, J=7.0 Hz), 4.77 (dq, 1H, J=7.0 and 6.8 Hz), 6.39
(m, 1H), 6.50–6.57 (m, 3H), 7.16–7.21 ppm (m, 1H); 13C{1H} NMR
(C6D6): d=12.1, 12.4, 44.2, 100.7, 103.3, 106.6, 130.1, 141.8, 149.3,
ACTHNUTRGNEUNG
exception of [{Ru(h3:h3-C10H16)(m-Cl)Cl}2] (1),[37] allyl 2-chlorophenyl
ether (3b),[38] allyl 3-chlorophenyl ether (3c),[39] allyl 4-chlorophenyl
ether (3d),[40] allyl 4-formylphenyl ether (3e),[41] 4-(N-acetylamino)phenyl
allyl ether (3 f),[40] allyl 2-methylphenyl ether (3g),[42] allyl 4-methylphenyl
ether (3H),[42] 6-allyloxyquinoline (3k),[43] 2,2’-bis
ACTHNUTRGNE(UNG allyloxy)-1,1’-binaph-
thalene (3l),[44] 2-acetylphenyl allyl ether (3m),[45] 2-allyloxybenzophe-
none (3n),[46] 2-cyanophenyl allyl ether (3o),[47] allyl ethyl ether (3p),[48]
3-(allyloxypropyl)benzene (3s),[49] and allyl diphenylmethyl ether (3t),[50]
which were prepared by following the methods reported in the literature.
GC measurements were made with a Hewlett-Packard HP6890 equip-
ment on HP-INNOWAX cross-linked polyethylene glycol (30 m, 250 mm)
or Supelco Beta-Dex 120 (30 m, 250 mm) column. GC/MSD measure-
ments were performed on an Agilent 6890N equipment coupled to a
5973 mass detector (70 eV electron impact ionization) with a HP-1MS
column. Infrared spectra were recorded on a PerkinElmer 1720-XFT
spectrometer. NMR spectra were recorded on a Bruker DPX-300 instru-
ment at 300 MHz (1H) or 75.4 MHz (13C) using SiMe4 as standard.
159.4 ppm. 4k: Orange oil. Yield: 0.326 g (88%). E/Z ratio=9/1 (GC).
ꢀ1
IR (Nujol): n=1672 cm (m, C=C); MS (EI, 70 eV): m/z 185 [M+] (20),
~
170 (100), 144 (50%); NMR data for the E isomer: 1H NMR (CDCl3):
d=1.72 (dd, 3H, J=6.8 and 1.4 Hz), 5.50 (dq, 1H, J=12.2 and 6.8 Hz),
6.53 (dq, 1H, J=12.2 and 1.4 Hz), 7.21 (br, 1H), 7.34–7.43 (m, 2H),
8.02–8.06 (m, 2H), 8.79 ppm (dd, 1H, J=4.3 and 1.4 Hz); 13C{1H} NMR
(CDCl3): d=14.8, 111.7, 112.5, 124.0, 124.6, 131.5, 133.4, 137.6, 143.6,
147.2, 150.9, 157.9 ppm; NMR data for the Z isomer: 1H NMR (CDCl3):
d=1.75 (dd, 3H, J=6.7 and 1.5 Hz), 5.50 (m, 1H), 6.53 (m, 1H), 7.21
(br, 1H), 7.34–7.47 (m, 2H), 8.02–8.06 (m, 2H), 8.69 ppm (d, 1H, J=
4.5 Hz); 13C{1H} NMR (CDCl3): d=14.8, 111.3, 111.5, 123.5, 123.9, 131.5,
1
Copies of the H and 13C{1H} NMR spectra of all new compounds are in-
cluded in the Supporting Information.
Preparation of allyl 3-(diethylamino)phenyl ether (3j): K2CO3 (11.0 g,
80 mmol) was added to a stirred solution of 3-(diethylamino)phenol
(3.41 g, 20 mmol) in acetone (100 mL) at room temperature, and the re-
sulting mixture heated to reflux for 1 h. Allyl bromide (1.76 mL,
22 mmol) was then added, and reflux continued for additional 4 h. After
this time, the reaction mixture was cooled to room temperature, filtered,
and the filtrate evaporated to dryness. Purification by flash chromatogra-
132.9, 137.1, 142.7, 147.2, 149.4, 155.8 ppm. 4l: Orange oil. Yield: 0.601 g
ꢀ1
~
(82%). EE/ZZ ratio=7/1 (GC). IR (Nujol): n=1674 cm (s, C=C); MS
(EI, 70 eV): m/z 366 [M+] (15), 268 (20), 239 (30), 195 (20), 41 (100%);
NMR data for the EE isomer: 1H NMR (C6D6): d=1.35 (dd, 6H, J=7.0
and 1.6 Hz), 5.12 (dq, 2H, J=12.1 and 7.0 Hz), 6.42 (m, 2H), 7.14 (td,
2H, J=8.3 and 1.1 Hz), 7.25 (td, 2H, J=8.0 and 1.1 Hz), 7.40 (d, 2H, J=
8.9 Hz), 7.45 (d, 2H, J=8.3 Hz), 7.55 ppm (m, 4H); 13C{1H} NMR
(C6D6): d=12.0, 107.1, 118.1, 121.2, 124.5, 126.0, 126.8, 128.1, 129.8,
130.6, 134.5, 143.7, 153.1 ppm; NMR data for the ZZ isomer: 1H NMR
(C6D6): d=1.42 (dd, 6H, J=7.0 and 1.6 Hz), 4.55 (dq, 2H, J=7.0 and
7.0 Hz), 6.42 (m, 2H), 7.14 (td, 2H, J=8.3 and 1.1 Hz), 7.25 (td, 2H, J=
8.0 and 1.1 Hz), 7.40 (d, 2H, J=8.9 Hz), 7.45 (d, 2H, J=8.3 Hz),
7.55 ppm (m, 4H); 13C{1H} NMR (C6D6): d=9.1, 106.6, 117.2, 120.8,
124.5, 126.0, 126.8, 128.2, 129.9, 130.6, 134.5, 142.1, 153.1 ppm. 4q:
phy on silica gel with hexane/EtOAc (5/1) as eluent afforded 3j as a col-
ꢀ1
~
orless oil in 88% yield (3.11 g). IR (Nujol): n=1612 cm (m, C=C);
1H NMR (CDCl3): d=1.22 (t, 6H, J=7.1 Hz), 3.39 (q, 4H, J=7.1 Hz),
4.59 (dt, 2H, J=5.4 and 1.4 Hz), 5.34 (ddd, 1H, J=9.1, 1.4, and 1.4 Hz),
5.49 (ddd, 1H, J=17.3, 1.4, and 1.4 Hz), 6.13 (m, 1H), 6.36 (m, 3H),
7.17 ppm (t, 1H, J=8.0 Hz); 13C{1H} NMR (CDCl3): d=12.7, 44.5, 68.8,
99.2, 101.0, 105.3, 117.4, 129.9, 133.9, 149.2, 160.1 ppm; MS (EI, 70 eV):
m/z 205 [M+] (50), 190 (100), 149 (60), 120 (15%).
~
Orange oil. Yield: 0.306 g (91%). E/Z ratio=1/2 (GC). IR (Nujol): n=
1666 cmꢀ1 (s, C=C); MS (EI, 70 eV): m/z 168 [M+] (5), 111 (5), 70 (30),
Preparation of allyl cyclooctyl ether (3q): NaH (0.38 g, 15 mmol) was
added to a stirred solution of cyclooctyl alcohol (1.34 mL, 10 mmol) in
THF (50 mL) at room temperature, and the resulting mixture heated to
reflux for 1 h. Allyl bromide (1.76 mL, 22 mmol) was then added, and
reflux continued for an additional 6 h period. Then, the reaction mixture
was cooled to room temperature, quenched with saturated aqueous
NH4Cl (5 mL), and the aqueous phase extracted with Et2O (3ꢅ25 mL).
The combined organic phases were dried over anhydrous MgSO4, fil-
tered, and concentrated under reduced pressure. Purification by flash
chromatography on silica gel with hexane/EtOAc mixture (5/1) as eluent
1
41 (100%); NMR data for the E isomer: H NMR (CDCl3): d=1.41–1.80
(m, 17H), 3.78 (m, 1H), 4.80 (m, 1H), 6.01 ppm (dd, 1H, J=12.4 and
1.4 Hz); 13C{1H} NMR (CDCl3): d=12.5, 22.7, 25.3, 27.1, 34.7, 80.4, 100.3,
145.3 ppm; NMR data for the Z isomer: 1H NMR (CDCl3): d=11.41–
1.80 (m, 17H), 3.72 (m, 1H), 4.35 (m, 1H), 5.90 ppm (dd, 1H, J=6.2 and
1.4 Hz); 13C{1H} NMR (CDCl3): d=9.3, 23.0, 25.5, 27.3, 31.7, 81.7, 101.2,
144.4 ppm. 4t: Orange oil. Yield: 0.376 g (84%). E/Z ratio=2/1 (GC).
ꢀ1
IR (Nujol): n=1660 cm (s, C=C); MS (EI, 70 eV): m/z 224 [M+] (5),
~
209 (5), 167 (50), 77 (100%); NMR data for the E isomer: 1H NMR
(CDCl3): d=1.74 (dd, 3H, J=6.8 and 1.4 Hz), 5.29 (dd, 1H, J=12.4 and
6.8 Hz), 5.97 (s, 1H), 6.51 (dd, 1H, J=12.4 and 1.4 Hz), 7.46–7.65 ppm
(m, 10H); 13C{1H} NMR (CDCl3): d=12.8, 83.7, 102.4, 127.2, 127.9,
128.7, 141.8, 145.6 ppm; NMR data for the Z isomer: 1H NMR (CDCl3):
d=2.01 (dd, 3H, J=6.8 and 1.3 Hz), 4.74 (dc, 1H, J=6.8 and 6.8 Hz),
5.93 (s, 1H), 6.35 (dd, 1H, J=6.8 and 1.3 Hz), 7.46–7.65 ppm (m, 10H);
13C{1H} NMR (CDCl3): d=9.9, 84.8, 102.6, 127.2, 127.9, 128.7, 142.0,
144.5 ppm.
~
afforded 3q as a pale yellow oil in 87% yield (1.46 g). IR (Nujol): n=
1669 cmꢀ1 (m, C=C); H NMR (CDCl3): d=1.40–1.84 (m, 14H), 3.45 (m,
1
1H), 3.95 (dt, 2H, J=4.1 and 1.0 Hz), 5.12 (ddd, 1H, J=10.3, 1.0, and
1.0 Hz), 5.25 (ddd, 1H, J=17.2, 1.0 and 1.0 Hz), 5.90 ppm (m, 1H);
13C{1H} NMR (CDCl3): d=23.1, 25.5, 27.3, 31.5, 69.1, 79.1, 116.1,
135.7 ppm; MS (EI, 70 eV): m/z 168 [M+] (5), 125 (5), 97 (5), 70 (20), 41
(100%).
General procedure for catalytic isomerization of allyl ethers to 1-propen-
yl ethers: In
C10H16)Cl(m-Cl)}2] (1) (0.018 g, 0.03 mmol; 3 mol% of Ru) was added to
a
sealed tube under nitrogen atmosphere, [{Ru(h3:h3-
ACHTUNGTRENNUNG
a solution of allyl ether 3a–t (2 mmol) in water (10 mL), and the result-
ing mixture stirred at 758C for the indicated time (the course of the reac-
10596
www.chemeurj.org
ꢃ 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 2011, 17, 10583 – 10599

C=C Isomerization of O-Allylic Substrates
FULL PAPER
sponding enone, which further undergoes transfer hydrogenation of
the C=C bond via a pericyclic six-membered transition state.
Acknowledgements
[9] Grubbs and co-workers demonstrated, using labeled compounds,
This work was supported by the Ministerio de Ciencia e Innovaciꢆn of
Spain (MICINN) (Projects CTQ2007-67234-C02-01/BQU, CTQ2006-
08485/BQU, CTQ2010-14796/BQU and CSD2007-00006) and the Gobier-
no del Principado de Asturias (FICYT Projects IB08-023 and IB08-036).
N.N. thanks MEC and the European Social Fund for the award of a
Ph.D. grant.
that this mechanism is operative when [RuACTHUNRGTNEUNG(H2O)6]Tos2 is used as
precatalyst: D. V. McGrath, R. H. Grubbs, Organometallics 1994, 13,
224–235.
[10] a) Because the oxidation state of the metal must be raised by two,
this mechanism has been usually proposed for low-valent transition-
metal catalysts.[4] In line with this, Branchadell and Grꢇe recently
demonstrated by means of DFT calculations that such a mechanism
is operative in the conversion of allylic alcohols to carbonyl com-
pounds catalyzed by the Fe(CO)3 unit: V. Branchadell, C. Crꢇvisy,
R. Grꢇe, Chem. Eur. J. 2003, 9, 2062–2067; b) Esteruelas and co-
workers recently demonstrated, by isolation and structural charac-
terization of key intermediates, that half-sandwich OsII catalysts also
operate through this allyl metal hydride mechanism: M. Batuecas,
M. A. Esteruelas, C. Garcꢁa-Yebra, E. OÇate, Organometallics 2010,
29, 2166–2175.
[1] See, for example: a) B. M. Trost, Science 1991, 254, 1471–1477;
b) B. M. Trost, Angew. Chem. 1995, 107, 285–307; Angew. Chem.
Int. Ed. Engl. 1995, 34, 259–281; c) R. A. Sheldon, Pure Appl.
Chem. 2000, 72, 1233–1246; d) B. M. Trost, Acc. Chem. Res. 2002,
35, 695–705; e) B. M. Trost, M. U. Frederiksen, M. T. Rudd, Angew.
Chem. 2005, 117, 6788–6825; Angew. Chem. Int. Ed. 2005, 44, 6630–
6666; f) R. A. Sheldon, Green Chem. 2007, 9, 1273–1283.
[2] See, for example: a) Transition Metals in the Synthesis of Complex
Organic Molecules (Eds.: L. S. Hegedus, B. C. G. Soderberg), Uni-
versity Science Books, Sausalito, 2009; b) Transition Metals for Or-
ganic Synthesis: Building Blocks and Fine Chemicals (Eds.: M.
Beller, C. Bolm), Wiley-VCH, Weinheim, 2004.
[3] See, for example: a) Applied Homogeneous Catalysis with Organo-
metallic Compounds (Eds.: B. Cornils, W. A. Herrmann), Wiley-
VCH, Weinheim, 2002; b) P. W. N. M. van Leeuwen in Homogene-
ous Catalysis: Understanding the Art, Kluewer Academic Publishers,
Dordrecht, 2004; c) Metal-Catalysis in Industrial Organic Processes
(Eds.: G. P. Chiusoli, P. M. Maitlis), RSC, Cambridge, 2008.
[4] For reviews on this catalytic process, see: a) R. Uma, C. Crꢇvisy, R.
Grꢇe, Chem. Rev. 2003, 103, 27–51; b) R. C. van der Drift, E. Bouw-
man, E. Drent, J. Organomet. Chem. 2002, 650, 1–24; c) V. Cadier-
no, P. Crochet, J. Gimeno, Synlett 2008, 1105–1124.
[5] See, for example: a) M. Ito, S. Kitahara, T. Ikariya, J. Am. Chem.
Soc. 2005, 127, 6172–6173; b) F. Boeda, P. Mosset, C. Crꢇvisy, Tetra-
hedron Lett. 2006, 47, 5021–5024; c) V. Cadierno, J. Francos, J.
Gimeno, N. Nebra, Chem. Commun. 2007, 2536–2538; d) S. Bovo,
A. Scrivanti, N. Bertoldini, V. Beghetto, U. Matteoli, Synthesis 2008,
2547–2550; e) L. Mantilli, D. Gꢇrard, S. Torche, C. Besnard, C.
Mazet, Angew. Chem. 2009, 121, 5245–5249; Angew. Chem. Int. Ed.
2009, 48, 5143–5147; f) V. Cadierno, P. Crochet, J. Francos, S. E.
Garcꢁa-Garrido, J. Gimeno, N. Nebra, Green Chem. 2009, 11, 1992–
2000; g) D. H. Mac, T. Roisnel, V. Branchadell, R. Grꢇe, Synlett
2009, 1969–1973; h) L. Mantilli, C. Mazet, Chem. Commun. 2010,
46, 445–447; i) M. A. Fernꢂndez-Zfflmel, B. Lastra-Barreira, M.
Scheele, J. Dꢁez, P. Crochet, J. Gimeno, Dalton Trans. 2010, 39,
7780–7785; j) L. Mantilli, D. Gꢇrard, S. Torche, C. Besnard, C.
Mazet, Chem. Eur. J. 2010, 16, 12736–12745; k) L. Mantilli, D.
Gꢇrard, S. Torche, C. Besnard, C. Mazet, Pure Appl. Chem. 2010,
82, 1461–1469; l) H. C. Maytum, J. Francos, D. J. Whatrup, J. M. J.
Williams, Chem. Asian J. 2010, 5, 538–542; m) A. Quintard, A.
Alexakis, C. Mazet, Angew. Chem. 2011, 123, 2402–2406; Angew.
Chem. Int. Ed. 2011, 50, 2354–2358.
[6] a) A. Bouziane, T. Rꢇgnier, F. Carreaux, B. Carboni, C. Bruneau, J.-
L. Renaud, Synlett 2010, 207–210; b) G. Sabitha, S. Nayak, M. Bhik-
shapathi, J. S. Yadav, Org. Lett. 2011, 13, 382–385.
[7] a) C. Masters in Homogeneous Transition-Metal Catalysis, Chapman
and Hall, London, 1981, pp. 70–89; b) G. W. Parshall, S. D. Ittel, in
Homogeneous Catalysis, Wiley, New York, 1992, pp. 9–24; c) C.
Schultz, H. Grçger, C. Dinkel, K. Drauz, H. Waldmann in Applied
Homogeneous Catalysis with Organometallic Compounds, Vol. 2
(Eds.: B. Cornils, W. A. Herrmann), Wiley-VCH, Weinheim, 2002,
pp. 1034–1130.
[11] B. M. Trost, R. J. Kulawiec, J. Am. Chem. Soc. 1993, 115, 2027–
2036.
[12] See, for example: a) B. M. Trost, R. J. Kulawiec, Tetrahedron Lett.
1991, 32, 3039–3042; b) F. Stunnenberg, F. G. H. Niele, E. Drent,
Inorg. Chim. Acta 1994, 222, 225–233; c) R. C. van der Drift, M.
Vailati, E. Bouwman, E. Drent, J. Mol. Catal. A 2000, 159, 163–177;
d) R. C. van der Drift, J. W. Sprengers, E. Bouwman, W. P. Mul, H.
Kooijman, A. L. Spek, E. Drent, Eur. J. Inorg. Chem. 2002, 2147–
2155.
[13] See, for example: a) C. Slugovc, E. Rüba, R. Schmid, K. Kirchner,
Organometallics 1999, 18, 4230–4233; b) R. C. van der Drift, E.
Bouwman, E. Drent, H. Kooijman, A. L. Spek, A. B. van Oort, W. P.
Mul, Organometallics 2002, 21, 3401–3407; c) C. M. Standfest-
Hauser, T. Lummerstorfer, R. Schmid, K. Kirchner, H. Hoffmann,
M. Puchberger, Monatsh. Chem. 2003, 134, 1167–1175; d) R. C. van
der Drift, M. Gagliardo, H. Kooijman, A. L. Spek, E. Bouwman, E.
Drent, J. Organomet. Chem. 2005, 690, 1044–1055; e) B. Martꢁn-
Matute, K. Bogꢂr, M. Edin, F. B. Kaynak, J.-E. Bäckvall, Chem. Eur.
J. 2005, 11, 5832–5842; f) A. Bouziane, B. Carboni, C. Bruneau, F.
Carreaux, J.-L. Renaud, Tetrahedron 2008, 64, 11745–11750; g) A.
Bartoszewicz, M. Livendahl, B. Martꢁn-Matute, Chem. Eur. J. 2008,
14, 10547–10550; h) N. Ahlsten, B. Martꢁn-Matute, Adv. Synth.
Catal. 2009, 351, 2657–2666; i) N. Ahlsten, H. Lundberg, B. Martꢁn-
Matute, Green Chem. 2010, 12, 1628–1633.
[14] For a general review on the coordination chemistry and catalytic ap-
plications of complex 1, see: V. Cadierno, P. Crochet, S. E. Garcꢁa-
Garrido, J. Gimeno, Curr. Org. Chem. 2006, 10, 165–183.
[15] V. Cadierno, S. E. Garcꢁa-Garrido, J. Gimeno, A. Varela-ꢀlvarez,
J. A. Sordo, J. Am. Chem. Soc. 2006, 128, 1360–1370.
[16] These TOF and TON values are among the highest reported to date
in the literature for this catalytic transformation. See reference [4c],
and references therein.
[17] In recent years, increasing awareness of environmental concerns has
stimulated the development of organic reactions in aqueous media,
since water is the most benign and inexpensive solvent known. For
leading references, see: a) C.-J. Li, Chem. Rev. 1993, 93, 2023–2035;
b) A. Lubineau, J. Auge, Y. Queneau, Synthesis 1994, 741–760;
c) U. M. Lindstrçm, Chem. Rev. 2002, 102, 2751–2772; d) C.-J. Li,
Chem. Rev. 2005, 105, 3095–3166; e) C. K. Z. Andrade, L. M. Alves,
Curr. Org. Chem. 2005, 9, 195–218; f) C.-J. Li, L. Chen, Chem. Soc.
Rev. 2006, 35, 68–82; g) L. Chen, C.-J. Li, Adv. Synth. Catal. 2006,
348, 1459–1484; h) C. I. Herrerꢁas, X. Yao, Z. Li, C.-J. Li, Chem.
Rev. 2007, 107, 2546–2562; i) C.-J. Li, T. H. Chan in Comprehensive
Organic Reactions in Aqueous Media, Wiley, New York, 2007; j) Or-
ganic Reactions in Water: Principles, Strategies and Applications
(Ed.: U. M. Lindstrçm), Blackwell, Oxford, 2007; k) Handbook of
Green Chemistry, Vol. 5 (Eds.: P. T. Anastas, C.-J. Li), Wiley-VCH,
Weinheim, 2010.
[8] An alternative outer-sphere mechanism was suggested by Ikariya
and co-workers in the isomerization processes promoted by phosphi-
no-amine ruthenium complexes of type [RuClCp*{k
NH2}] (see reference [5a]). In this case, Ru amido complex
[RuCp*{k
2(P,N)-Ph2P-X-NH}] generated in situ dehydrogenates the
2(P,N)-Ph2P-X-
ACHTUNGTRENNUNG
[18] Other examples of catalytic redox isomerizations of allylic alcohols
in aqueous media can be found in references [9],[13i] and a) D. V.
McGrath, R. H. Grubbs, J. W. Ziller, J. Am. Chem. Soc. 1991, 113,
ACHTUNGTRENNUNG
alcohol to generate [RuHCp*{k
2(P,N)-Ph2P-X-NH2}] and the corre-
ACHTUNGTRENNUNG
Chem. Eur. J. 2011, 17, 10583 – 10599
ꢃ 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
10597

V. Cadierno, A. Varela-ꢀlvarez et al.
3611–3613; b) T. Karlen, A. Ludi, Helv. Chim. Acta 1992, 75, 1604–
1606; c) H. Bricout, E. Monflier, J. F. Carpentier, A. Mortreux, Eur.
J. Inorg. Chem. 1998, 1739–1744; d) H. Schumann, V. Ravindar, L.
Meltser, W. Baidossi, Y. Sasson, J. Blum, J. Mol. Catal. A 1997, 118,
55–61; e) C. de Bellefon, S. Caravieilhes, E. G. Kuntz, C. R. Acad.
Sci. Ser. IIc: Chim. 2000, 3, 607–614; f) C. Bianchini, A. Meli, W.
Oberhauser, New J. Chem. 2001, 25, 11–12; g) D. A. Knight, T. L.
Schull, Synth. Commun. 2003, 33, 827–831; h) V. Cadierno, P. Cro-
chet, S. E. Garcꢁa-Garrido, J. Gimeno, Dalton Trans. 2004, 3635–
3641; i) V. Cadierno, S. E. Garcꢁa-Garrido, J. Gimeno, Chem.
Commun. 2004, 232–233; j) A. E. Dꢁaz-ꢀlvarez, P. Crochet, M. Za-
blocka, C. Duhayon, V. Cadierno, J. Gimeno, J. P. Majoral, Adv.
Synth. Catal. 2006, 348, 1671–1679; k) P. Crochet, J. Dꢁez, M. A.
Fernꢂndez-Zfflmel, J. Gimeno, Adv. Synth. Catal. 2006, 348, 93–100;
l) M. Fekete, F. Joꢆ, Catal. Commun. 2006, 7, 783–786; m) T.
Campos-Malpartida, M. Fekete, F. Joꢆ, A. Kathꢆ, A. Romerosa, M.
Saoud, W. Wojtkꢆw, J. Organomet. Chem. 2008, 693, 468–474; n) B.
Lastra-Barreira, J. Dꢁez, P. Crochet, Green Chem. 2009, 11, 1681–
1686; o) A. Pontes da Costa, J. A. Mata, B. Royo, E. Peris, Organo-
metallics 2010, 29, 1832–1838; p) B. Gonzꢂlez, P. Lorenzo-Luis, M.
124, 13390–13391; c) W. A. L. van Otterlo, R. Pathak, C. B. de Kon-
ing, Synlett 2003, 1859–1861; d) B. Schmidt, Eur. J. Org. Chem.
2003, 816–819; e) W. A. L. van Otterlo, G. L. Morgans, S. D.
Khanye, B. A. A. Aderibigbe, J. P. Michael, D. G. Billing, Tetrahe-
dron Lett. 2004, 45, 9171–9175; f) W. A. L. van Otterlo, E. L. Ngidi,
S. Kuzvidza, G. L. Morgans, S. S. Moleele, C. B. de Koning, Tetrahe-
dron 2005, 61, 9996–10006.
[27] We note that 1) a change in substrate concentration does not signifi-
cantly affect either the efficiency or stereoselectivity of the process,
and virtually the same results are obtained when working with 0.1
or 0.3m aqueous solutions of 2a instead of 0.2m, and 2) almost negli-
gible isomerization of the C=C bond of 3a was observed when THF
was used as solvent (ca. 12% GC yield of 4a after 24 h of heating at
758C).
[28] The synthesis of bis- and polyfunctional UV-reactive 1-propenyl
ethers and their use as monomers in photopolymerization processes
is a field of current research interest. See, for example: a) S. Krom-
piec, M. Antoszczyszyn, M. Urbala, T. Bieg, Polish J. Chem. 2000,
74, 737–739; b) D. Martysz, M. Urbala, M. Antoszczyszyn, R. Pilaw-
ka, Polimery 2002, 47, 849–851; c) D. Martysz, M. Antoszczyszyn,
M. Urbala, S. Krompiec, E. Fabrycy, Prog. Org. Coat. 2003, 46, 302–
˝
Serrano-Ruiz, É. Papp, M. Fekete, K. Csꢇpke, K. Osz, A. Kathꢆ, F.
´
Joꢆ, A. Romerosa, J. Mol. Catal. A 2010, 326, 15–20; q) A. Azua, S.
Sanz, E. Peris, Organometallics 2010, 29, 3661–3664; r) S. E. Garcꢁa-
Garrido, J. Francos, V. Cadierno, J.-M. Basset, V. Polshettiwar,
ChemSusChem 2011, 4, 104–111.
311; d) S. Krompiec, N. Kuznik, M. Urbala, J. Rzepa, J. Mol. Catal.
A 2006, 248, 198–209; e) Z. Czech, M. Urbala, Polimery 2007, 52,
438–442; f) M. Urbala, Appl. Catal. A 2010, 377, 27–34.
[29] Efficient methodologies for the selective deprotection of N-allyl
amines, amides, and lactams in aqueous media using complex 1 have
already been described by some of us: a) V. Cadierno, S. E. Garcꢁa-
Garrido, J. Gimeno, N. Nebra, Chem. Commun. 2005, 4086–4088;
b) V. Cadierno, J. Gimeno, N. Nebra, Chem. Eur. J. 2007, 13, 6590–
6594.
[30] J. P. Perdew, S. Kurth in A Primer in Density Functional Theory
(Eds.: C. Fiolhais, F. Nogueira, M. Marques), Springer, Berlin, 2003.
[31] Y. Zhao, D. G. Truhlar, J. Phys. Chem. A 2004, 108, 6908–6918.
[32] J. Zheng, Y. Zhao, D. G. Truhlar, J. Chem. Theory Comput. 2009, 5,
808–821.
[19] The ability of dimer [{Ru(h3:h3-C10H16)Cl
ACTHNUTRGNENUG(m-Cl)}2] (1) to promote
isomerization allylic alcohols in water has not gone unnoticed for
the pharmaceutical industry. In this regard, a method for the large-
scale production of the analgesic drugs hydromorphone and hydro-
codone, by catalytic isomerization of morphine and codeine in aque-
ous media using catalytic amounts of 1 was recently patented: P. X.
Wang, T. Jiang, D. W. Berberich (Mallinckrodt Inc.), PCT Int. Appl.
WO2010/118271, 2010.
[20] a) For a review on metal-catalyzed isomerization of allyl ethers, see:
´
N. Kuznik, S. Krompiec, Coord. Chem. Rev. 2007, 251, 222–233;
b) For a recent example not involving transition metals, see: C. Su,
P. G. Williard, Org. Lett. 2010, 12, 5378–5381.
[33] W. J. Hehre, L. Radom, P. von R. Schleyer, J. A. Pople, Ab initio
Molecular Orbital Theory, Wiley, New York, 1986.
[21] Isomerization of allyl ether units is a key step in the preparation of
several polymers such as poly(vinyl ether)s. See, for example: a) K.
Yamamoto, T. Higashimura, J. Polym. Sci. Part A 1974, 12, 613–
626; b) M. Sangermano, G. Malucelli, R. Bongiovanni, A. Pirola, U.
Annby, N. Rehnberg, Eur. Polym. J. 2002, 38, 655–659; c) Y.-M.
Kim, L. K. Kostanski, F. J. MacGregor, Polymer 2003, 44, 5103–
5109; d) S. Minegishi, T. Otsuka, A. Kameyama, T. Nishikubo, J.
Polym. Sci. Polym. Chem. Ed. 2005, 43, 3105–3115.
[22] The use of allyl moieties as protecting groups in alcohols is rather
common in synthetic organic chemistry. See, for example: a) M.
Schelhaas, H. Waldman, Angew. Chem. 1996, 108, 2192–2219;
Angew. Chem. Int. Ed. Engl. 1996, 35, 2056–2083; b) F. Guibꢇ, Tet-
rahedron 1997, 53, 13509–13556; c) F. Guibꢇ, Tetrahedron 1998, 54,
2967–3042; d) T. W. Greene, P. G. M. Wuts in Greeneꢀs Protective
Groups in Organic Synthesis, Wiley-Interscience, New York, 2006.
[23] Location of TSI5H_H2O-I6H_H2O proved difficult due to SCF con-
vergence problems. A weaker criterion for the SCF convergence
(“conver=6”) and the default criteria for optimization were adopt-
ed in the Gaussian 03 runs for this particular case.
[24] a) A. Varela-ꢀlvarez, D. Markovic, P. Vogel, J. A. Sordo, J. Am.
Chem. Soc. 2009, 131, 9547–9561; b) A. Gonzꢂlez-Lafont, J. M.
Lluch, A. Varela-ꢀlvarez, J. A. Sordo, J. Phys. Chem. B 2008, 112,
328–335; c) A. Gonzꢂlez-Lafont, J. M. Lluch, A. Varela-ꢀlvarez,
J. A. Sordo, J. Phys. Chem. A 2010, 114, 2768–2777.
[25] For a detailed discussion on this point see the following articles and
references therein: a) A. Varela-ꢀlvarez, V. M. Rayꢆn, P. Redondo,
C. Barrientos, J. A. Sordo, J. Chem. Phys. 2009, 131, 144309/1–
144309/11; b) A. Varela-ꢀlvarez, J. A. Sordo, P. Redondo, A. Largo,
C. Barrientos, V. M. Rayꢆn, Theor. Chem. Acc. 2011, 128, 609–618.
[26] See, for example: a) H.-G. Park, D.-H. Kim, M.-S. Yoo, M.-K. Park,
S.-S. Jew, Tetrahedron Lett. 2000, 41, 4579–4582; b) A. E. Sutton,
B. A. Seigal, D. F. Finnegan, M. L. Snapper, J. Am. Chem. Soc. 2002,
[34] M. Dolg, H. Stoll, H. Preuss, R. M. Pitzer, J. Phys. Chem. 1993, 97,
5852–5859.
[35] a) J. Tomasi, B. Menucci, R. Cammi, Chem. Rev. 2005, 105, 2999–
3094; b) J. Ho, A. Klamt, M. L. Coote, J. Phys. Chem. A 2010, 114,
13442–13444.
[36] Gaussian 03, Revision C.02, M. J. Frisch, G. W. Trucks, H. B. Schle-
gel, G. E. Scuseria, M. A. Robb, J. R. Cheeseman, J. A. Montgom-
ery, Jr., T. Vreven, K. N. Kudin, J. C. Burant, J. M. Millam, S. S.
Iyengar, J. Tomasi, V. Barone, B. Mennucci, M. Cossi, G. Scalmani,
N. Rega, G. A. Petersson, H. Nakatsuji, M. Hada, M. Ehara, K.
Toyota, R. Fukuda, J. Hasegawa, M. Ishida, T. Nakajima, Y. Honda,
O. Kitao, H. Nakai, M. Klene, X. Li, J. E. Knox, H. P. Hratchian,
J. B. Cross, C. Adamo, J. Jaramillo, R. Gomperts, R. E. Stratmann,
O. Yazyev, A. J. Austin, R. Cammi, C. Pomelli, J. W. Ochterski, P. Y.
Ayala, K. Morokuma, G. A. Voth, P. Salvador, J. J. Dannenberg,
V. G. Zakrzewski, S. Dapprich, A. D. Daniels, M. C. Strain, O.
Farkas, D. K. Malick, A. D. Rabuck, K. Raghavachari, J. B. Fores-
man, J. V. Ortiz, Q. Cui, A. G. Baboul, S. Clifford, J. Cioslowski,
B. B. Stefanov, G. Liu, A. Liashenko, P. Piskorz, I. Komaromi, R. L.
Martin, D. J. Fox, T. Keith, M. A. Al-Laham, C. Y. Peng, A. Na-
nayakkara, M. Challacombe, P. M. W. Gill, B. Johnson, W. Chen,
M. W. Wong, C. Gonzalez, J. A. Pople, Gaussian, Inc., Wallingford,
CT, 2004.
[37] a) L. Porri, M. C. Gallazzi, A. Colombo, G. Allegra, Tetrahedron
Lett. 1965, 6, 4187–4189; b) A. Salzer, A. Bauer, F. Podewils in Syn-
thetic Methods of Organometallic and Inorganic Chemistry, Vol. 9
(Ed.: W. A. Herrmann), Thieme, Stuttgart, 2000, pp. 36–38; c) A.
Salzer, A. Bauer, S. Geyser, F. Podewils, G. C. Turpin, R. D. Ernst,
Inorg. Synth. 2004, 34, 59–65.
[38] H. Buu, K.-W. Hiong, R. Royer, Bull. Soc. Chim. Fr. 1945, 12, 866–
869.
[39] W. N. White, C. D. Slater, J. Org. Chem. 1961, 26, 3631–3638.
10598
www.chemeurj.org
ꢃ 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 2011, 17, 10583 – 10599

C=C Isomerization of O-Allylic Substrates
FULL PAPER
[40] W. N. White, D. Gwynn, R. Schlitt, C. Girard, W. Fife, J. Am. Chem.
Soc. 1958, 80, 3271–3277.
[50] T. L. Loo, J. Am. Chem. Soc. 1952, 74, 4717–4718.
[51] P. Golborn, F. Scheinmann, J. Chem. Soc. Perkin Trans. 1 1973,
[41] H. L. Goering, R. R. Jacobsen, J. Am. Chem. Soc. 1958, 80, 3277–
3285.
2870–2875.
´
[52] S. Krompiec, N. Kuznik, R. Penczek, J. Rzepa, J. Mrowiec-Białꢆn, J.
[42] F. Kremers, F. Roth, E. Tietze, L. Claisen, Justus Liebigs Ann.
Chem. 1925, 442, 210–245.
[43] C. Pene, P. Demerseman, A. Cheutin, R. Royer, Bull. Soc. Chim. Fr.
1966, 586–594.
Mol. Catal. A 2004, 219, 29–40.
[53] W. Kirmse, G. Hçmberger, J. Am. Chem. Soc. 1991, 113, 3925–3934.
[54] K. Yamamoto, T. Higashimura, J. Polymer Sci. Polymer Chem. Ed.
1974, 12, 613–626.
[44] R. Kolodziuk, B. Kryczka, P. Lhoste, S. Ponwanski, D. Sinou, A. Za-
wisza, Synth. Commun. 2000, 30, 3955–3961.
[45] T. Shimizu, Y. Hayashi, M. Nakano, K. Teramura, Bull. Chem. Soc.
Jpn. 1984, 57, 134–141.
[46] S. Motoki, T. Watanabe, T. Saito, Tetrahedron Lett. 1989, 30, 189–
192.
[55] R. Lazzaroni, R. Settambolo, G. Uccello-Barretta, Organometallics
1995, 14, 4644–4650.
[56] a) E. Becker, C. Slugovc, E. Rüba, C. Standfest-Hauser, K. Mereit-
er, R. Schmid, K. Kirchner, J. Organomet. Chem. 2002, 649, 55–63;
b) A. Wille, S. Tomm, H. Frauenrath, Synthesis 1998, 305–308.
[57] K. Tomooka, T. Inoue, T. Nakai, Chem. Lett. 2000, 418–419.
[47] Z.-M. Wang, X.-L. Zhang, K. B. Sharpless, Tetrahedron Lett. 1993,
34, 2267–2270.
[48] W. M. Lauer, C. S. Benton, J. Org. Chem. 1959, 24, 804–806.
[49] T. Akiyama, H. Hirofuji, S. Ozaki, Bull. Chem. Soc. Jpn. 1992, 65,
1932–1938.
Received: April 12, 2011
Published online: August 17, 2011
Chem. Eur. J. 2011, 17, 10583 – 10599
ꢃ 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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10599