Palladium-Catalyzed Reductive Insertion of Alcohols into Aryl Ether Bonds

Article abstract of DOI:10.1002/anie.201709445

Palladium on carbon catalyzes C?O bond cleavage of aryl ethers (diphenyl ether and cyclohexyl phenyl ether) by alcohols (R?OH) in H₂. The aromatic C?O bond is cleaved by reductive solvolysis, which is initiated by Pd-catalyzed partial hydrogenation of one phenyl ring to form an enol ether. The enol ether reacts rapidly with alcohols to form a ketal, which generates 1-cyclohexenyl?O?R by eliminating phenol or an alkanol. Subsequent hydrogenation leads to cyclohexyl?O?R.

Full text of DOI:10.1002/anie.201709445

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Accepted Article
Title: Palladium catalyzed reductive insertion of alcohols in aryl ether
bonds
Authors: Meng Wang, Oliver Y Gutierrez, Donald Camaioni, and
Johannes Lercher
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10.1002/anie.201709445
Angewandte Chemie International Edition
COMMUNICATION
Palladium catalyzed reductive insertion of alcohols in aryl ether
bonds
Meng Wang,[a] Oliver Y. Gutiérrez,[a] Donald M. Camaioni,[a] and Johannes A. Lercher*[a][b]
Abstract: Pd/C catalyzes C-O bond cleavage of aryl ethers (diphenyl
ether and cyclohexyl phenyl ether) by alcohols (R-OH) in H2. The
aromatic C-O bond is cleaved by reductive solvolysis, which is
initiated by Pd-catalyzed partial hydrogenation of one phenyl ring to
form an enol ether. The enol ether reacts rapidly with alcohols to form
a ketal, which generates 1-cyclohexenyl-O-R by eliminating phenol or
an alkanol. Subsequent hydrogenation leads to cyclohexyl-O-R.
C4 alkanols are also proposed as environmentally benign solvents
for bio-oil upgrading under mild conditions.[8]
In principle, the enol ether intermediate (Eq. 1) may react in
alcoholic solvents to give reductive alcoholysis products.
However, while several examples of the conversion of aryl ethers
on supported metals in alcoholic solvents have been reported,[2a,
4a, 8]
reductive metal-catalyzed alcoholysis has not been
demonstrated. In contrast, reaction with supported Ni catalysts
led predominantly to hydrogenolysis,[3a, 3e] as also reported for
other supported metals.[3c, 8a, 9]
Lignin, which contains 40 % of the energy content in
lignocellulose, has been widely studied as feedstock for energy
and chemicals production.[1] These studies show that profoundly
new approaches are needed for the potential value in lignin to be
realized. New catalysts, reactions, and mechanistic insights are
required for efficient lignin depolymerization and selective
deoxygenation of the resulting fragments.[2] Because of the
strength and stability of the linkages, catalytic cleavage of C-O
bonds in aromatic ethers is an important step in this chemistry.[2c,
2f] Several ways of cleaving ether bonds have been reported in the
last decade in addition to the classic acid-catalyzed hydrolytic
cleavage. These include metal-catalyzed hydrogenolysis,
hydrolysis or oxidative cleavage.[3] Reductive cleavage of ether
bonds is conceptually an elegant pathway to convert (polymeric)
ethers to alkanes, alcohols and other ethers.[2a, 3a, 3e, 4] Of particular
interest is the catalysis of solvolytic routes that may conceptually
allow to catalyze more complex reaction products.
In order to develop quantitative alcoholysis, we report here
a mechanistic study of the reductive transetherification of diphenyl
ether and phenyl cyclohexyl ether, as examples of di-aryl ethers,
as well as aryl-alkyl ethers. Building upon our previous findings[5]
on reductive hydrolysis of aryl ethers (e.g., PhOPh and PhOR)
suggests that reduction in methanol should occur as in Scheme 1
to produce methoxycyclohexane and ROH, or when R = Ph,
phenol which ultimately is converted to methoxycyclohexane and
cyclohexanol. In the following, we first analyze in detail the
reactions of ethers in methanol. This is followed by exploring the
broader applicability of alcoholysis as synthetic approach.
Scheme 1. Reductive methanolysis of aryl ether on palladium
O
O
+ 3 H2
hydrogenation
+ H2
R
R
We reported recently the mechanism of selective hydrolytic
cleavage of the arene-oxygen bond in aromatic ethers.[5] Initiated
by partial hydrogenation of the arene ring to an enol ether, the
aromatic C-O bond is cleaved in this mechanism by addition of
water. Water rapidly reacts with the enol ether to form a hemi-
ketal, which undergoes elimination to cyclohexanone and
partial
hydrogenation
+ 2 H2
Hydrogenation products
Methanolysis products
O
O
O
O
O
+ CH
R
-ROH
+ H2
3OH
R
addtion
R-OH elimination
hydrogenation
phenol/alkanol (Eq. 1).[5-6]
In agreement with the above formulated hypothesis,
HO
diphenyl ether was almost fully converted with methanol on 5
wt. % Pd/C (conversion = 92 %) after 48 h in H2 (Entry 1, Table 1)
at 200 °C, while no reaction was observed in N2 atmosphere
(Entry 2, Table 1). Reductive methanolysis was the dominant
mechanism as indicated by the high selectivity to 1-
methoxycyclohexane (39 %). Hydrogenolysis occurred to a minor
extent, with only trace amounts of benzene and cyclohexane
having been detected (1 % selectivity). Although the non-
reductive methanolysis, i.e., transetherification generating phenol
and anisole, may occur in the presence of an acid or base
catalyst,[10] this pathway was not observed on Pd/C. The reaction
order of 0.4 for diphenyl ether (Figure S1) points to high coverage
of the ether. The reaction order of 1.7 for H2 indicates, assuming
stepwise H addition, that the formation of enol ether (4H-addition
product) is the rate-determining step.
As several intermediates were formed during the reaction of
diphenyl ether with methanol, and many secondary reactions
could occur, compounds b to f in Table 1 (entries 4-8) were also
reacted in the presence of Pd/C and H2 under identical conditions.
Compounds b to i were formed at low conversions of diphenyl
ether (Table 1, entry 3), while only c, f and g were final products
(Table 1, Entries 5, 8 and 7), because they did not react in
methanol on the same time scale.
O
O
O
O
2 H2
H2O
-ROH
R
R
R
(Eq. 1)
The question arises now, whether alcohols can also cleave
such ether bonds and can be used for transetherification.[7] Indeed,
mixtures of ethers and hydrocarbons were obtained from biogenic
polymers in supercritical methanol, indicating that such insertion
of alcohols into ether bonds could take place, if the carbon atom
is sufficiently reactive.[2a, 4a] It should be noted in passing that C1-
[a]
[b]
M. Wang, Dr. O. Y. Gutiérrez, Dr. D. M. Camaioni, Prof. Dr. J. A.
Lercher
Institute for Integrated Catalysis
Pacific Northwest National Laboratory
P.O. Box 999, Richland, WA 99352 (USA)
E-mail: Johannes.Lercher@ch.tum.de, johannes.lercher@pnnl.gov
Prof. Dr. J. A. Lercher
Department of Chemistry and Catalysis Research Institute
TU München
Lichtenbergstrasse 4, 85748 Garching (Germany)
Supporting information for this article is given via a link at the end of
the document.
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10.1002/anie.201709445
Angewandte Chemie International Edition
COMMUNICATION
Table 1. Reactions of related compounds on Pd/C in methanol.[a]
Carbon Selectivity/%
Entry
Reactant
Time/h
Conv./%
TOF/s-1 [b]
b
c
d
e
f
g
h
i
j + k
1
a
a
a
b
48
92
-
16
-
10
-
-
-
34
-
39
-
-
-
1
-
2[c]
3
48
-
-
-
-
-
0.25
0.25
16
10
80
<1
25
9
-
<1
2
<1
36
8
<1
1
<1
4
1
1
0.06
0.04
4
31
5
6
7
8
c
d
e
f
10
1
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
20
100
-
-
-
-
10
4
-
60
100
-
7
-
19
-
0.19
>4
-
0.1
10
-
-
-
-
-
[a]Reaction conditions: 20 mg 5 wt. % Pd/C (2.9 × 10−6 mol of Pd at the surface determined by H2 chemisorption), methanol (80 ml), reactant (1 mmol
for entries 1-5 and 10 mmol for entries 6-8), hydrogen (40 bar gauge pressure at RT), temperature (200 °C) and stirring (700 rpm); [b]Turnover
frequencies (TOF) were calculated from conversions of < 20 %. [c]N2 (4 bar at RT) was used instead of H2. The product distribution did not change
when the reaction time was varied from 0.1 to 10 h. The entries labeled with “-“ indicates that the concentrations were below the detection limits of
the method.
phenol and cyclohexanone are important contributors to
methoxycyclohexane. 1-Methoxycyclohexene, however, was not
detected as a major product, due to its high reactivity. As we show
later,
cyclohexanone,
methoxycyclohexene
and
dimethoxycyclohexane are hypothesized to be equilibrated.[11]
Hydrogenation was the dominant reaction of diphenyl ether
(Figure 1A) leading to cyclohexyl phenyl ether as the main product.
Dicyclohexyl ether started to form at 35 % conversion. For the
reaction of cyclohexyl phenyl ether (Figure 1B), the yields of three
major products, cyclohexanol, methoxycyclohexane and
dicyclohexyl ether, increased continuously during the reaction
period, with almost constant C-selectivities, 36 %, 37 % and 25 %,
respectively. For both reactants, diphenyl ether and cyclohexyl
phenyl ether, the initial C-O cleavage products were R-OH (R =
phenyl or cyclohexyl, respectively) and methoxycyclohexane at a
1:1 molar ratio.
The product distributions from diphenyl ether and phenyl
cyclohexyl ether are consistent with the reaction pathways in
Scheme 1. 1-Phenoxycyclohexene is hypothesized to form via
hydrogenation of diphenyl ether, just as 1-methoxycyclohexene
has been observed in anisole hydrogenation.[12]
Figure 1. Product distributions for the reactions of diphenyl ether (A) and
cyclohexyl phenyl ether (B) over Pd/C as a function of conversion. Reaction
conditions: ether (0.001 mol), 5 wt % Pd/C (20.0 mg, 2.9 µmol of Pdsurf.,
ether:Pdsurface = 350), methanol (80 ml), H2 (40 bar), 200 °C, stirring (700 rpm).
As it takes 15 min to heat up the reactor from room temperature to 200 °C, the
conversion at 0 min occurred during heat up. Time-yield-conversion plots are
presented in Figure S2.
For methanolysis, cyclohexyl phenyl ether (80 %), phenol
(9 %) and methoxycyclohexane (8 %) were the main products at
16 % conversion of diphenyl ether (Table 1, Entry 3), indicating
that hydrogenation (80 %) dominates the initial phase of the
reactions. In contrast, the selectivity to hydrogenation was much
lower (25 %) and methanolysis, i.e., the sum of products f, g, h,
and i in Table 1 was much higher (73 %) in the reaction of
cyclohexyl phenyl ether (Table 1, Entry 4). Phenol hydrogenation
in methanol occurred with a significantly faster rate (TOF = 0.19
s-1) than ether cleavage, forming methoxycyclohexane as the
major product (Table 1, Entry 6) and methoxycyclohexene and
dimethoxycyclohexane as minor products. Cyclohexanone
reacted with H2 and methanol forming methoxycyclohexane as
the only product at 100% conversion (Table 1, Entry 7), with a rate
(> 4 s-1) even faster than phenol hydrogenation. Thus, in methanol,
As 1-phenoxycyclohexene was generated during
hydrogenation of diphenyl ether, methanolysis to 1-
methoxycyclohexene and phenol was hypothesized to occur. To
test this hypothesis, 1-phenoxycyclohexene was reacted with
methanol in the presence and absence of H2 and of a catalyst. In
addition, the equilibration among 1-methoxylcyclohexene,
cyclohexanone, hemiketal and ketal in methanol was explored
under the reaction conditions (Eq. 2).
O
O
O
O
OH
-H
CH3OH
2O
CH3OH
O
(Eq. 2)
Figure 2 shows conversion/selectivity data for the reaction
of 1-phenoxycyclohexene in methanol under a variety of
conditions (with or without Pd/C, H2 or N2). With Pd/C and H2 at
200 °C, 1-phenoxycyclohexene was fully converted in 10 min,
which is much faster than the conversion rate of diphenyl ether
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10.1002/anie.201709445
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under the same conditions. The selectivity to hydrogenation
(cyclohexyl phenyl ether) was 28 %; the other products (72 %)
could all be attributed to methanolysis. Consistent with
methanolysis (Eq. 3), the molar ratio between phenol and
methoxycyclohexene or its derived compounds (including
cyclohexanone, methoxycyclohexene, dimethoxycyclohexane
and methoxycyclohexane) was 1:1.
entire reaction. In contrast, cyclohexanone increased gradually
with increasing reaction time, indicating that cyclohexanone was
a secondary product and that the interconversion between
cyclohexanone and 1-methoxycyclohexene was slow without
Pd/C. Since methanolysis of 1-phenoxycyclohexene is
competitive with hydrogenation and occurs even in the absence
of catalyst (Figure 2), we conclude that the C-O bonds in diphenyl
ether and cyclohexyl phenyl ether are cleaved via the enol ether
intermediates, e.g., as shown in Eq. 3 for 1-phenoxycyclohexene.
O
O
O
O
OH
CH3OH
O
O
CH3OH
+
- CH
3OH
rapid
- H2O
H
2O
O
+
CH
3OH
(Eq. 3)
While the conversion of 1-phenoxycyclohexene does not
require a catalyst to occur with appreciable rates, the presence of
Pd/C increases the rates tenfold. As a consequence, the
equilibrium between cyclohexanone–methoxycyclohexene is
reached about hundred times faster in the presence of catalyst
than in the uncatalyzed reaction. When cyclohexanone was the
starting reactant (2nd and 3rd experiments in Figure 3), the
equilibrium between cyclohexanone, methoxycyclohexene and
dimethoxycyclohexane (the ratio being 2:1:3, see details in
supporting information) was reached in ≤10 min in the presence
of Pd/C compared to 24 h in the absence of Pd/C at 200 °C.
Without H2, dehydrogenation of methoxycyclohexene
occurred on Pd forming anisole (3rd experiment in Figure 3). With
H2 (4th experiment in Figure 3), hydrogenation rapidly reached
completion within 10 min, producing only methoxycyclohexane
but not cyclohexanol. This indicates that the hydrogenation rate
of cyclohexanone is significantly slower than that of
methoxycyclohexene. To test whether methoxycyclohexane was
generated only from hydrogenation of methoxycylohexene and
not by etherification of cyclohexanol with methanol, cyclohexanol
was used as the reactant in a control experiment; products were
not detected after 24 h under the same reaction conditions (Table
1, entry 8; 5th experiment in Figure 3).
Figure 2. Control experiments using 1-phenoxycyclohexene as reactant.
Reaction conditions: ether (0.001 mol), 5 wt % Pd/C (0 or 10.0 mg), methanol
(80 ml), N2 (4 bar) or H2 (40 bar), 200 °C, stirring (700 rpm). Data points are
presented in Table S2.
The various pathways for the reaction of diphenyl ether are
summarized in Scheme 2. The C-O bond cleavage of diphenyl
ether in methanol is initiated by partial reduction and methanolysis
of the intermediate enol ether. The initial selectivity to reductive
methanolysis is 18 % for diphenyl ether and 73 % for cyclohexyl
phenyl ether, lower than the selectivities for reductive hydrolysis
in aqueous phase (49 % and 87 % for diphenyl ether and
cyclohexyl phenyl ether, respectively).[5] For diphenyl ether, the
difference in selectivities of the two solvents, water and methanol,
is attributed to the different rates of solvolysis of 1-
phenoxycyclohexene; e.g., in the absence of catalyst, 72 % of 1-
phenoxycyclohexene is converted in 10 min in water,[5] compared
to 66 % in 120 min in methanol (Figure 2). Thus, when 1-
phenoxycyclohexene is formed from partial hydrogenation of
diphenyl ether and desorbed from the metal surface, it reacts
rapidly with water, whereas in methanol it re-adsorbs on the metal
and is hydrogenated. Hydrogenation of diphenyl ether accounts
for 80% C-selectivity in methanol, as compared to 49% in
aqueous phase.[5] For the conversion of the primary product aryl
ether, the initial products from Pd-mediated reductive
methanolysis are methoxycyclohexene and cyclohexanol (1:1),
the former being rapidly hydrogenated to methoxycyclohexane.
Figure 3. Control experiments with cyclohexanone in methanol. Reaction
conditions: substrate (0.001 mol), 5 wt % Pd/C (0 or 10.0 mg), methanol (80 ml),
N2 (4 bar) or H2 (40 bar), RT or 200 °C, stirring (700 rpm).
Under N2, the Pd/C catalyzed conversion of 1-
phenoxycyclohexene was slower than the rates in H2, and
hydrogenation was not observed (Figure 2). The ratio between
cyclohexanone, 1-methoxycyclohexene and the ketal was
approximately 2:1:3 at both 10 min and 180 min reaction times,
suggesting that these compounds are equilibrated in the absence
of H2. Without the presence of a catalyst the reaction under H2
was even slower than in the presence of catalyst, while equimolar
amounts of phenol and 1-methoxycyclohexene-derived
compounds were formed (Eq. 3). After 10 min of reaction under
these conditions, only phenol, 1-methoxycyclohexene and 1-,1-
dimethoxycyclohexane were formed, while cyclohexanone was
not detected. The absence of cyclohexanone at the initial stage
excludes the possibility that 1-phenoxycyclohexene undergoes
hydrolysis (e.g., with adventitious water in the solvent) which
would produce cyclohexanone as initial product. The
interconversion between 1-methoxycyclohexene and the ketal
appeared to be fast, in view of the constant ratio of 1:3 during the
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10.1002/anie.201709445
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COMMUNICATION
Scheme 2. Reaction pathways and selectivities of diphenyl ether in methanol
under hydrogen over Pd/C catalyst
Acknowledgements
This work was supported by the U.S. Department of Energy,
Office of Science, Office of Basic Energy Sciences, Division of
Chemical Sciences, Geosciences, and Biosciences. Portions of
the work were performed at the William R. Wiley Environmental
Molecular Science Laboratory, a national scientific user facility
sponsored by the DOE’s Office of Biological and Environmental
Research located at Pacific Northwest National Laboratory, a
multi-program national laboratory operated for DOE by Battelle
Memorial Institute.
O
hydrogenation
25 %
O
O
hydrogenation
80 %
OH
+
O
O
hydrogenation
rapid
reductive methanolysis
73 %
hydrogenolysis
2 %
...
O
O
O
O
O
Keywords: aryl ether • hydrogenation • palladium •
methanolysis • selective cleavage
OH
+
reductive methanolysis
18 %
hydrogenation
rapid
[1]
a) J. R. Regalbuto, Science 2009, 325, 822-824; b) A. J. Ragauskas, C.
K. Williams, B. H. Davison, G. Britovsek, J. Cairney, C. A. Eckert, W. J.
Frederick, J. P. Hallett, D. J. Leak, C. L. Liotta, J. R. Mielenz, R. Murphy,
R. Templer, T. Tschaplinski, Science 2006, 311, 484-489; c) P. A.
Willems, Science 2009, 325, 707-708; d) R. Rinaldi, R. Jastrzebski, M.
T. Clough, J. Ralph, M. Kennema, P. C. A. Bruijnincx, B. M. Weckhuysen,
Angew. Chem. 2016, 128, 8296-8354; Angew. Chem. Int. Ed. 2016, 55,
8164-8215; e) P. Ferrini, R. Rinaldi, Angew. Chem. 2014, 126: 8778–
8783; Angew. Chem. Int. Ed. 2014, 53, 8634-8639.
+
O
O
CH
3
O
hydrogenolysis
...
OH
2 %
O
(major)
The generality of reductive transetherification was explored
using higher alcohols and other ethers. The results are shown in
Tables S3, S4 and S5. The selectivity for conversion of diphenyl
ether to products of reductive solvolysis (predominately,
cyclohexanol and C6H11-O-R) followed the trend (Table S3):
methanol (72%) > ethanol (47%) > 1-propanol (44%) > 2-propanol
(32%). As the selectivities are determined by the competition
between solvolysis and hydrogenation of the intermediate enol
ether, we suggest that addition of R-OH to the double bond in
cyclohexenyl phenyl ether becomes slower than hydrogenation,
because of steric hindrance induced in the transition state and
ketal product by the increasing size of the R group (from CH3 to
isopropyl). When 2-phenylethyl phenyl ether and p-tolyl ether
were reacted in methanol, the selectivity to methanolysis was
40 % and 34 % respectively (Table S5). These selectivities are
comparable to the selectivities reported above for diphenyl ether
(72 %) and cyclohexyl phenyl ether (73 %). These observations
show that solvolysis on Pd is generally available to aryl ethers,
although alcohols that have bulky alkyl groups are expected to
yield low yields.
In conclusion, the solvolytic cleavage of C-O bonds in diaryl
and aryl alkyl ethers on Pd occurs in alcohols under relatively mild
conditions following partial reduction of the aryl ring. Thus, for aryl
alkyl ethers, the aryl C-O bond, rather than the alkyl C-O bond, is
cleaved because it becomes a vinylic C-O bond in the
intermediate enol ether. Reductive alcoholysis is initiated by
selective partial hydrogenation of the aryl ring to an enol ether
intermediate that is susceptible to attack by alcohols. The attack
however, is slower than attack by water, thus, the selectivity to
alcoholysis is lower than for hydrolysis under comparable
conditions.[5] We infer that this solvolysis mechanism applies also
to a variety metal catalysts in the presence of H2 or reducing
equivalents. A determining factor is the selectivity of the metal to
catalyze hydrogenation of the enol ether, a feature that remains
to explore in greater detail.
[2]
[3]
a) K. Barta, P. C. Ford, Acc. Chem. Res. 2014, 47, 1503-1512; b) G. W.
Huber, S. Iborra, A. Corma, Chem. Rev. 2006, 106, 4044-4098; c) C. Li,
X. Zhao, A. Wang, G. W. Huber, T. Zhang, Chem. Rev. 2015, 115,
11559-11624; d) P. Gallezot, ChemSusChem 2008, 1, 734-737; e) R.
Rinaldi, F. Schuth, Energy Environ. Sci. 2009, 2, 610-626; f) J. Zakzeski,
P. C. A. Bruijnincx, A. L. Jongerius, B. M. Weckhuysen, Chem. Rev. 2010,
110, 3552-3599.
a) A. G. Sergeev, J. F. Hartwig, Science 2011, 332, 439-443; b) P. C. A.
Bruijnincx, B. M. Weckhuysen, Nat. Chem. 2014, 6, 1035-1036; c) M.
Chatterjee, A. Chatterjee, T. Ishizaka, H. Kawanami, Catal. Sci. Technol.
2015, 5, 1532-1539; d) S. K. Hanson, R. Wu, L. A. P. Silks, Angew. Chem.
2012, 124: 3466–3469; Angew. Chem. Int. Ed. 2012, 51, 3410-3413; e)
F. Gao, J. D. Webb, J. F. Hartwig, Angew. Chem. 2016, 128, 1496-1500;
Angew. Chem. Int. Ed. 2016, 55, 1474-1478.
[4]
[5]
a) T. D. Matson, K. Barta, A. V. Iretskii, P. C. Ford, J. Am. Chem. Soc.
2011, 133, 14090-14097; b) J. A. Barrett, Y. Gao, C. M. Bernt, M. Chui,
A. T. Tran, M. B. Foston, P. C. Ford, ACS Sustainable Chem. Eng. 2016,
4, 6877-6886.
M. Wang, H. Shi, D. M. Camaioni, J. A. Lercher, Angew.
Chem. 2017, 129, 2142-2146; Angew. Chem. Int. Ed. 2017, 56, 2110-
2114.
[6]
[7]
[8]
Q. Meng, M. Hou, H. Liu, J. Song, B. Han, Nat. Commun. 2017, 8, 14190.
W. H. Watanabe, L. E. Conlon, J. Am. Chem. Soc. 1957, 79, 2828-2833.
a) Q. Song, J. Cai, J. Zhang, W. Yu, F. Wang, J. Xu, Chin. J. Catal. 2013,
34, 651-658; b) V. Molinari, C. Giordano, M. Antonietti, D. Esposito, J.
Am. Chem. Soc. 2014, 136, 1758-1761; c) X. Cui, A. E. Surkus, K. Junge,
C. Topf, J. Radnik, C. Kreyenschulte, M. Beller, Nat. Commun. 2016, 7,
11326.
[9]
J. Zhang, J. Teo, X. Chen, H. Asakura, T. Tanaka, K. Teramura, N. Yan,
ACS Catal. 2014, 4, 1574-1583.
[10] Y. Ogata, M. Okano, J. Am. Chem. Soc. 1949, 71, 3212-3213.
[11] D. Kubler, L. Sweeney, J. Org. Chem. 1960, 25, 1437-1440.
[12] J. A. Widegren, R. G. Finke, Inorg. Chem. 2002, 41, 1558-1572.
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COMMUNICATION
Meng Wang, Oliver Y. Gutiérrez, Donald
M. Camaioni and Johannes A. Lercher*
Page No. – Page No.
Palladium catalyzed reductive
insertion of alcohols in aryl ether
bonds
Reductive alcoholysis of aryl ethers catalyzed by palladium in alcoholic solvent is
initiated by partial hydrogenation of the arene ring to an enol ether. Thus cleavage
of the strong aryl C-O bond is achieved via achohol addition to the enol ether and
R-OH elimination.
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