Highly selective hydrogenation and hydrogenolysis using a copper-doped porous metal oxide catalyst

Article abstract of DOI:10.1039/c5gc01464f

A copper-doped porous metal oxide catalyst in combination with hydrogen shows selective and quantitative hydrogenolysis of benzyl ketones and aldehydes, and hydrogenation of alkenes. The approach provides an alternative to noble-metal catalysed reductions and stoichiometric Wolff-Kishner and Clemmensen methods.

Full text of DOI:10.1039/c5gc01464f

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Journal Name
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Highly Selective Hydrogenation and
Hydrogenolysis using a Copperꢀdoped Porous
Metal Oxide Catalyst
Cite this: DOI: 10.1039/x0xx00000x
Received 00th January 2012,
Accepted 00th January 2012
Laurene Petitjeana, Raphael Gagneb, Evan S. Beacha, Dequan Xiaob*, Paul T.
Anastasa*
DOI: 10.1039/x0xx00000x
www.rsc.org/
A copper-doped porous metal oxide catalyst in combination substituted compounds is even more difficult to effect selectively.
with hydrogen shows selective and quantitative Catalytic methods commonly use noble metals and typically require
hydrogenolysis of benzyl ketones and aldehydes, and forcing conditions3. A recent report of selective catalytic vanillin
hydrogenation of alkenes. The approach provides an hydrogenolysis utilizes Au on carbon nanotubes10
, while another
alternative to noble-metal catalysed reductions and employs Pd nanoparticles supported on mesoporous N-doped carbon
stoichiometric Wolff-Kishner and Clemmensen methods.
to provide creosol11. Various other supported Pd catalysts have been
used but show lower selectivity in the reduction of vanillin to creosol12-
14, yielding mixtures of creosol and vanillyl alcohol.
Sustainability has emerged as a global concern and has prompted
chemists to develop procedures that minimize impact on the
environment. Catalysis is the basis for many improvements in
sustainable chemical transformations, facilitating the use of reduced
energy and material inputs for processes that society requires1.
Heterogeneous catalysis, in particular, provides many advantages
such as increased catalyst stability and lifetime, as well as ease of
catalyst separation from the product mixture2. Additionally, methods
based on supported heterogeneous catalysts show superior
applicability for industrial scale-up3. Supply vulnerabilities and
depletion of natural resources have increased the attractiveness of
catalysts based on earth-abundant metals1.
Alternatively, selective but stoichiometric methods such as Wolff-
Kishner15 or Clemmensen16 conditions are extensively utilized for
carbonyl removal. They historically employ toxic reagents such as
hydrazine and mercury and generate hazardous waste. Recently,
methods have been developed to avoid use of noble metals or the
above stoichiometric reactions for hydrogenation and hydrogenolysis.
Both Ni nanoparticles17 and a Ni/Al alloy catalyst18 are capable of
hydrogenating eugenol to propyl-guaiacol. Unfortunately, the
catalysts’ synthesis either employs several equivalents of toxic
reagent or is energy intensive. Thus, easily synthesized green
catalysts based on earth abundant elements could provide promising
solutions for the large-scale applications of catalytic hydrogenation
and hydrogenolysis.
The hydrogenation of unsaturated functional groups such as
carbon-carbon double bonds and the hydrogenolysis of carbon-
oxygen bonds are both important reactions in synthetic chemistry4
A general challenge for all catalytic methods of hydrogenation or
hydrogenolysis, particularly by those based on earth abundant
elements, is improving selectivity. For example, using a CoMo/Al2O3
catalyst to reduce vanillin at 300oC and 5 MPa H2 showed poor
conversion and provided mixtures of over four compounds including
creosol19. Copper has the advantages of being an earth-abundant
metal and having low tendency to catalyze arene hydrogenation,
preventing over-reduction and thus improving selectivity3. Recently,
Kong et al. reported the use of copper-doped HZSM-5 zeolite for
hydrogenolysis of aryl aldehydes and ketones20. Porous metal oxides
(PMOs), derived from hydrotalcite-like precursors of general formula
Mg6Al2CO3(OH)16. 4H2O, are promising catalysts for a wide range of
applications. This is due to their high potential for tunability through
altering the M2+:M3+ ratio and metal dopants. Other advantages
particularly in the liquid fuels sector5 where catalytic methods are
6
used to reduce oxygen content and improve hydrogen/carbon ratios
.
Reductions of alkenes are typically conducted with high selectivity
using noble metal catalysts that are active under mild conditions3. For
example, hydrogenation of the propene moiety in eugenol can be
performed using Pd/C in combination with stoichiometric
triethylsilane and an acid quench7. One of the earliest reports of
eugenol reduction used an insoluble rhodium catalyst in water8. Even
with noble metal catalysts, selectivity can frequently be difficult to
achieve. The reduction of eugenol with a heterogeneous Pt/γ-Al2O3
catalyst in combination with 0.14 MPa of N2/H2 stream (90/10) at 300
°C yielded dozens of products in addition to guaiacol and n-
propylguaiacol9. Hydrogenolysis of ketones or aldehydes from aryl-
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VJieowuArrtnicalelONnlainme e
DOI: 10.1039/C5GC01464F
include high surface area, stability against sintering, simplicity of
To examine the chemoselectivity of eugenol reduction, DFT
preparation, and ease of handling21, 22. Thus, doping copper into calculations were performed to evaluate the thermodynamic
hydrotalcite-derived compounds can be a promising strategy for a feasiblity of potential products at varying pressures of hydrogen
wide range of reduction methods. For example, Kaneda et Al.
(a)
successfully utilised a copper-nanoparticle catalyst synthesized from
Cu-Al hydrotalcite to effect the quantitative hydrogenolysis of
O
O
H2 (1 equiv.)
Path 1
H
glycerol to 1,2-propanediol23
.
H
HO
HO
Eugenol
S1
In this communication, the reactivity and selectivity of copper-
H2 (1 equiv.)
Path 2
doped PMO (Cu-PMO) is evaluated. Our previous work with the
catalyst suggested it was capable of very selective transformations24
H2 (1 equiv.)
Path 3
.
This work clarifies the scope of the reactivity towards various C-C and
C-O bond configurations. Density functional theory (DFT) calculations
were performed to evaluate the thermodynamic bias of each reaction
at relevant pressures. The computational results are integrated with
experimental data from Cu-PMO catalysed reductions to show
improvements in efficiency and selectivity provided by the catalyst.
Cu-PMO is synthesized by co-precipitation of Cu, Mg and Al
O
H
O
+
H3C
H
S1'
HO
S1''
HO
H
H
40
30
20
10
0
(b)
nitrate salts in aqueous media. Copper constitutes 20 mol% of M2+
,
with M2+:M3+ kept at 3:1. Elemental analyses proved that the metals
are incorporated in the anticipated amounts, furnishing a catalyst with
metal ratios of Cu0.57Mg2.25Al1.00 (See ESI). XRPD measurements
indicate that Cu-PMO changes from a hydrotalcite-like structure to
become an amorphous material after calcination in air for 24 hours at
460oC. Cu-PMO was previously reported to have a surface area of ~137
Path1
Path2
Path3
0.1
0.5
1.0
2.0
3.0
4.0
5.0
6.0
ꢀ10
ꢀ20
ꢀ30
m2/g25
.
H2 Pressure(MPa)
The Gibbs free energy of different reaction pathways was
determined using the high-performance computational chemistry
software NWChem26. The structures were built in .xyz format using
the model-building program Avogadro27. Initial molecular geometries
were then optimized using density functional theory at the B3LYP/6-
31g* level. The optimized structures were subjected to
thermochemistry analysis based on vibrational frequency calculations
and solvation energy calculations using the COSMO solvation
model28. The output of the vibrational frequency calculations provided
the zero-point correction to energy (E1), thermal correction to
enthalpy (H) and total entropy (S). The solvation calculation provided
the total density function theory (DFT) energy (E0) and the
electrostatic solvation energy (Es). Equation 1 was used to determine
the change in Gibbs free energy (dG).
Fig 1 (a) Potential pathways of eugenol reduction (b) Changes in Gibbs free
energy with varying H2 pressure at 180oC
Table 1 Reduction of eugenola
O
O
S1
H2 (x equiv.)
HO
O
HO
MeOH (0.21 M)
Eugenol
IsoE
HO
Yieldb
Conversionb Yieldb
c
H2
Catalyst
Time
(h)
Temp
(oC)
Entry
ꢀꢁ = ꢂ − ꢃꢄ (1)
IsoE (%)
(%)
S1 (%)
(MPa)
(mol%)
This information was then used to compute Gibbs free energy (G) of
each structure in gas phase by equation 2.
(1)
(2)
(3)
(4)
(5)
(6)
(7)
(8)
(9)
(10)
Cu-PMO (11)
Cu-PMO (11)
Cu-PMO (11)
Cu-PMO (11)
Cu-PMO (11)
Cu-PMO (11)
Cu-PMO (11)
Cu-PMO (11)
PMO (250 mg)
-
180
100
60
18
18
18
18
3
0
0
4
4
4
4
4
4
1
1
4
4
4
1
1
1
100
100
53
> 95
> 95
39
0
ꢁ = ꢀꢁ + ꢅꢆ + ꢅꢇ (2)
0
For specific hydrogenation or hydrogenolysis reactions, we followed
the Born-Haber cycle to compute the reaction Gibbs energy in
solutions (see ESI). R is the organic molecule prior to hydrogenation,
H2 is molecular hydrogen, and RH2 is the organic molecule after
hydrogenation. In the notations of ∆ꢁ terms, ‘g’ denotes gas phase,
‘solu’ denotes solution, and ‘s’ denotes solvation.
22
0
0
100
70
0
100
< 5
40
> 95
tr
3
0
100
100
180
180
3
0
40
> 95
35
15
60
0
4
0
100
57.5
26
18
18
18
4
18
0
The reaction Gibbs free energy in gas phase was first computed using
equation (3):
(11)
(12)
(13)
(14)
Cu(OAc) H O (0.3)
180
100
100
100
0
90
2.
2
PMO (250 mg)
0
0
ꢉ
ꢍ
ꢉ
ꢍ
ꢉ
ꢍ
∆ꢁꢈ = ꢁ ꢊꢂꢋ, ꢌ − ꢁ ꢊ, ꢌ − ꢁ ꢂꢋ, ꢌ (3)
Then, the reaction Gibbs free energy in solution was computed by
equation (4):
-
4
0
< 5
15
tr
Cu(OAc) H O (0.3)
4
0
2.
2
tr
(a) All reactions were carried out in a high pressure 100 mL Parr Reactor
using Eugenol (6.456 mmol) in MeOH (30 mL) (b) Conversion and Yield
determined by 1H NMR Spectroscopy using DMF or Dodecane as internal
standards (c) Pressure as added at room temperature; tr = trace
∆ꢁꢎꢏꢐꢑ = ∆ꢁꢈ + ∆ꢁꢎ,ꢒꢓ − ∆ꢁꢎ,ꢒ − ∆ꢁꢎ,ꢓ (4)
ꢔ
ꢔ
2 | J. Name., 2012, 00, 1-3
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calcined catalyst is utilized in polar methanol, yet isomerization is still
(Figure 1). At reaction conditions over 1 MPa of hydrogen pressure at observed. This suggests that the rate of PMO-catalysed
180 °C, several pathways are calculated to be thermodynamically hydrogenation of both eugenol and isoeugenol are low enough to
favourable: hydrogenation of the alkene, as well as hydrogenolysis of allow isoeugenol to be observed as a co-product.
the methoxy-aryl bonds. Interestingly, the most thermodynamically
The use of a homogeneous copper catalyst for eugenol
favorable product at H2 pressures of 0.1-6 MPa is predicted to be the hydrogenation is not as effective as Cu-PMO (Table 1, Entry 11). The
catechol resulting from aryl-ether bond cleavage (Path 2, Figure 1). Cu-PMO loading (11 mol %) furnishes 0.3 mol % of Cu which is
This is potentially due to the added entropy gain from methane identical to the absolute amount of Cu in the Cu(OAc)2 experiment,
release after bond cleavage. However, experiments with Cu-PMO did
not yield catechol product, suggesting that the production of catechol milder conditions were performed (Table 1, Entries 12-14) and it is
is subjected to the kinetic control of the catalysis. evident that the Cu-PMO structure and composition are essential for
The hydrogenation of the propene group occurs under our overcoming the transition state energy barrier leading to the
reaction conditions, as it is thermodynamically allowed at various H2 reduction product S1
pressure (see Figure 1b, path 1),, Experiments also found that the In an effort to explore the applicability of our method towards C-O
yet Cu-PMO performs significantly better. Control experiments with
.
hydrogenation of propene is under the control of reaction kinetics bonds, DFT calculations of vanillin reduction products thermodynamic
(Table 1). Product S1 is obtained quantitatively after stirring for 18 h in stability, at varying hydrogen pressure, were first performed (Figure
a sealed Parr Reactor at 180 °C with an initial pressure of 4 MPa of 2). As for eugenol, the most thermodynamically favored product is
hydrogen (Table 1, Entry 1). The efficiency was excellent at predicted to be that from cleavage of the aryl-methoxy moiety, due to
temperatures as low as 100 °C, but dropped with further decrease in entropy gain. For analogous reasons, formation of creosol also
temperature (Table 1, Entries 2-4). Optimal conditions appear to be displays negative Gibbs free energy at all studied hydrogen pressures.
around 3 h reaction at 100 °C (Table 1, Entry 5). Lowering hydrogen Hydrogenation of the aromatic unit is calculated to be particularly
pressure slows the reaction, yet quantitative yields of S1 can be disfavored. It is more difficult to obtain the product of aromatic
obtained in only 4 h at 100 °C and 1 MPa of hydrogen (Table 1, hydrogenation for vanillin than eugenol, correlating with the
comparing Entries 5, 7 and 8). The control experiments suggest that increased electron-donating ability of the propene unit versus the
hydrogenation of eugenol is kinetically controlled. Only trace aldehyde (as also indicated by a pKa of 10.19 for eugenol and 7.38 for
reactivity was observed even after 21 h at 180 °C with 4 MPa of vanillin)35
. Hydrogenation of the aldehyde to the corresponding
hydrogen (Table 1, Entry 10). benzylic alcohol also displays a positive change in Gibbs free energy,
The phase of the reaction mixture could play an important role in most likely because the conjugation of the aldehyde to the aromatic
the efficiency and selectivity of reduction, by altering the mechanism unit makes it more difficult to reduce.
of catalysis29, 30. In the present system, methanol remains in the liquid
H
H
H
phase throughout the reaction under all conditions reported31. The
system pressure increased as the temperature approached the set
point, typically reaching 1.4 MPa at 100 °C and 5.9 MPa at 180 °C.
Accordingly the density varies in the early stages of the reaction. For a
(a)
O
O
H
H2 (1 equiv.)
Path 4
O
O
S3
HO
HO
Vanillin
H2 (2 equiv.)
Path 1
transformation performed at 180 °C and
4 MPa, the hydrogen
H2 (1 equiv.)
H2 (1 equiv.)
H2 (1 equiv.)
Path 2
pressure is introduced at room temperature and a density of 790.5
g/mL is expected for methanol31. Once the set temperature is reached,
the pressure has increased and the density of methanol is calculated
to be 608.6 g/mL31. For the milder reaction conditions, the effect is
lower; at the start of the reaction, a density of 787.6 g/mL is expected
at room temperature and 1 MPa H2. A lower experimental density of
methanol at 712.6 g/mL can be reached with 100 °C and 1.4 MPa H2. A
lower solvent density may facilitate hydrogen solvation and increase
the reaction rate. Changes in solvent density could also alter solvent
Path 3
H
H
H
H
O
O
H
O
O
O
H
S2''
S2'
S2
HO
H
HO
+
HO
H3C
H
H
HO H
+
(b)
40
30
20
polarity, in turn affecting reduction efficiency and selectivity32
.
10
Cu-PMO is able to overcome the transition state barrier
associated with hydrogenation of eugenol. Interestingly, the Cu-free
porous-metal oxide (PMO) material derived from Mg/Al hydrotalcite is
also active for eugenol hydrogenation (Table 1, Entry 9). This control
indicates that Cu is essential for reaction efficiency as well as
selectivity, since the PMO-promoted hydrogenation of eugenol yields
isoeugenol in 15% yield (2:1 ratio trans:cis). Eugenol isomerization is
known to be catalyzed by hydrotalcite-like compounds due to their
solid base character33. With hydrotalcite-like compounds, reduced
reactivity for isomerization is observed if the catalyst is calcined to a
PMO, or when polar solvents are utilized34. In the present case, a
0
0.1
0.5
1.0
2.0
3.0
4.0
5.0
6.0
ꢀ10
ꢀ20
ꢀ30
ꢀ40
Path3
Path4
Path2
Path1
H2 Pressure(MPa)
Fig 2 (a) Potential pathways of vanillin reduction (b) Changes in Gibbs free
energy with varying H2 pressure at 180oC
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J. Name., 2012, 00, 1-3 | 3

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VJieowuArrtnicalelONnlainme e
DOI: 10.1039/C5GC01464F
Table 2 Reduction of vanillina
Table 3 Reduction of acetovanillonea
O
O
O
S2
O
H2 (2 equiv.)
HO
O
+ H2O
MeOH (0.21 M)
HO
HO
O
R
S6
Acetovanillone
O
H2 (x equiv.)
R=OH S3
Yieldb
S6 (%)
H2 Conversionb
d
Catalyst
(mol%)
Time
MeOH (0.21 M)
- x H2O
Temp
HO
R=OMe S4
Entry
HO
(oC)
(h)
OMe
(MPa)
(%)
Vanillin
O
(1)
(2)
(3)
100
0c
0
Cu-PMO (11)
PMO (250 mg)
-
> 95
0
180
180
180
180
100
40
40
40
40
10
18
18
18
18
4
OMe
S5
HO
0
(4)
(5)
0
Yieldb
Cu(OAc)2.H2O (0.3)
Cu-PMO (11)
0
Conversionb
H2
c
Catalyst
(mol%)
Time
(h)
Temp
(oC)
Entry
< 5
nd.
S2:S3:S4:S5 (%)
(%)
(MPa)
(a) All reactions were carried out in a high pressure 100 mL Parr
Reactor using acetovanillone (6.456 mmol) in MeOH (30 mL) (b)
Conversion and Yield determined by 1H NMR Spectroscopy using DMF
as internal standard (c) Conversion determined by recovery of starting
material (d) Pressure as measured at room temperature; nd = not
determined
(1)
(2)
(3)
(4)
Cu-PMO (11)
4
4
4
4
1
1
1
1
180
180
180
180
100
100
100
100
18
18
18
18
4
100
75
77
45
52
15
40
0
90:0:0:0
tr:tr:15:0
tr:0:(19):0
0:0:tr:0
PMO (250 mg)
-
Cu(OAc)2.H2O (0.3)
Cu-PMO (11)
PMO (250 mg)
-
(5)
(6)
(7)
(8)
tr:(36):tr:tr
0:0:0:15
0:0:0:23
0:0:0:0
4
4
4 MPa of hydrogen and 180 °C for 18 h, full hydrogenolysis of vanillin
to creosol (S2) was observed (Table 2, Entry 1). Interestingly, the
catalyst seems to be required for hydrogenolysis, as a different
product distribution is seen in its absence (Table 2, Entries 2-3). S4 is
obtained in 15-19% yield with poor mass balance using Cu-free PMO
or no catalyst. Using homogeneous copper acetate, conversion of
vanillin and formation of S4 is suppressed compared to the same
reaction with no catalyst (Table 2, Entries 3 & 4). Importantly, no
creosol was observed with copper acetate, suggesting that both the
Cu loading (overall composition) and structure of Cu-PMO are
necessary for selective conversion to S2. At lower temperature, lower
Cu(OAc)2.H2O (0.3)
4
(a) All reactions were carried out in a high pressure 100 mL Parr Reactor
using vanillin (6.572 mmol) in MeOH (31.3 mL) (b) Conversion and yield
determined by 1H NMR spectroscopy using Dodecane or DMF as internal
standards, isolated yield in parentheses (c) Pressure measured at room
temperature; tr = trace
(a)
H
H
O
O
O
H2 (2 equiv.)
Path 1
S6
HO
HO
Acetovanillone
HO
H
+
hydrogen pressure and shorter time, Cu-PMO yields
a different
H2 (1 equiv.)
product distribution, mainly S3 (Table 2, Entry 5). This result suggests
that S3 may be an intermediate in the formation of S2, as expected.
This was confirmed by the direct quantitative reduction of S3 to S2
using Cu-PMO at 180 °C and 4 MPa H2 (see ESI). If Cu is excluded from
the reaction at lower temperature and pressure, no reduction of
vanillin is observed (Table 2, Entries 6-7). Instead, acetal S5 is
obtained which probably results from addition of methanol to the
aldehyde, followed by elimination of water and addition of a second
equivalent of methanol. The observation of product S5 is significant
since acetal formation is typically effected by acid catalysis, yet there
is no explicit source of acid in the present conditions39. The catalysis
provided by PMO or Cu(OAc)2 is not sufficient to overcome transition
state barriers for hydrogenolysis of vanillin. Overall, the vanillin
studies again lead to the conclusion that the Cu-PMO structure and
copper loading are essential for efficiency and selectivity.
Path 2
O
H
O
+
HO
H
S7
(b)
0
0.1
0.5
1.0
2.0
3.0
4.0
5.0
6.0
Path1
Path2
ꢀ5
ꢀ10
ꢀ15
ꢀ20
ꢀ25
H2 Pressure(MPa)
The effect of increased steric hindrance and a more electron rich
reduction centre was probed by studying acetovanillone (Figure 3).
Calculations of the change in Gibbs free energy with varying pressure
at 180 °C indicate that both hydrogenolysis of the aryl ketone and
cleavage of the aryl ether are thermodynamically favored. Although
fission of the phenolic ring appears more thermodynamically
favourable than hydrogenolysis of the ketone, the catalyst biases
selectivity so that solely the ethyl-substituted phenol is obtained
experimentally (Table 3). Indeed, no conversion of acetovanillone
Fig 3 (a) Potential pathways of acetovanillone reduction (b) Changes in Gibbs
free energy with varying H2 pressure at 180oC
It is interesting that experimentally, Cu-PMO does not favor
cleavage of the methoxy bond that is predicted to be the most
thermodynamically favored pathway (Table 2), implicating highly
selective kinetic control by the Cu-PMO catalyst. Many other systems
have shown similar, although less pronounced, selectivity10-14, 36-38. At
4 | J. Name., 2012, 00, 1-3
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Table 4 Scope of hydrogenolysis of ketones by Cu-PMOa,c
Recycling experiments of eugenol hydrogenation (see ESI)
showed that it was possible to recycle the catalyst up to 11 times
before noticing a decrease in activity. Analyses by ICP-OES of the
spent catalyst revealed that the original metal ratio is retained after
reaction. SEM and TEM images of Cu-PMO before and after reaction
show little changes in the aggregation pattern and structure of the
catalyst. XRPD pattern of spent Cu-PMO shows it is still amorphous
after reaction. XPS investigations of recovered Cu-PMO versus fresh
catalyst indicate some reduction of Cu(II) to Cu(I) and possibly Cu(0)
after reaction (see ESI).
Condition A: Cu-PMO (11 mol%)
MeOH (0.21 M)
O
HO
R
H
H
H
180oC, 18 h, H2 (4 MPa)
or
R
R'
R'
R
R'
Condition B: MeOH (0.21 M)
180oC, 18 h, H2 (4 MPa)
P2
P1
Yield (%)b
Condition B
P1:P2
Yield (%)b
Condition A
P1:P2
Substrate
In summary, we have developed a very selective method for
O
hydrogenolysis of benzyl ketones and aldehydes as
a greener
alternative to Wolff-Kishner and Clemmensen conditions or noble-
metal catalysed reductions. Additionally, our method allows selective
reductions of alkenes. Ongoing investigations in our laboratory aim to
extend the utility of the Cu-PMO system and elucidate its mechanism
of reduction.
0 : > 95
0 : > 95
> 95 : 0
0 : > 95
0 : < 5
13 : < 5
0 : 0
O
Research at University of New Haven is supported by the new
faculty start-up fund and 2014 summer research grant and research
fellowship of the University of New Haven. The Center for Green
Chemistry and Green Engineering at Yale U. thanks the Yale School of
Forestry and Environmental Studies for its support. We thank Amanda
Lounsbury for the TEM images of Cu-PMO.
O
O
0 : 0
HO
Notes and references
(a) All reactions were carried out in a high pressure 100 mL Parr
Reactor using 6.456 mmol substrate (b) Conversion and Yield
determined by 1H NMR Spectroscopy using DMF as internal standard
(s) Pressure as measured at room temperature; nd = not determined
1. P. T. Anastas and J. C. Warner, Green Chemistry: Theory and Practice,
Oxford University Press, Oxford, 1998.
2. R. A. Sheldon, I. Arends and U. Hanefeld, Green Chemistry and Catalysis,
WILEY-VCH, Weinheim, Germany, 2007.
3. S. Nishimura, Handbook of Heterogeneous Catalytic Hydrogenation for
Organic Synthesis, John Wiley & Sons, Inc., United States of America,
2001.
4. M. R. Arnold, Industrial & Engineering Chemistry, 1956, 48, 1629-1642.
5. D. D. Laskar, B. Yang, H. Wang and J. Lee, Biofuels, Bioprod. Biorefin.,
2013, 7, 602-626.
6. C. Zhang, J. Xing, L. Song, H. Xin, S. Lin, L. Xing and X. Li, Catal. Today,
2014, 234, 145-152.
7. S. Tuokko and P. M. Pihko, Org. Process Res. Dev., 2014, 18, 1740-1751.
8. C. Larpent, R. Dabard and H. Patin, Tet. Lett., 1987, 28, 2507-2510.
9. T. Nimmanwudipong, R. C. Runnebaum, S. E. Ebeler, D. E. Block and B.
C. Gates, Catal. Lett., 2012, 142, 151-160.
was seen except when using Cu-PMO at 180 °C, 4 MPa of hydrogen
for 18 h (Table 3, Entry 1) which effected selective and efficient
hydrogenolysis of the ketone, yielding S6 quantitatively.
To investigate the robustness, selectivity and utility of Cu-PMO,
several other ketones were investigated (Table 4). Benzyl ketones are
very well tolerated, as evidenced by the quantitative hydrogenolysis
of 2-acetonaphthone, 4’-hydroxyacetophenone and benzophenone.
In contrast, the aliphatic ketone benzylacetone furnishes the
corresponding alcohol quantitatively under the same conditions.
Control experiments attribute both reactivity and selectivity to Cu-
PMO.
10.X. Yang, Y. Liang, X. Zhao, Y. Song, L. Hu, X. Wang, Z. Wang and J. Qiu,
RSC Adv., 2014, 4, 31932-31936.
Even though the hydrogenolysis of methoxy-aryl bonds or phenol
groups are also thermodynamically allowed, our Cu-PMO catalyst
showed has a high selectivity (with mostly >95% yields) for the
hydrogenation or hydrogenolysis of carbonyl groups and C-C double
bonds, indicating strong kinetic control of the catalysis. Many other
catalytic systems have shown similar product distributions but with
11.X. Xu, Y. Li, Y. Gong, P. Zhang, H. Li and Y. Wang, J. Am. Chem. Soc.,
2012, 134, 16987-16990.
12.Z. Zhu, H. Tan, J. Wang, S. Yu and K. Zhou, Green Chem., 2014, 16, 2636-
2643.
13.A. Modvig, T. L. Andersen, R. H. Taaning, A. T. Lindhardt and T.
Skrydstrup, J. Org. Chem., 2014, 79, 5861-5868.
14.Q. Wang, Y. Yang, Y. Li, W. Yu and Z. J. Hou, Tetrahedron, 2006, 62,
6107-6112.
15.L. Wolff, Justus Liebigs Annalen der Chemie, 1912, 394, 86-108.
16.E. Clemmensen, Berichte der deutschen chemischen Gesellschaft, 1913,
46, 1837-1843.
17.F. Alonso, P. Riente and M. Yus, Tetrahedron, 2009, 65, 10637-10643.
18.J. Petro, L. Hegedus and I. E. Sajo, Appl. Catal., A, 2006, 308, 50-55.
19.A. L. Jongerius, R. Jastrzebski, P. C. A. Bruijnincx and B. M. Weckhuysen,
J. Catal., 2012, 285, 315-323.
lower selectivity10-14, 36-38
.
Moreover, our Cu-PMO catalyst has the advantage of being
composed entirely of earth-abundant materials and of operating at
very low loadings of Cu (0.3 mol%). Compared to other earth-
abundant metal catalysts20, 21, Cu-PMO is resilient to phenolic units
and is able to accommodate electron-rich and sterically hindered
substrates.
20.
X. Kong and L. Chen, Catal. Commun., 2014, 57, 45-49.
This journal is © The Royal Society of Chemistry 2012
J. Name., 2012, 00, 1-3 | 5

Green Chemistry
Page 6 of 7
COMMUNICATION
VJieowuArrtnicalelONnlainme e
DOI: 10.1039/C5GC01464F
21.M. R. Sturgeon, M. H. O'Brien, P. N. Ciesielski, R. Katahira, J. S. Kruger,
S. C. Chmely, J. Hamlin, K. Lawrence, G. B. Hunsinger, T. D. Foust, R. M.
Baldwin, M. J. Biddy and G. T. Beckham, Green Chem., 2014, 16, 824-
835.
22.
D. P. Debecker, E. M. Gaigneaux and G. Busca, Chem. Eur. J.,
2009, 15, 3920-3935.
23.T. Mizugaki, R. Arundhathi, T. Mitsudome, K. Jitsukawa and K. Kaneda,
Chem. Lett., 2013, 42, 729-731.
24.
25.
26.
K. Barta, G. R. Warner, E. S. Beach and P. T. Anastas, Green
Chem., 2014, 16, 191-196.
G. S. Macala, T. D. Matson, C. L. Johnson, R. S. Lewis, A. V.
Iretskii and P. C. Ford, ChemSusChem, 2009, 2, 215-217.
M. Valiev, E. J. Bylaska, N. Govind, K. Kowalski, T. P. Straatsma,
H. J. J. Van Dam, D. Wang, J. Nieplocha, E. Apra, T. L. Windus and W. A.
de Jong, Comp. Phys. Comm., 2010, 181, 1477-1489.
27.M. Hanwell, D. Curtis, D. Lonie, T. Vandermeersch, E. Zurek and G.
Hutchison, J. Cheminformatics, 2012, 4, 17.
28. A. Klamt and G. Schuurmann, J. Chem. Soc., Perkin Trans. 2,
1993, DOI: 10.1039/P29930000799, 799-805.
29.
H. Wang, A. Sapi, C. M. Thompson, F. Liu, D. Zherebetskyy, J. M.
Krier, L. M. Carl, X. Cai, L.-W. Wang and G. A. Somorjai, J. Am. Chem.
Soc., 2014, 136, 10515-10520.
30.U. K. Singh and M. A. Vannice, App. Cat. A.: Gen., 2001, 213, 1-24.
31.I. H. Bell, J. Wronski, S. Quoilin and V. Lemort, Ind. & Eng. Chem. Res.,
2014, 53, 2498-2508.
32.C. Reichardt and T. Welton, Solvents and Solvent Effects in Organic
Chemistry, Wiley-VCH, Weinheim, Germany, 4th edn., 2011.
33.C. M. Jinesh, C. A. Antonyraj and S. Kannan, Catal. Today, 2009, 141,
176-181.
34.D. Kishore and S. Kannan, App. Cat. A.: Gen., 2004, 270, 227-235.
35.N. V. Shorina, D. S. Kosyakov and K. G. Bogolitsyn, Russ J Appl Chem,
2005, 78, 125-129.
36.X. Yang, Y. Liang, Y. Cheng, W. Song, X. Wang, Z. Wang and J. Qiu,
Catal. Commun., 2014, 47, 28-31.
37.F. H. Mahfud, S. Bussemaker, B. J. Kooi, G. H. Ten Brink and H. J. Heeres,
J. Mol. Cat. A: Chem., 2007, 277, 127-136.
38.M. B. Ezhova, A. Z. Lu, B. R. James and T. Q. Hu, Chem. Ind. (Boca Raton,
FL, U. S.), 2005, 104, 135-143.
39.P. G. M. Wuts and T. W. Greene, Greene's Protective Groups in Organic
Synthesis, John Wiley & Sons, Inc., Hoboken, New Jersey, 4th edn., 2007.
6 | J. Name., 2012, 00, 1-3
This journal is © The Royal Society of Chemistry 2012

DOI: 10.1039/C
Page 7 of 7
Green Chemistry
HYDROGENOLYSIS
O
H
H
H
O
2 H-H
O
H
O
HO
HO
Cu-PMO
- Earth Abundant Elements -
- Robust -
- Selective -
H
H
O
O
H-H
HO
HO
HYDROGENATION