Ruthenium and Formic Acid Based Tandem Catalytic Transformation of Bioderived Furans to Levulinic Acid and Diketones in Water

Article abstract of DOI:10.1002/cctc.201501021

Efficient tandem catalytic transformations of bioderived furans, such as furfural, 5-hydroxymethylfurfural (5-HMF), and 5-methylfurfural (5-MF), to levulinic acid (LA) and diketones, 1-hydroxyhexane-2,5-dione (1-HHD), 3-hydroxyhexane-2,5-dione (3-HHD), and hexane-2,5-dione (2,5-HD), was achieved by using water-soluble arene-Ru^II complexes, containing ethylenediamine-based ligands, as catalysts in the presence of formic acid. The catalytic conversion of furans depends on the catalyst, ligand, formic acid concentration, reaction temperature, and time. Experimental evidence, including time-resolved ¹H NMR spectral studies, indicate that the catalytic reaction proceeds first with formyl hydrogenation followed by hydrolytic ring opening of furans. The ruthenium-formic acid tandem catalytic transformation of fructose to diketones and LA was also achieved. Finally, the molecular structures of the four representative arene-Ru^II catalysts were established by single-crystal X-ray diffraction studies.

Full text of DOI:10.1002/cctc.201501021

DOI: 10.1002/cctc.201501021
Full Papers
Ruthenium and Formic Acid Based Tandem Catalytic
Transformation of Bioderived Furans to Levulinic Acid and
Diketones in Water
Ambikesh D. Dwivedi,[a] Kavita Gupta,[a] Deepika Tyagi,[a] Rohit K. Rai,[a] Shaikh M. Mobin,[a]
and Sanjay K. Singh*[a, b]
Efficient tandem catalytic transformations of bioderived furans,
such as furfural, 5-hydroxymethylfurfural (5-HMF), and 5-meth-
ylfurfural (5-MF), to levulinic acid (LA) and diketones, 1-hydrox-
yhexane-2,5-dione (1-HHD), 3-hydroxyhexane-2,5-dione (3-
HHD), and hexane-2,5-dione (2,5-HD), was achieved by using
water-soluble arene–RuII complexes, containing ethylenedi-
amine-based ligands, as catalysts in the presence of formic
acid. The catalytic conversion of furans depends on the cata-
lyst, ligand, formic acid concentration, reaction temperature,
and time. Experimental evidence, including time-resolved
1H NMR spectral studies, indicate that the catalytic reaction
proceeds first with formyl hydrogenation followed by hydrolyt-
ic ring opening of furans. The ruthenium–formic acid tandem
catalytic transformation of fructose to diketones and LA was
also achieved. Finally, the molecular structures of the four rep-
resentative arene–RuII catalysts were established by single-crys-
tal X-ray diffraction studies.
Introduction
Development of new methodologies for biomass transforma-
tion is gaining extensive attention. As biomass, a viable re-
source of carbon and extensively dispersed in nature, has
shown its potential for the production of carbon-based energy
sources and several valuable platform chemicals, it can proba-
bly replace or provide an alternative to the currently used
fossil fuel and fine chemicals.[1] As direct usage of biomass is
not sustainable to date, the transformation of carbohydrates
(monosaccharides or disaccharides)[2–4] or bioderived furans
(such as 5-hydroxymethylfurfural (5-HMF) or furfural)[5] to fuel
components or chemicals has been extensively studied in
recent years, as these are regarded as the key components of
biomass. In particular, the furans (5-HMF or furfural) have re-
ceived considerable attention for transformation to several val-
uable chemicals and biofuel, possibly owing to the inherent
structural patterns available in these furans.[5–7] Several chemi-
cal processes such as hydrogenation and/or hydrolysis direct
transformations of furans to important chemicals such as levu-
linic acid (LA), succinic acid, diketones, furfuryl alcohol, 2,5-di-
methyl furan, 2,5-bis(hydroxymethyl)furan, pentane-2,5-diol,
and others,[5,6] whereas furan carboxylic acids can be obtained
by selective oxidation of formyl groups of furfural and its deriv-
atives.[7] Complete hydrogenation and hydrolytic ring opening
of furans and its aldol adducts with extended carbon chains,
obtained by aldol condensation of furfural or its derivatives
with acetone, may produce C5–C9 alkanes for direct applica-
tion as fuel.[8] Moreover, one of the diketone products, 3-hy-
droxyhexane-2,5-dione (3-HHD), also known as Henze’s ketol,
obtained during the catalytic transformation of 5-methylfurfu-
ral (5-MF), is known for its significant biological activity and
was also identified in plant extracts.[9] Ketoacids and diketones
obtained from the catalytic transformation of furans have been
extensively used as platform chemicals for the production of
several important fine chemicals (e.g., esters, alcohols, lac-
tones, amines, and cycloketones) or biofuel components such
as blenders for gasoline.[10] Particularly, ketoacid (LA) has been
identified by the US Department of Energy (DOE) as one of the
important target chemicals in their biomass program.[11] Some
of the key features, such as the presence of a carbonyl group,
carboxylic group, and an a-H present in LA, have resulted in
its usage as an important key starting material in several im-
portant reactions for industrial applications (Scheme 1).[12]
Some of the very important end products obtained from LA
are calcium levulinate (a new supplement for calcium), 5-ami-
nolevulinic acid (used for photodynamic therapy (PDT) of
tumor-like human meningioma, and a biodegradable herbi-
cide), g-valerolactone (GVL), and 2-methyltetrahydrofuran
(used as a fuel blender), and so on.
[a] A. D. Dwivedi, K. Gupta, D. Tyagi, R. K. Rai, Dr. S. M. Mobin, Dr. S. K. Singh
Discipline of Chemistry, School of Basic Sciences
Indian Institute of Technology (IIT) Indore
Indore 452 017, Madhya Pradesh (India)
Several new and diverse catalytic processes for the selective
transformation of furan derivatives into open-ring components
are being explored, particularly, by using heterogeneous cata-
lysts.[5–7,13–15] For instance, Au nanoparticles were reported for
the direct conversion of 5-HMF to the corresponding diketones
by hydrogenation/hydrolytic ring opening in the presence of
[b] Dr. S. K. Singh
Centre for Material Science and Engineering
Indian Institute of Technology (IIT) Indore
Indore 452 017, Madhya Pradesh (India)
Supporting information for this article is available on the WWW under
http://dx.doi.org/10.1002/cctc.201501021.
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standing about the ruthenium-catalyst-based transformation of
furans, the development of new highly active and water-solu-
ble catalytic systems are highly required.
In our continuous efforts in this direction, we report here
the use of highly water soluble arene–RuII complexes contain-
ing simple ethylenediamine-based ligands for the tandem cata-
lytic transformation of bioderived furans to open-ring compo-
nents (ketoacids and diketones), in water under moderate reac-
tion conditions. A structure–activity relationship in terms of
NÀH bond availability was also explored. An important reac-
tion intermediate, furfuryl alcohol, was identified by 1H NMR
spectroscopy, which provided additional insights into the
mechanism of the catalytic transformation of furfural to LA,
and also the role of the ruthenium catalyst and the formic
acid. Moreover, the biomass feedstock of furans, fructose, was
also catalytically transformed to diketones with limited conver-
sion. Herein, we also report the X-ray structural characteriza-
tion of the representative arene–RuII complexes employed for
the catalytic reactions.
Scheme 1. Selected applications of levulinic acid.
H3PO4.[14] In the same direction, Pd/C-based catalysis has also
been reported for similar transformations of 5-HMF/furfural to
diketones and ketoacids by using CO2/H2O (1208C) or Amber-
lyst 70 (1708C).[15] However, homogenous catalysts for this class Results and discussion
of reactions are seldom reported. Zhang et al. reported Cp*–
Syntheses and characterization of arene–RuII catalysts
iridium complexes (Cp*=pentamethylcyclopentadiene) cata-
lyzed the conversion of furans to ketones under 20 bar of H2
gas at 110 8C. The reaction proceeded with initial catalytic hy-
drogenation of 5-HMF followed by a ring-opening reaction fa-
cilitated by in situ generated acid.[16] Recently, we also explored
the catalytic efficacy of 8-aminoquinoline-coordinated arene–
ruthenium(II) catalyst for the transformation of furans to LA
and diketones.[17]
Cationic monometallic arene–RuII complexes ([Ru]-1–[Ru]-8)
containing ethylenediamine ligand or its derivatives were syn-
thesized by treating the dichloro-bridged arene–RuII dimer
with the appropriate bidentate ethylenediamine-based ligand
in methanol at room temperature.[22] The identities of the syn-
thesized complexes were established by NMR spectroscopy, el-
emental analysis, and ESI mass spectrometry, and the results
corroborated well with the proposed formula of the complexes
as [(h6-arene)RuCl(k2L)]+ (where h6-arene=C6H6 or C10H14,
and L=H2NCH2CH2NH2 (en), H2NCH2CH2NH(CH3) (Me1en),
H2NCH2CH2N(CH3)2 (Me2en), or (CH3)HNCH2CH2N(CH3)2 (Me3en)
(Figure 1). Suitable crystals of arene–RuII complexes [Ru]-2,
[Ru]-6, [Ru]-7, and [Ru]-8 were grown by slow evaporation of
the methanol/dichloromethane solution of the respective com-
plexes. The crystals were subjected to single-crystal X-ray
diffraction analysis to confirm the structures as [(h6-
Arene–RuII complexes, such as ethylenediamine-based ruthe-
nium complexes or Shvo’s catalyst, represent a well-established
class of active catalysts for efficient hydrogenation of carbonyl
groups in ketones, aldehydes, esters, C=N bonds in imines, or
C=C bonds in styrene or furfuryl alcohol.[18] The excellent syner-
gistic cooperation between the metal and ligand in these com-
plexes, such as the availability of NÀH bonds to facilitate trans-
fer hydrogenation reactions, accounts for the high catalytic
performances of the complexes in hydrogenation reactions
using H2 or other H-donors, for example, formic acid.[18,19]
These insights encouraged us to employ the arene–RuII com-
plexes containing simple ethylenediamine-based ligands in the
highly efficient transformation of bioderived furans to open-
ring components. Moreover, using formic acid not only satisfies
the requirement of a H-donor but also provides plenty of H+
ions. However, it is worth mentioning here that using excess
acid may lead to humin formation from furan derivatives.[20]
Furthermore, the high aqueous solubility and stability dis-
played by most of the arene–RuII complexes may offer easy re-
covery and reuse of the catalyst. Although literature reports
highlight the competence of several ruthenium complexes for
hydrogenation of furfural and 5-hydroxymethylfurfural (5-HMF)
to the corresponding alcohols (furfuryl alcohol and 2,5-bis(hy-
droxymethyl)furan),[21] employing arene–RuII complexes with
formic acid for tandem catalytic transformation of furans is
rarely explored.[17] Therefore, to enrich and enhance the under-
C6H6)RuCl(Me1en)]PF6
([Ru]-2),
[(h6-C10H14)RuCl(Me1en)]PF6
([Ru]-6), [(h6-C10H14)RuCl(Me2en)]PF6 ([Ru]-7), and [(h6-
C10H14)RuCl(Me3en)]PF6 ([Ru]-8) (Figure 1 and Tables S1–S2 in
the Supporting Information).
All the complexes display analogous molecular structures
with the characteristic piano-stool geometry of arene–RuII com-
plexes, with the h6-coordinated arene ring as the top and the
two nitrogen atoms of the respective ethylenediamine-based
ligand and one chloride ligand as the three legs. The com-
plexes [Ru]-2, [Ru]-7, and [Ru]-8 crystallize in the monoclinic
P21 space group, whereas the complex [Ru]-6 is in the triclinic
6
6
¯
P1 space group. The arene ring (h -benzene or h -p-cymene)
appears almost planar for all the complexes; the centroid of
the arene ring is displaced by 1.65–1.69 Š from the RuII center.
The RuÀnitrogen and RuÀchloride bond lengths are within the
ranges 2.11–2.19 Š and 2.40–2.42 Š, respectively, which are
close to those reported previously for related arene–RuII com-
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Catalytic transformation of furan derivatives
The catalytic efficacy of the water-soluble catalysts [Ru]-1–
[Ru]-8 was explored for the aqueous-phase tandem transfor-
mation of furan derivatives into LA and diketones. Readily
available furan derivative, furfural (1a), was selected as the
model substrate for the catalytic reaction. In the first set of ex-
periments, the influence of the additive (formic acid), tempera-
ture, structural parameters such as h6-coordinated arene and
the NÀH bonds in the ethylenediamine-based ligands, on the
catalytic transformation of furfural to LA were investigated.
Initial results indicated that complete conversion of furfural
(1a) to LA (2a) with >99% selectivity was achieved with
5 mol% of [Ru]-1 in the presence of 12 equivalents of formic
acid after reaction for 24 h at 808C. Analysis of the product by
1H NMR spectroscopy (d=2.73 (t, ÀCH2, C2), 2.60 (t, ÀCH2, C3),
and 2.17 ppm (s, ÀCH3, C5)), 13C NMR and HRMS analysis fur-
ther confirmed the formation of LA (m/z found=139.0365
[C5H8O3+Na+] and m/z calculated=139.0366 [C5H8O3+Na+])
(Figure 2). These results, indeed, indicate the decisive role of
the [Ru]-1 catalyst, with a positive cooperation from formic
acid, for the tandem catalytic transformation of furfural with
high selectivity to LA.
Further, the reaction completion time was fine-tuned by op-
timizing the reaction temperature (Figure 3(a)). Decreasing the
reaction temperature to 608C resulted in a significant loss of
the catalytic activity, and at 408C catalytic reaction was
stopped. However, reactions performed at 1008C displayed
complete conversion of furfural to LA in a shorter reaction
time (8 h). To further optimize the formic acid amount, reac-
tions were performed with the formic acid amount ranging
from 0 to 24 equivalents (Figure 3(b)). Complete conversion of
furfural with >99% selectivity for LA was achieved in the pres-
ence of ꢀ12 equivalents of formic acid, whereas decreasing
the formic acid amount below 12 equivalents resulted a de-
crease in conversion of furfural and the selectivity for LA was
Figure 1. Schematic representation of the arene–RuII catalysts [Ru]-1–[Ru]-8
(left), and the X-ray crystal structures of the representative catalysts [Ru]-2,
[Ru]-6, [Ru]-7, and [Ru]-8 (right; thermal ellipsoids drawn at the 30% proba-
bility level) used for water-based catalytic transformation of furanic com-
pounds. Counter anions, PF6, and hydrogen atoms (except those on nitro-
gen atoms) are omitted for clarity.
plexes.[22,23] Moreover, the ClÀRuÀN and NÀRuÀN bond angle
ranges are 82.4–88.18 and 78.3–79.88, respectively, and those
between the legs and the centroid of the h6-arene ring is
124.5–133.88; the observed values are comparable with those
reported for other analogous complexes.[22,23]
Figure 2. Catalytic transformation of furfural to LA in the presence of [Ru]-1 catalyst and formic acid in water, and the identification of LA by (a) HRMS and
(b) 1H NMR spectroscopy.
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Figure 3. Effect of (a) reaction temperature and (b) formic acid concentration on the catalytic transformation of furfural to LA in the presence of [Ru]-1 in
water. Reaction conditions: (a) furfural (1.0 mmol), catalyst (5 mol%), formic acid (12 equiv.), and water (10 mL) at different temperatures for 8 h. (b) Furfural
(1.0 mmol), catalyst (5 mol%), formic acid (as specified), and water (10 mL) at 1008C for 8 h.
also compromised. Interestingly, for the catalytic reaction with
lower formic acid amounts, the hydrogenated intermediate,
furfuryl alcohol, was also observed along with the LA. More-
over, it is worth mentioning that no conversion of furfural was
observed for the catalytic reaction performed in the absence
of formic acid (Figure 3(b) and Figure S1 in the Supporting In-
formation). Interestingly, when furfural was treated with formic
acid, in the absence of the catalyst, only humin formation was
observed (Figure S1).[20] Furthermore, replacement of formic
acid with short-chain or bulky acids such as acetic acid, pro-
pionic acid, or iso-butyric acid also resulted in no conversion of
furfural (Table S3 in the Supporting Information). As the forma-
tion of metal–hydride bond, a crucial step in the transfer hy-
drogenation reaction, is only possible in the presence of formic
Figure 4. Catalytic transformation of furfural to LA by arene–RuII complexes
in water. Reaction conditions: furfural (1.0 mmol), catalyst (5 mol%), formic
acid (12 equiv.), and water (10 mL) at 1008C for 8 h.
acid, other acids could not contribute to the metal-catalyzed
transfer hydrogenation for the transformation of furfural to fur-
furyl alcohol, and therefore resulted in no reaction. Further evi-
dence to support the dual role of the formic acid during the
catalytic reaction was gained by performing the transformation
of furfural in the presence of [Ru]-1 catalyst and replacing
formic acid with hydrogen gas under optimized reaction con-
ditions. Contrary to the high activity achieved in the presence
of formic acid, replacing formic acid with hydrogen gas result-
ed in no conversion of furfural. These observations strongly
support the significant role of formic acid for the tandem cata-
lytic transformation of furfural to levulinic acid via furfuryl alco-
hol, where the crucial transfer hydrogenation step can only
take place in the presence of formic acid, but not with other
organic acids or hydrogen gas under our optimized reaction
conditions.
place of ethylenediamine, was found to be only slightly less
active than the [Ru]-1 catalyst. Although the Ru-p-cymene cat-
alyst ([Ru]-5) was found to be slightly less active than its close
analogue, Ru-benzene catalyst ([Ru]-1), an analogous trend in
the catalytic activity was also observed with the change in the
NÀH entities for the catalysts [Ru]-6–[Ru]-8 (Figure S2 in the
Supporting Information).
These observations indicated a significant structure–activity
relationship driving the catalytic activity of the studied arene–
RuII complexes. The role of NÀH bonds present in the rutheni-
um complexes during the transfer hydrogenation process is
well established.[24] The mechanistic study of the catalytic
transformation of furfural inferred an initial transfer hydrogena-
tion of furfural to furfuryl alcohol, which subsequently under-
goes formic acid assisted hydrolytic ring opening to levulinic
acid. We strongly believe that, in our case, NÀH bonds also
play a significant role in controlling the catalytic activity of the
studied ruthenium complexes, particularly for the initial trans-
formation of furfural to furfuryl alcohol, and therefore [Ru]-1,
with a high availability of NÀH bonds, showed the highest cat-
alytic activity. Moreover, the higher activity of the benzene
complex over p-cymene complex was presumably due to the
combined steric and electronic effect of the arene ligands.[24]
Thus, all the further optimizations and explorations of the cata-
Having optimized the reaction conditions, the influence of
the other arene–RuII catalysts, [Ru]-2–[Ru]-8, containing either
varying ethylenediamine derivatives or h6-arene ligands, on the
catalytic transformation of furfural to LA was investigated. As
depicted in Figure 4, of the various ethylenediamine ligands
used, the ruthenium catalysts [Ru]-1 and [Ru]-5, with unsubsti-
tuted ethylenediamine, performed the best. The catalytic activ-
ity was in the order of [Ru]-1>[Ru]-2>[Ru]-3>[Ru]-4, which
clearly indicates the significant role of the NÀH bond in the en-
hanced catalytic activity of the [Ru]-1 catalyst. Moreover,
a close analogue of the highly active [Ru]-1 catalyst, an analog
that contains the N-tosylated ethylenediamine (Ts-en) ligand in
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lytic transformation reactions of furan derivatives was done
using the highly active ruthenium catalyst [Ru]-1.
centration of furfural (0.05 to 0.15 molLÀ1). The initial rates in-
dicated that the catalytic reaction follows first-order kinetics
with furfural concentration (Figure S3 in the Supporting Infor-
mation). Moreover, the kinetic study performed by using
a fixed concentration of furfural (0.10 molLÀ1) with varying
formic acid concentrations (0.6 to 2.4 molLÀ1) indicated that,
contrary to the trends observed with furfural concentration,
the reaction rate was not sensitive to the concentration of
formic acid (Table S4 in the Supporting Information).
To further investigate the progress of the catalytic reaction
and to identify any possible intermediate components (possi-
1
bly hydrogenated products), UV/Vis and H NMR spectra were
collected as a function of time for the catalytic transformation
of furfural to LA in the presence of [Ru]-1, in water at 1008C
(Figures 5 and 6). With increasing reaction time, a gradual de-
1
Time-resolved H NMR spectra were recorded to monitor the
progress of the [Ru]-1-catalyzed transformation of furfural over
a period of 12 h. We observed that the intensities of the reso-
nances resulting from LA at d=2.73 (t, ÀCH2, C2), 2.60 (t, ÀCH2,
C3), and 2.17 ppm (s, ÀCH3, C5) increase with the progress of
the catalytic reaction (Figure 6). The reaction profiles with re-
spect to time, shown in Figure 6(b), depict that, in the initial
hours of the catalytic reaction, there is formation of the hydro-
genated intermediate, furfuryl alcohol; however, this intermedi-
ate soon disappeared with the progress of the catalytic reac-
tion and LA appeared as the only major product. These results
are in accordance with previous reports, where in the reaction
performed employing furfuryl alcohol, instead of furfural, its
facile transformation to LA was comfortably achieved even in
the absence of catalyst.[17] The assumption that the intermedi-
ate, furfuryl alcohol, presumably undergoes facile ring opening
in the presence of formic acid, was further supported by the
appearance of furfuryl alcohol in the reactions performed with
lower amounts (<12 equivalents) of formic acid. However, fur-
furyl alcohol soon disappeared with increased formic acid
amounts. These important observations and the isolation of
the intermediate, furfuryl alcohol, inferred that, presumably,
the [Ru]-1 catalyst initially catalyzed the hydrogenation of fur-
fural to the corresponding furfuryl alcohol by transfer hydroge-
nation by using formic acid as the hydrogen source, and later
the furfuryl alcohol instantly undergoes ring opening to LA by
an acid-promoted hydrolysis to achieve the tandem catalytic
transformation of furfural to levulinic acid, as exemplified in
Figure S4 (in the Supporting Information).[16,17]
Figure 5. UV/Vis spectra as a function of time for the catalytic transformation
of furfural to LA in water. Inset: kinetic profile for the initial 8 h at 276 nm.
Reactions were performed by using 5 mol% arene–RuII catalyst [Ru]-1 in the
presence of formic acid (12 equiv.) at 1008C.
crease was observed in the intensity of the absorption band at
276 nm in the UV/Vis spectra, which corresponds to furfural
(Figure 5). Although the band from LA was not distinguishable,
the observed UV/Vis pattern indicated that furfural was being
used up during the course of the reaction. The kinetic plot
(Figure 5, inset) of the catalytic reaction, based on the absorb-
ance values at 276 nm for the initial 8 h, showed a linear corre-
lation between ln(Ct/C0) and reaction time, which suggests that
the reaction follows pseudo-first-order kinetics (k=5.67”
10À5 sÀ1). A series of reactions for the catalytic transformation
of furfural was further carried out by using a fixed initial con-
centration (1.2 molLÀ1) of formic acid while varying the con-
To further investigate the generality of the [Ru]-1 catalyst,
catalytic transformations of other furan derivatives with differ-
1
Figure 6. (a) Time-resolved H NMR spectra and (b) corresponding reaction profiles for the catalytic transformation of furfural to LA in water by using 5 mol%
[Ru]-1 catalyst in the presence of formic acid (12 equiv.) at 1008C.
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1H NMR spectroscopy, where no evidence of decomposition
was observed (Figure S5 in the Supporting Information). More-
over, the TGA graphs clearly indicated that [Ru]-1 catalyst is
stable up to 2008C (Figure S6 in the Supporting Information).
Further, mercury poisoning experiments showed no significant
change in the catalytic activity of [Ru]-1 catalyst in the pres-
ence of an excess of Hg0, which strongly indicates the homo-
genous nature of the catalyst. Although the homogeneous
nature of the catalyst provides several advantages, the easy re-
covery of catalysts of homogeneous catalytic reactions remains
an inherent limitation. However, we are fortunate that the high
aqueous solubility of the [Ru]-1 catalyst gave us an opportuni-
ty for easy recovery of the catalyst and its reuse for further cat-
alytic cycles for the transformation of furfural to LA. After each
catalytic run, reaction mixture was extracted by using a suitable
organic solvent, while the catalyst, which remains in the aque-
ous phase, was immediately used for the next catalytic run by
adding additional specified amounts of the furfural and formic
acid. The [Ru]-1 catalyst was recycled for at least five consecu-
tive catalytic cycles, without significant loss of the catalytic ac-
tivity (Figure 7).
Scheme 2. Catalytic transformation of furan by [Ru]-1 in water.
ent substituents at the 2 and 5 positions, such as 5-HMF (1b),
5-MF (1c), and N-(furan-2-ylmethylene)propan-2-amine (1d),
were investigated under the optimized reaction conditions
(5 mol% [Ru]-1, 12 equiv. formic acid, 1008C, 8 h) (Scheme 2).
Complete conversion of furfural with >99% selectivity to LA
(isolated yield 42%) was achieved in 8 h (Scheme 2(a)). Under
identical reaction conditions, 92% conversion of 5-HMF was
achieved, where 1-hydroxyhexane-2,5-dione (1-HHD, 2b), 3-
HHD (2c), LA (2a), and hexane-2,5-dione (2,5-HD; 2d) were ob-
served as the products with selectivities of 41, 36, 18, and 5%,
respectively (Scheme 2(b)). Conversion of 5-HMF to 1-HHD also
occurred in accordance with previous reports, where it was re-
ported as one of the major products when using catalytic sys-
tems based on Pd/C, Cp*–Ir complexes, or arene–RuII cata-
lysts.[15–17] Reaction with 5-MF (1c) yielded 60% 3-HHD (2c),
where the relative selectivity for 3-HHD and 2,5-HD were 68
and 32%, respectively (Scheme 2(c)). Moreover, the reaction
was also performed with N-(furan-2-ylmethylene)propan-2-
amine (1d), obtained by the condensation of furfural with iso-
propylamine. Interestingly, the reaction products obtained
were LA and isopropylamine-condensed LA (N-(isopropylimi-
no)pentanoic acid, 2e) in approximately 1:1 molar ratio
(Scheme 2(d)). The formation of the product 2e indicated that,
presumably, the imine bond in the substrate 1d hydrolyzed
during the catalytic reaction and later condensed with the ke-
tonic group of the LA to yield 2e.
Figure 7. Recyclability of [Ru]-1 catalyst for the catalytic transformation of
furfural to LA in the presence of formic acid (12 equiv.) in water at 1008C.
These results further demonstrated the high stability of the
[Ru]-1 catalyst in water. Moreover, scanning electron micro-
scopic (SEM) images (Figure S7 in the Supporting Information)
of the fresh catalyst and the catalyst recovered after the cata-
lytic reaction showed no remarkable morphological changes of
the [Ru]-1 catalyst during the reaction. These observations
were further authenticated by the presence of peaks corre-
sponding to the protons and carbon atoms of the ethylenedia-
mine and arene ligands in the NMR spectra of the [Ru]-1 cata-
lyst recovered after the catalytic reactions (Figure S8 in the
Supporting Information), peaks that are consistent with the
those of the fresh [Ru]-1 catalyst. Moreover, ESI mass spectral
data of the catalyst recovered after the catalytic reaction was
also found to be analogous to that of the fresh catalyst (Fig-
ure S9 in the Supporting Information). The above analyses
ensure that there is no significant deformation in the catalyst
structure, which is consistent with the observed high catalytic
Catalyst stability, recovery, and recycling
The thermal stability of the ruthenium catalyst [Ru]-1 was
1
studied by performing H NMR experiments and thermal gravi-
metric analysis (TGA) measurements. The decomposition of the
catalyst was monitored at certain intervals of time (0–72 h) by
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recyclability, up to five consecutive catalytic runs, for the cata-
lyst in the studied catalytic transformation.
furans, catalysts are generally active at higher temperatures
[Pd/C (1208C), Au/Nb2O5 (1408C), Pd/Al2O3 (1408C), Ni–Al2O3
(1808C)].[14,15b,28,29] Catalytic transformations with homogene-
ous catalysts show narrow product distributions and greater
selectivity towards the open-ring products, for instance, with
Cp*–Ir catalysts and arene–RuII catalysts.[16,17] Moreover, ruthe-
nium-based homogeneous catalysts were found to be highly
active and recyclable even in aqueous media.[17] In the present
study, arene–Ru complexes containing ethylenedia-
mine ligands were also found to be highly active and
stable even at 1008C in water and open atmospheric
conditions, and can be recycled in up to five consec-
utive catalytic cycles without any significant loss in
the catalytic activity. Moreover, the studied arene–Ru
catalyst [Ru]-1 has shown potential to convert fruc-
tose to LA and diketones (1-HHD, 3-HHD, 2,5-HD) in
water under moderate reaction conditions.
Catalytic transformation of fructose to LA and diketones
Next, we explored the catalytic transformation of fructose to
LA and diketones in the presence of 5 mol% [Ru]-1 catalyst
(Scheme 3).
Scheme 3. Catalytic transformation of fructose to LA and diketones.
After heating fructose at 1008C for 8 h in the presence of
12 equivalents of formic acid, conversion of fructose to 1-HHD
and LA as the major products were achieved with 27 and 51%
selectivity, respectively, along with 5-HMF (5%), diketone (4%),
and 3-HHD (13%) as minor products. The reaction products
obtained from fructose transformation were found to be analo-
gous to the products obtained with 5-HMF, suggesting that,
presumably, the reaction proceeds through the initial forma-
tion of 5-HMF.[3] Moreover, by increasing the reaction time to
16 h or doubling the formic acid amount (24 equiv.), the selec-
tivity for 1-HHD increased and 87% selectivity was observed
when the reaction was performed at 1008C for 16 h in the
presence of 12 equivalents of formic acid. Unfortunately, at-
tempts to use glucose in place to fructose failed, possibly be-
cause the [Ru]-1 catalyst cannot catalyze the isomerization of
glucose to fructose. Despite the low fructose transformation
observed for the catalytic reaction, it is worth noting that the
direct catalytic transformation of fructose to open-ring compo-
nents such as LA and diketones can also be achieved with
ruthenium-based homogenous catalysts.
Conclusions
Highly active water-soluble homogenous catalysts based on
arene–ruthenium(II) complexes containing simple and readily
available ethylenediamine (or its derivatives) ligands, were suc-
cessfully employed for the catalytic transformation of bio-
derived furans into open-ring value-added ketoacid (LA) and
diketones (1-HHD, 3-HHD, and 2,5-HD) in the presence of
formic acid. Depending upon the furan used, formic acid con-
centration, reaction temperature, and the catalyst, catalytic
conversion, selectivity, and the product distribution can be
fine-tuned. The NÀH bonds present in the ruthenium catalyst
were shown to exert a significant on the catalytic transforma-
tion, where the most active catalyst has the highest number of
NÀH bonds. Moreover, direct catalytic transformation of fruc-
tose to 1-HHD and LA was also achieved with limited conver-
1
sion. Mechanistic studies involving H NMR spectroscopy and
experiments with variable formic acid concentrations revealed
a tandem mode of catalytic transformation of furfural to LA via
the hydrogenated intermediate, furfuryl alcohol. Furthermore,
high aqueous solubility and stability of the ruthenium catalyst
offers the potential for easy recovery and reusability in at least
five consecutive catalytic runs without any significant loss of
the catalytic activity. Through our study, we have demonstrat-
ed a significant cooperation between the ruthenium catalyst
and formic acid to achieve high catalytic turnover for the trans-
formation of furans. We believe that this work will encourage
extensive research on the design and development of simple
yet active catalysts for this or several other important catalytic
transformations in the fine chemical industry and biofuel-
based energy sector.
Most of the studies on the transformation of furans have
been performed in autoclaves by using mineral acids or H2 gas
with high pressure and temperature.[15,16,25–28] Among these,
there are many reports on the catalytic transformation of 5-
HMF to ketoacids and diketones, particularly by using hetero-
geneous catalysts, whereas studies with homogeneous catalyst
are relatively few.[14,15b,16,17,25–30] Li et al. employed Amberlyst 70
for furfural transformation in water, as well as methanol, and
observed that furfural converted to a polymer in both reaction
media.[15a] Even by using Pd/Al2O3 with Amberlyst 70 and
70 bar H2 at 1658C in methanol, only low yields (23.1 and
2.4%) of methyl-levulinate and levulinic acid were achieved,
whereas Pd/Al2O3 on its own was found to be inactive.[26]
Riisager et al. explored Ru(OH)x/Al2O3 catalysts for the aerobic
oxidation of 5-HMF at 1408C, where LA was observed as a side
product along with the oxygenated products 2,5-furandi-
carboxylic acid and so on.[30] Also, LA was observed as a by-
product during the catalytic hydrogenation of furfural and 5-
HMF over a Pd–Ir/SiO2 catalyst.[27] In the transformation of
Experimental Section
Materials and methods
All reactions were performed without inert gas protection, using
chemicals of high purity purchased from Aldrich or Alfa Aesar. Di-
chloro-bridged arene–RuII precursors [{(h6-C6H6)RuCl2}2] and [{(h6-
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C10H14)RuCl2}2] were synthesized according to the literature proce-
dures.[31] The catalytic reactions were monitored by using a thin
layer chromatography (TLC). 1H NMR (400 MHz), 13C NMR
(100 MHz), and 31P NMR (161.97 MHz) spectra were recorded at
298 K by using CDCl3, D2O, or [D6]DMSO as the solvent on a Bruker
Avance 400 spectrometer. Tetramethylsilane (TMS) was used as an
external standard and the chemical shifts in ppm are reported rela-
tive to the center of the singlet at 7.26 ppm for CDCl3, 4.75 for
D2O, and 2.49 ppm for [D6]DMSO in 1H NMR spectra and to the
center of the triplet at 77.0 ppm for CDCl3 and 39.50 ppm for
[D6]DMSO in 13C NMR spectra. Suitable single crystals of the arene–
RuII complexes [Ru]-2, [Ru]-6, [Ru]-7, and [Ru]-8 were subjected to
single-crystal X-ray structural studies by using an Agilent Technolo-
gies Supernova CCD system. ESI (positive and negative mode) and
high-resolution mass spectra (HRMS) were recorded on a micro
TF-Q II mass spectrometer. UV/Vis spectra were performed on
a Varian Cary 100 Bio UV/Vis spectrophotometer and a Shimadzu
UV-1700 PharmaSpec UV/Vis spectrophotometer using 10 mm
quartz cuvettes. To study the kinetics of the catalytic reactions by
UV/Vis spectrophotometry, a small portion of the reaction mixture
(100 mL), taken at different time intervals, was added to distilled
water (3 mL) and the spectra were obtained. To calculate the rate
constant of the catalytic reaction, the ratio of Ct and C0, where Ct is
the concentration at time ‘t’ and C0 is the initial concentration, was
measured by using the relative intensity ratio of the respective ab-
sorbance At/A0 at 276 nm. GC-MS analysis was performed on
a PerkinElmers GC gas chromatograph Clarus 680 coupled with
a PerkinElmers mass spectrometer Clarus SQ8T in the EI (Electron
Impact) mode and using a capillary column ELITE 5 (30 m”
0.25 mm). Thermal gravimetric analyses (TGA) were performed on
the Mettler Toledo thermal analysis system. Scanning electron mi-
croscopy (SEM) images and elemental mapping data were collect-
ed on a Carl Zeiss supra 55 (operating voltage 15 kV), by using
amorphous carbon-coated 400 mesh copper grids for the deposit-
ed sample.
fied by column chromatography on silica gel with a 10% ethylace-
tate/hexane mixture (400 mL). Then, the product was isolated by
removing the solvent in vacuo. The product levulinic acid (LA) was
obtained by adding saturated sodium bicarbonate solution to the
organic extract (reduced volume to ca. 5 mL) until effervescence
ceases. Then, the mixture was washed with ethylacetate (4”
10 mL). The combined water portion was neutralized with dilute
hydrochloric acid, and the product was extracted with ethylacetate
(4”10 mL). LA was isolated by removing the solvent in vacuo.
During the extraction, separation, and purification processes, the
organic and aqueous portions were continuously monitored by
thin layer chromatography (TLC) under a UV chamber or by stain-
1
ing with iodine. The reaction products were identified by H NMR,
13C NMR, HRMS, and GCMS analysis. Conversions and selectivities
1
were determined by H NMR spectroscopy. Isolated yields were de-
termined from the products obtained from the purification process
as described above.
Acknowledgments
The authors thank IIT Indore, CSIR, New Delhi, and SERB (DST),
New Delhi, for financial support. SIC, IIT Indore is acknowledged
for use of its instrumental facilities. Sincere thanks go to Prof.
Pratibha Sharma, DAVV, Indore, for her help in performing the ki-
netic study. A.D.D. thanks the CSIR New Delhi research scheme
(01(2722)/13/EMR-II) for a JRF grant. K.G. and R.K.R. thank CSIR
New Delhi for their SRF grants. D.T. thanks UGC New Delhi for
a SRF grant.
Keywords: diketones
catalysis · water
· furans · levulinic acid · tandem
[1] a) D. L. Klass, Biomass for Renewable Energy, Fuels, and Chemicals, Aca-
demic Press, San Diego, 1998; b) R. A. Sheldon, Green Chem. 2014, 16,
950–963; c) M. J. Climent, A. Corma, S. Iborra, Green Chem. 2014, 16,
516–547; d) L. Hu, G. Zhao, W. Hao, X. Tang, Y. Sun, L. Lin, S. Liu, RSC
Adv. 2012, 2, 11184–11206; e) S. Van de Vyver, J. Geboers, P. A. Jacobs,
B. F. Sels, ChemCatChem 2011, 3, 82–94; f) A. Corma, S. Iborra, A. Velty,
Chem. Rev. 2007, 107, 2411–2502; g) L. Petrus, M. A. Noordermeer,
Green Chem. 2006, 8, 861–867; h) G. W. Huber, J. N. Chheda, C. J. Bar-
rett, J. A. Dumesic, Science 2005, 308, 1446–1450.
[2] a) A. M. Ruppert, K. Weinberg, R. Palkovits, Angew. Chem. Int. Ed. 2012,
51, 2564–2601; Angew. Chem. 2012, 124, 2614–2654; b) R. Xing, A. V.
Subrahmanyam, H. Olcay, W. Qi, G. P. van Walsum, H. Pendse, G. W.
Huber, Green Chem. 2010, 12, 1933–1946.
[3] a) K. Tajvidi, P. J. C. Hausoul, R. Palkovits, ChemSusChem 2014, 7, 1311–
1317; b) A. Yepez, A. Garcia, M. S. Climent, A. A. Romero, R. Luque,
Catal. Sci. Technol. 2014, 4, 428–434; c) R. Alamillo, A. J. Crisci, J. M. R.
Gallo, S. L. Scott, J. A. Dumesic, Angew. Chem. Int. Ed. 2013, 52, 10349–
10351; Angew. Chem. 2013, 125, 10539–10541; d) A. Yepez, A. Pineda,
A. Garcia, A. A. Romero, R. Luque, Phys. Chem. Chem. Phys. 2013, 15,
12165–12172; e) H. Kimura, M. Nakahara, N. Matubayasi, J. Phys. Chem.
A 2013, 117, 2102–2113; f) J. Zhang, E. Weitz, ACS Catal. 2012, 2, 1211–
1218; g) T. Thananatthanachon, T. B. Rauchfuss, ChemSusChem 2010, 3,
1139–1141.
[4] a) X. Yi, I. Delidovich, Z. Sun, S. Wang, X. Wang, R. Palkovits, Catal. Sci.
Technol. 2015, 5, 2496–2502; b) N. A. S. Ramli, N. A. S. Amin, J. Mol.
Catal. A 2015, 407, 113–121; c) H. Huang, C. A. Denard, R. Alamillo, A. J.
Crisci, Y. Miao, J. A. Dumesic, S. L. Scott, H. Zhao, ACS Catal. 2014, 4,
2165–2168; d) L. Wu, J. Song, B. Zhang, B. Zhou, H. Zhou, H. Fan, Y.
Yang, B. Han, Green Chem. 2014, 16, 3935–3941; e) J. Song, H. Fan, J.
Ma, B. Han, Green Chem. 2013, 15, 2619–2635; f) F. H. Richter, K. Pupo-
vac, R. Palkovits, F. Schüth, ACS Catal. 2013, 3, 123–127; g) A. J. Crisci,
M. H. Tucker, M.-Y. Lee, S. G. Jang, J. A. Dumesic, S. L. Scott, ACS Catal.
Synthesis of ruthenium catalysts ([Ru]-1–[Ru]-8)
Arene–RuII complexes [Ru]-1–[Ru]-8 were synthesized by using
a modified literature method.[22] A methanol solution (25 mL) of
the dichloro-bridged arene–RuII dimer (0.2 mmol) and the suitable
ethylenediamine or N-substituted ethylenediamine (0.4 mmol) was
stirred at room temperature (298 K) for 3 h, filtered, and NH4PF6
(1.0 mmol) was added to the filtrate. The total volume of the solu-
tion was slowly reduced to approximately 10 mL on a rotary evap-
orator and, after cooling overnight at 48C, the microcrystalline
product was obtained, which was collected by filtration, washed
with ether, and recrystallized from methanol/CH2Cl2/ether.
Catalytic reaction for the conversion of furans/fructose to
LA/diketones
Furan/fructose (1.0 mmol) and formic acid (as specified) were
added to an aqueous suspension (10 mL) of arene–RuII catalyst
(5 mol%), and the reaction mixture was stirred for a specified time
at 1008C (oil bath). After the catalytic reaction was complete, the
reaction mixture was extracted with ethylacetate (4”10 mL), the
organic extract was washed with brine (5 mL), and dried with
Na2SO4. The solvent was removed in vacuo. The obtained products
were separated by column chromatography on silica gel with
n-hexane/ethylacetate (98:2 to 90:10) as the eluents. The product
3-hydroxyhexane-2,5-dione (3-HHD) obtained from the catalytic
transformation of 5-methylfurfural (5-MF) was separated and puri-
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2011, 1, 719–728; h) S. Hu, Z. Zhang, J. Song, Y. Zhou, B. Han, Green
Chem. 2009, 11, 1746–1749.
[13] M. Sankar, N. Dimitratos, P. J. Miedziak, P. P. Wells, C. J. Kiely, G. J. Hutch-
ings, Chem. Soc. Rev. 2012, 41, 8099–8139.
[5] a) R. J. van Putten, J. C. van der Waal, E. de Jong, C. B. Rasrendra, H. J.
Heeres, J. G. de Vries, Chem. Rev. 2013, 113, 1499–1597; b) Y. Nakagawa,
M. Tamura, K. Tomishige, ACS Catal. 2013, 3, 2655–2668; c) J. C. Serra-
no-Ruiz, R. Luque, A. Sepulveda-Escribano, Chem. Soc. Rev. 2011, 40,
5266–5281.
[6] a) S. Liu, Y. Amada, M. Tamura, Y. Nakagawa, K. Tomishige, Green Chem.
2014, 16, 617–626; b) Y. Yang, Z. Du, Y. Huang, F. Lu, F. Wang, J. Gao, J.
Xu, Green Chem. 2013, 15, 1932–1940; c) J. Chen, F. Lu, J. Zhang, W. Yu,
F. Wang, J. Gao, J. Xu, ChemCatChem 2013, 5, 2822–2826; d) Y. Nakaga-
wa, H. Nakazawa, H. Watanabe, K. Tomishige, ChemCatChem 2012, 4,
1791–1797; e) W. Xu, H. Wang, X. Liu, J. Ren, Y. Wang, G. Lu, Chem.
Commun. 2011, 47, 3924–3926.
[7] a) J. Artz, S. Mallmann, R. Palkovits, ChemSusChem 2015, 8, 672–679;
b) J. M. R. Gallo, D. M. Alonso, M. A. Mellmer, J. A. Dumesic, Green Chem.
2013, 15, 85–90; c) F. L. Grasset, B. Katryniok, S. Paul, V. Nardello-Rataj,
M. Pera-Titus, J.-M. Clacens, F. D. Campo, F. Dumeignil, RSC Adv. 2013, 3,
9942–9948; d) T. Pasini, M. Piccinini, M. Blosi, R. Bonelli, S. Albonetti, N.
Dimitratos, J. A. Lopez-Sanchez, M. Sankar, Q. He, C. J. Kiely, G. J. Hutch-
ings, F. Cavani, Green Chem. 2011, 13, 2091–2099; e) S. E. Davis, L. R.
Houk, E. C. Tamargo, A. K. Datye, R. J. Davis, Catal. Today 2011, 160, 55–
60.
[8] a) Q.-N. Xia, Q. Cuan, X.-H. Liu, X.-Q. Gong, G.-Z. Lu, Y.-Q. Wang, Angew.
Chem. Int. Ed. 2014, 53, 9755–9760; Angew. Chem. 2014, 126, 9913–
9918; b) M. Li, X. Xu, Y. Gong, Z. Wei, Z. Hou, H. Li, Y. Wang, Green
Chem. 2014, 16, 4371–4377; c) G. Li, N. Li, S. Li, A. Wang, Y. Cong, X.
Wang, T. Zhang, Chem. Commun. 2013, 49, 5727–5729; d) A. D. Sutton,
F. D. Waldie, R. Wu, M. Schlaf, L. A. P. Silks, III, J. C. Gordon, Nat. Chem.
2013, 5, 428–432; e) S. Sitthisa, D. E. Resasco, Catal. Lett. 2011, 141,
784–791; f) Z. Xinghua, W. Tiejun, M. Longlong, W. Chuangzhi, Fuel
2010, 89, 2697–2702.
[14] J. Ohyama, R. Kanao, A. Esaki, A. Satsuma, Chem. Commun. 2014, 50,
5633–5636.
[15] a) X. Hu, R. J. M. Westerhof, L. Wu, D. Dong, C.-Z. Li, Green Chem. 2015,
17, 219–224; b) F. Liu, M. Audemar, K. D. O. Vigier, J.-M. Clacens, F. D.
Campo, F. Jerome, ChemSusChem 2014, 7, 2089–2095.
[16] Z. Xu, P. Yan, W. Xu, X. Liu, Z. Xia, B. Chung, S. Jia, Z. C. Zhang, ACS
Catal. 2015, 5, 788–792.
[17] K. Gupta, D. Tyagi, A. D. Dwivedi, S. M. Mobin, S. K. Singh, Green Chem.
2015, 17, 4618–4627.
[18] a) P. Kumar, R. K. Gupta, D. S. Pandey, Chem. Soc. Rev. 2014, 43, 707–
733; b) M. C. Warner, C. P. Casey, J.-E. Bäckvall, Top. Organomet. Chem.
2011, 37, 85–125; c) B. L. Conley, M. K. Pennington-Boggio, E. Boz, T. J.
Williams, Chem. Rev. 2010, 110, 2294–2312; d) R. Karvembu, R. Prabha-
karan, K. Natarajan, Coord. Chem. Rev. 2005, 249, 911 –918.
[19] L. H. Gong, Y.-Y. Cai, X.-H. Li, Y.-N. Zhang, J. Su, J.-S. Chen, Green Chem.
2014, 16, 3746–3751.
[20] a) F.-F. Wang, A.-W. Shi, X.-X. Qin, C.-L. Liu, W.-S. Dong, Carbohydr. Res.
2011, 346, 982–985; b) X. Hu, R. J. M. Westerhof, D. Dong, L. Wu, C.-Z.
Li, ACS Sus. Chem. Eng. 2014, 2, 2562–2575.
[21] a) T. Pasini, G. Solinas, V. Zanotti, S. Albonetti, F. Cavani, A. Vaccari, A.
Mazzanti, S. Ranieri, R. Mazzoni, Dalton Trans. 2014, 43, 10224–10234;
b) L. Busetto, D. Fabbri, R. Mazzoni, M. Salmi, C. Torri, V. Zanotti, Fuel
2011, 90, 1197–1207.
[22] R. E. Morris, R. E. Aird, P. d. S. Murdoch, H. M. Chen, J. Cummings, N. D.
Hughes, S. Parsons, A. Parkin, G. Boyd, D. I. Jodrell, P. J. Sadler, J. Med.
Chem. 2001, 44, 3616–3621.
[23] a) D. Tyagi, R. K. Rai, A. D. Dwivedi, S. M. Mobin, S. K. Singh, Inorg. Chem.
Front. 2015, 2, 116–124; b) S. K. Singh, M. Trivedi, M. Chandra, A. N.
Sahay, D. S. Pandey, Inorg. Chem. 2004, 43, 8600–8608.
[24] A. Fujii, S. Hashiguchi, N. Uematsu, T. Ikariya, R. Noyori, J. Am. Chem.
Soc. 1996, 118, 2521–2522.
[9] D. G. Alberg, T. B. Poulsen, S. Bertelsen, K. L. Christensen, R. D. Birkler, M.
Johannsen, K. A. Jørgensen, Bioorg. Med. Chem. Lett. 2009, 19, 3888–
3891.
[25] B. Girisuta, L. P. B. M. Janssen, H. J. Heeres, Green Chem. 2006, 8, 701–
709.
[26] X. Hu, Y. Song, L. Wu, M. Gholizadeh, C.-Z. Li, ACS Sus. Chem. Eng. 2013,
1, 1593–1599.
[10] J. Zhang, S. B. Wu, B. Li, H. D. Zhang, ChemCatChem 2012, 4, 1230–
1237.
[27] Y. Nakagawa, K. Takada, M. Tamura, K. Tomishige, ACS Catal. 2014, 4,
2718–2726.
[28] J. Tuteja, H. Choudhary, S. Nishimura, K. Ebitani, ChemSusChem 2014, 7,
96–100.
[29] X. Kong, R. Zheng, Y. Zhu, G. Ding, Y. Zhu, Y.-W. Li, Green Chem. 2015,
17, 2504–2514.
[30] Y. Y. Gorbanev, S. Kegnæs, A. Riisager, Top. Catal. 2011, 54, 1318–1324.
[31] a) M. A. Bennett, T. Huang, T. W. Matheson, A. K. Smith, Inorg. Synth.
1982, 21, 74–78; b) R. A. Zelonka, M. C. Baird, Can. J. Chem. 1972, 50,
3063–3072.
[11] J. J. Bozell, G. R. Petersen, Green Chem. 2010, 12, 539–554.
[12] a) J. Song, L. Wu, B. Zhou, H. Zhou, H. Fan, Y. Yang, Q. Meng, B. Han,
Green Chem. 2015, 17, 1626–1632; b) A. Phanopoulos, A. J. P. White,
N. J. Long, P. W. Miller, ACS Catal. 2015, 5, 2500–2512; c) X. Tang, X.
Zeng, Z. Li, W. Li, Y. Jiang, L. Hu, S. Liu, Y. Sun, L. Lin, ChemCatChem
2015, 7, 1372–1379; d) J. Tan, J. Cui, T. Deng, X. Cui, G. Ding, Y. Zhu, Y.
Li, ChemCatChem 2015, 7, 508–512; e) X. Tang, Z. Li, X. Zeng, Y. Jiang,
S. Liu, T. Lei, Y. Sun, L. Lin, ChemSusChem 2015, 8, 1601–1607; f) I. Podo-
lean, V. Kuncser, N. Gheorghe, D. Macovei, V. I. Parvulescu, S. M. Coman,
Green Chem. 2013, 15, 3077–3082; g) W. R. H. Wright, R. Palkovits,
ChemSusChem 2012, 5, 1657–1667; h) G. Berkovitch, D. Doron, A. Nu-
delman, Z. Malik, A. Rephaeli, J. Med. Chem. 2008, 51, 7356–7369; i) R.
Vallinayagam, F. Schmitt, J. Barge, G. Wagnieres, V. Wenger, R. Neier, L.
Juillerat-Jeanneret, Bioconjugate Chem. 2008, 19, 821–839.
Received: September 13, 2015
Revised: October 9, 2015
Published online on November 23, 2015
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