Noble metal-free upgrading of multi-unsaturated biomass derivatives at room temperature: Silyl species enable reactivity

Article abstract of DOI:10.1039/c8gc02934b

Biomass derivatives are a class of oxygen-rich organic compounds, which can be selectively upgraded to various value-added molecules by partial or complete hydrogenation over metal catalysts. Here, we show that Cs₂CO₃, a low-cost commercial chemical, enables the selective reduction of dicarbonyl compounds including bio-derived carboxides to monohydric esters/amides, hydroxylamines or diols with high yields (82-99%) at room temperature using eco-friendly and equivalent hydrosilane as a hydride donor. The in situ formation of silyl ether enables the developed catalytic system to tolerate other unsaturated groups and permits a wide substrate scope with high selectivities. Spectroscopic and computational studies elucidate reaction pathways with an emphasis on the role of endogenous siloxane.

Full text of DOI:10.1039/c8gc02934b

Green Chemistry
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PAPER
Noble metal-free upgrading of multi-unsaturated
biomass derivatives at room temperature: silyl
species enable reactivity†
Cite this: Green Chem., 2018, 20,
5327
Hu Li, a Wenfeng Zhao,a Wenshuai Dai,b Jingxuan Long,a Masaru Watanabe,c
Sebastian Meier, *d Shunmugavel Saravanamurugan, *e Song Yang*a and
d
Anders Riisager
Biomass derivatives are a class of oxygen-rich organic compounds, which can be selectively upgraded to
various value-added molecules by partial or complete hydrogenation over metal catalysts. Here, we show
that Cs2CO3, a low-cost commercial chemical, enables the selective reduction of dicarbonyl compounds
including bio-derived carboxides to monohydric esters/amides, hydroxylamines or diols with high yields
(82–99%) at room temperature using eco-friendly and equivalent hydrosilane as a hydride donor. The
in situ formation of silyl ether enables the developed catalytic system to tolerate other unsaturated groups
and permits a wide substrate scope with high selectivities. Spectroscopic and computational studies eluci-
date reaction pathways with an emphasis on the role of endogenous siloxane.
Received 16th September 2018,
Accepted 26th October 2018
DOI: 10.1039/c8gc02934b
rsc.li/greenchem
on the other hand may lead to accelerated catalyst
deactivation.3
Introduction
Catalytic hydrogenation of unsaturated carbon-containing
Currently, much attention is being paid to the selective
bonds (CvC, CvN, and CvO) in organic compounds with hydrogenation of unsaturated functionalities. For example,
metal complexes or particles is a prolific approach that is partial or complete reduction of oxygenates to alcohols or
extensively applied in the petroleum, pharmaceutical, fine alkanes,4 regioselective reduction of polyols or polyenes,5 and
chemical, perfume and flavoring industries.1 Noble (e.g., Au, selective hydrogenation of α,β-unsaturated carbonyl com-
Pt, Ru, and Rh) and transition (e.g., Fe, Co, Ni, and Cu) metals pounds6 can be achieved using well-designed metal catalysts.
prevail in both heterogeneous and homogeneous catalytic Given the significance of selectivity in reduction reactions, it
hydrogenation processes as catalysts with favourable activity would be especially attractive to control the hydrogenation
and selectivity.2 The co-use of unique organic/inorganic capability toward multi-unsaturated functional groups with
ligands, suitable acidic species, or additional metallic addi- similar redox potentials. As the most abundant organic carbon
tives with relatively harsh reaction conditions is a prerequisite source derived from photosynthesis, lignocellulosic biomass
to ensure good reactivity in the hydrogenation process, which has been explored as promising renewable feedstock for pro-
ducing a wide range of platform molecules that can compete
with petroleum-based products.7 One of the bottlenecks for
the efficient upgrading of biomass is the selective hydrogen-
ation of oxygenated species that are rich in downstream deriva-
aState Key Laboratory Breeding Base of Green Pesticide & Agricultural
Bioengineering, Key Laboratory of Green Pesticide & Agricultural Bioengineering,
tives such as sugar, organic acids, and aromatic and furanic
carbonyl compounds,8 especially those concurrently contain-
ing two or more different types of carbonyl groups. Levulinic
acid (LA) and its esters are a class of biomass-derived dicarbo-
nyl compounds,9 which can be selectively hydrogenated to
value-added products, especially γ-valerolactone (GVL) and 1,4-
pentanediol (1,4-PD) over metal catalysts.10 Significant pro-
gress has been achieved with metal-mediated biomass valori-
sation processes in the presence of excessive hydrogen donors
along with high pressure and reaction temperature
(Table S1†), while the development of more benign and cost-
effective catalytic systems would be desirable.
Ministry of Education, State-Local Joint Engineering Lab for Comprehensive
Utilization of Biomass, Center for R&D of Fine Chemicals, Guizhou University,
Guiyang, Guizhou 550025, China. E-mail: jhzx.msm@gmail.com
bBeijing National Laboratory of Molecular Science, State Key Laboratory of Molecular
Reaction Dynamics, Institute of Chemistry, Chinese Academy of Sciences;
University of Chinese Academy of Sciences, Beijing 100049, China
cResearch Center of Supercritical Fluid Technology, Graduate School of Engineering,
Tohoku University, 6-6-11, Aoba, Aramaki, Aoba-ku, Sendai 980-8579, Japan
dDepartment of Chemistry, Technical University of Denmark, DK-2800 Kgs. Lyngby,
Denmark. E-mail: semei@kemi.dtu.dk
eLaboratory of Bioproduct Chemistry, Center of Innovative and Applied Bioprocessing
(CIAB), Mohali 140 306, Punjab, India. E-mail: saravana@ciab.res.in
†Electronic supplementary information (ESI) available. See DOI: 10.1039/
c8gc02934b
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Results and discussion
Controllable hydrogenation of bio-based ethyl levulinate
Initial screening studies were conducted to investigate the
selective hydrogenation of ethyl levulinate (EL) to GVL or 1,4-
PD over Cs2CO3 using triethoxysilane (EtO)3SiH as a reducing
agent in the biomass-derived solvent 2-methyltetrahydrofuran
(MTHF), and the results are shown in Table 1. At room tem-
perature (25 °C) in the presence of Cs2CO3 and 1.5 equiv. H−,
74% yield of GVL could be achieved from EL in 0.5 h, while
the silyl ether Si-1 (21%) was found to be the dominant bypro-
duct (Table S2,† entry 1). After treatment with ethanol under
Fig. 1 Selective hydrogenation of dicarbonyl compounds to hydroxy-
ester/amide or diol/hydramine catalysed by alkali carbonates (M2CO3).
In most cases, precious or transition metal species coupled stirring at 25 °C for 2 h, the GVL yield increased to 87% by
with suitable additives have been reported to be efficient cata- partial consumption of Si-1 (10% yield; Table S2,† entry 2).
lysts for the hydrogenation reactions.11 Due to significantly Upon further increase of the post-treatment temperature to
enhanced sustainability, alkali carbonates, which are low-cost, 80 °C, a high GVL yield of 98% was obtained with a TOF value
pollution-free and obtainable from CO2,12 seem to be better of 39.2 h−1 (Table 1, entry 1), giving tetraethyl orthosilicate
candidates for the hydrogenation reactions. In the present [Si(OEt)4] as the co-product (Fig. S1 and S2†).
study, we present a sustainable carbonate-based catalytic
In addition to Cs2CO3, other alkali carbonates including
process (Fig. 1) that is able to selectively hydrogenate dicarbo- K2CO3, Na2CO3, and Li2CO3 were examined and were proved to
nyl compounds and tolerate other unsaturated moieties by be almost inactive for the hydrogenation of EL with no more
using environmentally benign, cheap, and air-stable hydro- than 2% conversion (Table S2,† entries 3–5). This finding
silanes13 as a hydride source. The silyl ether species formed seems to imply a positive role of cesium in the hydrogenation
in situ in the hydrogenation process enable the control of process. However, the inactivity of CsCl, CsNO3 and CsOOCH
selectivity in the reduction of multi-unsaturated carbonyl com- (Table S2,† entries 6–8) is contradictory to the speculation,
pounds that bear aldehyde/ketone, ester/amide, and aromatic/ which on the other hand indicates the activation effect of the
furanic groups.
carbonate. The co-addition of 18-crown-6 (10 mol%) signifi-
Table 1 Selective hydrogenation of ethyl levulinate (EL) to γ-valerolactone (GVL) and 1,4-pentanediol (1,4-PD) via silyl ethers (Si-1 and Si-2)
Hydrogen-donor
Product yield (%)
Entry Catalyst
Type
H− dosage Temp. (°C) Time (h) EL conv. (%) Si-1 GVL Si-2 1,4-PD CBa (%) TOFb (h−1
)
1
2
3
4
5
6
7
8
Cs2CO3
CsOH
Cs2CO3
CsOH
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Pt/V2O5
Pt-Mo/HAP 3 MPa H2
Pt-Mo/SiO2 5 MPa H2
(EtO)3SiH 1.5 equiv.
(EtO)3SiH 1.5 equiv.
(EtO)3SiH 3.5 equiv.
(EtO)3SiH 3.5 equiv.
(EtO)3SiH 3.5 equiv.
25
25
25
25
25
25
25
60
130
130
130
160
25
0.5
0.5
0.5
0.5
2
0.5
6
2.5
6
24
24
10
0.5
2
>99
100
100
100
100
99
100
100
>99
>99
>99
100
95
<1
0
0
0
0
<1
0
0
—
—
—
—
0
98
82
92
51
77
72
2
<1
99
<1
0
<1
2
3
<1
1
1
0
13
4
99
97
99
89
98
>99
97
87
100
94
39.2
32.8
36.8
20.4
7.7
28.8
3.2
6.9
16.5
1.9
1.0
0.1
37.2
9.0
38
20
25
95
87
1
93
48
82.9
0
PhSiH3
PhSiH3
PhSiH3
5 MPa H2
3.5 equiv.
3.5 equiv.
3.5 equiv.
—
—
—
—
<1
0
9c
10c
11d
12e
13f
14g
—
—
—
—
<1
<1
93
99.9
98
CuAlZn
Cs2CO3
Cs2CO3
4 MPa H2
17
93
90
(EtO)3SiH 1.5 equiv.
PMHS 1.5 equiv.
25
96
<1
2
97
Reaction conditions: 1 mmol EL, 1.5 or 3.5 equiv. H−, 5 mol% catalyst, 2 mL MTHF; after the reaction, 2 mL ethanol was added into the reaction
mixture and stirred at 80 °C for 2 h. a CB: Carbon balance. b TOF (turnover frequency) is defined as (moles of the primary product)/(moles of
active species × time). c Ref. 14a. d Ref. 14b. e Ref. 14b. f LA instead of EL was used as the substrate. g Polymethylhydrosiloxane (PMHS) was used as
a reducing agent.
5328 | Green Chem., 2018, 20, 5327–5335
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cantly enhanced the performance of K2CO3 in the reaction reduced to ca. 87% (Table 1, entry 8), due to the formation of
(Table S2,† entry 9) by increasing its solubility, clearly proving some unidentified products. These results demonstrate that
the dominant role of the carbonate in the catalytic process. room temperature (25 °C) was preferable to warrant high
Although CsOH showed comparable activity to Cs2CO3 in carbon balance through the reaction process, while the dosage
terms of EL conversion, the selectivity toward GVL significantly and type of hydrosilane as well as the reaction time were key
dropped to 82% with 1,4-PD as the primary byproduct (13% factors determining the selectivity and product distribution.
yield; Table 1, entry 2). This result further indicates that the
For comparison, some previously reported results using
appropriate nucleophilicity of the dissociative carbonate is metal-based catalysts for the production of GVL and 1,4-PD are
crucial for the pronounced reactivity in the selective hydrogen- listed in Table 1, entries 9–12.14 The Pt/V2O5 catalyst could
ation of the dicarbonyl compound. In line with this finding, the afford a yield of GVL (99%) comparable to our catalytic system
type of solvent was illustrated to significantly influence the reac- (entry 9 vs. entry 1), but harsher reaction conditions (130 °C,
tivity (Fig. S3†), where MTHF is capable of dispersing Cs2CO3 6 h, and 5 MPa H2) were required and the reaction rate was
and (EtO)3SiH to enable their contact with the substrate EL. In much lower (TOF: 16.5 h−1 with Pt/V2O5 vs. 39.2 h−1 with
contrast, more polar solvents (DMSO and acetonitrile) were not Cs2CO3 at 25 °C). Even higher reaction temperature (160 °C),
able to completely convert EL (Fig. S3†), while a less polar longer reaction time (10–24 h), or higher H2 pressure (3–5
solvent (n-hexane) promoted the over-hydrogenation of GVL to MPa) was required over metallic catalysts to produce 1,2-PD
afford the corresponding acetal and 1,4-PD (Fig. S4 and S5†). In with yields of 48–93% and TOF values of 0.1–1.9 h−1 (entries
the case of using tetrahydrofuran (THF) as the solvent with a 10–12). It is also worth noting that the metal catalysts with
structure quite similar to that of MTHF, GVL was found to be serious leaching and toxicity issues are prone to cause the for-
the predominant product after post-treatment at variable temp- mation of a cyclic ether or mono-alcohol. For example, MTHF
eratures (Fig. S6†), while GVL-derived acetals (2-ethoxy-5-methyl- (19%), 2-pentanol (20%), and 1-pentanol (6%) were found to
tetrahydrofuran and triethyl (5-methyltetrahydrofuran-2-yl) sili- be the major byproducts using Pt-Mo/SiO2 (39), thus greatly
cate) without 1,4-PD and MTHF were detected by GC-MS annihilating the selectivity toward 1,4-PD (48%; entry 11). In
(Fig. S7†).
contrast, our catalytic system was able to selectively produce
Both the type and dosage of hydrosilanes were found to 1,4-PD in a higher yield of 95% with a TOF value of 3.2 h−1
directly affect both EL conversion and selectivity towards GVL (entry 7) by simply increasing the hydrosilane dosage from 1.5
or 1,4-PD. Among the tested hydrosilanes, (EtO)3SiH exhibited to 3.5 equiv. of H−. This finding manifests the advantages of
the highest activity in the synthesis of GVL from EL, while the the Cs2CO3-promoted hydrosilylation process in the selective
other hydrosilanes were either too active (with ca. 9% yield of hydrogenation of EL, a dicarbonyl compound, into GVL or 1,4-
1,4-PD obtained in the presence of PhSiH3) or inert (e.g., PD at room temperature.
Et3SiH and Ph2SiH2) for the reaction (Table S3†). 1.5 equiv. H−
Interestingly, when LA instead of EL was used as a sub-
of (EtO)3SiH were most favorable for the formation of GVL strate, a good GVL yield of 93% (Table 1, entry 13) was also
(Fig. S8†), while the use of a larger excess of hydrosilane obtained under the optimal reaction conditions, indicating
(2.5–5.5 equiv. H−) resulted in the reduction of the ester group that the developed catalytic system can be potentially used for
in either EL or GVL (Fig. S1†), giving 1,4-PD as the major co- the reduction of biomass-derived organic acids. As one of the
product in up to ca. 10% yield. Owing to its relatively low promising silanes used for hydrogenation, polymethyl-
nucleophilicity, Cs2CO3 showed inferior activity relative to hydrosiloxane (PMHS) is a polymeric byproduct of the silicone
CsOH in the formation of 1,4-PD (yield: 4% vs. 38%; Table 1, industry, which is non-toxic, inexpensive, safe, and water/air
entries 3 and 4). However, a low carbon balance was observed insensitive.15 Although a low GVL yield (25%) was obtained
in the latter case (89%), which could be ascribed to the pres- using PMHS after a short reaction time of 0.5 h (Table S3†),
ence of strongly basic OH− causing undesired side reactions the yield could be improved to ca. 90% over our developed
like condensation or the formation of stable intermediates catalytic system by prolonging the reaction time to 2 h
such as 2-ethoxy-5-methyltetrahydrofuran (Fig. S9†). It should (Table 1, entry 14). In order to examine the feasibility of the
be noted that an increased 1,4-PD yield of 71% with 21% GVL developed catalytic system in practical production, the reaction
could be obtained with Cs2CO3 and 3.5 equiv. H− of (EtO)3SiH was scaled up from 2 to 50 mL, and the amount of EL was
by prolonging the reaction time to 6 h (Fig. S10†). When the accordingly increased from 144 mg to 3.6 g. Although the sub-
more active phenylsilane (PhSiH3) was used as a reducing strate was scaled up from milligram to gram by 25-fold, GVL
agent in the presence of Cs2CO3, a 25% yield of 1,4-PD was and 1,4-PD could be obtained in good yields of 90 and 82%
obtained after 0.5 h, which is comparable to the yield (20%) with 5 mol% Cs2CO3 at 25 °C using 1.5 equiv. H− of (EtO)3SiH
achieved with (EtO)3SiH after 2 h under otherwise identical and 3.5 equiv. H− of PhSiH3 after 1 h and 8 h, respectively.
conditions (Table 1, entries 5 and 6). With an extension of the These results demonstrate the great potential of the Cs2CO3–
reaction time to 6 h, an unprecedented high yield of 1,4-PD hydrosilane catalytic system for industrial applications.
(95%) was attained using Cs2CO3 and PhSiH3 (Table 1,
NMR study of reaction pathways
entry 7). Although a slight increase of the reaction temperature
to 60 °C enhanced the reaction rate from 3.2 to 6.9 h−1, the To elucidate the reaction pathways, in situ NMR studies were
1,4-PD yield together with the carbon balance was markedly conducted to monitor the product distribution during the
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reduction process of EL to GVL in the presence of Cs2CO3 with
(EtO)3SiH. The in situ 13C NMR spectra of the EL hydrogen-
ation (Fig. 2A) display that silyl ether (Si-1) and ethyl 4-hydroxy-
pentanoate (EHP) are possibly key intermediates to the final
product GVL. EL was almost completely converted in 0.5 h
even without magnetic stirring, where Si-1 was observed as the
first intermediate, followed by gradual degradation to EHP
(Fig. S11†). On the other hand, the absence of signals in the
olefinic region in the in situ 13C NMR spectra of the reaction
mixture (Fig. 2B) validates the initial occurrence of the hydro-
genation step, rather than a possible initial cyclization of EL to
form α-angelica lactone (Fig. 3). After the reaction for different
intervals (3–60 min), the characteristic regions belonging to
EHP and GVL in ex situ NMR spectra of the reaction mixture
quenched by methanol were recorded (Fig. S12†). Clearly,
better selectivity toward GVL was observed after methanol
treatment, as compared with the in situ obtained results
(Fig. 2A) in the NMR tube. This finding verifies the importance
of the post-treatment process (e.g., with ethanol) at the specific
Fig. 4 In situ NMR spectra of the reaction mixture for ethyl levulinate
(EL) conversion. (A) In situ 1H–13C/29Si HMBC spectra of the intermedi-
ates [ethyl 4-hydroxypentanoate (EHP) and silyl ether (Si-1)], and (B)
in situ time-series of 13C NMR spectra for the hydrogenation of ethyl
levulinate (EL) to the intermediates [silyl ether (Si-1) and ethyl 4-hydro-
xypentanoate (EHP)]; tetraethyl orthosilicate is indicated by the asterisk
in the 1H–29Si HMBC spectrum (top).
temperature (ca. 80 °C) to accomplish the following cyclization
step, thus exclusively yielding GVL.
The simultaneous presence of the intermediates EHP and
Si-1 in the reaction mixture can also be distinguished by the
1H–13C HMBC spectra of the reaction mixture (Fig. 4A). The Si
1
attachment in Si-1 can be affirmed by H–29Si HMBC (Fig. 4A).
To some extent, the stable intermediates are not favorable for
directly producing GVL from EL, due to the requirement of
secondary post-treatment. Fortunately, the reaction rate is sig-
nificantly enhanced after a specific period (ca. 15–30 min) of
the steady reaction process, as shown in Fig. 4B. The formation
of the intermediates and the siloxane Si(OEt)4 most likely pro-
motes the dissolution of the catalytically active species
Fig. 2 In situ 13C NMR spectra for the hydrogenation of ethyl levulinate
(EL). (A) Formation of γ-valerolactone (GVL) via the silyl ether (Si-1) and
ethyl 4-hydroxypentanoate (EHP); (B) olefinic region in 13C NMR spectra
of the reaction mixture. Reaction conditions: 1 mmol EL, 1.5 equiv. H− of (carbonate), thus leading to a rapid or runaway reaction.
(EtO)3SiH, 5 mol% Cs2CO3, 2 mL MTHF, 25 °C.
Furthermore, the incorporation of the hydride from the hydro-
silane into the substrate EL can be illustrated by a comparison
of the obtained 1H NMR spectra (Fig. S13†) using normal
Ph2SiH2 and deuterium-labeled Ph2SiD2 as reducing agents. A
kinetic isotope effect (KIE) study disclosed a significant differ-
ence in the kH/kD value (ca. 2.4) when the hydride was supplied
either by Ph2SiH2 or Ph2SiD2, further supporting the fact that
the relative activity of the employed hydrosilane plays a key
role in the selective hydrogenation. On the other hand, 1H–13C
HSQC NMR spectra of the reaction mixture after post-
treatment with methanol-d4 at 60 °C for 2 h demonstrated the
Fig. 3 Reaction pathway for EL-to-GVL conversion.
5330 | Green Chem., 2018, 20, 5327–5335
complete conversion of the intermediates into GVL (Fig. S14†),
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which is in agreement with the corresponding 13C NMR
spectra (Fig. S15 and S16†).
Table 2 Selective reduction of carbonyl compounds bearing multi-
unsaturated groups to alcohols via silyl ethers
Upgrading of the carbonate
Although the used catalyst Cs2CO3 is cheap, widely available
and eco-friendly, attempts were made to investigate its recover-
ability for potential recycling or further upgrading. Initially,
the effect of Cs2CO3 dosage on the conversion of EL to GVL
was studied, where no more than 80% yield of GVL was
obtained using less than 5 mol% Cs2CO3 (Fig. S17†). This rela-
tively low yield shows the importance of using sufficient
Cs2CO3 (5 mol%) for good catalytic performance. However, the
amount of Cs2CO3 (separated out by centrifugation) was
decreased by around 68% after the first cycle of the reaction.
Notably, the recovered solids were characterized by STEM
(Fig. S18†) to be Cs2CO3 with additional silicon compounds,
thus underlining the difficulty in completely recycling the cata-
lyst. TEM images of both fresh and recovered Cs2CO3 pre-dis-
persed into THF indicated the formation of nano-sized par-
ticles (Fig. S19†), which is in agreement with the superior cata-
lytic results of the alkali carbonate salts which are more
soluble (Table S2,† entries 1–5). Instead, the addition of
ethanol (2 mL) into the liquid mixture after the reaction led to
Hydride
Time
(h)
Alcohol
yield (%)
Entry
1
Substrate
(H− equiv.)
2.5
1
92
2
3
2.5
2.5
1
1
87
95
4
5
6
2.5
2.5
2.5
1.5
6
97
96
12
>99
7
8
9
10
11
1.5
3.5
1.5
3.5
1.5
3.5
0.5
24
1
24
1
98
96
94
91
85
88
full conversion of the residual carbonate in both solid and 12
24
leached states into the formate (>95% yields) in 2 h (Fig. S20†),
which was confirmed by H NMR through the detection of a
singlet with a chemical shift of about 8.6 ppm belonging to
1HCOO– (Fig. S21†). Therefore, it would be more preferable to
co-synthesize the expected products together with the value-
added formate by post-treatment with ethanol.
1
Reaction conditions: 1 mmol substrate, 1.5–3.5 equiv. H− of PhSiH3,
5 mol% Cs2CO3, 2 mL MTHF, 25 °C; after the reaction, 2 mL ethanol
was added to the liquid mixture and stirred at 80 °C for 2 h.
reduced to diols in high yields of 88–96% from these dicarbo-
nyl compounds containing aldehyde/ketone and ester groups
(entries 8, 10 and 12).
Selective hydrogenation of dicarbonyl compounds to hydroxy
esters and diols
Cyclic ether or mono-alcohol is typically formed in the syn-
thesis of diols from dicarbonyl compounds.14b,16 To examine
Selective hydrogenation of multi-unsaturated amides
the versatility of the catalytic system developed in this study, Pyrrolidones are a class of amides extensively applied as sol-
the substrate scope was further expanded to other dicarbonyl vents and feedstocks for fibers or surfactants.17 In the present
compounds (Table 2). Both diketones and dialdehydes could study, starting from levulinic acid (LA) and amines, a variety of
be selectively reduced to diols with yields of 87–95% in 0.5–1 h N-substituted lactams (i.e., pyrrolidones) could be synthesized
(entries 1–3). The exclusive selectivity toward the diols further in good yields of 85–92% at 120 °C using formic acid both as
indicates the intact C–O bond during the processes of an acid and as a hydrogen source in the absence of a catalyst
reduction and post-treatment, which is unambiguously attribu- (Table S4†). The results are comparable to those obtained over
ted to the formation of silyl ether under the mild reaction con- metal catalysts such as Ir and Ni in the production of
ditions. Apart from the aromatic ring, the nitro group was also lactams.17,18 In general, the controllable reduction of lactams
intact during the hydrogenation process (entry 4). This makes is one of the promising ways to produce cyclamines. However,
the catalytic system capable of exclusively producing alcohols the cleavage of C–N bonds often occurs over metal (e.g., Ru,
with good compatibility with other multi-unsaturated func- Mn, and Fe) catalysts during the hydrogenation process, simul-
tional groups. By prolonging the reaction time to 6 h and taneously giving amines and alcohols as products.19 Typically,
increasing the hydrosilane dosage to 2.5 equiv. H− of PhSiH3, the lactam is more inert towards reduction compared with the
methyl benzoate and methyl p-methyl benzoate could be ester analogue,11e while the extension of the reaction time to
hydrogenated to benzyl alcohol (96% yield, entry 5) and 24–36 h could yield 81–99% cyclamine with a selectivity of
p-methylbenzyl alcohol (>99% yield, entry 6), respectively. In 95–100% in the presence of the hydrosilane/Cs2CO3 catalytic
the presence of both aldehyde/ketone and ester, the selective system at room temperature (Table 3). Notably, this catalytic
reduction of the aldehyde or ketone to an alcohol without system is compatible with aliphatic and aromatic
affecting the ester group could be achieved (entries 7, 9 and N-substituents, and it does not interfere with the halogen sub-
11). Importantly, both the presented carboxides could be stituent resulting in the hydrodechlorination reaction.
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Table 3 Selective hydrogenation of N-substituted lactams derived from
levulinic acid
or 94% in 1 or 2 h, respectively (entries 1 and 3), while the
amide remained almost unreacted (<1%). After reacting for 24
or 30 h with 4.5 equiv. H− of PhSiH3, the hydrogenation of the
amide to amine proceeded giving hydramine in ∼90% yield
(entries 2 and 4). This finding indicates that the initial
reduction of aldehydes or ketones to the corresponding silyl
ethers was kinetically favorable and proceeded to completion
relatively rapidly. On the other hand, the hydrogenation of the
amide group was most likely thermodynamically controlled,
where an increase of the reaction temperature from 25 to 60 °C
significantly shortened the reaction time from 24–30 h to
6–8 h with comparable hydramine yields (entries 2 and 4).
Even in the presence of other unsaturated functional groups
(e.g., –NO2 and –CN), the amide compounds were selectively
reduced at room temperature (entries 5 and 6), leaving the
other functional groups intact. This unprecedented selectivity
toward hydrogenates shows great potential in the controllable
reduction of multi-unsaturated carbonyl compounds. Thus,
the reaction system permits the selective reduction of amides
under mild conditions, which is an enduring challenge in
pharmaceutical processes.20 Overall, the chemistries described
herein thus have the potential to impact on the upgrading of
biomass-derived chemicals and on fine chemical production.
Cyclamine (%)
Entry
1
Lactam
Time (h)
24
Yield
92
Selectivity
97
2
36
81
95
3
4
36
36
99
85
100
96
5
24
93
98
Reaction conditions: 1 mmol substrate, 3 equiv. H− of PhSiH3, 5 mol%
Cs2CO3, 2 mL MTHF, 25 °C; after the reaction, 2 mL ethanol was
added to the reaction mixture and stirred at 80 °C for 2 h.
Computational study of representative reaction pathways
Regarding the selective synthesis of GVL and 1,4-PD from EL
in the presence of Cs2CO3 and (EtO)3SiH, the in situ formed
silyl ethers Si-1 and Si-2 were verified to be the key intermedi-
ates (vide supra), respectively. In particular, the efficiency in
the consecutive addition of one to three equiv. hydrides to EL
seemed essential for the formation of the silyl ethers
(Fig. S22†). DFT calculations were performed to examine the
free energies of the dominant products involved in the reac-
tion pathways, and the resulting energy profiles are shown in
Fig. S23.† Both Si-1 and Si-2 were found to have lower free
energies (−17.20 and −15.38 kcal mol−1, respectively) than the
starting material EL. These two silyl ethers with moderate
stability can not only remain intact during the reaction process
under mild conditions, but can also be further degraded to
remove the siloxane moiety at an elevated temperature, render-
ing them ideal precursors of GVL and 1,4-PD. It should be
noted that EL acetal derived from Si-1 was calculated to have a
higher free energy (−2.87 kcal mol−1, Fig. S22†), implying that
the dominant barrier toward 1,4-PD from EL was the ester
hydrogenation step. This finding is consistent with the experi-
mental results, where Si-1 (precursor of GVL) can be rapidly
and quantitatively formed in 0.5 h, while approximately 6 h
are required to obtain Si-2 (precursor of 1,4-PD).
Table 4 Selective reduction of amides bearing other unsaturated
groups to cyclic amines
Yield (%)
Hydride
Entry
R1
R2
(equiv.)
Time (h)
P-1
P-2
1
2
3
1.5
4.5
1.5
1
97
<1
94
<1
93(95)a
24(6)a
2
<1
4
4.5
30(8)a
<1
87(92)a
5
6
3
3
24
24
1
2
90
82
Reaction conditions: 1 mmol substrate, 1.5–4.5 equiv. H− of PhSiH3,
5 mol% Cs2CO3, 2 mL MTHF, 25 °C; after the reaction, 2 mL ethanol
was added into the reaction mixture and stirred at 80 °C for 2 h. a Data
in the parentheses were obtained at 60 °C under otherwise identical
conditions.
In addition, we note that a significant difference in product
distribution was observed when lactone and lactam were used
as substrates with PhSiH3 as the hydrogen source for reduction
(Fig. S24†). In the case of a lactone (e.g., GVL), a diol (1,4-PD)
With respect to the amides bearing multi-unsaturated was likely to be obtained, while the complete reduction of
groups, the substrate scope was also investigated at 25 °C for lactam (e.g., 1,5-dimethyl-2-pyrrolidinone (DPO)) gave cycla-
the selective hydrogenation (Table 4). Either the aldehyde or mine (1,2-dimethylpyrrolidine (DPI)) as the predominant
ketone could be hydrogenated to an alcohol with yields of 97 product. DFT calculations demonstrated the significance of
5332 | Green Chem., 2018, 20, 5327–5335
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dicarbonyl compounds into monohydric esters or diols in
85–99% yields using 1.5–3.5 equiv. H−. In particular, the cycli-
zation/lactonization of ethyl 4-hydroxypentanoate (EHP) or its
silyl ether (Si-1) formed in situ from biomass-derived ethyl
levulinate (EL) can take place through a facile post-treatment
process, quantitatively giving the valuable platform molecule
γ-valerolactone (GVL). The process exhibits a TOF value
(39.2 h−1) that is superior to previous results obtained using
metal catalysts. By an appropriate increase of the hydrosilane
dosage and by an extension of the reaction time, 1,4-pentane-
diol (1,4-PD) instead of GVL can become the dominant
product (up to 95% yield), while cyclic ether formation (self-
etherification) or monohydric alcohol formation (over-hydro-
genation) is absent. The in situ formation of silyl ether is most
likely responsible for the pronounced performance and selecti-
vity toward different types of carbonyl species, as demon-
strated by in situ NMR and computational studies. Despite
requiring longer reaction times, a variety of monohydric
amides and hydroxylamines can be synthesized from the
corresponding dicarboxides, while the other concurrent unsa-
turated species remain intact. The high selectivity and benign
reaction conditions make our catalytic system a promising
alternative to precious metal catalysts in the specific reduction
of carbonyl groups. In addition, the concept of in situ generat-
ing a labile silyl ether between the reactant and hydride bears
promise in the switchable reduction or transformation of
specific species from multi-functional groups in both biomass
feedstock and relevant molecules.
Fig. 5 DFT calculation results of silyl ether in situ formed from the
lactone and lactam using PhSiH3 as a H-donor. Energy profiles for the
reduction of (A) γ-valerolactone (GVL) to 2-methyltetrahydrofuran
(MTHF) and (B) 1,5-dimethyl-2-pyrrolidinone (DPO) to 1,2-dimethyl-
pyrrolidine (DPI) via the corresponding silyl ethers. The optimized tran-
sition state (TS1) structures are shown in blue. Computational free
energy values (in kcal mol−1) are displayed.
the type of silyl ether formed in situ (i.e., GVL/DPO acetals)
along with its preceding optimized transition state (TS1) in the
selectivity control (Fig. 5). The TS1 free energy for the initial
reduction of GVL was found to be slightly higher than that for
the initial hydrogenation of DPO (57.52 vs. 55.25 kcal mol−1),
indicating the need for a relatively higher energy barrier to form
a GVL-derived acetal: (5-methyltetrahydrofuran-2-yl)oxy phenyl-
silane. Moreover, the stability of this compound was higher
than that of the corresponding intermediate (DPO-derived
acetal), in view of their free energies (−1.86 vs. +5.96 kcal
mol−1). This finding rationalizes the difficulty in the synthesis
of MTHF from GVL, which is in agreement with the experi-
mental results. In fact, 1,4-PD was detected to be the main
product from the reduction of GVL, showing that the cyclic C–O
bond was more easily broken than the exocyclic bond of the
GVL acetal during the hydrosilylation process, as illustrated in
Fig. S24.† In contrast, the exocyclic C–O bond of the DPO-
derived acetal was susceptible to cleavage, affording the cycla-
mine (DPI) as the principal product. The presence of competing
reaction pathways dependent on the structures of in situ formed
silyl ethers makes the product distribution controllable.
Experimental
Materials
Tetrahydrofuran-d8 (99.5 atom % D), methanol-d4 (99.8 atom
% D), diphenylsilane-d2 (97 atom % D), and Amberlyst-15 (hydro-
gen ion form, wet) were purchased from Shanghai Sigma-Aldrich
Trading Co. Ltd. Cesium carbonate (Cs2CO3, 99%), 2-methyl-
tetrahydrofuran (MTHF, 99%), 18-crown-6 (99%), triethoxysilane
[(EtO)3SiH, 95%], phenylsilane (PhSiH3, 97%), ethyl levulinate
(EL, 99%), γ-valerolactone (GVL, 98%), 1,4-pentanediol (1,4-PD,
99%), naphthalene (99%), and xylene (99%) were purchased
from Beijing InnoChem Science & Technology Co., Ltd.
Reduction of multi-unsaturated carbonyl compounds
All the reduction reactions were carried out in Ace pressure
tubes (10 mL). In a typical procedure, 1 mmol carbonyl com-
pound, 1–5.5 equiv. H− of hydrosilane, 5 mol% Cs2CO3, and
2 mL MTHF were added into the tube. After stirring (500 rpm)
at room temperature (25 °C) for a specific reaction time, 2 mL
ethanol was added into the reaction mixture and stirring con-
tinued at 80 °C for another 2 h. The resulting solution was col-
lected and subjected to product analysis.
Conclusions
Product analysis
In summary, an economic and green catalytic system com-
posed of Cs2CO3, hydrosilane and the bio-based solvent MTHF Dominant products were identified by GC-MS (Agilent 6890N
has been developed for the room-temperature reduction of combined with 5973 MS), whereas the quantification of liquid
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products was performed using a GC system (Agilent 7890B)
fitted with a flame ionization detector (FID) and a HP-5
column (30 m × 0.320 mm × 0.25 μm) using naphthalene as an
internal standard and referring to standard curves. The
content of formate was determined by 1H NMR using xylene as
an internal standard.
C. J. Elsevier and B. de Bruin, Science, 2015, 350, 298–302;
(e) K. Yuan, T. Song, D. Wang, X. Zhang, X. Gao, Y. Zou,
H. Dong, Z. Tang and W. Hu, Angew. Chem., Int. Ed., 2018,
57, 5708–5713; (f) R. C. Cammarota and C. C. Lu, J. Am.
Chem. Soc., 2015, 137, 12486–12489; (g) L. Wang, E. Guan,
J. Zhang, J. Yang, Y. Zhu, Y. Han, M. Yang, C. Cen, G. Fu,
B. C. Gates and F. S. Xiao, Nat. Commun., 2018, 9, 1362.
4 (a) C. Pilar Jiménez-Gómez, J. A. Cecilia, D. Durán-Martín,
R. Moreno-Tost, J. Santamaría-González, J. Mérida-Robles,
R. Mariscal and P. Maireles-Torres, J. Catal., 2016, 336,
107–115; (b) G. W. Huber, J. N. Chheda, C. J. Barrett and
J. A. Dumesic, Science, 2005, 308, 1446–1450; (c) C. Zhao,
Y. Kou, A. A. Lemonidou, X. Li and J. A. Lercher, Angew.
Chem., Int. Ed., 2009, 48, 3987–3990.
NMR spectroscopic study
1
1H, 13C and 2D H–13C HSQC NMR spectra of the liquid mix-
tures were obtained with normal hydrosilanes in deuterated
solvents (typically, MTHF-d10) or in protonated solvents con-
taining 5% DMSO-d6 as a lock substance on a Bruker Avance
III 800 MHz spectrometer equipped with a TCI cryoprobe. The
ex situ samples of reaction progress were obtained by quench-
ing reactions with methanol-d4 at indicated times. For the
isotope-labeling study, 1H, 13C, DEPT-135 and 1H–13C HSQC
NMR spectra of the reaction mixtures, which were obtained
using deuterium reagents (diphenylsilane-d2 and THF-d8 with
5 (a) Q. Meng, M. Hou, H. Liu, J. Song and B. Han, Nat.
Commun., 2017, 8, 14190; (b) M. Tamura, N. Yuasa, J. Cao,
Y. Nakagawa and K. Tomishige, Angew. Chem., Int. Ed.,
2018, 57, 8058–8062.
or without CD3OD post-treatment), were recorded on
JEOL-ECX 500 NMR spectrometer.
a
6 (a) W. Liu, Y. Jiang, K. H. Dostert, C. P. O’Brien, W. Riedel,
A. Savara, S. Schauermann and A. Tkatchenko, Sci. Adv.,
2017, 3, e1700939; (b) Y. Zhu, H. Qian, B. A. Drake and
R. Jin, Angew. Chem., Int. Ed., 2010, 49, 1295–1298.
Conflicts of interest
7 (a) C. O. Tuck, E. Pérez1, I. T. Horváth, R. A. Sheldon and
M. Poliakoff, Science, 2012, 337, 695–699; (b) Y. S. Jang,
B. Kim, J. H. Shin, Y. J. Choi, S. Choi, C. W. Song, J. Lee,
H. G. Park and S. Y. Lee, Biotechnol. Bioeng., 2012, 109,
2437–2459; (c) H. Li, A. Riisager, S. Saravanamurugan,
A. Pandey, R. S. Sangwan, S. Yang and R. Luque, ACS Catal.,
2018, 8, 148–187; (d) H. Li and R. L. Smith, Nat. Catal.,
2018, 1, 176–177.
8 (a) Y. Román-Leshkov, C. J. Barrett, Z. Y. Liu and
J. A. Dumesic, Nature, 2007, 447, 982–985; (b) J. N. Chheda,
G. W. Huber and J. A. Dumesic, Angew. Chem., Int. Ed.,
2007, 46, 7164–7183; (c) D. M. Alonso, S. G. Wettstein and
J. A. Dumesic, Green Chem., 2013, 15, 584–595.
There are no conflicts to declare.
Acknowledgements
This work is financially supported by the National Natural
Science Foundation of China (21576059 and 21666008), Fok
Ying-Tong Education Foundation (161030), Guizhou Science &
Technology Foundation ([2018]1037 and [2017]5788), and Key
Technologies R&D Program of China (2014BAD23B01). We
acknowledge the NMR center DTU (Denmark) for recording
NMR spectra, and Institute of Chemistry (CAS) for DFT
calculations. S. S. thanks the Department of Biotechnology
(Government of India) New Delhi, India for support.
9 (a) W. Deng, Y. Wang and N. Yan, Curr. Opin. Green Sustain.
Chem., 2016, 2, 54–58; (b) H. Li, Z. Fang, J. Luo and
S. Yang, Appl. Catal., B, 2017, 200, 182–191.
10 (a) Z. Zhang, ChemSusChem, 2016, 9, 156–171;
(b) B. Banerjee, R. Singuru, S. K. Kundu, K. Dhanalaxmi,
L. Bai, Y. Zhao, B. M. Reddy, A. Bhaumik and J. Mondal,
Catal. Sci. Technol., 2016, 6, 5102–5115; (c) S. Pendem,
I. Mondal, A. Shrotri, B. S. Rao, N. Lingaiah and J. Mondal,
Notes and references
1 (a) D. Wang and D. Astruc, Chem. Rev., 2015, 115, 6621–
6686; (b) J. H. Xie, S. F. Zhu and Q. L. Zhou, Chem. Rev.,
2011, 111, 1713–1760; (c) J. Pritchard, G. A. Filonenko,
R. van Putten, E. J. M. Hensen and E. A. Pidko, Chem. Soc.
Rev., 2015, 44, 3808–3833.
2 (a) R. M. Bullock, Science, 2013, 342, 1054–1055;
(b) A. Corma and P. Serna, Science, 2006, 313, 332–334;
(c) P. Ryabchuk, G. Agostini, M. M. Pohl, H. Lund,
A. Agapova, H. Junge, K. Junge and M. Beller, Sci. Adv.,
2018, 4, eaat0761.
Sustainable
Energy
Fuels,
2018,
2,
1516–1529;
(d) K. Dhanalaxmi, R. Singuru, S. Mondal, L. Bai,
B. M. Reddy, A. Bhaumik and J. Mondal, ACS Sustainable
Chem. Eng., 2017, 5, 1033–1045; (e) D. Ren, X. Wan, F. Jin,
Z. Song, Y. Liu and Z. Huo, Green Chem., 2016, 18, 5999–
6003; (f) T. Mizugaki, Y. Nagatsu, K. Togo, Z. Maeno,
T. Mitsudome, K. Jitsukawa and K. Kaneda, Green Chem.,
2015, 17, 5136–5139; (g) J. Cui, J. Tan, Y. Zhu and F. Cheng,
ChemSusChem, 2018, 11, 1316–1320; (h) S. C. Patankar and
G. D. Yadav, ACS Sustainable Chem. Eng., 2015, 3, 2619–2630.
3 (a) K. Manna, T. Zhang, M. Carboni, C. W. Abney and
W. Lin, J. Am. Chem. Soc., 2014, 136, 13182–13185; (b) H. Li,
Z. Fang, R. L. Smith and S. Yang, Prog. Energy Combust. Sci., 11 (a) S. G. Wettstein, D. M. Alonso, Y. Chong and
2016, 55, 98–194; (c) M. Naruto and S. Saito, Nat. Commun.,
2015, 6, 8140; (d) T. J. Korstanje, J. I. van der Vlugt,
J. A. Dumesic, Energy Environ. Sci., 2012, 5, 8199–8203;
(b) W. Luo, M. Sankar, A. M. Beale, Q. He, C. J. Kiely,
5334 | Green Chem., 2018, 20, 5327–5335
This journal is © The Royal Society of Chemistry 2018

View Article Online
Green Chemistry
Paper
P. C. A. Bruijnincx and B. M. Weckhuysen, Nat. Commun.,
2015, 6, 6540; (c) A. Primo, P. Concepción and A. Corma,
Chem. Commun., 2011, 47, 3613–3615; (d) T. Mizugaki,
Y. Nagatsu, K. Togo, Z. Maeno, T. Mitsudome, K. Jitsukawa
and K. Kaneda, Green Chem., 2015, 17, 5136–5139;
2015, 17, 5136–5139; (b) T. Mizugaki, K. Togo, Z. Maeno,
T. Mitsudome, K. Jitsukawa and K. Kaneda, ACS Sustainable
Chem. Eng., 2016, 4, 682–685; (c) D. Ren, X. Wan, F. Jin,
Z. Song, Y. Liu and Z. Huo, Green Chem., 2016, 18, 5999–
6003.
(e) D. Addis, S. Das, K. Junge and M. Beller, Angew. Chem., 15 (a) K. K. Senapati, Polymethylhydrosiloxane (PMHS),
Int. Ed., 2011, 50, 6004–6011; (f) A. Volkov,
K. P. J. Gustafson, C. W. Tai, O. Verho, J. E. Bäckvall and
H. Adolfsson, Angew. Chem., Int. Ed., 2015, 54, 5122–5126;
Synlett, 2005, 1960–1961; (b) D. B. Nale and B. M. Bhanage,
Green Chem., 2015, 17, 2480–2486; (c) J. A. Caetano and
A. C. Fernandes, Green Chem., 2018, 20, 2494–2498.
(g) H. Li, W. Zhao and Z. Fang, Appl. Catal., B, 2017, 215, 16 M. Chia, Y. J. Pagán-Torres, D. Hibbitts, Q. Tan,
18–27.
H. N. Pham, A. K. Datye, M. Neurock, R. J. Davis and
12 F. Lehmann, Synlett, 2004, 2447–2448.
J. A. Dumesic, J. Am. Chem. Soc., 2011, 133, 12675–12689.
13 (a) X. Y. Li, R. Shang, M. C. Fu and Y. Fu, Green Chem., 17 S. Wang, H. Huang, C. Bruneau and C. Fischmeister,
2015, 17, 2790–2793; (b) W. Zhao, T. Yang, H. Li, W. Wu, ChemSusChem, 2017, 10, 4150–4154.
Z. Wang, C. Fang, S. Saravanamurugan and S. Yang, ACS 18 G. Gao, P. Sun, Y. Li, F. Wang, Z. Zhao, Y. Qin and F. Li,
Sustainable Chem. Eng., 2017, 5, 9640–9644; (c) X. F. Liu, ACS Catal., 2017, 7, 4927–4935.
C. Qiao, X. Y. Li and L. N. He, Green Chem., 2017, 19, 1726– 19 (a) J. R. Cabrero-Antonino, E. Alberico, K. Junge, H. Junge
1731; (d) H. Li, W. Zhao, A. Riisager, S. Saravanamurugan,
Z. Wang, Z. Fang and S. Yang, Green Chem., 2017, 19, 2101–
2106; (e) C. Wu, X. Luo, H. Zhang, X. Liu, G. Ji, Z. Liu and
Z. Liu, Green Chem., 2017, 19, 3525–3529; (f) H. Li,
W. Zhao, S. Saravanamurugan, W. Dai, J. He, S. Meier,
and M. Beller, Chem. Sci., 2016, 7, 3432–3442;
(b) N. M. Rezayee, D. C. Samblanet and M. S. Sanford, ACS
Catal., 2016, 6, 6377–6383; (c) V. Papa, J. R. Cabrero-
Antonino, E. Alberico, A. Spanneberg, K. Junge, H. Junge
and M. Beller, Chem. Sci., 2017, 8, 3576–3585.
S. Yang and A. Riisager, Chem. Commun., 2018, 1, 32; 20 (a) J. M. Woodley, Trends Biotechnol., 2008, 26, 321–327;
(g) C. Xu, B. Huang, T. Yan and M. Cai, Green Chem., 2018,
20, 391–397; (h) R. A. Pramudita and K. Motokura, Green
Chem., 2018, 20, 4834–4843.
(b) N. L. Lampland, M. Hovey, D. Mukherjee and
A. D. Sadow, ACS Catal., 2015, 5, 4219–4226; (c) Y. Q. Zou,
S. Chakraborty, A. Nerush, D. Oren, Y. Diskin-Posner,
Y. Ben-David and D. Milstein, ACS Catal., 2018, 8, 8014–
8019.
14 (a) T. Mizugaki, Y. Nagatsu, K. Togo, Z. Maeno,
T. Mitsudome, K. Jitsukawa and K. Kaneda, Green Chem.,
This journal is © The Royal Society of Chemistry 2018
Green Chem., 2018, 20, 5327–5335 | 5335