Copper encapsulated alkaloids composite: An effective heterogeneous catalyst for electrocatalytic asymmetric hydrogenation

Article abstract of DOI:10.1016/j.elecom.2016.08.004

A novel heterogeneous catalyst, alkaloid@Cu was prepared by the entrapment of commercially purchased alkaloids within non-noble metallic copper nanoparticles. This composite was compacted into a coin and directly used as cathode for electrocatalytic asymmetric hydrogenation of aromatic ketones. Using water as hydrogen source, optically active alcohols with 71% ee value and 93% yield were obtained under very mild conditions.

Full text of DOI:10.1016/j.elecom.2016.08.004

Copper encapsulated alkaloids composite: An effective heterogeneous catalyst
for electrocatalytic asymmetric hydrogenation
Heng-Pan Yang, Qiu Fen, Huan Wang, Jia-Xing Lu
PII:
DOI:
Reference:
S1388-2481(16)30181-3
doi: 10.1016/j.elecom.2016.08.004
ELECOM 5748
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Electrochemistry Communications
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Revised date:
Accepted date:
15 July 2016
3 August 2016
8 August 2016
Please cite this article as: Heng-Pan Yang, Qiu Fen, Huan Wang, Jia-Xing Lu, Cop-
per encapsulated alkaloids composite: An effective heterogeneous catalyst for elec-
trocatalytic asymmetric hydrogenation, Electrochemistry Communications (2016), doi:
10.1016/j.elecom.2016.08.004
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ACCEPTED MANUSCRIPT
Copper encapsulated alkaloids composite: an effective
heterogeneous catalyst for electrocatalytic asymmetric
hydrogenation
Heng-Pan Yang, Qiu Fen, Huan Wang*, Jia-Xing Lu*
Shanghai Key Laboratory of Green Chemistry and Chemical Processes, School of
Chemistry and Molecular Engineering, East China Normal University, Shanghai
200062, China
Abstract: A novel heterogeneous catalyst, alkaloid@Cu was prepared by the
entrapment of commercially purchased alkaloids within non-noble metallic copper
nanoparticles. This composite was compacted into a coin and directly used as cathode
for electrocatalytic asymmetric hydrogenation of aromatic ketones. Using water as
hydrogen source, optically active alcohols with 71% ee value and 93% yield were
obtained under very mild conditions.
Keywords: Copper nanoparticles; Encapsulated alkaloids; Electrocatalytic
hydrogenation; Asymmetric hydrogenation
1. Introduction
The catalytic asymmetric reduction of pro-chiral ketones, especially asymmetric
hydrogenation and asymmetric transfer hydrogenation, has been recognized as one of
the most important methods for the synthesis of chiral alcohols, which are
widely-applied intermediates in the pharmaceutical, natural products, agrochemical,
fragrance, and other fine chemical industries [1-2].
In both academic laboratories and industrial operations, homogeneous catalysts
based on rare and expensive transition metals such as ruthenium, iridium and rhodium
have typically been used in this context [3]. As for heterogeneous catalyst, the
Pt/cinchona alkaloids catalyzed asymmetric hydrogenation of α-ketoester is one of the
few successful examples with both high enantiomeric excess (ee value) and yield
 Corresponding Author: Dr. Huan Wang (Tel: +8621-52134935, E-mail: hwang@chem.ecnu.edu.cn)
** Corresponding Author: Prof. Jia-Xing Lu (Tel: +8621-62233491, E-mail: jxlu@chem.ecnu.edu.cn)
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under favorable reaction conditions [4]. Although remarkable results have been
obtained in some cases, the limited availability, high cost, and toxicity of these
precious metals also brought some unsolved problems.
For this reason, asymmetric catalysts based on abundant, inexpensive, and nontoxic
metals have attracted increasing attention [5]. In our former work, we successfully
introduced metallic Ag and Cu instead of Pt into typical Pt/alkaloid catalyzed
asymmetric hydrogenation of α-ketoesters using electrochemical methods [6-8]. Both
Ag and Cu are far more abundant and cheaper than Pt. In addition, H2O acted as
hydrogen source in this procedure, which might be superior to the widely-used high
pressure H2. To the best of our knowledge, similar reports have never been seen
anywhere. Alkaloids were put into the reaction solution and electroadsorbed onto the
metallic Cu surface for asymmetric induction. The problem is that these modified
electrodes could hardly be reused because of the facile desorption of the alkaloid.
Similar issue also existed in homogeneous and Pt/alkaloid systems. Electrocatalytic
asymmetric hydrogenation was also investigated by other groups, but the ee value
were around 13% [9-11].
In our recent work, we further investigated the application of metallic Cu in
asymmetric hydrogenation. Unlike electrochemical catalysis in our former reports,
alkaloids were not adsorbed onto the surface but entrapped within Cu nanoparticles,
producing an alkaloid@Cu composite. This alkaloid@Cu composite belongs to the
so-called organically doped metals [12, 13], which have been demonstrated to be ideal
cathode material for electrochemical catalysis by our former reports [7, 14, 15]. In our
electrocatalytic asymmetric hydrogenation system, alkaloid@Cu composite directly
acted as chiral inducer without any alkaloids in the reaction solution. Corresponding
optically active products were successfully obtained under very mild conditions.
2. Experimental section
2.1. Apparatus and reagents
All reagents were used as received.
Electrocatalytic hydrogenation were performed with a direct-current-regulated
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power supply (HY3002D, HYelec®, China). The yield and ee value of products were
determined with a high-performance liquid chromatography (HPLC) instrument
(DIONEX Ultimate 3000 pump). The microstructure, morphology and EDX were
analyzed using Hitachi S-4800 field emission Scanning Electron Microscope
(FE-SEM) equipped with an energy dispersive X-ray fluorescence spectrometer (EDX,
Oxford; UK). X-ray diffraction (XRD) patterns were recorded with an Ultima IV
x-ray powder diffractometer. N2 adsorption-desorption was carried out at 77 K on a
BELSORP-MAX instrument.
2.2. General procedure
Synthesis of aklaloid@Cu: A solution of 0.85 g of CuCl2 in 25 mL of distilled water
was poured into a stirred solution of 9 mg alkaloid and 0.9 g of sodium dodecyl
sulfate in 25 mL of H2O. 0.35 g of zinc powder was added and the combined slurry
was stirred at room temperature for 6 h. The precipitate was filtered and washed with
10 mL 1 M HCl to remove zinc residues, then with 20 mL distilled water and
acetonitrile (MeCN) for three times and dried under vacuum for 6 hours. Pure Cu
nanoparticles (NPs) was prepared in the same way except for the absence of alkaloid
in the reducing solution.
Typical electrochemical hydrogenation was conducted in a mixture of 50 mM
substrate, 0.1 M tetraethylammonium iodide (TEAI) in a 20 mL co-solvent
(MeCN/H2O = 9/1) in an undivided glass cell with an alkaloid@Cu cathode and
sacrificial magnesium (Mg) anode. The current density was 10 mA cm-2 and the
charge was 300 C. The electrolyte was bubbled with high purity N2 throughout the
electrolysis. All the procedure was performed at room temperature.
3. Results and discussion
The entrapment of alkaloids within Cu nanoparticles was carried out according to
alkaloid (aq) + CuSO4 (aq) + Zn (s) = alkaloid@Cu (s) + ZnSO4 (aq). Cinchonidine
(CD, Fig. 1A) was chosen as model dopant. The resulting material, CD@Cu
composite, is a fine powder with the typical colour and shine of Cu, which was easily
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compacted into a coin using a tablet press (Fig. 1B). According to former reports,
metal crystallites act as a protecting matrix providing a confined environment around
the dopant molecules, allows the diffusion of substrate and product molecules in and
out the composite, yet not allowing the dopant to leach out [13]. Therefore, the two
issues were most important in our current system. Was the CD dopant entrapped
within the composite? Did the entrapped CD retain its property? We characterized
CD@Cu composite with multiple methods to get an answer to these two questions.
The typical FE-SEM patterns (Fig. 1C) of the CD@Cu composite reveal that Cu
nanograins gather into particles having an average size of 100 nm and aggregated
further into a macroporous solid. EDX spectra (Fig. 1E) provides a direct proof that
CD was entrapped within this composite: all relevant elements of this material are
observed, including copper, carbon, oxygen and nitrogen. Fig. 1F displays the powder
XRD patterns of pure CD (a), pure Cu NPs (b), and CD@Cu composite (c). Typical
diffraction peaks of Cu are contained in (b) and (c). CD@Cu (c) feature the extra
diffraction peaks (2θ=15-30), which are almost identical to those of pure CD (a).
These are additional evidence that CD was indeed entrapped within the CD@Cu
composite. It’s notable that shifting of the peaks compared with pure Cu NPs
reflections is very small. This finding is one of the indications that the CD molecules
are immobilized not within the copper lattice but within the small cages of the
aggregated nanocrystals [13].
Since CD@Cu composite would be applied to catalytic processes, this entrapment
should be stable and CD must remain intact through the process. Firstly, we want to
emphasize that the entrapment is completely different from adsorption [12, 13]. The
adsorbed CD on Cu surface was unstable, which could be easily washed away by
MeCN or water. In contrast, we washed the CD@Cu composite with water and
MeCN many times in filtering, but the presence of CD dopant could still be confirmed
by characterization methods as mentioned above, which revealed that entrapment was
very stable. Although MeCN and water couldn’t break the composite,
dimethylsulfoxide (DMSO) was found to be a good solvent for extraction of dopant
[13]. If CD@Cu composite was added into DMSO for extraction, distinct peaks were
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observed by FT-IR (Fig. 1G, a), which is the same as pure CD (Fig. 1G, b), indicating
that CD was entrapped and retained its property throughout the entrapment and
extraction process.
Beyond the preparation of a new organically doped metal composites, we wanted to
probe the applicability of such materials in catalysis and study the advantages they
offer with respect to the unsupported catalysts. With this aim, we describe herein the
suitability of the CD@Cu composite as heterogeneous catalysts in the asymmetric
electrocatalytic hydrogenation of aromatic ketones. CD@Cu powder has metallic
character and could be easily compacted into coin for electrolysis. A typical
asymmetric electrocatalytic hydrogenation was carried out in a mixture of 50 mM
substrate, 0.1 M TEAI in a 20 mL co-solvent (MeCN/H2O = 9/1), with a CD@Cu
composite cathode and an Mg anode (Fig. 2A). Methyl benzoylformate (Fig. 2A, 1a)
was used as a model substrate. It’s notable that no CD was found in the reaction
solution. Optically active R-methyl mandelate was obtained with a 78% ee and a 94%
yield were detected by HPLC (Fig. 2B). No by-product was detected by HPLC (or
below the limit of detection), asymmetric hydrogenation of 1a on CD@Cu composite
shows excellent selectivity. As comparison, we also tested the catalytic activity of
non-entrapped CD using metallic Cu cathode. Pure Cu NPs were also compacted into
coin as CD@Cu composite for asymmetric hydrogenation with 1.5 mM CD in
reaction solution as chiral inducer, other conditions being the same as with the
CD@Cu system. A similar yield, 93%, but a significantly lower ee value, 23%, were
obtained. For other entrapped-alkaloids, including cinchonine (CN), quinine (QN) and
quinidine (QD), obviously higher ee value were also achieved with CN@Cu, QD@Cu
and QN@Cu cathode, compared to non-entrapped ones, as shown in Fig. 2B. It’s
notable that R-configuration was observed using CD and QD catalysts; while
S-configuration was predominant for CN and QN. What’s more, 1b-1g were tested to
examine the substrate scope of CD@Cu composite using reaction conditions of 1a.
The results summarized in Fig. 2C show that moderate or good yields and ee values
could be obtained with all the substrates. Therefore, alkaloid@Cu composite could be
effective in the electrochemical asymmetric hydrogenation with a wide range of
substrates.
It’s an interesting question why the much higher ee value was observed at CD@Cu
system. CD@Cu and Cu NPs were prepared the similar way. According to N2
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adsorption-desorption, CD@Cu and Cu NPs have specific surface area of 3.2 and 2.9
m2 g-1, respectively. Larger specific surface area might explain part of the higher ee
value obtained at CD@Cu cathode, but it is not the whole truth. In our former work,
we synthesized a metallic nanostructure Cu NPs cathode with regular morphology,
smaller particle size and 7.5 m2 g-1 specific surface area [8]. Under the same
conditions, the best ee value achieved at this cathode was 61%, still lower than with
the CD@Cu cathode. According to previous research, alkaloid could be electrosorbed
on the metallic Cu surface [8, 16] and the ee value was shown to vary linearly with
the adsorption amount in actual electrolysis [8]. We can infer that more CD on (or
around) the cathode surface is conducive to accelerate electrolysis procedure. In this
report, 1.2 g CD@Cu composite was compacted into a cathode coin, containing
nearly 27 mg CD, which means 27 mg CD was around the inner surface of our
CD@Cu cathode. As for physical adsorption, if pure 1.2 g Cu NPs cathode was put
into 20 mL 1.5 mM CD solution for electrosorption, CD in solution only dropped less
than 0.1 mg. What’s more, the adsorbed CD was not stable and could be easily
washed by MeCN, but the entrapped CD was very stable. In a word, CD on the
CD@Cu cathode surface was 270 times more than these on pure Cu NPs, which
might explain why the ee value obtained at CD@Cu composite cathode was much
higher than the non-entrapped CD system.
The recyclability of the CD@Cu cathode was subsequently examined in the
asymmetric hydrogenation of 1a. After the reaction, the cathode was thoroughly
washed with MeCN and then reused for a next reaction run under identical conditions
with fresh reagents. As shown in Fig. 2D, the catalyst showed no appreciable
reduction of activity even after ten runs. SEM images and for the reused catalyst
suggested that the morphology and crystal structure was completely preserved after
several reuses (Fig. 1D). XRD patterns revealed that CD still existed in the reused
catalyst (Fig. 1F, d). What’s more, CD was extracted from the composite and
quantitate detected by HPLC, which was 27 mg, the same as that of the as-synthesized
sample. These results indicated that no leak of CD occurred during the reaction.
Hence, CD@Cu composite has excellent stability and reusability.
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4. Conclusions
Compared to noble metal platinum, copper is far more abundant and non-expensive.
Using electrochemical conditions, we successfully introduced metallic Cu instead of
Pt into typical Pt-alkaloid catalyzed asymmetric hydrogen system. Alkaloid, the chiral
inducer, was encapsulated within Cu particles rather than modified on the metal
surface by physical adsorption, which means that this alkaloid@Cu composite is an
absolute heterogeneous catalyst. Alkaloid@Cu composite could be directly used as
cathode for the electrocatalytic asymmetric hydrogenation of aromatic ketones
without any supporter or carrier, good ee value and excellent yield were obtained
under mild conditions. In addition, the alkaloid@Cu composite shows remarkable
stability and can be used multiple times, which would be crucial in possible practical
applications.
Acknowledgements
Financial support from National Natural Science Foundation of China (21373090,
21473060) is gratefully acknowledged.
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Fig. 1 A: Molecular structure of alkaloids; B: CD@Cu composite before (left) and
after press (right); FE-SEM patterns of CD@Cu before (C) and after using (D); E:
EDX spectra of CD@Cu; F: XRD patterns of pure CD (a), pure Cu NPs (b), CD@Cu
before (c) and after using (d); G: FT-IR spectra of dopant extracted from CD@Cu
composite (a) and pure CD (b).
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Fig. 2 A: reaction pathway; B: comparison of entrapped and non-entrapped alkaloid
catalysts using 1a as substrate; C: asymmetric hydrogenation with different substrates
at CD@Cu cathode; D: reuse test of CD@Cu composite using 1a as substrate.
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Graphical Abstract
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Highlights
 Asymmetric electrocatalytic hydrogenation was carried out on modified Cu
electrodes.
 Alkaloids were encapsulated within metallic Cu, alkaloid@Cu, instead of
being physisorbed.
 Alkaloid@Cu had a much higher activity than pure Cu NPs.
 Alkaloid@Cu had excellent stability and reusability.
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