Highly efficient three-component coupling reaction catalysed by atomically precise ligand-protected Au38(SC2H4Ph)24 nanoclusters

Article abstract of DOI:10.1039/c6cc07825g

The catalytic potential of atomically precise quantum-sized gold nanoclusters (Au₃₈(SC₂H₄Ph)₂₄) is explored for the three-component coupling of an aldehyde, an alkyne and an amine to synthesize propargylamines.

Full text of DOI:10.1039/c6cc07825g

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Highly efficient three-component coupling
reaction catalysed by atomically precise
Cite this:DOI: 10.1039/c6cc07825g
ligand-protected Au38(SC2H4Ph)24 nanoclusters†
Received 26th September 2016,
Accepted 14th November 2016
Qi Li, Anindita Das,‡ Shuxin Wang, Yuxiang Chen and Rongchao Jin*
DOI: 10.1039/c6cc07825g
www.rsc.org/chemcomm
The catalytic potential of atomically precise quantum-sized gold Among them, gold catalysts, especially Au(III) salts, show the
nanoclusters (Au38(SC2H4Ph)24) is explored for the three-component highest catalytic efficiency. For example, in 2003 Wei et al.17
coupling of an aldehyde, an alkyne and an amine to synthesize first demonstrated that both Au(III) and Au(I) salts can be used
propargylamines. A high catalytic efficiency with a very low loading as highly efficient catalysts for the A3 coupling reaction, with a
(0.01 mol%) is achieved. Furthermore, the synergistic effect of the TOF up to B34 hÀ1 for Au(III) salts and B8.3 hÀ1 for Au(I) salts at
electron-deficient surface (i.e. Aud+, 0 o d+ o 1) and the electron- 99% conversion. However, the shortcomings of typical homo-
rich Au23 core of the ligand-protected nanoclusters is critical for this geneous catalysis are multi-fold, such as the difficulty in separa-
catalytic reaction.
tion, poor recyclability and thermal instability. Gold nanoparticles
can overcome such shortcomings. In 2007, Kidwai24 et al. first
reported that the A3 coupling reaction could be readily accom-
plished by using unsupported-Au(0) nanoparticles, although the
efficiency was very low. Several critical issues still remain for gold
nanoparticles to be used as the catalyst for A3 coupling. First,
to date, only those nanogold catalysts supported on some
specially designed supports which are usually laborious and
time-consuming to prepare (such as montmorillonite, magne-
sium oxide, mesoporous carbon nitride, mesoporous organosilica
with ionic liquid frameworks)25–28 have shown enhanced catalytic
performance (TOFs: 10–40 hÀ1). More importantly, the active site
of gold nanoparticle catalysts remains elusive. This is due to
several factors, including the unknown surface structure of the
gold nanoparticles, the complicated unknown effect of different
supports and also the probable residual Au(III) salt precursor on
the support that may significantly impact the reaction.
Herein, atomically precise and thermally stable Au38(SC2H4Ph)24
nanoclusters are explored as a catalyst for the A3 coupling reaction.
The atomic structure of the Au38(SC2H4Ph)24 nanocluster was
previously determined by X-ray crystallography,29 which is com-
posed of a face-fused biicosahedral core (Au23) protected by six
dimeric Au2(SR)3 and three monomeric Au(SR)2 staple-like sur-
face motifs (Fig. 1). This enables a detailed analysis of the relation
between the cluster structure and the catalytic performance,
which couldn’t be realized in previous research on larger gold
nanoparticles. We hypothesize that the electron-rich Au23 core
and the surface shell of Au atoms carrying partial positive charges
(0 o d+ o 1) on account of bonding to thiolates in the staple
motifs (Fig. 1b) may synergistically boost the catalytic perfor-
mance. Furthermore, ligand-off Au38 clusters with the Au(0)
Metal nanoparticles (1–100 nm) occupy an important position in
heterogeneous catalysis.1,2 The high activity of small particles
arises from their high surface area-to-volume ratio, surface geo-
metric effect, electronic properties, and quantum size effect.3–6
However, the elusive surface structure of nanoparticles poses a
major challenge to correlating the catalytic performance with
the catalyst structure.1–6 In recent research, atomically precise
gold nanoclusters (o2 nm) protected by thiolate ligands have
emerged as a new class of nanocatalysts, which have been
reported to exhibit good catalytic performance for a range of
reactions.7–15 Compared to conventional gold nanocatalysts
(for example, larger nanoparticles), whose surface structures are
unknown, atomically precise gold nanoclusters possess well-
defined atomic structures, so that they can serve as model
nanocatalysts for investigating how the atomic structure and
the catalytic properties are related.
Three-component coupling of an aldehyde, an alkyne and an
amine (generally called A3 coupling) is the most convenient and
general approach to synthesize propargylamines, which are
well-recognized as highly valuable synthetic building blocks in
the synthesis of various natural products and biologically active
compounds.16 To date, many transition-metal catalysts including
gold,17 silver,18 copper,19 iridium,20 nickel,21 iron,22 and indium23
have been explored for the synthesis of propargylamines.
Department of Chemistry, Carnegie Mellon University, Pittsburgh, PA 15213, USA.
E-mail: rongchao@andrew.cmu.edu
† Electronic supplementary information (ESI) available. See DOI: 10.1039/c6cc07825g
‡ Current address: Department of Chemistry, Northwestern University, Evanston
IL 60208, USA.
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the reaction reached the maximum conversion (98%); the
calculated turnover numbers (TONs) per Au38 cluster and per
gold atom are 9800 and 258, respectively.
We further characterized the Au38(SC2H4Ph)24 catalyst after
the A3 coupling reaction by UV-visible spectroscopy (Fig. S2, ESI†)
and ESI-mass spectrometry (Fig. S3, ESI†). The optical peaks of
the Au38(SC2H4Ph)24 cluster at 450 nm, 630 nm and 750 nm are
retained, indicating that the majority of the Au38(SC2H4Ph)24
clusters survived the reaction. This was further confirmed by
the ESI-mass spectrometric analysis of the Au38(SC2H4Ph)24
catalyst after the reaction, which shows peaks corresponding
to the Au38(SC2H4Ph)24 clusters.
The recyclability of the catalyst is also of high importance for
real-world applications, and we investigated this by recycling
the catalyst (i.e. adding excess methanol to precipitate clusters)
for reuse in fresh reactions. With the recycled catalyst, a fresh
reaction was performed with fresh reactants under identical
reaction conditions. It was observed that the conversion was
decreased from 98% to B68% after 3 cycles. The drop in conver-
sion should be caused by the gradual degradation of nanoclusters
in the multiple recycling tests. Overall, the gold nanocluster
catalysts show a reasonably good recyclability.
It should be noted that the Au38(SC2H4Ph)24 cluster, with
a well-defined structure, comprising an Au(0) core protected
by Aud+–thiolate (0 o d+ o 1) motifs, shows a much higher
catalytic efficiency for the A3 coupling reaction than any other
larger gold(0) nanoparticles and Au(I) salt/complex based cata-
lysts reported before. We rationalize that the electronic struc-
ture of the Au38(SC2H4Ph)24 nanocluster, including the surface
ligand protected partially charged Aud+ atoms and the electron-
rich Au23 core, is critical for this significant enhancement of
catalytic efficiency. To further verify this, another nanocluster with
an atomically well-defined structure, Au25(SC2H4Ph)18À (composed
of an icosahedral core Au13 and six Au2(SR)3 staple motifs),7,30
was also tested as the catalyst for the A3 coupling reaction. The
experimental results demonstrate that the Au25(SC2H4Ph)18À cluster
shows a similarly high catalytic performance to Au38(SC2H4Ph)24.
The kinetics and product conversion of A3 reaction catalyzed by
Au25(SC2H4Ph)18À are similar to the Au38 catalyzed case (shown in
Fig. S4, ESI†), which agrees well with our rationale.
Fig. 1 (a) The X-ray crystal structure of the Au38(SC2H4Ph)24 cluster. Magenta
is Au, yellow is sulfur, gray is carbon and white is hydrogen. (b) The core/shell
structure of the cluster: a face-fused biicosahedral Au23 core protected by six
dimeric Au2(SR)3 and three monomeric Au(SR)2 staple-like surface motifs
(carbon and hydrogen are omitted); Au atoms in the motifs (green) carry
partial positive charges (0 o d+ o 1) due to bonding with thiolate ligands.
surface can also be easily obtained after thermal pretreatment
(e.g. at 300 1C in N2 for 1 hour), which provides an exclusive com-
parison of the catalytic behavior of Au(0) and Aud+ (0 o d+ o 1)
surface sites on nanogold.
The three-component coupling reaction of an aldehyde, an
alkyne and an amine is shown in Fig. 2a. In this work, catalytic
tests indicate that the Au38(SC2H4Ph)24 clusters are highly effi-
cient catalysts for the A3-coupling reaction. An excellent conver-
sion up to 98% to the propargylamine product can be achieved in
5 h (indicated by NMR analysis, see Fig. S1, ESI†). The reaction
kinetics was studied by monitoring the conversion of reactants at
different time intervals, as shown in Fig. 2b. It was found that the
conversion to propargylamine increased rapidly during the first
few hours, reaching a maximum (490%) within 4 h and higher
for a prolonged period of time. The kinetics can be well fitted by a
first-order equation (Fig. 2c) and the reaction rate constant is
calculated to be k = 0.6 hÀ1. The turnover frequencies (TOFs) at
2.4% conversion after initial 6 min run are calculated to be
2465 hÀ1 per Au38 cluster and 65 hÀ1 per gold atom. After 5 hours,
We also investigated the Au38(SC2H4Ph)24 nanocluster sup-
ported on different metal-oxides, including cerium dioxide (CeO2),
titanium dioxide (TiO2), and silica (SiO2), for the A3 coupling.
As shown in Table 1, Au38(SC2H4Ph)24 clusters loaded on all the
different supports show similarly high catalytic performance to
the unsupported one. These results are totally different from
previously reported larger gold nanoparticle catalysts, in which
high catalytic performance can be achieved only by loading
gold nanoparticles on specially designed oxide supports.25–28
Our results suggest that the intrinsic electronic structure of the
Fig. 2 (a) Scheme of three-component coupling reaction of benzaldehyde,
piperidine, and phenylacetylene for the synthesis of propargylamine cata- ligand-protected nanoclusters plays a determinant role in their
lyzed by Au38(SC2H4Ph)24. (b) Conversion of benzaldehyde, phenylacetylene
catalytic performance, as opposed to the case of bare nanogold
on special supports.
To gain further insight into the relation between the cluster
structure and the catalytic performance, ligand-off Au38 clusters
and piperidine as a function of reaction time over Au38(SC2H4Ph)24 catalysts.
(c) Linear relation between the natural logarithm of conversion and time.
Reaction conditions: benzaldehyde (1.0 mmol), piperidine (1.2 mmol), and
phenylacetylene (1.3 mmol), 80 1C. Au38(SC2H4Ph)24: 1 mg (0.1 Â 10À3 mmol,
0.01 mol% loading).
supported on CeO2 were prepared through a thermal method
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Table 1 Three-component coupling of benzaldehyde, piperidine, and
phenylacetylene with the Au38(SC2H4Ph)24 cluster catalyst loaded on
different supports in different solventsa
Table 2 A3 coupling of an aldehyde, alkyne, and amine catalyzed by
Au38(SC2H4Ph)24
a
Catalyst
Solvent
T (1C)
Time (h)
Conv. (%)
Au38
No solvent
No solvent
No solvent
No solvent
Water
80
80
80
80
80
80
5
5
5
5
5
5
98
93
98
99
94
80
Au38/TiO2
Au38/SiO2
Au38/CeO2
Au38/CeO2
Au38/CeO2
Entry R1
R2R3NH
R4
Time (h) Yield [%]
1
2
3
4
5
6
7
8
Ph
Piperidine Ph
Piperidine Ph
Piperidine Ph
Piperidine Ph
Piperidine Ph
5
5
5
5
5
5
5
5
5
5
5
95
91
91
84
93
92
0
90
100
62
31
p-Br-Ph
p-CH3S-Ph
p-CH3-Ph
p-F-Ph
p-CH3O-Ph Piperidine Ph
p-NO2-Ph
Ph
Ph
Ph
Ph
Toluene
a
Reaction conditions: benzaldehyde (1.0 mmol), piperidine (1.2 mmol),
and phenylacetylene (1.3 mmol), 1 mg of Au38(SC2H4Ph)24 supported
by 100 mg of metal oxides, 1 mL of H2O (MilliQ) or toluene if needed,
5 h, 80 1C.
Piperidine Ph
Piperidine o-CH3-Ph
Piperidine p-CH3O-Ph
Piperidine Ph-(CH2)2
Piperidine CH3(CH2)5
9
10
11
reported previously.31,32 After thermal pretreatment under 300 1C
in N2, all the ligands can be removed, leaving exposed Au(0) atoms
on the cluster surface. The catalytic performance of the ligand-off
Au38/CeO2 was, however, found to be significantly decreased
(Fig. 3) compared with the ligand-on Au38(SC2H4Ph)24 nano-
clusters. This is against the traditional view that more bare
surface atoms would lead to higher catalytic performance. The
conversion to the product decreases from 495% to 70% after a
5 h-run and no more product can be obtained upon prolonging
the time. More importantly, the reaction kinetics change from
first-order to nearly zero-order when ligand-off Au38/CeO2 was used
as the catalyst, suggesting that the underlying reaction pathway
may have been changed.
For comparison, an Au(I)–S–C2H4Ph complex was also pre-
pared and its catalytic performance for the A3 coupling was
tested. The results show that the final conversion significantly
decreases to 60% (note: for Au(I)–S–C2H4Ph, an equivalent mole
of gold as the Aud+–thiolate on the Au38(SC2H4Ph)24 is used as
the catalyst under the same reaction conditions).
a
Reaction conditions: aldehyde (1 equiv., 1.0 mmol), amine (1.2 equiv.,
1.2 mmol), alkyne (1.3 equiv., 1.3 mmol), 0.01 mol% Au38(SC2H4Ph)24
catalyst.
reactions (entries 1–7), except for the one with 4-nitrobenz-
aldehyde, which contains a strongly electron-withdrawing
group (entry 7). On the other hand, different alkynes show
distinctly different yields. The phenylacetylene derivatives show
similarly high conversions (entries 8 and 9) under the same
reaction conditions, but other alkynes display decreasing yields
(entries 10 and 11).
The mechanism of the A3 coupling reaction has not been
well-explored in the literature.16 A general reaction pathway
involves C–H activation of the alkyne, forming an intermediate
p-metal–alkyne complex, which then reacts with the iminium
ion, resulting in the formation of propargylamine with simul-
taneous regeneration of the metal catalyst. It has been demon-
strated that phenylacetylene can be facially absorbed on the
Au cluster surface, with its phenyl ring facing an external gold
atom of the cluster which is well exposed with little steric
hindrance.9 Meanwhile, previous work also demonstrated the
various strong bonding modes of phenylacetylene on the surface
of gold nanoclusters.33 This is consistent with our experimental
results that alkynes (i.e. the lack of a phenyl ring and hence weaker
adsorption) show significantly decreased yields compared with the
phenylacetylene derivatives (Table 2, entries 8–11). Our results also
suggest that the benzaldehydes have strong adsorption energy with
the –CHO group in close contact with the S–Au–S groups.34 As
the –NO2 group can also interact with the S–Au–S motif, which can
influence the orientation of NO2–Ph–CHO on the cluster surface,34
this explains the result of NO2–Ph–CHO undergoing no conversion
to propargylamines. We performed NMR measurements for the
Au38 cluster after running the A3 reaction and being washed with
ethanol for many times, but no trace of phenylacetylene and
benzaldehydes could be found; this may arise from the relatively
weak interaction of the Au cluster with phenylacetylene and
benzaldehydes, so that they are easily washed away in the isolation
steps of the clusters from the reaction mixture.
The above results further demonstrate the importance of the
intact structure of Au38(SC2H4Ph)24 for the catalytic performance.
Both the Aud+–thiolate surface and the electron rich Au(0) core
are important and the synergistic effect of the core and the shell
results in an enhanced catalytic performance.
To test the scope of the A3 coupling reaction with the
Au38(SC2H4Ph)24 clusters, we extended our studies to different
combinations of aldehydes and alkynes. As shown in Table 2,
different benzaldehydes give excellent yields in the A3 coupling
Fig. 3 Conversion of benzaldehyde, phenylacetylene and piperidine as
a function of reaction time over Au38(SC2H4Ph)24, Au38(SC2H4Ph)24/CeO2,
and ligand-off Au38/CeO2 catalysts.
In summary, we have explored the Au38(SC2H4Ph)24 nano-
cluster as a catalyst for multi-component A3 coupling reaction.
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The Au38(SC2H4Ph)24 nanocluster is found to catalyze the
A3 reaction with a very high efficiency. We further demonstrate
the importance of the entire structure of the Au38(SC2H4Ph)24
cluster, i.e. the synergistic effect of the ligand protected Aud+
surface (0 o d+ o 1) and the electron-rich Au23 core for high
catalytic performance. Such nanocluster catalysts may find
promising application in other transformation reactions and
provide mechanistic insights.
R. J. acknowledges the financial support from the U.S. National
Science Foundation (DMREF-0903225).
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