Regiospecific Hydroamination of Unsymmetrical Electron-Rich and Electron-Poor Alkynes with Anilines Catalyzed by Gold(I) Immobilized in MCM-41

Article abstract of DOI:10.1002/adsc.201800621

The first heterogeneous gold(I)-catalyzed regiospecific hydroamination of ynamides and propiolic acid derivatives with anilines has been achieved by using a diphenylphosphine-functionalized MCM-41-supported gold (I) complex and AgNTf₂ as catalysts under mild conditions, yielding the corresponding (E)-N-arylimines and (Z)-enamines in good to excellent yields with broad substrate scope. The new heterogeneous gold(I) complex can easily be prepared via a two-step procedure from commercially available reagents and recovered by simple filtration of the reaction mixture. The recovered catalyst (Ph₂P-MCM-41-AuNTf₂) can be reused at least seven times without addition of AgNTf₂ as a co-catalyst and its catalytic efficiency remains unaltered. (Figure presented.).

Full text of DOI:10.1002/adsc.201800621

Title: Regiospecific Hydroamination of Unsymmetrical Electron-Rich
and Electron-Poor Alkynes with Anilines Catalyzed by Gold(I)
Immobilized in MCM-41
Authors: Dayi Liu, Quan Nie, Rongli Zhang, and Mingzhong Cai
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To be cited as: Adv. Synth. Catal. 10.1002/adsc.201800621
Link to VoR: http://dx.doi.org/10.1002/adsc.201800621

10.1002/adsc.201800621
Advanced Synthesis & Catalysis
FULL PAPER
DOI: 10.1002/adsc.201((will be filled in by the editorial staff))
Regiospecific Hydroamination of Unsymmetrical Electron-Rich
and Electron-Poor Alkynes with Anilines Catalyzed by Gold(I)
Immobilized in MCM-41
Dayi Liu, Quan Nie, Rongli Zhang and Mingzhong Cai*
Key Laboratory of Functional Small Organic Molecule, Ministry of Education and College of Chemistry & Chemical
Engineering, Jiangxi Normal University, Nanchang 330022, P. R. China
e-mail: mzcai@jxnu.edu.cn
Received: ((will be filled in by the editorial staff))
Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/adsc.201######.((Please
delete if not appropriate))
Abstract: The first heterogeneous gold(I)-catalyzed available reagents and recovered by simple filtration of the
regiospecific hydroamination of ynamides and propiolic reaction mixture. The recovered catalyst (Ph2P-MCM-41-
acid derivatives with anilines has been achieved by using a AuNTf2) can be reused at least seven times without
diphenylphosphine-functionalized MCM-41-supported gold addition of AgNTf2 as a co-catalyst and its catalytic
(I) complex and AgNTf2 as catalysts under mild conditions, efficiency remains unaltered.
yielding the corresponding (E)-N-arylimines and (Z)-
enamines in good to excellent yields with broad substrate
scope. The new heterogeneous gold(I) complex can easily
be prepared via a two-step procedure from commercially
Keywords: gold; hydroamination; ynamide; propiolic
acid derivative; heterogeneous catalysis
peratures and long reaction times are usually required
to achieve acceptable conversions. Furthermore, for
intermolecular hydroamination of unsymmetrical
internal alkynes, a mixture of regioisomers is often
formed with poor to moderate regioselectivity.
Introduction
Substituted amine, enamine or imine moieties are
widely encountered in the scaffolds of many complex
molecules such as natural products and synthetic
drugs. Besides their relevance as part of bioactive
naturally occurring products, amines, enamines and
imines are important intermediates in the synthesis of
natural products, pharmacological agents, N-hetero-
cycles, and fine chemicals.[1] Hydroamination of
alkynes is of great importance in synthetic organic
chemistry since this reaction offers an atom-econo-
mical route to various amine derivatives and provides
a convenient and practical method for the preparation
of numerous important synthetic intermediates and
fine chemicals.[2] A wide range of metal catalysts of
titanium,[3] zirconium,[4] ruthenium,[5] rhodium,[6]
palladium,[7] iridium,[8] platinum,[9] zinc,[10] nickel,[11]
copper,[12] silver,[13] lanthanide,[14] and actinide[15]
have been developed to catalyze this transformation.
The catalysts based on late transition metals are
preferred due to their lower oxophilicity and the
majority of the metal-catalyzed hydroaminations of
alkynes provide enamine or imine products. However,
in many cases, high catalyst loadings, elevated tem-
Homogeneous catalysis of organic reactions by
gold complexes is a landmark addition to the field of
synthetic organic chemistry and has been developed
into a highly efficient and powerful tool for the cons-
truction of various important building blocks.[16]
Recently, homogeneous gold(I)-catalyzed reactions
of ynamides have gained much attention due to their
high efficiency for the synthesis of nitrogen-contain-
ing heterocycles.[17] Gold complexes are considered
as excellent candidates for hydroamination catalysts
of alkynes due to their very low oxophilicity.
Cationic gold(I) or gold(III) complexes have been
shown to be highly efficient catalysts for the
intermolecular hydroamination of terminal alkynes[18]
and internal alkynes.[19] However, applications of
these homogeneous gold complexes in large-scale
synthesis or multistep syntheses remain a challenge
because gold is an expensive metal and the catalyst is
difficult to separate and recycle. The heterogenization
of the existing homogeneous gold catalysts appears to
be an attractive solution to this problem.[20] Although
gold nanoparticles supported on different matrices or
1
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10.1002/adsc.201800621
Advanced Synthesis & Catalysis
gold clusters have been used as heterogeneous
catalysts for the intermolecular hydroamination of
terminal alkynes in recent years,[21] only an example
of intermolecular hydroamination of terminal alkynes
catalyzed by supported gold complexes has been
described[20a] and no examples of intermolecular
hydroamination of internal alkynes catalyzed by
supported gold complexes have been reported so far.
Mesoporous MCM-41 materials have recently been
shown to be powerful supports for immobilization of
homogeneous catalysts due to their outstanding
advantages such as extremely high surface areas,
large and defined pore sizes, big pore volumes and
the presence of a large number of silanol (Si–OH)
groups on the inner surface, compared with other
solid supports.[22] In continuation of our efforts to
develop economical and eco-friendly synthetic
pathways for organic transformations,[20f-h] we here
report the first synthesis of diphenylphosphine-
functionalized MCM-41-supported gold(I) complex
[Ph2P-MCM-41-AuCl] and its successful application
to the intermolecular hydroamination of unsym-
metrical electron-rich and electron-poor alkynes with
anilines leading to the corresponding (E)-N-aryl-
imines and (Z)-enamines in good to excellent yields
with 100% regioselectivity under mild conditions
(Scheme 1). The new heterogeneous gold(I) catalyst
can easily be recovered by a simple filtration and its
catalytic efficiency remains unaltered even after
recycling eight times.
as a gray powder, the gold content of the complex
was found to be 0.36 mmol g-1 according to the ICP-
AES analyses.
Scheme 2. Synthesis of the Ph2P-MCM-41-AuCl complex.
The Ph2P-MCM-41-AuCl complex was charac-
terized by various physico-chemical techniques. The
small angle X-ray powder diffraction (XRD) patterns
of the parent MCM-41 and the Ph2P-MCM-41-AuCl
complex are illustrated in Fig. 1. XRD pattern of the
parent MCM-41 gave three peaks corresponding to
hexagonally ordered mesoporous phases. For the
Ph2P-MCM-41-AuCl, the (100) reflection of the
MCM-41 with decreased intensity was remained after
grafting phosphine-gold(I) complex, while the (110)
and (200) reflections became weak and diffuse,
which may be mainly due to contrast matching
between the silicate framework and organic moieties
which are located inside the channels of MCM-41.
These results indicate that the structure of the
mesoporous MCM-41 remains unchanged through
the grafting procedure and the formation of the
gold(I) catalyst has taken place preferentially inside
the pore system of MCM-41.
Scheme 1. Heterogeneous gold(I)-catalyzed intermolecular
hydroamination of unsymmetrical electron-rich and elec-
tron-poor alkynes with anilines.
Results and Discussion
Preparation of Ph2P-MCM-41-AuCl Complex and
Optimization of Reaction Conditions
The diphenylphosphine-functionalized MCM-41-sup-
ported gold(I) complex [Ph2P-MCM-41-AuCl] was
easily prepared according to the procedure shown in
Scheme 2. Firstly, the mesoporous MCM-41[20f] was
condensed with commercially available 2-(diphenyl-
phosphino)ethyltriethoxysilane in toluene under
reflux for 24 h, followed by silylation with Me3SiCl
at room temperature for 24 h to generate diphenyl-
phosphine-functionalized MCM-41 (Ph2P-MCM-41).
The latter was subsequently treated with Me2SAuCl
in dichloromethane (DCM) at room temperature to
afford the diphenylphosphine-functionalized MCM-
41-supported gold(I) complex [Ph2P-MCM-41-AuCl]
Fig. 1. XRD patterns of the parent MCM-41 (1) and Ph2P-
MCM-41-AuCl (2). a.u.: arbitrary units.
The N2 adsorption-desorption isotherms and pore
size distributions for the parent MCM-41 and the
Ph2P-MCM-41-AuCl complex are presented in Fig. 2
and Fig. 3, respectively. As expected, the isotherms
in Fig. 2 have remarkable changes before and after
grafting the gold(I) complex because the organic
moieties entered the channels, but both samples
2
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10.1002/adsc.201800621
Advanced Synthesis & Catalysis
showed type IV isotherms, characteristic of meso-
porous materials according to the IUPAC classifi-
cation. As shown in Fig. 3, the pore volume and size
of the Ph2P-MCM-41-AuCl complex reduced appa-
rently compared with the parent MCM-41, also
indicating that the organic moieties were introduced
into the inner channels, but the pore still remained a
narrow distribution. After the grafting the phosphine
gold(I) complex onto MCM-41, the surface area and
pore diameter decreased from 896 m2/g and 2.7 nm to
574 m2/g and 1.8 nm, respectively, demonstrating
that the ordered mesostructure of the parent MCM-41
remained almost unchanged.
The energy dispersive X-ray spectroscopy (EDS)
shows the elements present in the material. EDS
analysis of fresh Ph2P-MCM-41-AuCl complex
indicates the presence of Si, O, C, P, Cl and Au
elements (Fig. 4). The structure of supported phos-
phine gold(I) catalyst was also verified by X-ray
photoelectron spectroscopy (XPS). The XPS spectra
of the fresh Ph2P-MCM-41-AuCl (Fig. 5) displayed
the spin orbit pair at 84.8 eV (Au 4f7/2) and 88.5 eV
(Au 4f5/2) that can be assigned to Au(I).
Fig. 5. XPS spectra of the Ph2P-MCM-41-AuCl complex.
a.u.: arbitrary units.
Fig. 2. N2 adsorption/desorption isotherms of MCM-41
and Ph2P-MCM-41-AuCl. STP: standard temperature and
pressure.
The Ph2P-MCM-41-AuCl was then used as the
catalyst for the intermolecular hydroamination of
unsymmetrical electron-rich or electron-poor alkynes
with anilines. Initial experiments with 2-iodoaniline
(1a) and 3-(phenylethynyl)oxazolidin-2-one (2a)
were performed to optimize the reaction conditions,
and the results are listed in Table 1. At first, various
heterogeneous gold(I) complexes as catalysts were
tested at room temperature in DCE as solvent (entries
1-5). When Ph2P-MCM-41-AuCl was used as catalyst,
only trace of the desired product 3a was detected
(entry 1). To our delight, when various silver salts
such as AgOTf, AgNTf2, AgSbF6, and AgBF4 were
used as co-catalysts, the reaction gave the desired 3a
in 45-95% isolated yields and AgNTf2 was the best
choice (entries 2-5). The use of AgNTf2 alone as the
catalyst only afforded a low yield (entry 6) and no
reaction was observed in the absence of any catalyst
(entry 7). These results indicated that the real catalyst
was Ph2P-MCM-41-AuNTf2, generated in situ from
Ph2P-MCM-41-AuCl and AgNTf2. In order to further
confirm that the supported AuNTf2 is the real catalyst,
we prepared Ph2P-MCM-41-AuNTf2 by the reaction
of Ph2P-MCM-41-AuCl with AgNTf2 in DCM at 25
ºC for 0.5 h and used it as the catalyst, the desired
product 3a was isolated in 96% yield after 4 h (entry
8). Our next studies focused on the effect of solvent
on the model reaction and a significant solvent effect
was observed (entries 9-14). Among the solvents
examined, DCM, MeCN, toluene and dioxane also
afforded the desired 3a in good to excellent yields,
and DCM gave the best result, while DMF and
DMSO were less effective. Finally, we screened the
Fig. 3. Pore size distributions of MCM-41 and Ph2P-
MCM-41-AuCl.
Fig. 4. Energy dispersive spectra (EDS) of Ph2P-MCM-
41-AuCl.
3
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10.1002/adsc.201800621
Advanced Synthesis & Catalysis
amount of the supported gold catalyst and were
pleased to find that the reaction still proceeded
(2a) as substrate. Substituted benzenamines bearing
either electron-donating or electron-withdrawing
smoothly even with only 0.5 mol% catalyst (entry 15). groups 1b-1f can undergo the hydroamination with
But further reducing the amount of the catalyst to 0.2
mol% resulted in a lower yield and a long reaction
time was required (entry 16). When a homogeneous
gold(I) complex was used as catalyst, the desired 3a
was also isolated in 97% yield (entry 17), indicating
that the catalytic activity of Ph2P-MCM-41-AuNTf2
was comparable to that of Ph3PAuNTf2. Thus, the
optimized conditions for this hydroamination reaction
are the Ph2P-MCM-41-AuCl/AgNTf2 (1 mol%) in
DCM as solvent at room temperature for 4 h (Table 1,
entry 9).
2a smoothly under mild conditions to give the
corresponding (E)-N-arylimines 3b-3f in good to
excellent yields. But anilines bearing strong electron-
withdrawing groups 1e and 1f showed lower
reactivity and afforded the desired products 3e and 3f
in slightly lower yields on longer reaction time or by
using 2 mol% of catalysts. Alkyl-substituted 3-
ethynyloxazolidin-2-ones 2b and 2c proved to be also
suitable substrates and the reactions with 2-iodo-
aniline (1a) furnished the desired 3g and 3h in 92%
and 95% yield, respectively. This heterogeneous
hydroamination reaction was also applicable to the
ynamides comprising tosyl-substituted sulfonamide.
For example, N,4-dimethyl-N-(phenylethynyl)benze-
nesulfonamide (2d) underwent the intermolecular
hydroamination with electron-rich or electron-defi-
cient anilines efficiently to give the corresponding
(E)-N-arylimines 3i-3m in excellent yields. When
alkyl-substituted N-ethynyl-N,4-dimethylbenzenesul-
fonamides 2e and 2f were used as substrates, the
reactions with various anilines proceeded smoothly to
afford the expected products 3n and 3o in 90-93%
yields. In addition to 3-alkynyloxazolidin-2-ones 2a-
2c and N-alkynyl-N,4-dimethylbenzenesulfonamides
2d-2f, the hydroamination reaction worked equally
well with alkyl- or aryl-substituted N-ethynyl-N-
methylmethanesulfonamides 2g-2j, thus furnishing
the desired (E)-N-arylimines 3p-3s in 89-94% yields.
In all cases, (E)-N-arylimine was isolated as the sole
product and no other isomers were observed, which
should be attributed to the presence of strongly
polarized C–C triple bond in ynamide thereby
ensuring full regioselectivity. The results above
prompted us to investigate the intermolecular hydro-
amination of ynamides with aliphatic amines,
unfortunately, aliphatic amines were not reactive
under the conditions optimized for anilines even at
higher temperatures. Interestingly, this heterogeneous
gold(I)-catalyzed intermolecular hydroamination
reaction also worked well for allenamides. Under the
optimized conditions for ynamides, the reactions of
3-(propa-1,2-dienyl)oxazolidin-2-one with anilines
1a and 1f proceeded smoothly to give the corres-
ponding hydroaminated products A and B in
excellent yields (Scheme 3). The enamides were
obtained exclusively as the E-isomers, and the
addition of N–H bond to the activated allenamide
gave the Markovnikov product.
Table 1. Optimization of the reaction conditions[a]
t
Yield
Entry Silver salt (mol%)
Solvent
[h] [%][b]
1
–
DCE
12
12
4
trace
52
95
73
45
27
0
2
AgOTf (1)
AgNTf2 (1)
AgSbF6 (1)
AgBF4 (1)
AgNTf2 (1)
–
DCE
3
DCE
4
DCE
8
5
DCE
12
12
24
4
6[c]
7[c]
8[d]
9
DCE
DCE
–
DCE
96
97
91
87
75
16
12
92
81
97
AgNTf2 (1)
AgNTf2 (1)
AgNTf2 (1)
AgNTf2 (1)
AgNTf2 (1)
AgNTf2 (1)
AgNTf2 (0.5)
AgNTf2 (0.2)
–
DCM
MeCN
toluene
dioxane
DMF
DMSO
DCM
DCM
DCM
4
10
11
12
13
14
15
16
17[e]
4
4
4
12
12
12
24
4
[a]
Reaction conditions: 1a (1.1 mmol), 2a (1.0 mmol),
Ph2P-MCM-41-AuCl (1 mol%) in solvent (1.0 mL), stirred
[b]
[c]
at room temperature.
Isolated yield.
Without Ph2P-
MCM-41-AuCl. [d] Ph2P-MCM-41-AuNTf2 (1 mol%) was
used. [e] Ph3PAuNTf2 (1 mol%) was used.
Scope of the Reaction Catalyzed by Ph2P-MCM-
41-AuCl Complex
With the optimal reaction conditions (1 mol% of
Ph2P-MCM-41-AuCl/AgNTf2 in DCM at room tem-
perature for 4 h) in hand, we started to investigate the
scope of this heterogeneous gold(I)-catalyzed hydro-
amination reaction by using various anilines and
ynamides as substrates, and the results are sum-
marized in Table 2. First, the scope of anilines was
examined with 3-(phenylethynyl)oxazolidin-2-one
Scheme 3. Heterogeneous gold(I)-catalyzed hydroamina-
tion of allenamide with anilines.
Table 2. Heterogeneous gold(I)-catalyzed regiospecific
hydroamination of anilines with ynamides[a,b]
4
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10.1002/adsc.201800621
Advanced Synthesis & Catalysis
effects of unsymmetrical internal alkynes strongly
influence the regioselectivity in the heterogeneous
gold(I)-catalyzed intermolecular hydroaminations. In
principle, these (Z)-enamine products could also
result from a Michael addition of anilines to propiolic
acid derivatives. However, control experiments
showed that the reaction at 60 ºC did not occur at all
in the absence of the catalyst. We also performed the
reaction of propiolic acid derivatives with aliphatic
amines such as isobutylamine and benzylamine under
the optimized conditions, but the hydroamination
reaction did not work. In addition, common terminal
alkynes such as phenylacetylene proved to be also
compatible with the standard reaction conditions. In
the presence of Ph2P-MCM-41-AuCl (2 mol%) and
AgNTf2 (2 mol%), the reaction of phenylacetylene
with 2-iodoaniline (1.1 equiv) in DCM proceeded
smoothly at room temperature to afford the Markov-
nikov addition product (E)-2-iodo-N-(1-phenylethy-
lidene)aniline (C) in 90% yield within 5 h.
To ensure that the observed catalysis arises from
the heterogeneous catalyst Ph2P-MCM-41-AuNTf2
and not from the leached gold species in solution, we
performed the addition of 2-iodoaniline (1a) to 3-
(phenylethynyl)oxazolidin-2-one (2a) and removed
the catalyst from the reaction mixture by filtration at
approximately 50% conversion of 2a. After removal
of the Ph2P-MCM-41-AuNTf2 catalyst, the filtrate
was again stirred at room temperature for 4 h. In this
case, no significant increase in conversion of 2a was
observed, indicating that leached gold species from
the catalyst (if any) are not responsible for the
observed activity. It was further confirmed by ICP-
AES analysis that no gold species could be detected
in the filtrate (below the detection limit). These
results rule out any contribution to the observed
catalysis from a homogeneous gold species demon-
strating that the observed catalysis was intrinsically
heterogeneous.
[a] Reaction conditions: 1 (1.1 mmol), 2 (1.0 mmol), Ph2P-
MCM-41-AuCl (1 mol%), AgNTf2 (1 mol%) in DCM (1.0
mL) at room temperature for 4 h. [b] Isolated yield. [c] For 8
h. [d] 2 mol% of catalysts were used.
Encouraged by the above results, we next applied
this catalytic system to the intermolecular hydro-
amination of propiolic acid derivatives with anilines,
and the results are summarized in Table 3. Generally,
these unsymmetrical electron-deficient alkynes
displayed a lower reactivity than the electron-rich
ones. So, longer reaction times and higher catalyst
loading (2 mol%) were required for these substrates,
but in all cases examined, high yields of the (Z)-
enamines were isolated as the sole products. For
example, ethyl 3-phenylpropiolate (4a) can undergo
the intermolecular hydroamination smoothly with
anilines bearing various substituents, regardless of
their electronic properties and substitution positions,
yielding the corresponding (Z)-enamines 5a-5f in
good to excellent yields within 6-24 h. Alkyl-
substituted ethyl propiolates 4b and 4c showed a
similar reactivity with 4a and afforded the desired
(Z)-enamines 5g-5l in 85-89% yields. Besides
propiolates, propiolamides 4d and 4e also proved to
be suitable substrates and the reactions with various
anilines gave the expected products 5m-5r in high
yields within 24 h. Interestingly, the intermolecular
hydroamination of sterically hindered 2-iodoaniline
with sterically hindered ethyl propiolate 4f furnished
exclusively a 95% yield of the (Z)-enamine 5s
resulting from attack on the more sterically hindered
carbon of strongly polarized C–C triple bond in 4f,
which indicating that the electronics of the alkynes
can be used to ensure full regioselctivity overruling
steric effects. These results show how the electronic
Next, we carried out palladium(0)-catalyzed ring
closing reaction of (E)-N-arylimine 3a and (Z)-
enamine 5a to prepare indole derivatives (Scheme 4).
In the presence of 5 mol% Pd(dba)2 and 6 mol%
XPhos, the cyclization reactions of compounds 3a
and 5a proceeded smoothly at 80 ºC in dioxane with
K3PO4 as base to give the desired indole derivatives
6a and 6b in 87% and 97% yield, respectively.
Scheme 4. Pd(0)-catalyzed indole synthesis
5
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10.1002/adsc.201800621
Advanced Synthesis & Catalysis
0.35 mmol g-1, which revealing almost the same gold
content as the fresh one. In our opinion, the high
catalytic activity and excellent reusability of the gold
catalyst relates to the efficient site isolation, to the
optimal dispersion of the active sites on the inner
channel walls and to the relatively strong interaction
between the phosphine ligand and the gold centre
supported on the MCM-41.
Table 3. Heterogeneous gold(I)-catalyzed regiospecific
hydroamination of various anilines with propiolic acid
derivatives[a,b]
Fig. 6. Recycle of the Ph2P-MCM-41-AuNTf2 catalyst.
Conclusions
In conclusion, we have developed a highly regio-
selective heterogeneous gold(I)-catalyzed intermo-
lecular hydroamination of ynamides and propiolic
acid derivatives with anilines, leading to only one of
the two possible regioisomers. This heterogeneous
intermolecular hydroamination has many attractive
features, such as: (1) the substrate scope is broad, and
a wide range of ynamides and propiolic acid deri-
vatives are allowed; (2) a variety of (E)-N-arylimines
and (Z)-enamines were obtained in mostly excellent
yields; (3) the reaction proceeds smoothly at room
temperature under air; (4) this new heterogeneous
gold(I) catalyst can easily be prepared via a simple
procedure from commercially available reagents and
recovered by filtration of the reaction solution. The
recovered catalyst (Ph2P-MCM-41-AuNTf2) can be
reused at least seven times without any loss of
activity. Our catalytic system not only solves the
basic problems of catalyst separation and recovery
but also avoids the use of AgNTf2 as a co-catalyst in
recycling process. This makes our protocol facile,
economical, and environmentally benign.
[a] Reaction conditions: 1 (1.1 mmol), 4 (1.0 mmol), Ph2P-
MCM-41-AuCl (2 mol%), AgNTf2 (2 mol%) in DCM (1.0
mL) at room temperature. [b] Isolated yield.
Under the optimized conditions, the stability and
recyclability of Ph2P-MCM-41-AuNTf2 were eva-
luated in the reaction between 2-iodoaniline (1a) and
3-(phenylethynyl)oxazolidin-2-one (2a). Filtration of
the crude mixture followed by washing of the
resulting solid with NH3·H2O, distilled water and
acetone allowed the easy recovery of the gold(I)
catalyst. The recovered catalyst could be recycled up
to seven times, and almost the same yield of 3a was
observed (Fig. 6). It is noteworthy that the reaction
catalyzed by the recovered catalyst didn’t need the
addition of AgNTf2 because the Ph2P-MCM-41-AuCl
had been changed to the Ph2P-MCM-41-AuNTf2 after
the first cycle. In addition, ICP-AES analysis was
conducted on the recovered catalyst after eight
consecutive runs, the gold content was found to be
Experimental Section
General Comments
All chemicals were reagent grade and used as purchased.
Mesoporous MCM-41,[20f] ynamides 2a-j,[23] propiolic acid
derivatives 4d-f[24] and 3-(propa-1,2-dienyl)oxazolidin-2-
one[25] were prepared according to literature procedures.
DCM was dried over CaH2 and distilled before use. All
6
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10.1002/adsc.201800621
Advanced Synthesis & Catalysis
reactions were carried out at room temperature under air in
oven-dried glassware. The products were purified by flash
chromatography on silica gel. Mixture of EtOAc and light
petroleum ether was generally used as eluent. All products
were characterized by comparison of their spectra and
physical data with authentic samples. IR spectra were
recorded on an FT-IR spectrometer. 1H and 13C NMR
spectra were recorded at 400 or 100 MHz with CDCl3 as
the solvent and TMS as an internal standard. Chemical
shifts are reported in δ (ppm) relative to TMS. HRMS
spectra were recorded on a Q-Tof spectrometer with
micromass MS software using electro-spray ionization
(ESI). Melting points are uncorrected. Gold content was
determined with inductively coupled plasma atom
emission spectrometry (ICP-AES). X-ray diffraction
(XRD) measurements were carried out at room tempera-
ture using an X-ray powder diffractmeter. X-ray energy
dispersive spectroscopy (EDS) was performed using a
microscope. Nitrogen adsorption/desorption isotherms
were measured at 77K, using a gravimetric adsorption
apparatus equipped with a CI electronic MK2-M5 micro-
balance and an Edwards Barocel pressure sensor. X-ray
photoelectron spectra (XPS) were recorded on a Kratos
Axis Ultra Imaging X-ray photoelectron spectrometer
equipped with a Mg anode and a multichannel detector.
catalyst was washed with NH3·H2O (2 × 3 mL), distilled
water (3 mL), and acetone (2 × 3 mL) and reused in the
next run. The filtrate was concentrated under reduced
pressure and the residue was purified by chromatography
on silica gel (eluent: light petroleum ether/ethyl acetate) to
afford the desired product.
General Procedure for the Heterogeneous Gold(I)-
Catalyzed Intermolecular Hydroamination of Propiolic
Acid Derivatives or Phenylacetylene with Anilines.
A small Schlenk tube was charged with Ph2P-MCM-41-
AuCl (56 mg, 0.02 mmol), AgNTf2 (7.8 mg, 0.02 mmol)
and dry DCM (0.5 mL) and the resulting mixture was
stirred at room temperature for 30 min. To this mixture
was added the aniline 1 (1.1 mmol), the propiolic acid
derivative 4 or phenylacetylene (1.0 mmol), and dry DCM
(0.5 mL) and the tube was sealed. The reaction mixture
was stirred at room temperature for 5-24 h and then diluted
with ethyl acetate (10 mL) and filtered. The gold catalyst
was washed with NH3·H2O (2 × 3 mL), distilled water (3
mL), and acetone (2 × 3 mL) and reused in the next run.
The filtrate was concentrated under reduced pressure and
the residue was purified by chromatography on silica gel
(eluent: light petroleum ether/ethyl acetate) to afford the
desired product.
Preparation of Ph2P-MCM-41-AuCl Complex
General Procedure for the Pd(0)-Catalyzed Indole
Synthesis
2-(Diphenylphosphino)ethyltriethoxysilane (0.565 g, 1.5
mmol) was added to a suspension of 2.0 g of the MCM-41
in 120 mL of dry toluene. The mixture was stirred at
100 °C for 24 h under Ar. Then the solid was filtered,
washed with CHCl3 (20 mL), and dried in vacuum at
140 °C for 5 h. The dried white solid was then soaked in a
solution of 2.8 g of Me3SiCl in 100 mL of dry toluene at
room temperature under stirring for 24 h. The solid product
was filtered, washed with acetone (3 × 20 mL), and dried
in vacuum at 120 °C for 3 h to obtain 2.413 g of hybrid
material Ph2P-MCM-41. The phosphine content was found
to be 0.43 mmol g-1 by elemental analysis.
The hydroamination product 3a or 5a (0.5 mmol), Pd(dba)2
(5 mol%), XPhos (6 mol%), and K3PO4 (1.5 mmol) were
dissolved in dioxane (1.0 mL) under Ar and the reaction
mixture was stirred at 80 °C for 24 h. Then the reaction
mixture was allowed to cool to room temperature,
quenched with sat. NH4Cl (aq.) and extracted with EtOAc
(3 × 10 mL). The combined organic phases were washed
with brine, dried over MgSO4, filtered, and evaporated in
vacuo. The crude mixture was purified by chromatography
on silica gel (eluent: light petroleum ether/ethyl acetate) to
afford the desired product 6a or 6b.
In a small Schlenk tube, 1.00 g of the above-func-
tionalized MCM-41 (Ph2P-MCM-41) was mixed with
Me2SAuCl (112 mg, 0.38 mmol) in 30 mL of dry CH2Cl2.
The mixture was stirred at room temperature for 8 h under
an argon atmosphere. The solid product was filtered,
washed with CH2Cl2 and dried under vacuum to give 1.046
g of a gray gold complex (Ph2P-MCM-41-AuCl). The gold
content was found to be 0.36 mmol g-1 by ICP-AES.
Acknowledgements
We thank the National Natural Science Foundation of China (No.
21462021), the Natural Science Foundation of Jiangxi Province
of China (No. 20161BAB203086) and Key Laboratory of
Functional Small Organic Molecule, Ministry of Education (No.
KLFS-KF-201704) for financial support.
General Procedure for the Heterogeneous Gold(I)-
Catalyzed Intermolecular Hydroamination of Anilines
with Ynamides or Allenamide.
References
A small Schlenk tube was charged with Ph2P-MCM-41-
AuCl (28 mg, 0.01 mmol), AgNTf2 (3.9 mg, 0.01 mmol)
and dry DCM (0.5 mL) and the resulting mixture was
stirred at room temperature for 30 min. To this mixture
was added the aniline 1 (1.1 mmol), the ynamide 2 or
allenamide (1.0 mmol), and dry DCM (0.5 mL) and the
tube was sealed. Then the reaction mixture was stirred at
room temperature for 4 h, unless otherwise noted, and
diluted with ethyl acetate (10 mL) and filtered. The gold
[1] a) S. Kobayashi, H. Ishitani, Chem. Rev. 1999, 99,
1069-1094; b) J. S. Sandhu, B. Sain, Heterocycles
1987, 26, 777-818; c) S. Fustero, M. G. Torre, V.
Jofre, R. P. Carlon, A. Navarro, A. S. Fuentes, J.
Org. Chem. 1998, 63, 8825-8836; d) C. Spino,
Angew. Chem. Int. Ed. 2004, 43, 1764-1766; e) S.
Mukherjee, J. W. Yang, S. Hoffman, B. List, Chem.
Rev. 2007, 107, 5471-5569; f) D. M. Hodgson, N. S.
7
This article is protected by copyright. All rights reserved.

10.1002/adsc.201800621
Advanced Synthesis & Catalysis
Kaka, Angew. Chem. Int. Ed. 2008, 47, 9958-9960;
g) L. Huang, M. Arndt, K. Gooβen, H. Heydt, L. J.
Gooβen, Chem. Rev. 2015, 115, 2596-2697.
Tillack, N. Schwarz, M. Beller, ChemSusChem 2008,
1, 333-338.
[11] A. Reyes-Sanchez, I. Garcia-Ventura, J. J. Garcia,
Dalton Trans. 2014, 43, 1762-1768.
[2] a) T. E. Muller, M. Beller, Chem. Rev. 1998, 98,
675-704; b) M. Beller, J. Seayad, A. Tillack, H. J.
Jiao, Angew. Chem. Int. Ed. 2004, 43, 3368-3398; c)
R. Severin, S. Doye, Chem. Soc. Rev. 2007, 36,
1407-1420; d) T. E. Muller, K. C. Hultzsch, M. Yus,
F. Foubelo, M. Tada, Chem. Rev. 2008, 108, 3795-
3892; e) R. Chinchilla, C. Najera, Chem. Rev. 2014,
114, 1783-1826; f) E. Bernoud, C. Lepori, M.
Mellah, E. Schulz, J. Hannedouche, Catal. Sci.
Technol. 2015, 5, 2017-2037.
[3] a) E. Haak, I. Bytschkov, S. Doye, Angew. Chem. Int.
Ed. 1999, 38, 3389-3391; b) E. Haak, H.
Siebeneicher, S. Doye, Org. Lett. 2000, 2, 1935-
1937; c) F. Pohlki, S. Doye, Angew. Chem. Int. Ed.
2001,40, 2305-2308; d) J. S. Johnson, R. G.
Bergman, J. Am. Chem. Soc. 2001, 123, 2923-2924;
e) B. F. Straub, R. G. Bergman, Angew. Chem. Int.
Ed. 2001,40, 4632-4635; f) Y. Shi, J. T. Ciszewski,
A. L. Odom, Organometallics 2001, 20, 3967-3969;
g) C. Cao, Y. Shi, A. L. Odom, Org. Lett. 2002, 4,
2853-2856; h) A. Tillack, I. G. Castro, C. G.
Hartung, M. Beller, Angew. Chem. Int. Ed. 2002,41,
2541-2543.
[12] a) A. E. Panarina, A. V. Dogadina, V. I. Zakharov, B.
I. Ionin, Tetrahedron Lett. 2001, 42, 4365-4368; b)
D. W. Robbins, J. F. Hartwig, Science 2011, 333,
1423-1427; c) R. Bahri, R. Blieck, B. Jamoussi, M.
Taillefer, F. Monnier, Chem. Commun. 2015, 51,
11210-11212; d) R. Bahri, B. Jamoussi, A. van Der
Lee, M. Taillefer, F. Monnier, Org. Lett. 2015, 17,
1224-1227; e) J. G. Taylor, N. Whittall, K. K. Hii,
Org. Lett. 2006, 8, 3561-3564; f) C. Munro-Leighton,
S. A. Delp, N. M. Alsop, E. D. Blue, T. B. Gunnoe,
Chem. Commun. 2008, 111-113; g) R. L. Giles, J. D.
Sullivan, A. M. Steiner, R. E. Looper, Angew. Chem.
Int. Ed. 2009, 48, 3116-3120; h) T. Ishikawa, T.
Sonehara, M. Minakawa, M. Kawatsura, Org. Lett.
2016, 18, 1422-1425.
[13] a) R. S. Robinson, M. C. Dovey, D. Gravestock,
Tetrahedron Lett. 2004, 45, 6787-6789; b) N.
Lingaiah, N. S. Babu, K. M. Reddy, P. S. S. Prasad,
I. Suryanarayana, Chem. Commun. 2007, 278-279;
c) H. Cao, X. Wang, H. Jiang, Q. Zhu, M. Zhang, H.
Liu, Chem.-Eur. J. 2008, 14, 11623-11633.
[14] a) Y. Li, T. J. Marks, Organometallics 1996, 15,
3770; b) Y. Li, T. J. Marks, J. Am. Chem. Soc. 1998,
120, 1757-1771.
[4] a) P. J. Walsh, A. M. Baranger, R. G. Bergman, J.
Am. Chem. Soc. 1992, 114, 1708-1719; b) A. M.
Baranger, P. J. Walsh, R. G. Bergman, J. Am. Chem.
Soc. 1993, 115, 2753-2763; c) Q. Sun, Y. Wang, D.
Yuan, Y. Yao, Q. Shen, Organometallics 2014, 33,
994-1001.
[15] a) A. Haskel, T. Straub, M. S. Eisen, Organometallics
1996, 15, 3773-3775; b) T. Straub, A. Haskel, T. G.
Neyroud, M. Kapon, M. Botoshansky, M. S. Eisen,
Organometallics 2001, 20, 5017-5035.
[5] a) Y. Uchimaru, Chem. Commun. 1999, 1133-1134;
b) M. Tokunaga, M. Eckert, Y. Wakatsuki, Angew.
Chem. Int. Ed. 1999, 38, 3222-3225; c) C. S. Yi, S.
Y. Yun, I. A. Guzei, J. Am. Chem. Soc. 2005, 127,
5782-5783; d) C. S. Yi, S. Y. Yun, J. Am. Chem.
Soc. 2005, 127, 17000-17006; e) Y. Kuninobu, Y.
Nishina, K. Takai, Org. Lett. 2006, 8, 2891-2893.
[6] a) C. G. Hartung, A. Tillack, H. Trauthwein, M.
Beller, J. Org. Chem. 2001, 66, 6339-6343; b) Y.
Fukumoto, H. Asai, M. Shimizu, N. Chatani, J. Am.
Chem. Soc. 2007, 129, 13792-13793; c) K. Sakai, T.
Kochi, F. Kakiuchi, Org. Lett. 2011, 13, 3928-3931;
[16] For selected recent reviews of gold catalysis, see: a)
D. J. Gorin, F. D. Toste, Nature 2007, 446, 395-403;
b) A. S. K. Hashmi, Chem. Rev. 2007, 107, 3180-
3211; c) D. J. Gorin, B. D. Sherry, F. D. Toste,
Chem. Rev. 2008, 108, 3351-3378; d) H. A. Wegner,
M. Auzias, Angew. Chem. Int. Ed. 2011, 50, 8236-
8247; e) A. Corma, A. Leyva-Perez, M. J. Sabater,
Chem. Rev. 2011, 111, 1657-1712; f) C. Obradors, A.
M. Echavarren, Acc. Chem. Res. 2014, 47, 902-912;
g) R. Dorel, A. M. Echavarren, Chem. Rev. 2015,
115, 9028-9072; h) D. B. Huple, S. Ghorpade, R.-S.
Liu, Adv. Synth. Catal. 2016, 358, 1348-1367.
d) E. Kumaran, W. K. Leong, Organometallics 2012, [17] a) S. N. Karad, R.-S. Liu, Angew. Chem. Int. Ed.
31, 1068-1672; e) Q.-A. Chen, Z. Chen, V. M. Dong,
J. Am. Chem. Soc. 2015, 137, 8392-8395; f) E.
Kumaran, W. K. Leong, Organometallics 2015, 34,
1779-1782.
2014, 53, 9072-9076; b) C. Shu, Y.-H. Wang, B.
Zhou, X.-L. Li, Y.-F. Ping, X. Lu, L.-W. Ye, J. Am.
Chem. Soc. 2015, 137, 9567-9570; c) Y.-L. Chen, P.
Sharma, R.-S. Liu, Chem. Commun. 2016, 52, 3187-
3190; d) Z. Zeng, H. Jin, X. Song, Q. Wang, M.
Rudolph, F. Rominger, A. S. K. Hashmi, Chem.
Commun. 2017, 53, 4304-4307; e) W. Xu, G. Wang,
N. Sun, Y. Liu, Org. Lett. 2017, 19, 3307-3310; f) X.
Chen, J. T. Merrett, P. W. H. Chan, Org. Lett. 2018,
20, 1542-1545; g) S. S. Giri, R.-S. Liu, Chem. Sci.
2018, 9, 2991-2995.
[7] a) I. Kadota, A. Shibuya, L. M. Lutete, Y.
Yamamoto, J. Org. Chem. 1999, 64, 4570-4571; b)
T. Shimada, Y. Yamamoto, J. Am. Chem. Soc. 2002,
124, 12670-12671; c) T. Shimada, G. B.
Bajracharya, Y. Yamamoto, Eur. J. Org. Chem.
2005, 59-62.
[8] R.-Y. Lai, K. Surekha, A. Hayashi, F. Ozawa, Y.-H.
Liu, S.-M. Peng, S.-T. Liu, Organometallics 2007,
26, 1062-1068.
[9] J.-J. Brunet, N. C. Chu, O. Diallo, S. Vincendeau, J.
Mol. Catal. A; Chem. 2005, 240, 245-248.
[10] a) K. Alex, A. Tillack, N. Schwarz, M. Beller, Angew.
Chem. Int. Ed. 2008, 47, 2304-2307; b) K. Alex, A.
[18] a) C.-Y. Zhou, P. W. H. Chan, C.-M. Che, Org. Lett.
2006, 8, 325-328; b) Y. Zhang, J. P. Donahue, C.-J.
Li, Org. Lett. 2007, 9, 627-630; c) E. Alvarado, A. C.
Badaj, T. G. Larocque, G. G. Lavoie, Chem.- Eur. J.
2012, 18, 12112-12121; d) M. Katari, M. N. Rao, G.
Rajaraman, P. Ghosh, Inorg. Chem. 2012, 51, 5593-
8
This article is protected by copyright. All rights reserved.

10.1002/adsc.201800621
Advanced Synthesis & Catalysis
5604; e) V. Lavallo, J. H. Wright, F. S. Tham, S.
[21] a) A. Corma, P. Concepcion, I. Dominguez, V. Forne,
M. J. Sabater, J. Catal. 2007, 251, 39-47; b) N. T.
Patil, ChemCatChem 2011, 3, 1121-1125; c) A.
Seral-Ascaso, A. Luquin, M. J. Lazaro, G. F. de la
Fuente, M. Laguna, E. Munoz, Appl. Catal., A 2013,
456, 88-95; d) J. Zhao, Z. Zheng, S. Bottle, A. Chou,
S. Sarina, H. Zhu, Chem. Commun. 2013, 49, 2676-
2678; e) L.-C. Lee, Y. Zhao, ACS Catal. 2014, 4,
688-691; f) S. Liang, L. Hammond, B. Xu, G. B.
Hammond, Adv. Synth. Catal. 2016, 358, 3313-3318.
[22] a) C. T. Kresge, M. E. Leonowicz, W. J. Roth, J. C.
Vartuli, J. S. Beck, Nature 1992, 359, 710-712; b) A.
Corma, Top. Catal. 1997, 4, 249-260; c) R. M.
Martin-Aranda, J. Cejka, Top. Catal. 2010, 53, 141-
153.
Quinlivan, Angew. Chem. Int. Ed. 2013, 52, 3172-
3176; f) D. Malhotra, M. S. Mashuta, G. B.
Hammond, B. Xu, Angew. Chem. Int. Ed. 2014, 53,
4456-4459.
[19] a) E. Mizushima, T. Hayashi, M. Tanaka, Org. Lett.
2003, 5, 3349-3352; b) X. Zeng, G. D. Frey, S.
Kousar, G. Bertrand, Chem.- Eur. J. 2009, 15, 3056-
3060; c) S. Kramer, K. Dooleweerdt, A. T.
Lindhardt, M. Rottlander, T. Skrydstrup, Org. Lett.
2009, 11, 4208-4211; d) H. Duan, S. Sengupta, J. L.
Petersen, N. G. Akhmedov, X. Shi, J. Am. Chem.
Soc. 2009, 131, 12100-12102; e) K. D. Hesp, M.
Stradiotto, J. Am. Chem. Soc. 2010, 132, 18026-
18029.
[20] a) A. Corma, C. Gonzalez-Arellano, M. Iglesias, M.
T. Navarro, F. Sanchez, Chem. Commun. 2008,
6218-6220; b) A. Corma, E. Gutierrez-Puebla, M.
Iglesias, A. Monge, S. Perez-Ferreras, F. Sanchez,
Adv. Synth. Catal. 2006, 348, 1899-1907; c) M.
Raducan, C. Rodriguez-Escrich, X. C. Cambeiro, E.
C. Escudero-Adan, M. A. Pericas, A. M. Echavarren,
Chem. Commun. 2011, 47, 4893-4895; d) G.
Villaverde, A. Corma, M. Iglesias, F. Sanchez, ACS
Catal. 2012, 2, 399-406; e) S. Tsupova, A. Cadu, S.
A. C. Carabineiro, M. Rudolph, A. S. K. Hashmi, J.
Catal. 2017, 350, 97-102; f) W. Yang, R. Zhang, F.
Yi, M. Cai, J. Org. Chem. 2017, 82, 5204-5211; g)
Q. Nie, F. Yi, B. Huang, M. Cai, Adv. Synth. Catal.
2017, 359, 3968-3976; h) W. Yang, L. Wei, T. Yan,
M. Cai, Catal. Sci. Technol. 2017, 7, 1744-1755.
[23] a) K. Dooleweerdt, H. Birkedal, T. Ruhland, T.
Skrydstrup, J. Org. Chem. 2008, 73, 9447-9450; b) P.
W. Davies, A. Cremonesi, N. Martin, Chem.
Commun. 2011, 47, 379-381; c) R. Doi, I. Abdullah,
T. Taniguchi, N. Saito, Y. Sato, Chem. Commun.
2017, 53, 7720-7723; d) T. Hamada, X. Ye, S. S.
Stahl, J. Am. Chem. Soc. 2008, 103, 833-840; e) A.
Mukherjee, R. B. Dateer, R. Chaudhuri, S. Bhunia, S.
R. Karad, R.-S. Liu, J. Am. Chem. Soc. 2011, 133,
15372-15375.
[24] a) N. I. Nilov, A. V. Vasilyev, Tetrahedron Lett.
2015, 56, 5714-5715; b) X.-Y. Chang, K.-H. Low,
J.-Y. Wang, J.-S. Huang, C.-M. Che, Angew. Chem.
2016, 128, 10468-10472.
[25] A. W. Hill, M. R. J. Elsegood, M. C. Kimber, J. Org.
Chem. 2010, 75, 5406-5409.
9
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FULL PAPER
Regiospecific Hydroamination of Unsymmetrical
Electron-Rich and Electron-Poor Alkynes with
Anilines Catalyzed by Gold(I) Immobilized in
MCM-41
Adv. Synth. Catal. 2018, 360, Page – Page
Dayi Liu, Quan Nie, Rongli Zhang and Mingzhong
Cai*
10
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