Heterogeneous gold(I)-catalyzed hydroamination of allenamides with arylamines toward allylamino E-enamides

Article abstract of DOI:10.1080/00397911.2021.1902535

A novel and highly efficient heterogeneous gold(I)-catalyzed hydroamination of allenamides with arylamines has been developed that proceeds effectively under mild conditions and offers a general and practical route for the synthesis of allylamino E-enamides with good to excellent yields and high stereoselectivity. The supported gold(I) catalyst can be reused at least seven times without any apparent decrease in the catalytic activity.

Full text of DOI:10.1080/00397911.2021.1902535

Synthetic Communications
An International Journal for Rapid Communication of Synthetic Organic
Chemistry
ISSN: (Print) (Online) Journal homepage: https://www.tandfonline.com/loi/lsyc20
Heterogeneous gold(I)-catalyzed hydroamination
of allenamides with arylamines toward allylamino
E-enamides
Minhua Jiang, Dayi Liu & Mingzhong Cai
To cite this article: Minhua Jiang, Dayi Liu & Mingzhong Cai (2021) Heterogeneous gold(I)-
catalyzed hydroamination of allenamides with arylamines toward allylamino E-enamides, Synthetic
Communications, 51:11, 1700-1711, DOI: 10.1080/00397911.2021.1902535
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2021, VOL. 51, NO. 11, 1700–1711
https://doi.org/10.1080/00397911.2021.1902535
Heterogeneous gold(I)-catalyzed hydroamination of
allenamides with arylamines toward allylamino E-enamides
Minhua Jianga,b, Dayi Liub, and Mingzhong Caib
b
aSchool of New Energy Science and Engineering, Xinyu University, Xinyu, China; Key Laboratory of
Functional Small Organic Molecule, Ministry of Education, College of Chemistry & Chemical
Engineering, Jiangxi Normal University, Nanchang, China
ABSTRACT
ARTICLE HISTORY
Received 11 November 2020
A novel and highly efficient heterogeneous gold(I)-catalyzed hydroa-
mination of allenamides with arylamines has been developed that
proceeds effectively under mild conditions and offers a general and
practical route for the synthesis of allylamino E-enamides with good
to excellent yields and high stereoselectivity. The supported gold(I)
catalyst can be reused at least seven times without any apparent
decrease in the catalytic activity.
KEYWORDS
Gold; hydroamination;
enamide; allenamide;
heterogeneous catalysis
GRAPHICAL ABSTRACT
Introduction
The enamide moiety, especially the E-enamide framework, appears in many natural
products[1] and pharmaceuticals with antitumor, antibiotic, anthelmintic, cytotoxic, and
antifungal activities.[2] Enamides are also important synthetic intermediates in the con-
struction of heterocycles and amines,[3] and serve as useful substrates in various organic
transformations including cycloaddition,[4] cross-coupling/Heck reaction,[5] enantiose-
lective addition,[6] asymmetric hydrogenation/halogenation,[7] and C–H functionaliza-
tion.[8] The traditional routes to enamides involve the addition of amides to alkynes,[9]
condensation of carbonyl groups with amides,[10] acylation of imines,[11] or Curtius
rearrangement.[12] These approaches generally lack regioselectivity and/or E/Z stereo-
selectivity and usually require harsh reaction conditions. In recent years, transition
metal-catalyzed syntheses of enamides have been well developed including the addition
CONTACT Mingzhong Cai
caimzhong@163.com
Key Laboratory of Functional Small Organic Molecule, Ministry of
Education, College of Chemistry & Chemical Engineering, Jiangxi Normal University, Nanchang, China.
Supplemental data for this article can be accessed on the publisher’s website.
ß 2021 Taylor & Francis Group, LLC

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Scheme 1. Heterogeneous gold(I)-catalyzed hydroamination of allenamides with arylamines.
of amides to alkynes,[13] the isomerization of N-allylamides,[14] the cross-coupling of
amides with vinyl compounds,[15] and the semihydrogenation of ynamides,[16] but prob-
lems with functional group tolerance and non-recyclability of metals have persisted.
Gold catalysts have been widely employed in organic synthesis for their unique ability
to activate carbon–carbon p bonds, thereby allowing the construction of carbon–carbon
and carbon–heteroatom bonds by nucleophilic attack on these activated multiple
bonds.[17] Allenamides represent a fascinating and versatile functional group and have
been widely applied to various organic reactions including radical cyclizations,[18a]
cyclopropanations,[18b] tandem epoxidation/cycloadditions,[18c,d] [4 þ 2] and [4 þ 3]
cycloadditions,[18e–g] Pauson-Khand cyclizations,[18h] palladium-mediated transforma-
tions,[18i] acid-catalyzed cyclization/rearrangements,[18j] and base-catalyzed CO2 cap-
ture.[18k] Recently, Kimber et al. reported gold(I)-catalyzed nucleophilic addition of
electron-rich aromatics or heteroaromatics to allenamides leading to E-enamides and
hydroamination of allenamides with arylamines toward allylamino E-enamides.[19]
However, homogeneous gold catalysis suffers from the high cost and non-recyclability
of gold catalysts as well as the decay of cationic gold, which restrict their applications in
large-scale synthesis and in industry.[20] Recycling of transition metal catalysts, espe-
cially expensive and/or toxic heavy metal complexes, still remains an important chal-
lenge in the chemical and pharmaceutical industries. Anchoring homogeneous gold
complexes through covalent bond formation onto various solid supports appears to be
an effective way to solve this problem.[21] Xu and coworkers reported the synthesis of
Z-enamides through heterogeneous Au/TiO2-catalyzed stereoselective hydrogenation of
ynamides.[22] Recently, we report the synthesis of an MCM-41-anchored diphenylphos-
phine gold(I) complex [MCM-41-Ph2P-AuNTf2] and its successful application to oxida-
tive ring expansion of 2-alkynyl-1,2-dihydropyridines or -quinolines leading to
functionalized azepine derivatives under mild conditions.[23] To further expand applica-
tion range of this heterogeneous gold(I) catalyst, herein, we wish to report an efficient
heterogeneous gold(I)-catalyzed intermolecular hydroamination of allenamides with
arylamines using the MCM-41-Ph2P-AuNTf2 complex as the catalyst toward allylamino
E-enamides stereoselectively and in good to excellent yields (Scheme 1).
Results and discussion
Several ethyldiphenylphosphine-functionalized MCM-41-anchored gold(I) complexes
[MCM-41-Ph2P-AuX, X ¼ Cl, OTf, NTf2, SbF6, and BF4] were facilely prepared by a
simple procedure from commercially available starting materials as depicted
in Scheme 2.[23] First, the condensation of mesoporous MCM-41 with commercially
available 2-(diphenylphosphino)ethyltriethoxysilane in toluene at reflux, followed by
silylation with Me3SiCl at room temperature generated ethyldiphenylphosphine-func-
tionalized MCM-41 material (MCM-41-Ph2P). The MCM-41-Ph2P was then reacted

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M. JIANG ET AL.
Scheme 2. Preparation of the MCM-41-Ph2P-AuX complexes.
with Me2SAuCl in dichloromethane (DCM) at room temperature to provide MCM-41-
Ph2P-AuCl, which was subsequently treated with various silver salts (AgX ¼ AgOTf,
AgNTf2, AgSbF6 and AgBF4) in DCM at room temperature to give the ethyldiphenyl-
phosphine-functionalized MCM-41-anchored gold(I) complexes [MCM-41-Ph2P-AuX,
X ¼ OTf, NTf2, SbF6 and BF4] as gray powders.
Initial experiments with 3-(propa-1,2-dienyl)oxazolidin-2-one (1a) and aniline (2a)
were conducted to optimize the reaction conditions, and the results are given in
Table 1. At first, various supported gold(I) complexes were used as catalysts at room
temperature in 1,2-dichloroethane (DCE) to evaluate their catalytic efficiency (entries
1–5). When MCM-41-Ph2P-AuCl was used as the catalyst, only a trace of the product
3a was detected (entry 1). However, changing the counterion (Clˉ) on the gold catalyst
ˉ
ˉ
ˉ
to OTfˉ, NTf2 , SbF6 , or BF4 has an important influence on the reaction course, as the
desired 3a was obtained in 32–85% yields (entries 2–5) and MCM-41-Ph2P-AuNTf2
gave the best result (entry 3). The reaction did not occur in the absence of any catalyst
(entry 6). Also, the use of AgNTf2 alone as the catalyst did not deliver the desired 3a
(entry 7), which revealing the unique catalytic role of gold catalyst. We next examined
the effect of solvents on the model reaction (entries 8–13). Replacement of DCE with
MeCN, dichloromethane (DCM), or toluene afforded the desired 3a in 65–86% yields
and DCM was found to be the best option (entry 9), while other solvents such as
dioxane, DMF and DMSO were substantially less effective (entries 11–13). Reducing the
amount of MCM-41-Ph2P-AuNTf2 to 0.5 mol% resulted in a slight decrease in the yield
of 3a, but a long reaction time was required (entry 14). When the amount of MCM-41-
Ph2P-AuNTf2 was increased to 3 mol%, the reaction was completed within 2 h, but no
improvement in the yield was observed (entry 15). The use of homogeneous
Ph3PAuNTf2 (1 mol%) as the catalyst also delivered the desired 3a in 86% yield (entry
16), which indicating that the catalytic efficiency of heterogeneous MCM-41-Ph2P-
AuNTf2 was similar to that of homogeneous Ph3PAuNTf2. Thus, the optimized reaction
conditions for this transformation were the use of MCM-41-Ph2P-AuNTf2 (1 mol%) in
DCM as solvent at room temperature for 4 h (entry 9).
For an immobilized precious metal catalyst, it is important to evaluate its ease of sep-
aration, stability and recyclability. The MCM-41-Ph2P-AuNTf2 catalyst can be readily
separated and recovered through a simple filtration process. We next examined the

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Table 1. Optimization of reaction conditions.a.
Entry
Catalyst
Solvent
Time (h)
Yield (%)b
1
2
3
4
5
6
7
8
MCM-41-Ph2P-AuCl
MCM-41-Ph2P-AuOTf
MCM-41-Ph2P-AuNTf2
MCM-41-Ph2P-AuSbF6
MCM-41-Ph2P-AuBF4
–
DCE
DCE
DCE
DCE
DCE
DCE
DCE
MeCN
DCM
toluene
dioxane
DMF
DMSO
DCM
DCM
DCM
12
8
4
12
12
12
12
5
4
8
8
12
12
10
2
trace
83
85
62
32
0
AgNTf2 (5 mol%)
0
MCM-41-Ph2P-AuNTf2
MCM-41-Ph2P-AuNTf2
MCM-41-Ph2P-AuNTf2
MCM-41-Ph2P-AuNTf2
MCM-41-Ph2P-AuNTf2
MCM-41-Ph2P-AuNTf2
MCM-41-Ph2P-AuNTf2
MCM-41-Ph2P-AuNTf2
Ph3PAuNTf2 (1 mol%)
76
86
65
54
18
13
81
85
86
9
10
11
12
13
14c
15d
16
4
aReaction conditions: 1a (0.5 mmol), 2a (0.55 mmol), solvent (3.0 mL), and room temperature.
bIsolated yield.
cThe gold catalyst (0.5 mol%) was used.
dThe gold catalyst (3 mol%) was used.
recycling of the gold(I) catalyst in the hydroamination reaction of 3-(propa-1,2-dieny-
l)oxazolidin-2-one (1a) with 2-iodoaniline and the results are provided in Table 2. After
completion of the hydroamination reaction, the gold(I) catalyst was recovered by filtra-
tion of the reaction solution, followed by washing with acetone. After being air-dried,
the recovered catalyst can be reused directly without further purification. The recovered
gold catalyst was used in the next cycle, and almost the same yield was obtained for
eight consecutive runs. In addition, the gold content of the recovered catalyst after eight
consecutive cycles was measured to be 0.36 mmol gꢀ1 by ICP-AES analysis, which
showing almost the consistent gold content as the fresh one (0.37 mmol gꢀ1).
Compared with previously reported approach,[19b] the current method has significant
advantages of easy separation from the product and excellent recyclability of the hetero-
geneous gold(I) catalyst.
Having established the optimum reaction conditions, we started to explore the scope
of this heterogeneous gold(I)-catalyzed intermolecular hydroamination by using a var-
iety of arylamines and various allenamides as substrates, and the results are listed in
Table 3. para- or meta-Substituted anilines 2b–2f bearing either electron-withdrawing
or electron-donating groups successfully added to allenamide 1a to give the correspond-
ing E-enamides 3b–3f in 61–95% yields. The results indicated that the electronic nature
of substituents on anilines has a limited influence on the heterogeneous gold(I)-cata-
lyzed hydroamination reaction. Sterically hindered ortho-substituted anilines 2g–2j also
participated in the hydroamination reaction effectively to afford the desired E-enamides
3g–3j in 82–96% yields. Notably, a heteroarylamine 2k was compatible in the reaction,

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M. JIANG ET AL.
Table 2. Recycle of the MCM-41-Ph2P-AuNTf2 catalyst.a.
Entry
Gold catalyst
Yieldb (%)
Entry
Gold catalyst
Yieldb (%)
1
2
3
4
Fresh
96
95
95
94
5
6
7
8
Recycle 4
Recycle 5
Recycle 6
Recycle 7
95
93
94
93
Recycle 1
Recycle 2
Recycle 3
aReaction conditions: 1a (0.5 mmol), 2-iodoaniline (0.55 mmol), MCM-41-Ph2P-AuNTf2 (1 mol%), DCM (3.0 mL), room tem-
perature, 4 h.
bIsolated yield.
thereby providing the expected product 3k in a moderate yield of 65%. When N-meth-
ylanilines 2l–2m were used as substrates, the reaction proceeded smoothly to give the
corresponding N-methylenamides 3l–3m in 85–96% yields. A wide range of functional
groups such as methyl, methoxy, fluoro, chloro, bromo, iodo, nitro and ester were toler-
ated well.
We next performed the hydroamination reaction with chiral and acyclic allenamides
as substrates under the optimized conditions, and the results are also summarized in
Table 3. Chiral allenamide 1b could undergo hydroamination with electron-nuetral,
electron-deficient or electron-rich anilines smoothly giving the corresponding chiral
enamides 3n–3r in 70–89% yields. Besides, the reaction of chiral allenamide 1b with N-
methylanilines also worked well to deliver the expected chiral N-methylenamides 3s–3t
in good yields. Finally, acyclic allenamides 1c and 1d also readily participated in the
hydroamination reaction with various arylamines, but the desired enamides 3u–3y were
obtained in only moderate yields of 45–58% due to their poorer stability. The stereo-
1
chemistry of the E-enamide double bond was confirmed by their H NMR spectra, in
which vinyl proton shows a coupling constant of 14.0–14.4 Hz. In order to dismiss the
possibility of isomerization from cis to trans, we also conducted NMR studies of all the
products prior to workup, which indicating that no cis-isomers were observed in
all cases.
To verify whether the observed hydroamination was due to the heterogeneous MCM-
41-Ph2P-AuNTf2 catalyst or to a soluble gold species leached from this catalyst, we
focused on the hydroamination reaction of 3-(propa-1,2-dienyl)oxazolidin-2-one (1a)
with aniline (2a). We filtered off the MCM-41-Ph2P-AuNTf2 catalyst after 2 h and
allowed the catalyst-free filtrate to react further at room temperature for 2 h. It was
found that, after removal of the Au catalyst, no increase in the conversion of 1a was
observed, revealing that leached gold species from the catalyst (if any) should not be
responsible for the observed transformation. Besides, no gold species could be detected
in the clear filtrate based on ICP-AES analysis. These results indicate that the MCM-41-
Ph2P-AuNTf2 complex was stable during the hydroamination and the observed reaction
was intrinsically heterogeneous.

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Table 3. Heterogeneous gold(I)-catalyzed hydroamination of allenamides with arylamines.a,b
.
aReaction conditions: 1 (0.5 mmol), 2 (0.55 mmol), MCM-41-Ph2P-AuNTf2 (1 mol%), DCM (3.0 mL), room temperature, 4 h.
bIsolated yield.

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M. JIANG ET AL.
Scheme 3. Proposed catalytic cycle.
A possible mechanism for this heterogeneous gold(I)-catalyzed hydroamination reac-
tion of allenamides with arylamines is shown in Scheme 3.[19b] First, coordination of
the MCM-41-Ph2P-AuNTf2 complex to allene moiety in allenamides 1 produces an
MCM-41-bound gold(I)–allene–p complex intermediate A, which is further converted
into an MCM-41-bound conjugated vinylgold(I) intermediate B. Then intermediate B
undergoes 1,2-addition with the aniline derivatives 2 to provide intermediate C. Finally,
the protodeauration of intermediate C occurs to afford the desired E-enamide 3 and
regenerate the gold(I) complex to complete the catalytic cycle.
Conclusions
In summary, we have developed an efficient and practical heterogeneous
gold(I)-catalyzed hydroamination of allenamides with arylamines by using the MCM-
41-Ph2P-AuNTf2 complex as the catalyst leading to allylamino E-enamides which have
the potential to be important building blocks in organic synthesis since they have two
valuable functionalities, allyl amines and enamides, within one framework. The current
method has some attractive advantages including readily available starting materials,
simple procedure, mild reaction conditions, high yields, excellent stereoselectivity, and
easy recycle of the gold catalyst, thus offering an attractive alternative to synthesize
E-enamides.
Experimental
All chemicals were reagent grade and used as purchased. Dichloromethane (DCM) was
dried over P2O5 and distilled before use. The MCM-41-Ph2P-AuNTf2 complex was

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prepared from commercially easily available materials according to our previous proced-
ure,[23] the gold content was determined to be 0.37 mmol gꢀ1 according to the ICP-AES
analysis. Cyclic allenamides[24] and acyclic allenamides[25] were prepared by referring to
literature methods. The products were purified by flash chromatography on silica gel.
1
Mixture of petroleum ether and EtOAc was generally used as eluent. H NMR spectra
were recorded on a Bruker Avance 400 MHz spectrometer with TMS as an internal
standard in CDCl3 as solvent. 13C NMR spectra (100 MHz) were recorded on a Bruker
Avance 400 MHz spectrometer in CDCl3 as solvent. HRMS spectra were recorded on a
Q-Tof spectrometer with micromass MS software using electrospray ionization (ESI).
Gold content was determined with inductively coupled plasma atom emission
Atomscan16 (ICP-AES, TJA Corporation).
General procedure for heterogeneous gold(I)-catalyzed hydroamination reaction
of allenamides with arylamines
A mixture of allenamide 1 (0.5 mmol), arylamine 2 (0.55 mmol), and MCM-41-Ph2P-
AuNTf2 (14 mg, 0.005 mmol) in DCM (3 mL) was stirred at room temperature for 4 h
(TLC monitored). The reaction mixture was diluted with ethyl acetate (5 mL) and fil-
tered. The gold catalyst was washed with acetone (2 ꢁ 5 mL), air-dried and reused dir-
ectly in the next run. The filtrate was concentrated under reduced pressure and purified
by flash column chromatography on silica gel (petroleum ether: ethyl acetate ¼ 20:1) to
afford the desired E-enamide 3.
Full experimental detail, characterization data of all compounds. This material can be
found via the “Supplementary Content” section of this article’s webpage.
Funding
The authors thank the National Natural Science Foundation of China [No. 21462021], the
Project of Education Department of Jiangxi Province [No. GJJ202306, JY20223] and Key
Laboratory of Functional Small Organic Molecule, Ministry of Education [No. KLFS-KF-201704]
for financial support.
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