Cascade Reaction of α, β-Unsaturated Ketones and 2-Aminoaryl Alcohols for the Synthesis of 3-Acylquinolines by a Copper Nanocatalyst

Article abstract of DOI:10.1002/adsc.202100631

3-Acylquinolines possess widespread applications in functional chemicals. However, the convenient and selective synthesis of such important substructures has to date remained a challenge. Herein, we report a method to access 3-acylquinolines from α, β-unsaturated ketones and 2-aminoaryl alcohols in one pot with a copper nanocatalyst supported on nitrogen-silica-doped carbon (Cu/N?SiO₂?C). Mechanistically, the construction of the product involves a cascade procedure including radical-type oxidation of 2-aminoaryl alcohols, aza-Michael addition and annulation. This developed protocol proceeds with merits of mild reaction conditions, good functional group tolerance, earth-abundant and reusable copper catalyst, easily available stocks and O₂ as the sole oxidant, which provides an alternative way for the sustainable synthesis of quinoline derivatives. (Figure presented.).

Full text of DOI:10.1002/adsc.202100631

RESEARCH ARTICLE
doi.org/10.1002/adsc.202100631
Cascade Reaction of α, β-Unsaturated Ketones and 2-Aminoaryl
Alcohols for the Synthesis of 3-Acylquinolines by a Copper
Nanocatalyst
Yuan Liu,a Chen Wang,a Yixin Tong,a Yong Ling,a Changjian Zhou,b,* and
Biao Xionga,*
a
School of Pharmacy, Nantong University,
19 Qixiu Road, Nantong, Jiangsu Province 226001, People’s Republic of China
E-mail: hsiung1987@ntu.edu.cn
School of Chemistry and Chemical Engineering,
b
Yancheng Institute of Technology,
Yancheng, Jiangsu Province, 224051, People’s Republic of China
E-mail: zcj@ycit.cn
Manuscript received: May 24, 2021; Revised manuscript received: July 20, 2021;
Version of record online: ■■■, ■■■■
Supporting information for this article is available on the WWW under https://doi.org/10.1002/adsc.202100631
Abstract: 3-Acylquinolines possess widespread applications in functional chemicals. However, the convenient
and selective synthesis of such important substructures has to date remained a challenge. Herein, we report a
method to access 3-acylquinolines from α, β-unsaturated ketones and 2-aminoaryl alcohols in one pot with a
copper nanocatalyst supported on nitrogen-silica-doped carbon (Cu/NÀ SiO2À C). Mechanistically, the
construction of the product involves a cascade procedure including radical-type oxidation of 2-aminoaryl
alcohols, aza-Michael addition and annulation. This developed protocol proceeds with merits of mild reaction
conditions, good functional group tolerance, earth-abundant and reusable copper catalyst, easily available
stocks and O2 as the sole oxidant, which provides an alternative way for the sustainable synthesis of quinoline
derivatives.
Keywords: heterogeneous catalysis; doped carbon materials; cascade reaction; 3-acylquinolines
Introduction
To date, considerable efforts have been devoted to
the development of synthetic strategies for the for-
Functionalized quinolines are an important class of mation of 3-acylquinolines through various intramolec-
nitrogen-heterocycles with wide-ranging applications ular and intermolecular reactions. In the past decade,
across pharmaceutical, agrochemical, materials and substituted enamines,[4a] enynes[4b,c] and imines[4d] were
fine chemical research. The classic methods for the designed as ingenious scaffolds to access 3-acylquino-
synthesis of quinolines such as Skraup, Combes, lines by intramolecular CÀ C coupling. However, more
Doebner-von Miller and Friedländer reaction have synthetic methods focus on intermolecular reactions
[1]
been well established. As an outstanding member in which has advantage in avoiding the complex prepara-
the quinoline family, 3-acylquinoline derivatives ex- tion of substrates. For instance, Pd-catalyzed carbocyc-
hibit excellent performance in pharmaceutical includ- lizations of alkenylanilines and alkynes,[5] Cu-catalyzed
ing antihypertension,[2a] antitumor,[2b] antiplasmodial,[2c] cascade reactions of 2-azidobenzaldehydes and
etc.[2d] In addition, due to the functional group of ketones,[6] enaminone-modified Povarov reaction[7] and
carbonyl, 3-acylquinolines could be easily derived into double CÀ H functionalization of electron-deficient
a variety of valuable and complex compounds.[3] acetylenes[8] were well developed as the alternative
Therefore, the efficient construction of acyl-containing paths to obtain 3-acylquinolines not long ago. Besides,
quinolines is of high importance in synthetic organic Tiwari and Li group reported the efficient protocols to
chemistry.
access 3-acylquinolines by copper-catalyzed ring-open-
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ing/reconstruction of anthranils with oxo-compounds potential of silica-doped carbon materials to favor
using TEMPO as the oxidants.[9]
mass transfer as well as the adjustment of electronic
Among the various available starting materials, 2- properties of supporting materials by N-element.[16] We
aminobenzaldehyde serve as a versatile synthon, read- herein report the preparation and characterization of a
ily involving in the construction of CÀ C and CÀ N new copper nanocatalyst supported on NÀ SiO2-doped
bond to get high value-added quinoline derivatives. So carbon, and describe, for the first time, its application
far, the reported methods for the preparation of 3- to catalyze the one pot cascade reactions to afford 3-
acylquinolines from 2-aminobenzaldehyde include acylquinolines from α, β-unsaturated ketones and 2-
phosphine-catalyzed and transition-metal catalyzed aminoaryl alcohols (Scheme 2).
condensation of ynones with o-aminobenzaldehyde
(Scheme 1, a),[10] Cu–MOFs consisting of polyhedral
Results and Discussion
cages for 3-acylquinolines synthesis from β-dicarbonyl
compounds and so on (Scheme 1, b),[11] Zn-promoted Typically, the catalyst was prepared as follows: The
Friedländer-type synthesis of 3-aroylquinolines from mixture of Cu(OAc)2 and 1,10-phenanthroline in
enaminones (Scheme 1, c),[12] and Cu-catalyzed double ethanol was stirred at 80 C for 1 hour. Silica was then
°
C(sp3)À H bond functionalization of saturated ketones introduced into the above solution by in situ hydrolysis
(Scheme 1, d).[13] Despite all these advances, most of of the added Si(OC2H5)4 (TEOS) with aqueous
them suffer from the use of pre-functionalized ammonia. After that, the commercially available
reagents, harsh reaction conditions, less environmen- powder Vulcan XC-72R as the support was added and
°
tally friendly additives, high load of non-recoverable refluxed for 3 h at 80 C. Finally, the catalyst was
catalysts. Hence, the search for facile synthesis of 3- afforded by successive removal of the suspension,
°
acylquinolines from simple and readily available dried overnight, pyrolyzed at 800 C, which is named
starting materials with green and efficient catalyst is of as Cu/NÀ SiO2À C (the Cu content is 3.69 wt%, which
great significance.
is determined by ICP-OES measurements). Similarly,
Generally, 2-aminobenzyl alcohols as synthetic the materials prepared in absence of TEOS, 1,10-
materials are more stable and cheaper than the relevant phenanthroline and metal source are donated as Cu/
aldehydes, and a great diversity of α, β-unsaturated NÀ C, Cu/SiO2À C and NÀ SiO2À C, respectively. And
ketones are easily available. In our previous work, we the catalysts prepared with different metal sources are
realized the synthesis of quinolines from α, β-unsatu- denoted as Metal/NÀ SiO2À C, respectively.
rated ketones and 2-aminobenzyl alcohols using an
To examine our tentative idea, we chose the
iridium-catalyzed transfer hydrogenation strategy.[14] reaction of 2-aminobenzyl alcohol 1a with chalcone
With our continuous interest in the design of non-noble 2a as a model system. By performing the reaction in
°
metal catalysts as well as the construction of DMF at 50 C in the presence of t-BuOK under air
quinolones,[15] we were therefore motivated to develop condition, we tested the effect of four different nano-
a new method to synthesize 3-acylquinolines by catalysts, respectively (Table 1, entries 1–4). Gratify-
employing heterogeneous catalysts. In consideration of ingly, Cu/NÀ SiO2À C exhibited good catalytic activity
the natural abundance of copper and its capability in to give title product 3aa in 86% yield (entry 2).
the activation of inert substrates via oxidation, and the Subsequently, several different solvents were examined
Scheme 1. Synthesis of 3-acylquinolines from 2-amino-benzal-
dehyde.
Scheme 2. 1a with various α, β-unsaturated ketones.
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Table 1. Optimization of reaction conditions.[a]
screening of temperature reveals that DMF heated to
°
50 C is favorable, and a further increase of temper-
ature did not improve the yield any more (entry 16). In
addition, mixing all the substrates in one time
decreased the yield of 3aa, and no product was found
under argon atmosphere (entries 17, 18), suggesting
that the oxidation of 2-aminobenzyl alcohol is very
important to the reaction. Therefore, the optimal
conditions are as described in entry 2 of Table 1.
Entry Catalyst
Solvent Additive Yield (%)[b]
1
2
3
4
5
6
7
8
Co/NÀ SiO2À C DMF
t-BuOK
t-BuOK
t-BuOK
t-BuOK
29
86
37
trace
18
Cu/NÀ SiO2À C DMF
Mn/NÀ SiO2À C DMF
Characterization of Cu/NÀ SiO2À C was performed
by TEM, SEM, XPS, EDS and ICP-OES, respectively.
The micrograph in Figure 1 (a, b, c) and Figure S1
illustrate the morphology of Cu/NÀ SiO2À C. The
scanning electron microscope (SEM, Figure S1)
showed that Cu/NÀ SiO2À C displays relatively uniform
irregular sphere-like morphology. And the transmission
electron microscopy (TEM, Figure 1) showed the
existence of Cu nanoparticles, which are not com-
pletely uniformly distributed in the catalyst. Some of
the copper particles are clustered together, and portion
of the copper particles and nitrogen and silicon are
uniformly distributed in the catalyst, which indicates
that some of the copper exists on the surface of the
catalyst in other forms, and the specific form of
existence will be explained from the following charac-
terization. The element mapping images reveal the
distribution of Cu, N, Si and C (Figure 1), which is in
accordance with the result of EDS (Figure S2, SI).
Further, copper content of the Cu/NÀ SiO2À C was
detected as 3.69 wt% by means of ICP-OES analysis.
Fe/NÀ SiO2À C
DMF
Cu/NÀ SiO2À C Toluene t-BuOK
Cu/NÀ SiO2À C EtOH t-BuOK
12
Cu/NÀ SiO2À C CH3CN t-BuOK
trace
80
0
67
54
Cu/NÀ SiO2À C DMSO
t-BuOK
t-BuOK
t-BuOK
t-BuOK
t-BuOK
9
NÀ SiO2À C
Cu/NÀ C
DMF
DMF
DMF
DMF
10
11
12
13
14
15[c]
16[d]
17[e]
18[f]
Cu/SiO2À C
Cu(OAc)2
58
Cu/NÀ SiO2À C DMF
Cu/NÀ SiO2À C DMF
Cu/NÀ SiO2À C DMF
Cu/NÀ SiO2À C DMF
Cu/NÀ SiO2À C DMF
Cu/NÀ SiO2À C DMF
t-BuONa 61
K2CO3
0
t-BuOK
t-BuOK
t-BuOK
t-BuOK
(8, 86, 86)
(2, 79, 86)
52
0
[a] Unless otherwise stated, the mixture of 2-aminobenzyl
alcohol 1a (0.3 mmol), catalyst (15 mg, Cu: 2.88 mol%),
additive (0.3 mmol) and 1.0 mL of solvent was stirred at
°
50 C for 1 hour, chalcone 2a (0.3 mmol) was then added
successively under air atmosphere, the resulting mixture was
°
stirred at 50 C for 1 hour.
[b] GC yield.
[c] Yields are with respect to the use of 50 mol%, 150 mol%
and 200 mol% t-BuOK, respectively.
Yields are with respect to the temperature at 30 C, 40 C and
[d]
°
°
°
60 C, respectively.
[e] All the substrates were mixed in one time.
[f] Argon atmosphere.
with the effective catalyst Cu/NÀ SiO2À C under the
same employed reaction conditions (entries 5–8). So,
the results indicated the use of DMF as a solvent was
more effective for the formation of 3aa. In order to
investigate the structure-function relationship of the
copper-catalyst, we employed NÀ SiO2À C, Cu/NÀ C,
Cu/SiO2À C, Cu(OAc)2 to evaluate the reaction, respec-
tively (entries 9–12). Interestingly, NÀ SiO2À C was
unable to afford the compound 3aa, implying that the
Cu species is the catalytic active ingredient. In
comparison, Cu/NÀ SiO2À C (entry 2) showed higher
catalytic activity than Cu/SiO2À C (entry 11), suggest-
ing that the introduction of nitrogen improved the
catalytic activity. Next, we focused our attention on the
effects of different bases (entries 13–15). Obviously,
the weak inorganic base K2CO3 was difficult to afford
the desired compound, and an equivalent of t-BuOK
was found to be the most appropriate choice. Then, the
Figure 1. (a, b, c) TEM images of Cu/NÀ SiO2À C and (d, e, f, g,
h) the corresponding elemental mapping images of C, N, Si and
Cu, respectively.
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Subsequently, X-ray photoelectron spectroscopy material.[16] Combined with the above characterization
(XPS) analysis was employed to identify the surface and experimental results, it can be inferred that the
chemistry of the developed Cu/NÀ SiO2À C, the Cu2p CuÀ O serves as the catalytic active ingredient, and the
spectra shows three peaks. The peak at 935.3 eV can presence of N and silica could affect the catalytic
be attributed to copper phyllosilicate species.[17] And activity of the catalyst.
the peak at 932.2 eV can be assigned to copper (II)
Having established the optimal reaction conditions,
2p3/2, due to the relaxation effects the peak at we set out to explore the generality of this synthetic
933.6 eV can be ascribed to CÀ NÀ Cu.[18] The content protocol. First, the reactions of 1a in combination with
of copper phyllosilicate species, copper (II) and a wide range of α, β-unsaturated ketones (see the
CÀ NÀ Cu in Cu/N-SiO2À C is 52%, 34.5% and 13.5%, Scheme S2, substrates 2a–2n, SI) were examined. As
respectively (Table S1, SI). In the N region of Cu/ shown in Scheme 3, all the reactions proceeded
NÀ SiO2À C, there are three distinct peaks (Figure 2) smoothly with a good tolerance of various functional
with electron binding energies of 398.4 (pyridine- groups. Different substituted aryl groups connect with
type),[19] 400.6 (graphitic-type)[20] and 402.0 eV olefinic bond in α, β-unsaturated ketones had good
(NÀ Cu), and the peak at 402.0 eV in this case can be performance in the construction of desired products
assigned to NÀ Cu as the Cu associate with 1,10- (Scheme 2, 3aa–3ah). In addition, the aryl group link
phenanthroline frequently arise in the higher BE, while to carbonyl in α, β-unsaturated ketones also delivered
the graphitic-type N originates from the calcination of 3-acylquinolines in good isolated yields (3ai–3ak). To
the 1,10-phenanthroline. Deconvolution shows that some extent, the above results certify that electron
around 15% of the N atoms are bound to the copper withdrawing groups and electron donating groups in
metal (see Table S2, NÀ Cu, SI), which derives from substrates 2 have no obvious influence on the reaction.
the graphitization of the CuÀ Phen complex. In order to Furthermore, heterocyclic substituents such as thienyl
figure out the single factor influence for the surface and pyridine were successfully introduced to the
chemistry of the catalysts, the XPS analysis data of quinoline skeleton in excellent yields (3al, 3am).
Cu/NÀ C, Cu/SiO2À C and N-SiO2À C were shown in Interestingly, due to the special structure of 2-(pyridin-
Figure S3, Table S1 and S2. Compared with Cu/ 2-yl)quinoline, the product 3am could be utilized as a
NÀ SiO2À C, the contents of pyridine-type N and graph- practical bidentate ligand. For the aliphatic substitu-
itic-type N in the N region of the catalysts are similar, ents, 1-phenylbut-2-en-1-one 2n and 4,4-dimeth-
and they exhibit no catalytic activity (see Table 1, ylpent-1-en-3-one 2o resulted in a deficient conversion
entry 9). However, the only difference is the content of to the product 3an and 3ao, respectively, which is
NÀ Cu, indicating that NÀ Cu plays an important role in possibly owing to the unstable property of aliphatic α,
the catalytical process (Table S2). This may be due to β-unsaturated ketones 2n and 2o.
the introduction of nitrogen could change the electron
Subsequently, we turned our attention to the
structure of the catalytic material, and enhance the reactions of various α-aminoaryl alcohols 1 with
binding effect between the metal and the supporting different substitution patterns. Similar to the results
material, thus improving the catalytic performance of described in Scheme 2, all the reactions furnished the
the catalytic material.[21] In addition, compared with
Cu/NÀ C (Table 1, entry 10), Cu/NÀ SiO2À C (Table 1,
entry 2) exhibits better catalytic activity due to the
addition of silica to the catalyst. This may be due to
the potential of silica in modifying the micropore size
of carbon material to favor the mass transfer and
increasing the dispersion of active species, thus
improving the catalytic performance of the catalytic
Figure 2. Cu 2p (left) and N 1s (right) XPS spectra of Cu/
NÀ SiO2À C.
Scheme 3. Variation of 1 and 2.
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3-benzoylated products in moderate to excellent iso- tiny amount of by-product 2-phenylquinoline (eq 2).
lated yields (Scheme 3, 3ba–3ep). 2-amino-3-meth- Besides, without the catalyst, the same reaction
ylphenyl methanol 1b reacted with three different α, β- generated 3aa in 36% yield and a plenty of inter-
unsaturated ketones to afford desired compounds in mediate dihydrogen quinoline 3aa’ had not been
high yields (3ba, 3bb, 3bg), indicating that the oxidized in a prolonged time (eq 3). Furthermore, the
cascade annulations have good tolerance of the steric second step of the model reaction was interrupted after
influence of ortho-methyl substituent. Compared with 0.5 hour. By the GC-MS analysis, product 3aa and
2-aminophenyl methanol 1a, halogen-substituted α- 3aa’ were detected in 43% and 28% yields, respec-
aminobenzyl alcohol was well tolerated, as exemplified tively. So, the above results indicate that the copper-
by the presence of chlorine atom para to amino group nanocatalyst is very important to the selective oxida-
in the phenyl ring (3ca, 3cc, 3ce). In addition, furan tion of alcohols and dehydroaromatization of large
could be well installed on the skeleton of 3-acylquino- steric hindrance dihydrogen quinoline (eq 4). However,
line by the elegant synthetic strategy (3cp). Moreover, the excess BHT significantly suppressed the oxidation
the strong electron donating group, 5-methoxy of the of 1a, showing that, the reaction may involve a
aromatic alcohol also had great compatibility with radical-type oxidation (eq 5). Meanwhile, the gener-
transformation to deliver the target molecules in good ation of quinone is consistent with the Karlin’s
yields (3da, 3dd, 3dg). For the secondary alcohol 1- reports,[22] suggesting that the oxidative system of Cu/
(2-aminophenyl)ethanol 1e, large amounts of unde- NÀ SiO2À C with O2 possibly generate a superoxo
sired product 2-(4-methylquinolin-2-yl)aniline was copper(II) species.
formed by the bimolecular condensation of intermedi-
Based on the above-observed findings and the
ate ketone from the oxidation of 1e, so that the yield reported mechanisms,[22,23] the plausible reaction path-
of target compound 3ea is poor. As expected, 2- way is proposed in Scheme 5. In order to facilitate the
aminopyridin-3-yl methanol 1f could react with α, β- exhibition of mechanism, the catalyst Cu/NÀ SiO2À C
unsaturated ketones to afford product 3fi and 3fk in was written as O=CuIINx in Scheme 5. Here, O=CuII
excellent yields. Gratifyingly, ester-containing reactant denotes that a divalent copper species is formed
2q was also suitable for this method to supply the between copper and oxygen after calcination of the
corresponding product 3eq which could be easily used precursor Cu(OAc)2 which was confirmed by XPS
for further chemical synthesis.
analysis. The Nx means that the copper species
To gain insight into the product forming informa- contains an unknown amount of CuÀ N coordination
tion, 2-aminophenyl methanol 1a was treated by bonds which was also confirmed by XPS analysis.
standard conditions without α, β-unsaturated ketones in Initially, 2-aminophenyl methanol 1a proceeds depro-
1 hour (Scheme 4, eq 1). Oxidation product 2-amino-
benzaldehyde 1a’ was detected in 97% GC yield,
implying that the oxidative process was highly
efficient. Subsequently, 1a’ was used directly as the
substrate to react with 2a under the same conditions to
afford desired product 3aa in an excellent yield and a
Scheme 4. Control experiments.
Scheme 5. Possible reaction pathway.
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tonation by t-BuOK to generate alkoxide 1aa which the XPS results of used Cu/NÀ SiO2À C (Figure S3,
associate with nano-Cu (II) to give compound 1bb. Table S1), a relatively high loss of copper phyllosili-
Then, (hydroxo)copper species 1cc is formed by cate species was found, which maybe due to the
alcoholysis and followed by oxidation to produce weakened interaction between the carrier and the
copper(II)-hydroperoxide 1dd. Next, the radical hydro- metal. And a slight decrease of relative Cu (II) content
gen abstraction from the Cα carbon of 1bb by the was found, counting for the slight deactivation of the
homolytic cleavage of peroxy bond, resulting in water catalyst.
and a radical species 1ee. Further, the 1ee can be
Finally, we were interested in applying our syn-
transformed into the 2-aminobenzaldehyde 1a’ and thetic protocol for rapid synthesis of some complex
original nano-Cu (II) catalyst by elimination, thereby compounds. As shown in Scheme 6, 11-phenyl-11H-
completing the catalytic oxidation cycle. Finally, the indeno[1,2-b]quinoline 4a could be efficiently pre-
intermediate 1a’ proceeds aza-Michael addition, dehy- pared in 52% yield from 3aa by reduction and Friedel-
dration and dehydroaromatization to afford the product Crafts alkylation. Noteworthy, many azafluorene de-
3aa. However, the retro-aldol reaction of 2a produces rivatives are endowed with significant biological and
acetophenone, which can participate in the Friedlander medicinal activities.[24] Moreover, 3aa had a good
reaction with 1a’ to produce 2-phenylquinoline as a performance in Schmidt reaction[25] by using
by-product.
azidotrimethylsilane as a nucleophilic reagent to afford
To check the stability of the developed catalyst N,2-diphenylquinoline-3-carboxamide 5a in 64%
material (Cu/NÀ SiO2À C), it was recycled and reused yield.
for six consecutive runs with the model reaction. As
illustrated in Figure 3, the catalytic activity maintains
very well. After six recycles, the Cu content dropped
Conclusion
from 3.69 wt% to 3.28 wt% (determined by ICP-OES In summary, we have developed a method for the one
analysis). In comparison with the fresh catalyst (Cu/ pot synthesis of functionalized 3-acylquinolines from
NÀ SiO2À C), TEM and SEM images showed no 2-aminobenzyl alcohols and α, β-unsaturated ketones
obvious change of the morphology of the used catalyst by a copper nanocatalyst supported on NÀ SiO2-doped
(Figure S1 and Figure S4). In addition, according to carbon. The catalyst was easily prepared from low-cost
earth-abundant metal, which exhibited good catalytic
performance towards the cascade reactions. A wide
array of 3-acylquinolines were successfully obtained in
reasonable to good yields upon isolation. The pre-
sented synthetic protocol proceeds with the merits of
good functional tolerance, stable and reusable of
copper catalyst, simple operation, mild conditions and
molecular O2 as the sole oxidant, which offers an
alternative way for sustainable synthesis of functional-
ized quinolines.
Experimental Section
Procedure for the preparation of catalyst: The mixture of
Cu(OAc)2 (748 mg, 3.75 mmol) and 1,10-phenanthroline
(2025 mg, 11.25 mmol) (Cu:phenanthroline=1:3 molar ratio)
°
was added to ethanol (100 mL) and stirred at 80 C for 1 hour.
Figure 3. Recyclability of the Cu/NÀ SiO2À C catalyst.
Silica was then introduced into the above solution by in situ
hydrolysis of the added Si(OC2H5)4 (TEOS) with aqueous
ammonia. After that, the commercially available powder Vulcan
XC-72R (5000 mg) as the support was added to the solution
°
and refluxed for 3 h at 80 C, then the solvent of the suspension
was removed and the remained solid was dried overnight at
°
60 C under vacuum. Then, the sample was grounded to a fine
°
powder and then pyrolyzed at 800 C under a constant argon
flow for 2 hours, which is named as Cu/NÀ SiO2À C (the Cu
content is 3.69 wt%, which is determined by ICP-OES measure-
ments). Similarly, the materials prepared in absence of TEOS,
1,10-phenanthroline and metal source are donated as Cu/NÀ C,
Cu/SiO2À C and NÀ SiO2À C, respectively. And the catalysts
Scheme 6. Utility of the 3-acylquinolines.
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prepared with different metal sources are denoted as Metal/
J. T. Zhu, H. B. Xie, S. Li, Y. M. Wu, Y. F. Gong, Chem.
NÀ SiO2À C, respectively.
Commun. 2010, 46, 2145–2147.
[6] a) B. Kaewmee, V. Rukachaisirikul, J. Kaeobamrung, J.
Org. Biomol. Chem. 2017, 15, 7387–7395; b) X. F.
Zhang, X. M. Ma, W. Q. Qiu, J. Evansa, W. Zhang,
Green Chem. 2019, 21, 349–354.
[7] Y. Li, X. J. Cao, Y. Y. Liu, J. P. Wan, Org. Biomol.
Chem. 2017, 15, 9585–9589.
[8] B. A. Trofimov, K. V. Belyaeva, L. P. Nikitina, A. G.
Mal’kina, A. V. Afonin, I. A. Ushakov, A. V. Vashchen-
ko, Chem. Commun. 2018, 54, 5863–5866.
[9] a) D. K. Tiwari, M. Phanindrudu, S. B. Wakade, J. B.
Nanuboluc, D. K. Tiwari, Chem. Commun. 2017, 53,
5302–5305; b) L. H. Zou, H. Zhu, S. Zhu, K. Shi, C.
Yan, P. G. Li, J. Org. Chem. 2019, 84, 12301–12313.
[10] a) H. F. Li, X. L. Xu, J. Y. Yang, X. Xie, H. Huang, Y. Z.
Li, Tetrahedron Lett. 2011, 52, 530–533; b) S. Khong, O.
Kwon, J. Org. Chem. 2012, 77, 8257–8267; c) A. K.
Bagdi, S. Santra, M. Rahman, A. Majee, A. Hajra, RSC
Adv. 2013, 3, 24034–24037.
[11] a) W. Y. Gao, K. Y. Leng, L. Cash, M. Chrzanowski,
C. A. Stackhouse, Y. Y. Sun, S. Q. Ma, Chem. Commun.
2015, 51, 4827–4829; b) A. Hasaninejad, A. Zare, M.
Shekouhy, J. Ameri-Rad, Green Chem. 2011, 13, 958–
964; c) B. V. Subba Reddy, A. Venkateswarlu, G. Nir-
anjan Reddy, Y. V. Rami Reddy, Tetrahedron Lett. 2013,
54, 5767–5770; d) R. R. Rajawinslin, S. D. Gawande, V.
Kavala, Y. H. Huang, C. W. Kuo, T. S. Kuo, M. L. Chen,
C. H. He, C. F. Yao, RSC Adv. 2014, 4, 37806–37811.
[12] L. C. Luo, Z. B. Zhou, J. Y. Zhu, X. Lu, H. Wang,
Tetrahedron Lett. 2016, 57, 4987–4990.
Typical procedure for the synthesis of compound 3aa: 2-
aminobenzyl alcohol 1a (36.6 mg, 0.3 mmol), catalyst (15 mg,
Cu: 2.88 mol%), t-BuOK (39.2 mg, 100 mol%) and DMF
(1.0 mL) were introduced in a tube (25 mL), which was heated
°
to 50 C for 1 h under air atmosphere. Then, chalcone 2a
(62.4 mg, 0.3 mmol) was added successively and the resulting
°
reaction mixture was stirred at 50 C for 1 h. After cooling
down to room temperature, the reaction mixture was diluted by
water and was extracted with ethyl acetate (5 mL×3). The
combined organic layer was dried over by Na2SO4, followed by
removing the solvent under vacuum. The residue was purified
by preparative TLC on silica, eluting with petroleum ether (60–
°
90 C)/ethyl acetate (25/1) to give quinoline 3aa as yellow
solid.
Acknowledgements
We gratefully acknowledge the financial support by the National
Natural Science Foundation of China (Grant No. 21801138),
and also thank the testing service provided by Analysis and
Testing Center in Nantong University.
References
[1] a) S. Madapa, Z. Tusi, S. Batra, Curr. Org. Chem. 2008,
12 1116–1183; b) J. Marco-Contelles, E. Pérez-Mayoral,
A. Samadi, M. C. Carreiras, Chem. Rev. 2009, 109,
2652–2671; c) V. Sridharan, P. A. Suryavanshi, J. C.
Menéndez, Chem. Rev. 2011, 111, 7157–7259; d) Y.
Wang, C. Chen, J. Peng, M. Li, Angew. Chem. Int. Ed.
2013, 52, 5323–5327; Angew. Chem. 2013, 125, 5431–
5435; e) G. Liu, M. Yi, L. Liu, J. J. Wang, J. H. Wang,
Chem. Commun. 2015, 51, 2911–2914.
[13] Z. Wang, G. Chen, X. Y. Zhang, X. S. Fan, Org. Chem.
Front. 2017, 4, 612–616.
[14] B. Xiong, Y. Y. Wang, Y. Liu, Y. D. Bao, Z. G. Liu, Y. A.
Zhang, Y. Ling, Org. Biomol. Chem. 2018, 16, 5707–
5711.
[2] a) N. Muruganantham, R. Sivakumar, N. Anbalagan, V.
Gunasekaran, J. T. Leonard, Biol. Pharm. Bull. 2004, 27,
1683–1687; b) P. J. Zhang, Y. Q. Ye, Y. H. Qian, B. X.
Yin, J. M. Zhao, S. X. Zhu, L. Zhang, M. J. Yan, CNS
Neurol. Disord. Drug Targets 2017, 16, 724–736;
c) A. D. Yapi, N. Desbois, J. M. Chezal, O. Chavignon,
J. C. Teulade, A. Valentin, Y. Blache, Eur. J. Med. Chem.
2010, 45, 2854–2859; d) B. Tanwar, A. Kumar, P.
Yogeeswari, D. Sriram, A. K. Chakraborti, Bioorg. Med.
Chem. Lett. 2016, 24, 5960–5968.
[3] a) Y. Z. Hu, G. Zhang, R. P. Thummel, Org. Lett. 2003,
5, 2251–2253; b) K. Nakatani, S. Sando, I. Saito, J. Am.
Chem. Soc. 2000, 122, 2172–2177; c) C. L. Chiang, C. F.
Shu, Chem. Mater. 2002, 14, 682–687.
[4] a) P. J. Tsai, C. B. Kao, W. R. Chiow, C. P. Chuang,
Synthesis 2014, 46, 175–182; b) X. F. Xia, L. L. Zhang,
X. R. Song, X. Y. Liu, Y. M. Liang, Org. Lett. 2012, 14,
2480–2483; c) X. F. Xia, W. He, D. W. Wang, Adv.
Synth. Catal. 2019, 361, 2959–2964; d) K. C. Bharadwaj,
J. Org. Chem. 2018, 83, 14498–14506.
[15] a) C. J. Zhou, Z. D. Tan, H. F. Jiang, M. Zhang, Green
Chem. 2018, 20, 1992–1997; b) C. J. Zhou, Z. D. Tan,
H. F. Jiang, M. Zhang, ChemCatChem 2018, 10, 2887–
2892; c) Z. D. Tan, B. Xiong, J. Yang, C. G. Ci, H. F.
Jiang, M. Zhang, J. Catal. 2020, 392, 135–140.
[16] a) D. Forberg, T. Schwob, M. Zaheer, M. Friedrich, N.
Miyajima, R. Kempe, Nat. Commun. 2016, 7, 13201;
b) S. M. Sachau, M. Zaheer, A. Lale, M. Friedrich, C. E.
Denner, U. B. Demirci, S. Bernard, G. Motz, R. Kempe,
Chem. Eur. J. 2016, 22, 15508–15512; c) R. Xie, F. Xie,
C. J. Zhou, H. F. Jiang, M. Zhang, J. Catal. 2019, 377,
449–454; d) R. Xie, G. P. Lu, H. F. Jiang, M. Zhang, J.
Catal. 2020, 383, 239–243; e) L. He, F. Weniger, H.
Neumann, M. Beller, Angew. Chem. Int. Ed. 2016, 55,
12582–12594; Angew. Chem. 2016, 128, 12770–12783;
f) F. A. Westerhaus, R. V. Jagadeesh, G. Wienhöfer,
M. M. Pohl, J. Radnik, A. E. Surkus, J. Rabeah, K.
Junge, H. Junge, M. Nielsen, A. Brückner, M. Beller,
Nat. Chem. 2013, 5, 537–543.
[17] X. M. Huang, M. Ma, S. Miao, Y. P. Zheng, M. S. Chen,
W. J. Shen, J. Appl. Catal. A Gen. 2017, 531, 79–88.
[5] a) J. Zheng, Z. Li, L. B. Huang, W. Q. Wu, J. X. Li, H. F.
Jiang, Org. Lett. 2016, 18, 3514–3517; b) Z. X. Chen,
Adv. Synth. Catal. 2021, 363, 1–9
7
© 2021 Wiley-VCH GmbH
��
These are not the final page numbers!

RESEARCH ARTICLE
asc.wiley-vch.de
[18] a) N. McIntyre, M. Cook, Anal. Chem. 1975, 47, 2208–
2213; b) J. Haber, T. Machej, L. Ungier, J. Ziolkowski,
J. Solid State Chem. 1978, 25, 207–218.
[19] a) Y. Zheng, Y. Jiao, L. Ge, M. Jaroniec, S. Z. Qiao,
Angew. Chem. Int. Ed. 2013, 52, 3110–3116; Angew.
Chem. 2013, 125, 3192–3198; b) J. Liu, T. Zhang, Z.
Wang, G. Dawson, W. J. Chen, Mater. Chem. 2011, 21,
14398–14401.
H. H. Wang, Q. Y. Yu, X. H. Li, M. Antonietti, J. S.
Chen, J. Am. Chem. Soc. 2017, 139, 811–818.
[22] a) J. Y. Lee, R. L. Peterson, K. Ohkubo, I. Garcia-Bosch,
R. A. Himes, J. Woertink, C. D. Moore, E. I. Solomon, S.
Fukuzumi, K. D. Karlin, J. Am. Chem. Soc. 2014, 136,
9925–9937; b) D. Maiti, H. C. Fry, J. S. Woertink, M. A.
Vance, E. I. Solomon, K. D. Karlin, J. Am. Chem. Soc.
2007, 129, 264–265.
[20] a) T. Wang, Z. Dong, W. Cai, Y. Wang, T. Fu, B. Zhao, [23] a) J. K. Mobleya, M. Crocker, RSC Adv. 2015, 5, 65780–
L. Peng, W. Ding, Y. Chen, Chem. Commun. 2016, 52,
10672–10675; b) S. Wang, J. Wang, M. Zhu, X. Bao, B.
Xiao, D. Su, H. Li, Y. Wang, J. Am. Chem. Soc. 2015,
137, 15753–15759.
65797; b) C. E. Elwell, N. L. Gagnon, B. D. Neisen, D.
DharOrcid, A. D. SpaethOrcid, G. M. Yee, W. B. Tol-
man, Chem. Rev. 2017, 117, 2059–2107.
[24] G. Chen, Z. Wang, X. Y. Zhang, X. S. Fan, J. Org.
Chem. 2017, 82, 11230–11237.
[21] a) X. M. Ning, H. Yu, F. Peng, H. J. Wang, J. Catal.
2015, 325, 136–144; b) H. Su, K. X. Zhang, B. Zhang, [25] C. H. Tang, Y. Z. Yuan, N. Jiao, Org. Lett. 2015, 17,
2206–2209.
Adv. Synth. Catal. 2021, 363, 1–9
8
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RESEARCH ARTICLE
Cascade Reaction of α, β-Unsaturated Ketones and 2-
Aminoaryl Alcohols for the Synthesis of 3-Acylquinolines by
a Copper Nanocatalyst
Adv. Synth. Catal. 2021, 363, 1–9
Y. Liu, C. Wang, Y. Tong, Y. Ling, C. Zhou*, B. Xiong*