Porous polymeric ligand promoted copper-catalyzed C-N coupling of (hetero)aryl chlorides under visible-light irradiation

Article abstract of DOI:10.1007/s11426-020-9859-9

A porous polymeric ligand (PPL) has been synthesized and complexed with copper to generate a heterogeneous catalyst (Cu@PPL) that has facilitated the efficient C-N coupling with various (hetero)aryl chlorides under mild conditions of visible-light irradiation at 80 °C (58 examples, up to 99% yields). This method could be applied to both aqueous ammonia and substituted amines, and is compatible to a variety of functional groups and heterocycles, as well as allows tandem C-N couplings with conjunctive dihalides. Furthermore, the heterogeneous characteristic of Cu@PPL has enabled a straightforward catalyst separation in multiple times of recycling with negligible catalytic efficiency loss by simple filtration, affording reaction mixtures containing less than 1 ppm of Cu residue. [Figure not available: see fulltext.]

Full text of DOI:10.1007/s11426-020-9859-9

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Porous polymeric ligand promoted copper-catalyzed C-N coupling
of (hetero)aryl chlorides under visible-light irradiation
Erfei Wang1, Kaixuan Chen1, Yinan Chen1, Jiawei Zhang2, Xinrong Lin2* & Mao Chen1*
1State Key Laboratory of Molecular Engineering of Polymers, Department of Macromolecular Science, Fudan University,
Shanghai 200438, China;
2Key Laboratory of Medicinal Chemistry for Natural Resource, Ministry of Education and Yunnan Province, School of Chemical Science and
Technology, Yunnan University, Kunming 650091, China
Received July 13, 2020; accepted August 25, 2020; published online October 29, 2020
A porous polymeric ligand (PPL) has been synthesized and complexed with copper to generate a heterogeneous catalyst
(Cu@PPL) that has facilitated the efficient C-N coupling with various (hetero)aryl chlorides under mild conditions of visible-
light irradiation at 80 °C (58 examples, up to 99% yields). This method could be applied to both aqueous ammonia and
substituted amines, and is compatible to a variety of functional groups and heterocycles, as well as allows tandem C-N couplings
with conjunctive dihalides. Furthermore, the heterogeneous characteristic of Cu@PPL has enabled a straightforward catalyst
separation in multiple times of recycling with negligible catalytic efficiency loss by simple filtration, affording reaction mixtures
containing less than 1 ppm of Cu residue.
polymeric catalyst, heterogeneous catalysis, photocatalysis, C-N coupling
Citation:
Wang E, Chen K, Chen Y, Zhang J, Lin X, Chen M. Porous polymeric ligand promoted copper-catalyzed C-N coupling of (hetero)aryl chlorides under
visible-light irradiation. Sci China Chem, 2020, 63, https://doi.org/10.1007/s11426-020-9859-9
The development of versatile synthetic methods for the
formation of carbon-nitrogen (C–N) bonds can impact the
fields of pharmaceutical [1,2], agrochemical [3,4] and
natural-product synthesis [5,6], as well as material science
[7,8]. Consequently, a variety of synthetic strategies pro-
moted by transition-metal catalysis including Buchwald-
Hartwig [9,10] and Ullmann [11,12] coupling reactions, have
been developed. Despite the extraordinary advances ac-
complished with these diverse and robust reaction systems,
attaining desirable reaction characteristics such as mild
conditions (i.e., Ullmann coupling requires temperature
above 180 °C), straightforward catalyst separation, as well as
bond activation upon more economically competitive sub-
strates, remains challenges confronting researchers in pursuit
of enhanced sustainability and operational utility of the
chemistry [13,14].
Heterogeneous catalysts have received increasing attention
owing to their unique attribute of being recycled at ease [15–
17], which may carry important cost implications in in-
dustrial chemical manufacturing, and have promoted syn-
thetic transformations ranging from hydrogenation [18],
enyne cyclization [19] to Suzuki-Miyaura coupling [20].
While heterogeneous catalysis could provide an attractive
and convergent approach to form C–N bond between nitro-
gen nucleophiles and (hetero)aryl halides and access a broad
scope of N-containing molecules, such transformation pro-
cesses generally suffer from (1) decreased reactivity with
non-noble copper catalysts and aryl chlorides; (2) limited
tolerance to functional groups and heterocycles [21,22].
Furthermore, as equally challenging in homogeneous cata-
lysis, the direct amination with (hetero)aryl chlorides and
ammonia/amines has been rarely possible with hetero-
*Corresponding authors (email: xrlin@ynu.edu.cn; chenmao@fudan.edu.cn)
© Science China Press and Springer-Verlag GmbH Germany, part of Springer Nature 2020
chem.scichina.com link.springer.com

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Wang et al. Sci China Chem
geneous catalysts arising from the insufficient reactivity of
(hetero)aryl chlorides.
Beyond heterogeneous catalysts, Fu and co-workers
[23,24] have developed the photoinduced Ullmann C–N
coupling under mild conditions, which allowed the trans-
formation of electrophiles including aryl bromides/iodides.
Visible-light has also promoted other bond formations [25–
28]. Nevertheless, the utilization of aryl chlorides is still
difficult [29]. Ma and co-workers [30–32] have recently
made new breakthroughs in the Cu-catalyzed Ullmann-type
reaction of aryl chlorides. Upon applying elevated reaction
temperatures (110–130 °C) and making structural mod-
ifications based on the oxalamide ligand backbones, good
catalytic activities were achieved for the coupling reactions
between different types of nitrogen nucleophiles (i.e., am-
monia and alkyl amine) and aryl chlorides.
Figure 1 Cu-catalyzed C–N bond formation under visible-light irradia-
tion with oxalamide-linked porous polymeric ligand (PPL) (color online).
Table 1 C–N bond formation between 4-n-butyl-chlorobenzene and
We hypothesize that a heterogeneous system based on a
versatile and light-absorbing polymeric Cu-complex might
facilitate the Caryl–Cl bond cleavage via a photoinduced
process [23], thereby broadening the applicable scope of Cu-
catalyzed Ullman reaction at lower reaction temperatures
and simultaneously facilitating straightforward catalyst se-
paration/recycling. Meanwhile, the highly porous morphol-
ogy of the polymeric catalyst could effectively increase the
accessible surface area and suppress the catalytic efficiency
decay. Herein, we report that a novel porous polymeric li-
gand (PPL) was synthesized and coordinated with copper to
generate a heterogeneous catalyst (Cu@PPL), promoting a
general and efficient C–N bond formation between a broad
scope of (hetero)aryl chlorides and ammonia/alkyl amines
with good to excellent yields (58 examples, up to 99%
yields). This catalyst enabled a decrease in required reaction
temperature for as high as 40 °C when exposing to visible-
light irradiation (Figure 1). Furthermore, the heterogeneous
catalyst exhibited facile recyclability and excellent stability,
which results in repeated use in the reactions without di-
minishing its catalytic efficiency.
At the beginning of the investigation, polymeric ligands
L1–L6 were synthesized via condensation polymerization of
oxalyl chloride and diamine compounds, and complexed
with CuI to generate heterogeneous catalysts of Cu@Ligand.
The Cu-catalyzed C–N bond formation between 4-n-butyl-
chlorobenzene and aqueous ammonia was employed as a
model reaction using K3PO4 as a base in dimethyl sulfoxide
(DMSO). As shown in Table 1, when complexes made of
polymeric ligands L1–L6 were employed, the reactions
generated 4-n-butylaniline 1 at 12%–36% yields at 120 °C in
24 h as determined by gas chromatography (GC) analysis
(entries 1–6).
a)
aqueous ammonia
b)
Light
Temperature
(°C)
Entry Ligand
Time (h)
Yield
irradiation
1
2
L1
L2
L3
L4
L5
L6
L6
L6
L6
L6
L6
L6
No light
No light
No light
No light
No light
No light
White light
405 nm
120
120
120
120
120
120
100
100
80
24
24
24
24
24
24
24
24
48
48
48
48
15
32
3
12
4
29
5
18
6
36
7
76
8
92
>99 (99) c), 82 d)
56
9
405 nm
10
11
12
405 nm
60
405 nm
80
27–85 e)
f)
405 nm
80
88
a) Conditions: 4-nBu–Ph–Cl (0.5 mmol), aqueous ammonia (1 mmol),
Cu@Ligand (0.05 mmol), K3PO4 (0.6 mmol), DMSO (0.5 mL). b) GC
yield. c) Isolated yield in parentheses. d) 24 h. e) When DMF, DMAc or
tBuOH was used instead of DMSO, yield was 82%, 75% and 27%, re-
spectively; when Cs2CO3, K2CO3 or Na2CO3 was used instead of K3PO4,
yield was 85%, 54% and 36%, respectively. f) 5 mol% Cu@L6.
When the reactions between 4-n-butyl-chlorobenzene and
ammonia were exposed to visible-light irradiation with white
light-emitting diode (LED) light (10 W), clearly improved
yields of 4-n-butylaniline were obtained at decreased reac-
tion temperature (100 °C). Among polymeric ligands of L1
to L6, the employment of L6 (PPL) afforded the highest GC

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Wang et al. Sci China Chem
yield (76%, entry 7, Table S1, Supporting Information on-
line), which was further improved to >99% at even lower
temperature (80 °C) by using a purple LED light (emission at
405 nm, 10 W, entry 9). Subsequently, lower reaction tem-
peratures (i.e., 60 °C), other solvents (i.e., N,N-di-
methylformamide (DMF), DMAc and nBuOH) and bases
(i.e., Cs2CO3, K2CO3, Na2CO3) were investigated with
Cu@L6, providing 27%–85% yields of 4-n-butylaniline
(entries 10–11) in 48 h irradiation time. When 5 mol% cat-
alyst was used, 88% yield was obtained (entry 12).
Subsequently, L6 and Cu@L6 were characterized by a
variety of measurements. In the Fourier transform infrared
(FT-IR) spectra (Figure 2(a)), the signals in the range from
1,750–1,650 and 3,450–3,250 cm−1 were attributed to the
vibration of the C=O and N–H bonds, respectively, indicat-
ing the formation of amide during the condensation poly-
merization, and suggesting that the polymer’s backbone was
retained during the coordination with copper. When analyzed
by ultraviolet-visible (UV-Vis) spectroscopy (Figure 2(b)),
the copper complex gave the strongest adsorption at 410 nm
in the visible-light range, which was consistent with the
emission wavelength of LED employed in the coupling re-
action. As shown in Figures 2(c1, c2), the formation of
copper complex also caused a color change from light purple
to brown. The high thermal stability of L6 and Cu@L6 were
confirmed by thermo-gravimetric analysis (TGA), affording
5% mass loss at 372 and 395 °C, respectively (Figure S3,
Supporting Information online). Brunauer-Emmett-Teller
(BET) measurement was used to study the porosity of L6 and
Cu@L6 by analyzing the N2 adsorption and desorption iso-
therms (Figure 2(d)). In comparison to L6, a smaller surface
area of Cu@L6 was detected (396 vs. 237 m2/g), resulted
from partial occupation of the porous structure by the in-
troduced Cu. The hierarchically porous property was also
proven by the pore size distribution according to the nonlocal
density functional theory (NLDFT) [33]. The results shown
in Figure 2(e) demonstrated the presence of narrowly dis-
tributed pore sizes of about 2 and 5 nm, representing mixed
micropores and mesopores of Cu@L6, which is advanta-
geous for heterogeneous catalysis owing to the excellent
adsorption of substrates and efficient mass transport of
products that could be provided by porous carriers. When
analyzed by scanning electron microscopy (SEM), corre-
sponding images (Figure 2(f, g)) displayed distinctive
morphologies of porosity for L6 and Cu@L6. The high-
resolution transmission electron microscopy (HR-TEM)
images of L6 and Cu@L6 (Figure 2(h, i)) showed their
amorphous structures and the well dispersity of Cu in the
matrix. Otherwise, when L6 and Cu were mixed at their solid
states, Cu nanoparticles are clearly observed by HR-TEM as
confirmed by the lattice fringes with a spacing distance of
0.21 nm (Figure S3) [34]. Additionally, scanning transmis-
sion electron microscopy (STEM) and element mapping
Figure 2 Characterization of L6 and Cu@L6. (a, b) FT-IR and UV-Vis
spectra; (c) optical images; (d) adsorption (filled symbols) and desorption
(empty symbols) isotherms recorded under N2 atmosphere; (e) pore size
distribution obtained by NLDFT; (f, g) SEM images of L6 and Cu@L6,
respectively; (h, i) HR-TEM images of L6 and Cu@L6, respectively; (j1)
STEM image of Cu@L6; (j2–j4) element mapping images of Cu@L6
based on (j1) (color online).
images of Cu@L6 (Figure 2(j1–j4)) further confirm that the
Cu, C and N elements were evenly dispersed on the poly-
meric support, which prompts efficient catalytic process.
With the optimized conditions, we investigated the sub-
strate scope of the photo-promoted Cu-catalyzed C-N cou-
pling between (hetero)aryl chlorides and nitrogen
nucleophiles. As shown in Scheme 1, for nucleophiles of
both aqueous ammonia and substituted amines, the coupling
could be successfully carried out with para-, meta-, and
ortho-substituted aryl compounds and fused aryl substrates
at 80 °C; electron-rich, electron-neutral, and electron-defi-
cient aryl chlorides all represented excellent substrates.
Moreover, the reaction condition tolerated a variety of
functional groups including unprotected hydroxyl (6, 7, 27,
28), amine (8), acetyl (9, 29), sulfamide (10), amide (11, 30),
nitrile (12, 31) and ester (16, 34).
While heteroaryl amines have shown profound research
value for their biological activity [35,36], the copper-cata-
lyzed reactions for this class of substrates remain challenging
due to the proneness of heterocycles to coordinate to copper
species [37,38]. With this method, a variety of heterocyclic
compounds including pyridine (18, 36), thiophene (19, 37),

4
Wang et al. Sci China Chem
in a one-pot fashion as shown in Scheme 2. As promoted by
visible-light irradiation, the Cu-catalyzed C-N coupling
could be successfully conducted at 40 °C via the C–Br bond
cleavage. After reaction, the second nucleophile was subse-
quently added into the reaction mixture without additional
catalyst or base, which enabled the further transformation of
the C–Cl bond at 80 °C exposing to the same light irradia-
tion. The tandem reactions successfully generated un-
symmetrically substituted aromatic diamines in high isolated
yields (86%–95%) from conjunctive dihalides [42], which
has been rarely demonstrated with heterogeneous copper
catalyst.
The recycling stability of heterogeneous catalyst Cu@L6
was further examined in the reaction of 4-n-butyl-chlor-
obenzene and aqueous ammonia (Table 2). After reaction,
Cu@L6 was separated from the reaction mixture simply via
filtration, and rinsed with solvents. During 6 times of re-
cycling experiments, the catalyst provided consistent iso-
lated yields for 4-n-butylaniline. In addition, less than 1 ppm
of Cu was detected in the obtained solutions, highlighting the
advantages of ease-of-separation and low metal contamina-
tion of heterogeneous catalyst.
In conclusion, we have developed a novel highly porous
heterogeneous polymeric catalyst, enabling visible-light
promoted Cu-catalyzed C–N bond formation and tandem
reaction with (hetero)aryl chlorides and various nitrogen
nucleophiles under mild conditions for the first time. This
method allows the synthesis of a broad scope of primary or
secondary (hetero)aryl amines at good to excellent yields,
and is compatible to various functional groups. Furthermore,
the heterogeneous feature has facilitated the catalyst se-
paration and recycling during multiple times of use, enabling
transition-metal catalysis with low metal-contamination
without extra purification. Given the importance of C–N
bond formation and increasing interest in sustainable
chemistry, the photo-promoted heterogeneous reaction mode
Scheme 1 Cu@L6 Catalyzed C-N Coupling between (Hetero)aryl
chlorides and ammonia/amines. Conditions: (hetero)aryl chloride
(0.5 mmol), aqueous ammonia (1 mmol) or R–NH2 (0.6 mmol), Cu@L6
(0.05 mmol), K3PO4 (0.6 mmol), DMSO (0.5 mL), 80 °C, visible light at
405 nm, 48 h. Isolated yields are based on electrophiles (color online).
thionaphthen (20, 38), quinoline (21, 39), pyrazole (40) and
indole (41) could be efficiently coupled with ammonia or
amines under light-irradiated heterogeneous conditions.
In terms of amines, the tolerated substituent groups could
not only include benzyl (22–41), a protecting group usually
employed in organic synthesis, but also comprise n-alkyl
(42), cyclic alkyl (43, 44), hydroxyl substituted alkyl (45,
48), allyl (46), 2-furanylmethyl (47, 50), 2-thienylmethyl
(49–51) and phenethyl (52) groups. Taken together, this
method exhibited a good substrate scope for both (hetero)
aryl chlorides and nitrogen nucleophiles, enabling the gen-
eration of target products in good to excellent yields (81%–
99%) under mild conditions.
Tandem reactions from conjunctive dihalide electrophiles
could allow modular and rapid access to diversified mole-
cules for applications such as drug and material discovery
[39,40]. Based on the different reactivities of aromatic C–Br
and C–Cl bonds demonstrated in homogeneous transition-
metal-catalyzed couplings [41], the chemical selectivity of
Cu@L6 was evaluated in tandem heterogeneous couplings
Scheme 2 Cu@L6 catalyzed tandem C-N coupling of conjunctive diha-
lides. Conditions: Br–R1–Cl (0.5 mmol), R2–NH2 and R3–NH2 (amine=
0.51 mmol; aqueous ammonia=1.0 mmol), Cu@L6 (0.05 mmol), K3PO4
(1.2 mmol), DMSO (0.5 mL), visible light at 405 nm. Isolated yields are
based on Br–R1–Cl (color online).

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Wang et al. Sci China Chem
a)
2014, 43: 3525–3550
Table 2 Recycling experiments of Cu@L6 catalyzed C-N coupling
13 Senra JD, Aguiar LCS, Simas ABC. Curr Org Synth, 2011, 8: 53–78
14 Lipshutz BH. Chem, 2018, 4: 2004–2007
15 Dery S, Kim S, Haddad D, Cossaro A, Verdini A, Floreano L, Toste
FD, Gross E. Chem Sci, 2018, 9: 6523–6531
16 Ye R, Zhao J, Wickemeyer BB, Toste FD, Somorjai GA. Nat Catal,
2018, 1: 318–325
17 Li XF, Yu SB, Yang B, Tian J, Wang H, Zhang DW, Liu Y, Li ZT. Sci
China Chem, 2018, 61: 830–835
18 Chen F, Li W, Sahoo B, Kreyenschulte C, Agostini G, Lund H, Junge
K, Beller M. Angew Chem Int Ed, 2018, 57: 14488–14492
19 Lee JS, Kapustin EA, Pei X, Llopis S, Yaghi OM, Toste FD. Chem,
2020, 6: 142–152
20 Handa S, Wang Y, Gallou F, Lipshutz BH. Science, 2015, 349: 1087–
1091
21 Hirai Y, Uozumi Y. Chem Asian J, 2010, 5: 1788–1795
22 Baig RBN, Nadagouda MN, Varma RS. Green Chem, 2014, 16: 4333–
4338
23 Creutz SE, Lotito KJ, Fu GC, Peters JC. Science, 2012, 338: 647–651
24 Kainz QM, Matier CD, Bartoszewicz A, Zultanski SL, Peters JC, Fu
GC. Science, 2016, 351: 681–684
Run
1
Light irradiation Time (h)
GC yield
>99
>99
99
Isolated yield
405 nm
405 nm
405 nm
405 nm
405 nm
405 nm
48
48
48
48
48
48
>99
99
99
98
97
97
2
3
4
99
5
99
6
98
a) Conditions: 4-nBu–Ph–Cl (0.5 mmol), aqueous ammonia (1 mmol),
Cu@L6 (0.05 mmol), K3PO4 (0.6 mmol), DMSO (0.5 mL), 80 °C.
25 Feng Z, Zeng T, Xuan J, Liu Y, Lu L, Xiao WJ. Sci China Chem,
2016, 59: 171–174
26 Chen Z, Lu F, Yuan F, Sun J, Du L, Li Z, Gao M, Shi R, Lei A. Sci
China Chem, 2019, 62: 1497–1500
would provide new opportunities for catalyst design and
benefit related synthesis.
27 Miao M, Liao LL, Cao GM, Zhou WJ, Yu DG. Sci China Chem, 2019,
62: 1519–1524
28 Kibriya G, Ghosh D, Hajra A. Sci China Chem, 2020, 63: 42–46
29 Ziegler DT, Choi J, Muñoz-Molina JM, Bissember AC, Peters JC, Fu
GC. J Am Chem Soc, 2013, 135: 13107–13112
Acknowledgements This work was supported by the National Natural
Science Foundation of China (21704016, 21971044).
Conflict of interest The authors declare no conflict of interest.
30 Fan M, Zhou W, Jiang Y, Ma D. Org Lett, 2015, 17: 5934–5937
31 Zhou W, Fan M, Yin J, Jiang Y, Ma D. J Am Chem Soc, 2015, 137:
11942–11945
32 Chen Z, Ma D. Org Lett, 2019, 21: 6874–6878
33 Kupgan G, Liyana-Arachchi TP, Colina CM. Langmuir, 2017, 33:
11138–11145
Supporting information The supporting information is available online at
http://chem.scichina.com and http://link.springer.com/journal/11426. The
supporting materials are published as submitted, without typesetting or
editing. The responsibility for scientific accuracy and content remains en-
tirely with the authors.
34 Shen M, Liu H, Yu C, Yin Z, Muzzio M, Li J, Xi Z, Yu Y, Sun S. J Am
Chem Soc, 2018, 140: 16460–16463
35 Rauws TRM, Maes BUW. Chem Soc Rev, 2012, 41: 2463–2497
36 Kolodziej K, Romanowska J, Stawinski J, Boryski J, Dabrowska A,
Lipniacki A, Piasek A, Kraszewski A, Sobkowski M. Eur J Medicinal
Chem, 2015, 100: 77–88
1
2
Horton DA, Bourne GT, Smythe ML. Chem Rev, 2003, 103: 893–930
Cooper TWJ, Campbell IB, Macdonald SJF. Angew Chem Int Ed,
2010, 49: 8082–8091
Devendar P, Qu RY, Kang WM, He B, Yang GF. J Agric Food Chem,
2018, 66: 8914–8934
3
37 Hassan Z, Spuling E, Knoll DM, Lahann J, Bräse S. Chem Soc Rev,
2018, 47: 6947–6963
38 Haiduc I. J Coord Chem, 2019, 72: 2805–2903
39 Fyfe JWB, Seath CP, Watson AJB. Angew Chem Int Ed, 2014, 53:
12077–12080
40 Xu L, Zhang S, Li P. Chem Soc Rev, 2015, 44: 8848–8858
41 Wang E, Chen M. Chem Sci, 2019, 10: 8331–8337
42 Mikhailine AA, Grasa Mannino GA, Colacot TJ. Org Lett, 2018, 20:
2301–2305
4
5
6
7
8
9
Mosrin M, Knochel P. Chem Eur J, 2009, 15: 1468–1477
Evano G, Blanchard N, Toumi M. Chem Rev, 2008, 108: 3054–3131
Mari M, Bartoccini F, Piersanti G. J Org Chem, 2013, 78: 7727–7734
Eelkema R, Anderson HL. Macromolecules, 2008, 41: 9930–9933
Ruiz-Castillo P, Buchwald SL. Chem Rev, 2016, 116: 12564–12649
Surry DS, Buchwald SL. Angew Chem Int Ed, 2008, 47: 6338–6361
10 Vo GD, Hartwig JF. J Am Chem Soc, 2009, 131: 11049–11061
11 Ullmann F. Ber Dtsch Chem Ges, 1903, 36: 2382–2384
12 Sambiagio C, Marsden SP, Blacker AJ, McGowan PC. Chem Soc Rev,