Nickel-Catalyzed N, N-Diarylation of 8-Aminoquinoline with Large Steric Aryl Bromides and Fluorescence of Products

Article abstract of DOI:10.1021/acs.orglett.1c00463

A simple and efficient methodology for the synthesis of large sterically hindered triarylamines in a single step was developed. A direct N,N-diarylation of 8-aminoquinoline with sterically hindered bromides, making use of inexpensive nickel as a catalyst and simple sodium salt as a base, gives the products in good to excellent yields. Various bromides and substituted 8-aminoquinolines are tolerated. Preliminary fluorescence results indicate that these sterically hindered and conjugated triarylamines may have some potential in material chemistry.

Full text of DOI:10.1021/acs.orglett.1c00463

pubs.acs.org/OrgLett
Letter
Nickel-Catalyzed N,N‑Diarylation of 8‑Aminoquinoline with Large
Steric Aryl Bromides and Fluorescence of Products
Mingpan Yan,∥ Longzhi Zhu,∥ Xingxing Zhang, Shuang-Feng Yin, Nobuaki Kambe, and Renhua Qiu*
Cite This: Org. Lett. 2021, 23, 2514−2520
Read Online
sı
*
Metrics & More
Article Recommendations
Supporting Information
ACCESS
ABSTRACT: A simple and efficient methodology for the synthesis
of large sterically hindered triarylamines in a single step was
developed. A direct N,N-diarylation of 8-aminoquinoline with
sterically hindered bromides, making use of inexpensive nickel as a
catalyst and simple sodium salt as a base, gives the products in good
to excellent yields. Various bromides and substituted 8-amino-
quinolines are tolerated. Preliminary fluorescence results indicate
that these sterically hindered and conjugated triarylamines may have
some potential in material chemistry.
Scheme 1. Synthetic Routes of Triarylamines
arge sterically hindered triarylamines, especially those with
Llarge conjugated systems, such as carbazole and quino-
lines, have attracted wide attention in material chemistry.1
They are important skeletons in organic light-emitting diodes
(OLEDs), sensitized solar cells, and photochromic materials.
For example, as shown in Figure 1, TPD,2 TCTA,3 TPA-AC,4
and 4CzIPN5 and their structurally related compounds are well
known for their use in LED materials and photocatalysis.
Figure 1. Selected triarylamine skeleton in material chemistry.
have been disclosed.12 However, these copper systems usually
gave moderate yields when they were applied in the synthesis
of large hindered triarylamines from primary amines.13
Because of their wide applications in material chemistry, the
efficient synthesis of triarylamines, which were previously
obtained mainly from the Buchwald−Hartwig reaction and
Ullmann coupling, has attracted much attention in organic
synthesis. The first kind of reliable synthetic route is the N-
arylation of secondary arylamine with aryl halide under the
catalysis of Pd,6 Ni,7 or Cu8 salts (Scheme 1a). Another
straightforward route is the use of primary aryl amines to react
with two equivalents of aryl halides (Scheme 1b).9 With noble-
metal Pd catalysts, the relatively large sterically hindered
triarylamines can be synthesized in good yields.9e,10 The cheap
copper catalyst system with the second route has also been
disclosed but is mainly used in the occasion of active aryl
iodides as a coupling partner,11 and only a few examples with
more stable, cheaper, and relatively available aryl bromides
We are interested in the nickel catalysis.14 With the second
route, only one substrate was disclosed as a side product (26%)
catalyzed by a nickel/carbene complex.15 Although the yield is
somewhat lower, this pioneering work indicates that proper
coordination would be essential for the formation of
Received: February 7, 2021
Published: March 16, 2021
https://dx.doi.org/10.1021/acs.orglett.1c00463
© 2021 American Chemical Society
Org. Lett. 2021, 23, 2514−2520
2514

Organic Letters
pubs.acs.org/OrgLett
Letter
a
Table 1. Screening of Reaction Conditions
entry
catalyst (10 mol %)
base (3.0 equiv)
solvent (2.0 mL)
temperature (°C)
yield of 3a (%)
yield of 3a′ (%)
1
2
3
4
5
6
7
8
NiCl2(dppe)
NiCl2
Ni(OAc)2
Ni(OTf)2
NiCl2
NiCl2
NiCl2
NiCl2
NiCl2
NiCl2
NiCl2
NiCl2
NiCl2
CH3ONa
CH3ONa
CH3ONa
CH3ONa
KOH
Na2CO3
NaOH
NaOH
NaOH
NaOH
NaOH
NaOH
DMF
DMF
DMF
DMF
DMF
DMF
DMF
1,4-dioxane
toluene
CH3CN
DMF
DMF
DMF
150
150
150
150
150
150
150
150
150
150
140
160
150
150
72
93
91
90
trace
trace
96
ND
29
ND
72
94
24
trace
trace
trace
13
trace
0
trace
35
trace
19
9
10
11
12
13
14
trace
10
13
b
NaOH
NaOH
87
85
c
NiCl2
DMF
a
1a (0.2 mmol), 2a (0.6 mmol), catalyst (0.02 mmol), and base (0.6 mmol) in solvent (2.0 mL), 150 °C, N2, 16 h, sealed tube, isolated yield.
b
c
NiCl2 (0.01 mmol). NaOH (0.4 mmol). ND: not detected.
a
triarylamine by nickel catalysis. Our previous work demon-
strated that 8-aminoquinole exhibits excellent coordination
ability,14c−f,16 especially to nickel.14c−f Herein we developed a
highly efficient synthesis of large sterically hindered triaryl-
amines by a nickel-catalyzed N,N-diarylation of 8-aminoquino-
line with large sterically hindered bromides in the presence of a
simple sodium base (Scheme 1b-2).
Scheme 2. Substrate Scope for Aryl Bromides
Initially, 8-aminoquinoline (1a) and 9-(4-bromophenyl)-
9H-carbazole (2a) were selected as substrates for optimizing
the reaction conditions (Table 1). The target product 3a was
detected by adding 10 mol % nickel catalyst (NiCl2(dppe),
NiCl2, Ni(OAc)2, or Ni(OTf)2) and 3.0 equiv of CH3ONa as
the base (entries 1−4), and NiCl2 was found to be the best
(93%, entry 2). Among the bases investigated, NaOH was
found to be the best base, with a 96% yield of 3a (entries 5−7).
DMF was used prior to other investigated solvents, such as 1,4-
dioxane, toluene, and acetonitrile (entries 8−10). Among the
reaction temperatures investigated, 150 °C was the best
(entries 11 and 12). When we tried to reduce the amount of
NiCl2 (entry 13) or NaOH (entry 14), the reaction effect was
worse than before. The structure of 3a was unambiguously
confirmed by single-crystal X-ray analysis (shown in Scheme
2).17
With the optimized reaction conditions in hand, we
investigated the substrate scopes with respect to various aryl
bromides (Scheme 2). For the highly hindered 9-(4-
bromophenyl)carbazole analogues, the desired products 3a−
d could be obtained in high yields (79−96%). For 4-bromo-
N,N-diphenylaniline, the target product was obtained in 91%
yield (3e). For 4-bromobiphenyl and 4-bromoterphenyl
bromides, the corresponding products 3f and 3g were obtained
in 90 and 87% yields, respectively. With electron-withdrawing
groups of bromobenzene at the para position of the phenyl
moiety (4-F, 4-Cl, 4-CF3), the corresponding products 3h−j
were obtained in good yields (84−93%). When the methyl
group was attached to the meta or para position of the phenyl
group, the target compound could be obtained in good yield
(3l(m), 3l(m,m), and 3l(p): 73, 71, and 72%, respectively),
a
1a (0.2 mmol), 2 (3.0 equiv), NiCl2 (10 mol %), NaOH (3.0 equiv),
b
DMF (2.0 mL), N2, sealed tube, isolated yield. tBuONa (3.0 equiv)
and H2O (15.0 uL) was used instead of NaOH, 165 °C.
whereas when the methyl group was attached to the ortho
position, a higher temperature was required to obtain the
corresponding compound 3l(o) in moderate yield (22%).
Through the present method, the tetraphenyl ethylene (TPE)
motif that has been demonstrated to be one of the most
common structures in the aggregation-induced emission (AIE)
molecular library18 and its analogues can be introduced to 8-
aminoquinoline in good yields (3m−o).
As depicted in Scheme 3, we explored these reactions of 2a
with various 8-aminoquinoline derivatives. When different
substituent groups attached to the C2, C4, C5, C6, or C7
2515
https://dx.doi.org/10.1021/acs.orglett.1c00463
Org. Lett. 2021, 23, 2514−2520

Organic Letters
pubs.acs.org/OrgLett
Letter
a
Scheme 3. Substrate Scope for 8-Aminoquinolines
potential for further transformation,19 we achieved the
nitration of the large sterically hindered 3a in moderate yield
under the condition of Ni(NO3)2·6H2O as the nitrating
reagent (eq 2). The structure of 5 was confirmed by single-
crystal X-ray analysis.17
With two series of triarylamine compounds (3a−o; 4a−l) in
hand, we proceeded to characterize their fluorescence
performance (Figure 2, Table 2). The UV absorption
a
t
1 (0.2 mmol), 2a (3.0 equiv), NiCl2 (10 mol %), BuONa (3.0
equiv), H2O (15.0 uL), DMF (2.0 mL), N2, sealed tube, isolated
b
yield. NaOH (3.0 equiv) was used instead of tBuONa and H2O; the
isolated yield is listed in parentheses.
Figure 2. Fluorescence spectra of (A) 3a−o and (B) 4a−l in toluene
compared with Al(q)3 in CH2Cl2 as reference. For the full-size panels
A and B, see the SI (Figure S5).
position of the 8-aminoquinoline ring, the reactions proceeded
well with good yields of the corresponding products (4a−l) by
simply changing the base from NaOH to tBuONa and water. A
possible reason might be that different substituents would have
various steric and electronic effects on the coordination of the
nickel catalyst and aminoquinolines. Thus the in situ formation
wavelengths of all compounds ranged from 363 to 412 nm.
(See the Supporting Information, Figure S3 and S4.) The
maximum fluorescence emission wavelengths of these com-
pounds were from 435 to 584 nm, ranging from blue to
yellowish orange. Among the compounds 3a−o, compound 3g
had the highest fluorescence quantum yield of 23%. The
quantum yields of triarylamine products with different
substituents on the quinoline ring (4a−l) were higher than
those of the products without substitution (3a). Because of the
steric effect of the C2 methyl group of the quinoline ring on
the inhibition of rotation, 4a gave the best quantum yields
(31%), and the heterocyclic groups C5-furan (4i) and C5-
pyridine (4j) also increased the quantum yields to 27 and 25%,
respectively.
Previously, triarylamine was demonstrated to have good AIE
performance.21 We therefore tested the AIE performance of
compound 3a and found that the fluorescence intensity
increased two-fold when the water fraction was increased from
0 to 95% (Figure 3A), indicating some potential in AIE, but its
background signal was a problem. This property of 3a could be
modified after the introduction of a less conjugated and rigid
TPE motif, which was demonstrated to play an important role
in AIE by Tang et al.22 As shown in Figure 3B, 3m with two
TPE motifs exhibited a 9.5 times better AIE effect when the
water fraction was increased from 0 to 95%. Furthermore,
compared with the single TPE and 3a (Figure 3A−D), 3m had
t
of the base by BuONa and H2O was required in some case.
When the quinoline ring had a methyl substitution at the C2
position, it could react with 9-(4-bromophenyl)-9H-carbazole
to form the corresponding product 4a in 68% yield. When a
phenyl group was attached to the C4 position, the desired
product 4b was obtained in 95% yield. As for the C5
substituents, when electron-withdrawing groups (5-Br, 4-
fluorophenyl, 4-trifluoromethylphenyl) or electron-donating
groups (phenyl, 4-methylphenyl, 1-naphthyl) were attached to
the C5 position, the corresponding products were generated in
62−92% yields(4c−h). Furthermore, when a heterocyclic
group, such as 3-furanyl or 4-pyridyl, was attached to the C5
position, the corresponding products 4i and 4j were generated
in 67 and 89% yields, respectively. Other positions, such as a
methoxy group at the C6 position (4k) or a methyl group at
the C7 position (4l), of the 8-aminoquinoline core were also
investigated, and the desired products were obtained in good
yields.
To show the potential use of this protocol, a gram-scale
synthesis was carried out. When using 2.0 mmol of 1a and 6.0
mmol of 2a under standard conditions, the corresponding
triarylamine product 3a could be obtained in 83% yield (1.04
g) (eq 1). Because the nitro-substituted quinolines have the
2516
https://dx.doi.org/10.1021/acs.orglett.1c00463
Org. Lett. 2021, 23, 2514−2520

Organic Letters
pubs.acs.org/OrgLett
Letter
a
Table 2. UV Absorption and Fluorescence Properties
compd.
λmax (nm)
λem (nm)
Φ (%)
compd.
λmax (nm)
λem (nm)
Φ (%)
3a
3c
3e
3g
3i
3k
3m
3o
4b
4d
4f
388
385
412
358
384
387
373
385
397
399
399
397
408
381
508
515
584
501
477
493
509
513
522
519
515
512
537
502
12
6
4
23
7
10
5
16
16
27
23
18
25
17
3b
3d
3f
3h
393
405
395
385
363
399
385
379
385
405
402
398
379
381
519
524
501
491
435
511
512
496
512
530
519
513
499
518
11
20
12
1
5
9
3j
3l(p)
3n
4a
4c
4e
4g
4i
4k
Al(q)3
9
31
16
17
20
27
14
17
4h
4j
4l
a
UV absorption was controlled between 0.025 and 0.050 in toluene for the fluorescence quantum yield. The data of fluorescence emission were
excited at the maximum absorption wavelength. ΦF of Al(q)3 is 17% in CH2Cl2.20
Scheme 4. Control Experiments
Figure 3. Photoluminescence (PL) spectra of (A) 3a, (B) 3m, and
(C) TPE in THF with varying amounts of water (% fraction of
volume) with the same initial concentration of 5 μmol/L. (D)
Changes in the PL peak intensity with the water fraction. The
definition of fw is as follows: fw = Vwater/(VTHF + Vwater). For the full-
size panels A−D, see the SI (Figure S6).
which indicates that the N-arylated product 3a′ is a probable
intermediate.
On the basis of the previously described control experiments
and related literature,6c,7b,16a,23 we propose here a possible
mechanism (Scheme 5). First, the NiCl2 is reduced to Ni(0)
by 8-aminoquinoline (1a); then, catalytic cycle I starts. After
the oxidative addition of aryl bromide, intermediate B is
formed. Then, 1a coordinated with B forms intermediate C.
After successively undergoing deprotonation and reductive
elimination, the monosubstituted intermediate E is generated,
which then participates in the next catalytic cycle II. After
reacting with intermediate B for the second time, the
intermediate F is generated, which undergoes deprotonation
with the base to form G, followed by reductive elimination to
generate the N,N-diarylated product H, and the Ni(0) catalyst
is regenerated.
In summary, we have developed a simple and efficient
methodology for the synthesis of large sterically hindered
triarylamines in a one-pot manner. A series of triarylamines can
be obtained in good yields by using the inexpensive NiCl2 and
sodium base. Preliminary fluorescence results indicate that
these triarylamines with large conjugated systems may have
some potential in material chemistry.
a higher fluorescence intensity than that of TPE and a weaker
background signal than that of 3a at the same concentration.
To understand the reaction, we performed some control
experiments to explore the possible reaction mechanism
(Scheme 4). When using 1-naphthylamine (1a′) without a
bidentate coordination site to react with 2a under standard
conditions, neither the N,N-diarylated product 6 nor the N-
arylated product 6′ was obtained (Scheme 4a), indicating that
the bidentate coordination of quinoline is critical (Scheme 4a).
In addition, when Ni(COD)2 was used as the catalyst instead
of NiCl2 (Scheme 4b), the target product 3a was also obtained
in good yield (86%), indicating that the active species of the
reaction might involve a nickel(0)/nickel(II) process. Without
a base and with the addition of 15.0 μL of H2O to the DMF
solution, the N-arylated product 3a′ could be isolated in 40%
yield (Scheme 4c), but no N,N-diarylated product 3a was
detected, indicating that the strong base plays an important
role in the N,N-diarylation of quinoline. Then, we used 3a′ to
react with 2a with NaOH, and the target product 3a was
obtained in 95% yield under standard conditions (Scheme 4d),
2517
https://dx.doi.org/10.1021/acs.orglett.1c00463
Org. Lett. 2021, 23, 2514−2520

Organic Letters
pubs.acs.org/OrgLett
Letter
Xingxing Zhang − State Key laboratory of Chemo/Biosensing
and Chemometrics, Advanced Catalytic Engineering Research
Center of the Ministry of Education, College of Chemistry and
Chemical Engineering, Shenzhen Research Institute, Hunan
University, Changsha 410082, P. R. China
Scheme 5. Proposed Mechanism
Shuang-Feng Yin − State Key laboratory of Chemo/Biosensing
and Chemometrics, Advanced Catalytic Engineering Research
Center of the Ministry of Education, College of Chemistry and
Chemical Engineering, Shenzhen Research Institute, Hunan
University, Changsha 410082, P. R. China
Nobuaki Kambe − State Key laboratory of Chemo/Biosensing
and Chemometrics, Advanced Catalytic Engineering Research
Center of the Ministry of Education, College of Chemistry and
Chemical Engineering, Shenzhen Research Institute, Hunan
University, Changsha 410082, P. R. China; The Institute of
Scientific and Industrial Research, Osaka University, Ibaraki-
shi, Osaka 567-0047, Japan
Complete contact information is available at:
https://pubs.acs.org/10.1021/acs.orglett.1c00463
ASSOCIATED CONTENT
* Supporting Information
The Supporting Information is available free of charge at
https://pubs.acs.org/doi/10.1021/acs.orglett.1c00463.
■
Author Contributions
sı
∥M.Y. and L.Z. contribute equally to this work.
Notes
The authors declare no competing financial interest.
Detailed experimental procedures, characterization data,
1
spectra copies of the H, 19F, 13C NMR for obtained
ACKNOWLEDGMENTS
products, and X-ray data of 3a and 5 (PDF)
FAIR data, including the primary NMR FID files for
compounds 1b−j, 2c, 2o, 3a−o, 4a−l, 5, and 3a′ (ZIP)
■
We thank the Natural Science Foundation of China (nos.
21676076, 21878071, 21971060, and 21725602), the Natural
Science Foundation of Changsha (kq2004008), the Hu-Xiang
High Talent Project in Hunan Province (2018RS3042), and
the Recruitment Program for Foreign Experts of China
(WQ20164300353) for financial support. R.Q. thanks Prof.
Lin Yuan (Hunan University) and Prof. Wai-Yeung Wong
(The Hong Kong Polytechnic University) for the helpful
discussion.
Accession Codes
CCDC 2056743 and 2060002 contain the supplementary
crystallographic data for this paper. These data can be obtained
free of charge via www.ccdc.cam.ac.uk/data_request/cif, or by
emailing data_request@ccdc.cam.ac.uk, or by contacting The
Cambridge Crystallographic Data Centre, 12 Union Road,
Cambridge CB2 1EZ, UK; fax: +44 1223 336033.
REFERENCES
■
AUTHOR INFORMATION
Corresponding Author
■
(1) (a) Zhang, Y.; Zhou, X.; Zhou, C.; Su, Q.; Chen, S.; Song, J.;
Wong, W.-Y. High-efficiency Organic Electroluminescent Materials
Based on The D−A−D Type with Sterically Hindered Methyl
Groups. J. Mater. Chem. C 2020, 8, 6851−6860. (b) Chen, J.; Xia, J.;
Yu, H.-J.; Zhong, J.-X.; Wu, X.-K.; Qin, Y.-S.; Jia, C.; She, Z.; Kuang,
D.-B.; Shao, G. Asymmetric 3D Hole-Transporting Materials Based
on Triphenylethylene for Perovskite Solar Cells. Chem. Mater. 2019,
31, 5431−5441. (c) Gómez-Bombarelli, R.; Aguilera-Iparraguirre, J.;
Hirzel, T. D.; Duvenaud, D.; Maclaurin, D.; Blood-Forsythe, M. A.;
Chae, H. S.; Einzinger, M.; Ha, D.-G.; Wu, T.; Markopoulos, G.; Jeon,
S.; Kang, H.; Miyazaki, H.; Numata, M.; Kim, S.; Huang, W.; Hong, S.
I.; Baldo, M.; Adams, R. P.; Aspuru-Guzik, A. Design of Efficient
Molecular Organic Light-emitting Diodes by a High-throughput
Virtual Screening And Experimental Approach. Nat. Mater. 2016, 15,
1120−1127. (d) Wang, J.; Liu, K.; Ma, L.; Zhan, X. Triarylamine:
Versatile Platform for Organic, Dye-Sensitized, and Perovskite Solar
Cells. Chem. Rev. 2016, 116, 14675−14725.
(2) Thelakkat, M.; Hagen, J.; Haarer, D.; Schmidt, H. W.
Poly(triarylamine)s- synthesis and Application in Electroluminescent
Devices and Photovoltaics. Synth. Met. 1999, 102, 1125−1128.
(3) Kang, J.-W.; Lee, S.-H.; Park, H.-D.; Jeong, W.-I.; Yoo, K.-M.;
Park, Y.-S.; Kim, J.-J. Low Roll-off of Efficiency at High Current
Density in Phosphorescent Organic Light Emitting Diodes. Appl.
Phys. Lett. 2007, 90, 223508.
Renhua Qiu − State Key laboratory of Chemo/Biosensing and
Chemometrics, Advanced Catalytic Engineering Research
Center of the Ministry of Education, College of Chemistry and
Chemical Engineering, Shenzhen Research Institute, Hunan
University, Changsha 410082, P. R. China; orcid.org/
0000-0002-8423-9988; Email: renhuaqiu1@hnu.edu.cn
Authors
Mingpan Yan − State Key laboratory of Chemo/Biosensing
and Chemometrics, Advanced Catalytic Engineering Research
Center of the Ministry of Education, College of Chemistry and
Chemical Engineering, Shenzhen Research Institute, Hunan
University, Changsha 410082, P. R. China
Longzhi Zhu − State Key laboratory of Chemo/Biosensing and
Chemometrics, Advanced Catalytic Engineering Research
Center of the Ministry of Education, College of Chemistry and
Chemical Engineering, Shenzhen Research Institute, Hunan
University, Changsha 410082, P. R. China; Center for
Biomedical Optics and Photonics (CBOP) & College of
Physics and Optoelectronic Engineering, Key Laboratory of
Optoelectronic Devices and Systems, Shenzhen University,
Shenzhen 518060, P. R. China; orcid.org/0000-0001-
5161-9944
(4) (a) Zhou, C.; Zhang, T.; Zhang, S.; Liu, H.; Gao, Y.; Su, Q.; Wu,
Q.; Li, W.; Chen, J.; Yang, B. Isomerization Effect of Triphenylamine-
acridine Derivatives on Excited-state Modification, Photophysical
2518
https://dx.doi.org/10.1021/acs.orglett.1c00463
Org. Lett. 2021, 23, 2514−2520

Organic Letters
pubs.acs.org/OrgLett
Letter
Property and Electroluminescence Performance. Dyes Pigm. 2017,
146, 558−566. (b) Li, W.; Pan, Y.; Yao, L.; Liu, H.; Zhang, S.; Wang,
C.; Shen, F.; Lu, P.; Yang, B.; Ma, Y. A Hybridized Local and Charge-
Transfer Excited State for Highly Efficient Fluorescent OLEDs:
Molecular Design, Spectral Character, and Full Exciton Utilization.
Adv. Opt. Mater. 2014, 2, 892−901.
(5) Speckmeier, E.; Fischer, T. G.; Zeitler, K. A Toolbox Approach
To Construct Broadly Applicable Metal-Free Catalysts for Photo-
redox Chemistry: Deliberate Tuning of Redox Potentials and
Importance of Halogens in Donor−Acceptor Cyanoarenes. J. Am.
Chem. Soc. 2018, 140, 15353−15365.
Nucleophilic Aromatic Substitution. 2. Single Catalytic Species from
Three Different Oxidation States of Copper in an Ullmann Synthesis
of Triarylamines. J. Am. Chem. Soc. 1987, 109, 1496−1502.
(9) Select examples of the palladium-catalyzed N,N-diarylation of
primary aryl amines with aryl chlorides: (a) Tao, X.; Li, L.; Zhou, Y.;
Qian, X.; Zhao, M.; Cai, L.; Xie, X. PdCl2(Ph3P)2/Salicylaldimine
Catalyzed Diarylation of Anilines with Unactivated Aryl Chlorides.
Chin. J. Chem. 2017, 35, 1749−1754. (b) Harris, M. C.; Buchwald, S.
L. One-Pot Synthesis of Unsymmetrical Triarylamines from Aniline
Precursors. J. Org. Chem. 2000, 65, 5327−5333. (c) Hartwig, J. F.;
Kawatsura, M.; Hauck, S. I.; Shaughnessy, K. H.; Alcazar-Roman, L.
M. Room-Temperature Palladium-Catalyzed Amination of Aryl
Bromides and Chlorides and Extended Scope of Aromatic C−N
Bond Formation with a Commercial Ligand. J. Org. Chem. 1999, 64,
5575−5580. Select examples of the palladium-catalyzed N,N-
diarylation of primary aryl amines with aryl bromides: (d) Topchiy,
M. A.; Dzhevakov, P. B.; Rubina, M. S.; Morozov, O. S.; Asachenko,
A. F.; Nechaev, M. S. Solvent-Free Buchwald−Hartwig (Hetero)-
arylation of Anilines, Diarylamines, and Dialkylamines Mediated by
Expanded-Ring N-Heterocyclic Carbene Palladium Complexes. Eur. J.
Org. Chem. 2016, 2016, 1908−1914. (e) Cai, L.; Qian, X.; Song, W.;
Liu, T.; Tao, X.; Li, W.; Xie, X. Effects of Solvent and Base on the
Palladium-catalyzed Amination: PdCl2(Ph3P)2/Ph3P-catalyzed Selec-
tive Arylation of Primary Anilines with Aryl Bromides. Tetrahedron
2014, 70, 4754−4759. (f) Monguchi, Y.; Kitamoto, K.; Ikawa, T.;
Maegawa, T.; Sajiki, H. Evaluation of Aromatic Amination Catalyzed
by Palladium on Carbon: A Practical Synthesis of Triarylamines. Adv.
Synth. Catal. 2008, 350, 2767−2777. (g) Louie, J.; Hartwig, J. F.; Fry,
A. J. Discrete High Molecular Weight Triarylamine Dendrimers
Prepared by Palladium-Catalyzed Amination. J. Am. Chem. Soc. 1997,
119, 11695−11696. Palladium-catalyzed N,N-diarylation of primary
aryl amines with aryl iodides: (h) Nandakumar, M. V.; Verkade, J. G.
One-Pot Sequential N and C Arylations: An Efficient Methodology
for the Synthesis of Trans 4-N,N-Diaryl Aminostilbenes. Angew.
Chem., Int. Ed. 2005, 44, 3115−3118.
(6) Some reviews of the N-arylation of secondary arylamine with aryl
halide under the catalysis of Pd: (a) Forero-Cortés, P. A.; Haydl, A.
M. The 25th Anniversary of the Buchwald−Hartwig Amination:
Development, Applications, and Outlook. Org. Process Res. Dev. 2019,
23, 1478−1483. (b) Hartwig, J. F. Evolution of a Fourth Generation
Catalyst for the Amination and Thioetherification of Aryl Halides.
Acc. Chem. Res. 2008, 41, 1534−1544. (c) Hartwig, J. F. Transition
Metal Catalyzed Synthesis of Arylamines and Aryl Ethers from Aryl
Halides and Triflates: Scope and Mechanism. Angew. Chem., Int. Ed.
1998, 37, 2046−2067. Select examples of the N-arylation of
secondary arylamine with aryl halide under the catalysis of Pd:
(d) Kubota, K.; Seo, T.; Koide, K.; Hasegawa, Y.; Ito, H. Olefin-
accelerated Solid-state C−N Cross-coupling Reactions Using
Mechanochemistry. Nat. Commun. 2019, 10, 111. (e) Sá, S.;
Gawande, M. B.; Velhinho, A.; Veiga, J. P.; Bundaleski, N.;
Trigueiro, J.; Tolstogouzov, A.; Teodoro, O. M. N. D.; Zboril, R.;
Varma, R. S.; Branco, P. S. Magnetically Recyclable Magnetite−
Palladium (Nanocat-Fe−Pd) Nanocatalyst for the Buchwald−
Hartwig Reaction. Green Chem. 2014, 16, 3494−3500. (f) Hirai, Y.;
Uozumi, Y. Clean Synthesis of Triarylamines: Buchwald−Hartwig
Reaction in Water with Amphiphilic Resin-supported Palladium
Complexes. Chem. Commun. 2010, 46, 1103−1105. (g) Shen, Q.;
Ogata, T.; Hartwig, J. F. Highly Reactive, General and Long-Lived
Catalysts for Palladium-Catalyzed Amination of Heteroaryl and Aryl
Chlorides, Bromides, and Iodides: Scope and Structure−Activity
Relationships. J. Am. Chem. Soc. 2008, 130, 6586−6596.
(7) (a) Panahi, F.; Roozbin, F.; Rahimi, S.; Moayyed, M.; Valaei, A.;
Iranpoor, N. A Triazine-phosphite Polymeric Ligand Bearing Cage-
like P,N-ligation Sites: an Efficient Ligand in the Nickel-Catalyzed
Amination of Aryl Chlorides and Phenols. RSC Adv. 2016, 6, 80670−
80678. (b) Li, X.-L.; Wu, W.; Fan, X.-H.; Yang, L.-M. Nickel-
catalyzed Triarylamine Synthesis: Synthetic and Mechanistic Aspects.
Org. Biomol. Chem. 2014, 12, 1232−1236. (c) Gao, C.-Y.; Cao, X.;
Yang, L.-M. Nickel-catalyzed Cross-coupling of Diarylamines with
Haloarenes. Org. Biomol. Chem. 2009, 7, 3922−3925. (d) Chen; Yang,
L.-M. Arylation of Diarylamines Catalyzed by Ni(II)−PPh3 System.
Org. Lett. 2005, 7, 2209−2211.
(8) Some reviews of the N-arylation of secondary arylamine with aryl
halide under the catalysis of Cu: (a) Sambiagio, C.; Marsden, S. P.;
Blacker, A. J.; McGowan, P. C. Copper Catalysed Ullmann Type
Chemistry: from Mechanistic Aspects to Modern Development.
Chem. Soc. Rev. 2014, 43, 3525−3550. (b) Monnier, F.; Taillefer, M.
Catalytic C-C, C-N, and C-O Ullmann-Type Coupling Reactions.
Angew. Chem., Int. Ed. 2009, 48, 6954−6971. Select examples of the
N-arylation of secondary arylamine with aryl halide under the catalysis
of Cu: (c) Singh, G.; Kumar, M.; Bhalla, V. Ultrafine Hybrid Cu2O−
Fe2O3 Nanoparticles Stabilized by Hexaphenylbenzene-based Supra-
molecular Assemblies: a Photocatalytic System for the Ullmann−
Goldberg Coupling Reaction. Green Chem. 2018, 20, 5346−5357.
(d) Yoo, W.-J.; Tsukamoto, T.; Kobayashi, S. Visible Light-Mediated
Ullmann-Type C−N Coupling Reactions of Carbazole Derivatives
and Aryl Iodides. Org. Lett. 2015, 17, 3640−3642. (e) Xu, H.; Wolf,
C. Copper Catalyzed Coupling of Aryl Chlorides, Bromides and
Iodides with Amines and Amides. Chem. Commun. 2009, 1715−1717.
(f) Gujadhur, R. K.; Bates, C. G.; Venkataraman, D. Formation of
Aryl−Nitrogen, Aryl−Oxygen, and Aryl−Carbon Bonds Using Well-
defined Copper(I)-Based Catalysts. Org. Lett. 2001, 3, 4315−4317.
(g) Paine, A. J. Mechanisms and Models for Copper Mediated
(10) Some examples of the application of palladium-catalyzed
primary amines to synthesize large hindered triarylamines: (a) Lee,
C.-H.; Tang, M.-C.; Wong, Y.-C.; Chan, M.-Y.; Yam, V. W.-W. Sky-
Blue-Emitting Dendritic Alkynylgold(III) Complexes for Solution-
Processable Organic Light-Emitting Devices. J. Am. Chem. Soc. 2017,
139, 10539−10550. (b) Lin, Z.-M.; Zheng, C.; Xiao, J.-J.; Chen, R.-F.;
Zhao, P.; Song, J.; An, Z.-F.; Tian, H.; Huang, W. Facile Synthesis and
Optoelectronic Properties of N,N-difluorenevinylaniline-based Mole-
cules. New J. Chem. 2012, 36, 1512−1518. (c) Ince, M.; Cardinali, F.;
Yum, J.-H.; Martínez-Díaz, M. V.; Nazeeruddin, M. K.; Grätzel, M.;
Torres, T. Convergent Synthesis of Near-Infrared Absorbing, “Push−
Pull”, Bisthiophene-Substituted, Zinc(II) Phthalocyanines and Their
Application in Dye-Sensitized Solar Cells. Chem. - Eur. J. 2012, 18,
6343−6348. (d) Ye, H.; Zhao, B.; Liu, M.; Zhou, X.; Li, Y.; Li, D.; Su,
S.-J.; Yang, W.; Cao, Y. Dual-functional Conjugated Polymers Based
on Trifluoren-2-yl-amine for RGB Organic Light-emitting Diodes. J.
Mater. Chem. 2011, 21, 17454−17461.
(11) Select examples of the copper-catalyzed N,N-diarylation of
primary aryl amines with aryl iodides: (a) Modha, S. G.; Popescu, M.
V.; Greaney, M. F. Synthesis of Triarylamines via Sequential C−N
Bond Formation. J. Org. Chem. 2017, 82, 11933−11938. (b) Zhu, D.;
Liu, Q.; Luo, B.; Chen, M.; Pi, R.; Huang, P.; Wen, S. Synthesis of
Carbazoles via One-pot Copper-Catalyzed Amine Insertion into
Cyclic Diphenyleneiodoniums as a Strategy to Generate a Drug-Like
Chemical Library. Adv. Synth. Catal. 2013, 355, 2172−2178.
(c) Zhao, Y.; Wang, Y.; Sun, H.; Li, L.; Zhang, H. Ullmann Reaction
in Tetraethyl Orthosilicate: a Novel Synthesis of Triarylamines and
Diaryl Ethers. Chem. Commun. 2007, 3186−3188. (d) Liu, Y.-H.;
Chen, C.; Yang, L.-M. Diazabutadiene: a Simple and Efficient Ligand
for Copper-catalyzed N-arylation of Aromatic Amines. Tetrahedron
Lett. 2006, 47, 9275−9278. (e) Gajare, A. S.; Toyota, K.; Yoshifuji,
M.; Ozawa, F. Application of a Diphosphinidenecyclobutene Ligand
in The Solvent-free Copper-Catalysed Amination Reactions of Aryl
Halides. Chem. Commun. 2004, 1994−1995.
2519
https://dx.doi.org/10.1021/acs.orglett.1c00463
Org. Lett. 2021, 23, 2514−2520

Organic Letters
pubs.acs.org/OrgLett
Letter
(12) Examples of the copper-catalyzed N,N-diarylation of primary
aryl amines with aryl bromides: (a) Srinivas, K.; Sivakumar, G.;
Ramesh Kumar, C.; Ananth Reddy, M.; Bhanuprakash, K.; Rao, V. J.;
Chen, C.-W.; Hsu, Y.-C.; Lin, J. T. Novel 1,3,4-oxadiazole Derivatives
as Efficient Sensitizers for Dye-sensitized Solar Cells: A Combined
Experimental and Computational Study. Synth. Met. 2011, 161,
1671−1681. (b) Liu, X.; Zhang, S. Efficient Iron/Copper Cocatalyzed
N-Arylation of Arylamines with Bromoarenes. Synlett 2011, 2011,
1137−1142. (c) Li, Y.; Wang, H.; Jiang, L.; Sun, F.; Fu, X.; Duan, C.
Copper-Catalyzed Direct Synthesis of Di- and Triphenylamines: A
Dramatic Accelerating Effect of 2-Aminophenols. Eur. J. Org. Chem.
2010, 2010, 6967−6973. (d) Guo, X.; Rao, H.; Fu, H.; Jiang, Y.;
Zhao, Y. An Inexpensive and Efficient Copper Catalyst for N-
Arylation of Amines, Amides and Nitrogen-Containing Heterocycles.
Adv. Synth. Catal. 2006, 348, 2197−2202.
(13) Some examples of the application of copper-catalyzed primary
amines to synthesize large hindered triarylamines: (a) Zhang, C.-H.;
Wang, L.-P.; Tan, W.-Y.; Wu, S.-P.; Liu, X.-P.; Yu, P.-P.; Huang, J.;
Zhu, X.-H.; Wu, H.-B.; Zhao, C.-Y.; Peng, J.; Cao, Y. Effective
Modulation of an Aryl Acetylenic Molecular System Based on
Dithienyldiketopyrrolopyrrole for Organic Solar Cells. J. Mater. Chem.
C 2016, 4, 3757−3764. (b) Maeda, T.; Nitta, S.; Sano, Y.; Tanaka, S.;
Yagi, S.; Nakazumi, H. Near-infrared Squaraine Sensitizers Bearing
Benzo[c,d]indolenine as an Acceptor Moiety. Dyes Pigm. 2015, 122,
160−167. (c) Okumoto, K.; Shirota, Y. New Class of Hole-Blocking
Amorphous Molecular Materials and Their Application in Blue-
Violet-Emitting Fluorescent and Green-Emitting Phosphorescent
Organic Electroluminescent Devices. Chem. Mater. 2003, 15, 699−
707. (d) Goodbrand, H. B.; Hu, N.-X. Ligand-Accelerated Catalysis of
the Ullmann Condensation: Application to Hole Conducting
Triarylamines. J. Org. Chem. 1999, 64, 670−674.
(14) (a) Zhang, D.; Le, L.; Qiu, R.; Wong, W.-Y.; Kambe, N. Nickel-
and Palladium-Catalyzed Cross-Coupling Reactions of Organostibines
with Organoboronic Acids. Angew. Chem., Int. Ed. 2021, 60, 3104−
3114. (b) Tong, Z.; Tang, Z.; Au, C.-T.; Qiu, R. Nickel-Catalyzed
Decarbonyloxidation of 3-Aryl Benzofuran-2(3H)-ones to 2-Hydrox-
ybenzophenones. J. Org. Chem. 2020, 85, 8533−8543. (c) Zhu, L.;
Sheng, X.; Li, Y.; Lu, D.; Qiu, R.; Kambe, N. Nickel-Catalyzed
Remote C4−H Arylation of 8-Aminoquinolines. Org. Lett. 2019, 21,
6785−6789. (d) Wang, X.; Xie, P.; Qiu, R.; Zhu, L.; Liu, T.; Li, Y.;
Iwasaki, T.; Au, C.-T.; Xu, X.; Xia, Y.; Yin, S.-F.; Kambe, N. Nickel-
catalysed Direct Alkylation of Thiophenes via Double C(sp3)−H/
C(sp2)−H Bond Cleavage: the Importance of KH2PO4. Chem.
Commun. 2017, 53, 8316−8319. (e) Wang, X.; Zhu, L.; Chen, S.;
Xu, X.; Au, C.-T.; Qiu, R. Nickel-Catalyzed Direct C (sp3)−H
Arylation of Aliphatic Amides with Thiophenes. Org. Lett. 2015, 17,
5228−5231. (f) Wang, X.; Qiu, R.; Yan, C.; Reddy, V. P.; Zhu, L.; Xu,
X.; Yin, S.-F. Nickel-Catalyzed Direct Thiolation of C(sp3)−H Bonds
in Aliphatic Amides. Org. Lett. 2015, 17, 1970−1973.
Dcalc = 1.083 g/cm3, 14 549 reflections measured (4.002 ≤ 2θ ≤
49.998), 6768 unique (Rint = 0.0306, Rsigma = 0.0541), which were
used in all calculations. The final [(I > 2σ(I)] R1 was 0.0574, and wR2
was 0.1422. Crystal data for C45H29N5O2 (5) (M = 671.73 g/mol):
monoclinic, space group P21/n (no. 14), a = 18.984(6) Å, b =
10.280(2) Å, c = 20.565(6) Å, β = 115.39(4), V = 3626(2) Å3, Z = 4,
T = 149.99(10) K, μ(Mo Kα) = 0.077 mm−1, Dcalc = 1.231 g/cm3,
16 000 reflections measured (4.384 ≤ 2θ ≤ 49.998), 6379 unique
(Rint = 0.1510, Rsigma = 0.1720), which were used in all calculations.
The final [(I > 2σ(I)] R1 was 0.1114, and wR2 was 0.2701.
(18) (a) Song, F.; Liu, B.; Tang, B. Z. Celebration of the 20th
Anniversary of Aggregation-induced Emission with Research High-
lights from Royal Society of Chemistry journals. J. Mater. Chem. C
2020, 8, 7972−7974. (b) Chen, Y.; Lam, J. W. Y.; Kwok, R. T. K.;
Liu, B.; Tang, B. Z. Aggregation-induced Emission: Fundamental
Understanding and Future Developments. Mater. Horiz. 2019, 6,
428−433.
(19) (a) Trost, B. M.; Ehmke, V.; O’Keefe, B. M.; Bringley, D. A.
Palladium-Catalyzed Dearomative Trimethylenemethane Cycloaddi-
tion Reactions. J. Am. Chem. Soc. 2014, 136, 8213−8216.
(b) Wienhöfer, G.; Baseda-Kruger, M.; Ziebart, C.; Westerhaus, F.
̈
A.; Baumann, W.; Jackstell, R.; Junge, K.; Beller, M. Hydrogenation of
Nitroarenes Using Defined Iron−phosphine Catalysts. Chem.
Commun. 2013, 49, 9089−9091. (c) Delfourne, E.; Roubin, C.;
Bastide, J. The First Synthesis of the Pentacyclic Pyridoacridine
Marine Alkaloids: Arnoamines A and B. J. Org. Chem. 2000, 65,
5476−5479.
(20) (a) Yang, T.; Cao, X.; Zhang, X.-X.; Ou, Y.; Au, C.-T.; Yin, S.-
F.; Qiu, R. Iodine-Catalyzed Synthesis of N,N-Chelate Organoboron
Aminoquinolate. J. Org. Chem. 2020, 85, 12430−12443. (b) Nagata,
Y.; Chujo, Y. Main-Chain-Type N,N-Chelate Organoboron Amino-
quinolate Polymers: Synthesis, Luminescence, and Energy Transfer
Behavior. Macromolecules 2008, 41, 3488−3492.
(21) (a) Usuki, T.; Shimada, M.; Yamanoi, Y.; Ohto, T.; Tada, H.;
Kasai, H.; Nishibori, E.; Nishihara, H. Aggregation-Induced Emission
Enhancement from Disilane-Bridged Donor−Acceptor−Donor Lumi-
nogens Based on the Triarylamine Functionality. ACS Appl. Mater.
Interfaces 2018, 10, 12164−12172. (b) Ning, Z.; Chen, Z.; Zhang, Q.;
Yan, Y.; Qian, S.; Cao, Y.; Tian, H. Aggregation-induced Emission
(AIE)-active Starburst Triarylamine Fluorophores as Potential Non-
doped Red Emitters for Organic Light-emitting Diodes and Cl2 Gas
Chemodosimeter. Adv. Funct. Mater. 2007, 17, 3799−3807.
(22) (a) Mei, J.; Leung, N. L. C.; Kwok, R. T. K.; Lam, J. W. Y.;
Tang, B. Z. Aggregation-Induced Emission: Together We Shine,
United We Soar! Chem. Rev. 2015, 115, 11718−11940. (b) Ding, D.;
Li, K.; Liu, B.; Tang, B. Z. Bioprobes Based on AIE Fluorogens. Acc.
Chem. Res. 2013, 46, 2441−2453.
(23) (a) Surry, D. S.; Buchwald, S. L. Dialkylbiaryl Phosphines in
Pd-Catalyzed Amination: a User’s Guide. Chem. Sci. 2011, 2, 27−50.
(b) Yu, Q.; Yang, Y.; Wan, J.-P.; Liu, Y. Copper-Catalyzed C5−H
Sulfenylation of Unprotected 8-Aminoquinolines Using Sulfonyl
Hydrazides. J. Org. Chem. 2018, 83, 11385−11391.
(15) Matsubara, K.; Ueno, K.; Koga, Y.; Hara, K. Nickel−NHC-
Catalyzed α-Arylation of Acyclic Ketones and Amination of
Haloarenes and Unexpected Preferential N-Arylation of 4-Amino-
propiophenone. J. Org. Chem. 2007, 72, 5069−5076.
(16) (a) Lei, J.; Yang, Y.; Peng, L.; Wu, L.; Peng, P.; Qiu, R.; Chen,
Y.; Au, C.-T.; Yin, S.-F. Copper-Catalyzed Oxidative C(sp3)−H/N−H
Cross-Coupling of Hydrocarbons with P(O)−NH Compounds: the
Accelerating Effect Induced by Carboxylic Acid Coproduct. Adv.
Synth. Catal. 2019, 361, 1689−1696. (b) Peng, Y.; Lei, J.; Qiu, R.;
Peng, L.; Au, C.-T.; Yin, S.-F. Chelation-assisted C−N Cross-coupling
of Phosphinamides and Aryl Boronic Acids with Copper Powder at
Room Temperature. Org. Biomol. Chem. 2018, 16, 4065−4070.
(c) Zhu, L.; Qiu, R.; Cao, X.; Xiao, S.; Xu, X.; Au, C.-T.; Yin, S.-F.
Copper-Mediated Remote C−H Bond Chalcogenation of Quinolines
on the C5 Position. Org. Lett. 2015, 17, 5528−5531.
(17) ORTEP drawings are shown with thermal ellipsoids at the 50%
probability level. Crystal data for C45H30N4 (3a) (M = 626.73 g/mol):
̅
triclinic, space group P1 (no. 2), a = 11.2401(7) Å, b = 13.0003(9) Å,
c = 14.8333(10) Å, α = 101.689(6), β = 100.851(6), γ = 109.561(6),
V = 1921.5(2) Å3, Z = 2, T = 293(2) K, μ(Mo Kα) = 0.064 mm−1,
2520
https://dx.doi.org/10.1021/acs.orglett.1c00463
Org. Lett. 2021, 23, 2514−2520