Catalytic and Aerobic Oxidative Biaryl Coupling of Anilines Using a Recyclable Heterogeneous Catalyst for Synthesis of Benzidines and Bicarbazoles

Article abstract of DOI:10.1021/acs.joc.0c02020

In this study, a heterogeneous rhodium-catalyzed oxidative homocoupling reaction of anilines utilizing molecular oxygen as the sole oxidant is reported. Employing a commercially available and recyclable Rh/C catalyst enabled the oxidative dimerization of various anilines, including N,N-disubstituted and N-monosubstituted anilines, as well as diarylamines, triarylamines, and carbazoles. Additionally, the catalytic protocol was extended to the ortho-ortho coupling of anilines, affording 2,2′-diaminobiphenyls with high regioselectivity. Notably, the developed approach provides rapid access to diversely functionalized benzidines and diaminobiphenyls in an operationally simple, practical, and environmentally friendly manner.

Full text of DOI:10.1021/acs.joc.0c02020

pubs.acs.org/joc
Article
Catalytic and Aerobic Oxidative Biaryl Coupling of Anilines Using a
Recyclable Heterogeneous Catalyst for Synthesis of Benzidines and
Bicarbazoles
Kenji Matsumoto,* Yasunori Toubaru, Shohei Tachikawa, Ayaka Miki, Kentaro Sakai, Syota Koroki,
Tsukasa Hirokane, Mitsuru Shindo, and Masahiro Yoshida
Cite This: https://dx.doi.org/10.1021/acs.joc.0c02020
Read Online
sı
*
Metrics & More
Article Recommendations
Supporting Information
ACCESS
ABSTRACT: In this study, a heterogeneous rhodium-catalyzed
oxidative homocoupling reaction of anilines utilizing molecular
oxygen as the sole oxidant is reported. Employing a commercially
available and recyclable Rh/C catalyst enabled the oxidative
dimerization of various anilines, including N,N-disubstituted and
N-monosubstituted anilines, as well as diarylamines, triarylamines,
and carbazoles. Additionally, the catalytic protocol was extended to
the ortho−ortho coupling of anilines, affording 2,2′-diaminobi-
phenyls with high regioselectivity. Notably, the developed
approach provides rapid access to diversely functionalized
benzidines and diaminobiphenyls in an operationally simple,
practical, and environmentally friendly manner.
friendly protocols for the preparation of diverse diaminobiaryls
remains a significant challenge.
INTRODUCTION
■
Oxidation of aryl amines has been widely known and
extensively utilized for the synthesis of π-conjugated functional
materials, such as organic dyes, pigments, and organic light-
emitting diodes.1 Owing to their electron-rich character and
low oxidation potential, aryl amines are easily oxidized by
various oxidants and electrochemical reactions. These
processes not only lead to the formation of nitro-, azo-, and
Benzidines and the related diaminobiphenyls have in recent
years attracted considerable attention due to their diverse
applicability. From the viewpoint of improved atom and step
economies, oxidative coupling of aniline derivatives provides a
remarkably concise and efficient access to benzidines.9 Several
methods have been reported for the oxidative homocoupling of
anilines using stoichiometric oxidants, such as TiCl4,10 Cu,11
FeCl3,12 or organic oxidants.13−15 On the other hand,
electrochemical reactions also represent a valuable and clean
approach for the oxidative coupling of electron-rich arenes,
including anilines.16 For instance, Waldvogel described direct
anodic cross-coupling reactions of anilides, which gave
nonsymmetric 2,2′-diaminobiphenyls in a highly selective
manner.17 In addition, catalytic oxidative homo- and cross-
coupling reactions of anilides using palladium, rhodium, and
nitrosonium salts as catalysts have also been reported.18 While
extensive efforts have been dedicated to the establishment of
effective methods for the catalytic oxidative coupling of
anilides, their application in catalytic oxidative coupling of
amide-containing compounds but also enable C−C and C−N
2
̌
́
bond formation. In 1991, Kocovsky and co-workers reported
the Cu-mediated oxidative coupling of aryl amines, which was
the first aryl−aryl bond-forming reaction conducted via
oxidation of aryl amines.3 Nonetheless, oxidative couplings of
aryl amines typically suffer from low yields and uncontrollable
overoxidation.4 Consequently, until recently, such catalytic
methods have been considerably less explored. The first
catalytic approach for homocoupling of naphthylamines
employing FeCl3 and mCPBA as co-oxidants was developed
in 2011.5 Recently, catalytic oxidative homocoupling and cross-
coupling reactions of 2-aminoanthracenes and aminonaph-
thalenes were achieved by utilizing heterogeneous catalysts
under mild aerobic conditions.6,7 Most recently, an iron-
catalyzed oxidative coupling of aryl amines under aerobic
conditions was studied and cross-coupling of tertiary anilines
with arenols was also reported.8 Despite the aforementioned
advances, the existing catalytic methods remain limited in
comparison to the oxidative coupling of phenolic compounds.
Moreover, since molecular oxygen is considered to be an ideal
oxidant, the development of catalytic and environmentally
Received: August 20, 2020
https://dx.doi.org/10.1021/acs.joc.0c02020
© XXXX American Chemical Society
J. Org. Chem. XXXX, XXX, XXX−XXX
A

The Journal of Organic Chemistry
pubs.acs.org/joc
Article
Scheme 1. Catalytic Oxidative Biaryl Coupling of Anilines
̈
anilines remains a challenge. In 2017, Knolker described an
the benzyl substituents on the nitrogen atom of 2d, which are
useful protecting groups, were well tolerated. Notably, 3,5-
xylidines possessing various substituents, such as morpholino
and pyrrolidino moieties, also gave the corresponding
benzidines 2e and 2f in excellent yields. In addition to 3,5-
xylidines, meta-substituted anilines containing bromo, chloro,
and ester groups afforded benzidines 2g, 2h, and 2i in
moderate to high yields; however, longer reaction times were
required to achieve the desired products. In the case of aniline
1i with an ester group, Pd/Al2O3 catalyst was needed for
accelerating the reaction rate.24 It is noteworthy that the
electron-withdrawing ester group as well as halogen sub-
stituents was well tolerated in this reaction. Triarylamines and
diarylamines underwent rapid dimerization to yield the
corresponding N-aryl substituted benzidines 2j, 2k, 2l, 2m,
and 2n. Since triarylamines are more sensitive to oxidation
than N,N-dialkyl-substituted anilines, we speculated that it
might be possible to reduce the amount of TFA in the reaction.
Following comprehensive screening, the reaction of triphenyl-
amine proceeded in the presence of just 5 equiv of TFA under
aerobic conditions, affording N,N,N′,N′-tetraphenylbenzidine
2k in a quantitative yield (see the Supporting Information).
The homocoupling reactions also proceeded well in the case of
substituted triarylamines, giving the corresponding biaryls 2l
and 2m in 84 and 76% yields, respectively. In contrast, the
oxidative couplings of ortho-toluidine derivatives 1o and 1p
were not successful and mostly afforded recovered starting
materials, even under forcing conditions with Pd/C as a
catalyst. Interestingly, Xiong also reported analogous trends for
FeCl3-promoted homocoupling reactions of anilines, i.e., N,N-
dibenzyl anilines containing ortho substituents were unreacti-
ve.12a Although simple primary anilines such as 2,6-xylidine
(1q) failed to yield the corresponding benzidine 2q but
afforded complex mixtures, we previously reported an efficient
dimerization of an octahydroanthracene derivative, which is an
aniline with condensed substituents, to the corresponding
benzidine 2r in a quantitative yield.6a
iron-catalyzed oxidative homocoupling of diarylamines utilizing
an iron(II)-hexadecafluorophthalocyanine (FeF16Pc)/MsOH/
air system (Scheme 1A).8a Recently, we reported the
intramolecular biaryl coupling of diarylamines under mild
aerobic conditions.19,20 Furthermore, an efficient and highly
selective aerobic catalytic cross-coupling between two different
anilines was also established (Scheme 1B).21,22 Hence, we were
interested in extending the existing approaches involving
catalytic oxidative homocoupling of anilines under mild
aerobic conditions. In this study, we report a heterogeneous
metal-catalyzed aerobic oxidative homocoupling of anilines,
enabling facile access to various functionalized benzidines and
diaminobiaryls under mild conditions (Scheme 1C). Addi-
tionally, we also demonstrate the high catalytic activity and
recyclability of the employed heterogeneous rhodium catalyst.
RESULTS AND DISCUSSION
■
Catalytic Oxidative Homocoupling of Anilines for the
Synthesis of N,N,N′,N′-Tetrasubstituted Benzidines. The
oxidation of simple anilines is more difficult than that of other
aryl amines such as aminonaphthalenes, due to the difference
in their oxidation potentials. Thus, we wondered whether
anilines could be oxidized in our standard acidic conditions.
Based on the previous studies, we set out to examine the
oxidative homocoupling of N,N-disubstituted anilines (Figure
1). According to our previous developments, when N,N-
dimethylaniline was subjected to Rh/C-catalyzed coupling in
trifluoroacetic acid (TFA) as the solvent at room temperature
under an oxygen atmosphere, only a trace amount of the
homocoupled benzidines 2a was observed due to the slow
reaction rate.23 Therefore, the reaction was heated to 50 °C,
effectively affording 2a in an adequate yield. Anilines
containing substituents such as methyl groups on their benzene
rings are typically suitable substrates for oxidative coupling
reactions due to lower oxidation potentials. When N,N-
dimethyl-meta-toluidine and 3,5-xylidine were reacted, both
homocoupling reactions proceeded more efficiently, giving
biaryls 2b and 2c in 80 and 72% yields, respectively. Moreover,
The low reactivities of the ortho-substituted anilines are
potentially a result of steric repulsions between the ortho
B
https://dx.doi.org/10.1021/acs.joc.0c02020
J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
pubs.acs.org/joc
Article
Figure 1. Catalytic oxidative homocoupling of anilines 1 at para positions. [a] The reaction was performed at room temperature; [b] 5% Pd/Al2O3
was used; [c] the reaction was performed using 5 equiv of TFA at room temperature; and [d] 5% Pd/C was used.
substituents and amino moieties, which led to breaking of the
coplanar p−π conjugated structures of the aromatic carbon−
nitrogen bonds. Gould and co-workers revealed that the
oxidation potentials of N,N-dimethylanilines increase with
increasing bulkiness of the ortho substituents (Figure 2).25
Hence, we anticipated that if a cyclic nitrogen substituent was
fused to an aromatic ring, the resulting heterocycle would
exhibit enhanced reactivity for the oxidative coupling reaction
due to the restricted rotation of the aromatic carbon−nitrogen
bond (Figure 3). Pleasingly, N-methyltetrahydroquinoline (1s)
and N-methyldihydorobenzoxazine (1t) underwent rapid
homocouplings even at room temperature, affording the
corresponding biaryls 2s and 2t in moderate yields. Lower-
than-expected yields were probably a consequence of facile
C
https://dx.doi.org/10.1021/acs.joc.0c02020
J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
pubs.acs.org/joc
Article
Table 1. Conditions for Oxidative Homocoupling of
Anilines
Figure 2. Oxidation potentials (V vs saturated calomel electrode
(SCE)) reported by Gould et al.
overoxidizing properties. In addition, the coupling reaction of
N-methylindoline (1u) also proceeded smoothly, giving the
nonsymmetrical biaryl 2u in 52% yield, probably due to the
occurrence of the partial dehydorogenative reaction. Fur-
thermore, the reactions of N-methyl and N-phenylcarbazoles
resulted in the formation of bicarbazoles 2v and 2w at the para-
position from the amino groups.8b,26,27 As described above, the
developed catalytic approach for the oxidative coupling of
anilines as well as carbazoles is highly versatile.
The differences in the oxidative homocoupling of anilines
between our catalytic protocol and other oxidations are
summarized in Table 1. Although the majority of the methods
require the use of excess oxidants, Ichikawa reported that only
0.6 equiv of the organic dication 3 could oxidize N,N-
dialkylanilines to give the corresponding N,N,N′,N′-tetraalkyl-
benzidines in moderate to high yields (entry 2). Nevertheless,
these reactions usually required low temperatures and the N-
acylated anilines did not dimerize. When FeCl3 was employed
as a stoichiometric oxidant, the diversely functionalized
benzidines were successfully synthesized in moderate to high
yields from N,N-dialkylanilines and N-monoalkylanilines
(entry 5). The oxidative coupling of triarylamines was also
accomplished by utilizing Cu(ClO4)2 and chloranil as oxidants
(entries 6 and 7). The chloranil-mediated homocoupling
reactions were extensively evaluated using various substituted
triarylamines and diarylamines (entry 7). Unfortunately, the
reactions involving N,N-dialkylanilines proved unsuccessful
yield/
entry
oxidants
TiCl4
dication 3
CAN
CuBr
FeCl3·6H2O 2.5
equiv
temp.
R1, R2
%
refs
1
2
3
4
5
1.5
0.6
2
0 °C to rt
alkyl, alkyl 57−92
−78 °C to rt alkyl, alkyl 10−95
10
14
13
11a
12
rt
alkyl, alkyl 53−85
alkyl, alkyl 49−76
alkyl, alkyl 18−99
19−86
alkyl, alkyl 83−86
1
0 °C
85 °C
alkyl, H
6
7
Cu(ClO4)2
chloranil
1.5
2
rt
rt
11b
11c
15
aryl, aryl
aryl, aryl
aryl, alkyl
aryl, H
81−94
10−99
35−87
38−80
8
Rh/C
0.05 rt to 50 °C
alkyl, alkyl 27−98
aryl, alkyl
aryl, aryl
90
43−99
due to the relatively low oxidation potentials of these
compounds (Eox < 0.75 V vs SCE). Thus, for efficient
homocoupling, the reaction was limited to anilines containing
at least two aromatic groups. Among the available methods,
our catalytic approach is the only one that is versatile and
facilitates oxidative dimerization to afford variously substituted
Figure 3. Catalytic oxidative homocoupling of nitrogen-containing heterocycles. [a] The reaction was performed using TFA as the solvent.
D
https://dx.doi.org/10.1021/acs.joc.0c02020
J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
pubs.acs.org/joc
Article
benzidines in high yields under mild aerobic conditions (entry
8). Notably, diarylamines, triarylamines, and carbazoles can
also effectively participate in the described homocoupling
reaction at para positions of the amino group. On the other
hand, an iron-catalyzed method using FeF16Pc provided 2,2′-
diaminobiaryls from diarylamines and was also effectively
employed to synthesize bicarbazoles and naphthidines.8
Catalytic Oxidative Homocoupling of Anilines at
Ortho Positions. Having successfully achieved the oxidative
homocoupling of anilines at para positions, we subsequently
turned our attention to the oxidative ortho−ortho coupling of
anilines. We anticipated that the coupling reactions of 4-
substituted anilines 4 would selectively afford the ortho−ortho
coupling products 5 (Scheme 2). Moreover, if successful, it
Scheme 2. Catalytic Oxidative Coupling of Aryl Amines at
Ortho Positions
would represent an attractive synthesis of 2,2′-diaminobiphen-
yls, which have numerous applications, e.g., as ligands,
organocatalysts, and pharmaceuticals. While this type of
reaction with anilides is achieved,17,18 to the best of our
knowledge, oxidative coupling of anilines to afford 2,2′-
diaminobiphenyls has not been extensively evaluated.27 One of
̈
the very few examples is Knolker’s studies for the iron-
catalyzed oxidative homocoupling of biarylamines to provide
ortho, ortho-diaminobiphenyl products.8a Initially, a reaction
with N,N-dimethyl-4-tert-butylaniline (6a) was attempted at
50 °C; however, no product was obtained, possibly due to the
steric repulsion between the amino groups at the ortho
position of both anilines (Figure 4). Subsequently, N-methyl-4-
tert-butylaniline (6b) was subjected to the standard Rh/C-
catalyzed conditions. The reaction did not afford the expected
2,2′-diaminobiphenyl 7b, and instead, phenazine 8 was
obtained in 26% yield via oxidative demethylation followed
by C−N bond formation.28 Consequently, with a view to
avoiding the undesired demethylation of N-methylanilines, N-
propyl and N-ethylanilines were examined under aerobic
conditions. Pleasingly, the anticipated oxidative homocou-
plings proceeded at the ortho positions; however, the yields of
the symmetrical 2,2′-diaminobiaryls 7c and 7d were low and
prolonged reaction times were required. On the other hand, N-
monosubstituted 3,4-dimethoxyanilines smoothly underwent
oxidative homocoupling at room temperature to afford biaryls
7e, 7f, and 7g in moderate to high yields. Analogously to 3,4-
dimethoxyanilines, 3,4-methylenedioxyanilines were dimerized
at room temperature to provide the corresponding ortho−
ortho coupling products 7h, 7i, and 7j in moderate yields.
Consistent with our previous report,20d 3,4-dimethoxy-
substituted anilide was also dimerized at the ortho position
to afford biphenyl compound 7k in a high yield. Additionally,
N-arylpyrrolidine 6l was homocoupled at the ortho position to
give the corresponding biphenyl 7l in 52% yield.
Figure 4. Catalytic oxidative homocoupling of anilines at ortho
positions. [a] The reaction was performed at 50 °C under O2. [b] The
reaction was performed under air.
enable the control of their reactivities and prevent the
occurrence of side reactions, leading to the expected biaryl
coupling and formation of the desired dimer. To gain insight
into the reaction mechanism, we previously conducted electron
spin resonance (ESR) experiments in heterogeneous rhodium-
catalyzed coupling reaction of 2-aminoanthracenes, which
revealed that a radical cation intermediate was involved in the
catalytic cycle.6a Although the oxidation potentials of
ammonium salts generally increase, the ESR experiments
indicated that they are readily oxidized, even under our
standard acidic conditions. First, the ammonium salt 9
undergoes a single electron transfer to the rhodium catalyst,
affording the corresponding radical cation intermediate 10 and
Proposed Reaction Mechanism. We anticipated that
protonation of aryl amines under acidic conditions would
E
https://dx.doi.org/10.1021/acs.joc.0c02020
J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
pubs.acs.org/joc
Article
the reduced rhodium species (Scheme 3). Since the para-
position on the aniline is relatively more reactive than the
Table 2. Reactions at Low Loading of the Rh/C Catalyst
Scheme 3. Proposed Reaction Mechanism
entry
Rh/C (mol %)
time
yield/%
TON
1
2
3
4
2.0
40 min
4 h
6 h
94
88
79
80
47
176
316
0.50
0.25
0.025
16 days
3200
character of the reaction, we carried out a simple leaching test.
Following the removal of the Rh/C catalyst using a membrane
filter (0.45 mm), the reaction was performed under the same
conditions. No reaction occurred, which indicated that the
catalysis by the heterogeneous metal was key for the successful
progress.30
We subsequently examined the recyclability of Rh/C for the
oxidative coupling of 2-aminoanthracene (Scheme 5). After the
remaining positions, the radical cation is preferentially coupled
with another molecule of ammonium salt 9 at the para
positions and finally tautomerizes to produce the benzidine
diammonium salt 11. The catalyst is regenerated by the
oxidation of the reduced species under molecular oxygen.29 In
contrast, when para-substituted anilines are employed, the C−
C bond formation occurs at the ortho position of the amino
group to afford the corresponding 2,2′-diaminobiaryls with
high regioselectivities because the para-position was blocked by
the substituents. The ortho−ortho coupling reactions are
strongly affected by the steric bulkiness of the amino group and
thus the reactions with N,N-disubstituted aryl amines are
typically sluggish. Although the mechanism involving the
radical cations was proposed, other mechanisms such as aryl
rhodium species route cannot be ignored.
Scheme 5. Recyclability of Rh/C for the Oxidative Biaryl
Coupling
Recyclability of the Heterogeneous Rh/C Catalyst. To
assess the efficiency of the heterogeneous Rh/C catalyst, we
subsequently examined whether the loading amount of the Rh/
C catalyst could be reduced. We previously demonstrated that
the oxidative homocoupling reactions of 2-aminonaphthalenes
and anthracenes proceeded smoothly to afford 2,2′-diamino-
biaryls in excellent yields (Scheme 4).6a Accordingly, 2-
coupling reaction was performed under our standard
conditions, the catalyst was recovered by centrifuged
separation, washed with ethyl acetate, and then reused in the
next run. Notably, utilizing the recovered Rh/C catalyst, the
coupling reaction proceeded smoothly, affording the desired
biaryl product in 92% yield. Repeating the coupling reaction
using the same catalyst revealed that Rh/C could be recycled
at least eight times without any significant loss in the activity.31
Correspondingly, the recycling reactions provided biaryl 13 in
excellent yields; however, longer reaction times were required,
possibly due to the loss of the catalyst resulting from repeating
the experiment or chemical damage under the acidic
conditions. Since commercially available Rh/C catalysts were
employed in these experiments, the gradual decrease in the
catalytic efficiency could be attributed to their intrinsic
properties. At present, extensive efforts have been devoted to
the development of highly active heterogeneous catalysts for
green catalytic processes.32 Thus, improvements in the
recyclability of the existing catalysts as well as the design of
more efficient and robust ones are expected in the future.
Scheme 4. Rh/C-Catalyzed Oxidative Coupling of Aryl
Amines
aminoanthrace (12) was employed as the model substrate, and
in the presence of 2 mol % of the Rh/C catalyst, homocoupling
provided dimer 13 with a high efficiency (Table 2, entry 1).
When the loading amount of Rh/C was reduced to 0.25 mol
%, the dimerization also proceeded in equally high yields
(entries 2 and 3). Remarkably, the reaction with just 0.025 mol
% of the Rh/C catalyst afforded 13 in 80% yield and the
turnover number (TON) reached up to 3200, despite the
longer reaction time (entry 4). To verify the heterogeneous
CONCLUSIONS
■
In this study, we successfully developed a catalytic oxidative
biaryl coupling reaction of anilines to prepare diversely
functionalized benzidines utilizing molecular oxygen as the
sole oxidant. Our approach was effectively applied to
F
https://dx.doi.org/10.1021/acs.joc.0c02020
J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
pubs.acs.org/joc
Article
4-tert-Butyltriphenylamine (1l).35 The procedure for Buchwald−
Hartwig amination reaction was the same as the procedure described
for 1e starting from 1-bromo-4-tert-butylbenzene (2.1 g, 10 mmol)
and diphenylamine (1.7 g, 10 mmol). Purification by silica gel column
chromatography (CH2Cl2/hexane = 10−20%) provided 3.0 g
homocoupling of a variety of aryl amines, including N,N-
disubstituted anilines and N-monosubstituted anilines, as well
as diarylamines, triarylamines, and carbazoles. Additionally, the
catalytic protocol was extended to the ortho−ortho coupling of
anilines, giving 2,2′-diaminobiphenyls in adequate yields. We
also demonstrated the remarkably high catalytic activity and
efficient recyclability of the heterogeneous Rh/C catalyst. The
presented catalytic protocol is practically simple and environ-
mentally friendly, leading to rapid access to various valuable
biaryls.
1
(quant.) of the title compound as colorless solids. H NMR (500
MHz, CDCl3) δ: 7.26−7.18 (6H, m), 7.08−6.94 (8H, m), 1.31 (9H,
s). 13C{1H} NMR (125 MHz, CDCl3) δ: 148.0 (s), 145.7 (s), 145.0
(s), 129.1 (d), 126.0 (d), 124.0 (d), 123.8 (d), 122.3 (d), 34.3 (s),
31.4 (q). The spectral data were consistent with those reported in the
literature.
N-(2-Methylphenyl)pyrrolidine (1p). The procedure was the same
as the procedure described for 1f starting from 2-toluidine (3.4 g, 25
mmol). Purification by silica gel column chromatography (AcOEt/
hexane = 15%) provided 3.3 g (80%) of the title compound as a pale
brown oil. 1H NMR (500 MHz, CDCl3) δ: 7.13−7.08 (2H, m),
6.90−6.80 (2H, m), 3.20−3.16 (4H, m), 2.32 (3H, s), 1.94−1.89
(4H, m). 13C{1H} NMR (125 MHz, CDCl3) δ: 149.4 (s), 131.6 (d),
128.7 (s), 126.2 (d), 120.2 (d), 115.7 (d), 51.0 (t), 24.9 (t), 20.6 (q).
IR (neat): 2965, 1599, 1494, 1312, 754 cm−1. MS (EI) m/z: 160
(M+− H, 100%), 161 (M+). HRMS (EI) m/z: calcd for C11H15N
[M]+ 161.1204, found 161.1208.
EXPERIMENTAL SECTION
■
General information. NMR spectra were recorded on a Varian
400-MR (1H NMR at 400 MHz, 13C NMR at 100 MHz) and Bruker
AVANCE III HD-500 (1H NMR at 500 MHz, 13C NMR at 125
MHz) spectrometers using tetramethylsilane (1H NMR at 0.00 ppm)
and CDCl3 (13C NMR at 77.0 ppm) as reference standards. Chemical
shifts were reported in ppm. The following abbreviations were used to
denote peak multiplicities: s, singlet; d, doublet; t, triplet; q, quartet;
quin, quintet; sept, septet; m, multiplet; br, broadened. IR spectra
were recorded on a JASCO FT/IR-4200 spectrometer and reported as
the wavenumber (cm−1) of significant peaks. Mass spectra and high-
resolution mass spectra were recorded on a JEOL JMS-700 double-
focusing magnetic sector and Waters SYNAPT G2-Si HDMS TOF
mass spectrometer, respectively. Melting points were measured on a
Yanaco MP-500D instrument and SRS OptiMelt MPA100 melting
points apparatus and were uncorrected. Analytical thin-layer
chromatography (TLC) was performed on precoated plates (0.25
mm, silica gel Merck 60F245). Column chromatography was
performed on silica gel (40−50 μm, Kanto Chemical Co., Inc.).
Preparative high-performance liquid chromatography (HPLC) was
performed on a recycling system utilizing LC-9210 II Next and
LaboACE LC-5060 instruments (JAI Co., Inc.). Reactions were
performed under argon unless otherwise stated. The heating
experiments were conducted through an oil bath setup as a heat
source. Commercially available chemicals were used as purchased.
Aryl amines 1a−c, 1g−k, 1m−o, 1q, 1s−w, 6b, and 6d were
commercially available. Aryl amines 1d,12a 1r,6a 6a,21 and 6k20d were
prepared according to the literature procedure.
N-Propyl-4-tert-butylaniline (6c).36 To a solution of 4-tert-
butylaniline (1.5 g, 10 mmol) in dichloromethane (30 mL) were
added propanal (0.64 g, 11 mmol) and NaBH(OAc)3 (3.0 g, 14
mmol) at room temperature, and the mixture was stirred for 2 h. After
addition of a saturated NaHCO3 solution, the resulting mixture was
extracted with CH2Cl2 and the organic layer was washed with brine,
dried over MgSO4, filtered, and concentrated in vacuo to give a crude
product, which was purified by silica gel column chromatography
(CH2Cl2/hexane = 20−50%) to afford 1.1 g (55%) of the title
compound as a pale brown oil. 1H NMR (500 MHz, CDCl3) δ: 7.20
(2H, d, J = 8.5 Hz), 6.56 (2H, d, J = 8.5 Hz), 3.52 (1H, brs), 3.06
(2H, t, J = 7.5 Hz), 1.62 (2H, sext, J = 7.5 Hz), 1.28 (9H, s), 0.99
(3H, t, J = 7.5 Hz). 13C{1H} NMR (125 MHz, CDCl3) δ: 146.2 (s),
139.9 (s), 126.0 (d), 112.5 (d), 46.1 (t), 33.8 (s), 31.6 (q), 22.8 (t),
11.7 (q). The spectral data were consistent with those reported in the
literature.
N-Propyl-3,4-dimethoxyaniline (6e). To a solution of 3,4-
dimethoxyaniline (7.7 g, 50 mmol) in DMF (100 mL) were added
Cs2CO3 (17.9 g, 55 mmol) and 1-iodopropane (5.4 mL, 55 mmol) at
room temperature, and the mixture was heated to 100 °C for 114 h.
After addition of H2O, the resulting mixture was extracted with Et2O
and the organic layer was washed with brine, dried over MgSO4,
filtered, and concentrated in vacuo to give a crude product, which was
purified by silica gel column chromatography (AcOEt/hexane = 10−
20%) to afford 5.0 g (51%) of the title compound as a pale brown oil.
1H NMR (500 MHz, CDCl3) δ: 6.75 (1H, d, J = 8.5 Hz), 6.25 (1H, d,
J = 2.5 Hz), 7.38 (1H, dd, J = 2.5, 8.5 Hz), 3.84 (3H, s), 3.80 (3H, s),
3.35 (1H, brs), 3.04 (2H, t, J = 7.0 Hz), 1.64 (2H, sext, J = 7.0 Hz),
1.00 (3H, t, J = 7.0 Hz). 13C{1H} NMR (125 MHz, CDCl3) δ: 150.0
(s), 143.5 (s), 141.4 (s), 113.4 (d), 103.5 (d), 98.9 (d), 56.8 (q), 55.7
(q), 46.7 (t), 22.8 (t), 11.7 (q). IR (neat): 3387, 2958, 1617, 1518,
1234, 1026 cm−1. MS (EI) m/z: 166 (M+ − C2H5, 100%), 180 (M+ −
Me), 195 (M+). HRMS (EI) m/z: calcd for C11H17NO2 [M]+
195.1259, found 195.1263.
N-(3,5-Dimethylphenyl)morpholine (1e).33 To a solution of 1-
bromo-3,5-dimethylbenzene (2.2 g, 12 mmol) in toluene (70 mL)
were added morpholine (1.57 g, 18 mmol), t-BuOK (2.0 g, 18 mmol),
and Pd(t-Bu3P)2 (231 mg, 0.45 mmol) at room temperature, and the
mixture was refluxed for 4 h. After addition of H2O, the resulting
mixture was extracted with AcOEt, and the organic layer was washed
with brine, dried over MgSO4, filtered, and concentrated in vacuo to
give a crude product, which was purified by silica gel column
chromatography (AcOEt/hexane = 20%) to afford 2.3 g (99%) of the
1
title compound as a pale brown oil. H NMR (500 MHz, CDCl3) δ:
6.55 (3H, s), 3.86−3.82 (4H, m), 3.14−3.11 (4H, m), 2.28 (6H, s).
13C{1H} NMR (125 MHz, CDCl3) δ: 151.4 (s), 138.7 (s), 122.0 (d),
113.7 (d), 67.0 (t), 49.6 (t), 21.6 (q). The spectral data were
consistent with those reported in the literature.
N-(3,5-Dimethylphenyl)pyrrolidine (1f).34 To a solution of 3,5-
dimethylaniline (3.0 g, 25 mmol) in dimethylformamide (DMF; 30
mL) were added K2CO3 (3.8 g, 28 mmol) and 1,4-dibromobutane
(3.3 mL, 28 mmol) at room temperature, and the mixture was heated
to 100 °C for 18 h. After addition of H2O, the resulting mixture was
extracted with Et2O and the organic layer was washed with brine,
dried over MgSO4, filtered, and concentrated in vacuo to give a crude
product, which was purified by silica gel column chromatography
(AcOEt/hexane = 5%) to afford 3.3 g (76%) of the title compound as
N-Benzyl-3,4-dimethoxyaniline (6f).37 To a solution of 3,4-
dimethoxyaniline (1.5 g, 10 mmol) in 1,2-dichloroethane (40 mL)
were added NaBH(OAc)3 (3.2 g, 15 mmol) and acetic acid (0.86 mL,
15 mmol), and then benzaldehyde (1.1 mL, 11 mmol) was added
dropwise at room temperature. The reaction mixture was stirred for
17 h. After addition of a saturated NaHCO3 solution, the resulting
mixture was extracted with CH2Cl2 and the organic layer was washed
with brine, dried over MgSO4, filtered, and concentrated in vacuo to
give a crude product, which was purified by silica gel column
chromatography (AcOEt/hexane = 20−30%) to afford 2.4 g (quant.)
1
a pale brown oil. H NMR (500 MHz, CDCl3) δ: 6.33 (1H, s), 6.21
1
(2H, s), 3.28−3.23 (4H, m), 2.27 (s, 6H), 1.99−1.94 (4H, m).
13C{1H} NMR (125 MHz, CDCl3) δ: 148.2 (s), 138.7 (s), 117.5 (d),
109.7 (d), 47.6 (t), 25.4 (t), 21.7 (q). The spectral data were
consistent with those reported in the literature.
of the title compound as a pale brown oil. H NMR (500 MHz,
CDCl3) δ: 7.39−7.25 (5H, m), 6.74 (1H, d, J = 8.5 Hz), 6.28 (1H, d,
J = 2.5 Hz), 6.17 (1H, dd, J = 2.5, 8.5 Hz), 4.29 (2H, 2), 3.81 (3H, s),
3.80 (3H, s), 2.82 (1H, brs). 13C{1H} NMR (125 MHz, CDCl3) δ:
G
https://dx.doi.org/10.1021/acs.joc.0c02020
J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
pubs.acs.org/joc
Article
150.0 (s), 143.1 (s), 141.7 (s), 139.6 (s), 128.6 (d), 127.6 (d), 127.2
(d), 113.2 (d), 103.6 (d), 99.0 (d), 56.7 (q), 55.7 (q), 49.2 (t). The
spectral data were consistent with those reported in the literature.
N-[3,5-Bis(trifluoromethyl)benzyl]-3,4-dimethoxyaniline (6g).
The procedure for the reductive amination reaction was the same
as the procedure described for 6f starting from 3,4-dimethoxyaniline
(1.8 g, 12 mmol) and 3,5-bis(trifluoromethyl)benzaldehyde (2.0 mL,
12 mmol). Purification by silica gel column chromatography (AcOEt/
hexane = 20−30%) provided 3.9 g (86%) of the title compound as
(4H, m). 13C{1H} NMR (125 MHz, CDCl3) δ: 158.4 (s), 147.8 (s),
130.8 (d), 113.3 (s), 103.6 (d), 95.2 (d), 55.2 (q), 47.9 (t), 25.4 (t),
15.2 (q). IR (ATR): 1619, 1517, 1228, 805 cm−1. MS (EI) m/z: 190
(M+ − H), 191 (M+, 100%). HRMS (EI) m/z: calcd for C12H17NO
[M]+ 191.1310, found 191.1313.
Representative Procedure A for the Catalytic Aerobic Oxidative
Homocoupling of Anilines: N,N,N′,N′-Tetramethylbenzidine (2a).
To a solution of N,N-dimethylaniline (1a, 120 mg, 1.0 mmol) in TFA
(2 mL) was added 5% Rh/C (103 mg, 0.050 mmol, 5 mol % Rh).
Following stirring at 50 °C under O2 (balloon) for 84 h, the reaction
was quenched by the addition of a saturated NaHCO3 solution and
then extracted with AcOEt. The combined organic layers were
washed with brine, dried over MgSO4, and filtered, and the solvent
was evaporated to afford the crude product, which was purified by
silica gel column chromatography (AcOEt/hexane = 20%) to yield 2a
(86 mg, 72%). Recrystallization from AcOEt−hexane afforded 2a as a
brown solid (mp 189−191 °C). 1H NMR (500 MHz, CDCl3) δ: 7.45
(4H, d, J = 9.0 Hz), 6.80 (4H, d, J = 9.0 Hz), 2.97 (12H, s). 13C{1H}
NMR (125 MHz, CDCl3) δ: 149.3 (s), 129.8 (s), 127.0 (d), 113.1
(d), 40.8 (q). IR (ATR): 1608, 1505, 801 cm−1. MS (EI) m/z: 240
(M+, 100%), 241 (M+ + H). HRMS (EI) m/z: calcd for C16H20N2
[M]+ 240.1626, found 240.1633.
1
colorless solids. H NMR (500 MHz, CDCl3) δ: 7.85 (2H, s), 7.79
(1H, s), 6.73 (1H, d, J = 8.5 Hz), 6.27 (1H, d, J = 2.6 Hz), 6.10 (1H,
dd, J = 2.6, 8.5 Hz), 4.43 (2H, s), 3.81 (3H, s), 3.80 (3H, s), 3.04
(1H, brs). 13C{1H} NMR (125 MHz, CDCl3) δ: 150.1 (s), 142.7 (s),
142.3 (s), 142.1 (s), 131.9 (s, q: JC−F = 33 Hz), 127.4 (d, q: JC−F = 2.5
Hz), 123.3 (s, q: JC−F = 271 Hz), 121.2 (d, sept: JC−F = 3.8 Hz), 113.1
(d), 103.7 (d), 99.3 (d), 56.6 (q), 55.7 (q), 48.5 (t). IR (film): 3400,
1616, 1518, 1026 cm−1. MS (EI) m/z: 364 (M+ − Me), 379 (M+,
100%). HRMS (EI) m/z: calcd for C17H15F6NO2 [M]+ 379.1007,
found 379.1002.
N-Propyl-3,4-(methylenedioxy)aniline (6h). To a solution of 3,4-
(methylenedioxy)aniline (2.1 g, 15 mmol) in DMF (30 mL) were
added Cs2CO3 (5.8 g, 18 mmol), 1-bromopropane (1.5 mL, 16
mmol), and sodium iodide (2.7 g, 18 mmol) at room temperature,
and the mixture was heated to 100 °C for 4 h. After addition of H2O,
the resulting mixture was extracted with Et2O and the organic layer
was washed with brine, dried over MgSO4, filtered, and concentrated
in vacuo to give a crude product, which was purified by silica gel
column chromatography (AcOEt/hexane = 10−20%) to afford 1.5 g
Representative Procedure B for the Catalytic Aerobic Oxidative
Homocoupling of Anilines: N,N′-Bis(4-tert-butylphenyl)-N,N′-di-
phenylbenzidine (2l). To a solution of 4-tert-butyl-N,N-diphenylani-
line (1l, 150 mg, 0.50 mmol) in benzotrifluoride (2 mL) were added
5% Rh/C (51 mg, 0.025 mmol, 5 mol % Rh) and TFA (0.19 mL, 2.5
mmol). Following stirring at room temperature under O2 (balloon)
for 2 h, the reaction was quenched by the addition of a saturated
NaHCO3 solution and extracted with AcOEt. The combined organic
layers were washed with brine, dried over MgSO4, and filtered, and
the solvent was evaporated to afford the crude product, which was
purified by silica gel column chromatography (AcOEt/hexane = 5%)
to yield 2l (126 mg, 84%). Recrystallization from toluene-2-propanol
1
(54%) of the title compound as a pale brown oil. H NMR (500
MHz, CDCl3) δ: 6.65 (1H, d, J = 8.5 Hz), 6.24 (1H, s), 6.04 (1H, d, J
= 8.5 Hz), 5.84 (2H, s), 3.40 (1H, brs), 3.01 (2H, t, J = 7.0 Hz), 1.62
(2H, sext, J = 7.0 Hz), 0.99 (3H, t, J = 7.0 Hz). 13C{1H} NMR (125
MHz, CDCl3) δ: 148.3 (s), 144.4 (s), 139.4 (s), 108.6 (d), 104.3 (d),
100.5 (t), 95.9 (d), 46.8 (t), 22.7 (t), 11.6 (q). IR (neat): 3405, 2960,
1633, 1505, 1201, 1039, 928, 813 cm−1. MS (EI) m/z: 150 (M+ −
C2H5, 100%), 179 (M+). HRMS (EI) m/z: calcd for C10H13NO2
[M]+ 179.0946, found 179.0955.
1
afforded 2l as a pale pink solid (mp 225−227 °C). H NMR (500
MHz, CDCl3) δ: 7.43 (4H, d, J = 8.0 Hz), 7.30−7.22 (8H, m), 7.15−
7.07 (8H, m), 7.05 (4H, d, J = 8.0 Hz), 6.99 (2H, t, J = 7.5 Hz), 1.32
(18H, s). 13C{1H} NMR (125 MHz, CDCl3) δ: 147.9 (s), 146.8 (s),
145.9 (s), 144.9 (s), 134.5 (s), 129.1 (d), 127.2 (d), 126.1 (d), 124.1
(d), 124.0 (d), 123.8 (d), 122.5 (d), 34.3 (s), 31.4 (q). IR (ATR):
1594, 1489, 1271, 772 cm−1. MS (EI) m/z: 600 (M+, 100%), 601 (M+
+ H). HRMS (EI) m/z: calcd for C44H44N2 [M]+ 600.3504, found
600.3512.
N-Benzyl-3,4-(methylenedioxy)aniline (6i).37 The procedure for
the reductive amination reaction was the same as the procedure
described for 6f starting from 3,4-(methylenedioxy)aniline (1.5 g, 11
mmol) and benzaldehyde (1.1 mL, 11 mmol). Purification by silica
gel column chromatography (AcOEt/hexane = 10−20%) provided
1
2.5 g (quant.) of the title compound as a pale brown oil. H NMR
N,N,N′,N′-Tetramethyl-2,2′-dimethylbenzidine (2b). Yield 108
mg (80%) from 1b (135 mg, 1.0 mmol) according to representative
procedure A (conditions: 50 °C under O2 for 20 h). Eluent for
column chromatography: AcOEt/hexane = 20%. Colorless needles
(mp 91−94 °C; ethanol). 1H NMR (500 MHz, CDCl3) δ: 6.99 (2H,
d, J = 8.5 Hz), 6.64 (2H, d, J = 2.5 Hz), 6.61 (2H, dd, J = 2.5, 8.5 Hz),
2.97 (12H, s), 2.06 (6H, s). 13C{1H} NMR (125 MHz, CDCl3) δ:
149.5 (s), 137.1 (s), 130.7 (d), 130.5 (s), 113.8 (d), 110.0 (d), 40.7
(q), 20.5 (q). IR (ATR): 1606, 1498, 1348, 815 cm−1. MS (EI) m/z:
268 (M+, 100%), 269 (M+ + H). HRMS (EI) m/z: calcd for
C18H24N2 [M]+ 268.1939, found 268.1938.
(500 MHz, CDCl3) δ: 7.36−7.24 (5H, m), 6.64 (1H, d, J = 8.5 Hz),
6.25 (1H, d, J = 2.5 Hz), 6.06 (1H, dd, J = 2.5, 8.5 Hz), 5.83 (2H, s),
4.25 (2H, s), 3.81 (1H, brs). 13C{1H} NMR (125 MHz, CDCl3) δ:
148.3 (s), 143.9 (s), 139.7 (s), 139.4 (s), 128.6 (d), 127.5 (d), 127.2
(d), 108.6 (d), 104.4 (d), 100.6 (t), 96.0 (d), 49.2 (t). The spectral
data were consistent with those reported in the literature.
N-iso-Propylbenzo[d][1,3]dioxol-5-amine (6j). The procedure for
the reductive amination reaction was the same as the procedure
described for 6f starting from 3,4-(methylenedioxy)aniline (1.4 g, 10
mmol) and acetone (1.1 mL, 15 mmol). Purification by silica gel
column chromatography (AcOEt/hexane = 20−30%) provided 2.5 g
N,N,N′,N′-Tetramethyl-2,2′,6,6′-tetramethylbenzidine (2c).14b
Yield 107 mg (72%) from 1c (149 mg, 1.0 mmol) according to
representative procedure A (conditions: 50 °C under O2 for 2 h).
Eluent for column chromatography: AcOEt/hexane = 5%. Colorless
needles (mp 175−176 °C; ethanol). 1H NMR (500 MHz, CDCl3) δ:
6.52 (4H, s), 2.95 (12H, s), 1.88 (12H, s). 13C{1H} NMR (125 MHz,
CDCl3) δ: 149.2 (s), 137.0 (s), 129.2 (s), 111.7 (d), 40.7 (q), 20.5
(q). IR (ATR): 1605, 1487, 1231, 1162, 824 cm−1. MS (EI) m/z: 296
(M+, 100%), 297 (M+ + H). HRMS (EI) m/z: calcd for C20H28N2
[M]+ 296.2252, found 296.2255.
1
(quant.) of the title compound as a pale brown oil. H NMR (500
MHz, CDCl3) δ: 6.64 (1H, d, J = 8.3 Hz), 6.23 (1H, d, J = 2.3 Hz),
6.03 (1H, dd, J = 2.3, 8.3 Hz), 5.84 (2H, s), 3.51 (1H, sept, J = 6.3
Hz), 3.18 (1H, brs), 1.18 (6H, d, J = 6.3 Hz). 13C{1H} NMR (125
MHz, CDCl3) δ: 148.3 (s), 143.3 (s), 139.3 (s), 108.7 (d), 105.3 (d),
100.5 (t), 96.5 (d), 45.3 (d), 23.0 (q). IR (neat): 3402, 2966, 1633,
1505, 1201, 1038, 937 cm−1. MS (EI) m/z: 16450 (M+ − Me, 100%),
179 (M+). HRMS (EI) m/z: calcd for C10H13NO2 [M]+ 179.0946,
found 179.0952.
N-(3-Methoxy-4-methylphenyl)pyrrolidine (6l). The procedure
was the same as the procedure described for 1f starting from 3-
methoxy-4-methylaniline (1.7 g, 12 mmol). Purification by silica gel
column chromatography (AcOEt/hexane = 10%) provided 1.6 g
N,N,N′,N′-Tetrabenzyl-2,2′,6,6′-tetramethylbenzidine (2d).14b
Yield 534 mg (88%) from 1d (603 mg, 2.0 mmol) according to
representative procedure A (conditions: 50 °C under O2 for 21 h).
Eluent for column chromatography: AcOEt/hexane = 5%. A colorless
1
(69%) of the title compound as a pale brown solid. H NMR (500
1
MHz, CDCl3) δ: 6.96 (1H, d, J = 8.0 Hz), 6.10 (1H, s), 6.09 (1H, d, J
= 8.0 Hz), 3.83 (3H, s), 3.29−3.24 (4H, m), 2.11 (3H, s), 2.00−1.96
prism (mp 188−190 °C; hexane). H NMR (500 MHz, CDCl3) δ:
7.35−7.21 (20H, m), 6.53 (4H, s), 4.59 (8H, s), 1.82 (12H, s).
H
https://dx.doi.org/10.1021/acs.joc.0c02020
J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
pubs.acs.org/joc
Article
13C{1H} NMR (125 MHz, CDCl3) δ: 148.1 (s), 139.2 (s), 137.0 (s),
365 (M+ + H). HRMS (EI) m/z: calcd for C26H24N2 [M]+ 364.1939,
found 364.1927.
129.3 (s), 128.5 (d), 127.0 (d), 126.7 (d), 111.5 (d), 53.8 (t), 20.6
(q). IR (ATR): 1600, 1494, 772, 732, 697 cm−1. MS (EI) m/z: 509
(M+ − Bn), 600 (M+, 100%), 601 (M+ + H). HRMS (EI) m/z: calcd
for C44H44N2 [M]+ 600.3504, found 600.3509.
N,N,N′,N′-Tetraphenylbenzidine (2k).11c Yield 122 mg (99%)
from 1k (123 mg, 0.50 mmol) according to representative procedure
B (conditions: rt under O2 for 1 h). Eluent for column
chromatography: AcOEt/hexane = 5%. A colorless solid (mp 230−
N,N′-[4,4′-(2,2′,6,6′-Tetramethyl-1,1′-biphenyl)]dimorpholine
(2e). Yield 152 mg (80%) from 1e (191 mg, 1.0 mmol) according to
representative procedure A (conditions: 50 °C under O2 for 37 h).
Eluent for column chromatography: AcOEt/hexane = 10%. Pale
brown plates (mp 174−179 °C; CHCl3−hexane). 1H NMR (500
MHz, CDCl3) δ: 6.67 (4H, s), 3.90−3.85 (8H, m), 3.21−3.16 (8H,
m), 1.87 (12H, s). 13C{1H} NMR (125 MHz, CDCl3) δ: 149.7 (s),
137.0 (s), 132.0 (s), 114.6 (d), 67.1 (t), 49.5 (t), 20.4 (q). IR (ATR):
1601, 1447, 1263, 1110, 1012 cm−1. MS (EI) m/z: 380 (M+, 100%),
381 (M+ + H). HRMS (EI) m/z: calcd for C24H32N2O2 [M]+
380.2464, found 380.2459.
1
232 °C). H NMR (500 MHz, CDCl3) δ: 7.44 (4H, d, J = 8.5 Hz),
7.29−7.22 (8H, m), 7.15−7.08 (12H, m), 7.02 (4H, t, J = 7.5 Hz).
13C{1H} NMR (125 MHz, CDCl3) δ: 147.7 (s), 146.7 (s), 134.7 (s),
129.2 (d), 127.3 (d), 124.3 (d), 124.1 (d), 122.8 (d). IR (ATR):
1585, 1483, 1273 cm−1. MS (EI) m/z: 488 (M+, 100%), 489 (M+ +
H). HRMS (EI) m/z: calcd for C36H28N2 [M]+ 488.2252, found
488.2261.
N,N′-Bis(3-bromophenyl)-N,N′-diphenylbenzidine (2m).15 Yield
246 mg (76%) from 1m (324 mg, 1.0 mmol) according to
representative procedure B (conditions: rt under O2 for 1 h). Eluent
for column chromatography: AcOEt/hexane = 5%. A pale brown
amorphous solid. 1H NMR (500 MHz, CDCl3) δ: 7.47 (4H, d, J = 8.5
Hz), 7.32−7.27 (4H, m), 7.24−7.22 (2H, m), 7.14−7.06 (14H, m),
7.03−6.99 (2H, m). 13C{1H} NMR (125 MHz, CDCl3) δ: 149.2 (s),
147.0 (s), 146.2 (s), 135.4 (s), 130.4 (d), 129.5 (d), 127.6 (d), 125.9
(d), 125.2 (d), 124.9 (d), 124.7 (d), 123.7 (d), 122.8 (s), 121.8 (d).
IR (ATR): 1580, 1490, 754, 696 cm−1. MS (EI) m/z: 644 (M+), 646
(M+ + 2, 100%), 648 (M+ + 4). HRMS (EI) m/z: calcd for
C36H26Br2N2 [M]+ 644.0463, found 644.0463.
N,N′-[4,4′-(2,2′,6,6′-Tetramethyl-1,1′-biphenyl)]dipyrrolidine
(2f). Yield 172 mg (98%) from 1f (176 mg, 1.0 mmol) according to
representative procedure A (conditions: rt under O2 for 2 h). Eluent
for column chromatography: AcOEt/hexane = 30%. A colorless solid
1
(mp 161 °C (dec.); AcOEt). H NMR (500 MHz, CDCl3) δ: 6.36
(4H, s), 3.34−3.27 (8H, m), 2.02−1.96 (8H, m), 1.88 (12H, s).
13C{1H} NMR (125 MHz, CDCl3) δ: 146.4 (s), 137.3 (s), 128.1 (s),
110.4 (d), 47.5 (t), 25.5 (t), 20.5 (q). IR (ATR): 1603, 1477, 1362,
822 cm−1. MS (EI) m/z: 348 (M+, 100%), 349 (M+ + H). HRMS
(EI) m/z: calcd for C24H32N2 [M]+ 348.2565, found 348.2570.
N,N,N′,N′-Tetramethyl-2,2′-dibromobenzidine (2g). Yield 145
mg (72%) from 1g (200 mg, 1.0 mmol) according to representative
procedure A (conditions: 50 °C under O2 for 37 h). Eluent for
column chromatography: AcOEt/hexane = 10%. A colorless solid
(mp 173−177 °C; CHCl3−hexane). 1H NMR (500 MHz, CDCl3) δ:
7.09 (2H, d, J = 8.5 Hz), 6.96 (2H, d, J = 2.5 Hz), 6.68 (2H, dd, J =
2.5, 8.5 Hz), 2.98 (12H, s). 13C{1H} NMR (125 MHz, CDCl3) δ:
150.5 (s), 131.8 (d), 129.9 (s), 125.3 (s), 115.4 (d), 110.9 (d), 40.4
(q). IR (ATR): 1600, 1498, 1223, 772 cm−1. MS (EI) m/z: 396 (M+),
398 (M+ + 2, 100%), 400 (M+ + 4). HRMS (EI) m/z: calcd for
C16H18N2Br2 [M]+ 395.9837, found 395.9841.
N,N,N′,N′-Tetramethyl-2,2′-dichlorobenzidine (2h). Yield 131 mg
(84%) from 1h (155 mg, 1.0 mmol) according to representative
procedure A (conditions: 50 °C under O2 for 96 h). Eluent for
column chromatography: AcOEt/hexane = 10%. A colorless prism
(mp 152−153 °C; CHCl3−hexane). 1H NMR (500 MHz, CDCl3) δ:
7.12 (2H, d, J = 8.5 Hz), 6.78 (2H, d, J = 2.5 Hz), 6.64 (2H, dd, J =
2.5, 8.5 Hz), 2.98 (12H, s). 13C{1H} NMR (125 MHz, CDCl3) δ:
150.6 (s), 134.7 (s), 132.1 (d), 126.2 (s), 112.4 (d), 110.4 (d), 40.4
(q). IR (ATR): 1606, 1503, 1443, 1223, 772 cm−1. MS (EI) m/z: 308
(M+, 100%), 310 (M+ + 2), 312 (M+ + 4). HRMS (EI) m/z: calcd for
C16H18N2Cl2 [M]+ 308.0847, found 308.0839.
Dimethyl 4,4′-Bis(Dimethylamino)-1,1′-biphenyl-2,2′-dicarboxy-
late (2i). Yield 98 mg (54%) from 1i (179 mg, 1.0 mmol) according
to representative procedure A (conditions: 5% Pd/Al2O3, 50 °C
under O2 for 43 h). Eluent for column chromatography: AcOEt/
hexane = 20%. A yellow solid (mp 144−145 °C; CHCl3−hexane). 1H
NMR (500 MHz, CDCl3) δ: 7.27 (2H, d, J = 3.0 Hz), 7.07 (2H, d, J =
8.5 Hz), 6.86 (2H, dd, J = 2.5, 8.5 Hz), 3.62 (6H, s), 3.00 (12H, s).
13C{1H} NMR (125 MHz, CDCl3) δ: 168.7 (s), 149.0 (s), 131.6 (d),
131.0 (s), 130.5 (s), 115.2 (d), 113.3 (d), 51.8 (q), 40.6 (q). IR
(ATR): 1721, 1605, 1225, 1171, 1063 cm−1. MS (EI) m/z: 356 (M+,
100%), 357 (M+ + H). HRMS (EI) m/z: calcd for C20H24N2O4 [M]+
356.1736, found 356.1742.
N,N,N′,N′-Tetrakis(4-tolyl)benzidine (2n).11c Yield 120 mg (43%)
from 1n (273 mg, 1.0 mmol) according to representative procedure B
(conditions: rt under O2 for 20 min). Eluent for column
chromatography: AcOEt/hexane = 2%. A colorless solid (mp 212−
214 °C; methanol). 1H NMR (500 MHz, CDCl3) δ: 7.51−7.31 (4H,
m), 7.20−6.80 (20H, m), 2.32 (12H, s). 13C{1H} NMR (125 MHz,
CDCl3) δ: 147.0 (s), 145.4 (s), 134.1 (s), 132.4 (s), 129.8 (d), 127.0
(d), 124.5 (d), 122.9 (d), 20.8 (q). IR (ATR): 1599, 1489, 1273, 811
cm−1. MS (EI) m/z: 544 (M+, 100%), 545 (M+ + H). HRMS (EI) m/
z: calcd for C40H36N2 [M]+ 544.2878, found 544.2881.
N,N,N′,N′-Tetramethyl-3,3′-dimethylbenzidine (2o). Yield 43 mg
(31%) from 1o (135 mg, 1.0 mmol) according to representative
procedure A (conditions: 5% Pd/C, 50 °C under O2 for 30 h). Eluent
for column chromatography: AcOEt/hexane = 10%. A colorless solid
(mp 78−80 °C; pentane). 1H NMR (500 MHz, CDCl3) δ: 7.36 (2H,
d, J = 2.0 Hz), 7.34 (2H, dd, J = 2.0, 8.0 Hz), 7.06 (2H, d, J = 8.0 Hz),
2.73 (12H, s), 2.38 (6H, s). 13C{1H} NMR (125 MHz, CDCl3) δ:
151.6 (s), 135.3 (s), 132.1 (s), 129.7 (d), 124.7 (d), 118.5 (d), 44.3
(q), 18.6 (q). IR (ATR): 1488, 1119, 942, 819 cm−1. MS (EI) m/z:
253 (M+ − CH3), 268 (M+, 100%), 269 (M+ + H). HRMS (EI) m/z:
calcd for C18H24N2 [M]+ 268.1939, found 268.1933.
N,N′-[4,4′-(3,3′-Dimethyl-1,1′-biphenyl)]dipyrrolidine (2p). Yield
44 mg (27%) from 1p (160 mg, 1.0 mmol) according to
representative procedure A (conditions: 50 °C under O2 for 47 h).
Eluent for column chromatography: AcOEt/hexane = 10%. A light
brown solid (mp 101−102 °C; methanol). 1H NMR (500 MHz,
CDCl3) δ: 7.32 (2H, d, J = 2.3 Hz), 7.30 (2H, dd, J = 2.3, 8.0 Hz),
6.91 (2H, d, J = 8.0 Hz), 3.25−3.20 (8H, m), 2.37 (6H, s), 1.97−1.92
(8H, m). 13C{1H} NMR (125 MHz, CDCl3) δ: 148.1 (s), 133.1 (s),
129.9 (d), 128.7 (s), 124.3 (d), 116.0 (d), 51.1 (t), 25.0 (t), 20.8 (q).
IR (ATR): 1605, 1480, 1309, 807 cm−1. MS (EI) m/z: 320 (M+,
100%), 321 (M+ + H). HRMS (EI) m/z: calcd for C22H28N2 [M]+
320.2252, found 320.2260.
1,1′,2,2′,3,3′,4,4′,5,5′,6,6′,7,7′,8,8′-Hexadecahydro-9,9′-bian-
thracen-10,10′-diamine (2r).6a Yield 53 mg (99%) from 1r (52 mg,
0.25 mmol) according to procedure A (conditions: rt under air for 10
h). Eluent for column chromatography: AcOEt/hexane = 30%. Pink
needles (mp 90 °C; dec.). 1H NMR (400 MHz, CDCl3) δ: 1.56−1.62
(m, 8H), 1.76−1.81 (m, 8H), 2.05 (t, J = 6.4 Hz, 8H), 2.51 (d, J = 6.4
Hz, 8H), 3.54 (brs, 4H). 13C{1H} NMR (100 MHz, CDCl3) δ: 23.1
(t), 23.1 (t), 24.9 (t), 27.9 (t), 118.6 (s), 130.1 (s), 132.5 (s), 140.1
(d). The spectral data were consistent with those reported in the
literature.
N,N′-Dimethyl-N,N′-diphenylbenzidine (2j). Yield 82 mg (90%)
from 1j (92 mg, 0.50 mmol) according to representative procedure A
(conditions: rt under O2 for 1 h). Eluent for column chromatography:
AcOEt/hexane = 10%. A colorless solid (mp 233−236 °C; CHCl3−
hexane). 1H NMR (500 MHz, CDCl3) δ: 7.51−7.45 (4H, m), 7.32−
7.27 (4H, m), 7.11−7.02 (8H, m), 6.98 (2H, t, J = 8.5 Hz), 3.35 (6H,
s). 13C{1H} NMR (125 MHz, CDCl3) δ: 148.9 (s), 147.8 (s), 133.6
(s), 129.2 (d), 127.3 (d), 121.5 (d), 120.8 (d), 120.3 (d), 40.3 (q). IR
(ATR): 1591, 1495, 773, 697 cm−1. MS (EI) m/z: 364 (M+, 100%),
N,N′-Dimethyl-1,1′,2,2′,3,3′,4,4′-octahydro-6,6′-biquinoline (2s).
Yield 75 mg (51%) from 1s (147 mg, 1.0 mmol) according to
I
https://dx.doi.org/10.1021/acs.joc.0c02020
J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
pubs.acs.org/joc
Article
representative procedure B (conditions: rt under O2 for 4 h). Eluent
for column chromatography: AcOEt/hexane = 20%. Light brown
plates (mp 116−118 °C; hexane). H NMR (500 MHz, CDCl3) δ:
128.1 (d), 125.4 (d), 123.9 (s), 110.1 (d), 45.9 (t), 33.9 (s), 31.6 (q),
22.6 (t), 11.6 (q). IR (ATR): 3424, 2956, 1608, 1509, 1259, 1164
cm−1. MS (EI) m/z: 365 (M+ − Me), 380 (M+, 100%), 381 (M+ +
H). HRMS (EI) m/z: calcd for C26H40N2 [M]+ 380.3191, found
380.3191.
1
7.25 (2H, d, J = 8.5 Hz), 7.14 (2H, s), 6.63 (2H, d, J = 8.5 Hz), 3.22
(4H, t, J = 5.5 Hz), 2.90 (6H, s), 2.81 (4H, t, J = 5.5 Hz), 2.00 (4H,
quint, J = 5.5 Hz). 13C{1H} NMR (125 MHz, CDCl3) δ: 145.3 (s),
129.7 (s), 126.9 (d), 124.9 (d), 123.0 (s), 111.4 (d), 51.4 (t), 39.3
(q), 27.9 (t), 22.6 (t). IR (ATR): 1610, 1498, 1210, 803 cm−1. MS
(EI) m/z: 281 (M+ − CH3), 296 (M+, 100%), 297 (M+ + H). HRMS
(EI) m/z: calcd for C20H24N2 [M]+ 292.1939, found 292.1950.
N,N′-Dimethyl-3,3′,4,4′-tetrahydro-2H,2′H-7,7′-bibenzo[b][1,4]-
oxazine (2t). Yield 111 mg (37%) from 1t (298 mg, 2.0 mmol)
according to representative procedure A (conditions: rt under O2 for
2 h). Eluent for column chromatography: AcOEt/hexane = 20%. A
N,N′-Diethyl-5,5′-dimethyl-[1,1′-biphenyl]-2,2′-diamine (7d).
Yield 37 mg (14%) from 6d (270 mg, 2.0 mmol) according to
representative procedure A (conditions: 50 °C under O2 for 41 h).
Eluent for column chromatography: AcOEt/hexane = 10%. A
1
colorless solid (mp 41−43 °C). H NMR (500 MHz, CDCl3) δ:
7.06 (2H, dd, J = 1.5, 8.0 Hz), 6.89 (2H, d, J = 1.5 Hz), 6.64 (2H, d, J
= 8.0 Hz), 3.52 (2H, brs), 3.17−3.07 (4H, m), 2.26 (6H, s), 1.13
(6H, t, J = 7.0 Hz). 13C{1H} NMR (125 MHz, CDCl3) δ: 143.5 (s),
131.7 (d), 129.2 (d), 126.2 (s), 124.6 (s), 110.7 (d), 38.7 (t), 20.3
(q), 14.8 (q). IR (ATR): 3363, 3331, 1610, 1504, 1267, 1158 cm−1.
MS (EI) m/z: 208 (100%), 268 (M+), 269 (M+ + H). HRMS (EI) m/
z: calcd for C18H24N2 [M]+ 268.1939, found 268.1938.
1
colorless solid (mp 188−190 °C; AcOEt−hexane). H NMR (500
MHz, CDCl3) δ: 7.03 (2H, d, J = 8.5 Hz), 6.98 (2H, s), 6.70 (2H, d, J
= 8.5 Hz), 4.34−4.30 (4H, m), 3.30−3.25 (4H, m), 2.90 (6H, s).
13C{1H} NMR (125 MHz, CDCl3) δ: 144.4 (s), 135.2 (s), 131.4 (s),
4,4′,5,5′-Tetramethoxy-N,N′-dipropyl-[1,1′-biphenyl]-2,2′-dia-
mine (7e). Yield 97 mg (50%) from 6e (195 mg, 1.0 mmol) according
to representative procedure A (conditions: rt under O2 for 3 h).
Eluent for column chromatography: AcOEt/hexane = 30%. A
colorless prism (mp 75−77 °C; AcOEt−hexane). 1H NMR (500
MHz, CDCl3) δ: 6.68 (2H, s), 6.36 (2H, s), 3.93 (6H, s), 3.80 (6H,
s), 3.48 (2H, brs), 3.10−2.99 (4H, m), 1.53 (4H, sext, J = 7.5 Hz),
0.90 (6H, t, J = 7.5 Hz). 13C{1H} NMR (125 MHz, CDCl3) δ: 149.7
(s), 141.1 (s), 140.7 (s), 115.8 (d), 114.9 (s), 96.7 (d), 56.8 (q), 55.9
(q), 46.7 (t), 22.7 (t), 11.6 (q). IR (ATR): 3400, 1509, 1449, 1202,
1010 cm−1. MS (EI) m/z: 388 (M+, 100%), 389 (M+ + H). HRMS
(EI) m/z: calcd for C22H32N2O4 [M]+ 388.2362, found 388.2367.
N,N′-Dibenzyl-4,4′,5,5′-tetramethoxy-[1,1′-biphenyl]-2,2′-dia-
mine (7f). Yield 130 mg (53%) from 6f (243 mg, 1.0 mmol)
according to representative procedure A (conditions: rt under O2 for
2 h). Eluent for column chromatography: AcOEt/hexane = 30% to
50%. A colorless prism (mp 106−108 °C; AcOEt−hexane). 1H NMR
(500 MHz, CDCl3) δ: 7.31−7.20 (10H, m), 6.70 (2H, s), 6.31 (2H,
s), 4.37−4.26 (4H, m), 4.06 (2H, brs), 3.79 (6H, s), 3.77 (6H, s).
13C{1H} NMR (125 MHz, CDCl3) δ: 149.6 (s), 141.0 (s), 140.7 (s),
139.7 (s), 128.6 (d), 127.2 (d), 127.1 (d), 115.8 (d), 114.9 (s), 97.2
(d), 56.8 (q), 55.8 (q), 49.0 (t). IR (ATR): 3386, 1509, 1455, 1200,
1031 cm−1. MS (EI) m/z: 393 (M+ − Bn), 484 (M+, 100%), 485 (M+
+ H). HRMS (EI) m/z: calcd for C30H32N2O4 [M]+ 484.2362, found
484.2358.
N,N′-Bis[3,5-bis(trifluoromethyl)benzyl]-4,4′,5,5′-tetramethoxy-
[1,1′-biphenyl]-2,2′-diamine (7g). Yield 306 mg (81%) from 6g (380
mg, 1.0 mmol) according to representative procedure A (conditions:
rt under air for 1 h). Eluent for column chromatography: AcOEt/
hexane = 20%. A yellow amorphous solid. 1H NMR (500 MHz,
CDCl3) δ: 7.77 (4H, s), 7.75 (2H, s), 6.73 (2H, s), 6.18 (2H, s), 4.49
(2H, d, J = 16 Hz), 4.44 (2H, d, J = 16 Hz), 4.16 (2H, brs), 3.82 (6H,
s), 3.75 (6H, s). 13C{1H} NMR (125 MHz, CDCl3) δ: 149.9 (s),
142.9 (s), 141.8 (s), 139.5 (s), 131.9 (s, q: JC−F = 34 Hz), 127.1 (d, q:
119.3 (d), 113.8 (d), 112.8 (d), 65.0 (t), 49.3 (t), 38.9 (q). IR
(ATR): 1502, 799 cm−1. MS (EI) m/z: 281 (M+ − CH3), 296 (M+,
100%), 297 (M+ + H). HRMS (EI) m/z: calcd for C18H20N2O2 [M]+
296.1525, found 296.1527.
N-Methyl-5-(N-methylindolin-5-yl)-1H-indole (2u). Yield 68 mg
(52%) from 1u (130 mg, 1.0 mmol) according to representative
procedure B (conditions: rt under O2 for 1.5 h). Eluent for column
chromatography: AcOEt/hexane = 15%. Colorless needles (mp 144−
146 °C; hexane). 1H NMR (500 MHz, CDCl3) δ: 7.75 (1H, s), 7.44−
7.36 (3H, m), 7.33 (1H, d, J = 8.5 Hz), 7.05 (1H, d, J = 3.0 Hz), 6.57
(1H, d, J = 8.0 Hz), 6.49 (1H, d, J = 3.0 Hz), 3.80 (3H, s), 3.34 (2H,
t, J = 8.0 Hz), 3.01 (2H, t, J = 8.0 Hz), 2.80 (3H, s). 13C{1H} NMR
(125 MHz, CDCl3) δ: 152.2 (s), 135.7 (s), 133.6 (s), 132.8 (s), 130.9
(s), 129.1 (d), 128.9 (s), 126.5 (d), 123.6 (d), 121.3 (d), 118.6 (d),
109.2 (d), 107.4 (d), 101.0 (d), 56.4 (q), 36.5 (t), 32.9 (t), 28.8 (q).
R (ATR): 1610, 1467, 792, 771, 711 cm−1. MS (EI) m/z: 260 (M+ −
2H), 262 (M+, 100%), 263 (M+ + H). HRMS (EI) m/z: calcd for
C18H18N2 [M]+ 262.1470, found 262.1479.
9,9′-Dimethyl-9H,9′H-3,3′-bicarbazole (2v). Yield 426 mg (78%)
from 1v (543 mg, 3.0 mmol) according to representative procedure B
(conditions: rt under O2 for 19 h). Eluent for column chromatog-
raphy: AcOEt/hexane = 30−50%. A colorless solid (mp 210−212 °C;
AcOEt−hexane). 1H NMR (500 MHz, CDCl3) δ: 8.41 (2H, d, J = 2.1
Hz), 8.19 (2H, d, J = 7.5 Hz), 7.85 (2H, dd, J = 2.1, 7.5 Hz), 7.53−
7.47 (4H, m), 7.43 (2H, d, J = 7.5 Hz), 7.26 (2H, t, J = 7.5 Hz), 3.90
(6H, s). 13C{1H} NMR (125 MHz, CDCl3) δ: 141.5 (s), 140.1 (s),
133.4 (s), 125.8 (d), 125.6 (d), 123.4 (s), 123.0 (s), 120.4 (d), 118.91
(d), 118.87 (d), 108.6 (d), 108.5 (d), 29.2 (q). IR (ATR): 1458,
1245, 1220 cm−1. MS (EI) m/z: 345 (M+ − CH3), 360 (M+, 100%),
361 (M+ + H). HRMS (EI) m/z: calcd for C26H20N2 [M]+ 360.1626,
found 360.1632.
9,9′-Diphenyl-9H,9′H-3,3′-bicarbazole (2w). Yield 163 mg (67%)
from 1w (242 mg, 1.0 mmol) according to representative procedure B
(conditions: rt under O2 for 42 h). Eluent for column chromatog-
raphy: AcOEt/hexane = 30−50%. A pale blue prism (mp 84−96 °C;
CHCl3−hexane). 1H NMR (500 MHz, CDCl3) δ: 8.46 (2H, d, J = 2.0
Hz), 8.24 (2H, d, J = 7.5 Hz), 7.77 (2H, dd, J = 2.0, 7.5 Hz), 7.66−
7.60 (8H, m), 7.52−7.40 (8H, m), 7.33−7.28 (2H, m). 13C{1H}
NMR (125 MHz, CDCl3) δ: 141.4 (s), 140.0 (s), 137.8 (s), 134.4 (s),
129.9 (d), 127.4 (d), 127.1 (d), 126.0 (d), 125.8 (d), 124.0 (s), 123.6
(s), 120.4 (d), 120.0 (d), 118.9 (d), 110.0 (d), 109.9 (d). IR (ATR):
1594, 1498, 1449, 1229 cm−1. MS (EI) m/z: 484 (M+, 100%), 485
(M+ + H). HRMS (EI) m/z: calcd for C36H24N2 [M]+ 484.1939,
found 484.1941.
J
C−F = 2.7 Hz), 123.3 (s, q: JC−F = 271 Hz), 121.2 (d, sept: JC−F = 3.6
Hz), 115.5 (d), 114.9 (s), 97.2 (d), 56.6 (q), 55.9 (q), 48.0 (t). IR
(ATR): 3418, 1509, 1275, 1120 cm−1. MS (EI) m/z: 756 (M+,
100%), 757 (M+ + H). HRMS (EI) m/z: calcd for C34H28F12N2O4
[M]+ 756.1857, found 756.1860.
N,N′-Dipropyl-[5,5′-bibenzo[d][1,3]dioxole]-6,6′-diamine (7h).
Yield 92 mg (52%) from 6h (179 mg, 1.0 mmol) according to
representative procedure A (conditions: rt under air for 50 min).
Eluent for column chromatography: AcOEt/hexane = 10%. Colorless
1
needles (mp 112−114 °C; hexane). H NMR (500 MHz, CDCl3) δ:
6.56 (2H, s), 6.34 (2H, s), 5.91−5.86 (4H, m), 3.52 (2H, brs), 3.04−
2.92 (4H, m), 1.51 (4H, sext, J = 7.5 Hz), 0.88 (6H, t, J = 7.5 Hz).
13C{1H} NMR (125 MHz, CDCl3) δ: 148.2 (s), 141.6 (s), 139.5 (s),
139.2 (s), 128.6 (d), 127.05 (d), 127.03 (d), 115.3 (s), 111.2 (d),
100.7 (t), 94.2 (d), 48.7 (t). IR (ATR): 3407, 1614, 1502, 1450,
1187, 1036 cm−1. MS (EI) m/z: 327 (M+ − Et), 356 (M+, 100%),
357 (M+ + H). HRMS (EI) m/z: calcd for C20H24N2O4 [M]+
356.1736, found 356.1740.
5,5′-Di-tert-butyl-N,N′-dipropyl-[1,1′-biphenyl]-2,2′-diamine
(7c). Yield 109 mg (29%) from 6c (383 mg, 2.0 mmol) according to
representative procedure A (conditions: 50 °C under O2 for 44 h).
Eluent for column chromatography: AcOEt/hexane = 5%. Brown oil.
1H NMR (500 MHz, CDCl3) δ: 7.27 (2H, dd, J = 2.0, 8.5 Hz), 7.14
(2H, d, J = 2.0 Hz), 6.67 (2H, d, J = 8.5 Hz), 3.66 (2H, brs), 3.10−
2.99 (4H, m), 1.58−1.46 (4H, m), 1.29 (18H, s), 0.88 (6H, t, J = 7.5
Hz). 13C{1H} NMR (125 MHz, CDCl3) δ: 143.7 (s), 139.4 (s),
J
https://dx.doi.org/10.1021/acs.joc.0c02020
J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
pubs.acs.org/joc
Article
N,N′-Dibenzyl-[5,5′-bibenzo[d][1,3]dioxole]-6,6′-diamine (7i).
Yield 139 mg (61%) from 6i (227 mg, 1.0 mmol) according to
representative procedure A (conditions: rt under air for 30 min).
Eluent for column chromatography: AcOEt/hexane = 10%. A
AUTHOR INFORMATION
Corresponding Author
■
Kenji Matsumoto − Faculty of Pharmaceutical Sciences,
Tokushima Bunri University, Yamashiro-cho, Tokushima
770-8514, Japan; orcid.org/0000-0002-0294-7092;
Email: kmatsumoto@ph.bunri-u.ac.jp
1
colorless solid (mp 184−186 °C). H NMR (500 MHz, CDCl3) δ:
7.31−7.20 (10H, m), 6.60 (2H, s), 6.28 (2H, s), 5.87−5.84 (4H, m),
4.27 (4H, s), 4.10 (2H, brs). 13C{1H} NMR (125 MHz, CDCl3) δ:
148.2 (s), 141.6 (s), 139.5 (s), 139.2 (s), 128.6 (d), 127.05 (d),
127.03 (d), 115.3 (s), 111.2 (d), 100.7 (t), 94.2 (d), 48.7 (t). IR
(ATR): 3419, 1615, 1487, 1200, 1035, 927 cm−1. MS (EI) m/z: 361
(M+ − Bn), 452 (M+, 100%), 453 (M+ + H). HRMS (EI) m/z: calcd
for C28H24N2O4 [M]+ 452.1736, found 452.1740.
Authors
Yasunori Toubaru − Faculty of Pharmaceutical Sciences,
Tokushima Bunri University, Yamashiro-cho, Tokushima
770-8514, Japan
Shohei Tachikawa − Interdisciplinary Graduate School of
Engineering Sciences, Kyushu University, Kasuga, Fukuoka
816-8580, Japan
Ayaka Miki − Faculty of Pharmaceutical Sciences, Tokushima
Bunri University, Yamashiro-cho, Tokushima 770-8514,
Japan
Kentaro Sakai − Interdisciplinary Graduate School of
Engineering Sciences, Kyushu University, Kasuga, Fukuoka
816-8580, Japan
N,N′-Di-iso-propyl-[5,5′-bibenzo[d][1,3]dioxole]-6,6′-diamine
(7j). Yield 104 mg (58%) from 6j (179 mg, 1.0 mmol) according to
representative procedure A (conditions: rt under O2 for 1 h). Eluent
for column chromatography: AcOEt/hexane = 10%. Colorless needles
1
(mp 122−124 °C; hexane). H NMR (500 MHz, CDCl3) δ: 6.53
(2H, s), 6.35 (2H, s), 5.91 (2H, s), 5.87 (2H, s), 3.56−3.45 (2H, m),
3.30−3.23 (2H, m), 1.11 (6H, d, J = 6.3 Hz), 1.08 (6H, d, J = 6.3
Hz). 13C{1H} NMR (125 MHz, CDCl3) δ: 148.1 (s), 141.0 (s),
138.7 (s), 115.7 (s), 111.4 (d), 100.6 (t), 94.5 (d), 45.0 (d), 23.1 (q),
22.7 (q). IR (ATR): 3406, 3347, 1481, 1466, 1185, 1037 cm−1. MS
(EI) m/z: 341 (M+ − Me), 356 (M+, 100%), 357 (M+ + H). HRMS
(EI) m/z: calcd for C20H24N2O4 [M]+ 356.1736, found 356.1740.
N,N′-(4,4′,5,5′-Tetramethoxy-[1,1′-biphenyl]-2,2′-diyl)-
dibenzamide (7k).20d Yield 103 mg (quant.) from 6k (103 mg, 0.40
mmol) according to representative procedure A (conditions: 50 °C
under air for 2.5 h). Eluent for column chromatography: AcOEt/
hexane = 30−50%. A pale brown solid (mp 151−153 °C; AcOEt−
Syota Koroki − Faculty of Pharmaceutical Sciences,
Tokushima Bunri University, Yamashiro-cho, Tokushima
770-8514, Japan
Tsukasa Hirokane − Faculty of Pharmaceutical Sciences,
Tokushima Bunri University, Yamashiro-cho, Tokushima
770-8514, Japan; orcid.org/0000-0001-5727-1731
Mitsuru Shindo − Institute for Materials Chemistry and
Engineering, Kyushu University, Kasuga, Fukuoka 816-8580,
Japan; orcid.org/0000-0002-0588-8075
Masahiro Yoshida − Faculty of Pharmaceutical Sciences,
Tokushima Bunri University, Yamashiro-cho, Tokushima
770-8514, Japan
1
hexane). H NMR (500 MHz, CDCl3) δ: 8.15 (2H, s), 7.82 (2H,
brs), 7.57 (4H, d, J = 7.5 Hz), 7.48 (2H, t, J = 7.5 Hz), 7.38 (4H, t, J
= 7.5 Hz), 6.80 (2H, s), 4.01 (6H, s), 3.86 (6H, s). 13C{1H} NMR
(125 MHz, CDCl3) δ: 165.6 (s), 149.3 (s), 146.2 (s), 134.3 (s), 132.0
(d), 129.7 (s), 128.9 (d), 126.7 (d), 119.9 (s), 112.9 (d), 106.3 (d),
56.23 (q), 56.18 (q). IR (ATR): 3331, 1656, 1523, 1252, 1210 cm−1.
MS (EI) m/z: 105 (C6H5CO+), 512 (M+, 100%), 813 (M+ + H).
HRMS (EI) m/z: calcd for C30H28N2O6 [M]+ 512.1947, found
512.1953.
Complete contact information is available at:
https://pubs.acs.org/10.1021/acs.joc.0c02020
N,N′-[2,2′-(4,4′-Dimethoxy-5,5′-dimethyl-1,1′-biphenyl)]-
dipyrrolidine (7l). Yield 100 mg (52%) from 6l (191 mg, 1.0 mmol)
according to representative procedure A (conditions: rt under O2 for
2.5 h). Eluent for column chromatography: AcOEt/hexane = 7%. A
Notes
The authors declare no competing financial interest.
1
colorless solid (mp 149−150 °C; AcOEt−hexane). H NMR (500
MHz, CDCl3) δ: 6.92 (2H, s), 6.25 (2H, s), 3.85 (6H, s), 3.02−2.92
(8H, m), 2.11 (6H, s), 1.78−1.65 (8H, m). 13C{1H} NMR (125
MHz, CDCl3) δ: 156.6 (s), 146.3 (s), 135.0 (d), 121.9 (s), 114.1 (s),
97.1 (d), 55.2 (q), 49.8 (t), 25.4 (t), 15.1 (q). IR (ATR): 1610, 1507,
1158, 805 cm−1. MS (EI) m/z: 308 (100%), 380 (M+). HRMS (EI)
m/z: calcd for C24H32N2O2 [M]+ 380.2464, found 380.2467.
2,7-Di-tert-butylphenazine (8). Yield 38 mg (26%) from 6b (163
mg, 1.0 mmol) according to representative procedure A (conditions:
50 °C under O2 for 36 h). Eluent for column chromatography:
AcOEt/hexane = 5%. A yellow flake solid (mp 218−220 °C; hexane).
1H NMR (500 MHz, CDCl3) δ: 8.16 (2H, d, J = 9.0 Hz), 8.15 (2H, d,
J = 2.0 Hz), 7.94 (2H, dd, J = 2.0, 9.0 Hz), 1.49 (18H, s). 13C{1H}
NMR (125 MHz, CDCl3) δ: 153.3 (s), 143.3 (s), 142.3 (s), 130.1
(d), 128.7 (d), 124.0 (d), 35.5 (s), 30.8 (q). IR (ATR): 2951, 1633,
1505, 1361, 820 cm−1. MS (EI) m/z: 277 (M+ − Me, 100%), 292
(M+), 293 (M+ + H). HRMS (EI) m/z: calcd for C20H24N2 [M]+
292.1939, found 292.1939.
ACKNOWLEDGMENTS
■
This work was partly supported by JSPS KAKENHI Grant nos.
17K15430 and 19K06985 from MEXT, The Futaba
Foundation, and the Cooperative Research Program of the
Network Joint Research Center for Materials and Devices.
REFERENCES
■
̈
(1) (a) Mitschke, U.; Bauerle, P. The electroluminescence of organic
materials. J. Mater. Chem. 2000, 10, 1471−1507. (b) Murphy, A. R.;
́
Frechet, J. M. J. Organic semiconducting oligomers for use in thin film
transistors. Chem. Rev. 2007, 107, 1066−1096.
(2) Hiroto, S. Synthesis of π-Functional Molecules through
Oxidation of Aromatic Amines. Chem. Asian J. 2019, 14, 2514−2523.
̌
̌
̌
́
(3) (a) Smrcina, M.; Lorenc, M.; Hanus, V.; Kocovsky, P. A facile
synthesis of 2-amino-2′-hydroxy-1, 1′-binaphthyl and 2, 2′-diamino-1,
1′-binaphthyl by oxidative coupling using copper (II) chloride. Synlett
̌
̌
̌
́
1991, 1991, 231−232. (b) Smrcina, M.; Vyskocil, S.; Maca, B.;
ASSOCIATED CONTENT
́
̌
̌
́
Polasek, M.; Claxton, T. A.; Abbott, A. P.; Kocovsky, P. Selective
cross-coupling of 2-naphthol and 2-naphthylamine derivatives. A facile
synthesis of 2, 2′, 3-trisubstituted and 2, 2′, 3, 3′-tetrasubstituted 1, 1′-
■
sı
* Supporting Information
The Supporting Information is available free of charge at
https://pubs.acs.org/doi/10.1021/acs.joc.0c02020.
̌
̌
binaphthyls. J. Org. Chem. 1994, 59, 2156−2163. (c) Vyskocil, S.;
̌
̌
́
Smrcina, M.; Lorenc, M.; Tislerova, I.; Brooks, R. D.; Kulagowski, J.
̌
́
J.; Langer, V.; Farrugia, L. J.; Kocovsky, P. Copper (II)-Mediated
oxidative coupling of 2-aminonaphthalene homologues. Competition
between the straight dimerization and the formation of carbazoles. J.
Org. Chem. 2001, 66, 1359−1365.
1H and 13C NMR spectra of all new compounds;
reaction optimization for the oxidative coupling of
triphenylamine (PDF)
K
https://dx.doi.org/10.1021/acs.joc.0c02020
J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
pubs.acs.org/joc
Article
(4) (a) Wang, K.; Hu, Y.; Wu, M.; Li, Z.; Liu, Z.; Su, B.; Yu, A.; Liu,
Y.; Wang, Q. m-CPBA/TFA: an efficient nonmetallic reagent for
oxidative coupling of 1, 2-diarylethylenes. Tetrahedron 2010, 66,
9135−9140. (b) Zhang, S.; Wang, Y.; Song, Z.; Nakajima, K.;
Takahashi, T. MnI2-catalyzed Dimerization of 2-Hydroxyanthracene.
Chem. Lett. 2013, 42, 697−699. (c) Morimoto, K.; Koseki, D.; Dohi,
T.; Kita, Y. Oxidative biaryl coupling of N-aryl anilines by using a
hypervalent iodine (III) reagent. Synlett 2017, 28, 2941−2945.
(d) Goto, K.; Yamaguchi, R.; Hiroto, S.; Ueno, H.; Kawai, T.;
Shinokubo, H. Intermolecular Oxidative Annulation of 2-Amino-
anthracenes to Diazaacenes and Aza[7]helicenes. Angew. Chem., Int.
Ed. 2012, 51, 10333−10336.
(12) As for FeCl3, see: (a) Ling, X.; Xiong, Y.; Huang, R.; Zhang, X.;
Zhang, S.; Chen, C. Synthesis of benzidine derivatives via FeCl3·
6H2O-promoted oxidative coupling of anilines. J. Org. Chem. 2013,
78, 5218−5226. (b) Pan, J.; Li, J.; Huang, R.; Zhang, X.; Shen, H.;
Xiong, Y.; Zhu, X. Extension studies on iron (III)-promoted free
radical oxidation of anilines: self-coupling and self-bridged assembling
reactions. Tetrahedron 2015, 71, 5341−5346.
(13) As for CAN, see: Xi, C.; Jiang, Y.; Yang, X. Remarkably efficient
oxidative coupling of N,N-dialkylarylamines in water mediated by
cerium (IV) ammonium nitrate. Tetrahedron Lett. 2005, 46, 3909−
3911.
(14) As for dication, see: (a) Saitoh, T.; Yoshida, S.; Ichikawa, J. 1,8-
Bis(diphenylmethylium) naphthalenediyl dication as an organic
oxidant: Synthesis of benzidines via self-coupling of N,N-dialkylani-
lines. Org. Lett. 2004, 6, 4563−4565. (b) Saitoh, T.; Yoshida, S.;
Ichikawa, J. Naphthalene-1,8-diylbis(diphenylmethylium) as an
organic two-electron oxidant: Benzidine synthesis via oxidative self-
coupling of N,N-dialkylanilines. J. Org. Chem. 2006, 71, 6414−6419.
(15) As for chloranil, see: Maddala, S.; Mallick, S.; Venkatakrishnan,
P. Metal-free oxidative C−C coupling of arylamines using a quinone-
based organic oxidant. J. Org. Chem. 2017, 82, 8958−8972.
(16) For recent reviews on electrochemistry, see: (a) Jiang, Y.; Xu,
K.; Zeng, C. Use of electrochemistry in the synthesis of heterocyclic
structures. Chem. Rev. 2018, 118, 4485−4540. (b) Wiebe, A.;
(5) Li, X.-L.; Huang, J.-H.; Yang, L.-M. Iron (III)-Promoted
oxidative coupling of naphthylamines: Synthetic and mechanistic
investigations. Org. Lett. 2011, 13, 4950−4953.
(6) (a) Matsumoto, K.; Dougomori, K.; Tachikawa, S.; Ishii, T.;
Shindo, M. Aerobic oxidative homocoupling of aryl amines using
heterogeneous rhodium catalysts. Org. Lett. 2014, 16, 4754−4757.
(b) Matsumoto, K.; Yoshida, M.; Shindo, M. Heterogeneous
Rhodium-Catalyzed Aerobic Oxidative Dehydrogenative Cross-
Coupling: Nonsymmetrical Biaryl Amines. Angew. Chem., Int. Ed.
2016, 55, 5272−5276.
(7) Other catalytic oxidative coupling of aryl amines, see:
(a) Chandrasekharam, M.; Chiranjeevi, B.; Gupta, K. S. V.; Sridhar,
B. Iron-Catalyzed Regioselective Direct Oxidative Aryl−Aryl Cross-
Coupling. J. Org. Chem. 2011, 76, 10229−10235. (b) Ito, M.; Kubo,
H.; Itani, I.; Morimoto, K.; Dohi, T.; Kita, Y. Organocatalytic C−H/
C−H′ Cross-Biaryl Coupling: C-Selective Arylation of Sulfonanilides
with Aromatic Hydrocarbons. J. Am. Chem. Soc. 2013, 135, 14078−
14081. (c) Forkosh, H.; Vershinin, V.; Reiss, H.; Pappo, D.
Stereoselective synthesis of optically pure 2-amino-2′-hydroxy-1,1′-
binaphthyls. Org. Lett. 2018, 20, 2459−2463.
̈
Gieshoff, T.; Mohle, S.; Rodrigo, E.; Zirbes, M.; Waldvogel, S. R.
Electrifying organic synthesis. Angew. Chem., Int. Ed. 2018, 57, 5594−
̈
5619. (c) Mohle, S.; Zirbes, M.; Rodrigo, E.; Gieshoff, T.; Wiebe, A.;
Waldvogel, S. R. Modern Electrochemical Aspects for the Synthesis of
Value-Added Organic Products. Angew. Chem., Int. Ed. 2018, 57,
6018−6041.
(17) Schulz, L.; Enders, M.; Elsler, B.; Schollmeyer, D.; Dyballa, K.
M.; Franke, R.; Waldvogel, S. R. Reagent- and Metal-Free Anodic C−
C Cross-Coupling of Aniline Derivatives. Angew. Chem., Int. Ed. 2017,
56, 4877−4881.
̈
(8) (a) Fritsche, R. F.; Theumer, G.; Kataeva, O.; Knolker, H.-J.
Iron-Catalyzed Oxidative C−C and N−N Coupling of Diarylamines
and Synthesis of Spiroacridines. Angew. Chem., Int. Ed. 2017, 56, 549−
(18) (a) Bering, L.; Vogt, M.; Paulussen, F. M.; Antonchick, A. P.
Selective, Catalytic, and Metal-Free Coupling of Electron-Rich
Phenols and Anilides Using Molecular Oxygen as Terminal Oxidant.
Org. Lett. 2018, 20, 4077−4080. (b) Mei, C.; Lu, W. Palladium (II)-
Catalyzed Oxidative Homo-and Cross-Coupling of Aryl ortho-sp2 C−
H Bonds of Anilides at Room Temperature. J. Org. Chem. 2018, 83,
4812−4823. (c) Shi, Y.; Liu, J.; Yang, Y.; You, J. General rhodium-
catalyzed oxidative cross-coupling reactions between anilines: syn-
thesis of unsymmetrical 2, 2′-diaminobiaryls. Chem. Commun. 2019,
55, 5475−5478.
(19) Matsumoto, K.; Kobayashi, Y.; Hirokane, T.; Yoshida, M.
Aerobic Intramolecular Oxidative Coupling Using Heterogeneous
Catalyst for Synthesis of N-Substituted 2,3,6,7-Tetramethoxycarba-
zoles. Chem. Pharm. Bull. 2020, 68, 167−172.
(20) (a) Shindo, M.; Matsumoto, K. Metal Catalyzed Synthetic
Reactions via Aerobic Oxidation as a Key Step. In New Horizons of
Process Chemistry - Scalable Reactions and Technologies; Tomioka, K.;
Shioiri, T.; Sajiki, H., Eds.; Springer: Singapore, 2017; pp 11−27.
(b) Matsumoto, K. Development of the Direct Transformations of
Aromatic C-H Bonds Using a Heterogeneous Metal Catalyst. J.
Pharm. Soc. Jpn. 2018, 138, 1353−1361. (c) Fujimoto, S.; Matsumoto,
K.; Shindo, M. Aerobic oxidative intramolecular aromatic coupling via
heterogeneous metal catalysts. Adv. Synth. Catal. 2016, 358, 3057−
3061. (d) Fujimoto, S.; Matsumoto, K.; Iwata, T.; Shindo, M. Aerobic
oxidative homocoupling reaction of anilides using heterogeneous
metal catalysts. Tetrahedron Lett. 2017, 58, 973−976. (e) Matsumoto,
K.; Tachikawa, S.; Hashimoto, N.; Nakano, R.; Yoshida, M.; Shindo,
M. Aerobic C−H Oxidation of Arenes Using a Recyclable,
Heterogeneous Rhodium Catalyst. J. Org. Chem. 2017, 82, 4305−
4316. (f) Matsumoto, K.; Nakano, R.; Hirokane, T.; Yoshida, M.
Synthesis of bridgehead-functionalized triptycene quinones via Lewis
acid−promoted Diels-Alder reaction of 9-acyloxyanthracenes. Tetra-
hedron Lett. 2019, 60, 975−978.
553. (b) Brutting, C.; Fritsche, R. F.; Kutz, S. K.; Borger, C.; Schmidt,
̈
̈
̈
A. W.; Kataeva, O.; Knolker, H.-J. Synthesis of 1, 1′-and 2, 2′-
Bicarbazole Alkaloids by Iron (III)-Catalyzed Oxidative Coupling of
2-and 1-Hydroxycarbazoles. Chem.−Eur. J. 2018, 24, 458−470.
̈
(c) Purtsas, A.; Kataeva, O.; Knolker, H.-J. Iron-Catalyzed Oxidative
C−C Cross-Coupling Reaction of Tertiary Anilines with Hydroxyar-
enes by Using Air as Sole Oxidant. Chem.−Eur. J. 2020, 26, 2499−
̈
2508. (d) Purtsas, A.; Stipurin, S.; Kataeva, O.; Knolker, H.-J. Iron-
Catalyzed Synthesis, Structure, and Photophysical Properties of
Tetraarylnaphthidines. Molecules 2020, 25, No. 1608.
(9) For selected reviews, see: (a) Ashenhurst, J. A. Intermolecular
oxidative cross-coupling of arenes. Chem. Soc. Rev. 2010, 39, 540−
548. (b) Yeung, C. S.; Dong, V. M. Catalytic dehydrogenative cross-
coupling: forming carbon−carbon bonds by oxidizing two carbon−
hydrogen bonds. Chem. Rev. 2011, 111, 1215−1292. (c) Grzybowski,
M.; Skonieczny, K.; Butenschoen, H.; Gryko, D. T. Comparison of
oxidative aromatic coupling and the Scholl reaction. Angew. Chem.,
Int. Ed. 2013, 52, 9900−9930. (d) Grzybowski, M.; Sadowski, B.;
̈
Butenschon, H.; Gryko, D. T. Synthetic Applications of Oxidative
Aromatic CouplingFrom Biphenols to Nanographenes. Angew.
Chem., Int. Ed. 2020, 59, 2998−3027.
(10) As for TiCl4, see: Periasamy, M.; Jayakumar, K. N.; Bharathi, P.
Aryltitanium species through the reaction of N,N-dialkylarylamines
with TiCl4: Oxidative coupling, N-dealkylation, and reaction with
electrophiles. J. Org. Chem. 2000, 65, 3548−3550.
(11) As for CuBr, see: (a) Jiang, Y.; Xi, C.; Yang, X. CuBr/H2O2-
mediated oxidative coupling of N,N-dialkylarylamines in water: A
practical synthesis of benzidine derivatives. Synlett 2005, 1381−1384.
As for Cu(ClO4)2, see: (b) Kirchgessner, M.; Sreenath, K.; Gopidas,
K. R. Understanding reactivity patterns of the dialkylaniline radical
cation. J. Org. Chem. 2006, 71, 9849−9852. (c) Sreenath, K.; Suneesh,
C. V.; Kumar, V. K. R.; Gopidas, K. R. Cu(II)-mediated generation of
triarylamine radical cations and their dimerization. An easy route to
tetraarylbenzidines. J. Org. Chem. 2008, 73, 3245−3251.
L
https://dx.doi.org/10.1021/acs.joc.0c02020
J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
pubs.acs.org/joc
Article
(21) Matsumoto, K.; Takeda, S.; Hirokane, T.; Yoshida, M. A Highly
Selective Palladium-Catalyzed Aerobic Oxidative Aniline−Aniline
Cross-Coupling Reaction. Org. Lett. 2019, 21, 7279−7283.
(22) Other catalytic oxidative cross-coupling of anilines was recently
reported, see: (a) Paniak, T. J.; Kozlowski, M. C. Aerobic Catalyzed
Oxidative Cross-Coupling of N,N-Disubstituted Anilines and Amino-
naphthalenes with Phenols and Naphthols. Org. Lett. 2020, 22, 1765−
1770. (b) Luo, M.-J.; Li, Y.; Ouyang, X.-H.; Li, J.-H.; He, D.-L.
Electrochemical dehydrogenative cross-coupling of two anilines: facile
synthesis of unsymmetrical biaryls. Chem. Commun. 2020, 56, 2707−
2710.
(36) Larrosa, M.; Guerrero, C.; Rodriguez, R.; Cruces, J. Selective
copper-promoted cross-coupling of aromatic amines with alkyl
boronic acids. Synlett 2010, 2101−2105.
(37) Garibotto, F. M.; Sortino, M. A.; Kouznetsov, V. V.; Enriz, R.
D.; Zacchinoa, S. A. Synthesis and antifungal activity of N-aryl-N-
benzylamines and of their homoallyl analogues. ARKIVOC 2011, 7,
149−161.
(23) The 5% Rh/C is commercially available from Sigma-Aldrich
(No. 206164).
(24) We previously reported that Pd/Al2O3 showed high catalytic
activities for oxidative biaryl coupling reactions; see refs 20c20d, and
21.
(25) Dombrowski, G. W.; Dinnocenzo, J. P.; Zielinski, P. A.; Farid,
S.; Wosinska, Z. M.; Gould, I. R. Efficient unimolecular deprotonation
of aniline radical cations. J. Org. Chem. 2005, 70, 3791−3800.
(26) Mallick, S.; Maddala, S.; Kollimalayan, K.; Venkatakrishnan, P.
Oxidative Coupling of Carbazoles: A Substituent-Governed Regiose-
lectivity Profile. J. Org. Chem. 2019, 84, 73−93.
(27) As similar examples, the oxidative coupling of 2-hydroxycarba-
̈
zoles was reported, see: (a) Knolker, H.-J.; Goesmann, H.; Hofmann,
C. Transition Metal Complexes in Organic Synthesis, Part 31. A
Novel Molybdenum-Mediated Synthesis of Carbazole Derivatives:
Application to the Total Synthesis of Mukonal and 1,1′-Bis(2-
Hydroxy-3-Methylcarbazole). Synlett 1996, 737−740. (b) Kang, H.;
Herling, M. R.; Niederer, K. A.; Lee, Y. E.; Reddy, P. V. G.; Dey, S.;
Allen, S. E.; Sung, P.; Hewitt, K.; Torruellas, C.; Kim, G. J.;
Kozlowski, M. C. Enantioselective Vanadium-Catalyzed Oxidative
Coupling: Development and Mechanistic Insights. J. Org. Chem. 2018,
83, 14362−14384. (c) Sako, M.; Sugizaki, A.; Takizawa, S.
Asymmetric oxidative coupling of hydroxycarbazoles: Facile synthesis
of (+)-bi-2-hydroxy-3-methylcarbazole. Bioorg. Med. Chem. Lett. 2018,
28, 2751−2753.
(28) Kosugi, Y.; Itoho, K.; Okazaki, H.; Yanai, T. Unexpected
formation of dibenzo [a, h] phenazine in the reaction between 1-
naphthyliminodimagnesium dibromide and 1-nitronaphthalene. J.
Org. Chem. 1995, 60, 5690−5692.
(29) Under an argon atmosphere, the homocoupling did not
proceed at all. Thus, oxygen is necessary to promote the present
heterogeneous catalytic reaction.
(30) Similarly, the filtration test with aniline 1f was conducted at 50
°C under O2 atmosphere. After the removal of Rh/C, the reaction of
1f also did not proceed at all.
(31) The recycling experiment for homocoupling of 1c was also
conducted at 50 °C under O2 atmosphere. The reaction with the
recovered Rh/C catalyst afforded 72% of 2c, although the rection
time was slightly prolonged. This result revealed that Rh/C can be
reused in the coupling reaction using simple anilines.
(32) (a) Reay, A. J.; Fairlamb, I. J. S. Catalytic C−H bond
functionalisation chemistry: The case for quasi-heterogeneous
catalysis. Chem. Commun. 2015, 51, 16289−16307. (b) Santoro, S.;
Kozhushkov, S. I.; Ackermann, L.; Vaccaro, L. Heterogeneous
catalytic approaches in C−H activation reactions. Green Chem.
2016, 18, 3471−3493.
(33) Wolfe, J. P.; Tomori, H.; Sadighi, J. P.; Yin, J.; Buchwald, S. L.
Simple, efficient catalyst system for the palladium-catalyzed amination
of aryl chlorides, bromides, and triflates. J. Org. Chem. 2000, 65,
1158−1174.
(34) La, M. T.; Kang, S.; Kim, H. K. Metal-Free Synthesis of N-Aryl-
Substituted Azacycles from Cyclic Ethers Using POCl3. J. Org. Chem.
2019, 84, 6689−6696.
(35) Huang, X.; Anderson, K. W.; Zim, D.; Jiang, L.; Klapars, A.;
Buchwald, S. L. Expanding Pd-catalyzed C−N bond-forming
processes: the first amidation of aryl sulfonates, aqueous amination,
and complementarity with Cu-catalyzed reactions. J. Am. Chem. Soc.
2003, 125, 6653−6655.
M
https://dx.doi.org/10.1021/acs.joc.0c02020
J. Org. Chem. XXXX, XXX, XXX−XXX