A Gold(I)-Catalyzed Tandem Cyclization to Benzo[b]indeno[1,2-e][1,4]diazepines from o-Phenylenediamines and Ynones

Article abstract of DOI:10.1002/adsc.202000755

A gold-catalyzed tandem cyclization of o-phenylenediamines with ynones to synthesize benzo[b]indeno[1,2-e][1,4]diazepine has been developed. The mechanism was explored by control experiments. The method provides a way to access a range of benzo[b]indeno[1,2-e][1,4]diazepine derivatives in diversity-oriented synthesis aiming at discovering structurally diverse scaffolds. (Figure presented.).

Full text of DOI:10.1002/adsc.202000755

Title: A Gold(I)-Catalyzed Tandem Cyclization to Benzo[b]indeno [1,2-
e][1,4]diazepines from o-Phenylenediamines and Ynones
Authors: Fukai Xie, Bo Zhang, Yanyu Chen, Hongwei Jia, Lei Sun,
Kaitong Zhuang, Lili Yin, Maosheng Cheng, Bin Lin, and
Yongxiang Liu
This manuscript has been accepted after peer review and appears as an
Accepted Article online prior to editing, proofing, and formal publication
of the final Version of Record (VoR). This work is currently citable by
using the Digital Object Identifier (DOI) given below. The VoR will be
published online in Early View as soon as possible and may be different
to this Accepted Article as a result of editing. Readers should obtain
the VoR from the journal website shown below when it is published
to ensure accuracy of information. The authors are responsible for the
content of this Accepted Article.
To be cited as: Adv. Synth. Catal. 10.1002/adsc.202000755
Link to VoR: https://doi.org/10.1002/adsc.202000755

10.1002/adsc.202000755
Advanced Synthesis & Catalysis
FULL PAPER
DOI: 10.1002/adsc.202((will be filled in by the editorial staff))
A Gold(I)-Catalyzed Tandem Cyclization to Benzo[b]indeno
[1,2-e][1,4]diazepines from o-Phenylenediamines and Ynones
Fukai Xie,a,b,c Bo Zhang,a,b,c Yanyu Chen,a,b,c Hongwei Jia,a,c Lei Sun,a,b,c Kaitong
Zhuang,a,c Lili Yin,d Maosheng Cheng,a,c Bin Lin,a,c and Yongxiang Liua,b,c,
*
a
Key Laboratory of Structure-Based Drug Design and Discovery (Shenyang Pharmaceutical University), Ministry of
Education, Shenyang 110016, P. R. China
Phone: +86-24-45864056; Fax: +86-24-45864056
E-mail: yongxiang.liu@syphu.edu.cn
b
c
d
Wuya College of Innovation, Shenyang Pharmaceutical University, Shenyang 110016, P. R. China
Institute of Drug Research in Medicine Capital of China, Benxi 117000, P. R. China
Shenyang Heshi Pharmaceutical Co., Ltd., Shengyang 110163, P. R. China
Received: ((will be filled in by the editorial staff))
Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/adsc.201######.
Abstract. A gold-catalyzed tandem cyclization of o-
phenylenediamines with ynones to synthesize benzo[b]
indeno[1,2-e][1,4]diazepine has been developed. The
mechanism was explored by control experiments. The method
provides a way to access a range of benzo[b] indeno[1,2-
e][1,4]diazepine derivatives in diversity-oriented synthesis
aiming at discovering structurally diverse scaffolds.
Keywords: Benzodiazepines; Heterocycles; Gold;
Synthetic methods; Domino reactions; Homogeneous
catalysis
functionalization/intramolecular azide-alkyne 1,3-
dipolar cyclization method to synthesize 9H-
benzo[b]pyrrolo[1,2-g][1,2,3]triazolo[1,5-d][1,4]
diazepines (Scheme 1, c).[9i] In 2016, Goggiamani and
Introduction
Benzodiazepines are one of attractive frameworks in
medicinal chemistry due to their abundance in drugs
and high hit rates in lead discovery.[1] The
development of structurally diverse benzodiazepines
as privileged scaffolds for the preparation of molecular
libraries is important in diversity-oriented synthesis.[2]
Traditionally, they exhibit significant pharmacological
activities on the central nervous system such as
coworkers
advanced
a
gold-catalyzed
hydroamination/cyclization domino process to
construct 1,5-benzodiazepines using propargylic
alcohol and o-phenylenediamines as building blocks
(Scheme 1, d).[9j] Although these efforts have greatly
expanded the diversity of benzodiazepine scaffolds,
more synthetic transformations are urgently needed to
access complex benzodiazepine derivatives, ideally
constructed from relatively simple materials via
tandem cyclization.
antianxiety,
sedative,
antidepressive
and
anticonvulsant etc.[3] Recently, as more synthetic
compounds are available from novel methodologies,
chemists carried out expansive research on their
activities in treatment of HIV,[4] cancer,[5]
inflammation,[6] lipid peroxidation[7] and malaria.[8]
Due to the significance of these molecules, many
synthetic strategies have been developed in recent
years.[9] For example, in 2012, Dömling and coworkers
reported a Ugi four-component reaction strategy to
1,4-benzodiazepine-6-ones (Scheme 1, a).[9g] In 2014,
Dembinski and coworkers described a catalyst-free
microwave-accelerated condensation of alk-3-ynones
Recently,
homogeneous
gold-catalyzed
cycloisomerizations have emerged as robust and
versatile toolboxes for their atom-economical
assembly of a range of compounds from simple
noncyclic substrates.[10a,10n] They are featured as mild
conditions,
high
efficiency
and
excellent
selectivity.[10b,10m] Multiple carbon-carbon and carbon-
hetero bonds can be formed in one-pot fashion under
the catalysis of gold cation species, representing a
unique
approach
to
structurally
diverse
and
o-phenylenediamines
to
access
1,5-
heterocycles.[10c] Therefore, they have been applied in
extensive transformations such as the total syntheses
of natural products and synthetic methodologies.[10]
benzodiazepines (Scheme 1, b).[9h] In the same year,
Hajela and coworkers developed a tandem C-2
1
This article is protected by copyright. All rights reserved.

10.1002/adsc.202000755
Advanced Synthesis & Catalysis
As part of our persistent research interest in
allowed us to isolate the benzo[b]indeno[1,2-e]
[1,4]diazepine 2 successfully. We further investigated
this cascade process by screening the reaction
conditions using substrate 1 and o-phenylenediamine
under the catalysis of readily available cationic gold(I)
catalysts shown in Table 1. Except for Ph3PAuCl, all
of the catalysts allowed the formation of diazepine 2
and the combination of Ph3PAuCl and AgSbF6 gave
the best yield (Table 1, entries 1-6). The control
experiment showed that AgSbF6 alone could not
catalyze this transformation (Table 1, entry 7).
Examination of reaction temperature revealed that
70 °C was the best temperature for the condensation of
the two fragments to form diazepine 2 (Table 1, entries
8-9). Decreasing the catalyst loading to 3 mol% led to
a lower yield of the desired product (Table 1, entry 10).
Increasing the catalyst loading to 10 mol% did not
improve the yields (Table 1, entry 11). Investigation
on the amounts of o-phenylenediamine showed that 3
equivalents afforded the best result (Table 1, entries
12-13). Screening of solvents revealed that toluene
was the optimal one among the screened solvents such
as tetrahydrofuran (THF), 1,2-dichloroethane (DCE)
and acetonitrile (Table 1, entries 14-16). Finally, the
optimal condition for the one-pot tandem cyclization
was determined as stirring the substrates in the
catalysis of Ph3PAuCl/AgSbF6 in toluene at room
temperature followed by heating with o-
phenylenediamine at 70 °C.
constructing structurally diverse heterocyclic
molecules via gold-catalyzed cycloisomerizations, we
have developed a number of synthetic methods to
synthesize heterocycles such as multi-substituted
furofuran and furopyran,[11a] indeno-chromen-4-one
and indeno-quinolin-4-one,[11b] benzo[a]carbazole and
indeno[1,2-c]quinolone,[11c] 12H-benzo[a]xanthen-12-
one and benzo[a]acridin-12(7H)-one[11d] etc. Herein
we described a gold(I)-catalyzed intramolecular
cycloisomerization/ intermolecular Michael addition
and condensation cascade process to access a series of
structurally
novel
benzo[b]indeno[1,2-
e][1,4]diazepines using commercially available o-
phenylenediamines and facilely prepared ynones as
building blocks11b,12,13d (Scheme 1, e).
Table 1. Optimization of Reaction Conditions
temp. yield
entry[a] catalyst[b] additive[c] solvent
(°C)
(%)
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
Ph3PAuCl
Ph3PAuNTf2
Ph3PAuCl
Ph3PAuCl
Ph3PAuCl
IPrAuCl
toluene
toluene
toluene
toluene
70
70
70
70
70
70
70
80
60
70
70
70
70
70
70
70
0[d]
37
48
64
85
AgBF4
AgOTf
AgSbF6 toluene
AgSbF6 toluene
toluene
AgSbF6 toluene
AgSbF6 toluene
AgSbF6 toluene
AgSbF6 toluene
AgSbF6 toluene
AgSbF6 toluene
Scheme 1. Representative Methods and Our Tandem
Cyclization Strategy to Benzodiazepine Derivatives
80
AgSbF6
0[d]
57
Ph3PAuCl
Ph3PAuCl
Ph3PAuCl
Ph3PAuCl
Ph3PAuCl
Ph3PAuCl
Ph3PAuCl
Ph3PAuCl
Ph3PAuCl
73
68[e]
80[f]
61[g]
70[h]
40
Results and Discussion
We envisioned that cycloisomerization of substrate 1
via methoxyl migration/nucleophilic addition under
the catalysis of gold(I) species would furnish indenone
derivatives.11b,13 A sequential condensation between
the indenone with o-phenylenediamine would
generate benzo[b]indeno[1,2-e][1,4]diazepine 2 as a
structurally novel hybrid molecule in one pot (Table 1).
Based on this synthetic design, we treated substrate 1
with gold catalyst at room temperature followed by
addition of o-phenylenediamine at 70 °C, which
AgSbF6
AgSbF6
THF
DCE
AgSbF6 CH3CN
35
26
[a] 3 eq. o-phenylenediamine was utilized. [b] 5 mol% catalyst
was utilized. [c] 5 mol% additive was utilized. [d] Stirring for
24 h. [e] 3 mol% catalyst and additive were utilized. [f] 10 mol%
[g]
catalyst and additive were utilized.
1.5 eq. o-
2
This article is protected by copyright. All rights reserved.

10.1002/adsc.202000755
Advanced Synthesis & Catalysis
phenylenediamine was utilized.[h] 5 eq. o-phenylenediamine
was utilized.
With the optimal conditions in hand, we explored
the scope of this tandem transformation systematically
by using a variety of ynone substrates and o-
phenylenediamines. First, the substitutions on the
carbonyl group (R1) were investigated as illustrated in
Scheme 2. The substrates with monosubstituted
phenyl group on R1 underwent smoothly to yield
benzo[b]indeno[1,2-e][1,4] diazepines with good to
excellent yields regardless of
Scheme 2. Exploring the Scope of Various Substituents at
R1
electron-donating or withdrawing substitutions on
phenyl group (Scheme 2, 2a-2i, 2k-2o). The substrate
bearing sulfur substitution provided relatively lower
yield, which might be attributed to the attenuation of
gold catalysts by the sulfur atom via coordination
(Scheme 2, 2j). The substrate with multiple electron-
donating groups on phenyl ring also gave low yield
probably owing to the decreased electrophilic ability
of carbonyl group in the substrate (Scheme 2, 2p). The
3
This article is protected by copyright. All rights reserved.

10.1002/adsc.202000755
Advanced Synthesis & Catalysis
substrate with naphthyl substitution could afford the
corresponding product in a satisfactory yield (Scheme
2, 2q). The reaction was also compatible with the
substrates bearing thiophene moieties. However, only
moderate yield was achieved due to the instability of
the product during isolation (Scheme 2, 2r). The
substrates with aliphatic substitutions on the carbonyl
group (R1) were also investigated; however, no desired
products were isolated.
phenylenediamine with electron-donating substituents
was employed, the desired product was obtained in
excellent yield (Scheme 4, 5a). Interestingly, the o-
phenylenediamines bearing electron-withdrawing
substituents were also worked, resulting in acceptable
yields (Scheme 4, 5b-5d). The attempts by utilizing
unsymmetrically substituted o-phenylenediamines
proved unsuccessful because an unisolatable mixture
of two regioisomer was obtained.
Scheme 4. Exploring the Scope of Various Substituents at
R3
To gain an insight into the possible mechanism of
this tandem cyclization, control experiments were
carried out based on substrate 1 (Scheme 5). In order
to trap the intermediate of the gold-catalyzed reaction,
the substrate 1 was treated with gold(I) catalyst in the
absence of o-phenylenediamine, which resulted in the
generation of intermediate 7 via a gold-catalyzed
methoxyl rearrangement/cyclization (Scheme 5, a).
When the isolated intermediate 7 was subjected to the
standard conditions, the desired product 2 was
obtained in a satisfactory yield. To examine the
influence of the gold catalyst in the second cyclization,
the isolated intermediate 7 was heated with o-
phenylenediamine without the catalysts, leading to the
isolation of the desired product 2 in 89% yield. This
result indicated that the gold catalyst did not play a role
in the second cyclization (Scheme 5, b). Furthermore,
to elucidate the detailed process of the diazepine ring
construction, we employed aniline in place of o-
phenylenediamine to capture the possible intermediate.
The product 8, derived from the Michael addition of
aniline to the ,-unsaturated ketone/elimination of
methanol was isolated as the only product (Scheme 5,
c). On the basis of this observation, it could be inferred
that the intermolecular Michael addition of amino to
Scheme 3. Exploring the Scope of Various Substituents at
R2
Next, the scope of substituents on the phenyl ring
connected to the alkynyl (R2) was examined. A variety
of functional groups such as F, Cl, Me and OMe were
well-tolerated and excellent yields were obtained
(Scheme 3, 4a-4k). Gratifyingly, the substrates with
multiple electron-donating substituents on this phenyl
ring also underwent smoothly to give corresponding
products in acceptable yields (Scheme 3, 4l-4m).
Finally, several substituted o-phenylenediamines
were investigated (Scheme 4). When the o-
4
This article is protected by copyright. All rights reserved.

10.1002/adsc.202000755
Advanced Synthesis & Catalysis
,-unsaturated ketone rather than imine formation
happened preferentially in the diazepine formation.
Scheme 5. Control Experiments
Based on the experiments above and precedent
studies,9h,11b-11c,13,14 a plausible mechanism for the
tandem cyclization was proposed in Scheme 6. The
reaction commences with the activation of triple bonds
by gold(I) cation species followed by the migration of
methoxy group to afford vinylgold species 1-2. Then
the oxonium in 1-2 is attacked by vinyl ether through
an intramolecular nucleophilic addition to afford
intermediate 1-3, which is tautomerized into 7. Upon
o-phenylenediamine is added, an intermolecular
Michael addition of o-phenylenediamine to 7 affords
the adduct 7-1. Regeneration of ,-unsaturated
ketone by releasing methanol gives the intermediate 7-
2. Finally, product 2 is achieved through an
intramolecular condensation of free amino and
carbonyl group followed by a formation of highly
conjugated system via subsequent aromatization by
release of methanol.
diazepine compounds was ongoing in our lab and will
be reported in due course.
Scheme 6. Proposed Reaction Mechanism
Conclusion
Experimental Section
1. General Information
In conclusion, we have developed a gold(I)-catalyzed
tandem cyclization strategy to provide a series of
benzo[b]indeno[1,2-e][1,4]diazepines. This one-pot
cascade strategy was involved in construction of two
rings through cleavage of three chemical bonds and
formation of three new double bonds from
commercially available o-phenylenediamines and
readily prepared ynones. The scope of the
methodology was examined by a variety of substrates.
The possible mechanism of the transformation was
probed by isolation of the intermediate and carefully
designed control experiments. The study on the
bioactivity of the benzo[b]indeno[1,2-e][1,4]
Unless otherwise noted, reagents were obtained
commercially and used without further purification.
Tetrahydrofuran (THF) was distilled from sodium under a
nitrogen atmosphere. Dichloromethane (DCM) was distilled
from calcium hydride under a nitrogen atmosphere.
Chloroform was distilled from calcium hydride under a
nitrogen atmosphere. Toluene was distilled from sodium
under a nitrogen atmosphere. TLC analysis of reaction
mixtures was performed on Dynamicadsorbents silica gel F-
254 TLC plates. Flash column chromatography was carried
out on Zeoprep 60 (200-300 mesh) silica gel. H and 13C
1
NMR spectra were recorded with Bruker Avance-III 600
spectrometers or Bruker Ascend 400 and referenced to
CDCl3 and DMSO-d6. HR-ESI-MS was recorded on a
Bruker micro-TOFQ-Q instrument. IR spectra were
recorded on a Bruker IFS 55 spectrometer. Melting points
5
This article is protected by copyright. All rights reserved.

10.1002/adsc.202000755
Advanced Synthesis & Catalysis
(Mp) were tested on Thomas Hoover capillary melting point
apparatus.
give the product 2c (240 mg) as a red solid with a yield of
64%; Mp 204.4 – 205.6 °C; 1H NMR (400 MHz, CDCl3) δ
8.38 (d, J = 7.3 Hz, 1H), 8.17 – 8.07 (m, 1H), 7.95 – 7.86
(m, 3H), 7.81 (s, 1H), 7.79 (s, 1H), 7.71 – 7.62 (m, 2H), 7.62
– 7.56 (m, 3H), 7.49 (s, 1H); 13C NMR (150 MHz, CDCl3)
δ 162.4, 159.9, 145.5, 142.0, 141.7, 139.6, 136.8, 135.5,
135.4, 135.3, 131.6, 131.4 (q, J = 32.5 Hz), 130.7, 129.5,
128.9, 128.7, 128.1, 125.7 (q, J = 3.8 Hz), 124.2 (d, J =
272.1 Hz), 123.0, 122.9; IR (thin film, cm-1) 2923, 2853,
1603, 1463, 1403, 1382, 1332, 1168, 1106, 1066; HRMS
(ESI): m/z Calcd. for C23H14F3N2 [M+H]+ 375.1104, Found
375.1100.
2. General Procedures for the Preparation of
Benzo[b]indeno[1,2-e][1,4]diazepines 2, 2a-2r, 4a-4m,
5a-5d and Characterization Data
Ph3PAuCl (0.05 mmol, 25 mg) and AgSbF6 (0.05 mmol, 17
mg) were added in toluene (5 mL) and the mixture was
stirred at room temperature for 10 min. Substrates 1, 1a-1r,
3a-3m (1.0 mmol) were then added to the above solution
and the mixture was stirred at room temperature for 30 min
till TLC showed the consumption of the starting material. o-
Phenylenediamine (3.0 mmol) was added to the above
mixture and the solution was stirred at 70 °C for 3.5 h till
TLC showed the consumption of the intermediates. The
solvent was removed in vacuo and the residue was purified
Methyl 4-(benzo[b]indeno[1,2-e][1,4]diazepin-11-
yl)benzoate (2d)
Purified by a flash column chromatography on silica gel
with petroleum ether/dichloromethane (1:1) as an eluent to
give the product 2d (266 mg) as a red solid with a yield of
73%; Mp 208.2 – 210.1 °C; 1H NMR (600 MHz, CDCl3) δ
8.37 (d, J = 7.4 Hz, 1H), 8.20 (d, J = 8.2 Hz, 2H), 8.14 –
8.07 (m, 1H), 7.96 – 7.89 (m, 1H), 7.84 (d, J = 8.3 Hz, 2H),
7.65 (td, J = 7.4, 1.3 Hz, 1H), 7.61 (td, J = 7.4, 1.2 Hz, 1H),
7.59 – 7.56 (m, 3H), 7.48 (s, 1H), 3.98 (s, 3H); 13C NMR
(150 MHz, CDCl3) δ 166.9, 162.4, 160.3, 146.3, 142.1,
141.7, 139.6, 136.8, 135.5, 135.35, 135.26, 131.6, 130.9,
130.6, 130.0, 129.4, 128.7, 128.6, 128.0, 122.9, 122.8, 52.4;
IR (thin film, cm-1) 3426, 2922, 2852, 1719, 1628, 1435,
1384, 1278, 1101, 747; HRMS (ESI): m/z Calcd. for
C24H17N2O2 [M+H]+ 365.1285, Found 365.1287.
by
a
flash column chromatography (petroleum
ether/dichloromethane) on silica gel to afford the products
2, 2a-2r, 4a-4m, 5a-5d.
11-Phenylbenzo[b]indeno[1,2-e][1,4]diazepine (2)
Purified by a flash column chromatography on silica gel
with petroleum ether/dichloromethane (1:1) as an eluent to
give the product 2 (260 mg) as a red solid with a yield of
85%; Mp 213.2 – 214.9 °C; 1H NMR (400 MHz, CDCl3) δ
8.36 (d, J = 7.2 Hz, 1H), 8.12 – 8.06 (m, 1H), 7.96 – 7.89
(m, 1H), 7.85 – 7.73 (m, 2H), 7.67 – 7.61 (m, 1H), 7.61 –
7.54 (m, 5H), 7.54 – 7.51 (m, 3H); 13C NMR (100 MHz,
CDCl3) δ 162.5, 161.4, 142.2, 142.1, 141.8, 139.6, 136.9,
135.4, 135.3, 135.2, 131.4, 130.5, 129.5, 129.0, 128.9, 128.6,
128.5, 127.7, 122.9, 122.7; IR (thin film, cm-1) 2986, 2831,
1609, 1492, 1440, 1400, 1368, 1173, 1006, 799; HRMS
(ESI): m/z Calcd. for C22H15N2 [M+H]+ 307.1230, Found
307.1232.
11-(4-(Trifluoromethoxy)phenyl)benzo[b]indeno[1,2-e]
[1,4]diazepine (2e)
Purified by a flash column chromatography on silica gel
with petroleum ether/dichloromethane (1:1) as an eluent to
give the product 2e (250 mg) as a red solid with a yield of
64%; Mp 175.4 – 175.9 °C; 1H NMR (400 MHz, CDCl3) δ
8.36 (d, J = 7.2 Hz, 1H), 8.09 (dd, J = 6.0, 3.6 Hz, 1H), 7.90
(dd, J = 6.0, 3.6 Hz, 1H), 7.83 (d, J = 8.3 Hz, 2H), 7.69 –
7.54 (m, 5H), 7.52 (s, 1H), 7.38 (d, J = 8.2 Hz, 2H); 13C
NMR (150 MHz, CDCl3) δ 162.3, 159.8, 150.0, 142.0,
141.7, 140.7, 139.6, 136.7, 135.4, 135.34, 135.32, 131.5,
130.6, 130.2, 129.3, 128.7, 128.0, 122.9, 122.8, 121.0, 120.7
(q, J = 257.8 Hz); IR (thin film, cm-1) 2922, 2853, 2370,
2341, 1627, 1465, 1384, 1270, 1253, 1102; HRMS (ESI):
m/z Calcd. for C23H14F3N2O [M+H]+ 391.1053, Found
391.1051.
11-(4-Fluorophenyl)benzo[b]indeno[1,2-e][1,4]
diazepine (2a)
Purified by a flash column chromatography on silica gel
with petroleum ether/dichloromethane (1:1) as an eluent to
give the product 2a (227 mg) as a red solid with a yield of
70%; Mp 218.6 – 219.3 °C; 1H NMR (600 MHz, CDCl3) δ
8.36 (d, J = 7.3 Hz, 1H), 8.12 – 8.06 (m, 1H), 7.93 – 7.88
(m, 1H), 7.82 – 7.77 (m, 2H), 7.65 (td, J = 7.3, 1.2 Hz, 1H),
7.62 – 7.58 (m, 2H), 7.58 – 7.54 (m, 2H), 7.53 (s, 1H), 7.24
– 7.18 (m, 2H); 13C NMR (150 MHz, CDCl3) δ 163.6 (d, J
= 248.8 Hz) 162.4, 160.2, 142.0, 141.7, 139.5, 138.2 (d, J =
3.3 Hz), 136.7, 135.4, 135.3 (d, J = 7.1 Hz), 131.5, 130.6,
130.6, 130.5, 129.1, 128.9, 127.9, 122.9, 122.8, 115.6 (d, J
= 21.4 Hz); IR (thin film, cm-1) 2985, 2923, 2852, 1610,
1492, 1441, 1400, 1366, 1173, 1007, 799; HRMS (ESI): m/z
Calcd. for C22H14FN2 [M+H]+ 325.1136, Found 325.1132.
11-(p-Tolyl)benzo[b]indeno[1,2-e][1,4]diazepine (2f)
Purified by a flash column chromatography on silica gel
with petroleum ether/dichloromethane (1:1) as an eluent to
give the product 2f (234 mg) as a red solid with a yield of
73%; Mp 188.6 – 189.2 °C; 1H NMR (600 MHz, CDCl3) δ
8.36 (d, J = 7.4 Hz, 1H), 8.11 – 8.06 (m, 1H), 7.97 – 7.89
(m, 1H), 7.69 (d, J = 8.0 Hz, 2H), 7.64 (td, J = 7.3, 1.2 Hz,
1H), 7.61 – 7.57 (m, 3H), 7.57 – 7.53 (m, 2H), 7.33 (d, J =
7.8 Hz, 2H), 2.47 (s, 3H); 13C NMR (150 MHz, CDCl3) δ
162.5, 161.4, 142.3, 141.8, 139.58, 139.57, 139.3, 136.8,
135.37, 135.35, 135.2, 131.3, 130.5, 129.2, 129.1, 128.8,
128.5, 127.7, 122.8, 122.7, 21.6.; IR (thin film, cm-1) 2986,
2831, 1609, 1492, 1440, 1400, 1367, 1173, 1006, 799;
HRMS (ESI): m/z Calcd. for C23H17N2 [M+H]+ 321.1386,
Found 321.1389.
11-(4-Chlorophenyl)benzo[b]indeno[1,2-e][1,4]
diazepine (2b)
Purified by a flash column chromatography on silica gel
with petroleum ether/dichloromethane (1:1) as an eluent to
give the product 2b (262 mg) as a red solid with a yield of
77%; Mp 225.2 – 225.5 °C; 1H NMR (400 MHz, CDCl3) δ
8.36 (d, J = 7.4 Hz, 1H), 8.13 – 8.05 (m, 1H), 7.94 – 7.86
(m, 1H), 7.76 – 7.70 (m, 2H), 7.69 – 7.63 (m, 1H), 7.63 –
7.55 (m, 4H), 7.53 – 7.50 (m, 2H), 7.50 – 7.47 (m, 1H); 13C
NMR (100 MHz, CDCl3) δ 162.4, 160.1, 142.0, 141.7,
140.5, 139.6, 136.7, 135.5, 135.4, 135.3 (2C), 131.5, 130.6,
130.0, 129.2, 128.8, 128.7, 127.9, 122.9, 122.8; IR (thin film,
cm-1) 2985, 2926, 1636, 1603, 1491, 1448, 1368, 1174, 1066,
1011, 799, 764; HRMS (ESI): m/z Calcd. for C22H14ClN2
[M+H]+ 341.0840, Found 341.0840.
11-(4-Ethylphenyl)benzo[b]indeno[1,2-e][1,4]diazepine
(2g)
Purified by a flash column chromatography on silica gel
with petroleum ether/dichloromethane (1:1) as an eluent to
give the product 2g (227 mg) as a red solid with a yield of
68%; Mp 148.6 – 150.1 °C; 1H NMR (600 MHz, CDCl3) δ
8.37 (d, J = 7.3 Hz, 1H), 8.15 – 8.03 (m, 1H), 7.97 – 7.89
(m, 1H), 7.72 (d, J = 8.0 Hz, 2H), 7.64 (t, J = 7.3 Hz, 1H),
7.62 – 7.57 (m, 3H), 7.57 – 7.50 (m, 2H), 7.35 (d, J = 7.8
Hz, 2H), 2.76 (q, J = 7.6 Hz, 2H), 1.32 (t, J = 7.6 Hz, 3H);
11-(4-(Trifluoromethyl)phenyl)benzo[b]indeno[1,2-e]
[1,4]diazepine (2c)
Purified by a flash column chromatography on silica gel
with petroleum ether/dichloromethane (1:1) as an eluent to
6
This article is protected by copyright. All rights reserved.

10.1002/adsc.202000755
Advanced Synthesis & Catalysis
13C NMR (150 MHz, CDCl3) δ 162.5, 161.5, 145.9, 142.3,
141.9, 139.60, 139.59, 136.9, 135.42, 135.38, 135.2, 131.4,
130.5, 129.1, 128.8, 128.6, 128.1, 127.7, 122.9, 122.7, 29.0,
15.7; IR (thin film, cm-1) 2959, 2923, 2853, 1603, 1548,
1463, 1377, 1332, 1182, 1114, 764; HRMS (ESI): m/z Calcd.
for C24H19N2 [M+H]+ 335.1543, Found 335.1540.
11-(3-Fluorophenyl)benzo[b]indeno[1,2-e][1,4]
diazepine (2l)
Purified by a flash column chromatography on silica gel
with petroleum ether/dichloromethane (1:1) as an eluent to
give the product 2l (204 mg) as a red solid with a yield of
63%; Mp 212.8 – 213.8 °C; 1H NMR (400 MHz, CDCl3) δ
8.40 – 8.33 (m, 1H), 8.19 – 8.04 (m, 1H), 7.99 – 7.87 (m,
1H), 7.70 – 7.62 (m, 1H), 7.61 – 7.55 (m, 5H), 7.55 (s, 1H),
7.54 – 7.44 (m, 2H), 7.21 (tdd, J = 8.4, 2.6, 1.1 Hz, 1H); 13C
NMR (100 MHz, CDCl3) δ 162.9 (d, J = 246.7 Hz), 162.4,
159.8 (d, J = 2.4 Hz), 144.1 (d, J = 7.3 Hz), 142.0, 141.7,
139.6, 136.9, 135.4, 135.3 (2C), 131.5, 130.6, 130.2 (d, J =
8.1 Hz), 129.3, 128.6, 127.9, 124.2 (d, J = 3.0 Hz), 122.9,
122.8, 116.4 (d, J = 21.2 Hz), 115.8 (d, J = 22.5 Hz); IR
(thin film, cm-1) 3048, 2986, 2831, 1609, 1492, 1439, 1400,
1368, 1173, 1006, 798; HRMS (ESI): m/z Calcd. for
C22H14FN2 [M+H]+ 325.1136, Found 325.1138.
11-(4-Isopropylphenyl)benzo[b]indeno[1,2-e][1,4]
diazepine (2h)
Purified by a flash column chromatography on silica gel
with petroleum ether/dichloromethane (1:1) as an eluent to
give the product 2h (233 mg) as a red solid with a yield of
67%; Mp 158.0 – 159.6 °C; 1H NMR (400 MHz, CDCl3) δ
8.36 (d, J = 7.2 Hz, 1H), 8.14 – 8.04 (m, 1H), 8.00 – 7.89
(m, 1H), 7.73 (d, J = 8.1 Hz, 2H), 7.61 (t, J = 10.1 Hz, 4H),
7.57 – 7.53 (m, 2H), 7.38 (d, J = 8.0 Hz, 2H), 3.02 (hept, J
= 6.9 Hz, 1H), 1.34 (d, J = 6.9 Hz, 6H); 13C NMR (100 MHz,
CDCl3) δ 162.5, 161.5, 150.5, 142.3, 141.9, 139.7, 139.6,
136.9, 135.41, 135.35, 135.2, 131.3, 130.4, 129.1, 128.8,
128.6, 127.7, 126.6, 122.8, 122.7, 34.3, 24.1; IR (thin film,
cm-1) 2955, 2923, 2852, 1604, 1549, 1464, 1403, 1375, 1334,
1092, 766, 751; HRMS (ESI): m/z Calcd. for C25H21N2
[M+H]+ 349.1699, Found 349.1701.
11-(3-Chlorophenyl)benzo[b]indeno[1,2-e][1,4]
diazepine (2m)
Purified by a flash column chromatography on silica gel
with petroleum ether/dichloromethane (1:1) as an eluent to
give the product 2m (222 mg) as a red solid with a yield of
65%; Mp 196.3 – 197.3 °C; 1H NMR (400 MHz, CDCl3) δ
8.36 (d, J = 7.3 Hz, 1H), 8.10 (dt, J = 6.0, 3.7 Hz, 1H), 7.96
– 7.86 (m, 1H), 7.77 (s, 1H), 7.68 – 7.63 (m, 2H), 7.63 –
7.55 (m, 4H), 7.51 (s, 1H), 7.52 – 7.41 (m, 2H); 13C NMR
(100 MHz, CDCl3) δ 162.4, 159.8, 143.7, 142.0, 141.7,
139.6, 136.8, 135.4, 135.32, 135.29, 134.6, 131.5, 130.6,
129.9, 129.6, 129.3, 128.75, 128.67, 128.0, 126.6, 122.9,
122.8; IR (thin film, cm-1) 2986, 2922, 2831, 1609, 1492,
1440, 1401, 1367, 1173, 1006, 799, 774; HRMS (ESI): m/z
Calcd. for C22H14ClN2 [M+H]+ 341.0840, Found 341.0843.
11-(4-Methoxyphenyl)benzo[b]indeno[1,2-e][1,4]
diazepine (2i)
Purified by a flash column chromatography on silica gel
with petroleum ether/dichloromethane (1:1) as an eluent to
give the product 2i (279 mg) as a red solid with a yield of
83%; Mp 206.6 – 206.8 °C; 1H NMR (400 MHz, CDCl3) δ
8.39 – 8.30 (m, 1H), 8.11 – 8.03 (m, 1H), 7.95 – 7.88 (m,
1H), 7.83 – 7.75 (m, 2H), 7.66 – 7.61 (m, 2H), 7.61 – 7.50
(m, 4H), 7.09 – 7.00 (m, 2H), 3.90 (s, 3H); 13C NMR (100
MHz, CDCl3) δ 162.4, 160.82, 160.81, 142.2, 141.8, 139.5,
136.6, 135.4, 135.23, 135.15, 134.7, 131.3, 130.4, 130.2,
129.0, 128.6, 127.7, 122.8, 122.6, 113.9, 55.6; IR (thin film,
cm-1) 3047, 2986, 2922, 2831, 1607, 1492, 1441, 1367, 1253,
1174, 1007, 761; HRMS (ESI): m/z Calcd. for C23H17N2O
[M+H]+ 337.1335, Found 337.1333.
11-(m-Tolyl)benzo[b]indeno[1,2-e][1,4]diazepine (2n)
Purified by a flash column chromatography on silica gel
with petroleum ether/dichloromethane (1:1) as an eluent to
give the product 2n (266 mg) as a red solid with a yield of
83%; Mp 174.3 – 174.7 °C; 1H NMR (600 MHz, CDCl3) δ
8.39 – 8.35 (m, 1H), 8.12 – 8.07 (m, 1H), 7.97 – 7.91 (m,
1H), 7.65 (td, J = 7.3, 1.2 Hz, 1H), 7.62 – 7.57 (m, 3H), 7.57
– 7.51 (m, 4H), 7.40 (t, J = 7.6 Hz, 1H), 7.32 (d, J = 7.6 Hz,
1H), 2.47 (s, 3H); 13C NMR (150 MHz, CDCl3) δ 162.5,
161.8, 142.3, 142.1, 141.8, 139.7, 138.4, 137.1, 135.4 (2C),
135.2, 131.4, 130.5, 130.2, 129.2, 129.1, 128.9, 128.4, 127.8,
125.5, 122.9, 122.7, 21.7; IR (thin film, cm-1) 2986, 2831,
1608, 1492, 1440, 1400, 1366, 1173, 1006, 799; HRMS
(ESI): m/z Calcd. for C23H17N2 [M+H]+ 321.1386, Found
321.1390.
11-(4-(Methylthio)phenyl)benzo[b]indeno[1,2-e][1,4]
diazepine (2j)
Purified by a flash column chromatography on silica gel
with petroleum ether/dichloromethane (1:1) as an eluent to
give the product 2j (197 mg) as a red solid with a yield of
56%; Mp 201.9 – 202.6 °C; 1H NMR (400 MHz, CDCl3) δ
8.36 (dq, J = 7.2, 0.9 Hz, 1H), 8.12 – 8.04 (m, 1H), 7.94 –
7.86 (m, 1H), 7.77 – 7.71 (m, 2H), 7.67 – 7.62 (m, 1H), 7.62
– 7.52 (m, 5H), 7.43 – 7.34 (m, 2H), 2.57 (s, 3H); 13C NMR
(100 MHz, CDCl3) δ 162.4, 160.7, 142.2, 141.8, 140.6,
139.5, 138.7, 136.7, 135.35, 135.32, 135.2, 131.4, 130.5,
129.1, 128.88, 128.86, 127.8, 126.2, 122.9, 122.7, 15.7; IR
(thin film, cm-1) 2921, 2852, 1590, 1545, 1463, 1366, 1331,
1185, 1088, 763; HRMS (ESI): m/z Calcd. for C23H17N2S
[M+H]+ 353.1107, Found 353.1108.
11-(3-Methoxyphenyl)benzo[b]indeno[1,2-e][1,4]
diazepine (2o)
Purified by a flash column chromatography on silica gel
with petroleum ether/dichloromethane (1:1) as an eluent to
give the product 2o (209 mg) as a red solid with a yield of
62%; Mp 160.5 – 160.8 °C; 1H NMR (600 MHz, CDCl3) δ
8.36 (d, J = 7.4 Hz, 1H), 8.10 (dd, J = 6.1, 3.3 Hz, 1H), 8.00
– 7.89 (m, 1H), 7.64 (t, J = 7.3 Hz, 1H), 7.62 – 7.54 (m, 5H),
7.43 (t, J = 7.9 Hz, 1H), 7.35 (d, J = 7.5 Hz, 1H), 7.31 (s,
1H), 7.05 (dd, J = 8.2, 2.4 Hz, 1H), 3.89 (s, 3H); 13C NMR
(150 MHz, CDCl3) δ 162.5, 161.2, 159.8, 143.4, 142.2,
141.8, 139.7, 137.1, 135.41, 135.35, 135.2, 131.4, 130.5,
129.6, 129.02, 128.99, 127.8, 122.9, 122.8, 120.8, 115.3,
114.0, 55.6; IR (thin film, cm-1) 3048, 2987, 2924, 2831,
1599, 1552, 1490, 1463, 1368, 1333, 1269, 1174, 1045,
1006, 764; HRMS (ESI): m/z Calcd. for C23H17N2O [M+H]+
337.1335, Found 337.1339.
11-(3-nitrophenyl)benzo[b]indeno[1,2-e][1,4]diazepine
(2k)
Purified by a flash column chromatography on silica gel
with petroleum ether/dichloromethane (1:1) as an eluent to
give the product 2k (249 mg) as a red solid with a yield of
71%; Mp 244.1 – 244.7 °C; 1H NMR (600 MHz, CDCl3) δ
8.66 (s, 1H), 8.43 – 8.33 (m, 2H), 8.18 – 8.08 (m, 2H), 7.94
– 7.88 (m, 1H), 7.71 (t, J = 7.9 Hz, 1H), 7.67 (t, J = 7.3 Hz,
1H), 7.65 – 7.55 (m, 4H), 7.48 (s, 1H); 13C NMR (150 MHz,
CDCl3) δ 162.3, 158.5, 148.5, 143.6, 141.8, 141.6, 139.5,
136.5, 135.5, 135.4, 135.2, 134.6, 131.7, 130.8, 129.72,
129.77, 128.3, 128.2, 124.2, 123.8, 123.03, 122.99; IR (thin
film, cm-1) 3423, 2923, 2853, 1627, 1522, 1466, 1436, 1346,
1099, 759; HRMS (ESI): m/z Calcd. for C22H14N3O2
[M+H]+ 352.1081, Found 352.1085.
11-(Benzo[d][1,3]dioxol-5-yl)benzo[b]indeno[1,2-e][1,4]
diazepine (2p)
Purified by a flash column chromatography on silica gel
with petroleum ether/dichloromethane (1:1) as an eluent to
7
This article is protected by copyright. All rights reserved.

10.1002/adsc.202000755
Advanced Synthesis & Catalysis
give the product 2p (168 mg) as a red solid with a yield of
48%; Mp 133.6 – 134.5 °C; 1H NMR (400 MHz, CDCl3) δ
8.37 – 8.32 (m, 1H), 8.11 – 8.04 (m, 1H), 7.92 – 7.86 (m,
1H), 7.66 – 7.61 (m, 2H), 7.61 – 7.57 (m, 2H), 7.57 – 7.51
(m, 2H), 7.37 – 7.29 (m, 2H), 6.94 (d, J = 7.9 Hz, 1H), 6.06
(s, 2H); 13C NMR (100 MHz, CDCl3) δ 162.4, 160.4, 148.8,
147.8, 142.0, 141.7, 139.5, 136.7, 136.2, 135.4, 135.23,
135.18, 131.3, 130.5, 128.84, 128.79, 127.7, 122.83, 122.75,
122.7, 109.4, 108.2, 101.5; IR (thin film, cm-1) 2923, 2853,
1604, 1462, 1384, 1259, 1236, 1103, 1038, 802; HRMS
(ESI): m/z Calcd. for C23H15N2O2 [M+H]+ 351.1128, Found
351.1130.
7.54 (m, 2H), 7.54 – 7.50 (m, 3H), 7.48 (s, 1H); 13C NMR
(150 MHz, CDCl3) δ 161.1, 161.0, 143.0, 142.1, 141.8,
139.4, 137.3, 135.5, 135.2, 135.0, 133.3, 130.7, 129.8, 129.5,
129.1, 128.5, 128.4, 127.6, 123.8, 122.6; IR (thin film, cm-
1) 2921, 2852, 1620, 1598, 1549, 1521, 1461, 1419, 1357,
1191, 1102, 1063, 761, 698; HRMS (ESI): m/z Calcd. for
C22H14ClN2 [M+H]+ 341.0840, Found 341.0841.
2-Methoxy-11-phenylbenzo[b]indeno[1,2-e][1,4]
diazepine (4c)
Purified by a flash column chromatography on silica gel
with petroleum ether/dichloromethane (1:1) as an eluent to
give the product 4c (249 mg) as a red solid with a yield of
74%; Mp 179.1 – 180.6 °C; 1H NMR (600 MHz, CDCl3) δ
8.28 (d, J = 8.3 Hz, 1H), 8.11 – 8.06 (m, 1H), 7.98 – 7.92
(m, 1H), 7.78 (dd, J = 7.7, 1.8 Hz, 2H), 7.58 – 7.54 (m, 2H),
7.54 – 7.49 (m, 3H), 7.48 (s, 1H), 7.10 (dd, J = 8.4, 2.3 Hz,
1H), 7.06 (d, J = 2.2 Hz, 1H), 3.91 (s, 3H); 13C NMR (150
MHz, CDCl3) δ 163.0, 161.5, 160.8, 143.9, 142.2, 142.1,
139.7, 136.1, 135.4, 134.9, 129.9, 129.8, 129.4, 128.9,
128.56, 128.55, 128.1, 124.3, 114.1, 107.5, 55.8; IR (thin
film, cm-1) 3049, 2986, 2956, 2923, 2831, 1603, 1492, 1439,
1400, 1364, 1232, 1173, 1156, 1006, 799, 770, 698; HRMS
(ESI): m/z Calcd. for C23H17N2O [M+H]+ 337.1335, Found
337.1132.
11-(Naphthalen-2-yl)benzo[b]indeno[1,2-e][1,4]
diazepine (2q)
Purified by a flash column chromatography on silica gel
with petroleum ether/dichloromethane (1:1) as an eluent to
give the product 2q (249 mg) as a red solid with a yield of
70%; Mp 186.9 – 188.0 °C; 1H NMR (400 MHz, CDCl3) δ
8.43 – 8.36 (m, 1H), 8.28 (s, 1H), 8.16 – 8.08 (m, 1H), 8.00
(d, J = 8.5 Hz, 1H), 8.00 – 7.90 (m, 3H), 7.89 (dd, J = 8.4,
1.7 Hz, 1H), 7.68 – 7.60 (m, 3H), 7.60 – 7.54 (m, 5H); 13
C
NMR (100 MHz, CDCl3) δ 162.6, 161.4, 142.3, 141.9,
139.7, 139.5, 137.1, 135.45, 135.41, 135.3, 134.0, 133.2,
131.4, 130.6, 129.2, 129.0, 128.7, 128.4, 127.94, 127.89,
127.8, 126.9, 126.6, 126.3, 122.9, 122.8; IR (thin film, cm-
1) 3046, 2922, 2852, 1599, 1463, 1383, 1331, 1183, 1101,
756; HRMS (ESI): m/z Calcd. for C26H17N2 [M+H]+
357.1386, Found 357.1383.
3-Fluoro-11-phenylbenzo[b]indeno[1,2-e][1,4]diazepine
(4d)
Purified by a flash column chromatography on silica gel
with petroleum ether/dichloromethane (1:1) as an eluent to
give the product 4d (240 mg) as a red solid with a yield of
74%; Mp 182.9 – 183.5 °C; 1H NMR (600 MHz, CDCl3) δ
8.06 (dd, J = 7.5, 2.0 Hz, 1H), 8.01 (dd, J = 8.1, 2.4 Hz, 1H),
7.91 (dd, J = 7.4, 2.0 Hz, 1H), 7.82 – 7.73 (m, 2H), 7.60 –
7.54 (m, 2H), 7.54 – 7.50 (m, 4H), 7.50 (s, 1H), 7.32 (td, J
= 8.9, 2.4 Hz, 1H); 13C NMR (150 MHz, CDCl3) δ 162.8 (d,
J = 248.8 Hz), 161.6 (d, J = 3.1 Hz), 161.4, 142.3, 141.9,
139.3, 137.61 (d, J = 2.0 Hz), 137.55, 135.9 (d, J = 2.0 Hz),
135.44, 135.38, 131.0, 129.60, 129.55 (d, J = 4.6 Hz), 129.0,
128.6, 128.4, 123.9 (d, J = 8.5 Hz), 118.4 (d, J = 23.9 Hz),
110.2 (d, J = 24.2 Hz); IR (thin film, cm-1) 2986, 2919, 2849,
11-(Thiophen-2-yl)benzo[b]indeno[1,2-e][1,4]diazepine
(2r)
Purified by a flash column chromatography on silica gel
with petroleum ether/dichloromethane (1:1) as an eluent to
give the product 2r (144 mg) as a red solid with a yield of
1
46%; Mp 133.1 – 133.7 °C; H NMR (600 MHz, CDCl3)
δ 8.35 (d, J = 7.4 Hz, 1H), 8.11 (s, 1H), 8.05 (dd, J = 7.6,
1.8 Hz, 1H), 7.88 (dd, J = 7.7, 1.7 Hz, 1H), 7.81 (d, J = 3.2
Hz, 1H), 7.66 (d, J = 4.1 Hz, 2H), 7.63 – 7.58 (m, 1H), 7.58
– 7.50 (m, 3H), 7.17 (dd, J = 5.1, 3.7 Hz, 1H); 13C NMR
(150 MHz, CDCl3) δ 162.2, 153.1, 146.4, 141.7, 141.4,
139.2, 135.3, 135.1, 134.9, 134.8, 131.2, 130.3, 129.1, 128.6, 1607, 1550, 1492, 1458, 1440, 1369, 1263, 1191, 1173,
128.1, 127.7, 127.3, 127.2, 122.7, 122.6; IR (thin film, cm-
1) 2922, 2852, 1602, 1463, 1421, 1384, 1327, 1117, 1101,
762, 704; HRMS (ESI): m/z Calcd. for C20H13N2S [M+H]+
313.0794, Found 313.0790.
1095, 1005, 770, 696; HRMS (ESI): m/z Calcd. for
C22H14FN2 [M+H]+ 325.1136, Found 335.1140.
3-Chloro-11-phenylbenzo[b]indeno[1,2-e][1,4]diazepine
(4e)
2-Fluoro-11-phenylbenzo[b]indeno[1,2-e][1,4]diazepine
(4a)
Purified by a flash column chromatography on silica gel
with petroleum ether/dichloromethane (1:1) as an eluent to
give the product 4e (249 mg) as a red solid with a yield of
73%; Mp 194.0 – 194.9 °C; 1H NMR (400 MHz, CDCl3) δ
8.30 (d, J = 1.9 Hz, 1H), 8.12 – 8.03 (m, 1H), 7.96 – 7.89
(m, 1H), 7.81 – 7.72 (m, 2H), 7.61 – 7.55 (m, 3H), 7.55 –
7.51 (m, 3H), 7.50 – 7.45 (m, 2H); 13C NMR (100 MHz,
CDCl3) δ 161.3 (2C), 142.3, 141.9, 139.9, 139.4, 136.8,
135.7, 135.5, 135.4, 133.8, 131.2, 131.0, 129.6, 129.4, 129.2,
128.6, 128.4, 123.6, 123.1; IR (thin film, cm-1) 2921, 2852,
1626, 1591, 1550, 1440, 1382, 1253, 1059, 1002, 763;
HRMS (ESI): m/z Calcd. for C22H14ClN2 [M+H]+ 341.0840,
Found 341.0840.
Purified by a flash column chromatography on silica gel
with petroleum ether/dichloromethane (1:1) as an eluent to
give the product 4a (243 mg) as a red solid with a yield of
1
75%; Mp 232.1 – 232.9 °C; H NMR (400 MHz, CDCl3)
δ 8.34 (dd, J = 8.1, 5.2 Hz, 1H), 8.14 – 8.06 (m, 1H), 8.00 –
7.92 (m, 1H), 7.80 – 7.74 (m, 2H), 7.62 – 7.57 (m, 2H), 7.56
– 7.51 (m, 3H), 7.50 (s, 1H), 7.30 – 7.26 (m, 1H), 7.25 –
7.23 (m, 1H); 13C NMR (100 MHz, CDCl3) δ 165.2 (d, J =
250.7 Hz), 161.0, 160.9, 143.8 (d, J = 9.9 Hz), 142.1, 141.9,
139.5, 135.6, 135.23, 135.2 (d, J = 3.0 Hz), 131.1 (d, J = 2.4
Hz), 130.6, 130.1, 129.6, 129.2, 128.7, 128.5, 124.6 (d, J =
9.7 Hz), 114.8 (d, J = 24.0 Hz), 109.6 (d, J = 23.9 Hz); IR
(thin film, cm-1) 3051, 3024, 2986, 2831, 1610, 1492, 1440,
1400, 1365, 1173, 1005, 799, 774, 700; HRMS (ESI): m/z
Calcd. for C22H14FN2 [M+H]+ 325.1136, Found 325.1135.
3-Methyl-11-phenylbenzo[b]indeno[1,2-e][1,4]diazepine
(4f)
Purified by a flash column chromatography on silica gel
with petroleum ether/dichloromethane (1:1) as an eluent to
give the product 4f (244 mg) as a red solid with a yield of
76%; Mp 153.7 – 155.5 °C; 1H NMR (400 MHz, CDCl3) δ
8.18 (s, 1H), 8.11 – 8.04 (m, 1H), 7.95 – 7.88 (m, 1H), 7.82
– 7.73 (m, 2H), 7.58 – 7.52 (m, 3H), 7.52 – 7.48 (m, 3H),
7.45 (s, 2H), 2.58 (s, 3H); 13C NMR (100 MHz, CDCl3) δ
162.7, 161.6, 142.4, 142.2, 139.6, 139.3, 138.3, 137.2, 135.7,
135.4, 135.1, 132.3, 130.4, 129.4, 128.8, 128.7, 128.6, 128.5,
123.4, 122.5, 22.1; IR (thin film, cm-1) 3046, 2986, 2920,
2-Chloro-11-phenylbenzo[b]indeno[1,2-e][1,4]diazepine
(4b)
Purified by a flash column chromatography on silica gel
with petroleum ether/dichloromethane (1:1) as an eluent to
give the product 4b (256 mg) as a red solid with a yield of
1
75%; Mp 221.5 – 222.5 °C; H NMR (600 MHz, CDCl3)
δ 8.28 (d, J = 8.5 Hz, 1H), 8.13 – 8.05 (m, 1H), 7.99 – 7.91
(m, 1H), 7.82 – 7.71 (m, 2H), 7.62 – 7.57 (m, 2H), 7.57 –
8
This article is protected by copyright. All rights reserved.

10.1002/adsc.202000755
Advanced Synthesis & Catalysis
2852, 1610, 1551, 1492, 1441, 1440, 1368, 1173, 1127,
1008, 865, 799, 760, 703; HRMS (ESI): m/z Calcd. for
C23H17N2 [M+H]+ 321.1386, Found 312.1390.
Purified by a flash column chromatography on silica gel
with petroleum ether/dichloromethane (1:1) as an eluent to
give the product 4k (284 mg) as a red solid with a yield of
80%; Mp 153.7 – 154.9 °C; 1H NMR (400 MHz, CDCl3) δ
8.29 (d, J = 1.9 Hz, 1H), 8.10 – 8.02 (m, 1H), 7.97 – 7.90
(m, 1H), 7.61 – 7.51 (m, 5H), 7.51 – 7.45 (m, 2H), 7.40 (t, J
= 7.6 Hz, 1H), 7.32 (d, J = 7.6 Hz, 1H), 2.47 (s, 3H); 13C
NMR (100 MHz, CDCl3) δ 161.5, 161.2, 142.3, 141.8,
139.8, 139.4, 138.4, 136.7, 135.6, 135.43, 135.35, 133.7,
131.1, 130.9, 130.3, 129.4, 129.02, 129.01, 128.4, 125.4,
123.5, 123.0, 21.7; IR (thin film, cm-1) 2922, 2852, 1603,
1550, 1511, 1440, 1383, 1361, 1320, 1253, 1059, 773;
HRMS (ESI): m/z Calcd. for C23H16ClN2 [M+H]+ 355.0997,
Found 355.0993.
3-Methoxy-11-phenylbenzo[b]indeno[1,2-e][1,4]
diazepine (4g)
Purified by a flash column chromatography on silica gel
with petroleum ether/dichloromethane (1:1) as an eluent to
give the product 4g (246 mg) as a dark green solid with a
1
yield of 73%; Mp 174.6 – 174.8 °C; H NMR (600 MHz,
CDCl3) δ 8.06 (dd, J = 7.5, 2.0 Hz, 1H), 7.93 – 7.86 (m, 2H),
7.76 (dd, J = 7.7, 1.7 Hz, 2H), 7.57 – 7.51 (m, 3H), 7.51 –
7.45 (m, 4H), 7.20 (dd, J = 8.2, 2.4 Hz, 1H), 4.01 (s, 3H);
13C NMR (150 MHz, CDCl3) δ 162.7, 161.7, 160.4, 142.6,
142.2, 139.4, 137.5, 137.2, 135.3, 135.2, 134.9, 130.6, 129.4,
128.65, 128.57, 128.4, 128.2, 123.8, 118.8, 107.0, 56.0; IR
(thin film, cm-1) 3051, 3024, 2986, 2831, 1610, 1492, 1440,
1400, 1365, 1173, 1005, 799, 774; HRMS (ESI): m/z Calcd.
for C23H17N2O [M+H]+ 337.1335, Found 337.1333.
11-Phenyl-[1,3]dioxolo[4',5':5,6]indeno[1,2-e]benzo[b]
[1,4]diazepine (4l)
Purified by a flash column chromatography on silica gel
with petroleum ether/dichloromethane (1:1) as an eluent to
give the product 4l (235 mg) as a red solid with a yield of
67%; Mp 259.0 – 261.0 °C; 1H NMR (400 MHz, CDCl3) δ
8.14 – 8.06 (m, 1H), 8.02 – 7.91 (m, 1H), 7.83 (s, 1H), 7.80
– 7.73 (m, 2H), 7.61 – 7.54 (m, 2H), 7.54 – 7.49 (m, 3H),
7.47 (s, 1H), 7.02 (s, 1H), 6.13 (s, 2H); 13C NMR (150 MHz,
CDCl3) δ 161.1, 160.7, 151.2, 148.3, 142.4, 142.3, 139.3,
137.9, 135.7, 135.3, 135.2, 130.3, 130.2, 129.4, 128.6, 128.6,
128.5, 127.9, 103.6, 102.9, 102.2; IR (thin film, cm-1) 2923,
2852, 1550, 1521, 1466, 1440, 1381, 1320, 1233, 1140,
1036, 767; HRMS (ESI): m/z Calcd. for C23H15N2O2
[M+H]+ 351.1128, Found 351.1125.
11-(3-Chlorophenyl)-3-methylbenzo[b]indeno[1,2-
e][1,4]diazepine (4h)
Purified by a flash column chromatography on silica gel
with petroleum ether/dichloromethane (1:1) as an eluent to
give the product 4h (266 mg) as a red solid with a yield of
75%; Mp 159.8 – 160.3 °C; 1H NMR (400 MHz, CDCl3) δ
8.17 (d, J = 0.7 Hz, 1H), 8.10 – 8.03 (m, 1H), 7.93 – 7.84
(m, 1H), 7.76 (t, J = 1.7 Hz, 1H), 7.64 (dt, J = 7.1, 1.6 Hz,
1H), 7.59 – 7.52 (m, 2H), 7.51 – 7.42 (m, 5H), 2.58 (s, 3H);
13C NMR (100 MHz, CDCl3) δ 162.6, 159.9, 143.8, 142.1,
139.6, 139.2, 138.5, 137.0, 135.6, 135.4, 135.2, 134.6, 132.4,
130.5, 129.8, 129.5, 129.1, 128.7, 128.2, 126.6, 123.4, 122.6,
22.1; IR (thin film, cm-1) 3063, 2986, 2919, 2851, 2831,
1610, 1492, 1363, 1322, 1173, 1079, 1006, 893, 873, 775,
761, 701; HRMS (ESI): m/z Calcd. for C23H16ClN2 [M+H]+
335.0997, Found 335.0995.
2,3-Dimethoxy-11-phenylbenzo[b]indeno[1,2-e][1,4]
diazepine (4m)
Purified by a flash column chromatography on silica gel
with petroleum ether/dichloromethane (1:1) as an eluent to
give the product 4m (213 mg) as a brown solid with a yield
of 58%; Mp 174.6 – 175.7 °C; 1H NMR (600 MHz, CDCl3)
δ 8.16 – 8.07 (m, 1H), 7.98 – 7.93 (m, 1H), 7.90 (s, 1H),
7.80 – 7.75 (m, 2H), 7.59 – 7.54 (m, 2H), 7.54 – 7.47 (m,
4H), 7.07 (s, 1H), 4.10 (s, 3H), 3.98 (s, 3H); 13C NMR (150
MHz, CDCl3) δ 161.6, 160.7, 152.7, 149.7, 142.4, 139.2,
136.12, 136.09, 135.3, 134.9, 130.1, 129.3, 128.6 (3C),
128.5, 128.4, 128.3, 127.7, 105.4, 105.0, 56.5, 56.4; IR (thin
film, cm-1) 2922, 2851, 1584, 1518, 1471, 1320, 1238, 1213,
1156, 1116, 762; HRMS (ESI): m/z Calcd. for C24H19N2O2
[M+H]+ 367.1441, Found 367.1445.
3-Chloro-11-(3-chlorophenyl)benzo[b]indeno[1,2-
e][1,4]diazepine (4i)
Purified by a flash column chromatography on silica gel
with petroleum ether/dichloromethane (1:1) as an eluent to
give the product 4i (255 mg) as a red solid with a yield of
68%; Mp 178.6 – 180.2 °C; 1H NMR (600 MHz, CDCl3) δ
8.28 (d, J = 1.9 Hz, 1H), 8.14 – 8.01 (m, 1H), 7.98 – 7.83
(m, 1H), 7.75 (t, J = 1.9 Hz, 1H), 7.63 (dt, J = 7.4, 1.5 Hz,
1H), 7.61 – 7.55 (m, 3H), 7.51 – 7.47 (m, 2H), 7.47 – 7.43
(m, 2H); 13C NMR (150 MHz, CDCl3) δ 161.2, 159.6, 143.5,
142.0, 139.7, 139.4, 136.7, 135.53, 135.48, 134.7, 134.0,
131.3, 131.1, 129.9, 129.7, 129.5, 128.9, 128.7, 126.6, 123.7,
123.1; IR (thin film, cm-1) 2922, 2852, 1551, 1511, 1440,
7,8-Dimethyl-11-phenylbenzo[b]indeno[1,2-e][1,4]
diazepine (5a)
Purified by a flash column chromatography on silica gel
1418, 1360, 1320, 1253, 1060, 768; HRMS (ESI): m/z Calcd. with petroleum ether/dichloromethane (1:1) as an eluent to
for C22H13Cl2N2 [M+H]+ 375.0450, Found 375.0449.
give the product 5a (278 mg) as a brown solid with a yield
of 83%; Mp 158.0 – 159.6 °C; 1H NMR (600 MHz, CDCl3)
δ 8.35 (d, J = 7.3 Hz, 1H), 7.88 (s, 1H), 7.78 – 7.73 (m, 2H),
7.73 (s, 1H), 7.62 (td, J = 7.3, 1.2 Hz, 1H), 7.60 – 7.54 (m,
2H), 7.55 – 7.46 (m, 4H), 2.44 (s, 3H), 2.40 (s, 3H); 13C
NMR (150 MHz, CDCl3) δ 161.6, 160.7, 142.4, 141.7,
140.2, 140.1, 138.2, 137.6, 136.2, 135.9, 135.8, 135.4, 131.1,
129.3, 129.1, 128.6, 128.5, 127.4, 122.7, 122.5, 19.6, 19.4;
IR (thin film, cm-1) 2920, 2852, 1604, 1547, 1522, 1463,
1442, 1383, 1367, 1307, 1261, 1100, 1027; HRMS (ESI):
m/z Calcd. for C24H19N2 [M+H]+ 335.1543, Found 335.1543.
3-Methyl-11-(m-tolyl)benzo[b]indeno[1,2-e][1,4]
diazepine (4j)
Purified by a flash column chromatography on silica gel
with petroleum ether/dichloromethane (1:1) as an eluent to
give the product 4j (237 mg) as a red solid with a yield of
71%; Mp 148.2 – 149.3 °C; 1H NMR (600 MHz, CDCl3) δ
8.17 (s, 1H), 8.09 – 8.05 (m, 1H), 7.94 – 7.89 (m, 1H), 7.57
(s, 1H), 7.56 – 7.52 (m, 3H), 7.51 (s, 1H), 7.48 – 7.43 (m,
2H), 7.40 (t, J = 7.6 Hz, 1H), 7.31 (d, J = 7.6 Hz, 1H), 2.58
(s, 3H), 2.47 (s, 3H); 13C NMR (150 MHz, CDCl3) δ 162.7,
161.9, 142.4, 142.1, 139.7, 139.3, 138.4, 138.3, 137.3, 135.7,
135.4, 135.2, 132.3, 130.4, 130.2, 129.1, 128.78, 128.77,
128.4, 125.5, 123.4, 122.5, 22.1, 21.7.; IR (thin film, cm-1)
2986, 2919, 2852, 2831, 1588, 1489, 1438, 1396, 1357,
1171, 1107, 1006, 876, 797, 774, 761; HRMS (ESI): m/z
Calcd. for C24H19N2 [M+H]+ 335.1543, Found 335.1547.
7,8-Difluoro-11-phenylbenzo[b]indeno[1,2-e][1,4]
diazepine (5b)
Purified by a flash column chromatography on silica gel
with petroleum ether/dichloromethane (1:1) as an eluent to
give the product 5b (246 mg) as a brown solid with a yield
of 72%; Mp 201.9 – 202.5 °C; 1H NMR (600 MHz, CDCl3)
δ 8.33 (d, J = 7.4 Hz, 1H), 7.86 (dd, J = 11.3, 8.6 Hz, 1H),
7.78 – 7.73 (m, 2H), 7.72 – 7.65 (m, 2H), 7.64 – 7.57 (m,
3H), 7.56 – 7.49 (m, 3H); 13C NMR (150 MHz, CDCl3) δ
162.9 (d, J = 3.3 Hz), 162.0 (d, J = 2.8 Hz), 150.8 (dd, J =
3-Chloro-11-(m-tolyl)benzo[b]indeno[1,2-e][1,4]
diazepine (4k)
9
This article is protected by copyright. All rights reserved.

10.1002/adsc.202000755
Advanced Synthesis & Catalysis
150.9, 13.7 Hz), 149.1 (dd, J = 149.2, 13.7 Hz), 141.8, 141.6, Ph3PAuCl (0.05 mmol, 25 mg) and AgSbF6 (0.05 mmol, 17
139.9 (dd, J = 9.2, 3.1 Hz), 137.7, 136.8 (dd, J = 8.5, 3.0
Hz), 135.1, 131.8, 129.8, 128.8, 128.7, 128.4, 128.1, 123.05,
122.96, 122.7 (d, J = 17.9 Hz), 122.4 (d, J = 17.5 Hz); IR
(thin film, cm-1) 2922, 2852, 1594, 1564, 1484, 1463, 1381,
1308, 1254, 1192, 889; HRMS (ESI): m/z Calcd. for
C22H13F2N2 [M+H]+ 343.1041, Found 343.1044.
mg) were added in toluene (5 mL) and the mixture was
stirred at room temperature for 10 min. Substrate 7 (1.0
mmol, 280 mg) was then added to the solution and the
mixture was stirred at room temperature for 10 min before
o-phenylenediamine (3.0 mmol, 324 mg) was added. The
resulting solution was stirred at 70 °C for 3.5 h till TLC
showed the consumption of 7. The solvent was removed in
vacuo and the residue was purified by a flash column
chromatography (dichloromethane/petroleum ether) on
silica gel to afford product 2 (276 mg) in 90% yield.
7,8-Dichloro-11-phenylbenzo[b]indeno[1,2-e][1,4]
diazepine (5c)
Purified by a flash column chromatography on silica gel
with petroleum ether/dichloromethane (1:1) as an eluent to
give the product 5c (248 mg) as a brown solid with a yield
of 66%; Mp 236.9 – 238.6 °C; 1H NMR (600 MHz, CDCl3)
δ 8.31 (d, J = 7.4 Hz, 1H), 8.15 (s, 1H), 8.00 (s, 1H), 7.78 –
7.72 (m, 2H), 7.67 (td, J = 7.4, 1.2 Hz, 1H), 7.64 – 7.57 (m,
3H), 7.56 – 7.49 (m, 3H); 13C NMR (150 MHz, CDCl3) δ
163.6, 162.7, 141.8, 141.58, 141.57, 138.9, 138.8, 136.1,
135.7, 135.2, 133.6, 132.0, 131.8, 129.9, 128.8, 128.7,
128.45, 128.36, 123.14, 123.10; IR (thin film, cm-1) 2922,
2853, 1626, 1581, 1545, 1460, 1383, 1327, 1256, 1100;
HRMS (ESI): m/z Calcd. for C22H13Cl2N2 [M+H]+ 375.0450,
Found 375.0452.
4.2 Conditions in the Absence of Catalysts
Substrate 7 (1.0 mmol, 280 mg) and o-phenylenediamine
(3.0 mmol, 324 mg) were dissolved in toluene (5 mL) and
the mixture was stirred at 70 °C for 3.5 h till TLC showed
the consumption of 7. The solvent was removed in vacuo
and the residue was purified by a flash column
chromatography (dichloromethane/petroleum ether) on
silica gel to afford product 2 (273 mg) in 89% yield.
5. Procedures for the Preparation of (1-Methoxy-1-
(phenylamino)-1H-inden-2-yl)(phenyl)methanone
(8)
from Intermediate 7 and Characterization Data
7,8-Dibromo-11-phenylbenzo[b]indeno[1,2-e][1,4]
diazepine (5d)
Substrate 7 (1.0 mmol, 280 mg) and aniline (3.0 mmol, 279
mg) were dissolved in toluene (5 mL) and the mixture was
stirred at 70 °C for 3.5 h till TLC showed the consumption
of 7. The solvent was removed in vacuo and the residue was
purified by a flash column chromatography on silica gel
with petroleum ether/ethyl acetate (3:1) as an eluent to give
the product 8 (256 mg) as a yellow solid with a yield of 75%;
Mp 73.5 – 74.2 °C; 1H NMR (400 MHz, CDCl3) δ 12.42 (s,
1H), 7.98 – 7.88 (m, 2H), 7.53 (d, J = 7.4 Hz, 1H), 7.52 –
7.40 (m, 5H), 7.42 – 7.33 (m, 4H), 7.10 (td, J = 7.7, 1.2 Hz,
1H), 6.77 (d, J = 7.9 Hz, 1H), 5.79 (s, 1H), 2.87 (s, 3H); 13C
Purified by a flash column chromatography on silica gel
with petroleum ether/dichloromethane (1:1) as an eluent to
give the product 5d (251 mg) as a brown solid with a yield
of 54%; Mp 197.8 – 198.8 °C; 1H NMR (600 MHz, CDCl3)
δ 8.33 – 8.29 (m, 2H), 8.17 (s, 1H), 7.77 – 7.73 (m, 2H),
7.67 (td, J = 7.4, 1.2 Hz, 1H), 7.64 – 7.61 (m, 2H), 7.61 –
7.58 (m, 1H), 7.55– 7.50 (m, 3H); 13C NMR (150 MHz,
CDCl3) δ 163.8, 162.9, 142.0, 141.8, 141.6, 139.4, 139.3,
138.9, 138.8, 135.3, 132.0, 129.9, 128.9, 128.7, 128.43,
128.41, 126.0, 124.0, 123.2, 123.1; IR (thin film, cm-1) 2958, NMR (150 MHz, DMSO-d6) δ 191.6, 161.6, 146.5, 141.7,
2919, 2853, 1599, 1459, 1372, 1325, 1261, 1096, 1029, 802;
138.8, 135.5, 130.9, 130.2, 129.4, 128.3, 128.2, 127.5, 127.2,
HRMS (ESI): m/z Calcd. for C22H13Br2N2 [M+H]+ 462.9440, 126.4, 124.9, 124.8, 108.7, 79.5, 50.5; IR (thin film, cm-1)
Found 462.9441.
3448, 1611, 1595, 1543, 1533, 1452, 1437, 1383, 1304,
1263, 1204, 1066, 746; HRMS (ESI): m/z Calcd. For
C23H19NO2Na [M+Na]+ 364.1308, Found 364.1310.
3. Procedures for the Preparation of Intermediate 7 and
Characterization Data
Ph3PAuCl (0.05 mmol, 25 mg) and AgSbF6 (0.05 mmol, 17
mg) were added in toluene (5 mL) and the mixture was
stirred at room temperature for 10 min. Substrate 1 (1.0
mmol, 280 mg) was then added to the above solution and
mixture was stirred at room temperature for 30 min till TLC
showed the consumption of the starting material. The
solvent was removed in vacuo and the residue was purified
by a flash column chromatography (EtOAc/petroleum
ether) on silica gel to afford the intermediate 7.
Acknowledgements
This project is supported by the Natural Science Foundation of
China (Grants 21977073), Liaoning Revitalization Talents
Program and Liaoning BaiQianWan Talents Program. The
authors acknowledge the program for the innovative research
team of the Ministry of Education and the program for the
Liaoning innovative research team in university and the Career
Development Support Plan for Young and Middle-aged Teachers
in Shenyang Pharmaceutical University.
(1,3-Dimethoxy-1H-inden-2-yl)(phenyl)methanone (7)
Purified by a flash column chromatography on silica gel
with petroleum ether/ethyl acetate (10:1) as an eluent to give
the product 7 (255 mg) as a yellow solid with a yield of 91%;
References
1
Mp 87.8 – 88.5 °C; H NMR (600 MHz, CDCl3) δ 7.96 –
[1] a) G. A. Archer, L. H. Sternbach, Chem. Rev. 1968, 68,
747-784; b) L. H. Sternbach, Prog. Drug. Res. 1978, 22,
229-266; c) L. Pieri, R. Schaffner, R. Scherschlicht, P.
Polc, J. Sepinwall, A. Davidson, H. Mohler, R. Cumin,
M. Da Prada, W. P. Burkard, H. H. Keller, R. K. Muller,
M. Gerold, M. Pieri, L. Cook, W. Haefely, Arzneimittel-
Forsch. 1981, 31, 2180-2201; d) J. Lee, D. Gauthier, R.
A. Rivero, J. Org. Chem. 1999, 64, 3060-3065; e) I.
Cepanec, M. Litvić, I. Pogorelić, Org. Proc. Res. Dev.
2006, 10, 1192-1198; f) J. B. Bariwal, K. D. Upadhyay,
A. T. Manvar, J. C. Trivedi, J. S. Singh, K. S. Jain, A. K.
Shah, Eur. J. Med. Chem. 2008, 43, 2279-2290.
7.91 (m, 2H), 7.59 – 7.55 (m, 1H), 7.53 – 7.49 (m, 2H), 7.49
– 7.45 (m, 2H), 7.43 – 7.37 (m, 2H), 5.67 (s, 1H), 3.85 (s,
3H), 3.08 (s, 3H); 13C NMR (150 MHz, DMSO-d6) δ 194.0,
162.8, 141.7, 140.1, 138.5, 132.9, 129.25, 129.16 (3C),
128.7, 124.3, 120.8, 116.5, 83.1, 61.3, 52.9; IR (thin film,
cm-1) 1639, 1599, 1576, 1447, 1367, 1332, 1248, 1204,
1069; HRMS (ESI): m/z Calcd. For C18H16O3Na [M+Na]+
303.0992, Found 303.0996.
4. Procedures for the Preparation of Product 2 from
Intermediate 7
4.1 Standard Conditions
10
This article is protected by copyright. All rights reserved.

10.1002/adsc.202000755
Advanced Synthesis & Catalysis
[2] a) S. L. Schreiber, Science 2000, 287, 1964-1969; b) M.
D. Burke, S. L. Schreiber, Angew. Chem. Int. Ed. 2004,
43, 46-58; c) T. E. Nielsen, S. L. Schreiber, Angew.
Chem. Int. Ed. 2008, 47, 48-56; d) W. R. Galloway, A.
Isidro-Llobet, D. R. Spring, Nat. Commun. 2010, 1, 80;
e) C. J. Gerry, S. L. Schreiber, Nat. Rev. Drug. Discov.
2018, 17, 333-352.
Dembinski, Green Chem. 2014, 16, 1120-1124; i) M. K.
Hussain, M. I. Ansari, R. Kant, K. Hajela, Org. Lett.
2014, 16, 560-563; j) S. Cacchi, G. Fabrizi, A.
Goggiamani, A. Iazzetti, Org. Lett. 2016, 18, 3511-
3513; k) P. S. Fier, A. M. Whittaker, Org. Lett. 2017, 19,
1454-1457; l) A. Bosmani, A. Guarnieri-Ibanez, S.
Goudedranche, C. Besnard, J. Lacour, Angew. Chem. Int.
Ed. 2018, 57, 7151-7155; m) N. Martinez-Yanez, J.
Suarez, A. Cajaraville, J. A. Varela, C. Saa, Org. Lett.
2019, 21, 1779-1783.
[3] a) T. R. Browne, Arch. Neurol. 1976, 33, 326-332; b) W.
B. Wright, Jr., H. J. Brabander, E. N. Greenblatt, I. P.
Day, R. A. Hardy, Jr., J. Med. Chem. 1978, 21, 1087-
1089; c) G. B. Cassano, L. Conti, Br. J. Clin. Pharmacol.
1981, 11 Suppl 1, 23S-29S; d) J. G. Reves, R. J. Fragen,
H. R. Vinik, D. J. Greenblatt, Anesthesiology 1985, 62,
310-324; e) R. M. McKernan, T. W. Rosahl, D. S.
Reynolds, C. Sur, K. A. Wafford, J. R. Atack, S. Farrar,
J. Myers, G. Cook, P. Ferris, L. Garrett, L. Bristow, G.
Marshall, A. Macaulay, N. Brown, O. Howell, K. W.
Moore, R. W. Carling, L. J. Street, J. L. Castro, C. I.
Ragan, G. R. Dawson, P. J. Whiting, Nat. Neurosci.
2000, 3, 587-592; f) B. Narayana, K. K. Vijaya Raj, B.
V. Ashalatha, N. S. Kumari, Eur. J. Med. Chem. 2006,
41, 417-422.
[10] a) D. P. Day, P. W. H. Chan, Adv. Synth. Catal. 2016,
358, 1368-1384; b) Y. M. Wang, A. D. Lackner, F. D.
Toste, Acc. Chem. Res. 2014, 47, 889-901; c) H. S.
Yeom, S. Shin, Acc. Chem. Res. 2014, 47, 966-977; d)
B. Alcaide, P. Almendros, Acc. Chem. Res. 2014, 47,
939-952; e) L. Fensterbank, M. Malacria, Acc Chem Res
2014, 47, 953-965; f) A. S. Hashmi, Acc. Chem. Res.
2014, 47, 864-876; g) L. Zhang, Acc. Chem. Res. 2014,
47, 877-888; h) C. Obradors, A. M. Echavarren, Acc.
Chem. Res. 2014, 47, 902-912; i) D. H. Zhang, X. Y.
Tang, M. Shi, Acc. Chem. Res. 2014, 47, 913-924; j) A.
Furstner, Acc. Chem. Res. 2014, 47, 925-938; k) D.
Pflasterer, A. S. Hashmi, Chem. Soc. Rev. 2016, 45,
1331-1367; l) A. M. Asiri, A. S. Hashmi, Chem. Soc. Rev.
2016, 45, 4471-4503; m) W. Zi, F. Dean Toste, Chem.
Soc. Rev. 2016, 45, 4567-4589; n) Z. Zheng, Z. Wang,
Y. Wang, L. Zhang, Chem. Soc. Rev. 2016, 45, 4448-
4458; o) R. J. Harris, R. A. Widenhoefer, Chem. Soc.
Rev. 2016, 45, 4533-4551.
[4] L. D. Fader, R. Bethell, P. Bonneau, M. Bos, Y.
Bousquet, M. G. Cordingley, R. Coulombe, P. Deroy, A.
M. Faucher, A. Gagnon, N. Goudreau, C. Grand-Maitre,
I. Guse, O. Hucke, S. H. Kawai, J. E. Lacoste, S. Landry,
C. T. Lemke, E. Malenfant, S. Mason, S. Morin, J.
O'Meara, B. Simoneau, S. Titolo, C. Yoakim, Bioorg.
Med. Chem. Lett. 2011, 21, 398-404.
[11] a) Y. Liu, S. Jin, Y. Wang, S. Cui, X. Peng, Y. Niu, C.
Du, M. Cheng, Chem. Commun. 2016, 52, 6233-6236;
b) C. Jiang, Z. Xiong, S. Jin, P. Gao, Y. Tang, Y. Wang,
C. Du, X. Wang, Y. Liu, B. Lin, Y. Liu, M. Cheng, Chem.
Commun. 2016, 52, 11516-11519; c) X. Peng, L. Zhu, Y.
Hou, Y. Pang, Y. Li, J. Fu, L. Yang, B. Lin, Y. Liu, M.
Cheng, Org. Lett. 2017, 19, 3402-3405; d) Z. Xiong, X.
Zhang, Y. Li, X. Peng, J. Fu, J. Guo, F. Xie, C. Jiang, B.
Lin, Y. Liu, M. Cheng, Org. Biomol. Chem. 2018, 16,
7361-7374.
[5] a) A. Kamal, V. Devaiah, K. L. Reddy, M. S. Kumar,
Bioorg. Med. Chem. 2005, 13, 2021-2029; b) T. B.
Sundberg, G. M. Ney, C. Subramanian, A. W. Opipari,
Jr., G. D. Glick, Cancer Res. 2006, 66, 1775-1782; c) J.
Dourlat, W. Q. Liu, N. Gresh, C. Garbay, Bioorg. Med.
Chem. Lett. 2007, 17, 2527-2530; d) L. P. Tardibono, M.
J. Miller, Org. Lett. 2009, 11, 1575-1578.
[6] G. Grossi, European J. Med. Chem. 2002, 37, 933-944.
[7] C. G. Neochoritis, C. A. Tsoleridis, J. Stephanidou-
Stephanatou, C. A. Kontogiorgis, D. J. Hadjipavlou-
Litina, J. Med. Chem. 2010, 53, 8409-8420.
[12] a) L. Sun, Y. Zhu, P. Lu, Y. Wang, Org. Lett. 2013, 15,
5894-5897; b) S. K. Pawar, C. D. Wang, S. Bhunia, A.
M. Jadhav, R. S. Liu, Angew. Chem. Int. Ed. 2013, 52,
7559-7563; c) H. Shen, J. Fu, J. Gong, Z. Yang, Org.
Lett. 2014, 16, 5588-5591; d) E. S. Gutman, V.
Arredondo, D. L. Van Vranken, Org. Lett. 2014, 16,
5498-5501; e) X. J. Xu, H. S. Kim, W. M. Chen, X. Ma,
G. J. Correy, M. G. Banwell, C. J. Jackson, A. C. Willis,
P. D. Carr, Eur. J. Org. Chem. 2017, 2017, 4044-4053;
f) Y. Li, J. Yu, Y. Bi, G. Yan, D. Huang, Adv. Synth.
Catal. 2019, 361, 4839-4881; g) Z. Y. Wang, K. K.
Wang, R. X. Chen, H. Liu, K. J. Chen, Eur. J. Org. Chem.
2020, 2020, 2456-2474.
[8] L. Nallan, K. D. Bauer, P. Bendale, K. Rivas, K.
Yokoyama, C. P. Horney, P. R. Pendyala, D. Floyd, L.
J. Lombardo, D. K. Williams, A. Hamilton, S. Sebti, W.
T. Windsor, P. C. Weber, F. S. Buckner, D. Chakrabarti,
M. H. Gelb, W. C. Van Voorhis, J. Med. Chem. 2005,
48, 3704-3713.
[9]a) A. Shaabani, A. H. Rezayan, S. Keshipour, A. Sarvary,
S. W. Ng, Org. Lett. 2009, 11, 3342-3345; b) R. S.
Borisov, A. I. Polyakov, L. A. Medvedeva, V. N.
Khrustalev, N. I. Guranova, L. G. Voskressensky, Org.
Lett. 2010, 12, 3894-3897; c) J. R. Donald, S. F. Martin,
Org. Lett. 2011, 13, 852-855; d) K. G. Guggenheim, H.
Toru, M. J. Kurth, Org. Lett. 2012, 14, 3732-3735; e) B.
Jiang, Q. Y. Li, H. Zhang, S. J. Tu, S. Pindi, G. Li, Org.
Lett. 2012, 14, 700-703; f) J. Qian, Y. Liu, J. Cui, Z. Xu,
J. Org. Chem. 2012, 77, 4484-4490; g) Y. Huang, K.
Khoury, T. Chanas, A. Domling, Org. Lett. 2012, 14,
5916-5919; h) A. Solan, B. Nişanci, M. Belcher, J.
Young, C. Schäfer, K. A. Wheeler, B. Török, R.
[13] a) P. Dube, F. D. Toste, J. Am. Chem. Soc. 2006, 128,
12062-12063; b) H. J. Bae, B. Baskar, S. E. An, J. Y.
Cheong, D. T. Thangadurai, I. C. Hwang, Y. H. Rhee,
Angew. Chem. Int. Ed. 2008, 47, 2263-2266; c) H. Kim,
Y. H. Rhee, J. Am. Chem. Soc. 2012, 134, 4011-4014; d)
W. Zi, F. D. Toste, J. Am. Chem. Soc. 2013, 135, 12600-
12603; e) M. C. Blanco Jaimes, V. Weingand, F.
Rominger, A. S. Hashmi, Chem. Eur. J. 2013, 19,
11
This article is protected by copyright. All rights reserved.

10.1002/adsc.202000755
Advanced Synthesis & Catalysis
12504-12511; f) M. Ackermann, J. Bucher, M. Rappold,
i) H. Wu, W. Zi, G. Li, H. Lu, F. D. Toste, Angew. Chem.
Int. Ed. 2015, 54, 8529-8532.
K. Graf, F. Rominger, A. S. Hashmi, Chem. Asian. J.
2013, 8, 1786-1794; g) A. S. K. Hashmi, K. Graf, M.
Ackermann, F. Rominger, ChemCatChem 2013, 5,
1200-1204; h) H. V. Adcock, E. Chatzopoulou, P. W.
Davies, Angew. Chem. Int. Ed. 2015, 54, 15525-15529;
[14] A. S. Hashmi, Angew. Chem. Int. Ed. 2010, 49, 5232-
5241
12
This article is protected by copyright. All rights reserved.

10.1002/adsc.202000755
Advanced Synthesis & Catalysis
FULL PAPER
A Gold(I)-Catalyzed Tandem Cyclization to
Benzo[b]indeno [1,2-e][1,4]diazepines from o-
Phenylenediamines and Ynones
Adv. Synth. Catal. Year, Volume, Page – Page
Fukai Xie, Bo Zhang, Yanyu Chen, Hongwei Jia,
Lei Sun, Kaitong Zhuang, Lili Yin, Maosheng
Cheng, Bin Lin, and Yongxiang Liu*
13
This article is protected by copyright. All rights reserved.