Synthesis of phenanthridines by I2-mediated sp3C-H amination

Article abstract of DOI:10.1039/d0ob00433b

An I₂-mediated synthesis of phenanthridinesviaintramolecular sp³C-H amination of readily accessible aniline precursors is reported. The present synthetic process is straightforward and applicable to a broad variety of unprotected ani

Full text of DOI:10.1039/d0ob00433b

View Article Online
View Journal
Organic &
Biomolecular
Chemistry
Accepted Manuscript
This article can be cited before page numbers have been issued, to do this please use: B. Fang, J. Hou, J.
Tian, W. Yu and J. Chang, Org. Biomol. Chem., 2020, DOI: 10.1039/D0OB00433B.
Volume 15
Number 47
21 December 2017
Pages 9945-10124
This is an Accepted Manuscript, which has been through the
Royal Society of Chemistry peer review process and has been
accepted for publication.
Organic &
Biomolecular
Chemistry
Accepted Manuscripts are published online shortly after acceptance,
rsc.li/obc
before technical editing, formatting and proof reading. Using this free
service, authors can make their results available to the community, in
citable form, before we publish the edited article. We will replace this
Accepted Manuscript with the edited and formatted Advance Article as
soon as it is available.
You can find more information about Accepted Manuscripts in the
Information for Authors.
Please note that technical editing may introduce minor changes to the
text and/or graphics, which may alter content. The journal’s standard
Terms & Conditions and the Ethical guidelines still apply. In no event
ISSN 1477-0520
PAPER
I . J. Dmochowski et al.
Oligonucleotide modifi cations enhance probe stability for
shall the Royal Society of Chemistry be held responsible for any errors
single cell transcriptome in vivo analysis (TIVA)
or omissions in this Accepted Manuscript or any consequences arising
from the use of any information it contains.
rsc.li/obc

Page 1 of 36
Organic & Biomolecular Chemistry
View Article Online
DOI: 10.1039/D0OB00433B
3
Synthesis of Phenanthridines by I2-Mediated sp C−H
Amination
Benyao Fang, Jiao Hou, Jinyue Tian, Wenquan Yu,* and Junbiao Chang*
College of Chemistry, Zhengzhou University, Zhengzhou, Henan Province 450001, China.
Abstract: An I2-mediated synthesis of phenanthridines via intramolecular sp3 C−H
amination of readily accessible aniline precursors is reported. The present synthetic
process is straightforward and applicable to a broad variety of unprotected aniline
substrates, and provides facile and efficient access to phenanthridine derivatives. This
C–H amination protocol does not use transition metals, is operationally simple, and
can be achieved on a gram scale.

Organic & Biomolecular Chemistry
Page 2 of 36
View Article Online
DOI: 10.1039/D0OB00433B
. Introduction
Phenanthridine is a privileged scaffold widely distributed in natural products1 and
synthetic compounds with diverse pharmacologically important properties,2 including
anticancer,3 antibacterial,4 antituberculosis,5 and topoisomerase inhibitory6 activities.
Consequently, the synthesis of phenanthridine derivatives has drawn considerable
attention from organic chemists. Besides classical methods7 such as the Pictet-Hubert
reaction, several new synthetic pathways have been developed to access
phenanthridines.8 These include oxidative cyclization of 2-isocyanobiphenyls9 with
bromides, hydrazines, anilines, 1,4-dioxane or acyl peroxides, cross-ring (5+1)
annulation between 2-aminobiphenyls and alkene derivatives,10 cascade addition and
cyclization of biaryl-2-carbonitriles11 with Grignard or organolithium reagents, and
C‒H amination reactions involving azide compounds.12 One of the most
straightforward synthetic strategies, intramolecular C‒H animation of corresponding
aniline precursors was reported for the synthesis of 6-aryl phenanthridines by
t
Alabugin et al.,13 who used FeCl3-DDQ and BuOK-O2-DMF systems (Scheme 1a).
Despite these achievements, the search for facile and efficient approaches toward to
phenanthridines is still significant for industry and academia.
Direct sp3 C−H amination is a valuable but challenging transformation in organic
synthesis,14 especially in the construction of nitrogen-containing heterocyclic
frameworks. However, most of the current synthetic methods using this strategy
involve transition metals, and to date, only a few transition-metal-free protocols,13b, 15
such as the Hofmann-Loffler-Freytag reaction16 have been developed. As a
continuation of our studies on oxidative C−N bond construction employing molecular
iodine,15e-f, 17 we report herein the I2-mediated intramolecular sp3 C−H amination
reaction of readily accessible aniline substrates, producing phenanthridines under

Page 3 of 36
Organic & Biomolecular Chemistry
View Article Online
DOI: 10.1039/D0OB00433B
transition-metal-free conditions (Scheme 1).
a. Synthesis of phenanthridines by Alabugin et al.13
R1
R1
R3
FeCl3, DDQ, MeCN, 80 °C
N
H2
N
or
Ar
Ar
KOtBu, DMF, O2, rt or 120 °C
R3
b. Our previous work for the synthesis of 1H-pyrazoles and imidazo[1,5-a]pyridines15e-f
R2
N
R2
I2, NaOAc
I2, NaOAc
N
R1
toluene, reflux
N
R1
R2
N
DCE, reflux
N
Ar
N
R3
N
R3
Ar
2
N
HR
c. This work
R1
R3
R1
R3
I2, Cs2CO3
N
N
H2
R2
R2
R2 = aryl or alkyl
HMPA, 80 °C
Scheme 1 Synthesis of nitrogen-containing heterocycles by sp3 C‒H aminations
. Results and Discussion
The required aniline substrates can be readily prepared according to literature
18
procedures.13a,
Initially, 2’-(4-methylbenzyl)-[1,1’-biphenyl]-2-amine (1a) was
selected as the model substrate for investigation (Table 1). Solvent screening showed
that the I2-promoted sp3 C−H amination reaction with 1a proceeds well at room
temperature in hexamethylphosphoramide (HMPA) (entry 10) or pyridine (entry 14)
to form the phenanthridine product, 6-(4-methylbenzyl)phenanthridine (2a). With
HMPA as the solvent, the conversion was incomplete and 15% of 1a was recovered at
room temperature (entry 10). The yield increased with the rising reaction temperature
(entries 15–17), and HMPA was therefore selected for further optimization of the
reaction conditions. The optimal temperature was found to be 80 °C (entry 16 vs
entries 15 and 17) and Cs2CO3 was found to be the most effective base (entry 16 vs
entries 18–25) for this transformation. This C−H amination reaction requires at least
2.2 equiv of iodine (entry 16 vs entries 26–27) and pre-stirring of iodine and base in

Organic & Biomolecular Chemistry
Page 4 of 36
View Article Online
DOI: 10.1039/D0OB00433B
HMPA favors the formation of the product (2a) by diminishing the secondary
iodination reactions.19 The reaction was not affected when performed under an
atmosphere of nitrogen (entry 28). No expected product was observed when
2,6-di-tert-butyl-4-methylphenol (BHT), a free radical scavenger, was added to the
reaction system (entry 29). This result suggested that the present reaction might
undergo a radical pathway.
Table 1 Optimization of reaction conditionsa
I2, base
N
NH2
p-Tol
solvent, temp.
p-Tol
1a
2a
entry I2 (equiv)
base
solvent
toluene
CH2Cl2
DCE
temp.
rt
rt
rt
rt
rt
rt
rt
rt
rt
rt
rt
rt
rt
rt
60 °C
80 °C
100 °C
80 °C
80 °C
80 °C
80 °C
80 °C
80 °C
80 °C
80 °C
time (h) yield (%)b
1
2.2
2.2
2.2
2.2
2.2
2.2
2.2
2.2
2.2
2.2
2.2
2.2
2.2
2.2
2.2
2.2
2.2
2.2
2.2
2.2
2.2
2.2
2.2
2.2
2.2
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
NaHCO3
Na2CO3
K2CO3
K3PO4
KOH
NaOAc
Et3N
DBU
2
2
2
4
7
2
7
8
8
12
7
2
2
10
2
2
1
2
2
2
2
2
2
2
5
23
12
25
37
49
25
45
55
45
65c
48
21
22
65
75
80
74
0
2
3
4
5
6
7
8
9
THF
1,4-dioxane
MeCN
DMF
DMA
NMP
HMPA
DMSO
MeOH
EtOH
pyridine
HMPA
HMPA
HMPA
HMPA
HMPA
HMPA
HMPA
HMPA
HMPA
HMPA
HMPA
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
28
40
33
19
73
21
43

Page 5 of 36
Organic & Biomolecular Chemistry
View Article Online
DOI: 10.1039/D0OB00433B
26
27
28e
29f
2.0
2.4
2.2
2.2
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
HMPA
HMPA
HMPA
HMPA
80 °C
80 °C
80 °C
80 °C
5
2
2
2
75d
80
80
0
a
Optimal reaction conditions (entry 16): A well-stirred mixture of I2 (1.1 mmol) and
Cs2CO3 (2.5 mmol) in HMPA (5 mL) was treated with 1a (0.5 mmol) and then
maintained at 80 °C for 2 h. b Isolated yields. c With 15% of 1a recovered. d With 6%
of 1a recovered. e Under N2 atmosphere. f With 2.5 equiv of BHT.
Having established the optimized reaction conditions, we examined the scope and
generality of this methodology. As shown in Scheme 2, this synthetic process is
compatible with a variety of substrates bearing electron-donating groups (EDG) or
electron-withdrawing groups (EWG) at the R1, R3 or R4 positions. The presence of
EWGs, especially at the ortho- and/or para- position of the aniline moiety (2d–2h &
2j–2k), favors the formation of the phenanthridine products. The structure of the
phenanthridine (2d) was confirmed by X-ray crystallography.20 The reaction leading
to the product 2f can be successfully conducted on a gram scale. Replacement of the
aromatic R2 group with hydrogen or an aliphatic group also led to the corresponding
phenanthridines (2u–2w) but in decreased yields. The quinoline product (2ag) was
synthesized from the corresponding precursor in a satisfactory yield as well.

Organic & Biomolecular Chemistry
Page 6 of 36
View Article Online
DOI: 10.1039/D0OB00433B
R1
R3
R1
I2, Cs2CO3
NH2
N
HMPA, 80 °C
R2
R2
R3
1
2
(R1 = Me), 85%
(R1 = F), 81%
Cl
2b
2c
2d
2e
2f
R1
Cl
N
(R1 = Cl), 90%
N
N
(R1 = Br), 87%
N
(R1 = CF3), 95% (93%)a
(R1 = CN), 94%
(R1 = NO2), 92%
p-Tol
p-Tol
p-Tol
p-Tol
2g
2h
2a
, 80%
2i
, 80%
2j
, 87%
(R4 = OMe), 83%
(R4 = F), 71%
2m
Cl
Cl
2n
2o
2p
2q
2r
(R4 = Cl), 82%
(R4 = CF3), 82%
(R4 = CN), 86%
(R4 = NO2), 86%
N
N
N
N
, 90%
N
Me
Ph
p-Tol
R4
2k
2l
, 81%
2s
, 79%
R1
Me
(R3 = OMe), 81%
(R3 = F), 70%
2x
2y
2z
N
Me
N
N
(R3 = Cl), 83%
(R3 = CF3), 85%
(R3 = CN), 83%
(R3 = NO2), 84%
Ph
H
Me
2aa
2ab
2ac
(R1 = Me), 35%b
(R1 = CF3), 38%b
R3
2u
b
2t
, 75%
2w
, 37%
2v
N
N
N
N
NC
Ph
Ph
Ph
Ph
Ph
CN
NC
2ad
2ae
, 85%
2af
2ag
, 70%
, 83%
, 85%
Scheme 2 Substrate scope. Reaction conditions: A well-stirred mixture of I2 (1.1
mmol) and Cs2CO3 (2.5 mmol) in HMPA (5 mL) was treated with 1 (0.5 mmol) and
then maintained at 80 °C (Isolated yields are given). a Yield of a gram-scale reaction
(5 mmol). b At room temperature.
On the basis of the above experimental results and pioneering works,13 a tentative
mechanism is proposed for this I2-mediated sp3 C−H amination reaction and is shown
in Scheme 3. Initially, deprotonation of substrate 1a by base gives a plausible
N-centered anion A, which reacts with iodine to produce an N-iodo intermediate B.
Then, homolytic cleavage of the N‒I bond in B under heating generates an N-centered
radical species C, which may abstract the benzylic C‒H intramolecularly to form a

Page 7 of 36
Organic & Biomolecular Chemistry
View Article Online
C-center radical C'. Reaction of C' with iodine radical (I•) leadsDOtIo: 10.1t0h3e9/D0OB00433B
dihydrophenanthridine D. The resulting hydrogen iodie (HI) is neutralized by base.
Finally, further deprotonation of compound D and subsequent oxidative aromatization
by iodine under basic conditions affords the phenanthridine product (2a).
base
I
I
H
I
NH
Ar
N

NH
H
Ar
Ar
Ar = p-tolyl
1a
I
A
B
base
H
I
NH2
Ar
N
NH
Ar
Ar
HI
D
C
C'
I
I
I
N
N
N
Ar
Ar
H
Ar
base
E
F
2a
Scheme 3 Proposed mechanism
. Conclusions
We have developed a new and practical intramolecular sp3 C−H amination reaction of
aniline substrates, employing iodine as the oxidant under transition-metal-free
conditions, to synthesize phenanthridines. This straightforward synthetic approach is
operationally simple and applicable to a broad range of unprotected aniline
derivatives to afford various phenanthridine products in an efficient and scalable
fashion.
. Experimental Section
1. General Information. 1H and 13C{1H} NMR spectra were recorded on a 400 MHz

Organic & Biomolecular Chemistry
Page 8 of 36
View Article Online
DOI: 10.1039/D0OB00433B
13
(100 MHz for C{1H} NMR) spectrometer. Chemical shift values are reported in
ppm (parts per million) with tetramethylsilane (TMS) as an internal standard. The
peak patterns are indicated as follows: s, singlet; d, doublet; t, triplet; q, quartet; m,
multiplet; dd, doublet of doublets; ddd, doublet of doublet of doublets; td, triplet of
doublets. The coupling constants (J) are reported in hertz (Hz). Melting points were
determined on a micromelting point apparatus without corrections. High-resolution
mass spectra (HRMS) were obtained on a Q-TOF Mass Spectrometer equipped with
an electrospray ion source (ESI), operated in the positive mode. Flash column
chromatography was performed over silica gel 200–300 mesh and the solvents were
distilled prior to use. THF was dried over Na/benzophenone and then distilled, and
HMPA was dried over 4 Å molecular sieves before use. Toluene and EtOH were
analytical reagent grade and used without any pretreatment.
2. General Procedure for the Preparation of Substrates 1a, 1l–1t, and 1x–1af. The
required aryl bromides were prepared according to literature procedures.18a, 18b
A
mixture of the corresponding bromide (2 mmol), (2-aminophenyl)boronic acid (2.4
mmol), K2CO3 (6 mmol) in toluene (15 mL)/EtOH (6 mL)/H2O (3 mL) was stirred at
room temperature under N2 atmosphere for 0.5 h, and then treated with Pd(PPh3)4 (0.1
mmol).13a The reaction was heated to reflux under N2 atmosphere for 12 h (TLC
indicated the total consumption of the aryl bromide). After cooling to room
temperature, it was diluted with H2O (10 mL) and extracted with EtOAc (3 x 15 mL).
The combined organic layer was washed with brine (20 mL), dried over anhydrous
Na2SO4, concentrated, and purified through silica gel column chromatography to give
the substrate 1.

Page 9 of 36
Organic & Biomolecular Chemistry
View Article Online
DOI: 10.1039/D0OB00433B
Br
B(OH)2
NH2
Pd(PPh3)4, K2CO3
NH2
R4
R3
+
toluene/EtOH/H2O, reflux
R4
R3
1a 1l 1t 1x 1af
,
-
&
-
3. General Procedure for the Preparation of Substrates 1b–1k and 1u−1w. The
required aryl boronic acids are commercially available or were prepared according to
a literature procedure.18c A mixture of the corresponding boronic acid (2 mmol), the
substituted 2-bromo/iodo aniline (2.4 mmol), K2CO3 (6 mmol), toluene (15
mL)/EtOH (6 mL)/H2O (3 mL) was stirred at room temperature under N2 atmosphere
for 0.5 h, and then treated with Pd(PPh3)4 (0.1 mmol).13a The reaction was heated to
reflux under N2 atmosphere for 12 h (TLC indicated the total consumption of the
boronic acid). After cooling to room temperature, it was diluted with H2O (10 mL)
and extracted with EtOAc (3 x 15 mL). The combined organic layer was washed with
brine (20 mL), dried over anhydrous Na2SO4, concentrated, and purified through
silica gel column chromatography to give the substrate 1.
R1
X
B(OH)2
NH2
NH2
R2
Pd(PPh3)4, K2CO3
R2
+
R1
toluene/EtOH/H2O, reflux
X = Br or I
1b 1k 1u 1w
-
&
-
4. Preparation of Substrate 1ag. A solution of (2-aminophenyl)(phenyl)methanone
(3 mmol) in dry THF (10 mL) was treated with phenethylmagnesium bromide (1 M in
THF, 10 mL) under N2 atmosphere,21 and then heated to 50 °C for 12 h (TLC
indicated the total consumption of the ketone). After cooling to room temperature, the
reaction was quenched with aqueous HCl solution (2 M, 5 mL), stirred for 0.5 h,
diluted with brine (15 mL) and extracted with EtOAc (3 x 15 mL). The combined
organic layer was washed with brine (2 x 10 mL), dried over anhydrous Na2SO4, and
concentrated to give the tertiary alcohol intermediate. A reaction mixture of the above

Organic & Biomolecular Chemistry
Page 10 of 36
View Article Online
DOI: 10.1039/D0OB00433B
crude tertiary alcohol and p-TsOH (0.6 mmol) in toluene (15 mL) was refluxed for 24
h (TLC indicated the total consumption of the alcohol). After cooling to room
temperature, it was washed with H2O (3 x 15 mL) and brine (2 x 15 mL) in sequence,
and then extracted with EtOAc (3 x 15 mL). The combined organic layer was dried
over anhydrous Na2SO4, concentrated, and purified through silica gel column
chromatography to afford substrate 1ag.
NH2
Ph(CH2)2MgBr
THF, 50 °C
p-TsOH
NH2
Ph
Ph
NH2
Ph
toluene, reflux
Ph
O
Ph
OH
1ag
2'-(4-Methylbenzyl)-[1,1'-biphenyl]-2-amine (1a).13b EtOAc/petroleum ether (PE)
1
(eluent) 2:98; 388 mg, 71% yield; white solid, mp 66–67 °C; H NMR (400 MHz,
CDCl3) δ 7.30–7.20 (m, 4H, overlapped with the peak of chloroform), 7.18–7.14 (m,
1H), 7.00–6.96 (m, 3H), 6.86 (d, J = 8.0 Hz, 2H), 6.77 (td, J = 7.6, 1.2 Hz, 1H),
6.74–6.72 (m, 1H), 3.85–3.74 (m, 2H), 3.37 (s, 2H), 2.27 (s, 3H); 13C{1H} NMR (100
MHz, CDCl3) δ 144.0, 140.6, 138.5, 138.1, 135.3, 130.54, 130.53, 130.2, 129.04,
128.99, 128.6, 128.0, 127.2, 126.7, 118.3, 115.3, 38.7, 21.1; HRMS (m/z) [M + H]+
calcd for C20H20N 274.1590, found 274.1589.
5-Methyl-2'-(4-methylbenzyl)-[1,1'-biphenyl]-2-amine (1b). EtOAc/PE (eluent)
1
2:98; 482 mg, 84% yield; white solid, mp 68–69 °C ; H NMR (400 MHz, CDCl3) δ
7.29–7.19 (m, 4H, overlapped with the peak of chloroform), 7.01–6.96 (m, 3H), 6.86
(d, J = 8.0 Hz, 2H), 6.75 (s, 1H), 6.66 (d, J = 8.0 Hz, 1H), 3.85–3.73 (m, 2H), 3.26 (s,
13
2H), 2.28 (s, 3H), 2.22 (s, 3H); C{1H} NMR (100 MHz, CDCl3) δ 141.4, 140.6,
138.8, 138.2, 135.3, 131.1, 130.5, 130.1, 129.10, 129.05, 128.9, 127.9, 127.5, 127.3,
126.6, 115.4, 38.8, 21.1, 20.6; HRMS (m/z) [M + H]+ calcd for C21H22N 288.1747,
found 288.1748.
5-Fluoro-2'-(4-methylbenzyl)-[1,1'-biphenyl]-2-amine (1c). CH2Cl2/PE (eluent)

Page 11 of 36
Organic & Biomolecular Chemistry
View Article Online
DOI: 10.1039/D0OB00433B
20:80; 495 mg, 85% yield; white solid, mp 49–51 °C; 1H NMR (400 MHz, CDCl3) δ
7.33–7.24 (m, 3H, overlapped with the peak of chloroform), 7.19–7.17 (m, 1H), 7.00
(d, J = 8.0 Hz, 2H), 6.90–6.84 (m, 3H), 6.71–6.64 (m, 2H), 3.85–3.74 (m, 2H), 3.23 (s,
13
2H), 2.28 (s, 3H); C{1H} NMR (100 MHz, CDCl3) δ 156.1 (d, JC–F = 234.9 Hz),
140.4, 140.2 (d, JC–F = 2.1 Hz), 137.8, 137.6 (d, JC–F = 1.3 Hz), 135.5, 130.4, 130.3,
129.04, 128.96, 128.4, 128.3 (d, JC–F = 7.2 Hz), 126.8, 116.9 (d, JC–F = 22.0 Hz),
116.1 (d, JC–F = 7.8 Hz), 115.0 (d, JC–F = 22.1 Hz), 38.8, 21.1; HRMS (m/z) [M + H]+
calcd for C20H19FN 292.1496, found 292.1498.
5-Chloro-2'-(4-methylbenzyl)-[1,1'-biphenyl]-2-amine (1d). CH2Cl2/PE (eluent)
11:89; 480 mg, 78% yield; white solid; mp 98–100 °C; 1H NMR (400 MHz, CDCl3) δ
7.32–7.25 (m, 3H, overlapped with the peak of chloroform), 7.17–7.15 (m, 1H), 7.10
(dd, J = 8.4, 2.4 Hz, 1H), 7.00 (d, J = 8.0 Hz, 2H), 6.90 (d, J = 2.4 Hz, 1H), 6.84 (d, J
= 7.6 Hz, 2H), 6.64 (d, J = 8.8 Hz, 1H), 3.84–3.72 (m, 2H), 3.34 (s, 2H), 2.28 (s, 3H);
13C{1H} NMR (100 MHz, CDCl3) δ 142.7, 140.5, 137.7, 137.3, 135.5, 130.4, 130.1,
129.1, 129.0, 128.53, 128.46, 128.3, 126.9, 122.8, 116.3, 38.8, 21.1; HRMS (m/z) [M
+ H]+ calcd for C20H19ClN 308.1201, found 308.1204.
5-Bromo-2'-(4-methylbenzyl)-[1,1'-biphenyl]-2-amine (1e). CH2Cl2/PE (eluent)
20:80; 610 mg, 87% yield; white solid, mp 73–75 °C; 1H NMR (400 MHz, CDCl3) δ
7.32–7.22 (m, 4H, overlapped with the peak of chloroform), 7.17–7.15 (m, 1H),
7.02–6.99 (m, 3H), 6.84 (d, J = 7.6 Hz, 2H), 6.60 (d, J = 8.4 Hz, 1H), 3.84–3.72 (m,
13
2H), 3.36 (s, 2H), 2.28 (s, 3H); C{1H} NMR (100 MHz, CDCl3) δ 143.2, 140.5,
137.7, 137.2, 135.5, 133.0, 131.2, 130.38, 130.37, 129.1, 129.03, 128.99, 128.5, 126.9,
116.7, 109.9, 38.9, 21.1; HRMS (m/z) [M + H]+ calcd for C20H19BrN 352.0695, found
352.0696.
2'-(4-Methylbenzyl)-5-(trifluoromethyl)-[1,1'-biphenyl]-2-amine (1f). EtOAc/PE

Organic & Biomolecular Chemistry
Page 12 of 36
View Article Online
DOI: 10.1039/D0OB00433B
1
(eluent) 2:98; 550 mg, 81% yield; white solid, mp 63–66 °C; H NMR (400 MHz,
CDCl3) δ 7.40–7.38 (m, 1H), 7.34–7.28 (m, 3H), 7.20–7.18 (m, 1H), 7.13 (s, 1H),
6.98 (d, J = 7.6 Hz, 2H), 6.80 (d, J = 7.6 Hz, 2H), 6.74 (d, J = 8.4 Hz, 1H), 3.83–3.68
(m, 4H), 2.28 (s, 3H); 13C{1H} NMR (100 MHz, CDCl3) δ 147.1, 140.7, 137.6, 137.1,
135.6, 130.6, 130.5, 129.1, 128.9, 128.6, 127.9 (q, JC–F = 3.8 Hz), 127.0, 126.5, 125.8
(q, JC–F = 3.7 Hz), 124.9 (d, JC–F = 269.1 Hz), 120.0 (q, JC–F = 32.4 Hz), 114.5, 39.0,
21.1; HRMS (m/z) [M + H]+ calcd for C21H19F3N 342.1464, found 342.1465.
6-Amino-2'-(4-methylbenzyl)-[1,1'-biphenyl]-3-carbonitrile
(1g).
EtOAc/PE
(eluent) 27:73; 560 mg, 94% yield; white solid, mp 116–117 °C; 1H NMR (400 MHz,
CDCl3) δ 7.41(dd, J = 8.4, 2.0 Hz, 1H), 7.37–7.28 (m, 3H), 7.15–7.13 (m, 2H), 6.99
(d, J = 7.6 Hz, 2H), 6.78 (d, J = 8.0 Hz, 2H), 6.69 (d, J = 8.4 Hz, 1H), 3.87 (s, 2H),
13
3.80–3.68 (m, 2H), 2.28 (s, 3H); C{1H} NMR (100 MHz, CDCl3) δ 148.2, 140.5,
137.4, 136.1, 135.7, 134.7, 132.9, 130.7, 130.4, 129.1, 128.9, 128.8, 127.2, 126.9,
120.2, 114.7, 100.1, 39.0, 21.1; HRMS (m/z) [M + H]+ calcd for C21H19N2 299.1543,
found 299.1547.
2'-(4-Methylbenzyl)-5-nitro-[1,1'-biphenyl]-2-amine (1h). EtOAc/PE (eluent) 8:92;
513 mg, 80% yield; light yellow solid, mp 104–106 °C; 1H NMR (400 MHz, CDCl3)
δ 8.06 (dd, J = 8.8, 2.4 Hz, 1H), 7.82 (d, J = 2.4 Hz, 1H), 7.38–7.29 (m, 3H),
7.19–7.17 (m, 1H), 6.97 (d, J = 7.6 Hz, 2H), 6.78 (d, J = 8.0 Hz, 2H), 6.66 (d, J = 8.8
13
Hz, 1H), 4.09 (s, 2H), 3.83–3.70 (m, 2H), 2.26 (s, 3H); C{1H} NMR (100 MHz,
CDCl3) δ 150.5, 140.6, 138.9, 137.3, 135.9, 135.7, 130.8, 130.5, 129.10, 129.07,
128.8, 127.23, 127.18, 125.8, 125.4, 113.6, 39.0, 21.1; HRMS (m/z) [M + H]+ calcd
for C20H19N2O2 319.1441, found 319.1442.
4-Chloro-2'-(4-methylbenzyl)-[1,1'-biphenyl]-2-amine (1i). EtOAc/PE (eluent)
1
2:98; 345 mg, 56% yield; colorless oil; H NMR (400 MHz, CDCl3) δ 7.32–7.24 (m,

Page 13 of 36
Organic & Biomolecular Chemistry
View Article Online
DOI: 10.1039/D0OB00433B
3H, overlapped with the peak of chloroform), 7.18–7.15 (m, 1H), 7.00 (d, J = 8.0 Hz,
2H), 6.86–6.83 (m, 3H), 6.74–6.71 (m, 2H), 3.82–3.71 (m, 2H), 3.43 (s, 2H), 2.28 (s,
13
3H); C{1H} NMR (100 MHz, CDCl3) δ 145.3, 140.6, 137.8, 137.4, 135.5, 133.9,
131.6, 130.5, 130.4, 129.0, 128.9, 128.4, 126.8, 125.5, 118.2, 114.8, 38.7, 21.1;
HRMS (m/z) [M + H]+ calcd for C20H19ClN 308.1201, found 308.1202.
3-Chloro-2'-(4-methylbenzyl)-[1,1'-biphenyl]-2-amine (1j). EtOAc/PE (eluent)
1
1:99; 530 mg, 86% yield; colorless oil; H NMR (400 MHz, CDCl3) δ 7.33–7.24 (m,
4H, overlapped with the peak of chloroform), 7.20–7.18 (m, 1H), 6.99 (d, J = 8.0 Hz,
2H), 6.88–6.86 (m, 1H), 6.81 (d, J = 8.0 Hz, 2H), 6.69 (t, J = 7.6 Hz, 1H), 3.82–3.71
(m, 4H), 2.28 (s, 3H); 13C{1H} NMR (100 MHz, CDCl3) δ 141.0, 140.5, 137.8, 137.7,
135.4, 130.42, 130.38, 129.01, 128.97, 128.9, 128.6, 128.4, 128.1, 126.9, 119.3, 118.2,
38.8, 21.1; HRMS (m/z) [M + H]+ calcd for C20H19ClN 308.1201, found 308.1202.
3,5-Dichloro-2'-(4-methylbenzyl)-[1,1'-biphenyl]-2-amine (1k). EtOAc/PE (eluent)
1:99; 534 mg, 78% yield; white solid; mp 104–106 °C; 1H NMR (400 MHz, CDCl3) δ
7.35–7.25 (m, 4H, overlapped with the peak of chloroform), 7.16–7.14 (m, 1H), 7.00
13
(d, J = 8.0 Hz, 2H), 6.82–6.79 (m, 3H), 3.81–3.68 (m, 4H), 2.28 (s, 3H); C{1H}
NMR (100 MHz, CDCl3) δ 140.5, 139.9, 137.4, 136.6, 135.6, 130.6, 130.2, 129.1,
128.9, 128.8, 128.7, 128.0, 127.0, 122.1, 119.5, 39.0, 21.1; HRMS (m/z) [M + H]+
calcd for C20H18Cl2N 342.0811, found 342.0813.
2'-Benzyl-[1,1'-biphenyl]-2-amine (1l).13b EtOAc/PE (eluent) 5:95; 369 mg, 71%
1
yield; white solid, mp 67–69 °C; H NMR (400 MHz, CDCl3) δ 7.32–7.21 (m, 4H,
overlapped with the peak of chloroform), 7.19–7.10 (m, 4H), 6.96–6.94 (m, 3H), 6.77
(td, J = 7.6, 1.2 Hz, 1H), 6.72 (dd, J = 8.0, 0.8 Hz, 1H), 3.89–3.78 (m, 2H), 3.34 (s,
13
2H); C{1H} NMR (100 MHz, CDCl3) δ 144.0, 141.1, 140.4, 138.6, 130.6, 130.5,
130.3, 129.2, 128.6, 128.3, 128.0, 127.1, 126.8, 125.9, 118.3, 115.3, 39.3; HRMS

Organic & Biomolecular Chemistry
Page 14 of 36
View Article Online
DOI: 10.1039/D0OB00433B
(m/z) [M + H]+ calcd for C19H18N 260.1434, found 260.1436.
2'-(4-Methoxybenzyl)-[1,1'-biphenyl]-2-amine (1m). EtOAc/PE (eluent) 5:95; 313
1
mg, 54% yield; white solid, mp 65–66 °C; H NMR (400 MHz, CDCl3) δ 7.32–7.21
(m, 4H, overlapped with the peak of chloroform), 7.19–7.15 (m, 1H), 6.98–6.96 (m,
1H), 6.89–6.87 (m, 2H), 6.80–6.72 (m, 4H), 3.84–3.73 (m, 5H), 3.37 (s, 2H); 13C{1H}
NMR (100 MHz, CDCl3) δ 157.8, 144.0, 140.8, 138.5, 133.3, 130.6, 130.5, 130.2,
130.1, 128.6, 128.1, 127.2, 126.7, 118.4, 115.3, 113.7, 55.4, 38.4; HRMS (m/z) [M +
H]+ calcd for C20H20NO 290.1539, found 290.1541.
2'-(4-Fluorobenzyl)-[1,1'-biphenyl]-2-amine (1n).13b EtOAc/PE (eluent) 5:95; 477
1
mg, 86% yield; white solid, mp 76–78 °C; H NMR (400 MHz, CDCl3) δ 7.32–7.21
(m, 4H, overlapped with the peak of chloroform), 7.15 (t, J = 8.0 Hz, 1H), 6.92–6.82
13
(m, 5H), 6.78–6.71 (m, 2H), 3.86–3.75 (m, 2H), 3.32 (s, 2H); C{1H} NMR (100
MHz, CDCl3) δ 161.4 (d, JC–F = 242.0 Hz), 144.0, 140.3, 138.7, 136.8 (d, JC–F = 3.2
Hz), 130.7, 130.5 (d, JC–F = 1.1 Hz), 130.4, 130.2, 128.7, 128.1, 127.00, 126.97, 118.4,
115.3, 115.0 (d, JC–F = 21.0 Hz); HRMS (m/z) [M + H]+ calcd for C19H17FN 278.1340,
found 278.1342.
2'-(4-Chlorobenzyl)-[1,1'-biphenyl]-2-amine (1o). CH2Cl2/PE (eluent) 25:75; 480
1
mg, 82% yield; white solid, mp 48–50 °C; H NMR (400 MHz, CDCl3) δ 7.33–7.27
(m, 2H, overlapped with the peak of chloroform), 7.25–7.21 (m, 2H), 7.18–7.12 (m,
3H), 6.91 (dd, J = 7.6, 1.6 Hz, 1H), 6.85 (d, J = 8.4 Hz, 2H), 6.78–6.72 (m, 2H),
13
3.86–3.75 (m, 2H), 3.37 (s, 2H); C{1H} NMR (100 MHz, CDCl3) δ 143.9, 139.9,
139.6, 138.7, 131.6, 130.7, 130.5, 130.4, 130.2, 128.7, 128.3, 128.2, 127.1, 126.9,
118.4, 115.3, 38.7; HRMS (m/z) [M + H]+ calcd for C19H17ClN 294.1044, found
294.1045.
2'-(4-(Trifluoromethyl)benzyl)-[1,1'-biphenyl]-2-amine (1p). EtOAc/PE (eluent)

Page 15 of 36
Organic & Biomolecular Chemistry
View Article Online
DOI: 10.1039/D0OB00433B
1
5:95; 342 mg, 52% yield; white solid, mp 60–63 °C; H NMR (400 MHz, CDCl3) δ
7.41 (d, J = 8.0 Hz, 2H), 7.34–7.28 (m, 2H), 7.25–7.23 (m, 2H, overlapped with the
peak of chloroform), 7.18–7.14 (m, 1H), 7.03 (d, J = 8.4 Hz, 2H), 6.90 (dd, J = 7.2,
1.2 Hz, 1H), 6.77–6.72 (m, 2H), 3.96–3.85 (m, 2H), 3.38 (s, 2H); 13C{1H} NMR (100
MHz, CDCl3) δ 145.3, 143.9, 139.4, 138.8, 130.8, 130.5, 130.3, 129.4, 128.8, 128.23,
128.20 (q, JC–F = 32.0 Hz), 127.3, 126.8, 125.1 (q, JC–F = 3.8 Hz), 124.5 (q, JC–F
=
270.1 Hz), 118.4, 115.3, 39.2; HRMS (m/z) [M + H]+ calcd for C20H17F3N 328.1308,
found 328.1311.
4-((2'-Amino-[1,1'-biphenyl]-2-yl)methyl)benzonitrile (1q).13b EtOAc/PE (eluent)
1
9:91; 551 mg, 97% yield; white solid, mp 69–72 °C; H NMR (400 MHz, CDCl3) δ
7.44–7.42 (m, 2H), 7.35–7.31 (m, 2H), 7.26–7.23 (m, 2H, overlapped with the peak of
chloroform), 7.16 (td, J = 8.0, 1.6 Hz, 1H), 6.99 (d, J = 8.4 Hz, 2H), 6.85–6.82 (m,
13
1H), 6.75–6.71 (m, 2H), 3.96–3.86 (m, 2H), 3.37 (s, 2H); C{1H} NMR (100 MHz,
CDCl3) δ 146.8, 143.8, 138.9, 138.8, 132.0, 130.9, 130.41, 130.38, 129.7, 128.8,
128.3, 127.5, 126.6, 119.3, 118.4, 115.3, 109.6, 39.7; HRMS (m/z) [M + H]+ calcd for
C20H17N2 285.1386, found 285.1387.
2'-(4-Nitrobenzyl)-[1,1'-biphenyl]-2-amine (1r). CH2Cl2/PE (eluent) 50:50; 547 mg,
90% yield; light yellow solid, mp 103–105 °C; 1H NMR (400 MHz, CDCl3) δ 8.00 (d,
J = 8.8 Hz, 2H), 7.36–7.31 (m, 2H), 7.29–7.23 (m, 2H, overlapped with the peak of
chloroform), 7.18–7.14 (m, 1H), 7.03 (d, J = 8.4 Hz, 2H), 6.84 (dd, J = 8.0, 1.6 Hz,
13
1H), 6.74–6.71 (m, 2H), 4.01–3.91 (m, 2H), 3.39 (s, 2H); C{1H} NMR (100 MHz,
CDCl3) δ 149.0, 146.3, 143.8, 138.9, 138.8, 130.9, 130.41, 130.40, 129.7, 128.9,
128.3, 127.6, 126.5, 123.4, 118.4, 115.3, 39.5; HRMS (m/z) [M + H]+ calcd for
C19H17N2O2 305.1285, found 305.1288.
2'-(3-Methylbenzyl)-[1,1'-biphenyl]-2-amine (1s). EtOAc/PE (eluent) 9:91; 410 mg,

Organic & Biomolecular Chemistry
Page 16 of 36
View Article Online
75% yield; colorless oil; 1H NMR (400 MHz, CDCl3) δ 7.32–7.20 (m, 4H, ovDeOrlI:a1p0.p10e3d9/D0OB00433B
with the peak of chloroform), 7.18–7.14 (m, 1H), 7.06 (t, J = 7.6 Hz, 1H), 6.97–6.92
13
(m, 2H), 6.80–6.71 (m, 4H), 3.85–3.74 (m, 2H), 3.34 (s, 2H), 2.23 (s, 3H); C{1H}
NMR (100 MHz, CDCl3) δ 144.1, 141.0, 140.5, 138.6, 137.8, 130.6, 130.5, 130.3,
130.0, 128.6, 128.1, 128.0, 127.2, 126.7, 126.6, 126.2, 118.3, 115.3, 39.3, 21.5;
HRMS (m/z) [M + H]+ calcd for C20H20N 274.1590, found 274.1593.
2'-(2-Methylbenzyl)-[1,1'-biphenyl]-2-amine (1t). EtOAc/PE (eluent) 5:95; 350 mg,
64% yield; white solid, mp 102–103 °C; 1H NMR (400 MHz, CDCl3) δ 7.29–7.24 (m,
3H, overlapped with the peak of chloroform), 7.16 (t, J = 7.6 Hz, 1H), 7.12–7.05 (m,
3H), 7.01–6.96 (m, 3H), 6.80–6.74 (m, 2H), 3.88–3.75 (m, 2H), 3.24 (s, 2H), 2.03 (s,
13
3H); C{1H} NMR (100 MHz, CDCl3) δ 143.9, 139.7, 139.0, 138.7, 136.8, 130.4,
130.3, 130.2, 129.5, 128.6, 128.0, 127.2, 126.6, 126.3, 125.9, 118.5, 115.4, 36.6, 19.7;
HRMS (m/z) [M + H]+ calcd for C20H20N 274.1590, found 274.1588.
2',5-Dimethyl-[1,1'-biphenyl]-2-amine (1u).12a CH2Cl2/PE (eluent) 20:80; 355 mg,
90% yield; colorless oil; 1H NMR (400 MHz, CDCl3) δ 7.28–7.18 (m, 4H, overlapped
with the peak of chloroform), 6.98 (d, J = 8.0 Hz, 1H), 6.83 (s, 1H), 6.68 (d, J = 8.0
Hz, 1H), 3.31 (s, 2H), 2.27 (s, 3H), 2.18 (m, 3H); 13C{1H} NMR (100 MHz, CDCl3) δ
141.2, 138.9, 137.0, 130.7, 130.3, 130.2, 129.0, 127.7, 127.5, 126.2, 115.3, 20.6, 19.9;
HRMS (m/z) [M + H]+ calcd for C14H16N 198.1277, found 198.1279.
2'-Methyl-5-(trifluoromethyl)-[1,1'-biphenyl]-2-amine (1v).12a EtOAc/PE (eluent)
1
5:95; 455 mg, 91% yield; colorless oil; H NMR (400 MHz, CDCl3) δ 7.40–7.38 (m,
1H), 7.32–7.24 (m, 4H, overlapped with the peak of chloroform), 7.19–7.17 (m, 1H),
13
6.76 (d, J = 8.4 Hz, 1H), 3.79 (s, 2H), 2.16–2.15 (m, 3H); C{1H} NMR (100 MHz,
CDCl3) δ 146.8, 137.2, 137.1, 130.6, 130.1, 128.4, 127.4 (q, JC–F = 3.8 Hz), 126.8,

Page 17 of 36
Organic & Biomolecular Chemistry
View Article Online
DOI: 10.1039/D0OB00433B
126.5, 125.7 (q, JC–F = 3.8 Hz), 125.0 (q, JC–F = 268.9 Hz), 119.9 (q, JC–F = 32.3 Hz),
114.3, 19.7; HRMS (m/z) [M + H]+ calcd for C14H13F3N 252.0995, found 252.0996.
2'-Ethyl-5-methyl-[1,1'-biphenyl]-2-amine (1w).12a CH2Cl2/PE (eluent) 17:83; 262
1
mg, 62% yield; colorless oil; H NMR (400 MHz, CDCl3) δ 7.35–7.29 (m, 2H),
7.26–7.22 (m, 1H, overlapped with the peak of chloroform), 7.18–7.16 (m, 1H), 6.98
(dd, J = 8.0, 1.6 Hz, 1H), 6.84 (d, J = 2.0 Hz, 1H), 6.68 (d, J = 8.0 Hz, 1H), 3.30 (s,
13
2H), 2.58–2.42 (m, 2H), 2.27 (s, 3H), 1.08 (t, J = 7.6 Hz, 3H); C{1H} NMR (100
MHz, CDCl3) δ 143.1, 141.3, 138.3, 130.9, 130.3, 128.9, 128.7, 128.0, 127.5, 127.4,
126.2, 115.3, 26.2, 20.6, 15.4; HRMS (m/z) [M + H]+ calcd for C15H18N 212.1434,
found 212.1437.
2'-Benzyl-4'-methoxy-[1,1'-biphenyl]-2-amine (1x). EtOAc/PE (eluent) 9:91; 470
1
mg, 81% yield; colorless oil; H NMR (400 MHz, CDCl3) δ 7.20–7.10 (m, 5H),
13
6.97–6.94 (m, 3H), 6.84–6.71 (m, 4H), 3.86–3.75 (m, 5H), 3.37 (s, 2H); C{1H}
NMR (100 MHz, CDCl3) δ 159.3, 144.4, 141.8, 140.9, 131.6, 131.0, 129.1, 128.5,
128.3, 126.8, 125.9, 118.3, 116.0, 115.2, 111.8, 55.3, 39.5; HRMS (m/z) [M + H]+
calcd for C20H20NO 290.1539, found 290.1540.
2'-Benzyl-4'-fluoro-[1,1'-biphenyl]-2-amine (1y). EtOAc/PE (eluent) 9:91; 380 mg,
69% yield; colorless oil; 1H NMR (400 MHz, CDCl3) δ 7.26–7.12 (m, 7H, overlapped
with the peak of chloroform), 6.95–6.91 (m, 3H), 6.77 (td, J = 7.6, 1.2 Hz, 1H), 6.72
(dd, J = 8.0, 0.4 Hz, 1H), 3.85–3.75 (m, 2H), 3.34 (s, 2H); 13C{1H} NMR (100 MHz,
CDCl3) δ 162.5 (d, JC–F = 244.5 Hz), 144.2, 143.0 (d, JC–F = 7.2 Hz), 140.3, 134.4 (d,
JC–F = 3.2 Hz), 132.1 (d, JC–F = 8.1 Hz), 130.7, 129.2, 128.8, 128.4, 126.2, 126.0,
118.4, 116.9 (d, JC–F = 21.3 Hz), 115.3, 113.7 (d, JC–F = 20.9 Hz), 39.2 (d, JC–F = 1.4
Hz); HRMS (m/z) [M + H]+ calcd for C19H17FN 278.1340, found 278.1338.
2'-Benzyl-4'-chloro-[1,1'-biphenyl]-2-amine (1z). EtOAc/PE (eluent) 9:91; 420 mg,

Organic & Biomolecular Chemistry
Page 18 of 36
View Article Online
71% yield; colorless oil; 1H NMR (400 MHz, CDCl3) δ 7.27–7.12 (m, 7H, ovDeOrlI:a1p0.p10e3d9/D0OB00433B
with the peak of chloroform), 6.95–6.91 (m, 3H), 6.77 (td, J = 7.6, 1.2 Hz, 1H),
6.74–6.71 (m, 1H), 3.86–3.75 (m, 2H), 3.35 (s, 2H); 13C{1H} NMR (100 MHz, CDCl3)
δ 144.0, 142.5, 140.2, 137.1, 133.8, 131.9, 130.5, 130.2, 129.2, 128.9, 128.4, 127.0,
126.2, 125.8, 118.5, 115.4, 39.1; HRMS (m/z) [M + H]+ calcd for C19H17ClN
294.1044, found 294.1045.
2'-Benzyl-4'-(trifluoromethyl)-[1,1'-biphenyl]-2-amine (1aa). EtOAc/PE (eluent)
1
9:91; 540 mg, 83% yield; colorless oil; H NMR (400 MHz, CDCl3) δ 7.55–7.53 (m,
2H), 7.35 (d, J = 7.6 Hz, 1H), 7.21–7.12 (m, 4H), 6.93–6.90 (m, 3H), 6.79 (t, J = 7.6
13
Hz, 1H), 6.74 (d, J = 8.0 Hz, 1H), 3.95–3.84 (m, 2H), 3.32 (s, 2H); C{1H} NMR
(100 MHz, CDCl3) δ 143.7, 142.6, 141.5, 140.0, 131.2, 130.24 (q, JC–F = 32.1 Hz),
130.17, 129.2, 129.1, 128.5, 127.0 (q, JC–F = 3.7 Hz), 126.3, 125.7, 124.3 (q, JC–F
=
270.7 Hz), 123.7 (q, JC–F = 3.8 Hz), 118.6, 115.6, 39.2; HRMS (m/z) [M + H]+ calcd
for C20H17F3N 328.1308, found 328.1309.
2'-Amino-2-benzyl-[1,1'-biphenyl]-4-carbonitrile (1ab). EtOAc/PE (eluent) 9:91;
307 mg, 54% yield; white solid, mp 101–103 °C; 1H NMR (400 MHz, CDCl3) δ 7.56
(dd, J = 8.0, 2.0 Hz, 1H), 7.51 (d, J = 1.6 Hz, 1H), 7.34 (d, J = 7.6 Hz, 1H), 7.24–7.15
(m, 4H), 6.94–6.90 (m, 3H), 6.80 (td, J = 7.6, 1.2 Hz, 1H), 6.75 (dd, J = 8.0, 0.8 Hz,
13
1H), 3.92–3.81 (m, 2H), 3.35 (s, 2H); C{1H} NMR (100 MHz, CDCl3) δ 143.9,
143.5, 142.3, 139.4, 133.7, 131.6, 130.4, 129.9, 129.5, 129.1, 128.6, 126.5, 125.1,
119.0, 118.6, 115.7, 111.9, 38.9; HRMS (m/z) [M + H]+ calcd for C20H17N2 285.1386,
found 285.1387.
2'-Benzyl-4'-nitro-[1,1'-biphenyl]-2-amine (1ac). CH2Cl2/PE (eluent) 33:67; 368
1
mg, 61% yield; yellow solid, mp 132–133 °C; H NMR (400 MHz, CDCl3) δ
8.14–8.12 (m, 2H), 7.42–7.40 (m, 1H), 7.24–7.15 (m, 4H), 6.95–6.91 (m, 3H),

Page 19 of 36
Organic & Biomolecular Chemistry
View Article Online
13
6.84–6.80 (m, 1H), 6.77–6.75 (m, 1H), 3.99–3.88 (m, 2H), 3.34 (s, 2H); DOCI: 1{01.1H03}9/D0OB00433B
NMR (100 MHz, CDCl3) δ 147.8, 145.8, 143.4, 142.8, 139.4, 131.8, 129.9, 129.6,
129.1, 128.7, 126.6, 125.1, 124.9, 121.9, 118.7, 115.8, 39.2; HRMS (m/z) [M + H]+
calcd for C19H17N2O2 305.1285, found 305.1287.
2'-Amino-2-benzyl-[1,1'-biphenyl]-3-carbonitrile (1ad). EtOAc/PE (eluent) 17:83;
1
384 mg, 68% yield; white solid, mp 99–101 °C; H NMR (400 MHz, CDCl3) δ 7.69
(dd, J = 7.6, 1.6 Hz, 1H), 7.45 (dd, J = 7.6, 1.6 Hz, 1H), 7.39 (t, J = 8.0 Hz, 1H),
7.20–7.15 (m, 1H), 7.13–7.08 (m, 3H), 6.84–6.81 (m, 3H), 6.74 (td, J = 7.2, 1.2 Hz,
13
1H), 6.69 (dd, J = 8.0, 0.8 Hz, 1H), 4.20–4.10 (m, 2H), 3.18 (s, 2H); C{1H} NMR
(100 MHz, CDCl3) δ 144.1, 143.8, 140.7, 138.9, 135.8, 132.9, 130.4, 129.4, 128.8,
128.3, 127.7, 126.3, 125.0, 118.8, 118.6, 115.7, 114.4, 37.8; HRMS (m/z) [M + H]+
calcd for C20H17N2 285.1386, found 285.1388.
2'-Amino-6-benzyl-[1,1'-biphenyl]-3-carbonitrile (1ae). EtOAc/PE (eluent) 9:91;
1
370 mg, 65% yield; white solid, mp 86–87 °C; H NMR (400 MHz, CDCl3) δ
7.58–7.53 (m, 2H), 7.33 (d, J = 8.0 Hz, 1H), 7.25–7.14 (m, 4H), 6.94–6.90 (m, 3H),
13
6.82–6.78 (m, 1H), 6.76–6.74 (m, 1H), 3.94–3.83 (m, 2H), 3.35 (s, 2H); C{1H}
NMR (100 MHz, CDCl3) δ 146.5, 143.7, 140.0, 139.5, 134.3, 131.6, 131.0, 130.3,
129.5, 129.2, 128.6, 126.5, 124.6, 118.9, 118.7, 115.7, 110.8, 39.4; HRMS (m/z) [M +
H]+ calcd for C20H17N2 285.1386, found 285.1389.
2'-Amino-6-benzyl-[1,1'-biphenyl]-2-carbonitrile (1af). EtOAc/PE (eluent) 20:80;
1
517 mg, 91% yield; white solid, mp 95–96 °C; H NMR (400 MHz, CDCl3) δ 7.64
(dd, J = 7.6, 1.2 Hz, 1H), 7.47 (dd, J = 7.6, 1.2 Hz, 1H), 7.39 (t, J = 8.0 Hz, 1H),
7.26–7.16 (m, 4H), 6.96–6.93 (m, 3H), 6.84 (td, J = 7.2, 1.2 Hz, 1H), 6.78 (dd, J = 8.0,
13
0.8 Hz, 1H), 3.89–3.79 (m, 2H), 3.33 (s, 2H); C{1H} NMR (100 MHz, CDCl3) δ
143.7, 142.6, 142.2, 139.7, 134.5, 131.5, 130.2, 130.1, 129.2, 128.5, 126.4, 122.7,

Organic & Biomolecular Chemistry
Page 20 of 36
View Article Online
119.0, 118.1, 116.0, 114.6, 39.1; HRMS (m/z) [M + H]+ calcd for C20H17N2 2D8O5I.:1103.180639,/D0OB00433B
found 285.1389.
(E)-2-(1,3-Diphenylprop-1-en-1-yl)aniline (1ag).21 The E configuration was
assigned on the basis of NOE correlations between protons of CH2 and NH2 groups.
EtOAc/PE (eluent) 2:98; 477 mg, 56% yield; yellow oil; 1H NMR (400 MHz, CDCl3)
δ 7.33–7.16 (m, 11H, overlapped with the peak of chloroform), 7.06 (dd, J = 7.6, 1.6
Hz, 1H), 6.82 (td, J = 7.6, 1.2 Hz, 1H), 6.78–6.76 (m, 1H), 6.45 (t, J = 7.6 Hz, 1H),
13
3.59 (s, 2H), 3.40 (d, J = 7.2 Hz, 2H); C{1H} NMR (100 MHz, CDCl3) δ 144.3,
140.8, 140.4, 138.7, 131.0, 129.9, 128.7, 128.64, 128.61, 128.59, 127.5, 126.5, 126.1,
124.8, 118.5, 115.6, 36.2; HRMS (m/z) [M + H]+ calcd for C21H20N 286.1590, found
286.1592.
5. General Procedure for the Synthesis of Products 2. A mixture of I2 (1.1 mmol)
and Cs2CO3 (2.5 mmol) in HMPA (5 mL) was stirred at room temperature for 10 min,
and then treated with substrate 1 (0.5 mmol). The reaction was heated to 80 °C until
TLC indicated the disappearance of the substrate. After cooling to room temperature,
it was quenched with 5% Na2S2O3 (5 mL), followed by the addition of brine (10 mL),
and extracted with EtOAc (3 x 15 mL). The combined organic layer was washed with
H2O (20 mL) and brine (20 mL) in sequence, dried over anhydrous Na2SO4,
concentrated, and purified through silica gel column chromatography to give the
product 2.
6-(p-Tolyl)phenanthridine (2a). 2 h; CH2Cl2/PE (eluent) 33:67; 108 mg, 80% yield;
white solid, mp 80–82 °C (lit11d 80–82 °C); 1H NMR (400 MHz, CDCl3) δ 8.68 (d, J
= 8.4 Hz, 1H), 8.61–8.58 (m, 1H), 8.24 (dd, J = 8.4, 1.2 Hz, 1H), 8.14–8.12 (m, 1H),
7.83 (ddd, J = 8.4, 6.8, 1.2 Hz, 1H), 7.74 (ddd, J = 8.4, 7.2, 1.6 Hz, 1H), 7.69–7.63 (m,
13
3H), 7.60 (ddd, J = 8.4, 7.2, 1.2 Hz, 1H), 7.38–7.35 (m, 2H), 2.47 (s, 3H); C{1H}

Page 21 of 36
Organic & Biomolecular Chemistry
View Article Online
DOI: 10.1039/D0OB00433B
NMR (100 MHz, CDCl3) δ 161.4, 144.0, 138.7, 137.0, 133.5, 130.6, 130.4, 129.8,
129.2, 129.1, 128.9, 127.2, 126.9, 125.4, 123.8, 122.3, 122.0, 21.5; HRMS (m/z) [M +
H]+ calcd for C20H16N 270.1277, found 270.1279.
2-Methyl-6-(p-tolyl)phenanthridine (2b). 2 h; EtOAc/PE (eluent) 4:96; 121 mg, 85%
yield; white solid, mp 144–146 °C; 1H NMR (400 MHz, CDCl3) δ 8.66 (d, J = 8.0 Hz,
1H), 8.38–8.37 (m, 1H), 8.13–8.10 (m, 2H), 7.81 (ddd, J = 8.4, 7.2, 1.2 Hz, 1H),
7.64–7.61 (m, 2H), 7.60–7.55 (m, 2H), 7.37–7.35 (m, 2H), 2.64 (s, 3H), 2.47 (s, 3H);
13C{1H} NMR (100 MHz, CDCl3) δ 160.5, 142.3, 138.5, 137.1, 136.8, 133.3, 130.6,
130.4, 130.1, 129.8, 129.2, 129.0, 127.0, 125.5, 123.6, 122.2, 121.6, 22.2, 21.5;
HRMS (m/z) [M + H]+ calcd for C21H18N 284.1434, found 284.1437.
2-Fluoro-6-(p-tolyl)phenanthridine (2c). 1 h; EtOAc/PE (eluent) 4:96; 115 mg, 81%
yield; white solid, mp 134–135 °C; 1H NMR (400 MHz, CDCl3) δ 8.53 (d, J = 8.4 Hz,
1H), 8.22–8.13 (m, 3H), 7.85–7.81 (m, 1H), 7.65–7.61 (m, 3H), 7.47 (td, J = 8.8, 2.8
13
Hz, 1H), 7.36 (d, J = 8.0 Hz, 2H), 2.47 (s, 3H); C{1H} NMR (100 MHz, CDCl3) δ
161.3 (d, JC–F = 245.1 Hz), 160.7 (d, JC–F = 2.7 Hz), 140.8 (d, JC–F = 1.4 Hz), 138.8,
136.7, 133.0 (d, JC–F = 4.2 Hz), 132.6 (d, JC–F = 9.0 Hz), 130.6, 129.8, 129.3, 129.1,
127.8, 125.4, 125.1 (d, JC–F = 9.0 Hz), 122.4, 117.8 (d, JC–F = 24.0 Hz), 107.0 (d, JC–F
= 23.0 Hz), 21.5; HRMS (m/z) [M + H]+ calcd for C20H15FN 288.1183, found
288.1186.
2-Chloro-6-(p-tolyl)phenanthridine (2d). 3 h; EtOAc/PE (eluent) 4:96; 137 mg, 90%
yield; white solid, mp 171–173 °C; 1H NMR (400 MHz, CDCl3) δ 8.59 (d, J = 8.0 Hz,
1H), 8.55 (s, 1H), 8.15 (d, J = 8.8 Hz, 2H), 7.86 (t, J = 8.0 Hz, 1H), 7.69–7.62 (m,
4H), 7.37 (d, J = 8.0 Hz, 2H), 2.48 (s, 3H); 13C{1H} NMR (100 MHz, CDCl3) δ 161.7,
142.4, 139.0, 136.7, 132.8, 132.6, 131.9, 130.9, 129.8, 129.4, 129.3, 129.2, 127.9,

Organic & Biomolecular Chemistry
Page 22 of 36
View Article Online
DOI: 10.1039/D0OB00433B
125.6, 124.9, 122.3, 121.7, 21.6; HRMS (m/z) [M + H]+ calcd for C20H15ClN
304.0888, found 304.0890.
2-Bromo-6-(p-tolyl)phenanthridine (2e). 4 h; EtOAc/PE (eluent) 10:90; 151 mg, 87%
1
yield; white solid, mp 185–187 °C; H NMR (400 MHz, CDCl3) δ 8.72 (s, 1H), 8.59
(d, J = 8.0 Hz, 1H), 8.15 (d, J = 8.4 Hz, 1H), 8.08 (d, J = 8.8 Hz, 1H), 7.86 (t, J = 8.0
Hz, 1H), 7.81 (dd, J = 8.8, 1.6 Hz, 1H), 7.66–7.62 (m, 3H), 7.37 (d, J = 7.6 Hz, 2H),
13
2.48 (s, 3H); C{1H} NMR (100 MHz, CDCl3) δ 161.8, 142.7, 139.0, 136.7, 132.5,
132.12, 132.09, 130.9, 129.8, 129.3, 129.2, 127.9, 125.5, 125.3, 124.9, 122.3, 120.9,
21.6; HRMS (m/z) [M + H]+ calcd for C20H15BrN 348.0382, found 348.0383.
6-(p-Tolyl)-2-(trifluoromethyl)phenanthridine (2f). 3 h; EtOAc/PE (eluent) 5:95;
161 mg, 95% yield (0.5 mmol scale); 1.58 g, 93% (5 mmol scale); white solid, mp
1
255–257 °C; H NMR (400 MHz, CDCl3) δ 8.88 (s, 1H), 8.71 (d, J = 8.0 Hz, 1H),
8.32 (d, J = 8.4 Hz, 1H), 8.19 (d, J = 8.4 Hz, 1H), 7.95–7.89 (m, 2H), 7.70–7.64 (m,
13
3H), 7.39 (d, J = 8.0 Hz, 2H), 2.49 (s, 3H); C NMR (100 MHz, CDCl3) δ 163.7,
145.5, 139.3, 136.5, 133.3, 131.31, 131.27, 129.8, 129.4, 129.3, 128.5, (q, JC–F = 32.2
Hz), 128.1, 125.7, 124.9 (q, JC–F = 3.3 Hz), 124.5 (q, JC–F = 270.6 Hz), 123.4, 122.4,
119.9 (q, JC–F = 4.3 Hz), 21.6; HRMS (m/z) [M + H]+ calcd for C21H15F3N 338.1151,
found 338.1153.
6-(p-Tolyl)phenanthridine-2-carbonitrile (2g). 2 h; EtOAc/PE (eluent) 5:95; 138
mg, 94% yield; white solid, mp 235–236 °C; 1H NMR (400 MHz, CDCl3) δ 8.93 (d, J
= 1.2 Hz, 1H), 8.65 (d, J = 8.4 Hz, 1H), 8.28 (d, J = 8.8 Hz, 1H), 8.21 (d, J = 8.0 Hz,
1H), 7.96–7.90 (m, 2H), 7.72 (t, J = 7.6 Hz, 1H), 7.65 (d, J = 8.0 Hz, 2H), 7.39 (d, J =
13
8.0 Hz, 2H), 2.49 (s, 3H); C{1H} NMR (100 MHz, CDCl3) δ 164.5, 145.7, 139.6,
136.2, 132.6, 131.7, 131.5, 130.5, 129.8, 129.5, 129.4, 128.5, 127.9, 125.7, 123.9,

Page 23 of 36
Organic & Biomolecular Chemistry
View Article Online
DOI: 10.1039/D0OB00433B
122.3, 119.3, 110.1, 21.6; HRMS (m/z) [M + H]+ calcd for C21H15N2 295.1230, found
295.1232.
2-Nitro-6-(p-tolyl)phenanthridine (2h). 3 h; EtOAc/CH2Cl2/PE (eluent) 1:1:98; 144
1
mg, 92% yield; Light yellow solid, mp 255–256 °C; H NMR (400 MHz, CDCl3) δ
9.49 (d, J = 2.4 Hz, 1H), 8.74 (d, J = 8.4 Hz, 1H), 8.50 (dd, J = 9.2, 2.4 Hz, 1H), 8.30
(d, J = 8.8 Hz, 1H), 8.23 (d, J = 8.4 Hz, 1H), 7.96 (t, J = 8.0 Hz, 1H), 7.73 (t, J = 8.0
13
Hz, 1H), 7.67 (d, J = 8.0 Hz, 2H), 7.40 (d, J = 8.0 Hz, 2H), 2.50 (s, 3H); C{1H}
NMR (100 MHz, CDCl3) δ 165.1, 147.0, 145.8, 139.7, 136.2, 133.5, 131.8, 131.7,
129.9, 129.7, 129.4, 128.7, 125.7, 123.6, 122.8, 122.6, 118.9, 21.6; HRMS (m/z) [M +
H]+ calcd for C20H15N2O2 315.1128, found 315.1131.
3-Chloro-6-(p-tolyl)phenanthridine (2i). 2 h; EtOAc/PE (eluent) 1:99; 122 mg, 80%
yield; white solid, mp 126–127 °C (lit11d 128–129 °C); 1H NMR (400 MHz, CDCl3) δ
8.63 (d, J = 8.0 Hz, 1H), 8.52 (d, J = 8.8 Hz, 1H), 8.22 (d, J = 2.0 Hz, 1H), 8.16–8.14
(m, 1H), 7.86 (ddd, J = 8.4, 7.2, 1.2 Hz, 1H), 7.65–7.61 (m, 4H), 7.38 (d, J = 7.6 Hz,
13
2H), 2.48 (s, 3H); C{1H} NMR (100 MHz, CDCl3) δ 162.6, 144.7, 139.0, 136.7,
134.5, 133.2, 131.0, 129.8, 129.6, 129.3, 127.5, 127.4, 125.4, 123.5, 122.3, 122.2,
21.6; HRMS (m/z) [M + H]+ calcd for C20H15ClN 304.0888, found 304.0889.
4-Chloro-6-(p-tolyl)phenanthridine (2j). 2 h; EtOAc/PE (eluent) 0.5:99.5; 132 mg,
1
87% yield; white solid, mp 159–160 °C; H NMR (400 MHz, CDCl3) δ 8.66 (d, J =
8.4 Hz, 1H), 8.51 (dd, J = 8.4, 1.2 Hz, 1H), 8.24 (dd, J = 8.4, 0.8 Hz, 1H), 7.88–7.83
(m, 2H), 7.75–7.73 (m, 2H), 7.65 (ddd, J = 8.4, 7.2, 1.2 Hz, 1H), 7.56 (t, J = 8.4 Hz,
1H), 7.37 (d, J = 7.6 Hz, 2H), 2.48 (s, 3H); 13C{1H} NMR (100 MHz, CDCl3) δ 161.6,
140.3, 139.1, 136.7, 134.7, 133.5, 130.8, 130.4, 129.3, 129.21, 129.18, 127.7, 126.6,
125.4, 125.3, 122.6, 120.9, 21.6; HRMS (m/z) [M + H]+ calcd for C20H15ClN
304.0888, found 304.0889.

Organic & Biomolecular Chemistry
Page 24 of 36
View Article Online
2,4-Dichloro-6-(p-tolyl)phenanthridine (2k). 4 h; CH2Cl2/PE (eluent) 1:99;D1O5I:210m.10g39,/D0OB00433B
1
90% yield; white solid, mp 246–247 °C; H NMR (400 MHz, CDCl3) δ 8.58 (d, J =
8.0 Hz, 1H), 8.47 (d, J = 2.0 Hz, 1H), 8.27–8.24 (m, 1H), 7.88 (ddd, J = 8.4, 6.8, 1.6
Hz, 1H), 7.83 (d, J = 2.4 Hz, 1H), 7.74–7.67 (m, 3H), 7.39–7.37 (m, 2H), 2.48 (s, 3H);
13C{1H} NMR (100 MHz, CDCl3) δ 161.8, 139.4, 139.0, 136.5, 135.8, 132.6, 132.0,
131.1, 130.4, 129.4, 129.32, 129.26, 128.4, 125.9, 125.5, 122.7, 120.7, 21.6; HRMS
(m/z) [M + H]+ calcd for C20H14Cl2N 338.0498, found 338.0501.
6-Phenylphenanthridine (2l). 2 h; CH2Cl2/PE (eluent) 20:80; 104 mg, 81% yield;
white solid, mp 100–102 °C (lit11d 99–101 °C); 1H NMR (400 MHz, CDCl3) δ 8.70 (d,
J = 8.4 Hz, 1H), 8.62 (dd, J = 8.4, 1.2 Hz, 1H), 8.25 (dd, J = 8.0, 1.2 Hz, 1H), 8.10
(dd, J = 8.4, 0.8 Hz, 1H), 7.85 (ddd, J = 8.4, 7.2, 1.6 Hz, 1H), 7.78–7.73 (m, 3H), 7.69
(ddd, J = 8.4, 7.2, 1.2 Hz, 1H), 7.63–7.52 (m, 4H); 13C{1H} NMR (100 MHz, CDCl3)
δ 161.4, 143.9, 139.9, 133.5, 130.7, 130.5, 129.8, 129.04, 128.97, 128.8, 128.6, 127.2,
127.1, 125.4, 123.9, 122.3, 122.1; HRMS (m/z) [M + H]+ calcd for C19H14N 256.1121,
found 256.1123.
6-(4-Methoxyphenyl)phenanthridine (2m). 2 h; CH2Cl2/PE (eluent) 67:33; 119 mg,
1
83% yield; white solid, mp 147–148 °C (lit11d 144–146 °C); H NMR (400 MHz,
CDCl3) δ 8.69 (d, J = 8.4 Hz, 1H), 8.60 (d, J = 8.0 Hz, 1H), 8.23 (dd, J = 8.0, 0.8 Hz,
1H), 8.16 (d, J = 8.0 Hz, 1H), 7.87–7.83 (m, 1H), 7.77–7.60 (m, 5H), 7.10–7.08 (m,
13
2H), 3.91 (s, 3H); C{1H} NMR (100 MHz, CDCl3) δ 161.0, 160.2, 143.9, 133.6,
132.3, 131.3, 130.6, 130.3, 129.1, 128.9, 127.2, 126.9, 125.4, 123.7, 122.3, 122.0,
114.0, 55.6; HRMS (m/z) [M + H]+ calcd for C20H16NO 286.1226, found 286.1228.
6-(4-Fluorophenyl)phenanthridine (2n).13b 1 h; CH2Cl2/PE (eluent) 33:67; 97 mg,
1
71% yield; white solid, mp 130–131 °C; H NMR (400 MHz, CDCl3) δ 8.70 (d, J =
8.4 Hz, 1H), 8.61 (dd, J = 8.4, 1.6 Hz, 1H), 8.23 (dd, J = 8.4, 1.2 Hz, 1H), 8.07 (dd, J

Page 25 of 36
Organic & Biomolecular Chemistry
View Article Online
DOI: 10.1039/D0OB00433B
= 8.4, 0.4 Hz, 1H), 7.86 (ddd, J = 8.4, 7.2, 1.2 Hz, 1H), 7.78–7.67 (m, 4H), 7.63 (ddd,
J = 8.4, 7.2, 1.2 Hz, 1H), 7.29–7.23 (m, 2H, overlapped with the peak of chloroform);
13C{1H} NMR (100 MHz, CDCl3) δ 163.3 (d, JC–F = 246.5 Hz), 160.3, 143.8, 135.9 (d,
JC–F = 3.3 Hz), 133.6, 131.7 (d, JC–F = 8.3 Hz), 130.8, 130.4, 129.1, 128.7, 127.4,
127.2, 125.2, 123.8, 122.4, 122.1, 115.6 (d, JC–F = 21.5 Hz); HRMS (m/z) [M + H]+
calcd for C19H13FN 274.1027, found 274.1028.
6-(4-Chlorophenyl)phenanthridine (2o).11d 2 h; EtOAc/PE (eluent) 5:95; 119 mg,
1
82% yield; white solid, mp 159–161 °C; H NMR (400 MHz, CDCl3) δ 8.70 (d, J =
8.0 Hz, 1H), 8.61 (d, J = 8.0 Hz, 1H), 8.22 (d, J = 8.4 Hz, 1H), 8.06 (d, J = 8.0 Hz,
1H), 7.86 (t, J = 7.6 Hz, 1H), 7.76 (t, J = 7.6 Hz, 1H), 7.71–7.68 (m, 3H), 7.62 (t, J =
13
7.6 Hz, 1H), 7.54 (d, J = 8.0 Hz, 2H); C{1H} NMR (100 MHz, CDCl3) δ 160.1,
143.9, 138.3, 135.0, 133.6, 131.3, 130.8, 130.5, 129.1, 128.8, 128.6, 127.4, 127.3,
125.1, 123.9, 122.5, 122.1; HRMS (m/z) [M + H]+ calcd for C19H13ClN 290.0731,
found 290.0730.
6-(4-(Trifluoromethyl)phenyl)phenanthridine (2p). 2 h; EtOAc/PE (eluent) 1:99;
1
133 mg, 82% yield; white solid, mp 173–175 °C (lit8d 171–173 °C); H NMR (400
MHz, CDCl3) δ 8.71 (d, J = 8.0 Hz, 1H), 8.62 (d, J = 8.4 Hz, 1H), 8.23 (dd, J = 8.4,
1.2 Hz, 1H), 8.01 (dd, J = 8.4, 0.8 Hz, 1H), 7.89–7.82 (m, 5H), 7.77 (ddd, J = 8.4, 7.2,
13
1.6 Hz, 1H), 7.73–7.69 (m, 1H), 7.63 (ddd, J = 8.4, 7.2, 1.2 Hz, 1H); C{1H} NMR
(100 MHz, CDCl3) δ 159.8, 143.8, 143.5, 133.6, 131.0, 130.9 (q, JC‒F = 32.3 Hz),
130.5, 130.3, 129.2, 128.4, 127.5, 125.6 (q, JC‒F = 3.8 Hz), 124.9, 124.3 (q, JC‒F
=
270.5 Hz), 124.0, 122.5, 122.1; HRMS (m/z) [M + H]+ calcd for C20H13F3N 324.0995,
found 324.0996.
4-(Phenanthridin-6-yl)benzonitrile (2q). 2 h; EtOAc/PE (eluent) 9:91; 120 mg, 86%
yield; white solid, mp 176–177 °C (lit8d 179–181 °C); 1H NMR (400 MHz, CDCl3) δ

Organic & Biomolecular Chemistry
Page 26 of 36
View Article Online
8.74 (d, J = 8.4 Hz, 1H), 8.64 (dd, J = 8.0, 0.8 Hz, 1H), 8.23 (dd, J = 8.0, 1.2 DHOzI:,101.1H03)9,/D0OB00433B
7.98 (d, J = 8.4 Hz, 1H), 7.92–7.87 (m, 5H), 7.81–7.77 (m, 1H), 7.75–7.71 (m, 1H),
7.65 (ddd, J = 8.4, 7.2, 1.2 Hz, 1H); 13C{1H} NMR (100 MHz, CDCl3) δ 159.2, 144.4,
143.7, 133.7, 132.4, 131.1, 130.7, 130.5, 129.3, 128.1, 127.7, 127.6, 124.7, 124.0,
122.7, 122.2, 118.8, 112.7; HRMS (m/z) [M + H]+ calcd for C20H13N2 281.1073,
found 281.1074.
6-(4-Nitrophenyl)phenanthridine (2r). 2 h; EtOAc/PE (eluent) 17:83; 129 mg, 86%
1
yield; light yellow solid, mp 192–193 °C (lit22 192–193 °C); H NMR (400 MHz,
CDCl3) δ 8.75 (d, J = 8.4 Hz, 1H), 8.65 (d, J = 8.0 Hz, 1H), 8.43 (d, J = 8.8 Hz, 2H),
8.25–8.23(m, 1H), 8.00–7.89 (m, 4H), 7.82–7.73 (m, 2H), 7.66 (t, J = 8.0 Hz, 1H);
13C{1H} NMR (100 MHz, CDCl3) δ 158.8, 148.1, 146.2, 143.7, 133.6, 131.2, 131.0,
130.5, 129.3, 128.0, 127.8, 127.7, 124.7, 124.0, 123.8, 122.7, 122.2; HRMS (m/z) [M
+ H]+ calcd for C19H13N2O2 301.0972, found 301.0973.
6-(m-Tolyl)phenanthridine (2s).9e 2 h; CH2Cl2/PE (eluent) 33:67; 107 mg, 79%
yield; colorless oil; 1H NMR (400 MHz, CDCl3) δ 8.70 (d, J = 8.4 Hz, 1H), 8.62 (dd,
J = 8.0, 1.6 Hz, 1H), 8.26–8.24 (m, 1H), 8.12–8.10 (m, 1H), 7.85 (ddd, J = 8.4, 6.8,
1.6 Hz, 1H), 7.76 (ddd, J = 8.4, 6.8, 1.6 Hz, 1H), 7.69 (ddd, J = 8.4, 7.2, 1.6 Hz, 1H),
7.61 (ddd, J = 8.4, 7.2, 1.2 Hz, 1H), 7.56 (m, 1H), 7.52–7.50 (m, 1H), 7.44 (t, J = 7.6
Hz, 1H), 7.35–7.33 (m, 1H), 2.48 (s, 3H); 13C{1H} NMR (100 MHz, CDCl3) δ 161.6,
143.9, 139.8, 138.4, 133.5, 130.6, 130.5, 130.4, 129.6, 129.1, 128.9, 128.3, 127.2,
126.99, 126.96, 125.4, 123.8, 122.3, 122.1, 21.7; HRMS (m/z) [M + H]+ calcd for
C20H16N 270.1277, found 270.1279.
6-(o-Tolyl)phenanthridine (2t).11a 2 h; EtOAc/PE (eluent) 5:95; 101 mg, 75% yield;
colorless oil; 1H NMR (400 MHz, CDCl3) δ 8.71 (d, J = 8.4 Hz, 1H), 8.65 (dd, J = 8.0,
1.2 Hz, 1H), 8.25 (dd, J = 8.0, 1.2 Hz, 1H), 7.86 (ddd, J = 8.4, 6.8, 1.6 Hz, 1H),

Page 27 of 36
Organic & Biomolecular Chemistry
View Article Online
7.80‒7.76 (m, 1H), 7.74–7.70 (m, 2H), 7.58 (ddd, J = 8.4, 7.2, 1.2 Hz, 1H), 7D.4O4I:–107.1.03349/D0OB00433B
(m, 4H), 2.12 (s, 3H); 13C{1H} NMR (100 MHz, CDCl3) δ 162.1, 144.0, 139.3, 136.6,
133.2, 130.8, 130.51, 130.47, 129.4, 129.0, 128.8, 128.7, 127.5, 127.1, 126.0, 124.0,
122.3, 122.1, 20.0; HRMS (m/z) [M + H]+ calcd for C20H16N 270.1277, found
270.1279.
2-Methylphenanthridine (2u). 2 h; EtOAc/PE (eluent) 17:83; 34 mg, 35% yield;
white solid, mp 89–90 °C (lit23 90.1–91.1 °C); 1H NMR (400 MHz, CDCl3) δ 9.22 (s,
1H), 8.58 (d, J = 8.4 Hz, 1H), 8.34 (s, 1H), 8.08 (d, J = 8.0 Hz, 1H), 8.02 (dd, J = 8.0,
0.8 Hz, 1H), 7.83 (ddd, J = 8.4, 7.2, 1.6 Hz, 1H), 7.68 (ddd, J = 8.0, 7.2, 1.2 Hz, 1H),
13
7.58–7.55 (m, 1H), 2.63 (s, 3H); C{1H} NMR (100 MHz, CDCl3) δ 152.8, 142.9,
137.1, 132.4, 130.9, 130.5, 129.9, 128.8, 127.4, 126.6, 124.0, 121.9, 22.1; HRMS
(m/z) [M + H]+ calcd for C14H12N 194.0964, found 194.0965.
2-(Trifluoromethyl)phenanthridine (2v). 2 h; EtOAc/PE (eluent) 9:91; 47 mg, 38%
1
yield; white solid, mp 100–102 °C (lit11c 98–100 °C); H NMR (400 MHz, CDCl3) δ
9.38 (s, 1H), 8.86 (s, 1H), 8.65 (d, J = 8.4 Hz, 1H), 8.30 (d, J = 8.8 Hz, 1H), 8.11 (dd,
J = 8.0, 0.8 Hz, 1H), 7.97–7.93 (m, 2H), 7.80 (ddd, J = 8.0, 7.2, 0.8 Hz, 1H); 13C{1H}
NMR (100 MHz, CDCl3) δ 155.8, 146.0, 132.3, 131.9, 131.2, 129.2, 128.9 (d, JC‒F
=
32.2 Hz), 128.6, 126.7, 124.8 (q, JC‒F = 3.3 Hz), 124.4 (d, JC‒F = 270.6 Hz), 123.9,
122.1, 120.2 (q, JC‒F = 4.2 Hz); HRMS (m/z) [M + H]+ calcd for C14H9F3N 248.0682,
found 248.0683.
2,6-Dimethylphenanthridine (2w). 2 h; CH2Cl2/PE (eluent) 33:67; 38 mg, 37% yield;
light yellow solid, mp 65–67 °C (lit24 69–71 °C); 1H NMR (400 MHz, CDCl3) δ 8.61
(d, J = 8.4 Hz, 1H), 8.31 (s, 1H), 8.20 (dd, J = 8.4, 0.4 Hz, 1H), 7.99 (d, J = 8.4 Hz,
1H), 7.82 (ddd, J = 8.4, 7.2, 1.2 Hz, 1H), 7.68 (ddd, J = 8.4, 7.2, 1.2 Hz, 1H), 7.53 (dd,
13
J = 8.0, 1.6 Hz, 1H), 3.03 (s, 3H), 2.61 (s, 3H); C{1H} NMR (100 MHz, CDCl3) δ

Organic & Biomolecular Chemistry
Page 28 of 36
View Article Online
DOI: 10.1039/D0OB00433B
158.0, 142.1, 136.2, 132.5, 130.44, 130.39, 129.2, 127.3, 126.6, 126.1, 123.7, 122.4,
121.7, 23.5, 22.1; HRMS (m/z) [M + H]+ calcd for C15H14N 208.1121, found
208.1120.
8-Methoxy-6-phenylphenanthridine (2x). 2 h; CH2Cl2/PE (eluent) 33:67; 116 mg,
81% yield; light yellow solid, mp 128–129 °C (lit25 127–129 °C); 1H NMR (400 MHz,
CDCl3) δ 8.59 (d, J = 9.2 Hz, 1H), 8.51 (dd, J = 8.4, 1.6 Hz, 1H), 8.21 (dd, J = 8.0,
1.6 Hz, 1H), 7.76–7.74 (m, 2H), 7.71–7.62 (m, 2H), 7.58–7.46 (m, 5H), 3.81 (s, 3H);
13C{1H} NMR (100 MHz, CDCl3) δ 160.5, 158.5, 143.1, 140.0, 130.4, 129.6, 128.8,
128.6, 127.95, 127.91, 127.1, 126.6, 124.01, 123.95, 121.6, 121.1, 109.1, 55.5;
HRMS (m/z) [M + H]+ calcd for C20H16NO 286.1226, found 286.1227.
8-Fluoro-6-phenylphenanthridine (2y).25 1 h; CH2Cl2/PE (eluent) 34:66; 96 mg, 70%
yield; white solid, mp 134–135 °C; 1H NMR (400 MHz, CDCl3) δ 8.71–8.68 (m, 1H),
8.55 (d, J = 8.0 Hz, 1H), 8.26–8.24 (m, 1H), 7.78–7.68 (m, 5H), 7.63–7.54 (m, 4H).
13C{1H} NMR (100 MHz, CDCl3) δ 161.3 (d, JC–F = 246.4 Hz), 160.5 (d, JC–F = 3.8
Hz), 143.6 (d, JC–F = 1.3 Hz), 139.4, 130.6, 130.3 (d, JC–F = 1.9 Hz), 129.7, 129.1,
128.9, 128.8, 127.5, 126.7 (d, JC–F = 7.9 Hz), 124.9 (d, JC–F = 8.3 Hz), 123.4 (d, JC–F
=
0.8 Hz), 121.9, 119.9 (d, JC–F = 23.8 Hz), 113.4 (d, JC–F = 22.0 Hz); HRMS (m/z) [M
+ H]+ calcd for C19H13FN 274.1027, found 274.1026.
8-Chloro-6-phenylphenanthridine (2z). 2 h; CH2Cl2/PE (eluent) 33:67; 122 mg, 83%
yield; white solid, mp 123–125 °C (lit8d 120–122 °C); 1H NMR (400 MHz, CDCl3) δ
8.62 (dd, J = 8.8, 2.0 Hz, 1H), 8.55 (d, J = 8.0 Hz, 1H), 8.24 (dd, J = 8.4, 1.2 Hz, 1H),
8.07 (d, J = 2.0 Hz, 1H), 7.81–7.75 (m, 2H), 7.73–7.67 (m, 3H), 7.61–7.53 (m, 3H);
13C{1H} NMR (100 MHz, CDCl3) δ 160.3, 143.8, 139.2, 133.2, 132.0, 131.3, 130.6,
129.7, 129.3, 129.1, 128.8, 128.0, 127.5, 126.3, 124.2, 123.3, 122.0; HRMS (m/z) [M
+ H]+ calcd for C19H13ClN 290.0731, found 290.0733.

Page 29 of 36
Organic & Biomolecular Chemistry
View Article Online
DOI: 10.1039/D0OB00433B
6-Phenyl-8-(trifluoromethyl)phenanthridine (2aa).9b 2 h; CH2Cl2/PE (eluent) 33:67;
137 mg, 85% yield; white solid, mp 182–184 °C; 1H NMR (400 MHz, CDCl3) δ 8.81
(d, J = 8.8 Hz, 1H), 8.63 (d, J = 8.0 Hz, 1H), 8.41 (s, 1H), 8.28 (dd, J = 8.4, 1.2 Hz,
1H), 8.05 (dd, J = 8.8, 1.2 Hz, 1H), 7.86–7.82 (m, 1H), 7.76–7.73 (m, 3H), 7.63–7.55
(m, 3H); 13C{1H} NMR (100 MHz, CDCl3) δ 161.2, 144.6, 139.0, 135.8, 130.7, 130.2,
129.8, 129.4, 129.1 (q, JC–F = 32.8 Hz), 128.9, 127.7, 126.5 (q, JC–F = 3.2 Hz), 126.4
(q, JC–F = 4.3 Hz), 124.6, 124.1 (q, JC–F = 270.7 Hz), 123.5, 122.9, 122.4; HRMS (m/z)
[M + H]+ calcd for C20H13F3N 324.0995, found 324.0994.
6-Phenylphenanthridine-8-carbonitrile (2ab). 2 h; CH2Cl2/PE (eluent) 33:67; 116
mg, 83% yield; white solid, mp 193–195 °C; 1H NMR (400 MHz, CDCl3) δ 8.77 (d, J
= 8.4 Hz, 1H), 8.59 (dd, J = 8.4, 1.2 Hz, 1H), 8.46 (d, J = 1.6 Hz, 1H), 8.28 (dd, J =
8.4, 0.8 Hz, 1H), 8.01 (dd, J = 8.8, 1.6 Hz, 1H), 7.86 (ddd, J = 8.4, 7.2, 1.2 Hz, 1H),
13
7.75 (ddd, J = 8.4, 7.2, 1.2 Hz, 1H), 7.72–7.69 (m, 2H), 7.64–7.58 (m, 3H); C{1H}
NMR (100 MHz, CDCl3) δ 160.5, 144.8, 138.5, 136.1, 134.4, 131.8, 130.8, 129.8,
129.5, 128.9, 127.9, 124.8, 123.7, 122.6, 122.5, 118.7, 110.7; HRMS (m/z) [M + H]+
calcd for C20H13N2 281.1073, found 281.1074.
8-Nitro-6-phenylphenanthridine (2ac). 3 h; CH2Cl2/PE (eluent) 50:50; 126 mg, 84%
yield; yellow solid, mp 234–236 °C (lit8d 230–232 °C); 1H NMR (400 MHz, CDCl3) δ
9.03 (d, J = 2.4 Hz, 1H), 8.83 (d, J = 9.2 Hz, 1H), 8.65–8.62 (m, 2H), 8.30 (dd, J =
8.4, 0.8 Hz, 1H), 7.91‒7.87 (m, 1H), 7.80–7.74 (m, 3H), 7.65–7.58 (m, 3H); 13C{1H}
NMR (100 MHz, CDCl3) δ 161.4, 146.2, 145.1, 138.5, 137.6, 131.1, 130.9, 129.9,
129.7, 129.0, 128.1, 125.1, 124.7, 124.3, 124.2, 122.9, 122.5; HRMS (m/z) [M + H]+
calcd for C19H13N2O2 301.0972, found 301.0973.
6-Phenylphenanthridine-7-carbonitrile (2ad). 2 h; EtOAc/CH2Cl2/PE (eluent)
1
4:8:88; 116 mg, 83% yield; yellow solid, mp 196–198 °C; H NMR (400 MHz,