Pd(II)-catalyzed C(sp2)-H carbonylation of biaryl-2-amine: Synthesis of phenanthridinones

Article abstract of DOI:10.1016/j.tet.2013.05.025

A Pd(OAc)₂-catalyzed C(sp²)-H carbonylation protocol of arenes under carbon monoxide atmosphere has been developed. The scope of the carbonylation reaction is broad and tolerates a variety of useful functional groups. This reaction provides a novel and efficient method for the synthesis of biologically and pharmaceutically significant phenanthridinones.

Full text of DOI:10.1016/j.tet.2013.05.025

Tetrahedron 69 (2013) 6519e6526
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Tetrahedron
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Pd(II)-catalyzed C(sp2)eH carbonylation of biaryl-2-amine:
synthesis of phenanthridinones
,b,
Zunjun Liang a, Jitan Zhang a, Zhanxiang Liu a, Kai Wang a, Yuhong Zhang a
*
a Department of Chemistry, ZJU-NHU United R&D Center, Zhejiang University, Hangzhou 310027, China
b State Key Laboratory of Applied Organic Chemistry, Lanzhou University, Lanzhou 730000, China
a r t i c l e i n f o
a b s t r a c t
A Pd(OAc)2-catalyzed C(sp2)eH carbonylation protocol of arenes under carbon monoxide atmosphere
has been developed. The scope of the carbonylation reaction is broad and tolerates a variety of useful
functional groups. This reaction provides a novel and efficient method for the synthesis of biologically
and pharmaceutically significant phenanthridinones.
Article history:
Received 1 March 2013
Received in revised form 26 April 2013
Accepted 10 May 2013
Available online 16 May 2013
Ó 2013 Elsevier Ltd. All rights reserved.
Keywords:
Carbonylation
Phenanthridinone
Palladium-catalyzed
Free-amine
CeH activation
1. Introduction
Phenanthridinone possess a widespread occurrence as scaffold
in a wide variety of compounds with pharmacological properties
Carbonylation processes using carbon monoxide (CO) as a C1
building block have proven to be powerful tool to construct im-
portant scaffolds in natural products, pharmaceuticals, agrochem-
icals, and functional materials.1 Over the past few decades,
extensive efforts have been made to develop transition-metal-
catalyzed carbonylation of organic halides2 or organic pseudoha-
lides3 for the syntheses of carboxylic acids, esters, amides, and so
on. From atom-economic and environmentally benign points of
view, an attractive alternative to this approach is the development
of methods for direct CeH carbonylation reactions.4 In recent years,
carbonylation reactions of CeH bond have been extensively studied
under palladium, ruthenium, or rhodium catalysis assisted by
directing groups (DGs), such as pyridines,5 amides,6 pyridin-2-
ylmethylamine moieties,7 alkyl amines,8 hydroxyl groups,9 car-
boxylic acids,10 and so on.11 The combination of CeH carbonylation
with a subsequent intramolecular cyclization has allowed efficient
access to different heterocycles.12 Although great achievements
have been made, development of highly efficient and atom-
economic methods toward other significant targets would be also
highly desirable.
and biological activities.13 For example, PJ34 is a highly selective
PARP-1 inhibitors.14 There are a number of methods for the prep-
aration of 6(5H)-phenanthridinones15 and one of the conventional
approaches is through the treatment of fluorenone with NaN3 in
concentrated sulfuric acid, which leads to big environment prob-
lem.16 Based on the direct carbonylation strategy, Zhou and co-
workers developed Pd(OAc)2-catalyzed carbonylation of organo-
boron reagent with CO for the synthesis of phenanthridinones in
acetic acid (Fig. 1, Eq. 1).17 Later, Alper and Lu reported an efficient
method for the synthesis of phenanthridinone by intramolecular
carbonylation reaction of aryl iodide by palladium catalysis (Fig. 1,
Eq. 1).18 In 2007, Albert successfully applied selective carbonylation
of C(sp2)eH bond for the preparation of phenanthridinones by the
use of stoichiometric amount of palladium complex (Fig. 1, Eq. 2).19
However, these methods require the prefunctionalization of biaryl-
2 amine to their halide or metallic derivatives, which are not atom-
economic and environmentally benign processes. Our continuous
interest in transition-metal-catalyzed CeH bond activation
prompted us to explore the novel carbonylation of biphenylamine
for the economic preparation of phenanthridinones.20 Herein, we
report a direct carbonylation of C(sp2)eH for synthesis of phe-
nanthridinones with high efficiency under the mild reaction con-
ditions by the use of 3 mol % Pd(OAc)2 as catalyst and Cu(II)
trifluoroacetate as oxidant in trifluoroethanol (Fig. 1, Eq. 3).
* Corresponding author. Tel.: þ86 571 8795 2723; fax: þ86 571 8795 3244; e-mail
address: yhzhang@zju.edu.cn (Y. Zhang).
0040-4020/$ e see front matter Ó 2013 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tet.2013.05.025

6520
Z. Liang et al. / Tetrahedron 69 (2013) 6519e6526
entries 5 and 6). Palladium catalysts, including Pd(TFA)2 and
Pd(dba)2, also worked under the reaction conditions, but delivered
lower yields (Table 1, entries 7, 8). PdCl2 was almost inactive (Table
1, entry 9). The reaction did not proceed in the absence of palladium
catalysts or copper oxidants (Table 1, entries 10, 11). TFEtOH is the
best solvent for this transformation (Table 1, entries 12e16). Fur-
ther investigation21 of reaction temperature led us to establish the
optimized reaction conditions as follows: treatment of biphenyl-2-
amine with carbon monoxide (1 atm) in the presence of 3 mol % of
Pd(OAc)2 and Cu(TFA)2 (1.5 equiv) in trifluoroethanol at 70 ꢀC.
During the preparation of this paper, Zhu and co-workers reported
a similar aminocarbonylation of o-arylanilines by the use of
Pd(MeCN)2Cl2 as catalyst and Cu(TFA)2 as oxidant in the presence of
1.0 equiv of trifluoroacetic acid.22
Once the optimized reaction conditions had been established,
we explored the substrate scope of the direct carbonylation as
summarized in Table 2. Several structural modifications on the
Table 2
Carbonylation of biphenyl-2-amine derivativesa
Fig. 1. The synthesis of phenanthridinone.
2. Results and discussion
Initially, we chose biphenyl-2-amine 1a as a model substrate for
the studies of the direct carbonylation (Table 1). CO gas was de-
livered from a toy balloon at an atmospheric pressure. Gratifyingly,
we obtained the desired direct carbonylation product of C(sp2)eH
bond 2a in 6% yield by the use of 3 mol % Pd(OAc)2 and 1.5 equiv
Cu(OAc)2 at 70 ꢀC in trifluoroethanol (TFEtOH), while the aryl urea
2a0 was obtained in 25% yield (Table 1, entry 1). Further copper
oxidant screen led to a fruitful results: the yield of 2a increased to
24% by the use of CuSO4 (Table 1, entry 2), which was further
promoted to 54% by the use of Cu(OTf)2 (Table 1, entry 3). The best
result was obtained with Cu(II) trifluoroacetate (Cu(TFA)2), to give
2a in 86% isolated yield (Table 1, entry 4), and only small amounts of
urea byproduct 2a0 were observed. Other copper salts, such as
CuCO3$Cu(OH)2 and CuO, were found to be ineffective (Table 1,
Entry
1
Substrate 1
Product 2
Yield (%)b
86
2a
1a
2
3
81
84
1b
1c
2b
2c
Table 1
Optimization of reaction conditionsa
Entry
Catalyst
Oxidant
Solvent
Yield (%)b
4
5
6
57
63
55
1
2
3
4
5
6
7
8
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(TFA)2
Pd(dba)2
PdCl2
Cu(OAc)2
CuSO4
Cu(OTf)2
Cu(TFA)2
CuCO3$Cu(OH)2
CuO
Cu(TFA)2
Cu(TFA)2
Cu(TFA)2
/
Cu(TFA)2
Cu(TFA)2
Cu(TFA)2
Cu(TFA)2
Cu(TFA)2
Cu(TFA)2
TFEtOH
TFEtOH
TFEtOH
TFEtOH
TFEtOH
TFEtOH
TFEtOH
TFEtOH
TFEtOH
TFEtOH
TFEtOH
EtOH
6 (25)
23 (24)
54 (0)
86 (tr)
tr (19)
tr (21)
82 (tr)
52 (tr)
tr (tr)
1d
1e
1f
2d
2e
2f
9
10
11
12
13
14
15
16
Pd(OAc)2
/
0 (16)
0 (0)
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
20 (13)
14 (25)
37 (60)
62 (34)
50 (38)
DMSO
Toluene
DCE
THF
a
Reaction conditions: 1a (0.5 mmol), Pd catalyst (0.015 mmol, 3 mol %), oxidant
(0.75 mmol, the amount of Cu(TFA)2 based on anhydrate), solvent (1 mL), 70 ꢀC, 3 h.
b
Isolated yield based on biphenylamine 1a, the isolated yield of 2a0 is in the
parentheses.

Z. Liang et al. / Tetrahedron 69 (2013) 6519e6526
Table 2 (continued )
6521
Table 2 (continued )
Entry Substrate 1
Product 2
Yield (%)b
Entry
Substrate 1
Product 2
Yield (%)b
17
0
7
94
1q
2q
1g
1h
1i
2g
2h
2i
18
19
52
30
8
9
95
65
2r
2a
1r
1s
a
Reaction conditions: 1 (0.5 mmol), Pd(OAc)2 (0.015 mmol), Cu(TFA)2 (217 mg,
1.5 equiv), TFEtOH (1.0 mL), 70 ꢀC, 3 h.
b
Isolated yields based on biphenylamine 1.
biphenyl moiety were introduced, including methyl (Table 2, en-
tries 2, 7, and 10), methoxy (Table 2, entries 3 and 8), chloride.
(Table 2, entry 4), fluoride (Table 2, entry 5), and trifluoromethyl
(Table 2, entry 6). Noteworthy, the hydroxyl group was tolerated
under the reaction conditions and phenanthridinone 2i was ob-
tained in 65% yield (Table 2, entry 9). The electronic properties of
substituent groups have a significant effect on the reaction. It was
found that electron-rich biphenylamines (Table 2, entries 1e3, 7, 8,
and 10) exhibited better reactivity and gave higher yields than
those of the electron-deficient biphenylamines (Table 2, entries
4e6 and 11). It is noteworthy that the carbonylation reaction was
compatible with aromatic heterocycle to deliver the desired prod-
uct in moderate yield (Table 2, entry 12). 2-(Naphthalen-2-yl)ani-
line underwent the carbonylation reaction smoothly to give the
two isomers (2m:2m0, detected by 1H NMR) in 1:1 M ratio (Table 2,
entry 13). The steric hindrance played a role in this transformation.
The meta-position substituted substrates gave the major products
with the carbonylation at the less hindered ortho position (2n/2n0
and 2o/2o0; Table 2, entries 14 and 15). In addition, 20-methyl
substrate 1p showed a lower efficiency to give the product 2p in
57% yield (Table 2, entry 16). When 30,50-dimethyl substrate (1q)
was used, the desired product was not observed (Table 2, entry 17).
To our delight, N-aryl protected biphenyl-2-amine 1r tolerated the
carbonylation reaction conditions and generated the corresponding
N-phenyl 6(5H)-phenanthridinones 2r in moderate yield (Table 2,
entry 18). Surprisingly, only detosylation product was detected
when N-Ts substituted biphenyl-2-amine was subjected into the
reaction (Table 2, entry 19).23
In our experiments, traces of aryl ureas as byproducts were al-
ways observed. We performed the reaction of 1-(biphenyl-2-yl)-3-
(biphenyl-2-ylmethyl)urea 2a0 with carbon monoxide under stan-
dard reaction conditions (Scheme 1), and the desired phenan-
thridinone 2a was not found, illustrating that the product 2a was
not transformed from urea 2a0. To obtain more information about
the reaction mechanism, the palladacycle complex A was synthe-
sized by a method previously described in the literature.19,24
Treatment of the palladacycle complex A with carbon monoxide
in the absence of copper oxidant indeed afforded the desired
product 2a in 70% yield (Scheme 1). These results indicate that the
free-amine group works as the directing group and palladacycle
complex A may be the key reactive intermediate in this C(sp2)eH
activation process.
10
11
12
96
80
65
1j
2j
1k
1l
2k
2l
13
52
2m:2m’ = 1:1
2n:2n’ = 1:9
1m
1n
14
51
15
16
65
57
1o
1p
2o:2o’ = 2:5
2p

6522
Z. Liang et al. / Tetrahedron 69 (2013) 6519e6526
Scheme 2. The synthesis of PJ34.
Scheme 1. Mechanism studies on the carbonylation reaction.
the synthesis of biologically important phenanthridinones. De-
tailed mechanistic studies of this carbonylation reaction and ap-
plication of this catalysis to other substrates are ongoing in our
laboratory.
A plausible reaction mechanism has been proposed based on the
experiment results and the chemistry of CeH bond activation
(Fig. 2).25 First, free-amine assisted palladation of C(sp2)eH bond
occurs to form the key six-membered palladacycle intermediate A,
followed by the coordination of CO to give the intermediate B. The
subsequent insertion of CePd bond to CO leads to the formation of
intermediate C. A proton of amine (NH2) abstraction may take place
to give intermediate D, which undergoes the reductive elimination
to afford the final product 2a. The direct carbonylation of amine
(NH2) leads to the formation of the urea byproduct,26 which can be
suppressed in our experiment by the suitable choice of copper
oxidant. The formed Pd(0) is oxidized to Pd(II) by Cu(II) salts in the
system to fulfill the catalytic cycle.
4. Experimental section
4.1. General experimental methods
The materials and solvents were purchased from common com-
mercial sources and used without additional purification, if there is
no special version. NMR spectra were recorded for 1H NMR at
400MHzor500MHz, and13C NMRat100MHzor125MHzusingTMS
as internal standard. The following abbreviations were used to de-
scribe peak patterns were appropriate: singlet (s), doublet (d), triplet
(t), multiplet (m), doublet of doublet (dd), broad resonances (br).
Mass spectroscopy data of the products were collected on an HRMS-
APCI instrument or a low-resolution MS instrument using EI or ESI
ionization. Infrared spectra were recorded on an FTIR spectrometer.
4.2. General procedure for preparation of biphenylamine
derivatives29
A vessel with a magnetic stir bar was charged with Na2CO3
(2.120 g, 20 mmol, 2.0 equiv), Pd(OAc)2 (112 mg, 0.500 mmol, 5 mol
%), 2-bromoaniline (10 mmol,1.0 equiv), arylboronic acid (15 mmol,
1.5 equiv), distilled water (35 mL), and acetone (30 mL). Then the
mixture was stirred for 12 h at 35 ꢀC. Afterward the resulting so-
lution was filtered through a plug of Celite and the residue was
washed with ethyl acetate (30 mL). The filtrate was extracted three
times with diethyl ether (3ꢁ30 mL). The combined organic phases
were washed with brine (40 mL), dried over anhydrous sodium
sulfate, filtered, and concentrated. The residue was purified by flash
column chromatography with ethyl acetate (EA) and petroleum
ether (Pet) as eluent to afford the corresponding 2-amidobiphenyl
derivatives (1be1k, 1me1o, and 1q).
Fig. 2. A plausible mechanism.
4.2.1. 40-Methylbiphenyl-2-amine (1b). 1H NMR (400 MHz, CDCl3,
To illustrate the suitability of this methodology, the known
bioactive molecules Phenaglydon (2g)27 and PJ34 were synthesized
(Scheme 2). Phenaglydon (2g) can be obtained in 94% yield in one
step (Table 2). Phenanthridin-6(5H)-one (2a), precursor of PJ34, can
be obtained in 81% yield up to a 5 mmol level scale. The bioactive
phenanthridinone PJ34 was synthesized from 2a by consecutive
nitration, reduction, and amidation in 38% overall yield.28
TMS)
2H), 6.76e6.84 (m, 2H), 3.75 (br s, 2H), 2.39 (s, 3H); 13C NMR
(125 MHz, CDCl3, TMS) 143.5, 136.8, 136.5, 130.4, 129.5, 128.9,
d
7.34 (d, 2H, J¼8.0 Hz), 7.25 (t, 2H, J¼4.0 Hz), 7.11e7.16 (m,
d
128.3, 127.6, 118.6, 115.6, 21.2.
4.2.2. 40-Methoxybiphenyl-2-amine (1c). 1H NMR (400 MHz, CDCl3,
TMS)
2H), 6.80 (t, J¼7.0 Hz, 1H), 6.74 (d, J¼8.4 Hz, 1H), 3.83 (s, 3H), 3.60
(br s, 2H); 13C NMR (125 MHz, CDCl3, TMS)
158.8, 143.6, 131.8,
d
7.37 (d, J¼6.4 Hz, 2H), 7.09e7.12 (m, 2H), 6.97 (d, J¼6.8 Hz,
3. Conclusions
d
In summary, we have developed a novel protocol for free-amine
directed carbonylation of C(sp2)eH by palladium catalysis. Various
substituents of biphenylamines were tolerated under the standard
conditions. This transformation provided an efficient method for
130.5, 130.2, 128.2, 127.4, 118.7, 115.6, 114.3, 55.4.
4.2.3. 40-Chlorobiphenyl-2-amine (1d). 1H NMR (400 MHz, CDCl3,
TMS)
d
7.38e7.42 (m, 4H), 7.16 (t, 1H, J¼7.6 Hz), 7.08 (d, J¼7.2 Hz,

Z. Liang et al. / Tetrahedron 69 (2013) 6519e6526
6523
1H), 6.82 (t, J¼7.6 Hz, 1H), 6.75 (d, J¼7.6 Hz, 1H), 3.70 (br s, 2H); 13
C
130.3, 128.9, 126.3, 124.8 (d, J¼3.8 Hz), 118.8, 116.1 (d, J¼21.3 Hz),
115.8, 114.1 (d, J¼21.1 Hz).
NMR (125 MHz, CDCl3, TMS)
128.8, 126.3, 118.8, 115.7.
d 143.4, 137.9, 133.1, 130.5, 130.3, 129.0,
4.2.14. 30,50-Dimethylbiphenyl-2-amine (1q). 1H NMR (400 MHz,
4.2.4. 40-Fluorobiphenyl-2-amine (1e). 1H NMR (400 MHz, CDCl3,
CDCl3, TMS) d 7.19e7.21 (m, 2H), 7.15 (s, 2H), 7.07 (s, 1H), 6.89 (t,
TMS)
d
7.39e7.43 (m, 2H), 7.07e7.17 (m, 4H), 6.81 (t, J¼7.6 Hz, 1H),
J¼7.4 Hz, 1H), 6.82 (d, J¼8.0 Hz, 1H), 3.79 (br s, 2H), 2.45 (s, 6H); 13C
6.75 (d, J¼8.0 Hz, 1H), 3.64 (br s, 2H); 13C NMR (125 MHz, CDCl3,
NMR (100 MHz, CDCl3, TMS) d 143.5,139.4,138.3,130.3,128.7,128.2,
TMS)
d
162.1 (d, J¼244.8 Hz), 143.5, 135.4 (d, J¼3.6 Hz), 130.8 (d,
127.9, 126.8, 118.5, 115.5, 21.3.
J¼7.9 Hz), 130.5, 128.7, 126.7, 118.8, 115.8 (d, J¼11.3 Hz), 115.7.
4.2.15. 2-(Thiophen-2-yl)aniline (1l).30 To a dry round bottom flask,
equipped with a magnetic stir bar, thiophen-2-ylboronic acid
(7.5 mmol, 1.5 equiv), K2CO3 (2.760 g, 20 mmol, 4.0 equiv), and
PdCl2(PPh3)2 (344 mg, 0.500 mmol,10 mol %)were dissolved in 50mL
of DMF and 10 mL of H2O (DMF:H2O¼5:1). 2-Bromoaniline (860 mg,
5.0 mmol,1.0 equiv) was added, and the resulting mixture was heated
to 80 ꢀC and stirring for 24 h. After cooling to room temperature, the
reaction mixture was poured into water, and then the product was
extracted with CH2Cl2 (3ꢁ30 mL), washed with brine (40 mL), dried
over Na2SO4, and concentrated in vacuo. The residue was purified by
flash column chromatography on silica gel to give 2-(thiophen-2-yl)
4.2.5. 40-(Trifluoromethyl)biphenyl-2-amine (1f). 1H
NMR
(400 MHz, CDCl3, TMS)
d
7.69 (d, J¼8.0 Hz, 2H), 7.57 (d, J¼7.6 Hz,
2H), 7.18 (t, J¼7.6 Hz, 1H), 7.10 (d, J¼7.6 Hz, 1H), 6.84 (t, J¼7.6 Hz,
1H), 6.76 (d, J¼8.0 Hz, 1H), 3.73 (br s, 2H); 13C NMR (100 MHz,
CDCl3, TMS) d 143.4, 132.6, 130.4, 129.5, 129.3, 128.4, 126.1, 125.8 (q,
J¼3.8 Hz), 124.3 (q, J¼270.3 Hz), 118.9, 116.0.
4.2.6. 30-Methylbiphenyl-2-amine (1g). 1H NMR (400 MHz, CDCl3,
TMS)
6.81 (t, J¼7.6 Hz, 1H), 6.76 (d, J¼7.6 Hz, 1H), 3.68 (br s, 2H), 3.39 (s,
3H); 13C NMR (125 MHz, CDCl3, TMS)
143.0, 139.4, 138.5, 130.5,
d
7.33 (t, J¼7.2 Hz, 1H), 7.24e7.26 (m, 2H), 7.11e7.16 (m, 3H),
d
aniline (1l). 1H NMR (400 MHz, CDCl3, TMS)
d
7.33 (d, J¼5.2 Hz, 1H),
129.9, 128.7, 128.4, 128.1, 128.0, 126.1, 119.0, 115.9, 21.5.
7.27 (d, J¼7.6 Hz, 1H), 7.19 (d, J¼3.2 Hz, 1H), 7.10e7.16 (m, 2H),
6.75e6.80 (m, 2H), 3.94 (br s, 2H); 13C NMR (125 MHz, CDCl3, TMS)
4.2.7. 30-Methoxybiphenyl-2-amine (1h). 1H NMR (400 MHz, CDCl3,
d 144.1, 141.1, 131.0, 129.1, 127.6, 125.8, 125.3, 120.0, 118.6, 115.9.
TMS)
d
7.35 (t, J¼8.0 Hz, 1H), 7.12e7.17 (m, 2H), 7.03 (d, J¼7.2 Hz,
1H), 6.99 (s,1H), 6.89 (d, J¼8.0 Hz,1H), 6.81 (t, J¼7.6 Hz,1H), 6.76 (d,
4.2.16. 20-Methylbiphenyl-2-amine (1p).31 To a 100 mL round bot-
tom flask equipped with a magnetic stir bar, o-tolylboronic acid
(15 mmol, 1.5 equiv), K2CO3 (5.520 g, 40 mmol, 4.0 equiv), and
Pd(PPh3)4 (1154 mg, 1.000 mmol, 0.1 equiv) were dissolved in
45 mL toluene followed by the addition of 9 mL of H2O and 15 mL of
EtOH. Then 2-bromoaniline (10 mmol,1.0 equiv) was added and the
resulting mixture was stirred at 100 ꢀC for 16 h. After cooling to
room temperature, the biphasic solution was diluted with 50 mL of
saturated aqueous NH4Cl, and 30 mL of CH2Cl2. The aqueous phase
was extracted with diethyl ether (3ꢁ30 mL) and the combined
organic layers were washed with brine (40 mL), dried over anhy-
drous sodium sulfate, filtered, and concentrated. The residue was
purified by flash column chromatography with ethyl acetate (EA)
and petroleum ether (Pet) as eluent to afford the corresponding 20-
methylbiphenyl-2-amine (1p). 1H NMR (400 MHz, CDCl3, TMS)
J¼8.0 Hz, 1H), 3.83 (s, 3H), 3.66 (br s, 2H); 13C NMR (125 MHz,
CDCl3, TMS)
d 159.9, 143.1, 140.9, 130.4, 129.9, 128.6, 127.7, 121.4,
118.9, 115.8, 114.5, 113.0, 55.3.
4.2.8. 20-Aminobiphenyl-3-ol (1i). 1H NMR (400 MHz, CD3SOCD3,
TMS)
d
9.47 (br s,1H), 7.24 (t, J¼8.2 Hz,1H), 7.03 (t, J¼7.8 Hz,1H), 6.96
(d, J¼7.2 Hz, 1H), 6.81e6.82 (m, 2H), 6.73e6.74 (m, 2H), 6.62 (t,
J¼7.4 Hz, 1H), 4.68 (br s, 2H); 13C NMR (100 MHz, CD3SOCD3, TMS)
d
157.8, 145.1, 141.3, 130.1, 130.1, 128.4, 126.2, 119.6, 117.1, 115.7, 115.5,
114.1.
4.2.9. 5-Methylbiphenyl-2-amine (1j). 1H NMR (400 MHz, CDCl3,
TMS)
d 7.41e7.46 (m, 4H), 7.31e7.35 (m, 1H), 6.96e6.99 (m, 2H),
6.70 (d, J¼8.0 Hz, 1H), 3.54 (br s, 2H), 2.28 (s, 3H); 13C NMR
(125 MHz, CDCl3, TMS)
d
141.0, 139.7, 131.0, 129.1, 129.0, 128.8, 127.9,
d
7.16e7.28 (m, 5H), 7.01 (d, J¼7.2 Hz, 1H), 6.80 (t, J¼7.4 Hz,1H), 6.76
127.8, 127.1, 115.9, 20.5.
(d, J¼7.6 Hz, 1H), 3.44 (br s, 2H), 2.17 (s, 3H); 13C NMR (100 MHz,
CDCl3, TMS)
d 143.5, 138.6, 136.9, 130.2, 130.0, 130.0, 128.3, 127.7,
4.2.10. 5-Fluorobiphenyl-2-amine (1k). 1H NMR (400 MHz, CDCl3,
127.4, 126.1, 118.2, 115.0, 19.6.
TMS) 7.43e7.46 (m, 4H), 7.36e7.37 (m, 1H), 6.85e6.87 (m, 2H),
d
6.67e6.70 (m, 1H), 3.60 (br s, 2H); 13C NMR (100 MHz, CDCl3, TMS)
4.2.17. N-Phenyl-[1,10-biphenyl]-2-amine (1r). To a 50 mL round
bottom flask equipped with a magnetic stir bar, biphenyl-2-amine
1a (1.69 g, 10 mmol, 1.0 equiv), boronic acid (30 mmol, 3.0 equiv),
Pd(OAc)2 (112 g, 0.5 mmol, 0.05 equiv), Cu(OAc)2$H2O (1.99 g,
10 mmol, 1.0 equiv), and HOAc (20 mmol) were dissolved in 30 mL
of trifluoroethanol and the resulting mixture was stirred at 90 ꢀC
for 20 h. After cooling to room temperature, 50 mL of saturated
aqueous Na2CO3, and 30 mL of ethyl acetate were added and the
organic layer was collected. The aqueous phase was extracted with
ethyl acetate (3ꢁ20 mL). The combined organic phases were
washed with brine (40 mL), dried over anhydrous sodium sulfate,
filtered, and concentrated. The residue was purified by flash col-
umn chromatography with ethyl acetate (EA) and petroleum ether
(Pet) as eluent to afford the corresponding products 1r. 1H NMR
d
156.3 (d, J¼235.5 Hz),139.4, 138.4, 128.9, 128.8, 128.6 (d, J¼7.7 Hz),
127.5, 116.6 (d, J¼28.6 Hz), 116.5, 114.8 (d, J¼22.1 Hz).
4.2.11. 2-(Naphthalen-2-yl)aniline (1m). 1H NMR (400 MHz, CDCl3,
TMS)
7.18e7.22 (m, 2H), 6.87 (t, J¼7.6 Hz,1H), 6.81 (d, J¼8.0 Hz,1H), 3.88 (br
s,2H);13CNMR(125MHz,CDCl3,TMS)
143.7, 137.0,133.7, 132.5, 130.7,
d
7.85e7.93 (m, 4H), 7.59 (d, J¼8.8 Hz, 1H), 7.19e7.52 (m, 2H),
d
128.7, 128.5, 128.0, 127.9, 127.8, 127.6, 127.5, 126.4, 126.1, 118.8, 115.8.
4.2.12. 30-Chlorobiphenyl-2-amine (1n). 1H NMR (400 MHz, CDCl3,
TMS)
J¼7.6 Hz, 1H), 6.83 (t, J¼7.4 Hz, 1H), 6.76 (d, J¼8.0 Hz, 1H), 3.74 (br s,
2H); 13C NMR (125 MHz, CDCl3, TMS)
143.2, 141.3, 134.7, 130.4,
d
7.46 (s, 1H), 7.31e7.39 (m, 3H), 7.16 (t, J¼7.6 Hz, 1H), 7.09 (d,
d
130.1, 129.2, 129.0, 127.4, 127.3, 126.3, 118.9, 115.9.
(400 MHz, CDCl3, TMS) d 7.32e7.45 (m, 6H), 7.22e7.26 (m, 4H),
6.97e7.04 (m, 3H), 6.91 (t, J¼7.4 Hz, 1H), 5.41 (br s, 1H); 13C NMR
4.2.13. 30-Fluorobiphenyl-2-amine (1o). 1H NMR (400 MHz, CDCl3,
(100 MHz, CDCl3, TMS) d 143.4,140.2,139.1,131.6,131.0,129.4,129.4,
TMS)
d
7.36e7.42 (m, 1H), 7.22e7.24 (m, 1H), 7.14e7.18 (m, 2H), 7.10
129.0, 128.3, 127.5, 121.1, 121.1, 118.3, 117.5.
(d, J¼7.2 Hz, 1H), 7.01e7.05 (m, 1H), 6.82 (t, J¼7.74 Hz, 1H), 6.76 (d,
J¼7.6 Hz, 1H), 3.64 (br s, 2H); 13C NMR (125 MHz, CDCl3, TMS)
4.2.18. N-([1,10-Biphenyl]-2-yl)-4-methylbenzenesulfonamide (1s).
Methylbenzene-1-sulfonyl chloride (2.85 g, 15 mmol, 1.5 equiv) in
d
163.0 (d, J¼244.0 Hz), 143.3, 141.7 (d, J¼7.8 Hz),130.3 (d, J¼8.4 Hz),

6524
Z. Liang et al. / Tetrahedron 69 (2013) 6519e6526
20 mL of THF was added dropwise to the mixture of biphenyl-2-
amine 1a (1.69 g, 10 mmol, 1.0 equiv), Et3N (10 mL), and THF
(15 mL) at room temperature in 30 min. The result mixture was
heated to 60 ꢀC and stirred until completion of the reaction. After
cooling to room temperature, 50 mL of saturated aqueous Na2CO3,
and 30 mL of ethyl acetate were added and the organic layer was
collected. The aqueous phase was extracted with ethyl acetate
(3ꢁ20 mL). The combined organic phases were washed with brine
(40 mL), dried over anhydrous sodium sulfate, filtered, and con-
centrated. The residue was purified by flash column chromatogra-
phy with ethyl acetate (EA) and petroleum ether (Pet) as eluent to
afford the corresponding products 1s. 1H NMR (400 MHz, CDCl3,
124.5,122.6,122.2,121.6,117.7,115.9,108.7, 55.4; MS (EI) m/z (%) 225
(100) [Mþ], 210 (16), 195 (12), 182 (21), 154 (49), 127 (22); IR (KBr
plate, cmꢂ1
) n 3436, 3026, 2965, 2903, 1666, 1616, 1486, 1367, 1276,
1220, 832, 750.
4.3.5. 8-Chlorophenanthridin-6(5H)-one (2d).34 57% yield; 1H NMR
(500 MHz, CD3SOCD3, TMS)
d
11.86 (br s, 1H), 8.54 (d, J¼9.0 Hz, 1H),
8.38 (d, J¼8.0 Hz, 1H), 8.25 (d, J¼2.0 Hz, 1H), 7.89 (dd, J¼8.5, 2.3 Hz,
1H), 7.52 (t, J¼7.8 Hz, 1H), 7.39 (d, J¼8.0 Hz, 1H), 7.29 (t, J¼7.8 Hz,
1H); 13C NMR (125 MHz, CD3SOCD3, TMS)
d 159.7,136.4,133.1,132.7,
132.7, 130.0, 127.1, 126.5, 125.1, 123.4, 122.5, 116.8, 116.2; MS (EI) m/z
(%) 229 (100) [Mþ], 201 (7), 166 (35), 139 (27); IR (KBr plate, cmꢂ1
3436, 3026, 2889, 1675, 1606, 1468, 741.
) n
TMS)
d
7.71 (dd, J¼8.0, 0.8 Hz, 1H), 7.46 (d, J¼8.4 Hz, 2H), 7.30e7.36
(m, 4H), 7.18 (d, J¼8.4 Hz, 2H), 7.08e7.16 (m, 2H), 6.84e6.86 (m,
2H), 6.58 (s, 1H), 2.39 (s, 3H); 13C NMR (100 MHz, CDCl3, TMS)
4.3.6. 8-Fluorophenanthridin-6(5H)-one (2e).33 63% yield; 1H NMR
(500 MHz, CD3SOCD3, TMS) 11.85 (br s, 1H), 8.58e8.61 (m, 1H),
d
143.9, 137.2, 136.2, 134.0, 133.8, 130.3, 129.6, 129.1, 128.9, 128.7,
d
128.1, 127.2, 124.9, 121.4, 21.6.
8.37 (d, J¼8.0 Hz, 1H), 7.99 (dd, J¼9.5, 3.0 Hz,1H), 7.72e7.76 (m, 1H),
7.51 (t, J¼7.8 Hz,1H), 7.39 (d, J¼8.0 Hz,1H), 7.28 (t, J¼7.5 Hz,1H); 13C
4.3. General procedure for carbonylation of biphenylamines
NMR (125 MHz, CD3SOCD3, TMS)
d
161.5 (d, J¼244.6 Hz), 159.9 (d,
J¼3.1 Hz), 136.0, 131.0 (d, J¼2.0 Hz), 129.4, 127.6 (d, J¼7.6 Hz), 125.8
(d, J¼8.3 Hz), 123.2, 122.5, 120.9 (d, J¼23.4 Hz), 117.0, 116.2, 112.5 (d,
J¼21.6 Hz); MS (EI) m/z (%) 213 (100) [Mþ], 185 (33), 157 (26), 131
Pd(OAc)2 (3 mg, 0.015 mmol), Cu(TFA)2$xH2O (217 mg,
0.75 mmol), biphenylamine (0.5 mmol), and trifluoroethanol
(1.0 mL) was added to a three-necked flask equipped with a mag-
netic stirring bar and reflux condenser. Then a toy balloon filled
with carbon monoxide gas was connected to the flask. The mixture
was stirred for 3 h at 70 ꢀC. After cooled to room temperature, the
mixture was filtered through a plug of Celite, and the residue was
washed with ethyl acetate (2ꢁ20 mL). The filtrate was evaporated
in vacuo. The residue was purified by flash column chromatography
on silica gel with ethyl acetate (EA) and petroleum ether (Pet) as
eluent to afford the corresponding products.
(8); IR (KBr plate, cmꢂ1
1484, 1362, 817, 748.
) n 3436, 3179, 3033, 2899, 1685, 1677, 1619,
4.3.7. 8-(Trifluoromethyl)phenanthridin-6(5H)-one
yield; 1H NMR (500 MHz, CD3SOCD3, TMS)
11.97 (br s, 1H miss),
(2f).35 55%
d
8.73 (d, J¼8.5 Hz, 1H), 8.56 (s, 1H), 8.46 (d, J¼8.0 Hz, 1H), 8.15 (dd,
J¼8.5,1.3 Hz,1H), 7.59 (t, J¼7.5 Hz,1H), 7.41 (d, J¼8.0 Hz,1H), 7.32 (t,
J¼7.8 Hz, 1H); 13C NMR (125 MHz, CD3SOCD3, TMS)
d 159.9, 137.5,
137.2, 130.9, 128.6 (q, J¼3.5 Hz), 127.9 (q, J¼32.3 Hz), 125.8, 124.4 (q,
J¼4.3 Hz), 124.3, 124.0, 123.9 (q, J¼271.5 Hz), 122.6, 116.5, 116.4; MS
(EI) m/z (%) 263 (100) [Mþ], 235 (15), 166 (20), 155 (18),139 (17),127
4.3.1. Phenanthridin-6(5H)-one (2a).17 86% yield; 1H NMR
(500 MHz, CD3SOCD3, TMS)
d
11.71 (br s, 1H miss), 8.52 (d, J¼8.5 Hz,
(21); IR (KBr plate, cmꢂ1
) n 3436, 3166, 3030, 2900,1667,1623,1423,
1H), 8.40 (d, J¼7.5 Hz, 1H), 8.35 (dd, J¼8.0, 1.0 Hz,1H), 7.85e7.89 (m,
1319, 1271, 1148, 1124, 1104, 828, 751.
1H), 7.65e7.68 (m, 1H), 7.49e7.53 (m, 1H), 7.39e7.40 (m, 1H),
7.27e7.30 (m, 1H); 13C NMR (125 MHz, CD3SOCD3, TMS)
d
160.7,
4.3.8. 9-Methylphenanthridin-6(5H)-one (2g).32 94% yield; 1H NMR
136.4, 134.2, 132.8, 129.6, 127.9, 127.4, 125.6, 123.2, 122.6, 122.3,
(400 MHz, CD3SOCD3, TMS)
d
11.61 (br s, 1H), 8.37 (d, J¼8.4 Hz, 1H),
117.5, 116.0; MS (EI) m/z (%) 195 (100) [Mþ], 167 (41), 139 (34), 113
8.32 (s, 1H), 8.21 (d, J¼8.0 Hz, 1H), 7.45e7.50 (m, 2H), 7.35e7.37 (m,
(12); IR (KBr plate, cmꢂ1
1424, 1369, 749, 727.
) n 3468, 3166, 3047, 1663, 1631, 1609, 1470,
1H), 7.24e7.28 (m, 1H), 2.54 (s, 3H); 13C NMR (125 MHz, CD3SOCD3,
TMS)
d 160.8, 142.9, 136.7, 134.2, 129.4, 129.1, 127.4, 123.4, 123.1,
122.4, 122.1, 117.5, 116.0, 21.5; MS (EI) m/z (%) 209 (100) [Mþ], 180
4.3.2. 1,3-Di(biphenyl-2-yl)urea (2a0, new compound). White solid;
mp 189e190 ꢀC; 1H NMR (500 MHz, CDCl3, TMS)
(56), 152 (22); IR (KBr plate, cmꢂ1
1617, 1366, 751, 671.
) n 3438, 3036, 3007, 2917, 1672,
d
7.73 (d, J¼8.0 Hz,
2H), 7.30e7.35 (m, 6H), 7.23e7.26 (m, 2H), 7.19e7.21 (m, 6H),
7.12e7.141 (m, 2H), 6.38 (br s, 2H); 13C NMR (125 MHz, CDCl3, TMS)
4.3.9. 9-Methoxyphenanthridin-6(5H)-one (2h).33 95% yield; 1H
NMR (400 MHz, CD3SOCD3, TMS) 11.63 (br s, 1H), 8.39 (d,
d
153.3, 138.2, 134.7, 134.1, 130.3, 129.1, 128.9, 128.6, 127.7, 124.6,
d
122.9; HRMS (EI) calcd for C25H20N2O [Mþ] 364.1576; Found,
J¼8.5 Hz, 1H), 8.34 (d, J¼8.0 Hz, 1H), 8.14 (s, 1H), 7.68 (dd, J¼8.0,
1.0 Hz, 1H), 7.46 (t, J¼7.8 Hz, 1H), 7.36 (d, J¼8.0 Hz, 1H), 7.25 (t,
J¼7.5 Hz, 1H), 2.49 (s, 3H); 13C NMR (125 MHz, CD3SOCD3, TMS)
364.1579; MS (EI) m/z (%) 364 (19) [Mþ], 178 (26), 169 (100), 167
(78), 152 (21), 139 (16), 115 (10); IR (KBr plate, cmꢂ1
1622, 1566, 754, 743, 697.
) n 3255, 3058,
d
162.8, 160.6, 137.0, 136.4, 129.6, 129.5, 123.6, 121.9, 119.2, 117.4,
116.2, 116.0, 105.1, 55.8; MS (EI) m/z (%) 225 (100) [Mþ], 196 (8), 182
4.3.3. 8-Methylphenanthridin-6(5H)-one (2b).32 81% yield; 1H NMR
(500 MHz, CD3SOCD3, TMS)
(26), 154 (41), 127 (22); IR (KBr plate, cmꢂ1
) n
3451, 3140, 2880,
d
11.63 (br s, 1H), 8.39 (d, J¼8.5 Hz, 1H),
1659, 1608, 1508, 1459, 1428, 1362, 1235, 1221, 1031, 839, 744.
8.34 (d, J¼8.0 Hz,1H), 8.14 (s,1H), 7.68 (dd, J¼8.0,1.0 Hz,1H), 7.46 (t,
J¼7.8 Hz, 1H), 7.36 (d, J¼8.0 Hz, 1H), 7.25 (t, J¼7.5 Hz, 1H), 2.49 (s,
4.3.10. 9-Hydroxyphenanthridin-6(5H)-one (2i).36 65% yield; 1H
NMR (400 MHz, CD3SOCD3, TMS) d 11.41 (br s, 1H), 10.47 (br s, 1H),
3H); 13C NMR (125 MHz, CD3SOCD3, TMS)
d
160.8, 137.6, 136.2,
133.9, 131.8, 129.0, 127.2, 125.6, 122.9, 122.6, 122.2, 117.7, 116.0, 20.9;
8.16e8.19 (m, 2H), 7.69 (d, J¼2.4 Hz, 1H), 7.46 (t, J¼7.4 Hz, 1H), 7.33
MS (EI) m/z (%) 209 (100) [Mþ], 180 (32), 152 (18), 127 (14); IR (KBr
(d, J¼7.6 Hz, 1H), 7.23 (t, J¼7.6 Hz, 1H), 7.08 (dd, J¼8.8, 2.2 Hz, 1H);
plate, cmꢂ1
)
n
3435, 3022, 2890, 1680, 1619, 1486, 1359, 820, 746.
13C NMR (125 MHz, CD3SOCD3, TMS)
d 161.5, 160.7, 137.0, 136.3,
129.8, 129.4, 123.0, 121.9, 118.0, 117.4, 116.9, 116.0, 106.8; MS (EI) m/z
4.3.4. 8-Methoxyphenanthridin-6(5H)-one (2c).33 84% yield; 1H
(%) 211 (100) [Mþ], 182 (7), 154 (22), 127 (13); IR (KBr plate, cmꢂ1
3423, 3173, 1653, 1629, 1611, 1446, 1416, 1377, 1241, 749.
) n
NMR (500 MHz, CD3SOCD3, TMS)
d
11.72 (br s,1H), 8.43 (d, J¼9.0 Hz,
1H), 8.30 (d, J¼8.0 Hz, 1H), 7.78 (d, J¼3.0 Hz, 1H), 7.43e7.46 (m, 2H),
7.37 (d, J¼7.5 Hz, 1H), 7.23e7.26 (m, 1H), 3.93 (s, 3H); 13C NMR
4.3.11. 2-Methylphenanthridin-6(5H)-one (2j).37 96% yield; 1H NMR
(500 MHz, CD3SOCD3, TMS)
11.63 (br s, 1H), 8.49 (d, J¼8.0 Hz, 1H),
(125 MHz, CD3SOCD3, TMS)
d
160.5, 159.0, 135.5, 128.4, 127.6, 127.1,
d

Z. Liang et al. / Tetrahedron 69 (2013) 6519e6526
6525
8.34 (dd, J¼8.0, 0.5 Hz, 1H), 8.20 (s, 1H), 7.83e7.86 (m, 1H), 7.64 (t,
CD3SOCD3, TMS)
d
9.40 (br s, 2H), 7.59 (t, J¼4.2 Hz, 1H), 7.49 (d,
J¼7.3 Hz, 1H), 7.28e7.33 (m, 2H), 2.43 (s, 3H); 13C NMR (125 MHz,
J¼7.6 Hz, 1H), 7.43 (d, J¼7.6 Hz, 1H), 7.20e7.22 (m, 2H), 7.08e7.17
CD3SOCD3, TMS)
d
160.6, 134.4, 134.2, 132.6, 131.2, 130.5, 127.7,
(m, 3H), 1.81 (s, 3H); IR (KBr plate, cmꢂ1
1560, 1495, 1418, 1022, 751, 739.
) n 3436, 3234, 3048, 1578,
127.4, 125.7, 123.0, 122.5, 117.4, 116.0, 20.7; MS (EI) m/z (%) 209 (28)
[Mþ], 180 (15), 152 (32), 126 (21), 101 (38), 75 (69), 63 (64), 51 (91),
39 (100); IR (KBr plate, cmꢂ1
1561, 1370, 1153, 772, 650.
)
n
3436, 3164, 3018, 2869, 1659, 1609,
4.5. General procedure for synthesis of PJ34
4.5.1. Preparation of 5-H-phenanthridin-6-one (2a). The synthesis of
2a is according to the method of carbonylation reaction. 2a can be
obtained in 81% isolated yield (790 mg) from 1a (0.845 g, 5 mmol).
4.3.12. 2-Fluorophenanthridin-6(5H)-one (2k).37 80% yield; 1H
NMR (500 MHz, CD3SOCD3, TMS) 11.75 (br s, 1H), 8.52 (d,
d
J¼8.0 Hz, 1H), 8.35 (dd, J¼7.5, 0.5 Hz, 1H), 8.27 (dd, J¼10.0, 1.5 Hz,
1H), 7.86e7.89 (m, 1H), 7.70 (t, J¼7.5 Hz, 1H), 7.39e7.41 (m, 2H); 13C
4.5.2. 2-Nitrophenanthridin-6(5H)-one (3a).40 5-H-Phenanthridin-
6-one 2a (975 mg, 5.0 mmol) was dissolved in 10 mL nitric acid
with stirring for 12 h. A thick yellow precipitate formed. The mix-
ture was filtered through a plug of Celite and the residue was
washed with cold water (20 mL), ethyl ether (20 mL), dried under
vacuum at 50 ꢀC. The crude product 3a was obtained in 83% yield
(996 mg), which was used directly in the next step without further
purification.
NMR (125 MHz, CD3SOCD3, TMS)
d
160.5, 157.8 (d, J¼234.6 Hz),
133.5 (d, J¼2.0 Hz), 133.1, 132.8, 128.5, 127.5, 125.8, 123.2, 118.8 (d,
J¼7.9 Hz), 117.7 (d, J¼8.4 Hz), 117.1 (d, J¼23.6 Hz), 109.1 (d,
J¼24.4 Hz); MS (EI) m/z (%) 213 (100) [Mþ], 185 (38), 184 (37), 164
(7), 157 (24); IR (KBr plate, cmꢂ1
1507, 1369, 1269, 1151, 766.
) n 3436, 3035, 2878, 1686, 1664,
4.3.13. Thieno[3,2-c]quinolin-4(5H)-one (2l).37 65% yield; 1H NMR
(500 MHz, CD3SOCD3, TMS)
d
11.75 (br s, 1H), 7.84 (d, J¼8.0 Hz, 1H),
4.5.3. 2-Aminophenanthridin-6(5H)-one (4a).28 The crude product
3a was dissolved in DMF (20 mL), 10% NH4Cl (15 mL) was added,
followed by addition of iron powder (4.0 g). The mixture was stir-
ring at 100 ꢀC for 1 h. After cooled to room temperature, the mix-
ture was filtered, and the filtrate was extracted three times with
CHCl3 (3ꢁ30 mL). The combined organic layers were washed with
brine (40 mL), dried over anhydrous sodium sulfate, filtered, and
concentrated. The residue was purified by flash column chroma-
tography with ethyl acetate (EA) as eluent to afford 2-
aminophenanthridin-6(5H)-one (4a)13e (410 mg, 65%). 1H NMR
7.79 (d, J¼5.0 Hz, 1H), 7.60 (d, J¼5.5 Hz, 1H), 7.48e7.51 (m, 1H),
7.42e7.44 (m, 1H), 7.23e7.26 (m, 1H); 13C NMR (125 MHz,
CD3SOCD3, TMS)
d 158.1, 145.5, 136.2, 131.1, 129.3, 126.6, 125.2,
123.3, 122.4, 116.2, 116.1; MS (EI) m/z (%) 201 (100) [Mþ], 173 (14),
155 (9),127 (14); IR (KBr plate, cmꢂ1
1655, 1591, 1325, 745.
) n 3436, 3152, 3017, 2883,1664,
4.3.14. 9-Chlorophenanthridin-6(5H)-one
(400 MHz, CD3SOCD3, TMS)
(2n0).38 1H
11.79 (br s, 1H), 8.61 (d, J¼2.0 Hz, 1H),
NMR
d
8.45 (d, J¼8.0 Hz, 1H), 8.31 (d, J¼8.8 Hz, 1H), 7.68 (dd, J¼8.6, 1.8 Hz,
(400 MHz, CD3SOCD3, TMS)
d
11.36 (br s, 1H), 8.30 (d, J¼8.0 Hz, 1H),
1H), 7.53 (t, J¼7.4 Hz, 1H), 7.37 (d, J¼8.0 Hz, 1H), 7.27 (t, J¼7.8 Hz,
8.21 (d, J¼8.0 Hz, 1H), 7.81 (t, J¼7.6 Hz, 1H), 7.59 (t, J¼7.4 Hz, 1H),
7.47 (d, J¼1.2 Hz, 1H), 7.10 (d, J¼8.0 Hz, 1H), 6.82 (dd, J¼8.4, 1.4 Hz,
1H); 13C NMR (125 MHz, CD3SOCD3, TMS)
d 160.1, 138.2, 137.0, 136.1,
130.3, 129.7, 128.1, 124.4, 123.8, 122.4, 116.6, 116.2, 20.9; MS (EI) m/z
1H), 5.03 (br s, 2H); 13C NMR (125 MHz, CD3SOCD3, TMS)
d 160.5,
(%) 229 (100) [Mþ], 201 (9), 195 (23), 166 (41), 139 (32); IR (KBr
144.5, 134.7, 132.9, 128.2, 128.1, 127.9, 126.4, 122.6, 118.7, 118.3, 117.3,
plate, cmꢂ1
)
n
3436, 3025, 2872, 1675, 1606, 1431, 1360, 834, 748.
106.4; MS (EI) m/z (%) 210 (100) [Mþ], 181 (27), 154 (15), 127 (14); IR
(KBr plate, cmꢂ1
) n 3450, 3359, 3001, 1652, 1606, 1512, 1470, 1420,
4.3.15. 10-Methylphenanthridin-6(5H)-one (2p).37 57% yield; 1H
1378, 1156, 846, 776.
NMR (500 MHz, CD3SOCD3, TMS)
d
11.71 (br s,1H), 8.45 (d, J¼8.5 Hz,
1H), 8.33 (d, J¼7.5 Hz, 1H), 7.72 (d, J¼7.5 Hz, 1H), 7.54 (t, J¼7.8 Hz,
1H), 7.50 (t, J¼7.5 Hz, 1H), 7.42 (d, J¼8.0 Hz, 1H), 7.27 (t, J¼7.5 Hz,
4.5.4. 2-(Dimethylamino)-N-(6-oxo-5,6-dihydrophenanthridin-2-yl)
acetamide (PJ34).41 To a 10 mL round flask was charged with 4a
(210 mg, 1.0 mmol), N,N0-dicyclohexylcarbodiimide (DCC, 412 mg,
2.0 mmol), N,N-dimethyl-pyridin-4-amine (DMAP, 6 mg, 5 mol %),
N,N-Dimethylglycine (155 mg, 1.5 mmol), CH2Cl2 (2 mL). The mix-
ture was stirring for 12 h at room temperature. Then the mixture
was filtered through a plug of Celite and the residue was washed
with ethyl acetate (3ꢁ20 mL). The filtrate was evaporated in vacuo.
The residue was purified by flash column chromatography on silica
gel with ethyl acetate (EA) and methanol (10:1) as eluent to afford
the corresponding products PJ34 (257 mg, 87%). 1H NMR (400 MHz,
1H), 2.93 (s, 3H); 13C NMR (125 MHz, CD3SOCD3, TMS)
d 160.9,
137.0, 136.9, 135.1, 133.3, 128.7, 127.4, 127.3, 127.2, 126.0, 121.6, 118.8,
116.2, 25.6; MS (EI) m/z (%) 209 (100) [Mþ], 190 (13), 180 (36), 165
(11), 152 (27); IR (KBr plate, cmꢂ1
1597, 1512, 1372, 732, 692.
) n 3436, 3110, 2970, 2894, 1654,
4.3.16. 5-Phenylphenanthridin-6(5H)-one (2r).39 52% yield; 1H
NMR (400 MHz, CD3SOCD3, TMS)
d
8.61 (d, J¼8.0 Hz, 1H), 8.54 (dd,
J¼8.0, 1.2 Hz, 1H), 8.37 (dd, J¼8.0, 1.2 Hz, 1H), 7.90e7.94 (m, 1H),
7.64e7.72 (m, 3H), 7.56e7.60 (m, 1H), 7.37e7.41 (m, 3H), 7.31e7.35
(m, 1H), 6.55 (dd, J¼8.2, 1.0 Hz, 1H); 13C NMR (100 MHz, CD3SOCD3,
CD3SOCD3, TMS)
d
11.69 (br s, 1H), 9.87 (br s, 1H), 8.69 (d, J¼2.0 Hz,
1H), 8.31e8.35 (m, 2H), 7.87e7.91 (m, 1H), 7.83 (dd, J¼8.8, 2.0 Hz,
1H), 7.66 (t, J¼7.6 Hz, 1H), 7.32 (d, J¼8.8 Hz, 1H), 3.13 (s, 2H), 2.33 (s,
TMS)
d 160.4, 138.8, 138.2, 133.7, 133.2, 130.1, 129.5, 129.3, 128.7,
128.3, 128.0, 125.2, 123.6, 122.6, 122.6, 118.3, 116.4; MS (EI) m/z (%)
272 (16) [Mþ1]þ, 271 (86) [Mþ], 270 (100) [Mꢂ1]þ, 241 (27), 151
(15), 140 (18), 139 (19), 77 (25), 50 (31), 43 (19), 39 (13); IR (KBr
6H); 13C NMR (100 MHz, CD3SOCD3, TMS)
d 168.6, 160.5, 134.0,
133.6, 132.8, 132.6, 128.0, 127.6, 125.8, 122.2, 122.0, 117.4, 116.2,
113.4, 63.3, 45.4; MS (EI) m/z (%) 295 (3) [Mþ], 209 (8), 182 (4), 153
plate, cmꢂ1
723, 696.
)
n
3058, 1656, 1605, 1584, 1486, 1345, 1321, 748,
(4), 127 (7), 58 (100), 42 (21); IR (KBr plate, cmꢂ1
2852, 1654, 1576, 1461, 1384, 1150, 774.
) n 3431, 2929,
4.4. General procedure for preparation of palladacycle A19,24
Acknowledgements
A suspension formed by 2-phenylaniline 1a (507 mg, 3.0 mmol),
Pd(OAc)2 (672 mg, 3.0 mmol), and MeOH (20 mL) was stirred at
room temperature for 24 h. The precipitate was filtered, washed
with 10 mL of MeOH and 10 mL of diethyl ether, and dried under
vacuum. A brown powder, 839 mg, yield: 84%. 1H NMR (400 MHz,
Funding from National Basic Research Program of China (No.
2011CB936003) and NSFC (No. 21072169 and No. 21272205) is
highly acknowledged. The work was also supported by the National
Key Technology Research and Development Program (No.
2012BAK25B03).

6526
Z. Liang et al. / Tetrahedron 69 (2013) 6519e6526
Vieira, T. O.; Alper, H. Org. Lett. 2011, 13, 11; (e) Wu, X.-F.; Neumann, H.; Beller,
Supplementary data
M. Chem.dEur. J. 2012, 18, 12599.
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