Palladium catalyzed annulation of benzylamines and arynes via C–H activation to construct 5,6-dihydrophenanthridine derivatives

Article abstract of DOI:10.1016/j.tet.2019.05.011

An efficient and versatile strategy employing palladium catalyst to synthesize 5,6-dihydrophenanthridine derivatives by annulation of benzylamines and arynes through C–H activation has been reported. This is promising one pot methodology which includes the use of Kobayashi's aryne precursor to construct plethora of 5,6-dihydrophenanthridine derivatives in moderate to good yield.

Full text of DOI:10.1016/j.tet.2019.05.011

Tetrahedron xxx (xxxx) xxx
Contents lists available at ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Palladium catalyzed annulation of benzylamines and arynes via CeH
activation to construct 5,6-dihydrophenanthridine derivatives
Manjoorahmed Asamdi a, Prakashsingh M. Chauhan b, Janki J. Patel b,
,
*
Kishor H. Chikhalia b
a Department of Chemistry, Gujarat University, Ahmedabad, 380009, Gujarat, India
b Department of Chemistry, Veer Narmad South Gujarat University, Surat, 395007, Gujarat, India
a r t i c l e i n f o
a b s t r a c t
Article history:
An efficient and versatile strategy employing palladium catalyst to synthesize 5,6-
dihydrophenanthridine derivatives by annulation of benzylamines and arynes through CeH activation
has been reported. This is promising one pot methodology which includes the use of Kobayashi's aryne
precursor to construct plethora of 5,6-dihydrophenanthridine derivatives in moderate to good yield.
© 2019 Elsevier Ltd. All rights reserved.
Received 1 April 2019
Received in revised form
27 April 2019
Accepted 6 May 2019
Available online xxx
Keywords:
Annulation
Aryne
Fluoride source
Palladacycle
Pd catalyst
1. Introduction
of 2,6-disubstituted-1-bromoaryls [11], ruthenium catalyzed
intramolecular CeH amination [12], enantioselective hydrogena-
The scientific community has witnessed the growing number of
reports for the synthesis of phenanthridine and their analogue due
to their promising biological activities and pharmaceutical appli-
cations [1]. Among them 5,6-dihydrophenanthridine skeleton have
been emanated as potent alkaloid which inhibits acetylcholines-
terase [2] and acts as a bradykinin B1 receptor antagonists [3].
However, being efficient scaffold methods leading to access
them directly in one step are much less abundant. Some of the
synthetic routes that have been documented to construct 5,6-
dihydrophenanthridine skeleton are palladium-catalyzed domino
N-benzylation/intramolecular direct arylation [4], palladium-
catalyzed enantioselective CeH arylation [5], palladium-catalyzed
tion of phenanthridine derivatives employing ruthenium catalyst
[13] (Fig. 1). Therefore, the search for alternative methods offering
clean and shortest route to construct these frameworks is of fore-
most interest. In these context transition metal-catalyzed annula-
tion of arynes encompassing CeH activation as a key step has
emerged as powerful and versatile tool to synthesize numerous
ring systems in one pot under mild condition [14].
Over the years, aryne chemistry has received significant atten-
tion due to its wide range of application in organic synthesis [15].
The remarkable success in this field is due to the development of
arynes under mild condition from ortho-(trimethylsilyl)aryltri-
flates employing fluoride source by Kobayashi and co-workers [16].
To the best of our knowledge till date only one report had been
documented to access 5,6-dihydrophenanthridine skeleton
employing Kobayashi's aryne precursor [17] (Scheme 1). Moreover,
synthetic protocols involving these precursors and transition metal
catalyst includes cycloaddition [18], insertion into sigma bond [19],
CeH activation [20], annulations [21] etc. Among these strategies,
the ease of forming CeC and C-heteroatom bond can be achieved by
palladium mediated CeH activation methodology which is other-
wise difficult to generate by conventional methods [22].
domino
SuzukieMiyaura/Aza-Michael
Reactions
[6],
PicteteSpengler reaction mediated by propylphosphonic anhy-
dride (T3P) [7], modified PicteteSpengler reaction of biphenyl-2-
amines and aromatic aldehydes [8], sequential cyclization-
reduction reaction of N-acylcarbamates [9], retro-carbopalladation
of chiral o-bromobenzylamines [10], intramolecular CeC coupling
* Corresponding author.
E-mail address: Chikhalia_kh@yahoo.com (K.H. Chikhalia).
Looking at the advantage of this strategy and our continuing
https://doi.org/10.1016/j.tet.2019.05.011
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Please cite this article as: M. Asamdi et al., Palladium catalyzed annulation of benzylamines and arynes via CeH activation to construct 5,6-
dihydrophenanthridine derivatives, Tetrahedron, https://doi.org/10.1016/j.tet.2019.05.011

2
M. Asamdi et al. / Tetrahedron xxx (xxxx) xxx
Fig. 1. Various synthetic route to construct 5,6-dihydrophenanthridine skeleton.
Scheme 1. Synthesis of Dihydrophenanthridines by Yun He and Co-workers.
interest in CeH activation [23] herein we report a new method to
synthesize 5,6-dihydrophenanthridine derivatives by the annula-
tion of readily available benzylamines and arynes employing
palladium catalyst.
under Pd(II) catalyst in the presence of Cu(OAc)2 as oxidant
(Table 1). It was observed that employing catalyst Pd(TFA)2 or PdCl2
with KF/18-crown-6 as fluoride source under Cu(OAc)2 in CH3CN at
120 ꢀC for 24 h gave the desired product in low yield along with the
generation of byproduct (Table 1, entries 1e2). A slight increase in
yield of 3a was obtained when fluoride source was changed to CsF
(Table 1, entries 3e4). In view of catalyst [Ru(p-cymene)Cl2]2 was
also tested but no improvement in yield was observed (Table 1,
entry 5). To our delight, when Pd(OAc)2 was used as a catalyst the
resultant transformation was achieved in highest yield and
2. Results and discussion
Our investigation on 5,6-dihydrophenanthridine begins by
reacting N-methyl-1-phenylmethanamine (1a) and o-(trime-
thylsilyl)phenyl triflate (2a) as aryne precursor and fluoride source
Please cite this article as: M. Asamdi et al., Palladium catalyzed annulation of benzylamines and arynes via CeH activation to construct 5,6-
dihydrophenanthridine derivatives, Tetrahedron, https://doi.org/10.1016/j.tet.2019.05.011

M. Asamdi et al. / Tetrahedron xxx (xxxx) xxx
3
Table 1
Optimization of the reaction conditions.a
Entry
Catalyst
Fluoride source
Solvent
Yieldb
3a (%)
4a(%)
1
2
3
4
5
6
7
8
Pd(TFA)2
PdCl2
Pd(TFA)2
PdCl2
[Ru(p-cymene)Cl2]2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
e
KF/18-crown-6
KF/18-crown-6
CsF
CsF
CsF
CsF
CsF
CsF
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
DMSO
13
11
23
34
9
86
43
47
65
51
59
31
0
19
24
32
11
0
6
16
30
23
15
9
37
0
13
28
17
DMF
9
CsF
CsF
toluene
1,1-dioxane
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
10
11
12
13
14c
15d
16e
KF/18-crown-6
TBAT
CsF
CsF
CsF
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
44
33
57
CsF
a
Reaction conditions: 1a (0.30 mmol, 1 equiv.), 2a (0.60 mmol, 2 equiv.), Pd(II) catalyst (10 mol%), CsF (0.90 mmol, 3 equiv.), Cu(OAc)2 (0.30 mmol, 1 equiv.) in 3.0 mL of
solvent for 24 h at 120 ꢀC.
b
Isolated yield.
Oxidant is Cu(TFA)2.
Oxidant is CuCl2..
Reaction carried out at room temperature.
c
d
e
formation of byproduct was least (Table 1, entry 6). Next, replacing
CH3CN with different solvent systems could not improve the yield
of 3a (Table 1, entries 7e10). Further evaluation of several fluoride
source with catalyst Pd(OAc)2 showed no increase in the yield of
the desied product (Table 1, entries 11e12). Moreover, no product
was formed when reaction was performed without Pd catalyst
(Table 1, entry 13). When oxidant Cu(OAc)2 was replaced by
Cu(TFA)2 or CuCl2 or carrying out the reaction at room temperature
couldn't make any difference (Table 1, entries 14e16).
With the successful establishment of optimized reaction con-
dition for palladium mediated annulation strategy to construct 3a,
the substrate scope of this transformation was explored by testing
wide range of benzylamines (1a e 1i) with aryne precursor 2a. It
was noted that all the combinations which were tested gave the
desired product irrespective of electron donating or electron
withdrawing group at R1 which revealed the existence of high
functional group tolerance (Table 2, entries 3a-3i). The reaction of
electron donating substituent at substrate 1 generated the products
with good to high yields (Table 2, entries 3a-3f), whereas with
electron withdrawing substituents the yields were lowered
(Table 2, entries 3g-3h). In addition, it was also observed that
alkoxy-substituted benzylic amine 1i underwent the desired
transformation smoothly resulting into the formation of product in
71% (Table 2, entry 3i).
desired cyclic product was decreased with 1g due to the presence of
electron withdrawing group on it (Table 2, entries 3p-3q). More-
over, the reaction of 6-(trimethylsilyl)-2,3-dihydro-1H-inden-5-yl
trifluoromethanesulfonate (2d) with 1a, 1b, 1c and 1g provided
the desired product in good to moderate yields (Table 2, entries 3r-
3u).
On the basis of the above results and literature reports [24], a
possible reaction mechanism is proposed in Fig. 2. Initially 1a
would react with Pd(OAc)2 to form PdeN adduct Z1 followed by
CeH bond activation which generated five-membered palladacycle
Z2. Seven membered-palladacycle Z3 is formed by coordinative
insertion of aryne into PdeC bond of Z3. Finally, Z3 would undergo
reductive elimination to give desired product 3 leaving behind
Pd(0) catalyst which was reoxidized to Pd(II) by Cu(OAc)2.. How-
ever, in accordance with the proposed catalytic cycle it is note-
worthy that intermediate Z3 can undergo a b-hydride elimination
reaction to afford byproduct 4a and regenerate the Pd(0) catalyst.
3. Conclusion
In summary, we have developed a prominent and efficient
strategy to synthesize 5,6-dihydrophenanthridines by annulation
of benzylamines with aryne through CeH activation in the pres-
ence of palladium(II) catalyst in one pot. The proposed synthetic
methodology proved to be an effective one as it overshadows the
long synthetic route to access this framework. In addition, the
desired compounds were synthesized in good to excellent yields
with high functional group tolerance. Moreover, efforts to construct
biologically active cyclic scaffolds through CeH activation are un-
derway in our laboratory.
Furthermore, the scope of other arynes 2b, 2c and 2d was also
investigated with benzylamine 1a, 1b, 1c and 1g under optimized
reaction condition. Electron rich aryne precursors 4,5-dimethyl-2-
(trimethylsilyl)phenyl trifluoromethanesulfonate (2b) and 4,5-
dimethoxy-2-(trimethylsilyl)phenyl
trifluoromethanesulfonate
(2c) gave 5,6-dihydrophenanthridines in good yields on treatment
with 1a, 1b and 1c (Table 2, entries 3j-3o), however, the yields of
Please cite this article as: M. Asamdi et al., Palladium catalyzed annulation of benzylamines and arynes via CeH activation to construct 5,6-
dihydrophenanthridine derivatives, Tetrahedron, https://doi.org/10.1016/j.tet.2019.05.011

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M. Asamdi et al. / Tetrahedron xxx (xxxx) xxx
Table 2
Substrate scope.
Entry
1
1
2
3
Yield
86%
2
2a
88%
3
4
5
2a
2a
2a
81%
87%
90%
6
2a
84%
7
8
2a
2a
58%
60%
Please cite this article as: M. Asamdi et al., Palladium catalyzed annulation of benzylamines and arynes via CeH activation to construct 5,6-
dihydrophenanthridine derivatives, Tetrahedron, https://doi.org/10.1016/j.tet.2019.05.011

M. Asamdi et al. / Tetrahedron xxx (xxxx) xxx
5
Table 2 (continued )
Entry
9
1
2
3
Yield
2a
71%
10
11
12
13
1a
1b
1c
1a
73%
80%
70%
78%
2b
2b
14
1b
2c
91%
15
16
17
1c
1g
1g
2c
2b
2c
75%
61%
66%
(continued on next page)
Please cite this article as: M. Asamdi et al., Palladium catalyzed annulation of benzylamines and arynes via CeH activation to construct 5,6-
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M. Asamdi et al. / Tetrahedron xxx (xxxx) xxx
Table 2 (continued )
Entry
18
1
2
3
Yield
1a
62%
19
1b
2d
77%
20
21
1c
1g
2d
2d
68%
63%
4. Experimental section
was purified by column chromatography (EtOAc/hexane) on silica
gel to afford the 5,6-dihydrophenanthridine 3a. Compound 1i was
synthesized in accordance with reported literature [25].
4.1. General information
Characterization data of compounds 3a, 3c, and 3e were found
exactly similar as reported in the literature (References of above
compounds are mentioned in Supplementary data).
All the reagents and solvents were purchased from Sigma-
Aldrich and Merck and were used as recieved without any further
purification. The synthesized compounds were characterized by 1H
NMR, 13C NMR, and elemental analysis. Melting points were
determined in open capillaries on a Veego electronic apparatus
VMP-D (Veego Instrument Corporation, Mumbai, India) and are
uncorrected. 1H NMR and 13C NMR spectra were recorded on a
Bruker AVANCE III 400 spectrometer (400 MHz for 1H NMR and
100 MHz for 13C NMR) using CDCl3 as a solvent and tetrame-
thylsilane (TMS) as internal standard. HRMS spectra were recorded
on XEVO G2-XS QTOF spectrophotometer. 1H NMR and 13C NMR
chemical shifts are reported as parts per million (ppm) downfield
from TMS. The splitting patterns are designated as follows: s,
singlet; d, doublet; t, triplet; m, multiplet. Elemental analysis (C, H,
N) were performed using a Heraeus CarloErba 1180 CHN analyzer
(Hanau, Germany).
4.2.1. 8-Methoxy-5-methyl-5,6-dihydrophenanthridine (3b)
Yield: 88%. white solid; mp: 136e137 ꢀC; 1H NMR (400 MHz,
CDCl3)
d
7.42 (d, J ¼ 8.1 Hz, 1H), 7.22 (td, J ¼ 7.4, 1.6 Hz, 1H), 7.15 (dd,
J ¼ 7.1, 2.2 Hz, 1H), 6.96 (dd, J ¼ 5.9, 2.2 Hz, 1H), 6.89 (d, J ¼ 7.8 Hz,
1H), 6.73 (td, J ¼ 7.8, 1.2 Hz, 1H), 6.68 (dd, J ¼ 6.7, 1.4 Hz, 1H), 4.67 (s,
2H), 3.82 (s, 3H), 2.84 (s, 3H). 13C NMR (100 MHz, CDCl3)
d 159.83,
4.2. General procedure to prepare 5,6-dihydrophenanthridines (3)
from benzylamines (1) employing palladium catalyst
142.72, 133.27, 129.16, 126.64, 126.03, 125.05, 124.54, 118.75, 113.33,
113.18, 111.28, 56.05, 50.90, 39.93. Anal. Calcd. For C15H15NO: C:
79.97; H: 6.71; N: 6.22; O: 7.10. Found: C: 79.95; H: 6.70; N: 6.23; O:
7.08. HRMS-ESI (m/z) calcd. for C15H15NO [M þ H]þ 226.1228, found
226.1241.
A
mixture of Pd(OAc)2 (6.7 mg, 0.030 mmol, 10 mmol%),
Cu(OAc)2 (54.45 mg, 0.30 mmol, 1 equiv.), 1a (32.1 mg, 0.30 mmol, 1
equiv.), CsF (136.7 mg, 0.90 mmol, 3 equiv.) was dissolved in a sol-
vent of acetonitrile (3 mL) followed by addition of 2a (179 mg,
0.60 mmol, 2 equiv.). The reaction mixture was stirred at 120 ꢀC for
24 h and progress of the reaction was monitored continuously by
TLC with ethyl acetate: hexane eluent system. Upon completion of
reaction the mixture was cooled to room temperature, poured into
brine, and extracted with EtOAc. The combined extracts were dried
over MgSO4 and filtered through pad of Celite eluting with ethyl
acetate. The filtrate was concentrated under reduced pressure and
4.2.2. 9-Methoxy-5-methyl-5,6-dihydrophenanthridine (3d)
Please cite this article as: M. Asamdi et al., Palladium catalyzed annulation of benzylamines and arynes via CeH activation to construct 5,6-
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M. Asamdi et al. / Tetrahedron xxx (xxxx) xxx
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Fig. 2. Plausible mechanism.
Yield: 87%. white solid; mp: 155e156 ꢀC; 1H NMR (400 MHz,
CDCl3)
Yield: 58%. yellow solid; mp: 116e117 ꢀC; 1H NMR (400 MHz,
CDCl3)
d
7.39 (dd, J ¼ 7.2, 2.4 Hz, 1H), 7.33 (d, J ¼ 8.1 Hz, 1H), 7.17 (d,
d
, 8.21 (dd, J ¼ 6.1, 2.2 Hz, 1H), 8.13 (d, J ¼ 8.1 Hz, 1H), 7.72 (d,
J ¼ 8.0 Hz, 1H), 7.13 (td, J ¼ 7.6, 1.4 Hz, 1H), 6.91 (dd, J ¼ 5.9, 2.2 Hz,
J ¼ 7.9 Hz, 1H), 7.25 (td, J ¼ 7.4, 1.6 Hz, 1H), 7.18 (dd, J ¼ 7.1, 2.2 Hz,
1H), 6.75 (td, J ¼ 7.8, 1.2 Hz, 1H), 6.73 (dd, J ¼ 6.8, 1.6 Hz, 1H), 4.65 (s,
1H), 6.74 (td, J ¼ 7.8, 1.2 Hz, 1H), 6.69 (dd, J ¼ 6.7, 1.4 Hz, 1H), 4.68 (s,
2H), 3.83 (s, 3H), 2.85 (s, 3H). 13C NMR (100 MHz, CDCl3)
d
160.28,
2H), 2.86 (s, 3H). 13C NMR (100 MHz, CDCl3)
d 147.47, 142.72, 135.96,
142.78, 130.46, 129.45, 128.81, 126.09, 124.74, 123.82, 118.43, 113.69,
113.18, 109.48, 56.06, 51.65, 39.93. Anal. Calcd. For C15H15NO: C:
79.97; H: 6.71; N: 6.22; O: 7.10. Found: C: C: 79.96; H: 6.69; N: 6.20;
O: 7.11. HRMS-ESI (m/z) calcd. for C15H15NO [M þ H]þ 226.1228,
found 226.1234.
133.33, 130.61, 129.14, 126.04, 124.95, 124.52, 123.88, 118.73, 113.34,
50.91, 39.92. Anal. Calcd. For C14H12N2O2: C: 69.99; H: 5.03; N:
11.66; O: 13.32. Found: C: 69.98; H: 5.01; N: 11.63; O: 13.33. HRMS-
ESI (m/z) calcd. for C14H12N2O2 [M þ H]þ 241.0919, found 241.0922.
4.2.5. Methyl 5-methyl-5,6-dihydrophenanthridine-9-carboxylate
(3h)
4.2.3. 5,8,9-Trimethyl-5,6-dihydrophenanthridine (3f)
Yield: 60%. white solid; mp: 187e188 ꢀC; 1H NMR (400 MHz,
CDCl3)
d
8.33 (d, J ¼ 8.2 Hz, 1H), 7.95 (dd, J ¼ 6.1, 1.6 Hz, 1H), 7.50 (d,
Yield: 84%. white solid; mp: 143e144 ꢀC; 1H NMR (400 MHz,
J ¼ 7.8 Hz, 1H), 7.43 (dd, J ¼ 7.2, 2.4 Hz, 1H), 7.15 (td, J ¼ 7.6, 1.4 Hz,
CDCl3)
d
, 7.41 (s, 1H), 7.38 (dd, J ¼ 7.9, 1.8 Hz, 1H), 7.11 (td, J ¼ 7.5,
1H), 6.76 (td, J ¼ 7.8, 2.6 Hz, 1H), 6.74 (dd, J ¼ 6.8, 1.6 Hz, 1H), 4.66 (s,
2.6 Hz, 1H), 7.07 (s, 1H), 6.76 (td, J ¼ 7.8, 2.6 Hz, 1H), 6.72 (dd, J ¼ 6.5,
2H), 3.96 (s, 3H), 2.86 (s, 3H). 13C NMR (100 MHz, CDCl3)
d 166.70,
2.1 Hz,1H), 4.66 (s, 2H), 2.85 (s, 3H), 2.34 (s, 6H). 13C NMR (100 MHz,
142.77, 135.68, 129.90, 129.45, 129.18, 127.47, 127.12, 126.08, 124.73,
124.41, 118.43, 113.16, 52.09, 51.66, 39.92. Anal. Calcd. For
CDCl3)
d 142.77, 138.06, 132.90, 132.47, 131.40, 129.44, 128.47,
127.53, 126.08, 124.75, 118.43, 113.146, 50.90, 39.91, 20.36. Anal.
Calcd. For C16H17N: C: 86.05; H: 7.67; N: 6.28. Found: C: 86.06; H:
7.66; N: 6.25. HRMS-ESI (m/z) calcd. for C16H17N [M þ H]þ 224.1487,
found 224.1481.
C16H15NO2: C: 75.87; H: 5.97; N: 5.53; O: 12.63. Found: C: 75.88; H:
5.94; N: 5.55; O: 12.61. HRMS-ESI (m/z) calcd. for C16H15NO2 [M þ
H]þ 254.1146, found 254.1161.
4.2.6. 5-Methyl-5,6-dihydro-[1,3]dioxolo[4,5-j]phenanthridine (3i)
4.2.4. 5-Methyl-8-nitro-5,6-dihydrophenanthridine (3g)
Please cite this article as: M. Asamdi et al., Palladium catalyzed annulation of benzylamines and arynes via CeH activation to construct 5,6-
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M. Asamdi et al. / Tetrahedron xxx (xxxx) xxx
Yield: 71%. white solid; mp: 130e131 ꢀC; 1H NMR (400 MHz,
CDCl3)
(m/z) calcd. for C17H19N [M þ H]þ 238.1609, found 238.1627.
d
, 7.34 (dd, J ¼ 6.8, 2.1 Hz, 1H), 7.25 (s, 1H), 7.10 (td, J ¼ 7.5,
2.6 Hz, 1H), 7.01 (s, 1H), 6.75 (td, J ¼ 7.8, 2.5 Hz, 1H), 6.71 (dd, J ¼ 6.8,
4.2.10. 2,3-Dimethoxy-5-methyl-5,6-dihydrophenanthridine (3 m)
2.4 Hz, 1H), 5.91 (s, 2H), 4.68 (s, 2H), 2.86 (s, 3H). 13C NMR
(100 MHz, CDCl3)
d 148.37, 147.98, 142.79, 129.47, 127.16, 126.04,
124.73, 121.93, 118.45, 113.15, 109.93, 107.16, 102.11, 50.90, 39.90.
Anal. Calcd. For C15H13NO2: C: 75.30; H: 5.48; N: 5.85; O: 13.37.
Found: C: 75.32; H: 5.44; N: 5.82; O: 13.38. HRMS-ESI (m/z) calcd.
for C15H13NO2 [M þ H]þ 240.1030, found 240.1024.
4.2.7. 2,3,5-Trimethyl-5,6-dihydrophenanthridine (3j)
Yield: 78%. white solid; mp: 126e127 ꢀC; 1H NMR (400 MHz,
CDCl3)
(s, 1H), 4.67 (s, 2H), 2.84 (s, 3H), 2.36 (s, 3H), 2.26 (s, 3H). 13C NMR
(100 MHz, CDCl3) 150.06, 147.08, 143.53, 142.99, 132.69, 130.71,
d, 7.62 (d, J ¼ 7.6 Hz, 1H), 7.31e7.35 (m, 3H), 7.12 (s, 1H), 6.47
d
128.78, 127.77, 127.54, 124.95, 116.20, 112.14, 107.25, 56.79, 51.67,
39.92. Anal. Calcd. For C16H17NO2: C: 75.81; H: 7.11; N: 5.20; O:
11.88. Found: C: 75.80; H: 7.14; N: 5.18; O: 11.86. HRMS-ESI (m/z)
calcd. for C16H17NO2 [M þ H]þ 256.1392, found 256.1378.
Yield: 73%. white solid; mp: 152e154 ꢀC; 1H NMR (400 MHz,
CDCl3)
(s, 1H), 4.68 (s, 2H), 2.85 (s, 3H), 2.37 (s, 3H), 2.25 (s, 3H). 13C NMR
(100 MHz, CDCl3) 147.62, 135.46, 132.70, 130.73, 129.80, 128.79,
d, 7.66 (d, J ¼ 7.8 Hz, 1H), 7.30e7.35 (m, 3H), 7.14 (s, 1H), 6.46
4.2.11. 2,3,8-Trimethoxy-5-methyl-5,6-dihydrophenanthridine (3n)
d
127.77, 127.56, 127.20, 124.95, 119.35, 110.56, 51.64, 39.91, 20.38.
Anal. Calcd. For C16H17N: C: 86.05; H: 7.67; N: 6.28. Found: C: 86.04;
H: 7.69; N: 6.24. HRMS-ESI (m/z) calcd. for C16H17N [M þ H]þ
224.1487, found 224.1496.
4.2.8. 8-Methoxy-2,3,5-trimethyl-5,6-dihydrophenanthridine (3k)
Yield: 91%. white solid; mp: 138e139 ꢀC; 1H NMR (400 MHz,
CDCl3)
J ¼ 8.2 Hz,1H), 6.83 (s,1H), 6.18 (s,1H), 4.71 (s, 2H), 3.81 (s, 9H), 2.85
(s, 3H). 13C NMR (100 MHz, CDCl3)
160.21, 150.06, 143.52, 142.97,
d, 7.61 (d, J ¼ 7.9 Hz,1H), 6.95 (dd, J ¼ 8.0, 2.8 Hz,1H), 6.85 (d,
d
133.63, 127.11, 124.73, 116.21, 113.42, 112.12, 111.41, 107.23, 56.78,
56.03, 50.90, 39.92. Anal. Calcd. For C17H19NO3: C: 71.56; H: 6.71; N:
4.91; O: 16.82. Found: C: 71.54; H: 6.72; N: 4.89; O: 16.81. HRMS-ESI
(m/z) calcd. for C17H19NO3 [M þ H]þ 286.1433, found 286.1439.
Yield: 80%. white solid; mp: 170e171 ꢀC; 1H NMR (400 MHz,
CDCl3)
d
, 7.60 (d, J ¼ 7.6 Hz, 1H), 7.07 (s, 1H), 6.94 (dd, J ¼ 6.4, 2.2 Hz,
1H), 6.86 (d, J ¼ 7.8 Hz, 1H), 6.45 (s, 1H), 4.68 (s, 2H), 3.82 (s, 3H),
2.85 (s, 3H), 2.35 (s, 3H), 2.26 (s, 3H). 13C NMR (100 MHz, CDCl3)
4.2.12. 2,3-Dimethoxy-5,9-dimethyl-5,6-dihydrophenanthridine
(3ꢀ)
d
160.21, 147.62, 135.47, 133.60, 129.81, 127.18, 127.11, 124.73, 119.34,
113.42, 111.41, 110.56, 56.05, 50.91, 39.92, 20.36. Anal. Calcd. For
C
17H19NO: C: 80.60; H: 7.56; N: 5.53; O: 6.31. Found: C: 80.58; H:
7.57; N: 5.51; O: 6.30. HRMS-ESI (m/z) calcd. for C17H19NO [M þ H]þ
254.1568, found 254.1576.
4.2.9. 2,3,5,9-Tetramethyl-5,6-dihydrophenanthridine (3l)
Yield: 75%. white solid; mp: 140e141 ꢀC; 1H NMR (400 MHz,
CDCl3)
6.54 (s, 1H), 6.13 (s, 1H), 4.67 (s, 2H), 3.83-3.82 (s, 6H), 2.83 (s, 3H),
2.31 (s, 3H). 13C NMR (100 MHz, CDCl3)
150.64, 143.33, 143.02,
d
7.31 (d, J ¼ 7.2 Hz, 1H), 7.16 (d, J ¼ 5.6 Hz, 1H), 7.14 (s, 1H),
d
137.19, 129.66, 128.27, 127.91, 127.12, 126.30, 115.60, 112.18, 107.01,
56.78, 51.67, 39.92, 21.20. Anal. Calcd. For C17H19NO2: C: 75.81; H:
7.11; N: 5.20; O: 11.88. Found: C: 75.80; H: 7.12; N: 5.17; O: 11.84.
HRMS-ESI (m/z) calcd. for C17H19NO2 [M þ H]þ 270.1488, found
270.1502.
Yield: 70%. white solid; mp: 181e182 ꢀC; 1H NMR (400 MHz,
CDCl3)
J ¼ 6.7, 1.6 Hz, 1H), 7.11 (s, 1H), 6.46 (s, 1H), 4.66 (s, 2H), 2.85 (s, 3H),
2.35e2.37 (s, 6H), 2.25 (s, 3H). 13C NMR (100 MHz, CDCl3)
147.68,
d, 7.44 (d, J ¼ 8.3 Hz, 1H), 7.31 (d, J ¼ 8.3 Hz, 1H), 7.15 (dd,
d
137.19, 135.95, 129.68, 129.06, 128.27, 127.89, 127.53, 127.11, 126.30,
118.82, 110.81, 51.67, 39.92, 21.20, 20.37. Anal. Calcd. For C17H19N: C:
86.03; H: 8.07; N: 5.90. Found: C: 86.01; H: 8.08; N: 5.89. HRMS-ESI
4.2.13. 2,3,5-Trimethyl-8-nitro-5,6-dihydrophenanthridine (3p)
Please cite this article as: M. Asamdi et al., Palladium catalyzed annulation of benzylamines and arynes via CeH activation to construct 5,6-
dihydrophenanthridine derivatives, Tetrahedron, https://doi.org/10.1016/j.tet.2019.05.011

M. Asamdi et al. / Tetrahedron xxx (xxxx) xxx
9
Yield: 77%. white solid; mp: 121e122 ꢀC; 1H NMR (400 MHz,
CDCl3)
Yield: 61%. yellow solid; mp: 150e151 ꢀC; 1H NMR (400 MHz,
CDCl3)
, 8.21 (dd, J ¼ 8.6, 2.4 Hz, 1H), 8.10 (d, J ¼ 4.2 Hz, 1H), 7.91 (d,
J ¼ 6.8 Hz, 1H), 7.20 (s, 1H), 6.48 (s, 1H), 4.70 (s, 2H), 2.86 (s, 3H),
2.38 (s, 3H), 2.26 (s, 3H). 13C NMR (100 MHz, CDCl3)
147.62, 147.08,
135.88, 135.45, 133.86, 130.48, 129.81, 127.18, 124.73, 124.39, 119.35,
110.55, 50.90, 39.91, 20.37. Anal. Calcd. For C16H16N2O2: C: 71.62; H:
6.01; N: 10.44; O: 11.93. Found: C: 71.64; H: 6.02; N: 10.41; O: 11.91.
HRMS-ESI (m/z) calcd. for C16H16N2O2 [M þ H]þ 269.1245, found
269.1257.
d
, 7.60 (d, J ¼ 7.6 Hz, 1H), 7.32 (s, 1H), 6.94 (dd, J ¼ 8.3, 1.8 Hz,
d
1H), 6.85 (d, J ¼ 7.9 Hz, 1H), 6.69 (s, 1H), 4.67 (s, 2H), 3.80 (s, 3H),
2.99 (t, J ¼ 7.6 Hz, 2H) 2.89 (t, J ¼ 7.2 Hz, 2H), 2.84 (s, 3H), 2.15 (m,
d
2H). 13C NMR (100 MHz, CDCl3)
d 160.21, 143.38, 143.15, 139.11,
133.63, 127.10, 124.73, 123.48, 117.71, 113.44, 111.42, 106.07, 56.03,
50.91, 39.91, 33.84, 26.91. Anal. Calcd. For C18H19NO: C: 81.47; H:
7.22; N: 5.28; O: 6.03. Found: C: 81.46; H: 7.21; N: 5.30; O: 6.01.
HRMS-ESI (m/z) calcd. for C18H19NO [M þ H]þ 266.1575, found
266.1582.
4.2.14. 2,3-Dimethoxy-5-methyl-8-nitro-5,6-
dihydrophenanthridine (3q)
4.2.17. 2,6-Dimethyl-6,8,9,10-tetrahydro-5H-cyclopenta[b]
phenanthridine (3t)
Yield: 68%. white solid; mp: 110e111 ꢀC; 1H NMR (400 MHz,
Yield: 66%. yellow solid; mp: 163e164 ꢀC; 1H NMR (400 MHz,
CDCl3)
d
, 7.42 (d, J ¼ 8.4 Hz, 1H), 7.35 (s, 1H), 7.30 (s, 1H), 7.17 (dd,
CDCl3)
J ¼ 6.8 Hz, 1H), 6.91 (s, 1H), 6.24 (s, 1H), 4.68 (s, 2H), 3.81 (s, 6H),
2.85 (s, 3H). 13C NMR (100 MHz, CDCl3)
150.04, 147.09, 143.52,
d, 8.20 (dd, J ¼ 8.5, 2.9 Hz,1H), 8.08 (d, J ¼ 5.6 Hz,1H), 7.90 (d,
J ¼ 6.8, 1.6 Hz, 1H), 6.70 (s, 1H), 4.66 (s, 2H), 3.00 (t, J ¼ 7.8 Hz, 2H),
2.88 (t, J ¼ 7.2 Hz, 2H), 2.85 (s, 3H), 2.36 (s, 3H), 2.15 (m, 2H). 13C
d
NMR (100 MHz, CDCl3)
d 143.55, 143.42, 139.57, 137.17, 129.68,
142.98, 135.87, 133.86, 130.49, 124.75, 124.38, 116.20, 112.13, 107.25,
56.80, 50.91, 39.92. Anal. Calcd. For C16H16N2O4: C: 63.99; H: 5.37;
N: 9.33; O: 21.31. Found: C: 63.98; H: 5.38; N: 9.31; O: 21.28. HRMS-
ESI (m/z) calcd. for C16H16N2O4 [M þ H]þ 301.1178, found 301.1188.
129.29, 128.25, 127.91, 127.12, 123.31, 116.68, 105.94, 51.68, 39.92,
33.84, 26.92, 21.21. Anal. Calcd. For C18H19N: C: 86.70; H: 7.68; N:
5.62. Found: C: 86.69; H: 7.67; N: 5.60. HRMS-ESI (m/z) calcd. for
C
18H19N [M þ H]þ 250.1669, found 250.1656.
4.2.15. 6-Methyl-6,8,9,10-tetrahydro-5H-cyclopenta[b]
phenanthridine (3r)
4.2.18. 6-Methyl-3-nitro-6,8,9,10-tetrahydro-5H-cyclopenta[b]
phenanthridine (3u)
Yield: 62%. white solid; mp: 161e162 ꢀC; 1H NMR (400 MHz,
Yield: 63%. yellow solid; mp: 118e119 ꢀC; 1H NMR (400 MHz,
CDCl3)
d
, 7.62 (d, J ¼ 7.4 Hz, 1H), 7.36 (m, 1H), 7.35 (d, J ¼ 8.5 Hz, 1H),
CDCl3)
d
, 8.21 (dd, J ¼ 8.8, 2.8 Hz,1H), 8.09 (d, J ¼ 4.9 Hz,1H), 7.91 (d,
7.31e7.34 (m, 2H), 6.70 (s, 1H), 4.66 (s, 2H), 3.00 (t, J ¼ 7.8 Hz, 2H),
J ¼ 6.8 Hz, 1H), 7.40 (s, 1H), 6.71 (s, 1H), 4.70 (s, 2H), 3.01 (t,
2.90 (t, J ¼ 7.4 Hz, 2H), 2.83 (s, 3H), 2.15 (m, 2H). 13C NMR (100 MHz,
J ¼ 7.9 Hz, 2H), 2.92 (t, J ¼ 7.7 Hz, 2H), 2.85 (s, 3H), 2.15 (m, 2H). 13
C
CDCl3)
d
143.38, 143.15, 139.10, 132.66, 130.74, 128.79, 127.78,
NMR (100 MHz, CDCl3) d 147.08, 143.39, 143.14, 139.10, 135.87,
127.56, 124.93, 123.48, 117.71, 106.08, 51.67, 39.90, 33.84, 26.92.
Anal. Calcd. For C17H17N: C: 86.77; H: 7.28; N: 5.95. Found: C: 86.79;
H: 7.29; N: 5.87. HRMS-ESI (m/z) calcd. for C17H17N [M þ H]þ
236.1423, found 236.1431.
133.86, 130.48, 124.74, 124.38, 123.50, 117.71, 106.08, 50.90, 39.91,
33.84, 26.91. Anal. Calcd. For C17H16N2O2: C: 72.84; H: 5.76; N: 9.99;
O: 11.41. Found: C: 72.82; H: 5.77; N: 9.97; O: 11.40. HRMS-ESI (m/z)
calcd. for C17H16N2O2 [M þ H]þ 281.1254, found 281.1272.
4.2.16. 3-Methoxy-6-methyl-6,8,9,10-tetrahydro-5H-cyclopenta[b]
phenanthridine (3s)
Acknowledgement
Authors are thankful to NFDD centre Rajkot, IIT Ropar and
Please cite this article as: M. Asamdi et al., Palladium catalyzed annulation of benzylamines and arynes via CeH activation to construct 5,6-
dihydrophenanthridine derivatives, Tetrahedron, https://doi.org/10.1016/j.tet.2019.05.011

10
M. Asamdi et al. / Tetrahedron xxx (xxxx) xxx
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Please cite this article as: M. Asamdi et al., Palladium catalyzed annulation of benzylamines and arynes via CeH activation to construct 5,6-
dihydrophenanthridine derivatives, Tetrahedron, https://doi.org/10.1016/j.tet.2019.05.011