Synthesis of 8-aryl substituted benzo[a]phenanthridine derivatives by consecutive three component tandem reaction and 6-endo carbocyclization

Article abstract of DOI:10.1016/j.tet.2012.07.067

A concise construction of benzo[a]phenanthridines involving multicomponent tandem reaction/carbocyclization in a sequential format is described. The reaction proceeds initially via formation of a 4-aryl-3-arylethynyl-isoquinoline from 2-bromobenzaldehyde/tert-butylamine/1,3-diyne in a three component format followed by a second ring closure either via gold/silver catalyzed intramolecular hydroarylation or via iodo-catalyzed regioselective 6-endo-dig electrophilic cyclization. The salient feature of the strategy involves a three component reaction followed by transformation of the resulting product in to polyheterocycles with increased structural complexity in two steps.

Full text of DOI:10.1016/j.tet.2012.07.067

Tetrahedron 68 (2012) 8207e8215
Contents lists available at SciVerse ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Synthesis of 8-aryl substituted benzo[a]phenanthridine derivatives by
consecutive three component tandem reaction and 6-endo carbocyclizationq
*
Anil K. Mandadapu, Meena D. Dathi, Rajesh K. Arigela, Bijoy Kundu
Medicinal & Process Chemistry Division, Central Drug Research Institute, CSIR, Lucknow 226001, India
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 25 May 2012
Received in revised form 16 July 2012
Accepted 18 July 2012
Available online 23 July 2012
A concise construction of benzo[a]phenanthridines involving multicomponent tandem reaction/carbo-
cyclization in a sequential format is described. The reaction proceeds initially via formation of a 4-aryl-3-
arylethynyl-isoquinoline from 2-bromobenzaldehyde/tert-butylamine/1,3-diyne in a three component
format followed by a second ring closure either via gold/silver catalyzed intramolecular hydroarylation or
via iodo-catalyzed regioselective 6-endo-dig electrophilic cyclization. The salient feature of the strategy
involves a three component reaction followed by transformation of the resulting product in to poly-
heterocycles with increased structural complexity in two steps.
Keywords:
Alkynes
Metals
Ó 2012 Elsevier Ltd. All rights reserved.
Lewis acids
CeH bond activation
Functionalization
1. Introduction
structural diversity following the alkyne activation to enforce
a second annulation.
Multicomponent tandem reactions remain one of the most
powerful approaches for the one pot transformation of three or
more reactants into new products.1 They have been used widely for
the synthesis of natural products and heterocyclic structures of
therapeutic interest.1b,2 In an attempt to introduce further struc-
tural complexity in the multicomponent tandem reaction products,
post-multicomponent transformations are being combined with
multicomponent reactions either in tandem or in a sequential
format. This in turn, provides greater flexibility, novelty, and effi-
ciency for the rapid access to annulated polyheterocycles.3 In recent
years, terminal and internal alkynes have been extensively used as
versatile building blocks in multicomponent formats that have led
to the synthesis of structurally diverse five-, six-, seven-, and eight-
membered heterocycles of therapeutic importance.4 However, the
above applications predominantly remained limited to terminal/
internal alkynes only and report involving 1,3-diynes as reactants in
a multicomponent format is scarce.5 We envisaged that the use of
1,3-diyne as one of the reactants in a multicomponent format may
initially undergo annulation to furnish a functionalized heterocycle
with an alkynyl handle attached to it, which can then be subjected
to post-multicomponent transformation for enhancing the
In view of our ongoing interest in the synthesis of annulated
polyheterocycles involving alkynes as one of the reactants in one
pot/three component tandem formats,6 we proposed to extend the
studies to 1,3-diynes in a three component format by initially
synthesizing functionalized isoquinolines followed by their con-
version to afford tetracyclic scaffold benzophenanthridine and its
analogues.
Benzophenanathridines are one of the widely distributed alka-
loids and associated with DNA-chain intercalating ability and po-
tent antitumor and antiinfectious activities.7 A careful survey of the
literature revealed multistep synthetic strategies for this class of
compounds associated with low yields and poor generality8 and to
the best of our knowledge there is no report dealing with multi-
component format-based protocols. In this communication, we
report sequenced three component tandem reaction and 6-endo
carbocyclization reactions for the concise construction of benzo[a]
phenanthridines by treating 2-bromobenzaldehyde with tert-
butylamine and 1,3-diynes.
2. Results and discussion
In the first instance we explored the formation of functionalized
isoquinolines using 1,3-diyne in a three component format. For this,
we initially studied the condensation of the preformed imines with
1,3-diynes to afford functionalized isoquinolines.9 Accordingly, we
screened a variety of Pd-catalyzed conditions for the condensation
q
CDRI Communication No. 8271.
* Corresponding author. Tel.: þ91 522 2612411/18; fax: þ91 522 2623405; e-mail
addresses: bijoy_kundu@yahoo.com, b_kundu@cdri.res.in (B. Kundu).
0040-4020/$ e see front matter Ó 2012 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tet.2012.07.067

8208
A.K. Mandadapu et al. / Tetrahedron 68 (2012) 8207e8215
Table 2
of preformed (2-bromo-benzylidene)-tert-butylamine 1a with 1,3-
diyne 2a and the results have been summarized in Table 1. The
reactions were generally performed in the presence of a variety of
Pd-complex, LiCl, and a base by heating at 120 ꢀC in DMF from 22 to
42 h. For most of the Pd-catalyzed conditions examined, we
obtained formation of isoquinoline as a mixture of two isomers 3a
and 3ab with the former being obtained as a major isomer. In
general, use of strong bases was found to be detrimental (entry 2, 3,
6, and 9), whereas use of mild base furnished 3a in comparatively
higher yields (entry 1, 4, 7, 10). The highest isolated yields for the
isomer 3a was obtained either by employing Pd(PPh3)4/LiCl/K2CO3
in DMF under heating for 25 h (70%; entry 4) or by employing
Pd(PPh3)4/TPP/Na2CO3 in DMF under heating for 22 h (68%; entry
7). For our studies, we selected Pd(PPh3)4/LiCl/K2CO3 as the method
of choice for our further studies.
Three component tandem synthesis of isoquinoline derivatives 3aeo in one-pot
Br
Br
DMF
100 C, 1h
R1
+
R1
t-BuNH2
O
N
°
Bu-t
6 a-d
1 a-d
Pd(PPh3)4, LiCl
K2CO3, DMF,
120 °C, 24-32h
R2
R2
2 a-d
3 a-o
entry
R1
R2
Time
Compound no
(% yield)a
1
2
3
4
5
6
7
8
H
H
H
H
H
25
28
25
26
28
30
26
24
25
30
26
24
32
28
26
3a (65)
3b (64)
3c (66)
3d (65)
3e (68)
3f (65)
3g (66)
3h (64)
3i (70)
3j (65)
3k (68)
3l (62)
3m (60)
3n (58)
3o (61)
CH3
tBu
OCH3
H
CH3
tBu
OCH3
H
CH3
tBu
H
CH3
tBu
OCH3
Table 1
Screening of reaction conditions for the formation isoquinoline derivative 3a from
the preformed (2-bromo-benzylidene)-tert-butylamine 1a and 1,3-diyne 2a
5-OCH3
5-OCH3
5-OCH3
5-OCH3
4,5-di OCH3
4,5-di OCH3
4,5-di OCH3
5-F
9
10
11
12
13
14
15
Br
Reaction conditions
+
+
N
N
N
Bu-t
5-F
5-F
5-F
3a
3ab
1a
2a
Reaction condition: 5 mL of DMF, 1.0 mmol of 6, 1.5 mmol of tBuNH2 were
placed in a 4 dram vial heated at 100 ꢀC for 1 h followed by the addition of 1.2 mmol
of 2, 0.05 mmol of Pd(PPh3)4, 1.0 mmol of LiCl, and 2.0 mmol of K2CO3 and were
heated at 120 ꢀC for indicated time.
a
Entry
Pd-catalyst
Base
Time (h)
Yield (%)a
3a/3ab
1
2
3
4
5
6
7
8
9
Pd(OAc)2
Na2CO3
KOAc
KOAc
K2CO3
K2CO3
Cs2CO3
Na2CO3
K2CO3
KOAc
32
36
42
25
32
36
22
24
24
24
62:13
47:25
56:18
70:12
48:19
42:16
68:11
<10
Pd(dppf)2Cl2/LiCl
Pd(PPh3)4/LiCl
Pd(PPh3)4/LiCl
Pd(dppf)2Cl2
Pd(PPh3)4
Pd(PPh3)4/TPP
Pd(PPh3)4/TPP
Pd(PPh3)4/TPP
Pd(OAc)2/TPP
following the activation of the alkyne moiety with transition
metals.4e,9,10 The annulation of alkyne containing intramolecular
nucleophilic centers via activation of the alkyne moiety has been
documented11 as the most efficient strategy for the straight forward
and rapid access to heterocyclic scaffolds. Accordingly, we initiated
our studies by examining the ability of the isoquinoline in-
termediates 3a and 3ab to undergo intramolecular hydroarylation
by employing a variety of transition metal catalysts in different
solvents and the results have been summarized in Table 3. After
extensive screening of a metal catalysts, such as CuI (entry 1), AuCl3
<10
65:14
10
Na2CO3
a
Imine 1a (1.0 mmol, 0.239 g) and bis alkyne 2a (1.2 mmol, 0.286 g), 5 mL of
DMF, Pd catalyst (0.05 mmol), TPP (0.1 mmol, 0.027 g) or LiCl (1.0 mmol, 0.041 g),
and base (2.0 mmol) heated at 120 ꢀC.
Table 3
Optimization of reaction conditions for the conversion of 3a to 4a
Once the conditions for the synthesis of functionalized iso-
quinoline 3a was established, we embarked with the development
of a three component tandem format for its synthesis. For this, we
treated 2-bromobenzaldehyde 6a with tert-butylamine in DMF for
1 h followed by addition of 1,3-diyne 2a in the presence of the op-
timized reaction condition Pd(PPh3)4/LiCl/K2CO3 at 120 ꢀC for 25 h.
After work up, the product 3a was isolated in 65% yield, which was
marginally less than 70% yield obtained when preformed imine 1a
was treated with 1,3-diyne 2a (entry 4; Table 1). Next, the scope and
limitation of our methodology was established by treating a series of
1,3-diynes (2aed) with 2-bromobenzadehydes (6aed) in the pres-
ence of tert-butylamine in a three component tandem format and
the results have been summarized in Table 2. In all cases, the sub-
strates underwent annulation to afford 11 isoquinoline derivatives
(3aeo) in 58e70% yield. In general, the three component tandem
synthesis to isoquinoline was not sensitive to electronic substitution
present on 1,3-diynes and 2-bromobenzaldehydes.
Reaction conditions
3a
N
4a
Entry
Solvent
Catalyst(s)
Yield (%)a
1
2
3
4
5
6
7
8
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
DCE
DME
DMF
DMSO
THF
CuI
AuCl3
Cu(OTf)2
Zn(OTf)2
AgSbF6
AuClPPh3
NR
NR
NR
NR
NR
NR
65b
58b
17
AgSbF6/AuClPPh3
AgSbF6/AuClPPh3
AgSbF6/AuClPPh3
AgSbF6/AuClPPh3
AgSbF6/AuClPPh3
AgSbF6/AuClPPh3
9
10
11
12
NR
NR
NRc
After successfully establishing the reaction condition for the
synthesis of functionalized isoquinolines 3, we next screened the
reaction conditions for enforcing the second cyclization using 6-
endo carbocyclization route in these two isomers. In the first in-
stance we proposed to effect this via 6-endo-dig carbocyclization
a
All reactions were carried out with using 0.5 mmol of 3a (0.152 g), 0.05 mmol of
catalyst(s), and monitored for 24 h at 120 ꢀC. NR¼No Reaction.
b
Reaction completed in 5 h.
c
Reaction carried out at 60 ꢀC for 24 h.

A.K. Mandadapu et al. / Tetrahedron 68 (2012) 8207e8215
8209
Table 4
(entry 2), Cu(OTf)2 (entry 3), Zn(OTf)2 (entry 4), AgSbF6 (entry 5),
Scope and limitation of Au-catalyzed synthesis of benzo[a]phenanthridines 4aej
AuClPPh3 (entry 6) and pleasingly, the presence of AgSbF6/
AuClPPh3 in toluene (entry 7) afforded benzo[a]phenanthridine 4a
in 65% isolated yield. Switching solvent from toluene to DCE (entry
8), DME (entry 9) afforded 4a in 58 and 17% yield, respectively.
Whereas DMF (entry 10), DMSO (entry 11), THF (entry 12) failed to
yield the desired product. In contrast, intermediate 3ab completely
failed to undergo 6-endo-dig carbocyclization.
R
R
R
R
AuClPPh / AgSbF
R
R
dry toluene, under N
120 C, 3-8 h
N
N
3
4a-j
The plausible mechanism (Fig. 1) shown reveals that the co-
ordination of the triple bond of 3a to Au(I) catalyst enhances the
electrophilicity of alkyne and the subsequent nucleophilic attack of
the carbon of the arene ring to the electron-deficient alkyne would
form the intermediate Au(0) species, which on further proto-
demetallation affords 4a with the regeneration of cationic Au(I)
catalyst. Au(I) catalyst did not promote the reaction without the
presence of silver. AgSbF6 used as the activation factor to initiate
the gold catalysis.12
N
N
N
N
O
4a
, 65%, 5 h
4b, 67%, 8 h
4c
, 72%, 6 h
O
4d, 66%, 6 h
O
O
O
N
4e, 60%, 7 h
N
N
N
O
O
O
4f, 68%, 6 h
4g, 69%, 3 h
4h, 66%, 4 h
ICl
N
Au+L
O
3a
O
O
N
Cl-
N
N
O
A
H+
4j, 67%, 6 h
4i, 62%, 8 h
Reactions conditions: 0.5 mmol of 3 and 0.05 mmol of AgSbF6, 0.05 mmol
of AuClPPh3, 5 mL freshly dried toluene under N2 at 120 °C.
Au+L
I+
N
AuL
B
N
H+
bromocyclization using Br2/NBS (entries 7 and 8) furnished 7-
bromo-8-phenyl-benzo[a]phenanthridine 5p in 68% isolated yield.
Mechanistically (Fig. 1), in case of ICl mediated cyclization, it is
presumed that the iodine first forms iodonium complex co-
ordinating with alkyne thereby enhancing its electrophilicity to
generate intermediate B. The activated (electron-deficient) triple
bond then undergoes nucleophilic attack by the carbon from the
phenyl ring to form 5a via electrophilic 6-endo-dig iodocyclization.
The scope and limitation of the optimized reaction condition
leading to 6-endo-dig iodocyclization was examined on in-
termediates 3aeo obtained via three component tandem format
and the results have been summarized in Table 6.
Protodemetallation
Product
5a
HCl
Product
4a
Fig. 1. Plausible mechanism for the formation of 4a and 5a from 3a.
The scope and limitation of Au-catalyzed carbocyclization of the
isoquinoline derivative 3aeo was established by subjecting them to
hydroarylation by treating with AgSbF6/AuClPPh3 catalyst system.
The substrates 3aek underwent annulation to afford benzo[a]
phenanthridine derivatives 4aej in 60e72 % yield (Table 4).
However, substrates 3leo with 5-F group in the arene ring failed
to undergo 6-endo-dig carbocyclization, thereby limiting the ap-
plication of Au-activated hydroarylation. This prompted us to ex-
plore an alternative route for the carbocyclization by replacing
metal catalyzed cyclization with electrophilic iodo-reagents with
the view to develop a versatile method for the intramolecular cy-
clization step. The iodo-reagents are known to initiate intra-
molecular 6-endo-dig iodocyclization13 following the activation of
the alkyne moiety. Besides, such iodocyclizations, generally leave
an iodine atom attached to the product, that is, amenable to further
elaboration using palladium-catalyzed coupling reactions.14
Table 5
Optimization of reaction conditions for the conversion of 3a to 5a and 5p
Reaction conditions
3a
X
N
5a)
X = I (
5
X = Br (5p)
Entry
Solvent
Reagent system
% Yield (product)
Accordingly, we screened several electrophilic reagents with the
view to promote intramolecular iodocyclization of the intermediate
3a and results have been summarized in Table 5. In our initial ex-
periments, we treated intermediate 3a with molecular iodine
(3 equiv) in the presence of K2CO3 (entry 1) in acetonitrile at 0 ꢀC to
furnish cyclized product 7-iodo-8-phenyl-benzo[a]phenanthridine
5a in 48% isolated yield. Analogus iodo-cyclization using NIS
(3 equiv) furnished 5a in 35% isolated yield (entry 2). Switching
solvents from acetonitrile to THF and DCM had a detrimental effect
on the yield (entries 3e5). However, replacing the molecular iodine
with a strong iodo-based electrophile ICl in acetonitrile at 0 ꢀC
furnished 5a in 84% isolated yield (entry 6), whereas
1
2
3
4
5
6
7
8
MeCN
MeCN
THF
DCM
THF
MeCN
MeCN
MeCN
I2/K2CO3
NIS
I2/K2CO3
I2/K2CO3
NIS
ICl
NBS
Br2
48(5a)a
35(5a)a
NR
52(5a)a
35(5a)a
84(5a)b
42(5p)c
68(5p)c
NR¼No Reaction.
a
Conversion of 3a to 5a after prolong stirring for 48 h.
3a (0.5 mmol, 0.152 g), 0.75 mmol of ICl (0.076 mL) (1 M solution in DCM) used,
b
conversion of 3a to 5a completed in 20 min.
c
6-endo-cyclization using 0.6 mmol of Br2 (0.061 mL).

8210
A.K. Mandadapu et al. / Tetrahedron 68 (2012) 8207e8215
Table 6
OH
B
O
Scope and limitation of ICl-catalyzed synthesis of 7-iodo, 8-phenyl-benzo[a]phe-
nanthridines 5aeo
OH
O
R
Pd(PPh3)4, 2M Na2CO3
R
N
DMF, 80
°C, 1h
O
Ref. 14a
Ref. 14b
Ref. 14c
R
7a
, 82 %
R
O
ICl, MeCN
0 °C, 20-30 min
O
I
R
R
N
N
O
O
3a-o
5a-o
PdCl2(PPh3)2(10 mol%),
2.5 eqv. K2CO3,
DMF, 110 °C, 4h
N
O
7b, 78 %
5a
O
O
N
H
N
I
CuI(10 mol%)
I
I
5c, 93%, 20 m
I
N
N
N
Benzotriazole(20 mol%)
K3PO4, DMSO,120 °C,15h
N
N
7c
, 65 %
5d, 92%, 20 m
5a, 88%, 20 m
5b, 85%, 25 m
O
O
I
I
I
I
PdCl2(PPh3)2,3 eqv.NaCl,
3 eqv. KOAc, DMA, 120
N
N
N
N
O
Ref. 14d
N
O
O
O
7d, 60 %
°
C, 4 2h
5e, 89%, 20 m
5f, 91%, 25 m
5g
, 92%, 25 m
5h, 93%, 20 m
Scheme 1. Functionalization of 5a.
O
O
I
O
O
I
I
I
N
Further studies with the application of 1,3-diyne in a multicompo-
nent format followed by post-multicomponent conversion for the
synthesis of natural product inspired polyheterocycles is in prog-
ress and results will be published elsewhere.
N
N
O
N
F
O
5i
, 90%, 25 m
5k
5j, 92%, 30 m
, 94%, 25 m
5l, 86%, 25 m
O
O
4. Experimental section
4.1. General information
Br
I
I
I
N
N
5m, 84%, 30 m
N
N
F
F
F
5o, 91%, 25 m
5p, 68%, 40 m
5n, 90%, 25 m
All reagents and solvents were purchased from commercial
sources and used without purification. The 1H NMR spectra were
recorded with 300 or 600 MHz spectrometer, while 13C was
recorded with 50, 75, 100, 150 MHz spectrometer. Chemical shifts
a
Reaction conditions: 0.5 mmol of 3a, 0.75 mmol of ICl (1 M solution in
DCM) in acetonitrile (5 mL) under N2 atmoshere at 0 °C for 20-30 min.
# Reaction carried out with 0.5 mmol of 3a and 0.6 mmol Br2 at 0 °C
d
are given in parts per million relative to the residual signals of
tetramethylsilane in CDCl3 or deuterated solvent CDCl3 for 1H and
13C NMR. Multiplicities are reported as follows: singlet (s), doublet
(d), doublet of doublets (dd), doublet of triplets (dt), triplet (t),
quartet (q), multiplet (m). High resolution mass spectra were taken
with a 3000 mass spectrometer. Column chromatography was
performed using silica gel 60 Thomas Baker (100e200 mesh) as the
stationary phase. All reactions were monitored by thin layer chro-
matography (TLC). The purity and characterization of these com-
pounds were further established using HR/EI Mass spectroscopy.
High resolution mass spectra were taken with a 3000 mass spec-
trometer, using Waters Agilent 6520-Q-TofMS/MS system and
JEOL-AccuTOF JMS-T100LC. Melting points were determined with
Unlike hydroarylation involving Au-catalyzed 6-endo cyclization
where substrates 3leo having 5-F group in the arene ring failed to
undergo cyclization, iodocyclization in general were not sensitive
to substituents on substrates 3aeo thereby offering products 5aeo
with minimal variation in the yields (84e94%). Thus, iodocycliza-
tions in comparison to Au-catalyzed cyclization were fast, efficient,
versatile, and required mild reaction conditions.
In our subsequent studies, we proposed to demonstrate the
efficacy of iodo functionality in 7-iodo, 8-phenyl-benzo[a]phe-
nanthridines 5 (Scheme 1) for introducing further diversity. In the
first set of experiments, we applied metal catalyzed Suzuki cou-
pling and Heck reaction on 5a to furnish 7a and 7b in 82% and 78%
yield, respectively. In addition we treated 5a with pyrrole in the
presence of CuI/benzotriazole to furnish 7c in 65% isolated yield.
Finally, we demonstrated the utility of iodo functionality in 5a for
increasing the structural complexity by treating it with an internal
alkyne in the presence of PdCl2(PPh3)2 to afford a novel pentacyclic
aromatic annulated polycycle 7d in 60% isolated yield.
€
a Buchi B-545 apparatus and are uncorrected.
4.2. General annulation procedure for preparation of
4-phenyl-3-phenylethynyl-isoquinolines 3aeo
To a stirred solution of 2-bromobenzaldehydes 6aed (1 mmol)
in DMF (5 mL) was added tert-butylamine (1.5 mmol) and the re-
action mixture was allowed to stirr under a nitrogen atmosphere at
100 ꢀC for 1 h. This was followed by the sequential addition of the
Pd(PPh3)4 (0.05 mmol), K2CO3 (2 mmol), LiCl (1 mmol), and the bis
alkynes 2aed (1.2 mmol) to the reaction mixture and was left for
stirring at 120 ꢀC for indicated time (Table 2). The reaction was
monitored by TLC to establish completion and the reaction mixture,
3. Conclusion
In summary we have developed an efficient method for the
construction of benzo[a]phenanthridines involving multicompo-
nent tandem reaction/carbocyclization in a sequential format.

A.K. Mandadapu et al. / Tetrahedron 68 (2012) 8207e8215
8211
was cooled to room temperature and passed through bed of Celite,
and filtrate was diluted with EtOAc (100 mL) and washed with
saturated NH4Cl (50 mL) and brine solution (100 mL). The organic
layer was dried over anhydrous sodium sulfate and evaporated to
dryness under reduced pressure. The crude product so obtained
was purified by column chromatography by using EtOAc/hexane as
eluent to afford 3.
2.31 (3H, s) ppm; 13C NMR (75 MHz, CDCl3):
d
158.7, 150.5, 138.4,
137.7, 136.2, 133.9, 133.5, 131.6, 130.6, 129.0, 128.8, 127.3, 123.6,
120.1, 105.1, 91.8, 89.1, 55.6, 21.5, 21.4 ppm; HRMS (ESI) calcd for
C26H22NO [MþH] 364.1701 found 364.1696.
4.2.7. Methyl 4-(4-tert-butylphenyl)-3-[2-(4-tert-butylphenyl) ethy-
nyl]isoquinolin-7-yl ether (3g). Brown solid; yield 66% (0.295 g);
mp 174e176 ꢀC; Rf¼0.34 (2:8 EtOAc/hexane); FT-IR (KBr) 3019,
4.2.1. 4-Phenyl-3-(2-phenylethynyl)isoquinoline (3a). White solid;
yield 65% (0.198 g); mp 115e117 ꢀC; Rf¼0.48 (2:8 EtOAc/hexane);
2962, 1626, 1492, 1216 cmꢁ1; 1H NMR (300 MHz, CDCl3):
d 9.13 (1H,
s), 7.65e7.65 (2H, m), 7.45e7.32 (3H, m), 7.25e7.22 (3H, m), 7.14
(2H, d, J¼9.5 Hz), 7.06 (1H, d, J¼7.9 Hz), 3.96 (3H, s),1.27 (9H, s),1.25
FT-IR (KBr) 3061, 2958, 1619, 1559, 1490, 1217 cmꢁ1 1H NMR
;
(300 MHz, CDCl3):
m), 7.59e7.51 (5H, m), 7.25 (5H, s) ppm; 13C NMR (50 MHz, CDCl3):
152.2, 136.5, 135.5, 135.0, 131.8, 130.9, 130.7, 128.5, 128.3, 127.8,
d
9.26 (1H, s), 8.03e8.01 (1H, m), 7.69e7.60 (3H,
(9H, s) ppm; 13C NMR (75 MHz, CDCl3):
d 158.8, 151.6, 150.9, 150.6,
150.5, 138.5, 137.7, 133.7,133.5, 131.6,131.5,130.7,130.5,129.0, 128.9,
127.5, 127.4, 125.2, 125.1, 123.7, 120.2, 114.2, 105.2, 92.1, 89.2, 55.6,
34.8, 31.6, 31.2 ppm; HRMS (ESI) calcd for C32H34NO [MþH]
448.2640 found 448.2600.
d
127.7, 125.5, 122.9, 92.6, 89.5 ppm; HRMS (ESI) calcd for C23H16
N
[MþH] 306.1283 found 306.1282.
4.2.2. 4-(4-Methylphenyl)-3-[2-(4-methylphenyl)ethynyl] isoquino-
line (3b). Orange solid; yield 64% (0.213 g); mp 112e114 ꢀC;
Rf¼0.46 (2:8 EtOAc/hexane); FT-IR (KBr) 3051, 2930, 1640, 1560,
4.2.8. Methyl 4-(4-methoxyphenyl)-3-[2-(4-methoxyphenyl)ethynyl]
isoquinolin-7-yl ether (3h). Orange solid; yield 64% (0.253 g); mp
166e168 ꢀC; Rf¼0.30 (2:8 EtOAc/hexane); FT-IR (KBr) 3019, 2956,
1440, 1219 cmꢁ1
;
1H NMR (300 MHz, CDCl3):
d
9.22 (1H, s),
1617, 1513, 1217 cmꢁ1 1H NMR (300 MHz, CDCl3):
; d 9.12 (1H, s),
8.00e7.97 (1H, m), 7.69e7.58 (3H, m), 7.38 (4H, m), 7.17 (2H, d,
7.63e7.59 (1H, m), 7.45 (2H, d, J¼8.2 Hz), 7.25e7.22 (4H, m), 7.08
J¼7.9 Hz), 7.06 (2H, d, J¼7.7 Hz), 2.48 (3H, s), 2.31 (3H, s) ppm; 13C
(2H, d, J¼8.1 Hz), 6.79 (2H, d, J¼8.4 Hz), 3.96 (3H, s), 3.92 (3H, s),
NMR (75 MHz, CDCl3):
d
152.0, 138.7, 137.7, 136.1, 135.6, 135.1, 133.4,
3.78 (3H, s) ppm; 13C NMR (75 MHz, CDCl3):
d 159.7, 159.5, 158.7,
131.7, 130.8, 130.7, 129.0, 128.9, 127.8, 127.6, 127.5, 125.5, 119.9, 92.6,
89.0, 21.5, 21.4 ppm; HRMS (ESI) calcd for C25H20N [MþH] 334.1596
found 334.1596.
150.5, 135.6, 134.2, 133.2, 132.1, 130.8, 129.0, 128.8, 127.3, 123.7,
115.2,113.9,113.6,105.2, 91.7, 88.5, 55.6, 55.5, 55.3 ppm; HRMS (ESI)
calcd for C26H22NO3 [MþH] 396.1600 found 396.1574.
4.2.3. 4-(4-tert-Butylphenyl)-3-[2-(4-tert-butylphenyl)ethynyl] iso-
quinoline (3c). Light orange solid; yield 66% (0.275 g); mp
120e122 ꢀC; Rf¼0.44 (2:8 EtOAc/hexane); FT-IR (KBr) 3019, 2962,
4.2.9. 6,7-Dimethoxy-4-phenyl-3-(2-phenylethynyl)isoquinoline
(3i). Orange solid; yield 70% (0.256 g); mp 156e158 ꢀC; Rf¼0.30
(2:8 EtOAc/hexane); FT-IR (KBr) 3020, 2929, 1629, 1501, 1465,
1641, 1515, 1445, 1216 cmꢁ1; 1H NMR (300 MHz, CDCl3):
d
9.24 (1H,
1217 cmꢁ1; 1H NMR (300 MHz, CDCl3):
d
9.07 (1H, s), 7.56e7.51 (5H,
m), 7.27e7.24 (6H, m), 6.90 (1H, s), 4.06 (3H, s), 3.81 (3H, s) ppm;
13C NMR (50 MHz, CDCl3):
153.4, 150.7, 149.5, 136.9, 135.4, 134.2,
s), 8.02e7.99 (1H, m), 7.74e7.69 (1H, m), 7.65e753 (m, 4H), 7.45
(2H, d, J¼8.3 Hz), 7.25 (2H, d, J¼8.4 Hz), 7.14 (2H, d, J¼8.5 Hz), 1.46
d
(9H, s), 1.28 (9H, s) ppm; 13C NMR (100 MHz, CDCl3):
d
152.1, 151.8,
131.7, 130.6, 128.4, 128.2, 128.1, 124.0, 123.0, 105.7, 103.8, 91.8, 89.5,
56.2, 56.0 ppm; HRMS (ESI) calcd for C25H20NO2 [MþH] 366.1494
found 366.1477.
151.0, 136.5, 135.9, 135.1, 133.6, 132.1, 131.7, 131.0, 130.8, 130.7, 130.4,
130.2, 127.8, 127.6, 125.7, 125.4, 125.2, 120.0, 92.9, 89.2, 34.8, 31.7,
31.6 ppm; HRMS (ESI) calcd for C31H32N [MþH] 418.2535 found
418.2535.
4.2.10. 6,7-Dimethoxy-4-(4-methylphenyl)-3-[2-(4-methylphenyl)
ethynyl]isoquinoline (3j). Brown solid; yield 65% (0.255 g); mp
162e164 ꢀC; Rf¼0.28 (2:8 EtOAc/hexane); FT-IR (KBr) 3018, 2928,
4.2.4. 4-(4-Methoxyphenyl)-3-[2-(4-methoxyphenyl)ethynyl]
iso-
quinoline (3d). Gray solid; yield 65% (0.237 g); mp 132e134 ꢀC;
Rf¼0.38 (2:8 EtOAc/hexane); FT-IR (KBr) 2934, 2848, 1622, 1508,
1624, 1503, 1426, 1217 cmꢁ1; 1H NMR (300 MHz, CDCl3):
d 9.03 (1H,
s), 7.43 (2H, d, J¼7.8 Hz), 7.35 (2H, d, J¼7.8 Hz), 7.26 (2H, s), 7.16 (2H,
d, J¼7.8 Hz), 7.06 (2H, d, J¼7.8 Hz), 6.94 (1H, s), 4.05 (3H, s), 3.82
(3H, s), 2.49 (3H, s), 2.32 (3H, s) ppm; 13C NMR (75 MHz, CDCl3):
1425, 1258 cmꢁ1 1H NMR (300 MHz, CDCl3):
; d 8.90 (1H, s), 8.25
(1H, d, J¼8.2 Hz), 7.77e7.71 (2H, m), 7.35e7.23 (5H, m), 7.13e7.10
(2H, m), 6.88 (2H, d, J¼8.7 Hz), 3.91 (3H, s), 3.83 (3H, s) ppm; 13C
d
153.2, 150.5, 149.4, 138.4, 137.6, 135.0, 134.5, 133.8, 131.7, 131.6,
NMR (75 MHz, CDCl3):
d
160.1,159.2, 150.2,133.4,133.1,132.8, 132.2,
130.5, 129.0, 128.98, 124.0, 120.1, 105.7, 103.9, 91.7, 89.2, 56.2, 56.0,
21.5, 21.4 ppm; HRMS (ESI) calcd for C27H24NO2 [MþH] 394.1807
found 394.1799.
132.1, 131.5, 131.1, 127.9, 127.6, 127.4, 126.3, 125.5, 116.5, 114.2, 114.0,
113.5, 99.9, 84.0, 55.6, 55.5 ppm; HRMS (ESI) calcd for C25H20NO2
[MþH] 366.1494 found 366.1478.
4.2.11. 6,7-Dimethoxy-4-(4-tert-butylphenyl)-3-[2-(4-tert-butyl-
phenyl) ethynyl]isoquinoline (3k). Orange solid; yield 68% (0.324 g);
mp 166e168 ꢀC; Rf¼0.25 (2:8 EtOAc/hexane); FT-IR (KBr) 2926,
4.2.5. 7-Methoxy-4-phenyl-3-(2-phenylethynyl)isoquinoline
(3e). Brown solid; yield 68% (0.228 g); mp 136e138 ꢀC; Rf¼0.40
(2:8 EtOAc/hexane); FT-IR (KBr) 3018, 2844, 1622, 1564, 1492,
2838, 1624, 1504, 1425, 1254 cmꢁ1 1H NMR (300 MHz, CDCl3):
;
1215 cmꢁ1; 1H NMR (300 MHz, CDCl3):
d
9.15 (1H, s), 7.58e7.51 (6H,
m), 7.26e7.23 (7H, m), 3.95 (3H, s) ppm; 13C NMR (75 MHz, CDCl3):
158.9, 150.8, 136.6, 136.5, 133.7, 131.7, 130.7, 130.5, 129.1, 128.4,
d
9.05 (1H, s), 8.09 (2H, d, J¼8.3 Hz), 7.75 (1H, s), 7.52 (2H, d,
J¼8.3 Hz), 7.46e7.38 (4H, m), 7.25 (1H, d, J¼6.9 Hz), 4.11 (3H, s),
d
4.05 (3H, s),1.39 (9H, s),1.33 (9H, s) ppm; 13C NMR (75 MHz, CDCl3):
128.3, 128.1, 127.3, 123.8, 123.1, 105.3, 91.8, 89.5, 55.7 ppm; HRMS
d 153.3, 151.6, 150.9, 150.6, 149.3, 139.3, 135.4, 134.7, 133.9, 131.7,
(ESI) calcd for C24H18NO [MþH] 336.1388 found 336.1380.
131.6, 131.5, 130.5, 130.4, 129.0, 125.2, 125.1, 124.0, 120.1, 114.2, 105.7,
103.9, 92.1, 89.4, 56.2, 56.1, 34.88, 34.8, 31.5, 31.2 ppm; HRMS (ESI)
calcd for C33H36NO2 [MþH] 478.2746 found 478.2744.
4.2.6. Methyl
4-(4-methylphenyl)-3-[2-(4-methylphenyl)ethynyl]
isoquinolin-7-yl ether (3f). Light orange solid; yield 65% (0.236 g);
mp 186e188 ꢀC; Rf¼0.35 (2:8 EtOAc/hexane); FT-IR (KBr) 2951,
4.2.12. 7-Fluoro-4-phenyl-3-(2-phenylethynyl)isoquinoline
2844, 1631, 1417, 1234 cmꢁ1; 1H NMR (300 MHz, CDCl3):
d
9.13 (1H,
(3l). Gray solid; yield 62% (0.200 g); mp 126e128 ꢀC; Rf¼0.30 (2:8
s), 7.60 (1H, d, J¼9.8 Hz), 7.37 (4H, m), 7.25 (2H, d, J¼5.8 Hz), 7.16
EtOAc/hexane); FT-IR (KBr) 3020, 2856, 1628, 1489, 1217 cmꢁ1 1H
;
(2H, d, J¼8.0 Hz), 7.06 (2H, d, J¼7.8 Hz), 3.96 (3H, s), 2.48 (3H, s),
NMR (300 MHz, CDCl3): d 9.21 (1H, s), 7.70e7.49 (7H, m), 7.43e7.36

8212
A.K. Mandadapu et al. / Tetrahedron 68 (2012) 8207e8215
(1H, m), 7.25 (5H, s) ppm; 13C NMR (75 MHz, CDCl3):
d
162.9, 159.6,
1H NMR (300 MHz, CDCl3):
d 9.36 (1H, s), 9.07 (2H, m), 8.17 (1H, d,
151.4,151.3,136.4,136.2,135.2,132.2,131.8,130.7,128.7,128.6,128.5,
128.4, 128.39, 128.3, 122.7, 121.6, 121.2, 111.1, 110.9, 92.6, 89.1 ppm;
HRMS (ESI) calcd for C23H15FN [MþH] 324.1189 found 324.1171.
J¼7.9 Hz), 8.06 (1H, s), 7.94e7.89 (2H, m), 7.76e7.71 (1H, m),
7.57e7.50 (3H, m), 7.36 (2H, d, J¼7.7 Hz), 2.52 (3H, s), 2.49 (3H, s)
ppm; 13C NMR (75 MHz, CDCl3):
d 152.5, 143.0, 141.3, 137.4, 137.2,
136.6, 132.6, 132.5, 131.1, 130.0, 129.3, 129.1, 128.5, 128.4, 128.3,
128.2, 127.9, 127.8, 126.8, 126.7, 126.6, 125.8, 21.8, 21.4 ppm; HRMS
(ESI) calcd for C25H20N [MþH] 334.1596 found 334.1596.
4.2.13. 7-Fluoro-4-(4-methylphenyl)-3-[2-(4-methylphenyl) ethynyl]
isoquinoline (3m). Light green solid; yield 60% (0.210 g); mp
130e132 ꢀC; Rf¼0.25 (2:8 EtOAc/hexane); FT-IR (KBr) 3018, 2927,
2854, 1629, 1513, 1440, 1218 cmꢁ1
;
1H NMR (300 MHz, CDCl3):
4.3.3. 10-tert-Butyl-8-(4-tert-butylphenyl)benzo[a]phenanthridine
(4c). Light yellow solid; yield 72% (0.150 g); mp 138e140 ꢀC; Rf¼0.40
(2:8 EtOAc/hexane); FT-IR (KBr) 3122, 2961, 1642, 1534, 1219 cmꢁ1; 1H
d
9.18 (1H, s), 7.73e7.68 (1H, m), 7.61 (1H, m), 7.41e7.35 (5H, m),
7.16 (2H, d, J¼8.0 Hz), 7.07 (2H, d, J¼7.9 Hz), 2.49 (3H, s), 2.32 (3H, s)
ppm; 13C NMR (75 MHz, CDCl3):
162.9, 159.5, 151.15, 151.1, 138.8,
d
NMR (300 MHz, CDCl3): d9.37 (1H, s), 9.14e9.07(2H, m), 8.18e8.14 (2H,
138.1, 136.2, 135.4, 133.1, 132.3, 131.7, 130.6, 129.1, 129.0, 128.7, 128.6,
128.5, 128.4, 121.4, 121.1, 119.8,111.1,110.8, 92.7, 88.7, 21.6, 21.5 ppm;
HRMS (ESI) calcd for C25H19FN [MþH] 352.1502 found 352.1482.
m), 8.10 (1H, s), 7.92e7.87 (1H, m), 7.80 (1H, dd, J1¼2.1 Hz, J2¼8.9 Hz),
7.72 (1H, t, J¼7.1 Hz), 7.62e7.55 (4H, m), 1.44 (9H, s), 1.39 (9H, s) ppm;
13C NMR (50 MHz, CDCl3):
d 152.7,150.6,149.4,143.4,141.6,137.2,134.4,
134.1, 132.6, 132.1, 130.9, 129.8, 129.5, 129.2, 129.0, 128.6, 128.3, 127.8,
126.7, 125.5, 125.0, 122.9, 120.1, 35.1, 34.8, 31.6, 31.4 ppm; HRMS (ESI)
calcd for C31H32N [MþH] 418.2535 found 418.2535.
4.2.14. 7-Fluoro-4-(4-tert-butylphenyl)-3-[2-(4-tert-butylphenyl)
ethynyl]isoquinoline (3n). Pale brown; yield 58% (0.252 g); mp
140e142 ꢀC; Rf¼0.22 (2:8 EtOAc/hexane); FT-IR (KBr) 2960, 2859,
1626, 1462, 1221 cmꢁ1
;
1H NMR (300 MHz, CDCl3):
d
9.18 (1H, s),
4.3.4. 3-Methoxy-8-phenylbenzo[a]phenanthridine (4d). Light yel-
low solid; yield 66% (0.111 g); mp 142e144 ꢀC; Rf¼0.38 (2:8 EtOAc/
7.77e7.72 (1H, m), 7.62e7.56 (3H, m), 7.44e7.38 (3H, m), 7.25 (2H,
d, J¼8.3 Hz), 7.13 (2H, d, J¼8.4 Hz), 1.45 (9H, s), 1.27 (9H, s) ppm; 13C
hexane); FT-IR (KBr) 2925, 2856, 1620, 1579, 1460, 1219 cmꢁ1 1H
;
NMR (75 MHz, CDCl3):
d
159.6, 151.9, 151.3, 151.2, 151.1, 136.5, 135.7,
NMR (300 MHz, CDCl3):
d, J¼7.9 Hz), 8.68 (1H, t, J¼7.0 Hz), 7.61e7.46 (8H, m), 4.00 (3H, s)
ppm; 13C NMR (75 MHz, CDCl3):
158.2, 152.2, 142.5, 140.5, 140.2,
d 9.32 (1H, s), 9.06e8.98 (2H, m), 8.07 (2H,
133.3, 132.3, 131.6, 130.5, 128.9, 128.8, 128.5, 128.4, 125.3, 125.2,
121.4, 121.1, 119.9, 114.2, 111.1, 110.8, 93.0, 88.9, 34.9, 31.6, 31.2 ppm;
HRMS (ESI) calcd for C31H31FN [MþH] 436.2441 found 436.2426.
d
139.4, 132.3, 130.2, 128.6, 128.3, 128.0, 127.7, 127.4, 127.1, 126.6,
126.4, 122.5, 114.2, 107.7, 55.7 ppm; HRMS (ESI) calcd for C24H18NO
[MþH] 336.1388 found 336.1384.
4.2.15. 4-{7-Fluoro-3-[2-(4-methoxyphenyl)ethynyl]isoquinolin-4-
yl}phenyl methyl ether (3o). Brown solid; yield 61% (0.234 g); mp
135e137 ꢀC; Rf¼0.20 (2:8 EtOAc/hexane); FT-IR (KBr) 2952, 2844,
4.3.5. 3-Methoxy-10-methyl-8-(4-methylphenyl)benzo[a]phenan-
thridine (4e). Yellow solid; yield 60% (0.109 g); mp 190e192 ꢀC;
Rf¼0.40 (2:8 EtOAc/hexane); FT-IR (KBr) 2924, 2853, 1635, 1441,
1619, 1512, 1217 cmꢁ1 1H NMR (300 MHz, CDCl3):
; d 9.19 (1H, s),
7.71e7.69 (1H, m), 7.61e7.58 (1H, m), 7.46e7.38 (3H, m), 7.26e7.22
(2H, m), 7.09 (2H, d, J¼6.8 Hz), 6.80 (2H, d, J¼7.0 Hz), 3.92 (3H, s),
1218 cmꢁ1 1H NMR (300 MHz, CDCl3):
; d 9.28 (1H, s), 9.01e8.94
3.79 (3H, s) ppm; 13C NMR (75 MHz, CDCl3):
d
162.8, 159.9, 159.7,
(2H, m), 8.02 (1H, s), 7.87 (1H, s), 7.51e7.45 (4H, m), 7.35 (1H, d,
151.1, 151.0, 135.6, 135.5, 133.3, 132.0, 128.7, 128.6, 128.5, 121.4, 121.1,
114.9, 114.0, 113.8, 111.1, 110.8, 92.6, 88.2, 55.5, 55.4 ppm; HRMS
(ESI) calcd for C25H19FNO2 [MþH] 384.1400 found 384.1405.
J¼7.7 Hz), 7.24 (2H, s) 4.01 (3H, s), 2.50 (3H, s), 2.48 (3H, s) ppm; 13C
NMR (75 MHz, CDCl3): d 158.1, 151.8, 142.3, 140.2, 139.4, 137.4, 137.3,
136.4, 132.5, 130.1, 129.3, 128.7, 128.3, 128.2, 127.9, 127.4, 126.5,
122.3, 114.2, 107.6, 55.7, 21.8, 21.4 ppm; HRMS (ESI) calcd for
C26H22NO [MþH] 364.1701 found 364.1678.
4.3. General procedure for the Au-catalyzed cyclizations 4aej
A 50 mL sealed tube equipped with a magnetic stir bar, was
charged with the substrate 4-phenyl-3-phenylethynyl-isoquinolines
3aek (0.5 mmol), 5 mL freshly dried toluene, Au(PPh3)Cl
(0.05 mmol), and AgSbF6 (0.05 mmol) under nitrogen atmosphere.
The reaction tube was transferred to an oil bath and continued to stir
at 120 ꢀC. After being allowed to stir vigorously for the appropriate
time, the reaction vessel was removed from the oil bath and cooled to
room temperature and filtered through bed of Celite-R, diluted with
water (50 mL) and the reaction mixture was extracted with ethyl
acetate (3ꢂ30 mL). The resulting organic solution was washed with
brine (25 mL), dried over anhydrous Na2SO4, filtered, and concen-
trated in vacuo. The resulting residue was purified by silica gel flash
columnchromatographyusingEtOAc/hexaneastheeluenttoafford 4.
4.3.6. 3-Methoxy-10-tert-butyl-8-(4-tert-butylphenyl)benzo[a]phe-
nanthridine (4f). Yellow solid; yield 68% (0.152 g); mp 144e146 ꢀC;
Rf¼0.35 (2:8 EtOAc/hexane); FT-IR (KBr) 2919, 2858, 1622, 1561,
1474, 1218 cmꢁ1; 1H NMR (300 MHz, CDCl3):
d 9.27 (1H, br s), 9.00
(2H, dd, J1¼2.8 Hz, J2¼9.2 Hz), 8.16 (1H, d, J¼1.8 Hz), 8.07 (1H, s),
7.76 (1H, dd, J1¼2.0 Hz, J2¼8.9 Hz), 7.60e7.54 (4H, m), 7.49 (1H, dd,
J1¼2.5 Hz, J2¼9.2 Hz), 7.42 (1H, d, J¼2.4 Hz), 3.97 (3H, s), 1.43 (9H,
s), 1.38 (9H, s) ppm; 13C NMR (50 MHz, CDCl3):
d 157.9, 150.4, 149.2,
140.4, 137.3, 132.0, 129.8, 128.8, 128.2, 127.8, 127.3, 125.3, 124.6,
122.7, 122.1, 107.4, 55.5, 35.0, 34.7, 31.5, 31.3 ppm; HRMS (ESI) calcd
for C32H34NO [MþH] 448.2640 found 448.2635.
4.3.7. 3,10-Dimethoxy-8-(4-methoxyphenyl)benzo[a]phenanthridine
(4g). Yellow solid; yield 69% (0.136 g); mp 162e164 ꢀC; Rf¼0.32
(2:8 EtOAc/hexane); FT-IR (KBr) 2920, 2878, 1621, 1532, 1458,
4.3.1. 8-Phenylbenzo[a]phenanthridine (4a). Light yellow solid; yield
65% (0.099 g); mp 132e134 ꢀC; Rf¼0.45 (2:8 EtOAc/hexane); FT-IR (KBr)
1262 cmꢁ1 1H NMR (300 MHz, CDCl3):
; d 9.26 (1H, s), 9.00e8.94
2924, 2853, 1634, 1460, 1218 cmꢁ1; 1H NMR (300 MHz, CDCl3):
d
9.42
(2H, m), 8.02 (1H, s), 7.59e7.50 (2H, m), 7.49e7.46 (2H, m),
7.36e7.32 (1H, m), 7.08 (2H, d, J¼8.5 Hz), 4.03 (3H, s), 3.92 (3H, s),
(1H, s), 9.15 (2H, dd, J1¼3.6 Hz, J2¼8.2 Hz), 8.21 (1H, d, J¼7.9 Hz),
8.14e8.09 (2H, m), 7.98e7.93 (1H, m), 7.80e7.72 (2H, m), 7.64e7.48 (6H,
3.85 (3H, s) ppm; 13C NMR (75 MHz, CDCl3):
d 159.3, 158.1, 158.0,
m) ppm; 13C NMR (50 MHz, CDCl3):
d
152.9, 141.6, 139.9, 132.5, 132.1,
151.3, 141.6, 139.4, 134.1, 132.7, 131.1, 129.5, 129.4, 129.1, 128.2, 127.2,
124.8, 122.3, 120.8, 116.8, 114.1, 107.6, 107.4, 55.7, 55.5, 55.4 ppm;
HRMS (ESI) calcd for C26H21NO3 [MþH] 396.1600 found 396.1574.
131.2,130.0,129.0,128.5,128.2,127.9,127.7,127.1,126.9,126.6,114.1 ppm;
HRMS (ESI) calcd for C23H16N [MþH] 306.1283 found 306.1271.
4.3.2. 10-Methyl-8-(4-methylphenyl)benzo[a]phenanthridine
4.3.8. 2-Methoxy-8-phenylbenzo[a]phenanthridin-3-yl methyl ether
(4b). Brown solid; yield 67% (0.112 g); mp 146e148 ꢀC; Rf¼0.44
(4h). Colorless solid; yield 66% (0.121 g); mp 185e187 ꢀC; Rf¼0.34
(2:8 EtOAc/hexane); FT-IR (KBr) 2926, 1602, 1550, 1460, 1218 cmꢁ1
;
(2:8 EtOAc/hexane); FT-IR (KBr) 2963, 1622, 1511, 1462, 1215 cmꢁ1
;

A.K. Mandadapu et al. / Tetrahedron 68 (2012) 8207e8215
8213
1H NMR (300 MHz, CDCl3):
(1H, s), 8.10 (2H, d, J¼7.9 Hz), 7.60e7.48 (8H, m), 4.07 (6H, s) ppm;
13C NMR (50 MHz, CDCl3):
153.3, 151.0, 149.6, 140.2, 134.2, 132.2,
d
9.25 (1H, s), 9.15 (1H, d, J¼7.9 Hz), 8.52
127.0, 121.6, 110.3, 21.7, 21.6 ppm; HRMS (ESI) calcd for C25H19IN
[MþH] 460.0562 found 460.0549.
d
130.2, 129.5, 128.6, 127.7, 127.4, 127.1, 126.4, 107.6, 106.7, 56.4 ppm;
HRMS (ESI) calcd for C25H20NO2 [MþH] 366.1494 found 366.1489.
4.4.3. 7-Iodo-10-tert-butyl-8-(4-tert-butylphenyl)benzo[a]phenan-
thridine (5c). Gray solid; yield 93% (0.252 g); mp 228e230 ꢀC;
Rf¼0.48 (2:8 EtOAc/hexane); FT-IR (KBr) 2960, 2868, 1618, 1503,
4.3.9. 2,3-Dimethoxy-10-methyl-8-(4-methylphenyl)benzo[a]phe-
nanthridine (4i). Off white solid; yield 62% (0.122 g); mp
136e138 ꢀC; Rf¼0.33 (2:8 EtOAc/hexane); FT-IR (KBr) 3015, 2922,
1461, 1215 cmꢁ1; 1H NMR (300 MHz, CDCl3):
d 9.42 (1H, s), 9.10 (1H,
d, J¼8.5 Hz), 8.98 (1H, d, J¼8.9 Hz), 8.21 (1H, d, J¼7.8 Hz), 7.94e7.89
(1H, m), 7.79e7.74 (2H, m), 7.60e7.55 (3H, m), 7.30e7.25 (2H, m),
1619, 1578, 1456, 1246 cmꢁ1; 1H NMR (300 MHz, CDCl3):
d
9.18 (1H,
1.45 (9H, s), 1.28 (9H, s) ppm; 13C NMR (50 MHz, CDCl3):
d 152.6,
s), 8.99 (1H, d, J¼8.5 Hz), 8.44 (1H, s), 8.00 (1H, s), 7.88 (1H, s),
7.50e7.48 (3H, m), 7.41 (1H, s), 7.34 (2H, d, J¼7.6 Hz), 4.12 (3H, s),
4.08 (3H, s), 2.50 (3H, s), 2.48 (3H, s) ppm; 13C NMR (50 MHz,
150.9, 149.9, 147.6, 141.8, 141.5, 133.8, 132.3, 131.0, 129.6, 128.7, 128.1,
127.6, 127.4, 127.0, 125.3, 124.3, 121.4, 109.5, 34.9, 31.6, 31.1 ppm;
HRMS (ESI) calcd for C31H31IN [MþH] 544.1501 found 544.1496.
CDCl3):
d 153.0, 150.5, 149.4, 142.6, 140.2, 139.3, 136.2, 132.4, 130.0,
129.2,128.7,128.5,128.3,128.1,126.9,126.7,123.7,119.9,114.2,107.5,
106.6, 56.2, 56.1, 21.7, 21.4 ppm; HRMS (ESI) calcd for C27H24NO2
[MþH] 394.1807 found 394.1802.
4.4.4. 7-Iodo-10-methoxy-8-(4-methoxyphenyl)benzo[a]phenan-
thridine (5d). Yellow solid; yield 92% (0.226 g); mp 214e216 ꢀC;
Rf¼0.45 (2:8 EtOAc/hexane); FT-IR (KBr) 3019, 2938, 1617, 1561,
1464, 1217 cmꢁ1; 1H NMR (300 MHz, CDCl3):
d 9.27 (1H, br s), 7.56
4.3.10. 2,3-Dimethoxy-10-tert-butyl-8-(4-tert-butylphenyl)benzo[a]
phenanthridine (4j). Yellow solid; yield 67% (0.159 g); mp
176e178 ꢀC; Rf¼0.28 (2:8 EtOAc/hexane); FT-IR (KBr) 3018, 2925,
(1H, d, J¼8.6 Hz), 7.36e7.30 (4H, m), 6.90 (2H, d, J¼8.7 Hz),
6.64e6.54 (4H, m), 3.96 (3H, s), 3.83 (3H, s) ppm; 13C NMR (75 MHz,
CDCl3):
d 159.9, 158.2, 154.8, 153.0, 150.2, 147.2, 132.3, 130.2, 129.5,
1615, 1580, 1512, 1460, 1262 cmꢁ1
;
1H NMR (300 MHz, CDCl3):
127.4, 126.9, 126.4, 125.2, 122.6, 113.8, 106.1, 103.1, 55.6, 55.3 ppm;
d
9.19 (1H, s), 8.99 (1H, d, J¼8.5 Hz), 8.44 (1H, s), 8.00 (1H, s), 7.88
HRMS (ESI) calcd for C25H19INO2 [MþH] 492.0460 found 492.0438.
(1H, s), 7.52e7.48 (3H, m), 7.42 (1H, s), 7.35 (2H, d, J¼7.7 Hz), 4.12
(3H, s), 4.08 (3H, s), 1.25 (9H, s), 1.23 (9H, s), ppm; 13C NMR
4.4.5. 7-Iodo-3-methoxy-8-phenylbenzo[a]phenanthridine
(5e). Light yellow solid; yield 89% (0.205 g); mp 229e231 ꢀC;
Rf¼0.48 (2:8 EtOAc/hexane); FT-IR (KBr) 3022, 2915, 1619, 1592,
(75 MHz, CDCl3):
d 153.0, 150.4, 149.4, 142.4, 142.2, 140.2, 139.3,
137.3, 137.2, 136.1, 132.3, 129.9, 129.2, 128.5, 128.4, 128.2, 128.0,
126.8, 126.6, 123.6, 119.9, 114.1, 107.5, 106.5, 56.2, 56.1, 32.0,
29.8 ppm; HRMS (ESI) calcd for C33H36NO2 [MþH] 478.2746 found
478.2735.
1428 cmꢁ1 1H NMR (300 MHz, CDCl3):
; d 9.37 (1H, s), 8.99 (2H, d,
J¼8.9 Hz), 7.69 (1H, t, J¼6.9 Hz), 7.60e7.46 (7H, m), 7.37e7.34 (2H,
m), 7.25 (1H, s), 4.06 (3H, s) ppm; 13C NMR (75 MHz, CDCl3):
d
158.7,
152.1,146.1,144.5,141.1,139.4,133.5,130.2,129.8,129.5,128.6,128.4,
128.0, 127.9, 127.1, 126.6, 122.7, 121.9, 114.2, 110.0, 107.1, 55.8 ppm;
HRMS (ESI) calcd for C24H17INO [MþH] 462.0355 found 462.0350.
4.4. General procedure for the 6-endo-iodocyclizations 5aeo
A flame dried round-bottom flask was charged with 5 mL of
acetonitrile and 4-phenyl-3-phenylethynyl-isoquinolines 3aeo
(0.5 mmol), under a nitrogen atmosphere, followed by dropwise
addition of 0.75 mmol of ICl (1 M solution in DCM) at 0 ꢀC. The
reaction mixture was allowed to stir for indicated time
(20e30 min), the disappearance of the starting material was de-
termined by TLC. The reaction was then quenched with a saturated
solution of NaHCO3 (10 mL) and extracted with EtOAc (3ꢂ20 mL).
The organic phases were combined, dried over Na2SO4, and con-
centrated under reduced pressure, and the crude mixture was
purified by column chromatography on silica gel (60e120 mesh)
using EtOAc/hexane as the eluent to afford 5.
4.4.6. 7-Iodo-10-methyl-8-(4-methylphenyl)benzo[a]phenanthridin-
3-yl methyl ether (5f). Colorless solid; yield 91% (0.223 g);
mp>250 ꢀC; Rf¼0.44 (2:8 EtOAc/hexane); FT-IR (KBr) 3022, 2929,
1625, 1512, 1217 cmꢁ1 1H NMR (300 MHz, CDCl3):
; d 9.32 (1H, s),
8.95 (1H, d, J¼9.1 Hz), 8.85 (1H, d, J¼8.5 Hz), 7.54e7.48 (3H, m), 7.39
(3H, d, J¼7.5 Hz), 7.23 (2H, d, J¼7.8 Hz), 4.04 (3H, s), 2.52 (3H, s),
2.44 (3H, s) ppm; 13C NMR (75 MHz, CDCl3):
d 158.6, 151.6, 145.8,
141.7, 140.8, 137.6, 137.0, 133.8, 130.0, 129.8, 129.3, 128.6, 128.5,
127.8, 127.5, 127.0, 122.6, 121.8, 114.2, 110.4, 107.1, 55.8, 21.7,
21.6 ppm; HRMS (ESI) calcd for C26H21INO [MþH] 490.0668 found
490.0644.
4.4.7. 7-Iodo-10-tert-butyl-8-(4-tert-butylphenyl)benzo[a]phenan-
thridin-3-yl methyl ether (5g). Brown solid; yield 92% (0.264 g); mp
225e227 ꢀC; Rf¼0.40 (2:8 EtOAc/hexane); FT-IR (KBr) 2957, 1628,
4.4.1. 7-Iodo-8-phenylbenzo[a]phenanthridine (5a). Light brown
solid; yield 88% (0.189 g); mp 192e194 ꢀC; Rf¼0.55 (2:8 EtOAc/
hexane); FT-IR (KBr) 2939, 2891, 1598, 1442, 1280 cmꢁ1
;
1H NMR
1510, 1459, 1222 cmꢁ1 1H NMR (300 MHz, CDCl3):
; d 9.34 (1H, s),
(300 MHz, CDCl3):
J¼7.8 Hz), 7.94 (1H, t, J¼7.1 Hz), 7.81e7.68 (2H, m), 7.62e7.47 (5H,
m), 7.37e7.35 (2H, m) ppm; 13C NMR (75 MHz, CDCl3):
153.0,
d
9.45 (s, 1H), 9.06 (t, J¼9.1 Hz, 2H), 8.23 (1H, d,
9.00 (1H, d, J¼9.2 Hz), 8.92 (1H, d, J¼8.8 Hz), 7.75 (1H, dd, J1¼1.9 Hz,
J2¼8.9 Hz), 7.59e7.48 (5H, m), 7.28 (2H, d, J¼8.3 Hz), 4.05 (3H, s),
d
1.45 (9H, s), 1.27 (9H, s) ppm; 13C NMR (75 MHz, CDCl3):
d 158.6,
147.1, 144.4, 142.0, 133.4, 132.2, 131.1, 130.1, 129.7, 128.7, 128.6, 128.4,
128.2, 128.0, 127.9, 127.5, 127.1, 126.8, 121.6, 109.9 ppm; HRMS (ESI)
calcd for C23H15IN [MþH] 432.0249 found 432.0244.
151.7, 150.8, 149.9, 146.5, 141.6, 141.0, 133.8, 129.7, 128.6, 127.6, 127.4,
127.1, 125.3, 125.0, 124.3, 122.6, 121.7, 109.7, 107.1, 55.8, 34.96, 34.9,
31.6, 31.1 ppm; HRMS (ESI) calcd for C32H33INO [MþH] 574.1607
found 574.1599.
4.4.2. 7-Iodo-10-methyl-8-(4-methylphenyl)benzo[a]phenanthridine
(5b). Light orange solid; yield 85% (0.195 g); mp 208e210 ꢀC;
Rf¼0.52 (2:8 EtOAc/hexane); FT-IR (KBr) 3024, 2926, 1625, 1507,
4.4.8. 7-Iodo-3,10-dimethoxy-8-(4-methoxyphenyl)benzo[a]phenan-
thridine (5h). Orange solid; yield 93% (0.242 g); mp 242e244 ꢀC;
Rf¼0.36 (2:8 EtOAc/hexane); FT-IR (KBr) 2922, 2854, 1619, 1580,
1454, 1217 cmꢁ1 1H NMR (300 MHz, CDCl3):
; d 9.38 (1H, s), 9.02
(1H, d, J¼8.5 Hz), 8.89 (1H, d, J¼8.6 Hz), 8.17 (1H, d, J¼7.5 Hz), 7.88
(1H, t, J¼7.1 Hz), 7.74 (1H, t, J¼7.2 Hz), 7.51 (1H, d, J¼7.4 Hz),
7.39e7.37 (3H, m), 7.23 (2H, d, J¼7.9 Hz), 2.52 (3H, s), 2.44 (3H, s)
1460, 1219 cmꢁ1; 1H NMR (300 MHz, CDCl3):
d 9.15 (1H, s), 7.37 (2H,
d, J¼8.8 Hz), 7.28 (1H, s), 6.90 (2H, d, J¼8.8 Hz), 6.81 (1H, s),
6.69e6.57 (4H, m), 4.03 (3H, s), 3.83 (3H, s), 3.80 (3H, s) ppm; 13C
ppm; 13C NMR (75 MHz, CDCl3):
d
152.5, 146.8, 141.6, 137.6, 137.1,
NMR (75 MHz, CDCl3):
d 160.0, 155.5, 154.0, 151.6, 150.3, 150.1, 147.6,
133.8, 132.2, 130.9, 129.9, 129.3, 128.7, 128.1, 127.8, 127.6, 127.4,
132.1, 130.1, 128.5, 126.6, 124.9, 124.4, 113.8, 106.5, 103.2, 98.7, 56.1,

8214
A.K. Mandadapu et al. / Tetrahedron 68 (2012) 8207e8215
56.0, 55.3 ppm; HRMS (ESI) calcd for C26H21INO3 [MþH] 522.0566
13C NMR (75 MHz, CDCl3):
d 162.7, 159.4, 151.5, 151.4, 150.9, 150.2, 147.5,
found 522.1478.
141.3, 133.9, 131.0, 129.7, 129.6, 127.5, 127.3, 125.4, 125.3, 124.4, 121.3,
120.7, 120.3, 114.2, 112.4, 112.1, 109.4, 35.0, 34.9, 31.6, 31.3 ppm; HRMS
(ESI) calcd for C31H30FIN [MþH] 562.1407 found 562.1408.
4.4.9. 7-Iodo-2,3-dimethoxy-8-phenylbenzo[a]phenanthridine
(5i). Pale brown solid; yield 90% (0.221 g); mp 210e212 ꢀC; Rf¼0.42
(2:8 EtOAc/hexane); FT-IR (KBr) 2924, 1622, 1509, 1459, 1262 cmꢁ1
;
4.4.15. 4-(3-Fluoro-7-iodo-10-methoxybenzo[a]phenanthridin-8-yl)
phenyl methyl ether (5o). Brown solid; yield 91% (0.232 g); mp
184e186 ꢀC; Rf¼0.33 (2:8 EtOAc/hexane); FT-IR (KBr) 2958, 1617,
1H NMR (300 MHz, CDCl3):
d
9.28 (1H, s), 9.03 (1H, d, J¼8.3 Hz),
8.44 (1H, s), 7.67 (1H, t, J¼7.0 Hz), 7.60e7.44 (6H, m), 7.35 (2H, d,
J¼6.4 Hz), 4.13 (6H, s) ppm; 13C NMR (50 MHz, CDCl3):
d
153.3,
1524, 1448, 1215 cmꢁ1 1H NMR (300 MHz, CDCl3):
; d 8.84 (1H, s),
150.9, 150.1, 146.2, 144.4, 141.4, 133.3, 130.1, 129.7, 128.6, 128.2,
128.0, 126.8, 126.5, 124.2, 121.1, 110.1, 107.1, 106.8, 56.3 ppm; HRMS
(ESI) calcd for C25H19INO2 [MþH] 492.0461 found 492.0433.
7.98e7.94 (2H, m), 7.81e7.78 (1H, m), 7.60e7.55 (1H, m), 7.49 (2H,
d, J¼8.6 Hz), 7.32e7.27 (2H, m), 6.98 (2H, d, J¼8.7 Hz), 3.91 (3H, s),
3.86 (3H, s) ppm; 13C NMR (50 MHz, CDCl3):
d 160.4, 159.4, 150.3,
144.1, 139.5, 135.8, 135.1, 132.9, 132.0, 131.5, 131.3, 130.6, 128.3, 127.7,
126.9, 125.7, 124.1, 117.1, 113.9, 113.2, 55.6, 55.5 ppm; HRMS (ESI)
calcd for C25H18FINO2 [MþH] 510.0366 found 510.1747.
4.4.10. 7-Iodo-2,3-dimethoxy-10-methyl-8-(4-methylphenyl)benzo
[a]phenanthridine (5j). Pale green solid; yield 92% (0.238 g); mp
216e218 ꢀC; Rf¼0.35 (2:8 EtOAc/hexane); FT-IR (KBr) 2924, 2854,
1617, 1511, 1460, 1218 cmꢁ1; 1H NMR (300 MHz, CDCl3):
d
9.25 (1H,
4.4.16. 7-Bromo-8-phenylbenzo[a]phenanthridine
(5p). Yellow
s), 8.93 (1H, d, J¼8.6 Hz), 8.42 (1H, s), 7.52e7.46 (2H, m), 7.38 (3H,
solid; yield 68% (0.130 g); mp 206e208 ꢀC; Rf¼0.50 (2:8 EtOAc/hex-
s), 7.22 (3H, d, J¼7.8 Hz), 4.12 (6H, s), 2.52 (3H, s), 2.45 (3H, s) ppm;
ane); FT-IR (KBr) 2935, 2888, 1578, 1442, 1278 cmꢁ1 1H NMR
;
13C NMR (75 MHz, CDCl3):
d
153.2, 150.5, 150.0, 146.0, 141.7, 141.2,
(300 MHz, CDCl3): d 9.49 (1H, s), 9.09e9.03 (2H, m), 8.22 (1H, d,
139.4, 137.6, 136.8, 133.7, 129.9, 129.3, 128.9, 128.4, 128.2, 128.0,
127.7, 126.8, 124.2, 114.2, 107.1, 106.9, 56.3, 21.7, 21.6 ppm; HRMS
(ESI) calcd for C27H23INO2 [MþH] 520.0773 found 520.0762.
J¼7.7 Hz), 7.96e7.90 (1H, m), 7.81e7.76 (1H, m), 7.72e7.67 (1H, m),
7.62e7.50 (5H, m), 7.41 (2H, d, J¼6.6 Hz) ppm; 13C NMR (75 MHz,
CDCl3): d153.1, 141.9, 140.7, 140.5, 133.5,132.2, 131.2, 130.1, 129.0, 128.8,
128.6, 128.0, 127.9, 127.8, 127.6, 127.1, 127.0, 126.7, 125.5, 122.2 ppm;
4.4.11. 7-Iodo-2,3-dimethoxy-10-tert-butyl-8-(4-tert-butylphenyl)
benzo[a]phenanthridine (5k). Light yellow solid; yield 94%
(0.283 g); mp 215e217 ꢀC; Rf¼0.33 (2:8 EtOAc/hexane); FT-IR (KBr)
HRMS (ESI) calcd for C23H15BrN [MþH] 384.0388 found 384.0369.
4.4.17. 7-(3,4-Dimethoxyphenyl)-8-diphenylbenzo[a]phenanthridine
(7a). Brown solid; yield 82% (0.181 g); mp 174e176 ꢀC; Rf¼0.30 (2:8
EtOAc/hexane); FT-IR (KBr) 3020, 2928, 2855, 1581, 1513, 1466,
2958, 1641, 1509, 1462, 1218 cmꢁ1 1H NMR (300 MHz, CDCl3):
;
d
9.26 (1H, s), 8.99 (1H, d, J¼8.5 Hz), 8.47 (1H, s), 7.75 (1H, d,
J¼8.3 Hz), 7.57 (3H, t, J¼7.3 Hz), 7.47 (1H, s), 7.28 (2H, d, J¼8.0 Hz),
1217 cmꢁ1 1H NMR (300 MHz, CDCl3):
; d 9.36 (1H, s), 9.11 (2H, dd,
4.15 (3H, s), 4.13 (3H, s), 1.45 (9H, s), 1.28 (9H, s) ppm; 13C NMR
J1¼2.7 Hz, J2¼8.2 Hz), 8.13 (1H, d, J¼7.4 Hz), 7.89 (1H, t, J¼7.1 Hz),
7.78e7.66 (3H, m), 7.53 (1H, t, J¼7.4 Hz), 7.25e7.00 (5H, m),
6.83e6.76 (2H, m), 6.68 (1H, s), 3.84 (3H, s), 3.64 (3H, s) ppm; 13C
(50 MHz, CDCl3):
d 153.3, 150.9, 150.5, 150.1, 149.7, 146.8, 141.5,
133.7, 129.7, 128.4, 127.7, 126.6, 125.3, 124.9, 124.6, 124.2, 121.0,
107.2, 106.9, 56.4, 56.3, 34.9, 31.6, 31.2 ppm; HRMS (ESI) calcd for
C33H35INO2 [MþH] 604.1713 found 604.1698.
NMR (75 MHz, CDCl3): d 152.3,147.7,147.3,142.8, 140.0,139.4, 138.2,
132.7, 132.3, 131.5,131.0, 130.6, 129.3,128.5, 127.7,127.4,127.0, 126.9,
126.8, 126.5, 126.1, 124.4, 120.7, 115.2, 110.1, 55.66, 55.6 ppm; HRMS
(ESI) calcd for C31H24NO2 [MþH] 442.1807 found 442.1799.
4.4.12. 3-Fluoro-7-iodo-8-phenylbenzo[a]phenanthridine (5l). Pale
yellow solid; yield 86% (0.193 g); mp 219e221 ꢀC; Rf¼0.44 (2:8
EtOAc/hexane); FT-IR (KBr) 2967, 1628, 1518, 1444, 1222 cmꢁ1
;
1H
4.4.18. Butyl (E)-3-(8-phenylbenzo[a]phenanthridin-7-yl)prop-2-
enoate (7b). Yellow solid; yield 78% (0.168 g); mp 194e196 ꢀC;
Rf¼0.42 (2:8 EtOAc/hexane); FT-IR (KBr) 3069, 2926, 1631, 1457,
NMR (300 MHz, CDCl3):
d
9.39 (1H, s), 9.08 (1H, dd, J1¼4.8 Hz,
J2¼9.1 Hz), 8.95 (1H, d, J¼8.4 Hz), 7.84 (1H, dd, J1¼2.5 Hz,
J2¼8.1 Hz), 7.74e7.67 (2H, m), 7.62e7.49 (5H, m), 7.35 (2H, d,
1218 cmꢁ1 1H NMR (300 MHz, CDCl3):
; d 9.43 (1H, s), 9.04 (2H, t,
J¼6.2 Hz) ppm; 13C NMR (75 MHz, CDCl3):
d
163.6, 158.6, 151.9,
J¼8.2 Hz), 8.25 (1H, s), 8.19 (1H, d, J¼7.8 Hz), 7.90 (1H, t, J¼7.0 Hz),
7.78e7.66 (3H, m), 7.54e7.49 (4H, m), 7.37e7.35 (2H, m), 6.62 (1H, d,
J¼16.3 Hz), 4.11 (2H, t, J¼6.5 Hz), 1.65 (2H, m), 1.34 (2H, q, J1¼7.5 Hz,
J2¼15.1 Hz), 0.92 (3H, t, J¼7.3 Hz) ppm; 13C NMR (75 MHz, CDCl3):
147.1, 144.2, 133.6, 130.0, 129.8, 129.6, 129.3, 129.0, 128.6, 128.5,
128.1, 127.8, 127.4, 127.0, 121.5, 120.9, 120.5, 112.5, 112.1, 109.7 ppm;
HRMS (ESI) calcd for C23H14FIN [MþH] 450.0155 found 450.0147.
d
167.5, 152.0, 142.0. 138.6, 135.9, 132.8, 132.3, 130.8, 130.7, 130.1,
4.4.13. 3-Fluoro-7-iodo-10-methyl-8-(4-methylphenyl)benzo[a]phe-
nanthridine (5m). Pale yellow solid; yield 84% (0.200 g); mp
232e234 ꢀC; Rf¼0.40 (2:8 EtOAc/hexane); FT-IR (KBr) 3015, 2922,
129.9, 128.6, 128.5, 128.4, 127.9, 127.8, 127.6, 127.2, 127.1, 126.7, 126.1,
125.7, 125.6, 120.7, 64.2, 30.8, 19.3, 13.9 ppm; HRMS (ESI) calcd for
C30H26NO2 [MþH] 432.1964 found 432.1950.
1614, 1507, 1453, 1218 cmꢁ1; 1H NMR (300 MHz, CDCl3):
d 9.35 (1H,
s), 9.06 (1H, dd, J1¼4.8 Hz, J2¼9.2 Hz), 8.84 (1H, d, J¼8.5 Hz), 7.82
(1H, dd, J1¼2.3 Hz, J2¼7.9 Hz), 7.71e7.64 (1H, m), 7.54 (1H, d,
J¼8.5 Hz), 7.41e7.38 (3H, m), 7.23 (2H, d, J¼7.9 Hz), 2.53 (3H, s), 2.46
4.4.19. 8-Phenyl-7-(1H-pyrrol-1-yl)benzo[a]phenanthridine
(7c). Colorless solid; yield 65% (0.120 g); mp 223e225 ꢀC; Rf¼0.40
(2:8 EtOAc/hexane); FT-IR (KBr) 3058, 2925, 1576, 1488, 1360 cmꢁ1
;
(3H, s) ppm; 13C NMR (75 MHz, CDCl3):
d
151.5, 151.4, 146.8, 141.5,
1H NMR (300 MHz, CDCl3):
d
9.39 (1H, s), 9.14 (2H, dd, J1¼2.8 Hz,
137.7, 137.4, 133.9, 129.9, 129.7, 129.6, 129.3, 129.2, 129.0, 128.9,
127.9, 127.7, 127.3, 121.5, 120.7, 120.3, 112.4, 112.0, 110.1, 21.8,
21.6 ppm; HRMS (ESI) calcd for C25H18FIN [MþH] 478.0468 found
478.0453H]þ.
J2¼7.8 Hz), 8.18 (1H, d, J¼7.7 Hz), 7.95 (1H, t, J¼7.1 Hz), 7.85e7.73
(3H, m), 7.60 (1H, t, J¼7.3 Hz), 7.37e7.29 (5H, m), 6.71 (2H, s), 6.16
(2H, s) ppm; 13C NMR (75 MHz, CDCl3):
d 153.6, 140.8, 138.4, 136.4,
135.5, 132.3, 132.2, 131.0, 130.0, 129.4, 128.8, 128.1, 128.0, 127.9,
127.6, 127.4, 126.9, 124.4, 121.4, 108.1 ppm; HRMS (ESI) calcd for
C27H19N2 [MþH] 371.1548 found 371.1542.
4.4.14. 3-Fluoro-7-iodo-10-tert-butyl-8-(4-tert-butylphenyl)benzo
[a]phenanthridine (5n). Yellow solid; yield 90% (0.252 g); mp
140e142 ꢀC;Rf¼0.37 (2:8 EtOAc/hexane); FT-IR (KBr) 2924, 2857,1610,
4.4.20. 7,8-Diphenylbenzo[a]naphtho[1,2-c]phenanthridine
(7d). Light orange solid; yield 60% (0.144 g); mp>250 ꢀC; Rf¼0.48
(2:8 EtOAc/hexane); FT-IR (KBr) 3006, 2926, 2858, 1638, 1437,
1457, 1218 cmꢁ1; 1H NMR (300 MHz, CDCl3):
d 9.36 (1H, s), 9.09 (1H,
dd, J1¼4.8 Hz, J2¼8.8 Hz), 8.88 (1H, d, J¼8.8 Hz), 7.83e7.76 (2H, m),
7.69e7.55 (4H, m), 7.28 (2H, d, J¼8.2 Hz),1.45 (9H, s),1.28 (9H, s) ppm;
1217 cmꢁ1; 1H NMR (600 MHz, CDCl3):
d
9.13 (1H, d, J¼9.0 Hz), 8.99

A.K. Mandadapu et al. / Tetrahedron 68 (2012) 8207e8215
8215
Synlett 2007, 1591e1594; (i) Saha, B.; Kumar, R.; Maulik, P. R.; Kundu, B. Tet-
rahedron Lett. 2006, 47, 2765e2769.
(1H, d, J¼8.4 Hz), 8.68 (1H, d, J¼7.8 Hz), 7.92 (2H, t, J¼9.0 Hz), 7.70
(1H, t, J¼7.2 Hz), 7.64 (1H, t, J¼7.3 Hz), 7.45 (1H, d, J¼7.0 Hz),
7.36e7.35 (2H, m), 7.28e7.25 (4H, m), 7.11e7.05 (5H, m), 6.90 (1H, t,
J¼7.2 Hz), 6.81 (2H, t, J¼7.2 Hz), 6.72 (2H, d, J¼8.4 Hz) ppm; 13C
7. (a) Krane, B. D.; Fagbule, M. O.; Shamma, M.; Gozler, B. J. Nat. Prod. 1984, 47,
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NMR (150 MHz, CDCl3):
d 159.1, 139.9, 135.9, 134.6, 132.6, 132.5,
131.59, 131.58, 130.9, 130.5, 130.4, 129.9, 128.8, 128.3, 128.2, 128.0,
127.4,127.3,127.2,127.1,127.0,126.5,126.2,125.9,125.8, 124.7,124.2,
110.6, 105.0 ppm; HRMS (ESI) calcd for C37H24N [MþH] 482.1909
found 482.1903.
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Acknowledgements
9. Roesch, K. R.; Zhang, H.; Larock, R. C. J. Org. Chem. 2001, 66, 8042e8051.
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A.K.M., M.D.D., and R.K.A. are thankful to CSIR, New Delhi, India
for fellowships. The authors would like to thank SAIF, CDRI, India
for providing analytical data.
Supplementary data
Copies of 1H, 13C NMR and HRMS spectra of 3aeo, 4aej, 5aep,
7aed. Supplementary data related to this article can be found
online at http://dx.doi.org/10.1016/j.tet.2012.07.067.
ꢀ
C. J. Org. Lett. 2007, 9, 627e630; (l) Chretien, J. M.; Mallinger, A.; Zammattio, F.;
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1781e1785; (m) Saito, T.; Nihei, H.; Otani, T.; Suyama, T.; Furukawa, N.; Saito, M.
Chem. Commun. 2008, 172e174; (n) Mamane, V.; Hannen, P.; Furstner, A. Chem.
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