Camphorsulfonic Acid Catalyzed One-Pot Three-Component Reaction for the Synthesis of Fused Quinoline and Benzoquinoline Derivatives

Article abstract of DOI:10.1021/acs.joc.7b02159

A simple and an efficient one-pot three-component reaction of arylamines, aromatic aldehydes, and cyclic ketones was described for the synthesis of various fused quinoline, benzoquinoline, and naphthoquinoline derivatives by using camphorsulfonic acid as a catalyst. The exploitation of pregnenolone steroid for benzoquinolines and terephthalaldehyde for bis-benzoquinolines synthesis was achieved with 68-75% yields. The reactivity of arylamines and the mechanistic study for the formation of benzoquinoline was described precisely. The present protocol offers a great potential for atom-economy under mild conditions.

Full text of DOI:10.1021/acs.joc.7b02159

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Article
Camphorsulfonic Acid Catalysed One-Pot Three Component Reaction
for the Synthesis of Fused Quinoline and Benzoquinoline Derivatives
Radhakrishna Gattu, Prasanta Ray Bagdi, R. Sidick Basha, and Abu Taleb Khan
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.7b02159 • Publication Date (Web): 20 Oct 2017
Downloaded from http://pubs.acs.org on October 20, 2017
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Camphorsulfonic Acid Catalysed One-Pot Three Component Reaction for
the Synthesis of Fused Quinoline and Benzoquinoline Derivatives
Radhakrishna Gattu, Prasanta Ray Bagdi,† R. Sidick Basha,† and Abu T. Khan*
Department of Chemistry, Indian Institute of Technology Guwahati, Guwahati 781 039, India
Tel.: +91 361 2582305; Fax: +91 361 2582349
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Email: atk@iitg.ernet.in (A T. Khan)
( )
n
R1
Ar
N
N
CHO
NH2
(10 mol%)
(+)
O
(
Ar
( )
)
n
CSA
-
+
+
MeCN
n
[One-pot]
n = 1, 2, 3, 4 & 8
Aryl Amine
1-Naphthylamine
2-Naphthylamine/2-Aminoanthracene
n
40 examples
up to 64-94% yield
Ar
N
ABSTRACT: A simple and an efficient oneꢀpot three component reaction of arylamines,
aromatic aldehydes and cyclic ketones was described for the synthesis of various fused
quinoline, benzoquinoline and napthoquinoline derivatives by using camphorsulfonic acid as
a
catalyst. The exploitation of pregnenolone steroid for benzoquinolines and
terephthalaldehyde for bisꢀbenzoquinolines synthesis was achieved with 68ꢀ75% yields. The
reactivity of aryl amines and the mechanistic study for the formation of benzoquinoline was
described precisely. The present protocol offers a great potential for atomꢀeconomy under
mild condition.
INTRODUCTION
Nꢀheterocyclics are an important class of compounds in biological, medicinal and material
chemistry. Of these, quinoline, benzoquinoline derivatives are an interesting class of
heterocyclic compounds having a large scope to be investigated by the synthetic chemists
because of their natural occurrence and having medicinal value.1ꢀ3 These scaffolds are found
to be having several applications in agrochemicals, pharmaceuticals, dyestuffs and functional
materials.4 They have wide range of biological activities including antitubercular,5a
anticancer,5b,c antipsychotics,5d antimicrobial,6a antiꢀHIV,6b and for the treatment of
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neurodegenerative diseases.7 Marinoquinolines are a class of fused quinolines isolated from
the marine bacteria having antibacterial and antifungal activities. Fused quinolines and
benzoquinolines core units are found in various alkaloids8a and commercial drugs8b as shown
in Figure 1.
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Figure 1. Biologically active Quinoline and Benzoquinoline core units
Quinolines act as effective ligands in cross coupling reaction9a and it also plays a crucial role
in asymmetric synthesis as a catalyst.9b,c In addition they are also used as ligands for
preparation of OLED complexes10a and with conjugated polymers acting as chemoꢀsensors of
metal ions.10b,c Due to its potential biological activity and tremendous applications, chemists
have developed various classical methods for the synthesis of quinolines such as Combes
reaction,11 Skraup reaction,12
Doebnerꢀvon Miller,13 ConradꢀLimpach14 and Knorr
synthesis15 which involve the formation of new CꢀC bond as shown in (Figure 2, 1a) whereas,
in Pfitzinger16 and Friedlander17 reactions new CꢀC and CꢀN bonds were formed as shown in
(Figure 2, 1b). In traditional approach there are new strategies emerged for the synthesis of
quinolines through intramolecular cyclisation that involve formation of new CꢀN bond18
(Figure 2, 1c), NꢀC bond19 (Figure 2, 1d) and new CꢀC bond20a through Cross
dehydrogenative coupling,20bꢀd Dual oxidative coupling,20e and Oxidative tandem reactions.20f
The formation of new CꢀC or CꢀN/NꢀC bond is an interesting and challenging one for the
synthesis of heterocyclic compounds. Herein, we have focused on the synthesis of fused
quinolines derivatives through MCR strategy.
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Figure 2. The various approaches of substituted quinoline synthesis with present work
In earlier, Currian et.al developed fused quinoline through formation of new CꢀC bond by
involving cyclization of in situ generated oꢀvinyl anilides (Scheme 1a).21a Takasu et.al also
explored quinoline through CꢀC bond formation from areneꢀynamide cyclization via highly
reactive keteniminium intermediate (Scheme 1b).21b Banwell and coꢀworkers have developed
fused quinoline involving a new NꢀC bond through reductive cyclisation of βꢀnitroarylꢀenal
(Scheme 1c).21c Movassaghi group synthesized fused quinoline by condensation of amide
with trimethylsilyl enol ether (Scheme 1d).21d Wang22a et.al synthesized Benzo[f]quinoline
derivatives using MCRs having a drawback, they were unable to synthesize the Quinoline
and Benzo[h]quinoline from aniline and 1ꢀnaphthylamine because of low reactivity of the
substrate in presence of iodine catalyst. Apart from these Kozlov22b obtained 1,2,3,4ꢀ
tetrahydrobenzo[a]phenanthridine derivative along with byproduct benzo[a]acridines through
reaction of aldehyde with initially formed enamine from 2ꢀnaphthylamine and
cyclohexanone. More recently, Stryker22c and coworkers developed the synthesis of
benzo/napthoquinoline containing steroidal biomarkers22d,e through condensation reaction.
Many of these reported methods suffers from drawbacks such as multistep23a,b process,
difficult in isolation procedures, harsh reaction23c conditions, unsatisfactory yields, prolonged
reaction time, complex starting materials and also less substrate scope. In this context, the
development of new procedures for the synthesis of quinoline derivatives with structural
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diversity involving readily available starting materials are challenging efforts to the modern
synthetic organic chemists. Thus, we have focused on the development of a simple and an
efficient method for the synthesis of fused quinoline and benzoquinoline derivatives through
intermolecular cyclization of aryl amines, aromatic aldehydes and cyclic ketones in the
presence 10 mol% CSA as shown in Scheme 1.
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Scheme 1a
O
NHCHO
M
HO
Curran work
+
C-C Bond
formation
N
NHCHO
M = Li/Na
Scheme 1b
R1
R1
H
Takasu work
R1
N
C-C Bond
formation
N
N
Boc
Boc
Scheme 1c
NO2
Br
NO2
Ulmann
Br
Banwell work
CHO coupling
+
CHO
Ar N-C Bond
formation
N
Scheme 1d
R1
R1
OSiMe3
O
O
HN
R1
Movassaghi work
+
+
N
H
H
C-C & Ar C-C
Bond formation
H
N
Present work
NH2
n
CHO
O
One-pot
+
+
N
C-C & Ar C-C
Bond formation
n
Scheme 1. The main strategies of fused quinoline synthesis with present work
In general, quinolines preferentially undergo electrophilic substitution24a at the carbocyclic
ring rather than the heterocyclic ring because sp2ꢀhybridized nitrogen atom decreases the
reactivity by interacting with electrophiles. Whereas, Nucleophilic substitution occurs in
presence of strong nucleophile, hence it is prerequisite to synthesize substitution on
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heterocyclic ring rather than carbocyclic ring. We have focused on to synthesize substituted
Quinolines by employing protic acid, Camphorsulfonic acid is a strong sulfur containing
protic acid24bꢀe having broad scope in asymmetric synthesis, cyclisation reactions and
monoalkylation of anilines which promoted us to employ this catalyst for the synthesis of
fused quinoline and benzoquinoline derivatives.
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RESULTS AND DISCUSSION
We initially, investigated on optimization study for the synthesis of fused quinoline using
pꢀanisidine 1 (1.0 mmol), pꢀtolualdehyde 2 (1.0 mmol) and 4ꢀ(tertꢀbutyl)cyclohexanone 3
(1.0 mmol) as model substrate under reflux condition and the results are summarized in Table
1. Primarily, when the reaction was carried out in the absence of catalyst proved futile (Table
1, entry 1). Next, the reaction was tested with various lewis acid catalysts. On screening the
reaction with Yb(OTf)3 (Table 1, entry 2) in CH3CN resulted in isolation of the desired
product 4a in 54% yield. The product 4a was confirmed through IR, H, 13C NMR and
1
HRMS. The other lewis acids Cu(OTf)2, Zn(OTf)2, In(OTf)3, AgOTf, Bi(OTf)3 and FeCl3 gave
unsatisfactory yields (Table 1, entries 3ꢀ8). Whereas by employing iodine as a catalyst
resulted in 54% and 48% yields of product 4a in THF and CH3CN respectively (Table 1,
entries 9 and 10). Then, we observed on the protic acid catalysts like AcOH, TfOH and Lꢀ
Proline the reaction were failed to obtain the desired product (Table 1, entries 11ꢀ13) but,
PTSA resulted with satisfactory yields (Table 1, entry 14). Further for inferior results, the
same set of reaction was executed with 10 mol% CSA and the desired product 4a was
isolated in 78% yield. (Table 1, entry 15).
Table 1. Optimization of Reaction Conditionsa
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Entry
1
Catalyst
No catalyst
Yb(OTf)3
Cu(OTf)2
Zn(OTf)2
In(OTf)3
AgOTf
Mol %
ꢀ
Solvent
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
THF
Time (h) Yield 4a (%)b
24.0
3.0
NR
54
2
10
3
10
6.0
42
4
10
2.5
64
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5
10
2.5
60
6
10
3.0
62
7
Bi(OTf)3
FeCl3
10
2.5
36
8
10
12.0
4.0
30
9
Iodine
10
54
10
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12
13
14
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20
21
22
23
24
25
Iodine
10
CH3CN
ꢀ
4.0
48
AcOH
1 equiv
10
3.0
NR
NR
NR
68
TfOH
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
EtOH
24.0
24.0
6.0
LꢀProline
pꢀTSA
10
10
10
1.5
78
(±)-CSA
(±)ꢀCSA
(±)ꢀCSA
(±)ꢀCSA
(±)ꢀCSA
(±)ꢀCSA
(±)ꢀCSA
(±)ꢀCSA
(±)ꢀCSA
(±)ꢀCSA
(±)ꢀCSA
20
1.5
78
05
2.0
75
10
2.0
72
10
MeOH
DMSO
DCE
2.0
68
10
24.0
12.0
24.0
12.0
12.0
8.0
20
10
35
10
DMF
NR
NR
NR
NR
10
THF
10
H2O
10
Toluene
aAll the reactions were performed using pꢀanisidine (1.0 mmol), pꢀtolualdehyde (1.0 mmol) and 4ꢀ(tertꢀ
butyl)cyclohexanone (1.0 mmol). bIsolated yields.
In order to obtain better results, the reaction was also scrutinized with 20 mol% and 5 mol%
CSA, but the increment in yield was not observed (Table 1, entries 16 and 17). However, the
other solvents such as EtOH, MeOH, DMSO and DCE gave lower yields (Table 1, entries 18ꢀ
21), whereas DMF, THF, H2O and toluene failed to give the desired product 4a (Table 1,
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entries 22ꢀ25). Thus, it was noted that 10 mol% CSA in CH3CN under reflux condition is the
optimized condition for our present protocol in terms of reaction time and yield.
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Table 2. Substrate scope of anilinea,b
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SO3H
n
CHO
NH2
O
O
(10 mol%)
CH3CN, Reflux
R1
R2
+
R1
+
N
n
2
3
1
4a-o
R2
n = 1, 2, 3 & 8
MeO
Et
Me
N
N
N
N
4a
4c
4d
4b
Me
Me
Me
Me
2.5 h, 76%
1.5 h, 78%
2.5 h, 70%
6.0 h, 71%
Cl
Br
Cl
MeO
N
N
N
N
4g
4e
4h
4f
Me
Me
OMe
OMe
4.0 h, 66%
6.5 h, 72%
5.0 h, 68%
2.0 h, 68%
Me
MeO
N
Cl
N
N
Cl
Me
N
4l
4j
4i
4k
Me
Me
6.5 h, 75%
1.5 h, 74%
1.5 h, 82%
2.0 h, 68%
Me
Me
MeO
N
S
N
4o
N
4m
4n
Cl
2.0 h, 74%
7.0 h, 64%
Me
3.0 h, 69%
aThe reactions were carried out using anilines (1.0 mmol), aldehydes (1.0 mmol) and cyclic ketones (1.0 mmol)
in CH3CN. bIsolated yields.
With standard optimisation reaction condition, the scope of the reaction was investigated
with 4ꢀ(tertꢀbutyl)cyclohexanone, aromatic aldehydes (4ꢀMe and 4ꢀOMe) and various
anilines having para substituents on aromatic ring such as ꢀMe, ꢀEt, ꢀCl, ꢀBr and ꢀOMe
which gave the products 4b-h in 66ꢀ78% yield (Table 2). The aniline derivatives such as 4ꢀ
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NO2, 2ꢀNO2, 2ꢀI and 2,4ꢀMe failed to produce desired product which might be due to the
strong withdrawing nature and steric crowding at ortho position.
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Table 3. Substrate scope of 1ꢀnaphthylaminea,b
NH2
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SO3H
O
CHO
O
(10 mol%)
CH3CN, Reflux
R2
+
+
n
N
R2
3
2
5
6a-q
n = 1, 2, 3, 4 & 8
N
N
N
OH
N
6b
6d
6c
6a
OMe
Me
OH
1.25 h, 90%
1.33 h, 92%
1.5 h, 94%
1.33 h, 95%
OMe
OMe
N
N
N
N
6h
6g
6e
6f
NO2
Br
Cl
1.5 h, 80%
2.0 h, 77%
MeO
1.33 h, 82%
1.25 h, 87%
OMe
OMe
N
Br
N
N
N
6j
6i
6k
6l
F
Me
1.25 h, 80%
1.0 h, 91%
1.5 h, 85%
1.5 h, 88%
MeO
S
N
N
N
6n
6o
6m
1.5 h, 76%
4.5 h, 67%
1.33 h, 85%
N
N
S
O
N
N
6q
6p
6r
1.75 h, 72%
1.0 h, 84%
1.5 h, 78%
aThe reactions were carried out using aldehydes (1.0 mmol), cyclic ketones (1.0 mmol) and 1ꢀnaphthylamine
(1.0 mmol) in CH3CN. bIsolated yields.
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On the other hand, the reaction of mꢀchloroaniline, pꢀtolualdehyde and different cyclic
ketones like cyclopentanone and cycloheptanone lead to the isolation of products 4i-j in 74ꢀ
82% yield. Since the formation of other tautomer was not observed in metaꢀsubstituted
aniline due to steric hindrance on ortho postion, it is to be considered as a regiospecfic
reaction. Next, the reaction was extended with various other cyclic ketones namely
cyclohexanone, cycloheptanone and cyclododecanone all the reactions proceeded smoothly to
produce the products 4k-n. In addition, the heterocyclic aldehyde, thiopheneꢀ2ꢀaldehyde on
reaction with pꢀtoluidine and cycloheptanone to afford the product 4o in 69% yield.
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1
13
All the products were characterized by recording IR, H and C NMR spectra and HRMS.
The structure of the compound 4a was further confirmed by singleꢀcrystal Xꢀray
crystallographic data (see the Supporting Information).
OMe
NH2
OMe
SO3H
O
(10 mol%)
OMe
N
+
O
5
7
CH3CN, Reflux
5.0 h
CHO
8
OMe
OMe
64%
MeO
OMe
OMe
2h
Scheme 2. Reaction of 1ꢀnaphthylamine with 6ꢀmethoxytetralone
Inspired by the above transformations, we have further explored the generality of the reaction
with 1ꢀnaphthylamine 5 instead of anilines which produced fused benzo[h]quinoline
derivatives and the results are summarised in Table 3. When the reaction was carried out with
1ꢀnaphthylamine 5 (1.0 mmol), pꢀtolualdehyde 2 (1.0 mmol) and 4ꢀ(tertꢀbutyl)cyclohexanone
3 (1.0 mmol) under similar reaction condition induced the product 6a in 94% yield without
any column chromatographic separation. Substituted aromatic aldehydes with electron
donating and electron withdrawing groups such as 4ꢀOMe, 4ꢀOH, 3ꢀOH, 3,4,5ꢀOMe, 4ꢀCl, 4ꢀ
Br, 4ꢀNO2 and 3ꢀBr underwent reaction with 4ꢀ(tertꢀbutyl)cyclohexanone to generate the
products 6b-i in 77ꢀ95% yields.
The reaction was also extended with various substituted benzaldehydes and cyclic
ketones such as cyclohexanone, cycloheptanone, cyclooctanone and cyclododecanone which
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lead to the formation of desired products 6j-m in 67ꢀ91% yields. The reaction with 2ꢀ
naphthaldehyde and cycloheptanone furnished the product 6n in 76% yield whereas
heteroaromatic aldehydes, thiopheneꢀ2ꢀaldehyde and pyridineꢀ2ꢀcarbaldehyde on reaction
with cyclopentanone gave the products 6o-p in 78ꢀ85% yields while, 2ꢀfurfural and
thiopheneꢀ2ꢀaldehyde on reaction with cycloheptanone deliver the products 6q and 6r in 72%
and 84% yields respectively.
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Scheme 3. Reaction of 1ꢀnaphthylamine, pꢀtolualdehyde and 4,4ꢀDimethylcyclohexenone
In addition, we have applied our present methodology for the synthesis of 3ꢀmethoxyꢀ14ꢀ
(3,4,5ꢀtrimethoxyphenyl)ꢀ5,6ꢀdihydrodibenzo[c,i]phenanthridine (8) by employing 1ꢀ
naphthylamine (5), 3,4,5ꢀtrimethoxybenzaldehyde (2h) and 6ꢀmethoxytetralone (7) in the
presence of 10 mol% CSA under similar reaction conditions as shown in Scheme 2.
Table 4. Substrate scope of 2ꢀnaphthylaminea,b
aThe reactions were performed using aldehydes (1.0 mmol), cyclic ketones (1.0 mmol) and 2ꢀnaphthylamine
(2.0 mmol) in CH3CN. bIsolated yields.
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The reactivity of other α,βꢀunsaturated cyclic ketone was investigated by performing the
reaction with 1ꢀnaphthylamine 5, pꢀtolualdehyde 2a and 4,4ꢀDimethylꢀ2ꢀcyclohexenꢀ1ꢀone 9
in the presence of 10 mol% CSA under reflux condition to give 8,8ꢀdimethylꢀ6ꢀ(pꢀtolyl)ꢀ7,8ꢀ
dihydrobenzo[c]phenanthridine 10 in 82 % yield as shown in Scheme 3.
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The present protocol was further explored for the synthesis of fused benzoquinoline
derivatives using 2ꢀnaphthylamine (11), with different substituted aromatic aldehydes (2) and
cyclic ketones (3) in the presence of catalytic amount of CSA under identical reaction
conditions to offer the corresponding products 12a-g with 72ꢀ80% yields as depicted in Table
4.
Table 5. Reaction of 16ꢀdehydroꢀpregnenolone acetate with aldehyde and 2ꢀnaphthylaminea,b
aThe reactions were performed using aldehyde (1.0 mmol), 16ꢀdehydroꢀpregnenolone acetate (1.0 mmol) and 2ꢀ
naphthylamine (2.0 mmol) in CH3CN. bIsolated yields.
Next, we put our forward effort for the synthesis of steroid substituted benzo[f]quinoline
derivatives from 16ꢀdehydroꢀpregnenolone acetate (13), 2ꢀnaphthylamine (11) and 4ꢀMe/4ꢀCl
benzaldehydes using 10 mol% CSA under identical reaction condition which offered the
desired products 14a-b in 68 and 72% yields as shown in Table 5.
Next, our protocol was well applied for the synthesis of fused bisꢀbenzoquinoline derivatives
by using 1ꢀnaphthylamine/2ꢀnaphthylamine (1.0 mmol), terephthalaldehyde (0.5 mmol) and
4ꢀ(tertꢀbutyl)cyclohexanone (1.0 mmol) in presence of 10 mol% CSA catalyst under similar
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reaction condition and the successful results are shown in Scheme 4 along with their reaction
time and yields. Unfortunately, pꢀanisidine failed to give the desired product under identical
reaction condition.
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Scheme 4. Reaction scope of Terephthalaldehyde
Finally, 2ꢀAminoanthracene 16 (1.0 mmol) on reaction with 2ꢀnaphthaldehyde 2m (1.0
mmol) and 4ꢀ(tertꢀbutyl)cyclohexanone 3a (1.0 mmol) in presence of 10 mol % CSA under
reflux
condition
gave
the
product
3ꢀ(tertꢀbutyl)ꢀ5ꢀ(naphthalenꢀ2ꢀyl)ꢀ1,2,3,4ꢀ
tetrahydronaphtho[2,3ꢀa]phenanthridine 17 as shown in Scheme 5. All the synthesised
1
products were characterized by IR, H and 13C NMR spectra and HRMS. In addition, the
structure of the compounds 6r, 8, 12e and 14b were further confirmed by singleꢀcrystal Xꢀray
crystallographic data (see the Supporting Information).
Scheme 5. Reaction scope of 2ꢀAminoanthracene
To understand the reactivity of aryl amines, we carried out three sets of reactions. Initially, pꢀ
anisidine (1.0 mmol), 1ꢀnaphthylamine (1.0 mmol), pꢀtolualdehyde (1.0 mmol), and 4ꢀ(tertꢀ
butyl)cyclohexanone (1.0 mmol) under same reaction condition produced single product 6a.
Next, the reaction of pꢀanisidine (1.0 mmol), 2ꢀnaphthylamine (1.0 mmol), pꢀtolualdehyde
(1.0 mmol) and 4ꢀ(tertꢀbutyl)cyclohexanone (1.0 mmol) gave only product 12g.
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tBu
NH2
SO3H
(a) MeO
tBu
CHO
O
10 mol%
1a
NH2
+
+
N
CH3CN, Reflux
1.5 h
Me
O
6a
Me
9
3a
2a
65%
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5
tBu
SO3H
tBu
CHO
(b)
NH2
MeO
O
10 mol%
1a
+
+
CH3CN, Reflux
1.5 h
NH2
N
Me
O
12g
58%
Me
tBu
3a
2a
11
NH2
(c)
MeO
NH2
SO3H
tBu
CHO
N
O
1a
10 mol%
6a, 42%
+
+
Me
CH3CN, Reflux
1.5 h
+
tBu
Me
O
NH2
5
2a
3a
N
11
12g, 31%
Me
Scheme 6. The reactivity of arylamines
Finally, a mixture of pꢀanisidine (1.0 mmol), 1ꢀnaphthylamine (1.0 mmol), 2ꢀnaphthylamine
(1.0 mmol), pꢀtolualdehyde (1.0 mmol) and 4ꢀ(tertꢀbutyl)cyclohexanone (1.0 mmol) afforded
products 6a and 12g. The product 4a was not observed, due to poor reactivity of pꢀanisidine
in presence of 1ꢀnaphthylamine and 2ꢀnaphthylamine and the results are represented in
Scheme 6.
To study the mechanism, we performed one pot three component reaction using 2ꢀ
naphthylamine, pꢀtolualdehyde and 4ꢀ(tertꢀbutyl)cyclohexanone in the presence of 10 mol%
CSA under reflux condition at argon atmosphere as shown in Scheme 7. As expected, we
have observed the formation of 19 in 15% yield, which on readily reacted with 4ꢀ(tertꢀ
butyl)cyclohexanone 3a to give the corresponding products 18 and 12g in 25% and 45% yield
respectively after 0.5 h. In addition, the product 18 was further refluxed with 2 mL CH3CN in
open atmosphere without any catalyst resulted aromatized product 12g with 100% conversion
in 86% yield in 2 h, where as in room temperature reaction time prolonged up to 24 h to
produce compound 12g with 100% conversion of 84% yield.
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Scheme 7. Experiment for mechanistic pathway
From the literature,22a the intermediate 20 is expected to be formed but we have not observed
such dihydroquinoline. All the compounds are isolated and characterised individually by IR,
1H and 13C NMR spectra and HRMS. In addition, product 18 was confirmed by single crystal
XRD (see the Supporting Information).
Scheme 8. Proposed Reaction Mechanism Pathway
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The plausible mechanism for the formation of fused quinoline is described as shown in
Scheme 8. Initially, the aryl amine 1 reacts with aldehyde 2 to form the imine A and the
cyclic ketone 3 to form an active species B which on tautomerize to most stable enol form C
in the presence of camphorsulfonic acid. The generated imine A further reacted with C to
form Micheal type addition product D, which subsequently undergoes an intramolecular
cyclization to give dihydroquinoline G which undergoes oxidative aromatization to give the
desired product 4.
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CONCLUSION
In summary, we have developed a simple and an efficient method for the synthesis of
fused quinoline and benzoquinoline derivatives from readily available starting materials aryl
amine, aromatic aldehyde and cyclic ketone through one pot three component reaction using
camphor sulphonic acid as a catalyst. The protocol offers several advantages which include
commercially available cheap catalyst, less reaction time, mild reaction condition, simple
isolation procedure, wide range of substrate scope, ecoꢀfriendly with high atom economy in
one pot with two new CꢀC bond formations. Along with these, we have developed the utility
of pregnenolone acetate and terephthalaldehyde for the synthesis of steroid substituted
benzo[f]quinoline and bisꢀbenzo[f]quinoline respectively. To the best of our knowledge, these
quinoline and benzoquinoline derivatives were reported first time in the literature using
camphor sulphonic acid as a catalyst.
EXPERIMENTAL SECTION
l. General Information and Methods
Melting points were determined on a melting point apparatus and are uncorrected. 1H and 13C
NMR spectra were recorded on 400 & 600 MHz and 100 & 150 MHz NMR spectrometer.
TMS as internal reference; chemical shifts (δ scale) are reported in parts per million (ppm).
1H NMR Spectra are reported in the order: multiplicity, coupling constant (J value) in hertz
(Hz) and no. of protons; signals were characterized as s (singlet), d (doublet), t (triplet), m
(multiplet) and bs (broad). IR spectra were recorded on IR spectrophotometer. HRMS spectra
were recorded using ESI and APCI (TOF) mode. The Xꢀray crystal structures were
determined using a single XRD diffractometer.
II. General Procedure for Synthesis of cycloalkyl fused quinolines 4
Into a dry 25 mL round bottem flask a mixture aniline 1 (1.0 mmol), aromatic aldehyde 2
(1.0 mmol) and cyclic ketone 3 was taken in 5 mL acetonitrile. Camphorsulfonic acid (0.023
g, 0.10 mmol) was added into it and stirring under reflux condition. The progress of the
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reaction was monitered by TLC, after completion of the reaction the solvent was removed
under reduced pressure and it was extracted with DCM (2 x 25 mL). The organic extract was
dried over sodium sulphate and concentrated under reduced pressure. Finally, the residue was
purified through silica gel (60ꢀ120 mesh) column chromatography with petroleum ether/ethyl
acetate (9.5 : 0.5, v/v) to obtain the pure product 4.
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III. General Procedure for Synthesis of cycloalkyl fused benzoquinolines 6, 8, 10 & 12
To a mixture 1ꢀnaphthylamine (1.0 mmol), aromatic aldehyde 2 (1.0 mmol) and cyclic ketone
3, camphorsulfonic acid (0.023 g, 0.10 mmol) 5 mL acetonitrile was added allowed to stir at
reflux condition. After completion of the reaction indicated by TLC. The reaction mixture
was allowed to cool at room temperature for complete precipitation. Then, the solid
precipitate was filtered off through a Büchner funnel, washed with acetonitrile and dried
under reduced pressure to obtain the pure products 6. The similar reaction procedures were
followed for the synthesis of products 8, 10 & 12.
IV. General procedure for synthesis of steroid substituted benzo[f]quinoline 14
Into a 25 mL round bottom flask a mixture of aromatic aldehyde 2, 2ꢀnaphthylamine (11) and
16ꢀdehydroꢀpregnenolone acetate (13) were taken in 5 mL acetonitrile. Then,
camphorsulfonic acid (0.023 g, 0.10 mmol) was added into the above reaction mixture and
refluxed for 2.5 to 3.0 h until the completion of the starting materials indicated by TLC. The
reaction mixture was allowed to cool at room temperature. The solvent was removed under
reduced pressure and extracted with DCM (2 x 25 mL), dried over sodium sulphate and
concentrated under reduced pressure. Then, the crude residue was purified through silica gel
(60ꢀ120) column chromatography with petroleum etherꢀethylacetate (9.5 : 0.5, v/v) to get the
pure product 14.
V. General procedure for synthesis of cycloalkyl fused bis-benzoquinolines 15 and 3-
(tert-butyl)-5-(naphthalen-2-yl)-1,2,3,4-tetrahydronaphtho[2,3-a]phenanthridine 17
To a mixture naphthylamine (1.0 mmol), terephthalaldehyde 2q (0.5 mmol) and 4ꢀ(tertꢀ
butyl)cyclohexanone 3a (1.0 mmol) in 3 mL acetonitrile camphorsulfonic acid (0.023 g, 0.10
mmol) was added and allowed to stir at reflux for 1.0ꢀ4.5 h. After completion of the reaction
indicated by TLC. The reaction mixture was allowed to cool at room temperature to obtain
the solid product. Then, the pure solid product 15a-b were obtained after washing with
acetonitrile and dried under reduced pressure. The NMR of products were analysed by
disolving in 2ꢀ3 drops of CF3COOH in CDCl3. The similar reaction procedures was followed
for the synthesis of 3ꢀ(tertꢀbutyl)ꢀ5ꢀ(naphthalenꢀ2ꢀyl)ꢀ1,2,3,4ꢀtetrahydronaphtho[2,3ꢀ
a]phenanthridine 17.
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8-(tert-butyl)-2-methoxy-6-(p-tolyl)-7,8,9,10-tetrahydrophenanthridine (4a): Yield 78%
1
(280 mg), white solid, mp 180ꢀ181˚C, H NMR (600 MHz, CDCl3):δ 8.01 (d, J = 8.4 Hz,
6
7
8
9
1H), 7.42 (d, J= 7.8 Hz, 2H), 7.31ꢀ7.29(m, 1H), 7.27ꢀ7.26 (m, 2H), 7.18 (m, 1H), 3.95 (s,
3H), 3.76 (dd, J = 17.4, 4.8 Hz, 1H), 2.99 (m, 1H), 2.74 (d, J = 16.8 Hz, 1H), 2.53 (t, J = 12.6
Hz, 1H), 2.42 (s, 3H), 2.20ꢀ2.19 (m, 1H), 1.49ꢀ1.44 (m, 1H), 1.40ꢀ1.36 (m, 1H), 0.90 (s, 9H);
13C NMR (150 MHz, CDCl3): δ 158.7, 157.8, 138.4, 137.7, 131.6, 129.4, 129.1, 128.9, 127.7,
120.3, 101.4, 55.7, 44.7, 32.6, 30.5, 27.6, 27.5, 23.9, 21.5; IR (KBr)νmax 3051, 2957, 2867,
1585, 1497, 1068, 1031, 957 cmꢀ1; HRMS (ESI) Calcd For C25H30NO 360.2322 (M + H+);
Found 360.2323.
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8-(tert-butyl)-6-(p-tolyl)-7,8,9,10-tetrahydrophenanthridine (4b): Yield 71% (233 mg),
brown solid, mp 145ꢀ146˚C, 1H NMR (600 MHz, CDCl3): δ 8.20 (s, 1H), 7.98 (d, J = 8.4 Hz,
1H), 7.66 (t, J = 7.2 Hz, 1H), 7.55 (t, J = 7.2 Hz, 1H), 7.45 (d, J = 7.8 Hz, 2H), 7.29 (d, J =
7.2 Hz, 2H), 3.48 (dd, J = 18.0, 4.2 Hz, 1H), 3.07 (m, 1H), 2.76 (d, J = 16.2 Hz, 1H), 2.55 (t,
J = 12.0 Hz, 1H), 2.43 (s, 3H), 2.23ꢀ2.20 (m, 1H), 1.51ꢀ1.45 (m, 1H), 1.42ꢀ1.37 (m, 1H), 0.91
(s, 9H); 13C NMR (150 MHz, CDCl3): δ 159.5, 158.3, 157.7, 141.8, 140.7, 133.9, 131.6,
130.3, 129.4, 127.6, 120.2, 113.8, 101.3, 55.7, 44.8, 32.5, 30.6, 27.6, 27.5, 23.9; IR (KBr)νmax
3059, 3029, 2984, 2867, 1683, 1585, 1559, 1110, 1040, 1016 cmꢀ1; HRMS (APCI) Calcd For
C24H28N 330.2216(M + H+); Found 330.2205.
8-(tert-butyl)-2-methyl-6-(p-tolyl)-7,8,9,10-tetrahydrophenanthridine (4c): Yield 70%
1
(240 mg), white solid, mp 182ꢀ183˚C, H NMR (600 MHz, CDCl3): δ 8.09 (s, 1H), 7.72 (s,
1H), 7.48 (d, J = 8.4 Hz, 1H), 7.45 (d, J = 7.8 Hz, 2H), 7.27 (d, J = 7.8 Hz, 2H), 3.44 (dd, J =
18.0, 4.8 Hz, 1H), 3.02 (m, 1H), 2.74 (d, J = 16.2 Hz, 1H), 2.56 (s, 3H), 2.52 (d, J = 16.2 Hz,
1H), 2.42 (s, 3H), 2.21ꢀ2.18 (m, 1H), 1.47ꢀ1.42 (m, 1H), 1.39ꢀ1.35 (m, 1H), 0.90 (s, 9H); 13C
NMR (150 MHz, CDCl3): δ 159.8, 143.6, 142.2, 138.0, 137.6, 136.2, 130.8, 129.3, 129.1,
128.9, 126.7, 121.8, 44.7, 32.5, 32.4, 30.4, 27.4, 23.8, 22.2, 21.5; IR (KBr)νmax 3043, 3016,
2941, 2864, 1646, 1585, 1471, 1102, 1010, 922 cmꢀ1; HRMS (APCI) Calcd For C25H30N
344.2373 (M + H+); Found 344.2361.
8-(tert-butyl)-2-ethyl-6-(p-tolyl)-7,8,9,10-tetrahydrophenanthridine (4d): Yield 76% (271
1
mg), white solid, mp 135ꢀ136˚C, H NMR (600 MHz, CDCl3): δ 8.08 (d, J = 7.8 Hz, 1H),
7.73 (s, 1H), 7.53ꢀ7.51 (m, 1H), 7.44 (d, J = 7.8 Hz, 2H), 7.27 (d, J = 7.8 Hz, 2H), 3.45 (dd, J
= 17.4, 4.8 Hz, 1H), 3.07ꢀ3.03 (m, 1H), 2.85 (m, 2H), 2.75 (d, J = 16.8 Hz, 1H), 2.54 (t, J =
12.0 Hz, 1H), 2.42 (s, 3H), 2.19 (m, 1H), 1.49ꢀ1.44 (m, 1H), 1.44ꢀ1.39 (m, 1H), 1.35 (t, J =
13
7.8 Hz, 3H), 0.91 (s, 9H); C NMR (150 MHz, CDCl3): δ 160.0, 144.1, 142.4, 142.1, 138.1,
137.9, 129.7, 129.6, 129.1, 129.0, 128.9, 126.8, 120.5, 44.7, 32.6, 32.5, 30.4, 29.5, 27.4, 23.8,
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21.5, 15.9; IR (KBr)νmax 3048, 3024, 2964, 2867, 1612, 1585, 1112, 1058, 1016, 932 cmꢀ1;
HRMS (ESI) Calcd For C26H32N 358.2530 (M + H+); Found 358.2540.
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8
9
8-(tert-butyl)-2-chloro-6-(p-tolyl)-7,8,9,10-tetrahydrophenanthridine (4e): Yield 72%
(261 mg), white solid, mp 230ꢀ231˚C,1H NMR (600 MHz, CDCl3): δ 8.01 (d, J = 9.0 Hz,
1H), 7.92 (d, J = 1.8 Hz, 1H), 7.56 (dd, J = 9.0, 2.4 Hz, 1H), 7.42 (d, J = 7.8 Hz, 2H), 7.27 (d,
J = 7.8 Hz, 2H), 3.37 (dd, J = 18.0, 5.4 Hz, 1H), 3.02ꢀ2.96 (m, 1H), 2.74 (d, J = 16.8 Hz, 1H),
2.54 (t, J = 16.8 Hz, 1H), 2.42 (s, 3H), 2.21ꢀ 2.18 (m, 1H), 1.47ꢀ1.42 (m, 1H), 1.39ꢀ1.35 (m,
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1H), 0.90 (s, 9H); C NMR (150 MHz, CDCl3): δ 161.4, 144.2, 141.4, 138.2, 138.0, 132.0,
131.7, 130.7, 130.2, 129.2, 128.8, 127.6, 121.9, 44.6, 32.5, 30.5, 27.4, 27.3, 23.7, 21.5; IR
(KBr)νmax 3042, 2948, 2922, 2863, 1586, 1062, 1011, 942 cmꢀ1; HRMS (ESI) Calcd For
C24H27ClN 364.1827 (M + H+); Found 364.1835.
2-bromo-8-(tert-butyl)-6-(p-tolyl)-7,8,9,10-tetrahydrophenanthridine (4f): Yield 68%
(276 mg), white solid, mp 237ꢀ238˚C,1H NMR (600 MHz, CDCl3): δ 8.25 (s, 1H), 8.14 (s,
1H), 7.74 (d, J = 8.4 Hz, 1H), 7.46 (d, J = 7.8 Hz, 2H), 7.30 (d, J = 7.2 Hz, 2H), 3.41 (dd, J =
18.0, 4.2 Hz, 1H), 3.03 (m, 1H), 2.75 (d, J = 16.8 Hz, 1H), 2.56 (t, J = 12.6 Hz, 1H), 2.43 (s,
3H), 2.23ꢀ2.20 (m, 1H), 1.51ꢀ1.44 (m, 1H), 1.38 (t, J = 10.2 Hz, 1H), 0.90 (s, 9H); 13C NMR
(150 MHz, CDCl3): δ 161.0, 143.5, 142.4, 138.6, 136.8, 132.2, 131.2, 130.4, 129.2, 128.9,
128.1, 125.3, 120.7, 44.5, 32.5, 30.4, 27.5, 27.4, 23.6, 21.6; IR (KBr)νmax 3043, 2947, 2896,
2864, 1584, 1182, 1072, 1016, 976 cmꢀ1; HRMS (ESI) Calcd For C24H27BrN 408.1322 (M +
H+); Found 408.1336.
8-(tert-butyl)-2-methoxy-6-(4-methoxyphenyl)-7,8,9,10-tetrahydrophenanthridine (4g):
1
Yield 68% (255 mg), brown solid, mp 145ꢀ146˚C, H NMR (400 MHz, CDCl3): δ 8.00 (d, J
= 9.2 Hz, 1H), 7.49 (d, J = 8.8 Hz, 2H), 7.29 (dd, J = 9.2, 2.8 Hz, 1H), 7.17 (d, J = 2.4 Hz,
1H), 6.92 (d, J = 6.0 Hz, 2H), 3.95 (s, 3H), 3.87 (s, 3H), 3.35 (dd, J = 17.6, 5.2 Hz, 1H), 3.03ꢀ
2.94 (m, 1H), 2.75 (d, J = 16.8 Hz, 1H), 2.50 (t, J = 11.6 Hz, 1H), 2.22ꢀ2.04 (m, 1H), 1.51ꢀ
1.39 (m, 1H), 1.38ꢀ1.34 (m, 1H), 0.91 (s, 9H); 13C NMR (100 MHz, CDCl3): δ 159.5, 158.3,
157.7, 141.8, 140.7, 133.9, 131.6, 130.3, 129.4, 127.6, 120.2, 113.8, 101.3, 55.7, 55.5, 44.8,
32.5, 30.6, 27.6, 27.5, 23.9; IR (KBr)νmax 3042, 2955, 2867, 2828, 1620, 1581, 1174, 1106,
1034, 958 cmꢀ1; HRMS (APCI) Calcd For C25H30NO2 376.2271 (M + H+); Found 376.2256.
8-(tert-butyl)-2-chloro-6-(4-methoxyphenyl)-7,8,9,10-tetrahydrophenanthridine
(4h):
Yield 66% (250 mg), white solid, mp 202ꢀ203˚C,1H NMR (600 MHz, CDCl3): δ 8.16 (s, 1H),
7.94 (s, 1H), 7.58 (d, J = 9.0 Hz,1H), 7.52 (d, J = 9.0 Hz, 2H), 7.01 (d, J = 8.4 Hz, 2H), 3.88
(s, 3H), 3.41ꢀ3.37(m, 1H), 3.04ꢀ2.98 (m, 1H), 2.76 (d, J = 16.8 Hz, 1H), 2.56 (t, J = 12.0 Hz,
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1H), 2.23ꢀ2.19 (m, 1H), 1.51ꢀ1.44 (m, 1H), 1.39ꢀ1.35 (m, 1H), 0.90 (s, 9H); C NMR (100
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MHz, CDCl3): δ 160.4, 160.2, 143.1, 142.7, 135.4, 132.4, 130.9, 130.6, 130.5, 129.7, 127.6,
122.0, 114.0, 55.9, 44.6, 32.6, 30.6, 27.5, 27.4, 23.6; IR (KBr)νmax 3005, 2952, 2917, 2864,
1608, 1573, 1558, 1149, 1082, 1035, 950 cmꢀ1; HRMS (ESI) Calcd For C24H27ClNO
380.1776 (M + H+); Found 380.1778.
7-chloro-4-(p-tolyl)-2,3-dihydro-1H-cyclopenta[c]quinoline (4i): Yield 74% (216 mg),
white solid, mp 127ꢀ128˚C, 1H NMR (400 MHz, CDCl3): δ 8.16 (d, J = 2.0 Hz, 1H), 7.74 (d,
J = 8.4 Hz, 2H), 7.68 (d, J = 8.8 Hz, 1H), 7.41 (dd, J = 6.8, 2.0 Hz, 1H), 7.30 (d, J = 8.4 Hz,
2H), 3.23 (m, 4H), 2.45 (s, 3H), 2.24 (m, 2H); 13C NMR (100 MHz, CDCl3): δ 157.1,
151.4,147.9, 138.9, 137.5, 135.4, 134.3, 129.2, 128.9, 128.8, 126.9, 125.6, 123.7, 33.9, 31.4,
25.1, 21.5; IR (KBr)νmax 3025, 2970, 2919, 2849, 1605, 1575, 1559, 1070, 1042, 969 cmꢀ1;
HRMS (ESI) Calcd For C19H17ClN 294.1044 (M + H+); Found 294.1050.
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3-chloro-6-(p-tolyl)-8,9,10,11-tetrahydro-7H-cyclohepta[c]quinoline (4j): Yield 82% (263
1
mg), white solid, mp 146ꢀ147˚C, H NMR (400 MHz, CDCl3): δ 8.08 (d, J = 2.4 Hz, 1H),
7.97 (d, J = 9.2 Hz, 1H), 7.41ꢀ7.38 (m, 3H), 7.26 (d, J = 8.4 Hz, 2H), 3.24 (t, J = 4.8 Hz, 2H),
2.95 (t, J = 5.6 Hz, 2H), 2.41 (s, 3H), 1.89 (t, J = 6.0 Hz, 2H), 1.73 (t, J = 4.8 Hz, 2H), 1.62
(t, J = 5.2 Hz, 2H); 13C NMR (100 MHz, CDCl3): δ 161.0, 149.6, 146.9, 138.7, 137.9, 134.7,
134.1, 129.1, 129.0, 128.9, 126.9, 124.7, 124.6, 31.9, 30.8, 28.3, 27.0, 26.1, 21.4; IR
(KBr)νmax 3048, 2978, 2919, 2852, 1637, 1576, 1489, 1069, 1019, 964 cmꢀ1; HRMS (ESI)
Calcd For C21H21ClN 322.1357 (M + H+); Found 322.1359.
2-methoxy-6-(p-tolyl)-7,8,9,10-tetrahydrophenanthridine (4k): Yield 68% (206 mg),
brown solid, mp 135ꢀ136˚C, 1H NMR (600 MHz, CDCl3): δ 8.00 (d, J = 9.0 Hz, 1H), 7.41 (d,
J = 7.8 Hz, 2H), 7.31ꢀ7.30 (m, 1H), 7.30ꢀ7.29 (m, 1H), 7.26 (d, J = 6.0 Hz, 1H), 7.19 (s, 1H),
3.96 (s, 3H), 3.13 (t, J = 6.0 Hz, 2H), 2.73 (t, J = 6.0 Hz, 2H), 2.42 (s, 3H), 1.98 (t, J = 5.4
Hz, 2H), 1.77 (t, J = 5.4 Hz, 2H); 13C NMR (150 MHz, CDCl3): δ 158.5, 157.8, 141.8, 140.8,
138.5, 137.8, 131.7, 129.1, 128.9, 127.9, 120.3, 101.2, 55.7, 29.0, 26.1, 22.9, 22.5, 21.5; IR
(KBr)νmax 3041, 2933, 2859, 1668, 1655, 1220, 1093, 946 cmꢀ1; HRMS (ESI) Calcd For
C21H22NO 304.1696 (M + H+); Found 304.1703.
2-methyl-6-phenyl-7,8,9,10-tetrahydrophenanthridine (4l): Yield 75% (204 mg), yellow
liquid, 1H NMR (600 MHz, CDCl3): δ 8.00 (d, J = 8.4 Hz, 1H), 7.74 (s, 1H), 7.53 (d, J = 7.2
Hz, 2H), 7.49ꢀ7.45 (m, 3H), 7.41 (t, J = 7.2 Hz, 1H), 3.18 (t, J = 5.4 Hz, 2H), 2.72 (t, J = 5.4
Hz, 2H), 2.57 (s, 3H), 1.97 (t, J = 4.8 Hz, 2H), 1.79ꢀ1.77 (m, 2H); 13C NMR (150 MHz,
CDCl3): δ 160.0, 144.4, 141.5, 141.5, 136.1, 130.6, 129.9, 128.9, 128.5, 128.4, 128.1, 127.1,
121.7, 28.9, 25.9, 22.9, 22.5, 22.2; IR (KBr)νmax 3055, 3025, 2932, 2859, 1733, 1621, 1582,
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1095, 1029, 1001, 988 cmꢀ1; HRMS (APCI) Calcd For C20H20N 274.1590 (M + H+); Found
274.1573.
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6-(4-chlorophenyl)-2-methyl-8,9,10,11-tetrahydro-7H-cyclohepta[c]quinoline
(4m):
Yield 74% (237 mg), white solid, mp 192ꢀ193˚C, 1H NMR (600 MHz, CDCl3): δ 8.00 (d, J =
8.4 Hz, 1H), 7.87 (s, 1H), 7.49 (d, J = 9.0 Hz, 1H), 7.46ꢀ7.43 (m, 4H), 3.29 (t, J = 4.8 Hz,
2H), 2.92 (t, J = 5.4 Hz, 2H), 2.57 (s, 3H), 1.93ꢀ1.90 (m, 2H), 1.77 (m, 2H), 1.63 (t, J = 4.8
Hz, 2H); 13C NMR (150 MHz, CDCl3): δ 157.7, 149.0, 145.1, 140.5, 136.1, 134.1, 133.9,
130.9, 130.6, 130.1, 128.5, 126.3, 122.1, 32.1, 30.8, 28.1, 27.1, 26.2, 22.2; IR (KBr)νmax
3061, 2991, 2972, 2921, 2851, 1682, 1105, 1090, 1012, 965 cmꢀ1; HRMS (ESI) Calcd For
C21H21ClN 322.1357 (M + H+); Found 322.1371.
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2-methoxy-6-(p-tolyl)-7,8,9,10,11,12,13,14,15,16-decahydrocyclododeca[c]quinoline (4n):
Yield 64% (247 mg), brown solid, mp 149ꢀ150 ˚C, 1H NMR (600 MHz, CDCl3): δ 7.98 (d, J
= 9.0 Hz, 1H), 7.35 (d, J = 8.4 Hz, 2H), 7.30ꢀ7.28(m, 2H), 7.24 (d, J = 7.8 Hz, 2H), 3.96 (s,
3H), 3.16 (t, J = 7.8 Hz, 2H), 2.81 (t, J = 7.8 Hz, 2H), 2.41 (s, 3H), 1.89ꢀ1.88 (m, 2H), 1.67ꢀ
1.64 (m, 4H), 1.53ꢀ1.52 (m, 2H), 1.52ꢀ1.45 (m, 6H), 1.25ꢀ1.24 (m, 2H); 13C NMR (150 MHz,
CDCl3): δ 159.4, 157.6, 145.0, 142.2, 139.6, 137.4, 132.4, 131.7, 128.9, 128.6, 128.1, 120.1,
102.9, 55.7, 28.9, 28.6, 28.5, 28.4, 28.0, 27.6, 27.4, 26.9, 22.8, 21.5; IR (KBr)νmax 3058,
2924, 2851, 1621, 1571, 1034, 968 cmꢀ1; HRMS (ESI) Calcd For C27H34NO 388.2635 (M +
H+); Found 388.2654.
2-methyl-6-(thiophen-2-yl)-8,9,10,11-tetrahydro-7H-cyclohepta[c]quinoline (4o): Yield
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69% (202 mg), white solid, mp 130ꢀ131˚C, H NMR (600 MHz, CDCl3): δ 7.98 (d, J = 8.4
Hz, 1H), 7.82 (s, 1H), 7.47 (d, J = 9.0 Hz, 1H), 7.43 (d, J = 4.8 Hz, 1H), 7.26 (s, 1H), 7.12 (t,
J = 7.8 Hz, 1H), 3.30 (t, J = 4.8 Hz, 2H), 3.18 (t, J = 5.4 Hz, 2H), 2.55 (s, 3H), 1.95ꢀ1.94 (m,
2H), 1.78ꢀ1.77 (m,2H), 1.73ꢀ1.72 (m, 2H); 13C NMR (150 MHz, CDCl3): δ 151.9, 149.2,
145.3, 144.5, 136.2, 134.4, 130.9, 130.1, 127.6, 127.2, 126.9, 126.2, 122.1, 32.1, 30.7, 28.1,
27.0, 26.4, 22.3; IR (KBr)νmax 3070, 2995, 2917, 2852, 1637, 1568, 1056, 1019 cmꢀ1; HRMS
(APCI) Calcd For C19H20NS 294.1311(M + H+); Found 294.1325.
8-(tert-butyl)-6-(p-tolyl)-7,8,9,10-tetrahydrobenzo[c]phenanthridine (6a): Yield 94%
1
(356 mg), white solid, mp 211ꢀ212˚C, H NMR (600 MHz, CDCl3): δ 9.37 (d, J = 6.6 Hz,
1H), 7.91ꢀ7.87 (m, 2H), 7.81 (d, J = 9.0 Hz, 1H), 7.64ꢀ7.62 (m, 4H), 7.32 (d, J = 7.8 Hz, 2H),
3.56ꢀ3.50 (m, 1H), 3.15ꢀ3.11 (m, 1H), 2.91ꢀ2.88 (m, 1H), 2.69 (t, J = 12.0 Hz, 1H), 2.47 (s,
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3H), 2.25ꢀ2.22 (m, 1H), 1.57ꢀ1.49 (m, 1H), 1.43ꢀ1.39 (m, 1H), 0.94 (s, 9H); C NMR (150
MHz, CDCl3): δ 158.7, 143.4, 142.3, 138.9, 137.9, 133.2, 132.3, 129.7, 129.6, 128.9, 127.6,
127.2, 126.8, 125.2, 124.1, 120.9, 44.7, 32.6, 30.6, 27.8, 27.5, 24.1, 21.6; IR (KBr)νmax 3045,
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3022, 2955, 2867, 2837, 1573, 1099, 1019 cmꢀ1; HRMS (ESI) Calcd For C28H30N 380.2373
(M + H+); Found 380.2376.
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8-(tert-butyl)-6-(4-methoxyphenyl)-7,8,9,10-tetrahydrobenzo[c]phenanthridine
(6b):
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Yield 90% (355 mg), brown solid, mp 270ꢀ271˚C, H NMR (400 MHz, CDCl3): δ 9.34 (d, J
= 7.6 Hz, 1H), 7.86 (d, J = 9.2 Hz, 2H), 7.77 (d, J = 9.2 Hz, 1H), 7.69 (d, J = 8.8 Hz, 2H),
7.64 (t, J = 6.4 Hz, 2H), 7.04 (d, J = 8.8 Hz, 2H), 3.89 (s, 3H), 3.51ꢀ3.46 (m, 1H), 3.12ꢀ3.03
(m, 1H), 2.87 (d, J = 16.0 Hz, 1H), 2.68 (t, J = 12.0 Hz, 1H), 2.21ꢀ2.19 (m, 1H), 1.53ꢀ1.43
(m, 1H), 1.36 (t, J = 10.0 Hz, 1H), 0.93 (s, 9H); 13C NMR (100 MHz, CDCl3): δ 159.7, 158.2,
143.3, 142.4, 134.1, 133.1, 132.1, 131.0, 129.6, 127.7, 127.6, 127.1, 126.8, 125.1, 123.9,
120.8, 113.6, 58.5, 44.7, 32.5, 30.7, 27.8, 27.5, 23.9; IR (KBr)νmax 3051, 2956, 2897, 1608,
1506, 1174, 1073, 1012 cmꢀ1; HRMS (ESI) Calcd For C28H30NO 396.2322 (M + H+); Found
396.2322.
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4-(8-(tert-butyl)-7,8,9,10-tetrahydrobenzo[c]phenanthridin-6-yl)phenol (6c): Yield 92%
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(350 mg), white solid, mp 256ꢀ257˚C, H NMR (400 MHz, CDCl3): δ 9.35ꢀ9.33 (m, 1H),
7.91ꢀ7.87 (m, 2H), 7.81 (d, J = 9.6 Hz, 1H), 7.66ꢀ7.63 (m, 4H), 6.96 (d, J = 8.8 Hz, 2H),
3.56ꢀ3.49 (m, 1H), 3.16ꢀ3.06 (m, 1H), 2.87 (d, J = 16.4 Hz, 1H), 2.69 (t, J = 12.4 Hz, 1H),
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2.54ꢀ2.18 (m, 1H), 1.57ꢀ1.47 (m, 1H), 1.41ꢀ1.38 (m, 1H), 0.94 (s, 9H); C NMR (100 MHz,
CDCl3): δ 158.3, 157.3, 142.8, 142.2, 132.9, 132.3, 131.7, 130.8, 129.5, 127.4, 127.3, 126.7,
126.5, 124.7, 123.6, 120.7, 115.1, 44.5, 32.3, 30.5, 27.6, 27.2, 23.8; IR (KBr)νmax 3473, 3049,
2962, 2915, 2858, 1636, 1518, 1100, 1022 cmꢀ1; HRMS (ESI) Calcd For C27H28NO 382.2166
(M + H+); Found 382.2166.
3-(8-(tert-butyl)-7,8,9,10-tetrahydrobenzo[c]phenanthridin-6-yl)phenol (6d): Yield 95%
1
(362 mg), white solid, mp 220ꢀ221˚C, H NMR (600 MHz, CDCl3): δ 9.32 (d, J = 7.8 Hz,
1H), 7.86 (d, J = 7.2 Hz, 1H), 7.83 (d, J = 9.0 Hz, 1H), 7.78 (d, J = 9.0 Hz, 1H), 7.65ꢀ7.61
(m, 2H), 7.29ꢀ7.27 (m, 1H), 7.13ꢀ7.12 (m, 2H), 6.86ꢀ6.84 (m, 1H), 3.46ꢀ3.42 (m, 1H), 3.07ꢀ
3.01 (m, 1H), 2.78 (d, J = 6.2 Hz, 1H), 2.54 (t, J = 12.6 Hz, 1H), 2.18ꢀ2.15 (m, 1H), 1.45ꢀ
1.38 (m, 1H), 1.35ꢀ1.31 (m, 1H), 0.89 (s, 9H); 13C NMR (150 MHz, CDCl3): δ 158.4, 156.0,
143.5, 142.6, 141.9, 133.2, 131.4, 130.1, 129.4, 127.9, 127.8, 127.6, 127.1, 125.0, 124.4,
121.6, 120.7, 116.9, 115.8, 44.5, 32.5, 30.2, 27.9, 27.4, 23.8; IR (KBr)νmax 3446, 3051, 2956,
2861, 1636, 1121, 996 cmꢀ1; HRMS (ESI) Calcd For C27H28NO 382.2166 (M + H+); Found
382.2161.
8-(tert-butyl)-6-(3,4,5-trimethoxyphenyl)-7,8,9,10-tetrahydrobenzo[c]phenanthridine
1
(6e): Yield 77% (350 mg), white solid, mp 196ꢀ197˚C, H NMR (600 MHz, CDCl3): δ
9.41,(s, 1H), 7.90 (t, J = 3.6 Hz, 2H), 7.83, (d, J = 9.6 Hz, 1H), 7.71ꢀ7.64, (m, 2H), 6.95, (s,
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2H), 3.96, (s, 3H), 3.94, (s, 6H), 3.54ꢀ3.51, (m, 1H), 3.15ꢀ3.09, (m, 1H), 2.93, (d, J = 16.2
Hz, 1H), 2.67, (t, J = 12.6 Hz, 1H), 2.24, (t, J = 4.2 Hz, 1H), 1.55ꢀ1.48,(m, 1H), 1.42 (t, J =
10.2 Hz, 1H), 0.95, (s, 9H); 13C NMR (150 MHz, CDCl3): δ 158.1, 153.1, 142.8, 141.4,
138.4, 136.5, 133.3, 131.6, 129.7, 127.9, 127.8, 127.7, 127.1, 125.3, 124.3, 120.7, 107.2,
61.2, 56.5, 44.7, 32.6, 30.6, 27.9, 27.5, 23.9; IR (KBr)νmax 3042, 2997, 2956, 2886, 1637,
1585, 1127, 1006 cmꢀ1; HRMS (ESI) Calcd For C30H34NO3 456.2533 (M + H+); Found
456.2527.
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8-(tert-butyl)-6-(4-chlorophenyl)-7,8,9,10-tetrahydrobenzo[c]phenanthridine (6f): Yield
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87% (347 mg), white solid, mp 217ꢀ218 ˚C, H NMR (400 MHz, CDCl3): δ 9.40, (s, 1H),
7.90ꢀ7.89, (m, 2H), 7.85,(s, 1H), 7.67ꢀ7.66, (m, 4H), 7.51ꢀ7.50, (m, 2H), 3.53, (d, J = 17.2
Hz, 1H), 3.12ꢀ3.11, (m, 1H), 2.82, (d, J = 16.0 Hz, 1H), 2.65, (t, J = 12.8 Hz, 1H), 2.24ꢀ2.23,
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(m, 1H), 1.51, (d, J = 12.0 Hz, 1H),1.41,(d, J = 11.0 Hz, 1H), 0.94, (s, 9H); C NMR (100
MHz, CDCl3): δ 157.1, 143.3, 143.0, 139.6, 134.4, 133.2, 131.7, 131.1, 129.6, 128.5, 127.9,
127.7, 127.1, 125.1, 124.4, 1207, 44.6, 32.6, 30.5, 27.8, 27.5, 23.9;.IR (KBr)νmax 3022, 2958,
2873, 2840, 1652, 1573, 1123, 1090, 1014 cmꢀ1; HRMS (ESI) Calcd For C27H27ClN 400.1827
(M + H+); Found 400.1825.
6-(4-bromophenyl)-8-(tert-butyl)-7,8,9,10-tetrahydrobenzo[c]phenanthridine (6g): Yield
1
82% (363 mg), white solid, mp 215ꢀ216 ˚C, H NMR (400 MHz, CDCl3): δ 9.45 (s, 1H),
7.89(s, 2H), 7.87, (s, 1H), 7.68ꢀ7.66 (m, 4H), 7.61(s, 2H), 3.54 (d, J = 17.2 Hz, 1H), 3.14 (s,
1H), 2.82 (d, J = 16.0 Hz, 1H), 2.64 (t, J = 12.8 Hz, 1H), 2.23 (s, 1H), 1.51 (d, J = 11.6 Hz,
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1H), 1.41 (d, J = 11.2 Hz, 1H), 0.94, (s, 9H); C NMR (100 MHz, CDCl3): δ 157.0, 143.7,
142.8, 139.6, 133.3, 131.5, 131.4, 129.7, 128.1, 127.9, 127.8, 127.2, 125.2, 124.5, 122.8,
120.6, 44.5, 32.5, 30.4, 27.9, 27.4, 23.9; IR (KBr)νmax 2953, 2869, 2840, 1573, 1122, 1099,
1073, 1010 cmꢀ1; HRMS (ESI) Calcd For C27H27BrN 444.1322 (M + H+); Found 444.1323.
8-(tert-butyl)-6-(4-nitrophenyl)-7,8,9,10-tetrahydrobenzo[c]phenanthridine (6h): Yield
1
80% (328 mg), yellow solid, mp > 350 ˚C, H NMR (400 MHz, CDCl3): δ 9.27 (d, J = 8.8
Hz, 1H), 8.39 (d, J = 8.8 Hz, 2H), 7.93ꢀ7.89 (m, 4H), 7.86 (d, J = 9.2 Hz, 1H), 7.68 (t, J =
3.6 Hz, 2H), 3.56 (dd, J = 17.6, 5.2Hz, 1H), 3.18ꢀ3.09 (m, 1H), 2.79 (d, J = 15.2 Hz, 1H),
2.69 (t, J = 12.0 Hz, 1H), 2.26 (dd, J = 12.4, 5.6Hz, 1H), 1.57ꢀ1.49 (m, 1H), 1.44ꢀ1.39 (m,
13
1H), 0.93 (s, 9H); C NMR (100 MHz, CDCl3): δ 156.1, 148.2, 147.7, 143.6, 143.2, 133.3,
132.1,130.7, 129.3, 128.2, 128.0, 127.8, 127.2, 124.9, 124.7, 123.5, 120.7, 44.6, 32.6, 30.4,
27.8, 27.4, 23.9; IR (KBr)νmax 3069, 2957, 2926, 2896, 2864, 1639, 1599, 1108, 1014 cmꢀ1;
HRMS (APCI) Calcd For C27H27N2O2 411.2067 (M + H+); Found 411.2064.
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6-(3-bromophenyl)-8-(tert-butyl)-7,8,9,10-tetrahydrobenzo[c]phenanthridine (6i): Yield
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80% (354 mg), white solid, mp 185ꢀ186 ˚C, H NMR (400 MHz, CDCl3): δ 9.32 (d, J = 8.0
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Hz, 1H), 7.96 (s, 1H), 7.88 (d, J = 8.0 Hz, 1H), 7.76 (s, 2H), 7.68ꢀ7.61 (m, 4H), 7.38 (t, J =
8.0 Hz, 1H), 3.35ꢀ3.30 (m, 1H), 2.98ꢀ2.92 (m, 1H), 2.80 (d, J = 16.0 Hz, 1H), 2.62ꢀ2.55 (m,
1H), 2.12 (d, J = 12.0 Hz, 1H), 1.37ꢀ1.30 (m, 2H), 0.94 (s, 9H); 13C NMR (100 MHz,
CDCl3): δ 156.7, 143.6, 143.3, 142.6, 133.1,132.8, 132.0, 131.0, 129.5, 129.2, 128.1, 127.7,
127.6, 127.4, 126.9, 124.9, 124.2, 122.4, 120.7, 44.3, 32.4, 30.3, 27.5, 27.4, 23.7; IR
(KBr)νmax 3067, 3053, 2960, 2886, 1556, 1549, 1129, 1064, 1022, 997 cmꢀ1; HRMS (ESI)
Calcd For C27H27BrN 444.1321 (M + H+); Found 444.1330.
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6-(3,4,5-trimethoxyphenyl)-7,8,9,10-tetrahydrobenzo[c]phenanthridine (6j): Yield 88%
1
(351 mg), brown solid, mp 138ꢀ139 ˚C, H NMR (600 MHz, CDCl3): δ 9.37 (d, J = 7.2 Hz,
1H), 7.90 (t, J = 9.0 Hz, 2H), 7.83 (d, J = 9.6 Hz, 1H), 7.69ꢀ7.64 (m, 2H), 6.91 (s, 2H), 3.95
(s, 3H), 3.94 (s, 6H), 3.28 (t, J = 6.0 Hz, 2H), 2.89 (t, J = 6.0 Hz, 2H), 2.04ꢀ2.00 (m, 2H),
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1.84ꢀ1.80 (m, 2H); C NMR (150 MHz, CDCl3): δ 158.2, 153.2, 143.2, 143.0, 138.3, 136.6,
133.3, 131.7, 129.3, 127.9, 127.7, 127.6, 127.0, 125.3, 124.6, 120.6, 107.1, 61.2, 56.5, 29.1,
26.5, 22.9, 22.6; IR (KBr)νmax 3051, 2996, 2936, 2860, 2834, 1622, 1584, 1170, 1126, 1006
cmꢀ1; HRMS (ESI) Calcd For C26H26NO3 400.1907 (M + H+); Found 400.1927.
6-(4-fluorophenyl)-8,9,10,11-tetrahydro-7H-benzo[h]cyclohepta[c]quinoline (6k): Yield
1
91% (310 mg), white solid, mp 159ꢀ160 ˚C, H NMR (600 MHz, CDCl3): δ 9.35 (d, J = 5.4
Hz, 1H), 8.04 (d, J = 9.6 Hz, 1H), 7.88ꢀ7.87 (m, 1H), 7.81 (d, J = 9.0 Hz, 1H), 768ꢀ7.64 (m,
4H), 7.21 (t, J = 8.4 Hz, 2H), 3.38 (t, J = 5.4 Hz, 2H), 3.08ꢀ3.06 (m, 2H), 1.97ꢀ1.93 (m, 2H),
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1.84ꢀ1.81 (m, 2H), 1.73ꢀ1.69(m, 2H); C NMR (100 MHz, CDCl3): δ 164.1, 161.6, 156.4,
150.0, 144.3, 138.2, 134.8, 133.2, 132.2, 131.7, 131.6, 128.0, 127.5, 127.4, 126.9, 125.2,
123.7, 121.2, 115.3, 115.1, 32.1, 30.9, 28.7, 27.5, 26.5; IR (KBr)νmax 3046, 2981, 2936, 2910,
2875, 1635, 1538, 1052, 1014 cmꢀ1; HRMS (ESI) Calcd For C24H21FN 342.1653 (M + H+);
Found 342.1659.
6-(p-tolyl)-7,8,9,10,11,12-hexahydrobenzo[h]cycloocta[c]quinoline (6l): Yield 85% (298
mg), white solid, mp 151ꢀ152 ˚C, 1H NMR (600 MHz, CDCl3): δ 9.32ꢀ9.31 (m, 1H), 7.98 (d,
J = 9.0 Hz, 1H), 7.88ꢀ7.86 (m, 1H), 7.80 (d, J = 9.0 Hz, 1H), 7.63ꢀ7.62 (m, 2H), 7.50 (d, J =
7.8 Hz, 2H), 7.31 (d, J = 7.8 Hz, 2H), 3.37ꢀ3.36 (m, 2H), 3.02 (t, J = 5.4 Hz, 2H), 2.46 (s,
3H), 1.94ꢀ1.93 (m, 2H), 1.64ꢀ1.63 (m, 2H), 1.46ꢀ1.45 (m, 2H), 1.39ꢀ1.38 (m, 2H); 13C NMR
(150 MHz, CDCl3): δ 158.8, 146.6, 144.2, 139.9, 137.5, 133.1, 132.4, 129.3, 128.8, 127.7,
127.5, 127.2, 126.8, 125.2, 123.8, 121.7, 32.1, 30.4, 28.8, 26.9, 26.8, 26.2, 21.5; IR (KBr)νmax
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3054, 2925, 2846, 1634, 1570, 1117, 1068, 1027 cmꢀ1; HRMS (APCI) Calcd For C26H26N
352.2060 (M + H+); Found 352.2074.
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6-phenyl-7,8,9,10,11,12,13,14,15,16-decahydrobenzo[h]cyclododeca[c]quinoline
(6m):
1
Yield 67% (263 mg), white solid, mp 166ꢀ167 ˚C, H NMR (400 MHz, CDCl3): δ 9.31 (s,
1H), 7.96, (d, J = 9.2 Hz, 1H), 7.87 (s, 1H), 7.80 (d, J = 9.2 Hz, 1H), 7.63 (s, 4H), 7.50ꢀ7.45
(m, 3H), 3.25 (t, J = 6.8 Hz, 2H), 2.93 (t, J = 7.2 Hz, 2H), 1.92ꢀ1.91 (m, 2H), 1.67ꢀ1.66 (m,
4H), 1.58ꢀ1.48 (m, 8H), 1.35ꢀ1.34 (m, 2H); 13C NMR (100 MHz, CDCl3): δ 159.5, 146.7,
143.0, 133.1, 132.6, 132.4, 129.2, 128.2, 127.8, 127.5, 127.2, 126.8, 125.2, 124.8, 122.1,
29.1, 28.9, 28.6, 28.5, 28.4, 27.7, 27.4, 27.0, 22.8; IR (KBr)νmax 3058, 2925, 2845, 1570,
1118, 1072, 1025 cmꢀ1; HRMS (ESI) Calcd For C29H32N 394.2530 (M + H+); Found
394.2530.
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6-(naphthalen-2-yl)-7,8,9,10,11,12-hexahydrobenzo[h]cycloocta[c]quinoline (6n): Yield
76% (294 mg), white solid, mp 166ꢀ167 ˚C, 1H NMR (600 MHz, CDCl3): δ 9.36 (s, 1H), 8.09
(s, 1H), 8.02 (d, J = 9.6 Hz, 1H), 7.98 (d, J = 8.4 Hz, 1H), 7.94 (d, J = 3.0 Hz, 2H), 7.89 (t, J
= 3.0 Hz, 1H), 7.84 (d, J = 9.0 Hz, 1H), 7.76 (d, J = 8.4 Hz, 1H), 7.65 (dd, J = 5.4, 3.0 Hz,
2H), 7.55 (dd, J = 5.4, 2.4 Hz, 2H), 3.41 (t, J = 5.4 Hz, 2H), 3.06 (t, J = 6.0 Hz, 2H), 1.97 (t, J
= 5.4 Hz, 2H), 1.64ꢀ1.63 (m, 2H), 1.47ꢀ1.46 (m, 2H), 1.43ꢀ1.42 (m, 2H); 13C NMR (150
MHz, CDCl3): δ 158.3, 147.5, 143.8, 139.6, 133.4, 133.2, 133.1, 133.0, 131.9, 128.7, 128.6,
128.0, 127.9, 127.8, 127.7, 127.6, 127.0, 126.4, 126.3, 125.3, 124.0, 121.6, 32.0, 30.5, 28.9,
27.1, 26.7, 26.3; IR (KBr)νmax 3042, 2929, 2854, 1608, 1549, 1082, 1036, 1012, 956 cmꢀ1;
HRMS (APCI) Calcd For C29H26N 388.2060 (M + H+); Found 388.2045.
6-(thiophen-2-yl)-8,9-dihydro-7H-benzo[h]cyclopenta[c]quinoline (6o): Yield 85% (255
1
mg), white solid, mp 166ꢀ167 ˚C, H NMR (400 MHz, CDCl3): δ 9.40 (d, J = 8.4 Hz, 1H),
7.85 (d, J = 8.0 Hz, 1H), 7.74 (t, J = 6.8 Hz, 1H), 7.69ꢀ7.67 (m, 2H), 7.63ꢀ7.62 (m, 1H), 7.61ꢀ
7.56 (m, 1H), 7.51 (d, J = 18.8 Hz, 1H), 7.17 (t, J = 4.4 Hz, 1H), 3.29 (t, J = 7.6 Hz, 2H),
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3.23 (t, J = 7.6 Hz, 2H), 2.31ꢀ2.24 (m, 2H); C NMR (100 MHz, CDCl3): δ 152.1, 147.5,
147.1, 144.6, 133.6, 133.5, 131.8, 128.2, 128.1, 127.9, 127.8, 127.1, 127.0, 126.7, 125.2,
122.6, 122.2, 33.8, 31.2, 24.5; IR (KBr)νmax 3053, 2954, 2915, 2847, 1577, 1119, 1055, 1024
cmꢀ1; HRMS (ESI) Calcd For C20H16NS 302.0998 (M + H+); Found 302.1012.
6-(pyridin-2-yl)-8,9-dihydro-7H-benzo[h]cyclopenta[c]quinoline (6p): Yield 78% (230
1
mg), brown solid, mp 128ꢀ129 ˚C, H NMR (600 MHz, CDCl3): δ 9.45 (d, J = 8.4 Hz, 1H),
8.74 ( d, J = 4.2 Hz, 1H), 8.67 (d, J = 7.8 Hz, 1H), 7.90 (d, J = 7.2 Hz, 2H), 7.81 (d, J = 8.4
Hz, 1H), 7.75ꢀ7.71 (m, 2H), 7.67 (t, J = 7.2 Hz, 1H), 7.33 (t, J = 6.0 Hz, 1H), 3.68 (t, J = 7.2
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Hz, 2H), 3.35 (t, J = 7.8 Hz, 2H), 2.33ꢀ2.28 (m, 2H); C NMR (150 MHz, CDCl3): δ 153.1,
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147.3, 144.8, 139.1, 137.2, 133.6, 132.1, 128.7, 128.1, 128.0, 127.4, 125.5, 124.6, 124.2,
123.7, 122.2, 34.2, 31.3, 25.1; IR (KBr)νmax 3052, 2921, 2850, 1574, 1192, 1097, 1022, 987
cmꢀ1; HRMS (APCI) Calcd For C21H17N2 297.1386 (M + H+); Found 297.1376.
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6-(furan-2-yl)-8,9,10,11-tetrahydro-7H-benzo[h]cyclohepta[c]quinoline (6q): Yield 72%
(225 mg), brown solid, mp 83ꢀ84 ˚C, 1H NMR (400 MHz, CDCl3): δ 9.37 (d, J = 7.6 Hz, 1H),
7.99 (d, J = 8.8 Hz, 1H), 7.86 (d, J = 7.2 Hz, 1H), 7.77 (d, J = 9.2 Hz, 1H), 7.70 (d, J = 6.8
Hz, 1H), 7.68ꢀ7.65 (m, 2H), 7.08 (d, J = 3.2 Hz, 1H), 6.62ꢀ6.61 (m, 1H), 3.78 (t, J = 5.6 Hz,
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2H), 3.31 (t, J = 5.2 Hz, 2H), 1.94 (d, J = 5.6 Hz, 2H), 1.79 (d, J = 3.2 Hz, 4H); C NMR
(100 MHz, CDCl3): δ 155.5, 150.4, 146.8, 144.6, 143.1, 134.6, 133.2, 132.2, 128.0, 127.5,
127.4, 127.0, 125.2, 123.7, 121.2, 111.6, 111.5, 31.9, 29.9, 28.3, 27.0, 26.6; IR (KBr)νmax
3049, 2921, 2853, 1621, 1571, 1163, 1126, 1076, 1009 cmꢀ1; HRMS (ESI) Calcd For
C22H20NO 314.1540 (M + H+); Found 314.1547.
6-(thiophen-2-yl)-8,9,10,11-tetrahydro-7H-benzo[h]cyclohepta[c]quinoline (6r): Yield
84% (276 mg), brown solid, mp 142ꢀ143 ˚C, 1H NMR (400 MHz, CDCl3): δ 9.39 (d, J = 8.0
Hz, 1H), 7.96 (d, J = 9.2 Hz, 1H), 7.86 (d, J = 7.6 Hz, 1H), 7.76 (d, J = 9.2 Hz, 1H), 7.71 (t, J
= 10.0 Hz, 1H), 7.66 (t, J = 7.6 Hz, 1H), 7.51 (d, J = 5.2 Hz, 1H), 7.40 (d, J = 2.8 Hz, 1H),
7.18 (t, J = 3.6 Hz, 1H), 3.55, (t, J = 5.2 Hz, 2H), 3.31 (t, J = 5.2 Hz, 2H), 1.97 (d, J = 4.8 Hz,
2H), 1.80, (s, 4H); 13C NMR (100 MHz, CDCl3): δ 150.5, 150.1, 145.7, 144.2, 134.4, 133.2,
131.9, 128.1, 127.6, 127.6,127.5, 127.4, 127.4, 127.0, 125.3, 123.4, 121.1, 31.9, 30.4, 28.5,
27.0, 26.6; IR (KBr)νmax 3062, 2966, 2923, 2853, 1683, 1652, 1101, 1079, 1027 cmꢀ1; HRMS
(ESI) Calcd For C22H20NS 330.1311 (M + H+); Found 330.1311.
10-methoxy-6-(3,4,5-trimethoxyphenyl)-7,8-dihydrodibenzo[c,k]phenanthridine
(8):
Yield 64% (305 mg), brown solid, mp 208ꢀ209 ˚C, 1H NMR (400 MHz, CDCl3): δ 9.41 (d, J
= 6.8 Hz, 1H), 8.33 (d, J = 8.8 Hz, 1H), 7.91 (t, J = 8.0 Hz, 2H), 7.80 (d, J = 9.6 Hz, 1H),
7.23ꢀ7.66 (m, 2H), 7.02 (s, 2H), 6.99 (d, J = 8.4 Hz, 1H), 6.97 (s, 1H), 3.96 (s, 3H), 3.94 (s,
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6H), 3.92 (s, 3H), 3.03 (t, J = 6.4 Hz, 2H), 2.77 (t, J = 7.2 Hz, 2H); C NMR (100 MHz,
CDCl3): δ 160.1, 156.4, 153.2, 145.9, 142.5, 141.6, 138.5, 136.8, 133.2, 132.2, 131.3, 129.2,
128.1, 127.5, 127.2, 126.9, 125.6, 125.2, 123.5, 121.5, 113.6, 111.8, 107.3, 61.2, 56.5, 55.6,
30.2, 27.8; IR (KBr)νmax 3062, 2935, 2834, 1607, 1584, 1123, 1064, 1034, 1005 cmꢀ1; HRMS
(ESI) Calcd For C31H28NO4 478.2013 (M + H+); Found 478.2014.
8,8-dimethyl-6-(p-tolyl)-7,8-dihydrobenzo[c]phenanthridine (10): Yield 82% (286 mg),
1
brown solid, mp 174ꢀ175 ˚C, H NMR (400 MHz, CDCl3): δ 9.37 (d, J = 8.0 Hz, 1H), 8.01
(d, J = 12.0 Hz, 1H), 7.89ꢀ7.87 (m, 1H), 7.81 (d, J = 8.0 Hz, 1H), 7.68ꢀ7.63 (m, 3H), 7.36 (d,
J =12.0 Hz, 2H), 7.25 (d, J = 12.0 Hz, 1H), 6.25 (d, J = 8.0 Hz, 1H), 4.45 (s, 1H), 2.96 (s,
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2H), 2.48 (s, 3H), 1.07 (s, 6H); C NMR (100 MHz, CDCl3): δ 157.0, 145.1, 144.7, 138.2,
137.8, 136.6, 133.0, 131.9, 129.6, 128.8, 127.7, 127.4, 127.1, 126.7,124.9, 124.8, 120.5,
120.2, 120.1, 39.9, 32.0, 29.7, 27.2, 21.4; IR (KBr)νmax 3029, 2956, 2918, 2895, 2857, 1627,
1583, 1564, 1115, 1024, 1000 cmꢀ1; HRMS (ESI) Calcd For C26H24N 350.1903 (M + H+);
Found 350.1908.
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4-(2,3-dihydro-1H-benzo[f]cyclopenta[c]quinolin-4-yl)phenol (12a): Yield 78% (242 mg),
white solid, mp 308ꢀ309 ˚C, 1H NMR (600 MHz, CDCl3): δ 9.42 (s, 1H), 8.56 (d, J = 8.4 Hz,
1H), 7.91ꢀ7.83 (m, 3H), 7.72 (d, J = 7.8 Hz, 2H), 7.59ꢀ7.55 (m, 2H), 6.89 (d, J = 8.4 Hz, 2H),
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3.65ꢀ3.62 (m, 2H), 3.18ꢀ3.16 (m, 2H), 2.17ꢀ2.15 (m, 2H); C NMR (150 MHz, CDCl3): δ
156.9, 152.6, 149.5, 146.0, 134.9, 130.9, 129.6, 129.1, 128.9, 128.6, 127.6, 127.3, 125.3,
125.2, 125.1, 121.0, 114.0, 35.8, 31.8, 24.6; IR (KBr)νmax 3446, 1636, 1607, 1548, 1145,
1104, 1018 cmꢀ1; HRMS (ESI) Calcd For C22H18NO 312.1383 (M + H+); Found 312.1382.
3-(tert-butyl)-5-(4-methoxyphenyl)-1,2,3,4-tetrahydrobenzo[a]phenanthridine
(12b):
Yield 72% (284 mg), brown solid, mp 206ꢀ207 ˚C, 1H NMR (600 MHz, CDCl3): δ 8.76 (d, J
= 8.4 Hz, 1H), 7.98 (d, J = 8.4 Hz, 1H), 7.95ꢀ7.94 (m, 1H), 7.88 (d, J = 9.0 Hz, 1H), 7.64ꢀ
7.61 (m, 2H), 7.52 (d, J = 8.4 Hz, 2H), 7.03 (d, J = 8.4 Hz, 2H), 3.89 (s, 3H), 3.70 (d, J =
16.2 Hz, 1H), 3.63ꢀ3.61 (m, 1H), 3.01 (dd, J = 16.8, 5.4 Hz, 1H), 2.56 (dd, J = 16.8, 11.4 Hz,
1H), 2.16 (dd, J = 12.6, 2.4 Hz, 1H), 1.64ꢀ1.63 (m, 1H), 1.26ꢀ1.22 (m, 1H), 0.90 (s, 9H); 13C
NMR (150 MHz, CDCl3): δ 159.6, 159.2, 146.6, 145.2, 133.9, 133.5, 130.4, 130.3, 130.1,
130.0, 129.4, 129.1, 128.5, 126.3, 125.7, 124.6, 113.9, 55.5, 44.3, 34.6, 32.7, 30.4, 27.2, 24.9;
IR (KBr)νmax 3016, 2948, 2858, 1635, 1609, 1109, 1033, 834 cmꢀ1; HRMS (ESI) Calcd For
C28H30NO 396.2322 (M + H+); Found 396.2341.
5-(p-tolyl)-1,2,3,4-tetrahydrobenzo[a]phenanthridine (12c): Yield 74% (239 mg), white
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solid, mp 146ꢀ147 ˚C, H NMR (600 MHz, CDCl3): δ 8.77 (d, J = 9.0 Hz, 1H), 8.04 (d, J =
8.4 Hz, 1H), 7.96ꢀ7.95 (m, 1H), 7.90 (d, J = 8.4 Hz, 1H), 7.66ꢀ7.61 (m, 2H), 7.44 (d, J = 7.8
Hz, 2H), 7.30 (d, J = 7.8 Hz, 2H), 3.62 (t, J = 6.0 Hz, 2H), 2.89 (t, J = 6.6 Hz, 2H), 2.44 (s,
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3H), 1.92ꢀ1.83 (m, 4H); C NMR (150 MHz, CDCl3): δ 159.1, 146.3, 145.7, 138.0, 133.6,
130.4, 130.3, 129.3, 129.2, 129.1, 128.9, 128.6, 126.4, 125.8, 124.9, 33.5, 28.7, 23.3, 22.4,
21.5; IR (KBr)νmax 3049, 3027, 2936, 2860, 1613, 1559, 1118, 1020 cmꢀ1; HRMS (ESI) Calcd
For C24H22N 324.1747 (M + H+); Found 324.1746.
5-(2-fluorophenyl)-1,2,3,4-tetrahydrobenzo[a]phenanthridine (12d): Yield 78% (255
mg), brown solid, mp 108ꢀ109 ˚C, 1H NMR (600 MHz, CDCl3): δ 8.78ꢀ8.76 (m, 1H), 8.01 (d,
J = 9.0 Hz, 1H), 7.96ꢀ7.94 (m, 1H), 7.90 (d, J = 8.4 Hz, 1H), 7.65ꢀ7.61 (m, 2H), 7.49ꢀ7.47
(m, 1H), 7.46ꢀ7.42 (m, 1H), 7.30 (t, J = 6.6 Hz, 1H), 7.21ꢀ6.98 (m, 1H), 3.62 (t, J = 5.4 Hz,
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2H), 2.90ꢀ2.69 (m, 2H), 1.91ꢀ1.90 (m, 4H); 13C NMR (150 MHz, CDCl3): δ 160.7, 159.1,
154.5, 146.7, 145.5, 133.6, 131.2, 131.1, 130.5, 130.3, 130.2, 129.1, 129.0, 128.6, 126.6,
125.8, 125.5, 124.8, 116.0, 115.9, 33.5, 27.4, 23.4, 22.2; IR (KBr)νmax 3055, 2935, 2861,
1616, 1579, 1122, 1092, 1030, 1006 cmꢀ1; HRMS (ESI) Calcd For C23H19FN 328.1496 (M +
H+); Found 328.1496.
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5-(furan-2-yl)-1,2,3,4-tetrahydrobenzo[a]phenanthridine (12e): Yield 75% (224 mg),
brown solid, mp 116ꢀ118 ˚C, 1H NMR (400 MHz, CDCl3): δ 8.74ꢀ8.72 (m, 1H), 8.00ꢀ7.98 (d,
J = 8.0 Hz, 1H), 7.94ꢀ7.92 (m, 1H), 7.89ꢀ7.87 (d, J = 9.2 Hz, 1H), 7.68ꢀ7.67 (m, 1H), 7.62ꢀ
7.59 (m, 2H), 7.06 (d, J = 3.6 Hz, 1H), 6.60ꢀ6.59 (m, 1H), 3.58 (t, J = 6.0 Hz, 2H), 3.22 (t, J
= 6.8 Hz, 2H), 2.03ꢀ1.99 (m, 2H), 1.86ꢀ1.84 (m, 2H); 13C NMR (150 MHz, CDCl3): δ 153.8,
147.9, 146.9, 145.8, 143.5, 133.7, 130.4, 130.3, 129.4, 129.1, 128.7, 128.6, 126.4, 125.8,
124.9, 112.7, 111.6, 33.9, 27.9, 23.2, 22.5; IR (KBr)νmax 3054, 2962, 2905, 1944, 1605, 1543,
1096 cmꢀ1; HRMS (APCI) Calcd For C21H18NO 300.1383 (M + H+); Found 300.1391.
8-phenyl-9,10,11,12,13,14-hexahydrobenzo[f]cycloocta[c]quinoline (12f): Yield 80% (269
1
mg), brown solid, mp 128ꢀ129 ˚C, H NMR (600 MHz, CDCl3): δ 8.83 (d, J = 8.4 Hz, 1H),
8.05 (s, 1H), 7.95 (d, J = 7.8 Hz, 1H), 7.91 (d, J = 9.0 Hz, 1H), 7.69ꢀ7.63 (m, 2H), 7.51ꢀ7.49
(t, J = 7.8 Hz, 4H), 7.47ꢀ7.43 (m, 1H), 3.62 (s, 2H), 2.97 (t, J = 6.0 Hz, 2H), 2.26 (t, J = 4.8
Hz, 2H), 1.72ꢀ1.71 (m, 2H), 1.70ꢀ1.64 (m, 2H), 1.54ꢀ1.53 (m, 2H); 13C NMR (100 MHz,
CDCl3): δ 159.6, 148.8, 147.2, 142.1, 133.6, 133.2, 130.7, 130.3, 129.5, 129.4, 128.8, 127.9,
127.8, 126.4, 126.3, 124.8, 31.2, 31.1, 30.8, 28.5, 27.4, 26.0; IR (KBr)νmax 3055, 2925, 2852,
1737, 1605, 1548, 1118, 1072, 1029, 1009 cmꢀ1; HRMS (ESI) Calcd For C25H24N 338.1903
(M + H+); Found 338.1903.
3-(tert-butyl)-5-(p-tolyl)-1,2,3,4-tetrahydrobenzo[a]phenanthridine (12g): Yield 75%
1
(284 mg), white solid, mp 255ꢀ256 ˚C, H NMR (600 MHz, CDCl3): δ 8.76 (d, J = 6.0 Hz,
1H), 7.99 (d, J = 12.0 Hz, 1H), 7.95 (d, J = 6.0 Hz, 1H), 7.89 (d, J = 6.0 Hz. 1H), 7.62ꢀ7.61
(t, J = 6.0 Hz, 2H), 7.46 (d, J = 12.0 Hz, 2H), 7.31 (d, J = 6.0 Hz, 2H), 3.71 (d, J = 18.0 Hz,
1H), 3.63 (d, J = 6.0 Hz, 1H), 3.0 (dd, J = 6.0, 12.0 Hz, 1H), 2.56 (t, J = 12.0 Hz, 1H), 2.45
13
(s, 3H), 2.17 (d, J = 12.0 Hz, 1H), 1.64 (s, 1H), 1.26ꢀ1.22 (m, 1H), 0.90 (s, 9H); C NMR
(150 MHz, CDCl3): δ 159.6, 146.6, 145.2, 138.5, 137.8, 133.5, 130.4, 130.1, 129.4, 129.2,
129.1, 128.9, 128.5, 126.3, 125.7, 124.7, 44.3, 34.6, 32.7, 30.3, 27.2, 24.9, 21.5; IR (KBr)νmax
3016, 2931, 2868, 1619, 1554, 1180, 1121, 1016 cmꢀ1; HRMS (ESI) Calcd For C28H30N
380.2373 (M + H+); Found 380.2387.
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(3S,8R,9S,10R,13S,14S)-10,13-dimethyl-17-(3-(p-tolyl)benzo[f]quinolin-1-yl)-
2,3,4,7,8,9,10,11,12,13,14,15-dodecahydro-1H-cyclopenta[a]phenanthren-3-yl
acetate
(14a): Yield 68% (395 mg), white solid, mp 216ꢀ217 ˚C, 1H NMR (600 MHz, CDCl3): δ 9.46
(d, J = 6.0 Hz, 1H), 8.11 (d, J = 6.0 Hz, 2H), 8.07 (d, J = 6.0 Hz, 1H), 7.95 (d, J = 12.0 Hz,
1H), 7.90 (d, J = 6.0 Hz, 1H), 7.59 (d, J = 6.0 Hz, 1H), 7.55 (s, 2H), 7.35(d, J = 6.0 Hz, 2H),
6.03 (s, 1H), 5.45 (s, 1H), 4.59 (s, 1H), 2.62 (d, J = 12.0 Hz, 1H), 2.44 (s, 3H), 2.37ꢀ2.25 (m,
3H), 2.16 (s, 1H), 2.03 (s, 3H), 1.97 (s, 1H), 1.80 (s, 3H), 1.71 (d, J = 12.0 Hz, 1H), 1.54 (t, J
= 12.0 Hz, 1H), 1.37 (s, 1H), 1.27 (d, J = 18.0 Hz, 2H), 1.06 (t, J = 12.0 Hz, 3H), 0.99 (s,
3H), 0.92 (s, 3H); 13C NMR (150 MHz, CDCl3): δ 170.8, 157.7, 155.5, 149.3, 144.9, 140.3,
139.5, 136.7, 132.6, 131.2, 131.1, 129.7, 129.5, 128.6, 128.4, 128.1, 127.5, 126.9, 125.7,
123.8, 122.4, 122.2, 57.5, 51.7, 50.4, 38.3, 37.0, 33.2, 32.8, 32.0, 31.3, 27.9, 21.6, 21.5, 20.8,
19.4, 17.2; IR (KBr)νmax 3157, 2967, 2722, 1647, 1567, 1167, 1102, 1019, 952 cmꢀ1; HRMS
(ESI) Calcd For C41H44NO2 582.3367 (M + H+); Found 582.3371.
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(3S,8R,9S,10R,13S,14S)-17-(3-(4-chlorophenyl)benzo[f]quinolin-1-yl)-10,13-dimethyl-
2,3,4,7,8,9,10,11,12,13,14,15-dodecahydro-1H-cyclopenta[a]phenanthren-3-yl
acetate
(14b): Yield 72% (432 mg), white solid, mp 229ꢀ230 ˚C, 1H NMR (600 MHz, CDCl3): δ 9.47
(d, J = 12.0 Hz, 1H), 8.17 (d, J = 6.0 Hz, 2H), 8.05 (d, J = 6.0 Hz, 1H), 7.96 (d, J = 12.0 Hz,
1H), 7.90, (d, J = 6.0 Hz, 1H), 7.61 (d, J = 6.0 Hz, 1H), 7.57 (d, J = 6.0 Hz, 1H), 7.54 (s, 1H),
7.51 (d, J = 6.0 Hz, 2H), 6.00 (s, 1H), 5.45 (s, 1H), 4.60 (s, 1H), 2.63 (d, J = 12.0 Hz, 1H),
2.37 (d, J = 6.0 Hz, 1H), 2.33ꢀ2.25 (m, 2H), 2.18 (d, J = 18.0 Hz, 1H), 2.03 (s, 3H), 1.99 (s,
1H), 1.85ꢀ1.81 (m, 3H), 1.71ꢀ1.69 (d, J = 18.0 Hz, 2H), 1.56ꢀ1.50 (m, 1H), 1.38ꢀ1.37 (m,
1H), 1.28 (s, 2H), 1.09ꢀ1.02 (m, 2H), 0.99 (s, 3H), 0.92 (s, 3H); 13C NMR (150 MHz,
CDCl3): δ 170.7, 157.5, 154.2, 149.4, 145.2, 140.3, 137.9, 135.6, 132.7, 131.4, 131.1, 129.3,
129.2, 128.8, 128.7, 128.4, 128.3, 127.1, 125.9, 124.1, 122.4, 121.9, 74.0, 57.5, 51.5, 50.4,
38.3, 36.9, 33.2, 32.8, 31.9, 31.3, 27.9, 21.6, 20.7, 19.4, 17.2; IR (KBr)νmax 3047, 3028, 2926,
1689, 1653, 1589, 1030, 964 cmꢀ1; HRMS (ESI) Calcd For C40H41ClNO2 602.2820 (M + H+);
Found 602.2823.
1,4-bis(8-(tert-butyl)-7,8,9,10-tetrahydrobenzo[c]phenanthridin-6-yl)benzene
(15a):
Yield 68% (443 mg), pale yellow solid, mp > 350 ˚C, 1H NMR (600 MHz, CDCl3): δ 9.00 (t,
J = 12.0 Hz, 2H), 8.25 (d, J = 6.0 Hz, 2H), 8.17 (s, 4H), 7.98 (d, J = 6.0 Hz, 2H), 7.94 (s,
2H), 7.90 (s, 4H), 3.90 (d, J = 18.0 Hz, 2H), 3.47 (d, J = 12.0 Hz, 2H), 2.88 (d, J = 18.0 Hz,
2H), 2.67 (d, J = 12.0 Hz, 2H), 2.42 (s, 2H), 1.62 (d, J = 12.0 Hz, 4H), 0.93 (s, 9H); 13C
NMR (150 MHz, CDCl3): δ 161.7, 161.5, 161.2, 160.9, 158.2, 151.1, 135.2, 134.8, 134.2,
133.1, 132.8, 132.3, 130.2, 130.1, 129.9, 127.3, 122.8, 122.3, 119.4, 117.7, 115.8, 113.9,
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111.9, 43.5, 32.5, 29.6, 29.5, 26.9, 22.9; IR (KBr)νmax 3082, 2996, 2956, 2867, 1581, 1551,
1081, 1019, 999 cmꢀ1; HRMS (ESI) Calcd For C48H49N2 653.3890 (M + H+); Found
653.3887.
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1,4-bis(3-(tert-butyl)-1,2,3,4-tetrahydrobenzo[a]phenanthridin-5-yl)benzene (15b): Yield
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75% (489 mg), pale yellow solid, mp > 350 ˚C, H NMR (600 MHz, CDCl3): δ 8.93 (d, J =
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8.0 Hz, 2H), 8.37ꢀ8.34 (m, 2H), 8.20ꢀ8.17 (m, 2H), 7.99ꢀ7.92 (m, 6H), 7.89ꢀ7.86 (m, 4H),
4.05ꢀ3.90 (m, 4H), 3.05ꢀ2.99 (m, 2H), 2.77ꢀ2.68 (m, 2H), 2.38 (d, J = 18.0 Hz, 2H), 1.79 (s,
2H), 1.48ꢀ1.38(m, 2H), 0.91 (s, 9H); 13C NMR (150 MHz, CDCl3): δ 161.6, 161.2, 160.8,
160.4, 160.1, 149.3, 138.4, 138.3, 134.1, 133.5, 133.4, 130.9, 130.1, 129.9, 129.7, 128.7,
128.2, 127.4, 119.2, 117.5, 116.3, 113.5, 110.6, 43.3, 36.1, 32.6, 29.7, 26.7, 23.9; IR
(KBr)νmax 3136, 3080, 2968, 2874, 1683, 1555, 1057, 1021, 998 cmꢀ1; HRMS (APCI) Calcd
For C48H49N2 653.3890 (M + H+); Found 653.3897.
3-(tert-butyl)-5-(naphthalen-2-yl)-1,2,3,4-tetrahydronaphtho[2,3-b]phenanthridine (17):
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Yield 92% (428 mg), brown solid, mp 285ꢀ286 ˚C, H NMR (600 MHz, CDCl3): δ 9.24 (s,
1H), 8.43 (s, 1H), 8.15ꢀ8.14 (m, 1H), 8.07ꢀ8.04 (m, 2H), 7.98ꢀ7.96 (m, 2H), 7.94ꢀ7.92 (m,
2H), 7.89 (d, J = 8.4 Hz, 1H), 7.69 (d, J = 8.4 Hz, 1H), 7.60 (t, J = 4.2 Hz, 2H), 7.54 (t, J =
4.2 Hz, 2H), 3.84ꢀ3.80 (m, 2H), 3.08 (dd, J = 16.8, 5.4Hz, 1H), 2.62 (dd, J = 16.8, 11.4 Hz,
1H), 2.24 (d, J = 12.0 Hz, 1H), 1.69 (t, J = 12.0 Hz, 2H), 0.85 (s, 9H); 13C NMR (150 MHz,
CDCl3): δ 158.9, 147.3, 145.9, 138.8, 133.7, 133.2, 131.9, 131.5, 131.4, 130.9, 130.3, 128.9,
128.7, 128.6, 128.5, 128.4, 128.1, 127.9, 127.7, 127.1, 127.0, 126.6, 126.4, 126.3, 126.1,
125.0, 44.4, 34.7, 32.8, 30.3, 27.2, 25.1; IR (KBr)νmax 3064, 2926, 2847, 1639, 1558, 1105,
1017, 885 cmꢀ1; HRMS (ESI) Calcd For C35H32N 466.2530 (M + H+); Found 466.2532.
(4aR,5S)-3-(tert-butyl)-5-(p-tolyl)-2,3,4,4a,5,6-hexahydrobenzo[a]phenanthridine (18):
Yield 25% (93.5 mg), brown solid, mp 120ꢀ121 ˚C, 1H NMR (400 MHz, CDCl3): δ 8.08 (d, J
= 8.0 Hz, 1H), 7.55 (d, J = 4.0 Hz, 1H), 7.37ꢀ7.34 (m, 1H), 7.25ꢀ7.21 (m, 3H), 7.15 (d, J =
8.0 Hz, 2H), 7.02 (t, J = 8.0 Hz, 1H), 6.89ꢀ6.86 (m, 1H), 6.24 (s, 1H), 6.15 (d, J = 4.0 Hz,
1H), 4.47 (d, J = 12.0 Hz, 1H), 2.49ꢀ2.47 (d, J = 8.0 Hz, 1H), 2.31 (s, 3H), 2.23 (s, 1H), 2.16ꢀ
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2.08 (m, 1H), 1.45 (d, J = 12.0 Hz, 2H), 1.35 (dd, J = 12.0, 4.0 Hz, 2H), 0.81 (s, 9H); C
NMR (100 MHz, CDCl3): δ 141.0, 140.6, 137.9, 132.8, 130.9, 129.4, 128.6, 128.1, 127.9,
126.3, 125.3, 123.7, 121.4, 116.8, 114.3, 110.1, 62.8, 39.4, 38.4, 32.4, 27.7, 27.4, 25.1, 21.4;
IR (KBr)νmax 3042, 2957, 2925, 2856, 1619, 1569, 1152, 1082, 1020, 968 cmꢀ1; HRMS
(APCI) Calcd For C28H32N 382.2529 (M + H+); Found 382.2526.
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