Lewis Acid Promoted Oxonium Ion Driven Carboamination of Alkynes for the Synthesis of 4-Alkoxy Quinolines

Article abstract of DOI:10.1021/acs.joc.6b02896

Lewis acid mediated multisegment coupling cascade is designed for the synthesis of densely substituted 4-alkoxy quinolines via an oxonium ion triggered alkyne carboamination sequence involving C-C and C-N bond formations. Cyclic ether fused-quinolines cou

Full text of DOI:10.1021/acs.joc.6b02896

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Article
Lewis Acid Promoted Oxonium Ion Driven Carboamination
of Alkynes for the Synthesis of 4-Alkoxy Quinolines
Santosh J. Gharpure, Santosh Kumar Nanda, Priyanka Adhikarao Adate, and Yogesh Gangaram Shelke
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.6b02896 • Publication Date (Web): 20 Jan 2017
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Lewis Acid Promoted Oxonium Ion Driven Carboamination of Alkynes for the
Synthesis of 4-Alkoxy Quinolines
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8
9
Santosh J. Gharpure,* Santosh K. Nanda, Priyanka A. Adate and Yogesh G. Shelke
Department of Chemistry, Indian Institute of Technology Bombay, Powai, Mumbai –
400076, India
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R2
( )n
R3
R2
R3
R4
O
O
N
O
R3 OH
TMSOTf
R2-OH
R3
R4
( )n
H
R1
TMSOTf
CH2Cl2, 0 °C
R1
R1
CH2Cl2, 0 °C
N3
N
R2
OMe
OMe
NEt2
O
N
O
O
N
N
OH
On-Pr
Graveoline
anti-tumor activity
ERβ ligand
agonist for inflammation
NorA efflux pump inhibitor
ABSTRACT: Lewis acid mediated multisegment coupling cascade is designed for
the synthesis of densely substituted 4-alkoxy quinolines via an oxonium ion triggered
alkyne carboamination sequence involving C-C and C-N bond formations. Cyclic
ether fused-quinolines could also be accessed using this fast, operationally simple,
high yielding, chemoselective and functional group tolerant method. Versatility and
utility of this methodology is demonstrated by post functionalization of products
obtained and its use in synthesis of potent drug molecules.
INTRODUCTION
Polysubstituted quinoline moiety is an integral part of many natural products and
agrochemicals.1a-f It is backbone of several potent drugs and pharmaceuticals
exhibiting diverse range of activities such as antimalarial, schistosomiasis and
antifungal.1g-i Among these, 4-alkoxy quinolines are quite prevalent pharmacophores
(Figure 1). For example, graveoline (1) shows anti-tumour activity whereas ERβ
ligand 2 possessing 4-alkoxy quinoline core acts as selective agonist in treating
inflammation. On the other hand, quinoline derivative 3 is used as neuroprotective
drug, 4-ethoxy quinoline (4) shows IGF-1R inhibition activity and 7-PPyQ (5) is an
antiproliferative drug. Quinoline derivative 6 is found to be an efficient NorA efflux
pump inhibitor.2 Apart from the classical methods, recent years has seen emergence of
not only transition metal-mediated transformations but also metal-free approaches for
the synthesis of quinolines.3,4,5 Interestingly, while significant progress has been made
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on the synthesis of substituted quinolines, methods giving direct access to 4- alkoxy
quinolines are typically fraught with multistep transformations resulting in lower
yields.6 Moreover, there are only scattered reports on the synthesis of cyclic ether
fused quinolines.7 Given the biological activity of the 4-alkoxy quinoline derivatives,
a general, concise and efficient synthesis of these scaffolds is highly desirable. Herein
we disclose a simple and scalable multisegment cascade coupling strategy for the
synthesis of diversely substituted 4-alkoxy quinolines as well as cyclic ether-fused
quinoline derivatives.
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OMe
OMe
O
O
O
N
N
OH
OH
N
OH
Graveoline (1)
anti-tumor activity
ERβ ligand (2)
agonist for inflammation polyphenol fiestin (3)
neuroprotective
Aza analogue of
activity (7 nM)
O
Me
NH2
N
Et
N
N
O
Et
N
Ph
N
OR1
N
N
R2
N
Me
HO
Ph
On-Pr
NorA efflux pump inhibitor
IGF-1F (4)
anti-tumor activity
7-PPyQs (5)
antiproliferative durg
6
Figure 1. Biologically active 4-alkoxy quinoline pharmacophores.
RESULTS AND DISCUSSION
Transition metal catalysed carboamination of alkynes for the simultaneous formation
of C-C and C-N bonds has attracted considerable attention in recent times.8 These
studies have opened new avenues for the synthesis of nitrogen heterocycles, providing
impetus for the development of transition metal-free carboamination reactions, which
are amenable to cascade processes. In a programme directed at developing methods
for synthesis of various functionalized heterocycles, we envisioned an oxoniumion
driven carboamination of alkynes for the synthesis of 4-alkoxy quinolines (Scheme
1).9 We anticipated that treating the azido aldehyde 7 with the alcohol 8 in the
presence of a Lewis/ Brønsted acid would generate an oxonium ion, which upon
reaction with alkyne 9 would form new intermediate vinyl cation forming C-C bond.
This vinyl cation would be further trapped by azide in an intramolecular fashion
followed by a 1,4-Elimination of H+ and N2 from this intermediate leading to the 4-
alkoxy quinoline 10.
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Scheme 1: Proposed synthesis of 4-alkoxy quinolines 10
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6
7
8
R2
R3
O
O
Lewis/
R3
R4
R2-OH
H
+
+
R1
Bronsted
acid
R1
R4
9
N3
N
9
7
8
10
10
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To test the feasibility of the proposed hypothesis, cyclization of azido aldehyde 7a
with benzyl alcohol (8a) and phenylacetylene (9a) was attempted using TMSOTf (1
equiv.) as a Lewis acid in CH2Cl2 as solvent. Gratifyingly, the reaction proceeded
smoothly to give the desired 4-benzyloxy quinoline 10a in excellent yield (Table 1,
entry 1). Various other Lewis as well as Brønsted acids were screened for optimizing
the reaction. In(OTf)3 and Sc(OTf)3 were found to give the quinoline product 10a in
comparable yield, albeit with longer reaction time (Table 1, entries 2-3). Milder Lewis
acids like Cu(OTf)2 and Zn(OTf)2 failed to give the quinoline 10a, with complete
recovery of starting compounds (Table 1, entries 4-5). Lewis acids such as FeCl3,
TiCl4, AlCl3 and BF3·OEt2 furnished the quinoline 10a in moderate yield (Table 1,
entries 9-12). TfOH too was found to promote the reaction, however, in lower yield
(Table 1, entry 16). Reaction did not proceed at all in acetonitrile as a solvent (Table
1, entry 6), whereas (CH2Cl)2 proved to be an inferior solvent (Table 1, entries 7-8).
In order to make the process economical, we tried to reduce the catalyst loading.
However, it led to sluggish reactions and significant amounts of starting materials
were recovered back (Table 1, entries 13-15). After all this screening, TMSOTf (1
o
equiv.) in CH2Cl2 at 0 C was identified as optimal condition to carry out the
synthesis of quinolines 10.
The scope and limitation of this three component, ‘one pot’ - cascade cyclization
process for the synthesis of various 4-alkoxy quinoline derivatives 10 was studied in
detail. The reaction was found to work efficiently with a broad range of aldehydes 7,
alcohols 8 and alkynes 9. The azido aldehyde 7a and phenylacetylene (9a) reacted
with alcohols such as MeOH (8b), isopropanol (8c) and allyl alcohol (8d) to furnish
the corresponding quinolines 10b-d in excellent yields (Scheme 2). Use of
cyclohexanol (8e), 2-chloroethanol (8f) and 9-fluorenylmethanol (8g) resulted in
slightly diminished yield of quinolines 10e-g. D-(-)-Menthol (8h) and cholesterol (8i)
also gave the quinolines 10h-i in 85% and 45%, respectively. Ethyl (S)-lactate (8j)
reacted with azido aldehyde 7a and phenylacetylene (9a) leading to the quinoline 10j
in poor yield along with formation of the 2-phenylquinolin-4-ol (11) as the major
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Table 1. Optimization of 4-alkoxy quinoline synthesis.
5
O
OBn
catalyst
solvent
6
7
H
BnOH
+
+
Ph
8
9
N3
N
Ph
7a
8a
9a
10a
10
11
12
13
14
15
16
17
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22
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Entry
Acid
Equiv.
Solvent
Temp.
Time (h) Yield
(%)[a]
(°C)
0
1
TMSOTf
In(OTf)3
Sc(OTf)3
Cu(OTf)2
Zn(OTf)2
TMSOTf
In(OTf)3
Sc(OTf)3
FeCl3
1
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH3CN
(CH2Cl)2
(CH2Cl)2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
0.25
17
17
18
18
18
2
78 (78)[b]
77 (77)[b]
2
1
0-rt
0
3
1
74
[c]
4
1
rt
-
[c]
5
1
rt
-
[c]
6
1
0-rt
0
-
7
1
69
70[b]
44
54
43
32
30
25
12
40
8
1
0
2
9
1
rt
18
20
18
20
18
12
18
18
10
11
12
13
14
15
16
TiCl4
1
rt
AlCl3
1
rt
BF3·OEt2
TMSOTf
Sc(OTf)3
In(OTf)3
TfOH
1
0-rt
0
0.5
0.2
0.2
1
rt-40
rt-40
0
All the reactions were carried out with azido aldehyde 7a (1.0 equiv.),
phenylacetylene 9a (1.0 equiv.) and benzyl alcohol 8a (1.0 equiv.). [a]yield was
1
determined on the basis of H NMR using trimethoxybenzene as internal standard,
[b]isolated yield, [c]starting material was recovered.
product. Formation of the latter is perhaps an outcome of an elimination reaction
under the strongly acidic conditions employed. N-Tosyl amino alcohols 8k-m also
participated in the reaction efficiently furnishing corresponding quinolines 10k-m in
excellent yields exhibiting high chemoselectivity. Interestingly, using 1,4-butanediol
(8n) as an alcohol variant afforded only quinoline 10n with no trace of bis-quinoline
derivative even on using excess amounts of azido aldehyde (7a), phenylacetylene (9a)
or TMSOTf. Anticipating that basicity of quinoline could be the reason for
inefficiency of the second quinoline formation step, we also attempted this reaction by
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adding stoichiometric amount of TFA in addition to two equivalents of TMSOTf,
albeit without much success.
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8
Scheme 2: Alcohol substrate scope
R
9
O
O
TMSOTf
10
11
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H
R-OH +
Ph
CH2Cl2
0 °C
N3
N
Ph
7a
8
9a
10
Me
Cl
OMe
N
O
O
N
O
Me
O
Ph
N
Ph
Ph
N
10c
Ph
N
10e
50%
Ph
10b
95%
10d
95%
10f
67%
85%
Me
Me
Me
CO2Et
Me
Me
Me
H
Me
O
N
Me
O
N
Me
H
H
O
N
O
N
Ph
Ph
Ph
10g
60%
10j
15%
10h
81%
Ph 10i
45%
TsHN
O
Me
NHTs
OH
O
NHTs
O
N
O
N
N
Ph
Ph
10n
Ph
N
10m
93%
Ph
10k
92%
10l
89%
70%
Me
Me
Me
O
CBr3
Ph
O
CF3
Ph
O
O
N
N
N
10o
0%
Ph
N
10p
0%
Ph
10q
0%
10r
0%
It is also pertinent to mention that tert-butyl alcohol (8o) led to extensive
decomposition, while phenol (8p) 2,2,2-tribromoethanol (8q) and 2,2,2-
triflouroethanol (8r) failed to give the desired quinolines 10o-r. In all the cases, the
structure and regioselectivity of the quinoline products was established based on their
spectral data. It was further unambiguously confirmed in the cases of quinolines 10g,
10i and 10k by single crystal X-ray diffraction studies.10
The multisegment coupling strategy for the synthesis of quinolines 10 was further
explored by changing the alkynes 9 and azido aldehydes 7. While p-Methoxyphenyl
acetylene (9b) participated in the reaction with azido aldehyde (7a) furnishing the
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quinolines 10s in good yield, p-nitrophenyl acetylene (9c) gave the product 10t in
only trace amounts (Scheme 3). This is due to the presence of strong electron
withdrawing nitro group on the aromatic ring that destabilizes the vinyl carbocation
intermediate thus slowing this reaction. Heteroaryl substituted alkyne 9d, pyrene
substituted alkyne 9e as well as 1-hexyne 9f gave the corresponding quinolines 10u-
w. Even internal alkynes 9g-h were found to be good reaction partners in this
synthesis furnishing the quinolines 10x-y, respectively, in good to moderate yields.
Formation of the 10x can be rationalized as follows: the nucleophilic attack of
unsymmetrical alkyne onto the oxonium ion may occur in two different ways. In
one approach it forms secondary vinyl carbocataion and in other it forms
secondary as well as benzylic carbocataion, which is more stabilized hence
leading to the formation of 10x as the product. Interestingly, alkynyl bromide 9i
also participated in this transformation giving rise to trisubstituted quinoline 10z.
When 2-azidoethanol (8s) was reacted with azido aldehyde 7a and alkyne 9j, the
quinoline 10aa was formed in good yield, clearly indicating that only the azide
conjugated with aryl aldehyde moiety participates in this reaction.
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11
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Scheme 3: Alkyne and azidoaldehyde substrate scope
R2
R3
O
O
TMSOTf
R3
R4
2
H
+
+
R -OH
R1
R1
CH2Cl2
0 °C
R4
9
N3
N
7
8
10
OBn
N
OBn
OBn
N
OBn
S
N
N
NO2
OMe
10s
79%
10t
trace
10u
78%
10v
65%
OBn
OBn
OBn
N
OBn
N
Ph
Ph
Br
Me
Me
N
N
Ph
Ph
10w
45%
10y
65%
10x
35%
10z
72%
N3
O
OBn
OBn
OBn
O2N
Br
O
N
O
N
Ph
N
Ph
N
Ph
O-nPr
10aa
78%
10ab
65%
10ac
83%
10ad
72%
Finally, scope of differently substituted azido aldehydes 7b-d was tested by reacting
these under optimized conditions with phenylacetylene (9a) and benzyl alcohol (8a)
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and it was observed that irrespective of the nature of group linked to the aryl moiety
quinolines 10ab-ad were obtained in good to excellent yield. Structures and
regioselectivity of the products were unambiguously confirmed by single crystal X-
ray diffraction studies on quinoline derivatives 10s and 10z.10
Scheme 4: Synthesis of cyclic ether-fused quinolines
10
11
12
13
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R3
R2
O
O
TMSOTf
( )n
R2
H
+
( )n
R1
CH2Cl2
0 °C
R1
R3 OH
12
N3
N
7
13
Me
CH2OBn
Cy
Ph
Ph
O
O
O
N
O
O
N
Ph
N
Ph
Ph
N
Ph
N
13a
99%
13b
96%
13c
96%
13d
95%
13e
93%
Me Me
Me
Me
Ph
O
O
O
N
O
N
N
Et
N
NO2
OMe
OMe
13g
92%
13f
98%
13h
93%
13i
93%
O
Ph
O
O
O
N
Cl
Br
N
N
N
Ph
Ph
13j
93%
13k
98%
13l
93%
13m
95%
O
O
O
O
OH
N
N
N
Ph
N
Ph
Me
13p
93%
13q
98%
13n
89%
13o
96%
Me
Ph
O
O
O
O
O
O
N
Ph
N
Ph
N
Ph
N
Ph
13r
98%
13s
90%
13t
97%
13u
91%
In order to demonstrate the versatility of the established protocol, synthesis of cyclic
ether-fused quinolines employing alcohol tethered alkynes was planned next.
Towards this, alkynol 12a was treated with azido aldehyde 7a using optimized
o
condition (1 equiv. TMSOTf in CH2Cl2 at 0 C), which to our delight led to the
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furoquinoline 13a in quantitative yield (Scheme 4). The reaction was found to be very
general and a variety of alkyl and aryl group-substituted alkynols 12b-k participated
in the reaction with azido aldehyde 7a furnishing the corresponding furoquinolines
13b-k in excellent yields. It is pertinent to mention here that alkynols 12l-n bearing
alkyne, vinyl chloride and enyne functionality, respectively, were tolerated under the
reaction conditions employed and corresponding furoquinolines 13l-n were obtained
in good yield. The diol 12o also worked albeit giving only monoquinoline derivative
13o. The alkynols 12p-s reacted with azido aldehyde 7a giving almost quantitatively,
the pyranoquinolines 13p-s. Even the oxepinoquinoline 13t could be obtained
efficiently using the alkynol 12t. Azido aldehyde variant 7d bearing acetal moiety
was also smoothly transformed to the furoquinoline 13u. The structures of the
quinolines 13l and 13q were unambiguously confirmed by single crystal X-ray
diffraction studies.10
10
11
12
13
14
15
16
17
18
19
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To examine robustness of this multisegment coupling cascade, we devised a synthesis
of sugar-derived quinoline. Thus, known alkynol 14 synthesised from D-glucal11 was
reacted with azido aldehyde 7a under the optimized reaction conditions to furnish the
bis-cyclic ether-fused quinoline 15, a variant of conformationally constrained C-aryl
sugar derivatives (Scheme 5).12
Scheme 5: Synthesis of sugar-derived quinoline
H
H
O
O
HO
TMSOTf
H
+
O
CH2Cl2
0 °C
93%
O
H
H
14
N
N3
OAc
Ph
OAc
Ph
7a
15
After successfully establishing scope of the reaction, based on our mechanistic
hypothesis, we reasoned that this multisegment, cascade coupling for the synthesis of
quinolines can be further extrapolated in two ways. In the first approach, we planned
to explore the in situ synthesis of alkynol followed by its further reaction for
accessing quinoline. This approach required extrapolation of the one pot sequence by
incorporating an additional C-C bond formation process to this multisegment cascade.
To test the hypothesis, alkynal 16 was subjected to reaction with allyltributyltin (17)
o
and BF3×OEt2 in CH2Cl2 at 0 C. After the complete consumption of aldehyde 16
(TLC control), azido aldehyde 7a was added to reaction mixture to obtain the
quinoline 18 in good overall yield (Scheme 6).13 In the second approach, the azido
aldehyde 7a was allylated using allyltributyltin (17) and BF3×OEt2 in CH2Cl2 at 0 oC;
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phenylacetylene (9a) was added and it was refluxed to furnish the quinoline 19 in
5
6
moderate yield.
7
8
Scheme 6: ‘One-pot’ synthesis of functionalised quinolines
H
9
SnBu3
(17)
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47
48
49
50
51
52
53
54
55
56
57
58
59
60
.
BF3 OEt2
O
N
O
CH2Cl2, 0 °C
then 7a
78%
Ph
Ph
16
18
SnBu3
(17)
O
.
BF3 OEt2
H
CH2Cl2, 0 °C
then 9a, reflux
55%
N3
N
Ph
7a
19
Versatility of the obtained alkoxy quinolines was demonstrated by converting these
into functionalized scaffolds. The bromoquinoline 10z was found to be a good partner
in Suzuki coupling and furnished the quinoline 10ae upon reaction with PhB(OH)2
(20) in the presence of catalytic amounts of Pd(PPh3)2Cl2 (Scheme 7). Fascinatingly,
o
the quinoline 13a when treated with [Ph2I]BF4 21 and Pd(OAc)2 in AcOH at 120 C
participated in selective C-H activation at the ortho position of the phenyl substituent
leading to the quinoline 22 in moderate yield.14 Selective reduction of quinoline 13a
Scheme 7: Functionalization of quinolines
PhB(OH)2 (20)
5 mol% Pd[(PPh3)2Cl2]
OBn
OBn
Br
Ph
Ph
20% aq. Na2CO3
THF, 80 °C
99%
N
Ph
N
10z
10ae
O
O
[Ph2I]BF4 (21)
5 mol% Pd(OAc)2
Ph
AcOH, 120 °C
45%
N
N
13a
22
HO
O
O
H2 (1 atm)
10% Pd/C
NiCl2
NaBH4
MaOH
rt
48%
EtOAc
rt
quantitative
N
H
Ph
N
Ph
N
Ph
24
13a
23
was attempted in two directions. Catalytic hydrogenation using 10% Pd/C furnished
the densely substituted pyridine derivative 23.10 Alternatively, tetrahydroquinoline 24
was obtained as the major product with excellent diastereoselectivity when quinoline
13a was subjected to reduction using NiCl2 and NaBH4.
Finally, utility of this quinoline synthesis was exemplified in a new approach for
efficient assembly of natural products and drug molecules. A single step, divergent
synthesis of graveoline (1) and the drug candidate 6 could be accomplished starting
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7
8
9
from the azido aldehyde 7a with appropriate alcohol 8 and alkyne 9 (Scheme 8).
Similarly, ERβ ligand (2) could be accessed in excellent overall yields from the azido
aldehyde 7a employing an addition deprotection step. These are shortest and most
efficient syntheses of these molecules reported till date.15
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
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34
35
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40
41
42
43
44
45
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47
48
49
50
51
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54
55
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59
60
Scheme 8: Total synthesis of natural product and drug molecules
OMe
8b, 9k
TMSOTf
CH2Cl2
0 °C
78%
O
O
1. 8b, 9l
TMSOTf
CH2Cl2,
0 °C
N
OMe
O
H
Graveoline 1
2. K2CO3
MeOH
82%
N
N3
O
8t, 9j
TMSOTf
NEt2
7a
HO
ERβ Ligand 2
(2 steps)
CH2Cl2
0 °C
45%
N
6
OnPr
O
O
OnPr
OAc Et2N
OH
9j
9k
9l
8t
CONCLUSIONS
In conclusion, we have developed a metal free, Lewis acid mediated multisegment,
cascade coupling approach for the synthesis of diversely substituted quinolines.
Versatility of the method was demonstrated by its use in the synthesis of cyclic ether-
fused and sugar-fused quinoline derivatives. In all, the approach employed not only
worked efficiently with short reaction spans but also allowed for sequencing of the
multiple cascades. We have also shown that the protocol gave a rapid access to
biologically active natural products and drug molecules. Further functionalization of
the quinolines has opened up interesting possibilities.
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EXPERIMENTAL SECTION
5
6
General experimental:
7
8
9
Melting points are recorded using sigma melting point apparatus in capillary tubes
1
and are uncorrected. H and 13C NMR spectra were recorded either on 400 or 500
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
MHz spectrometer. The chemical shifts (d ppm) are reported in the standard fashion
with reference to either internal tetramethylsilane or residual solvent peak. The
coupling constants are reported in Hz. In the 13C{1H}NMR spectra, the nature of the
carbons (C, CH, CH2 or CH3) was determined by recording the DEPT-135
experiment, and is given in parentheses.
All commercial reagents were used as such without any further purification.
All other alkyne and alkynols were prepared using well established protocols
involving either Sonogashira coupling reaction or opening of epoxide with lithium
anion of appropriate phenylacetylene.
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General procedure of intermolecular multisegment coupling reaction for
synthesis of 4-alkoxy quinoline derivatives 10:
7
8
9
4-(benzyloxy)-2-phenylquinoline (10a
)
:
To a magnetically stirred solution of
L, 0.340 mmol)
azido aldehyde 7a (50 mg, 0.340 mmol), benzyl alcohol 8a (35
µ
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
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45
46
47
48
49
50
51
52
53
54
55
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58
59
60
and phenyl acetylene 9a (34
dropwise TMSOTf (65
µ
L, 0.340 mmol) in dry CH2Cl2 (8.0 ml) was added
o
µ
L, 0.340 mmol) at 0 C. Reaction was monitored by
TLC, quenched with saturated aq. solution of NaHCO3 upon completion,
extracted with CH2Cl2 (3 × 5 mL) and dried over anhydrous Na2SO4. Evaporation
of the solvent and purification of the residue over a silica gel column using
EtOAc-petroleum ether (2:98) as eluent furnished 4-alkoxy quinoline 10a (72 mg,
78%) as a colourless liquid; IR (neat): 3060, 3033, 2929, 1593, 1556, 1507, 1494,
1422, 1379, 1353, 1224, 1181, 1108, 982, 918, 839, 766, 696 cm–1; 1H NMR (400
MHz, CDCl3): δ 8.28 (dd, J = 8.4, 0.4 Hz, 1H), 8.19 (d, J = 8.4 Hz, 1H), 8.14-
8.12 (m, 2H), 7.57-7.71 (m, 1H), 7.56-7.52 (m, 4H), 7.51-7.41 (m, 5H), 7.25 (s,
1H), 5.34 (s, 2H); 13C{1H}NMR (100 MHz, CDCl3, DEPT): δ 161.9 (C), 158.7
(C), 149.1 (C), 140.1 (C), 135.8 (C), 130.1 (CH), 129.9 (CH), 129.1 (CH), 128.8
(4
× CH), 128.9 (CH), 127.6 (2 × CH), 127.5 (2 × CH), 125.5 (CH), 121.9 (CH),
120.5 (C), 99.8 (CH), 70.2 (CH2); HRMS (ESI-TOF) m/z [M+H]+ calcd. for
C22H18NO 312.1381, found 312.1386.
[16]
4-methoxy-2-phenylquinoline (10b
0.5 mmol), methanol 8b (22
mmol) with TMSOTf (91
):
Reaction of azido aldehyde 7a (73 mg,
L, 0.5
L, 0.5 mmol) in dry CH2Cl2 (8.0 mL) at 0 °C as
µ
L, 0.5 mmol) and phenyl acetylene 9a (55 µ
µ
described for the 4-alkoxy quinoline 9a followed by purification on a silica gel
column using ethyl acetate-petroleum ether (3:97) as eluent furnished the 4-
o
alkoxy quinoline 10a (111 mg, 95%) as white solid; m.p. 66-68 C; IR (neat):
3020, 2975, 1594, 1559, 1510, 1447, 1421, 1379, 1216, 1161, 1115, 760, 701,
669 cm–1; 1H NMR (400 MHz, CDCl3): d 8.23-8.17 (m, 1H), 8.17-8.08 (m, 3H), 7.72
(ddd, J = 8.4, 6.9, 1.51 Hz, 1H), 7.57-7.44 (m, 4H), 7.18 (s, 1H), 4.12 (d, J = 1.5 Hz,
3H); 13C{1H}NMR (125 MHz, CDCl3, DEPT): d 163.1 (C), 158.9 (C), 149.1 (C),
140.3 (C), 130.2 (CH), 129.5 (CH), 129.1 (CH), 128.9 (2
× CH), 127.7 (2 × CH),
125.6 (CH), 121.8 (CH), 120.5 (C), 98.2 (CH), 55.8 (CH3); HRMS (ESI-TOF) m/z
[M+H]+ calcd. for C16H14NO 236.1070, found 236.1069.
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4-isopropoxy-2-phenylquinoline (10c):[17] Reaction of azido aldehyde 7a (75 mg,
5
6
0.5 mmol), isopropyl alcohol 8c (40
µL, 0.5 mmol) and phenyl acetylene 9a (55
7
8
µ
L, 0.5 mmol) with TMSOTf (91 L, 0.5 mmol) in dry CH2Cl2 (8.0 mL) at 0 °C
µ
9
as described for the 4-alkoxy quinoline 10a followed by purification on a silica
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
gel column using ethyl acetate-petroleum ether (3:97) as eluent furnished the 4-
o
alkoxy quinoline 10c (134 mg, 85%) as a white solid; m.p. 94-96 C; IR (neat):
2981, 2934, 1591, 1508, 1494, 1446, 1381, 1221, 1113, 947, 760, 697 cm–1; 1H
NMR (400 MHz, CDCl3): d 8.22 (dd, J = 8.2, 1.0 Hz, 1H), 8.13-8.06 (m, 3 H),
7.73-7.68 (m, 1H), 7.56-7.44 (m, 4H), 7.16 (s, 1H), 4.95 (sept, J = 6.0 Hz, 1H), 1.53
(d, J = 6.0 Hz, 6H); 13C{1H}NMR (100 MHz, CDCl3, DEPT): d 161.2 (C), 158.9 (C),
149.6 (C), 140.7 (C), 129.9 (CH), 129.2 (CH), 128.8 (2 × CH), 128.7 (CH), 127.7 (2
×
CH), 125.2 (CH), 122.1 (CH), 121.1 (C), 99.4 (CH), 70.7 (CH), 21.9 (2
HRMS (ESI-TOF) m/z [M+H]+ calcd. for C18H18NO 264.1383, found 264.1381.
4-(allyloxy)-2-phenylquinoline (10d): Reaction of azido aldehyde 6a (50 mg, 0.34
mmol), allyl alcohol 7d (31 L, 0.342 mmol) and phenyl acetylene 9a (45 L,
0.34 mmol) with TMSOTf (61 L, 0.34 mmol) in dry CH2Cl2 (8.0 mL) at 0 °C as
× CH3);
µ
µ
µ
described for the 4-alkoxy quinoline 10a followed by purification on a silica gel
column using ethyl acetate-petroleum ether (3:97) as eluent furnished the 4-
alkoxy quinoline 10d (63 mg, 78%) as a yellow liquid; IR (neat): 3052, 2926,
1566, 1463, 1370, 1227, 1170, 1006, 678, 669 cm–1; 1H NMR (400 MHz, CDCl3):
δ 8.22 (d, J = 8.1 Hz, 1H), 8.17-8.14 (m, 2H), 8.03 (dd, J = 8.1, 0.8 Hz, 1H), 7.74
(s, 1H), 7.72-7.20 (m, 1H), 7.56-7.51 (m, 3H), 7.48-7.46 (m, 1H), 6.19-6.09 (m,
1H), 5.24-5.16 (m, 2H), 3.91 (dd, J = 6.4, 0.4 Hz, 2H); 13C{1H}NMR (100 MHz,
CDCl3, DEPT): δ 161.8 (C), 158.8 (C), 149.3 (C), 140.4 (C), 132.2 (CH), 130.1
(CH), 129.4 (CH), 129.2 (CH), 128.8 (2
× CH), 127.6 (2 × CH), 125.5 (CH),
121.8 (CH), 120.5 (C), 118.5 (CH2), 99.1 (CH), 69.1 (CH2); HRMS (ESI-TOF)
m/z [M+H]+ calcd. for C18H16NO 262.1266, found 262.1264.
4-(cyclohexyloxy)-2-phenylquinoline (10e): Reaction of azido aldehyde 7a (73
mg, 0.5 mmol), cyclohexanol 8e (52
µL, 0.5 mmol) and phenyl acetylene 9a (55
µ
L, 0.5 mmol) with TMSOTf (91 L, 0.5 mmol) in dry CH2Cl2 (8.0 mL) at 0 °C
µ
as described for the 4-alkoxy quinoline 10a followed by purification on a silica
gel column using ethyl acetate-petroleum ether (3:97) as eluent furnished the 4-
alkoxy quinoline 10e (75 mg, 50%) as a yellow viscous liquid; IR (neat): 3020,
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2975, 1594,1559, 1510, 1360, 1216, 1115, 900, 758, 678 cm–1; 1H NMR (400
5
6
MHz, CDCl3):
δ 8.28-8.22 (d, J = 8.2, 1H), 8.14-8.06 (m, 3H), 7.74-7.67 (m, 1H),
7
8
7.56-7.44 (m, 4H), 7.17 (s, 1H), 4.72 (tt, J = 7.9, 3.7 Hz, 1H), 2.10 (td, J = 7.7, 3.5
Hz, 2H), 1.96-1.86 (m, 2H), 1.86-1.75 (m, 2H), 1.68-1.58 (m, 1H), 1.58-1.42 (m, 3
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
13
H); C{1H}NMR (100 MHz, CDCl3):
δ
161.1 (C), 158.6 (C), 149.6 (C), 140.7 (C),
CH), 128.8 (2 CH), 127.7 (CH), 125.2 (CH),
122.1 (CH), 121.3 (C), 99.6 (CH), 75.5 (CH), 31.3 (2 CH2), 25.6 (2 CH2), 23.5
132.9 (CH), 129.9 (CH), 129.2 (2
×
×
×
×
(CH2); HRMS (ESI-TOF) m/z [M+H]+ calcd. for C21H22NO 304.1696, found
304.1694.
4-(2-chloroethoxy)-2-phenylquinoline (10f): Reaction of azido aldehyde 7a (73
mg, 0.5 mmol), 2-chloro ethanol 8f (35
µL, 0.5 mmol) and phenyl acetylene 9a
(55 L, 0.5 mmol) with TMSOTf (91 L, 0.5 mmol) in dry CH2Cl2 (8.0 mL) at 0
µ
µ
°C as described for the 4-alkoxy quinoline 10a followed by purification on a
silica gel column using ethyl acetate-petroleum ether (3:97) as eluent furnished
o
the 4-alkoxy quinoline 10f (95 mg, 67%) as a white solid; m.p. 90-92 C; IR
(neat): 3062, 3034, 2962, 1594, 1510, 1424, 1359, 1223, 1160, 1115, 1020, 927,
836, 768, 697 cm–1 1H NMR (400 MHz, CDCl3):
δ 8.24 (d, J = 8.2 Hz, 1H), 8.13 (d,
;
J = 8.5 Hz, 1H), 8.11-8.06 (m, 2H), 7.77-7.68 (m, 1H), 7.57-7.44 (m, 4H), 7.13 (s,
1H), 4.58-4.46 (t, J = 5.6 Hz, 2H), 4.00 (t, J = 5.6 Hz, 2H); 13C{1H}NMR (100 MHz,
CDCl3, DEPT):
δ
161.5 (C), 158.8 (C), 149.3 (C), 104.2 (C), 130.3 (C), 129.5 (CH),
129.3 (CH), 128.9 (2
×
CH), 127.7 (2 CH), 125.8 (CH), 121.8 (CH), 120.3 (C),
×
98.7 (CH), 68.2 (CH2), 41.6 (CH2); HRMS (ESI-TOF) m/z [M+H]+ calcd. for
C17H15ClNO, 284.0837 found 284.0836.
4-((9H-fluoren-9-yl)oxy)-2-phenylquinoline (10g): Reaction of azido aldehyde 7a
(73 mg, 0.5 mmol), alcohol 8g (100 mg, 0.5 mmol) and phenyl acetylene 9a (55
µ
L, 0.5 mmol) with TMSOTf (91 µL, 0.5 mmol) in dry CH2Cl2 (8.0 mL) at 0 °C
as described for the 4-alkoxy quinoline 10a followed by purification on a silica
gel column using ethyl acetate-petroleum ether (3:97) as eluent furnished the 4-
alkoxy quinoline 10g (120 mg, 60%) as a white solid; m.p. 150-154 oC; IR (neat):
3020, 2978, 1594, 1510, 1425, 1355, 1216, 1112, 928, 758, 670 cm–1; 1H NMR
(400 MHz, CDCl3): d 8.44-8.37 (m, 1H), 8.17 (d, J = 8.2 Hz, 1H), 8.10-8.03 (m, 2H),
7.89-7.75 (m, 5H), 7.64-7.58 (m, 1H), 7.52-7.42 (m, 5H), 7.40-7.34 (m, 2H), 7.15 (s,
1H), 4.64 (t, J = 7.2 Hz, 1H), 4.53 (d, J = 7.2 Hz, 2H); 13C{1H}NMR (100 MHz,
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CDCl3, DEPT): d 162.1 (C), 158.9 (C), 149.3 (C), 143.8 (2 × C), 141.5 (C), 140.2 (C),
5
6
7
8
135.9 (C), 130.2 (CH), 129.4 (2
×
CH), 128.9 (2
CH), 125.8 (CH), 125.4 (2
×
CH), 98.8 (CH) , 71.2 (CH2), 47.4 (CH); HRMS (ESI-TOF) m/z [M+H]+
×
CH), 128.2 (2
× CH), 127.7 (2
×
CH), 127.4 (2
×
× CH), 121.7 (CH), 120.4 (C), 120.3
9
(2
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
calcd. for C29H22NO 400.1696, found 400.1696.
4-(((1R,2S,5R)-2-isopropyl-5-methylcyclohexyl)oxy)-2-phenylquinoline (10h):
Reaction of azido aldehyde 7a (50 mg, 0.34 mmol), (1R,2S,5R)-(-)-menthol 8h
(64 mg, 0.34 mmol) and phenyl acetylene 9a (55
µL, 0.34 mmol) with TMSOTf
(70 L, 0.34 mmol) in dry CH2Cl2 (8.0 mL) at 0 °C as described for the 4-alkoxy
µ
quinoline 10a followed by purification on a silica gel column using ethyl acetate-
petroleum ether (2:98) as eluent furnished the 4-alkoxy quinoline 10h (96 mg,
78%) as a sticky solid; [ꢀ]ꢂꢁꢃ :-180.884 (c 0.500, CHCl3); IR (neat): 2952, 2926,
1466, 1453, 1350, 1217, 1180, 1016, 698, 668 cm–1; 1H NMR (400 MHz, CDCl3):
δ 8.25 (d, J = 8.4 Hz, 1H), 8.13 (t, J = 8.4 Hz, 3H), 7.74-7.70 (m, 1H), 7.56 (t, J =
7.6 Hz, 2H), 7.49 (t, J = 7.6 Hz, 2H), 7.21 (s, 1H), 4.49 (td, J = 10.4, 4.0 Hz, 2H),
2.37-2.34 (m, 1H), 2.26 (quind, J = 6.8, 2.0 Hz, 1H), 1.85-1.75 (m, 3H), 1.67-1.58
(m, 1H), 1.29-1.22 (m, 2H), 0.99 (dd, J = 6.4, 5.6 Hz, 6H), 0.83 (d, J = 7.2 Hz,
3H); 13C{1H}NMR (100 MHz, CDCl3, DEPT): δ 161.5 (C), 159.1 (C), 149.6 (C),
140.8 (C), 129.9 (CH), 129.3 (CH), 129.2 (2
× CH), 128.8 (CH), 127.8 (2 × CH),
125.2 (CH), 122.1 (CH), 121.2 (C), 98.9 (CH), 77.9 (CH), 48.1 (CH), 39.7 (CH2),
34.5 (CH2), 31.5 (CH), 26.6 (CH), 24.0 (CH2), 22.2 (CH3), 20.8 (CH3), 17.1
(CH3); HRMS (ESI-TOF) m/z [M+H]+ calcd. for C25H30NO 360.2322, found
360.2321.
4-(((3S,8S,9S,10R,13R,14S,17R)-10,13-dimethyl-17-((R)-6-methylheptan-2-yl)-
2,3,4,7,8,9,10,11,12,13,14,15,16,17-tetradecahydro-1H-
cyclopenta[a]phenanthren-3-yl)oxy)-2-phenylquinoline (10i): Reaction of azido
aldehyde 7a (45 mg, 0.306 mmol), cholesterol 10i (114 mg, 0.306 mmol) and
phenyl acetylene 9a (40 µL, 0.306 mmol) with TMSOTf (55 µL, 0.306 mmol) in
dry CH2Cl2 (8.0 mL) at 0 °C as described for the 4-alkoxy quinoline 10a followed
by purification on a silica gel column using ethyl acetate-petroleum ether (2:98)
as eluent furnished the 4-alkoxy quinoline 10i (80 mg, 45%) as a white solid; m.p.
o
170-172 C; [ꢀ]ꢂꢁꢃ: -35.618 (c 1.00, CHCl3); IR (neat): 3013, 2494, 1590, 1559,
1467, 1423, 1397, 1216, 1109, 1066, 999, 760 cm–1; 1H NMR (400 MHz, CDCl3):
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8
9
d 8.23 (d, J = 8.2 Hz, 1H), 8.16-8.04 (m, 3H), 7.74-7.65 (m, 1H), 7.57-7.42 (m, 4H),
7.17 (s, 1H), 5.48 (d, J = 4.77 Hz, 1H), 4.61-4.46(m, 1H), 2.72-2.55 (m, 2H), 2.20 (d,
J = 12.5 Hz, 1H), 2.11-1.96 (m, 3H), 1.95-1.79 (m, 2H), 1.67-1.45 (m, 6H), 1.45-
1.21(m, 6H), 1.21-1.10 (m, 12H), 0.94 (d, J = 6.4 Hz, 3H), 0.91-0.82 (m, 6H), 0.71
(s, 3H); 13C{1H}NMR (100 MHz, CDCl3, DEPT): δ 161.2 (C), 158.9 (C), 149.6 (C),
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
140.7 (C), 139.9 (C), 130.1 (CH), 129.3 (CH), 128.9 (2 × CH), 127.8 (2 × CH),
125.3 (CH), 123.2 (CH), 122.1 (CH), 121.1 (C), 118.2 (CH), 99.5 (CH), 76.8 (CH),
56.9 (CH), 56.3 (CH), 50.3 (CH), 42.5 (C), 39.9 (CH2), 39.7 (CH2), 38.5 (CH2), 37.2
(CH2), 37.03 (C), 36.3 (CH2), 35.9 (CH), 32.1 (CH2), 32.0 (CH), 28.4 (CH2), 28.2
(CH), 28.0 (CH2), 24.4 (CH2), 23.9 (CH2), 22.9 (C), 22.7 (CH3), 21.2 (CH2), 19.6
(CH3), 18.9 (CH3), 12.0 (2 ×
CH3); HRMS (ESI-TOF) m/z [M+H]+ calcd. for
C42H56NO 590.4356, found 590.4358.
ethyl (S)-2-((2-phenylquinolin-4-yl)oxy)propanoate (10j): Reaction of azido
aldehyde 7a (50 mg, 0.34 mmol), (-)-Ethyl L-lactate 10j (42
phenyl acetylene 9a (44 L, 0.34 mmol) with TMSOTf (65
µ
l, 0.34 mmol) and
µ
µL, 0.34 mmol) in
dry CH2Cl2 (8.0 mL) at 0 °C as described for the 4-alkoxy quinoline 10a followed
by purification on a silica gel column using ethyl acetate-petroleum ether (2:98)
as eluent furnished the 4-alkoxy quinoline 10j (17 mg, 15%) as a brown colour
sticky liquid; [ꢀ]ꢂꢁꢃ: -2.712 (c 0.500, CHCl3); IR (neat): 3060, 3017, 2984, 2926,
1
2851, 1749, 1594, 1558, 1494, 1423, 1367, 1216, 1113, 698, 668 cm–1; H NMR
(500 MHz, CDCl3): δ 8.29 (d, J = 8.5 Hz, 1H), 8.12 (d, J = 8.5 Hz, 1H), 8.04 (d, J
= 7.0 Hz, 2H), 7.72 (t, J = 7.5 Hz, 1H), 7.15 (dd, J = 7.5, 0.0 Hz, 3H), 7.46 (d, J =
7.0 Hz, 1H), 7.05 (s, 1H), 5.10 (q, J = 6.5 Hz, 1H), 4.29-4.22 (m, 2H), 1.81 (d, J =
7.0 Hz, 3H), 1.25 (t, J = 6.0 Hz, 3H); 13C{1H}NMR (125 MHz, CDCl3, DEPT): δ
171.3 (C), 163.9 (C), 158.6 (C), 147.5 (C), 140.1 (C), 130.4 (CH), 129.5 (CH),
129.2 (CH), 128.9 (2
× CH), 127.7 (2 × CH), 125.7 (CH), 122.1 (CH), 120.4 (C),
99.2 (CH), 73.1 (CH), 61.8 (CH2), 18.5 (CH3), 14.3 (CH3); HRMS (ESI-TOF) m/z
[M+Na]+ calcd. for C20H19NNaO3 344.1257, found 344.1250.
4-methyl-N-(2-((2-phenylquinolin-4-yl)oxy)ethyl)benzenesulfonamide
Reaction of azido aldehyde 7a (50 mg, 0.34 mmol), aminoalcohol 10k (81 mg,
0.374 mmol) and phenyl acetylene 9a (50 L, 0.34 mmol) with TMSOTf (70 L,
(10k):
µ
µ
0.34 mmol) in dry CH2Cl2 (8.0 mL) at 0 °C as described for the 4-alkoxy
quinoline 10a followed by purification on a silica gel column using ethyl acetate-
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petroleum ether (50:50) as eluent furnished the 4-alkoxy quinoline 10k (131 mg,
o
92%) as a white solid; m.p. 165-167 C; IR (neat): 3353, 2934, 2873, 1617, 1592,
1
1509, 1357, 1223, 1112, 1065, 912, 769, 732, 699 cm–1; H NMR (500 MHz,
CD3OD + CDCl3): δ 8.01 (t, J = 7.5 Hz, 2H), 7.91 (d, J = 8.0 Hz, 2H), 7.68-7.63
(m, 3H), 7.47-7.39 (m, 4H), 7.12 (d, J = 8.0 Hz, 2H), 6.94 (s, 1H), 4.21 (t, J = 5.5
Hz, 2H), 3.44 (d, J = 5.5 Hz, 2H), 2.25 (s, 3H); 13C{1H}NMR (125 MHz, CD3OD
+ CDCl3, DEPT): δ 161.5 (C), 159.0 (C), 148.1 (C), 142.8 (C), 139.4 (C), 137.2
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(C), 129.8 (CH), 130.0 (2
×
CH), 128.9 (CH), 128.1 (2
× CH), 127.2 (2 × CH),
126.1 (2 CH), 124.9 (2
×
× CH), 121.4 (CH), 119.7 (C), 98.7 (CH), 66.4 (CH2),
41.3 (CH2), 20.2 (CH3); HRMS (ESI-TOF) m/z [M+H]+ calcd. for C24H23N2O3S
419.1424, found 419.1424.
4-4-methyl-N-(1-((2-phenylquinolin-4-yl)oxy)propan-2-yl)benzenesulfonamide
(10l): Reaction of azido aldehyde 7a (100 mg, 0.675 mmol), aminoalcohol 8l
(155 mg, 0.675 mmol) and phenyl acetylene 9a (90
µL, 0.675 mmol) with
TMSOTf (125 L, 0.675 mmol) in dry CH2Cl2 (8.0 mL) at 0 °C as described for
µ
the 4-alkoxy quinoline 10a followed by purification on a silica gel column using
ethyl acetate-petroleum ether (50:50) as eluent furnished the 4-alkoxy quinoline
1ol (263 mg, 89%) as a sticky solid; IR (neat): 3383, 2924, 2863, 1627, 1582, 1519,
1
1367, 1224, 1115, 1067, 915, 768, 699 cm–1; H NMR (400 MHz, CDCl3): δ 8.08
(d, J = 8.8 Hz, 1H), 8.09-8.01 (m, 3H), 7.64 (d, J = 8.0 Hz, 2H), 7.52-7.47 (m,
3H), 7.45-7.39 (m, 2H), 7.06 (d, J = 8.0 Hz, 2H), 6.99 (s, 1H), 5.53 (bs, 1H),
4.80-4.72 (m, 1H), 3.38-3.27 (m, 2H), 2.24 (s, 3H), 1.39 (d, J = 6.0 Hz, 3H);
13C{1H}NMR (100 MHz, CDCl3, DEPT): δ 160.4 (C), 158.6 (C), 149.4 (C), 143.7
(C), 140.1 (C), 137.1 (C), 130.2 (CH), 129.8 (2
×CH), 129.4 (CH), 129.2 (CH),
128.9 (2 CH), 127.6 (2 CH), 126.9 (2 CH), 125.5 (CH), 121.7 (CH), 120.6
×
×
×
(C), 99.4 (CH), 72.8 (CH2), 47.7 (CH2), 21.5 (CH3), 17.1 (CH3); HRMS (ESI-
TOF) m/z [M+H]+ calcd. for C25H25N2O3S 433.1580, found 433.1577.
4-methyl-N-((1R*,2R*)-2-((2-phenylquinolin-4-yl)oxy)cyclohexyl)benzenesulfon-
amide (10m): Reaction of azido aldehyde 7a (80 mg, 0.544 mmol), aminoalcohol
10m (146 mg, 0.544 mmol) and phenyl acetylene 9a (75
µL, 0.544 mmol) with
TMSOTf (140 L, 0.544 mmol) in dry CH2Cl2 (8.0 mL) at 0 °C as described for
µ
the 4-alkoxy quinoline 10a followed by purification on a silica gel column using
ethyl acetate-petroleum ether (50:50) as eluent furnished the 4-alkoxy quinoline
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10m (241 mg, 93%) as a white solid; m.p. 215-217 C; IR (neat): 3274, 3060,
5
6
7
8
2914, 2861, 1616, 1591, 1493, 1320, 1223, 1155, 1109, 1091, 908, 762, 697, 664,
571, 549 cm–1; 1H NMR (500 MHz, CDCl3): δ 8.12 (d, J = 7.8 Hz, 2H), 8.06 (d, J
= 8.5 Hz, 1H), 7.88 (d, J = 8.5 Hz, 1H), 7.68-7.62 (m, 3H), 7.52 (t, J = 7.5 Hz,
2H), 7.45 (d, J = 7.0 Hz, 1H), 7.37 (d, J = 7.5 Hz, 1H), 7.22 (s, 1H), 6.98 (d, J =
7.8 Hz, 2H), 5.48 (d, J = 6.5 Hz, 1H), 4.60 (br s, 1H), 3.55 (d, J = 6.5 Hz, 1H),
2.42 (s, 3H), 2.16-2.09 (m, 2H), 1.78 (br s, 1H), 1.61 (br s, 2H), 1.42-1.41 (m,
3H); 13C{1H}NMR (125 MHz, CDCl3, DEPT): δ 160.5 (C), 158.8 (C), 149.5 (C),
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143.4 (C), 140.3 (C), 137.5 (C), 130.0 (CH), 129.7 (2
× CH), 129.4 (CH), 129.2
(CH), 128.9 (2 CH), 127.7 (2 CH), 126.9 (2 CH), 125.2 (CH), 120.0 (CH),
×
×
×
120.9 (C), 99.6 (CH), 76.8 (CH), 53.9 (CH), 30.4 (CH2), 28.3 (CH2), 22.6 (CH2),
22.1 (CH2), 21.5 (CH3); HRMS (ESI-TOF) m/z [M+H]+ calcd. for C28H29N2O3S
473.1893, found 473.1880.
4-((2-phenylquinolin-4-yl)oxy)butan-1-ol (10n): Reaction of azido aldehyde 7a
(163 mg, 1.109 mmol), butan-1,4-diol 8n (50 mg, 0.554 mmol) and phenyl
acetylene 9a (150 µL, 1.36 mmol) with TMSOTf (200µL, 1.109 mmol) in dry
CH2Cl2 (8.0 mL) at 0 °C as described for the 4-alkoxy quinoline 10a followed by
purification on a silica gel column using ethyl acetate-petroleum ether (50:50) as
eluent furnished the 4-alkoxy quinoline 10n (102 mg, 70%) as a yellow solid;
o
m.p. 85-87 C; IR (neat): 3420, 3062, 3030, 2955, 2927, 2869, 1596, 1567, 1507,
1
1424, 1358, 1211, 1113, 1025, 869, 765, 735, 697 cm–1; H NMR (500 MHz,
CDCl3): δ 8.16 (dd, J = 9.5, 1.0 Hz, 1H), 8.12 (d, J = 9.5 Hz, 1H), 8.06-8.05 (m,
2H), 7.69 (td, J = 6.5, 0.5 Hz, 1H), 7.51-7.48 (m, 2H), 7.46-7.42 (m, 2H), 7.48 (s,
1H), 4.22 (t, J = 6.5 Hz, 2H), 3.72 (t, J = 6.5 Hz, 2H), 2.04-1.97 (m, 2H), 2.51 (s,
1H), 1.82-1.77 (m, 2H); 13C{1H}NMR (125 MHz, CDCl3, DEPT): δ 162.2 (C),
159.0 (C), 149.1 (C), 140.3 (C), 130.1 (CH), 129.9 (CH), 128.9 (CH), 128.8 (2
×
CH), 127.7 (2 CH), 125.4 (CH), 121.8 (CH), 120.5 (C), 98.8 (CH), 68.2 (CH2),
×
62.2 (CH2), 29.9 (CH2), 25.6 (CH2); HRMS (ESI-TOF) m/z [M+H]+ calcd. for
C19H20NO2 294.1489, found 294.1481.
(benzyloxy)-2-(4-methoxyphenyl)quinoline (10s): Reaction of azido aldehyde 7a
(133 mg, 0.908 mmol), benzyl alcohol 8a (140
µL, 0.908 mmol) and alkyne 9b
(120 mg, 0.908 mmol) with TMSOTf (195 L, 0.908 mmol) in dry CH2Cl2 (8.0
µ
mL) at 0 °C as described for the 4-alkoxy quinoline 10a followed by purification
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on a silica gel column using ethyl acetate-petroleum ether (4:96) as eluent
5
6
7
8
furnished the 4-alkoxy quinoline 10s (248 mg, 79%) as a white solid; m.p. 118-
o
120 C; IR (neat): 3019, 2984, 2907, 1734, 1594, 1502, 1374, 1249, 1216, 1046,
757, 668 cm–1; 1H NMR (400 MHz, CDCl3): δ 8.25 (d, J = 8.0 Hz, 1H), 8.15 (d, J
= 8.0 Hz, 1H), 8.09 (d, J = 8.4 Hz, 2H), 7.71 (t, J = 7.6 Hz, 1H), 7.54 (d, J = 7.2
Hz, 2H), 7.48-7.41 (m, 4H), 7.16 (s, 1H), 7.04 (d, J = 8.4 Hz, 2H), 5.27 (s, 2H),
3.85 (s, 3H); 13C{1H}NMR (100 MHz, CDCl3, DEPT): δ 161.6 (C), 160.7 (C),
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158.1 (C), 149.2 (C), 135.9 (C), 132.6 (CH), 129.9 (CH), 128.9 (CH), 128.8 (2
CH), 128.7 (2 CH), 128.2 (CH), 127.4 (2 CH), 125.0 (CH), 121.7 (CH),
120.2 (C), 114.1 (2 CH), 98.5 (CH), 70.0 (CH2), 55.7 (CH3); HRMS (ESI-TOF)
×
×
×
×
m/z [M+H]+ calcd. for C23H20NO2 342.1489, found 342.1485.
4-(4-methoxyquinolin-2-yl)phenyl acetate (10t): Reaction of azido aldehyde 7a
(100 mg, 0.68 mmol), methanol 8b (28
µ
L, 0.68 mmol) and acetate protected
L, 0.68 mmol) in dry
alkyne 9c (158 mg, 0.68 mmol) with TMSOTf (123
µ
CH2Cl2 (8.0 mL) at 0 °C as described for the 4-alkoxy quinoline 10a followed by
purification on a silica gel column using ethyl acetate-petroleum ether (4:96) as
eluent furnished the 4-alkoxy quinoline 10t (175 mg, 88%) as a yellow sticky
solid; IR (neat): 2952, 2936, 1468, 1459, 1357, 1218, 1182, 1017, 688, 668 cm–1;
1H NMR (400 MHz, CDCl3): δ 8.16-8.09 (m, 4H), 7.70 (t, J = 7.2 Hz, 1H), 7.47
(t, J = 7.2 Hz, 1H), 7.26-7.24 (m, 2H), 7.12 (s, 1H), 4.06 (s, 3H), 2.33 (s, 3H);
13C{1H}NMR (100 MHz, CDCl3, DEPT): δ 169.4 (C), 162.9 (C), 157.8 (C), 151.7
(C), 149.1 (C), 138.0 (C), 130.1 (CH), 129.1 (CH), 128.8 (2
× CH), 125.5 (CH),
121.9 (2 CH), 121.7 (CH), 120.4 (C), 97.8 (CH), 55,7 (CH3), 21.2 (CH3);
×
HRMS (ESI-TOF) m/z [M+H]+ calcd. for C18H16NO3 294.1125, found 294.1123.
2-(benzo[b]thiophen-2-yl)-4-(benzyloxy)quinoline (10u): Reaction of azido
aldehyde 7a (50 mg, 0.316 mmol), benzyl alcohol 8a (55
µL, 0.316 mmol) and
alkyne 9d (46 mg, 0.316 mmol) with TMSOTf (65 L, 0.316 mmol) in dry
µ
CH2Cl2 (8.0 mL) at 0 °C as described for the 4-alkoxy quinoline 10a followed by
purification on a silica gel column using ethyl acetate-petroleum ether (3:97) as
eluent furnished the 4-alkoxy quinoline 10u (90 mg, 78%) as a yellow solid; m.p.
143-145 oC; IR (neat): 3018, 1617, 1591, 1560, 1425, 1365, 1215, 1109, 825, 759
1
cm–1; H NMR (400 MHz, CDCl3): δ 8.19 (d, J = 8.0 Hz, 1H), 8.09 (d, J = 8.4
Hz, 1H), 7.91-7.89 (m, 1H), 7.87 (s, 1H), 7.81-7.79 (m, 1H), 7.01 (t, J = 7.4 Hz,
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1H), 7.58-7.56 (m, 2H), 7.51-7.43 (m, 4H), 7.38-7.36 (m, 2H), 7.23 (s, 1H), 5.33
(s, 2H); 13C{1H}NMR (100 MHz, CDCl3, DEPT): δ 161.6 (C), 153.2 (C), 149.1
(C), 145.9 (C), 141.1 (C), 140.4 (C), 135.8 (C), 130.3 (CH), 128.9 (CH), 128.8 (2
×
CH), 128.5 (CH), 127.6 (2 × CH), 125.7 (CH), 125.3 (CH), 124.5 (CH), 124.3
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(CH), 122.6 (CH), 122.1 (CH), 121.7 (CH), 120.9 (C), 97.7 (CH), 70.4 (CH2);
HRMS (ESI-TOF) m/z [M+Na]+ calcd. for C24H17NNaOS 390.0923, found
390.0928.
4-(benzyloxy)-2-(3a1,5a1-dihydropyren-4-yl)quinoline (10v): Reaction of azido
aldehyde 7a (59 mg, 0.397 mmol), benzyl alcohol 8a (42
pyrene alkyne 9e (90 mg, 0.397 mmol) with TMSOTf (72
µ
L, 0.397 mmol) and
µ
L, 0.397 mmol) in dry
CH2Cl2 (8.0 mL) at 0 °C as described for the 4-alkoxy quinoline 10a followed by
purification on a silica gel column using ethyl acetate-petroleum ether (2:98) as
eluent furnished the 4-alkoxy quinoline 10v (110 mg, 62%) as a white sticky
solid; IR (neat): 3052, 2826, 1476, 1473, 1390, 1237, 1220, 1036, 658, 628 cm–1;
1H NMR (400 MHz, CDCl3): δ 8.41 (d, J = 8.4 Hz, 1H), 8.31-8.18 (m, 6H), 8.13
(s, 2H), 8.05-8.01 (m, 2H), 7.81 (t, J = 8.0 Hz, 1H), 7.61 (t, J = 8.0 Hz, 1H), 7.52
(d, J = 7.2 Hz, 2H), 7.45 (q, J = 8.0 Hz, 4H), 5.36 (s, 2H); 13C{1H}NMR (100
MHz, CDCl3, DEPT): δ 161.3 (C), 160.8 (C), 149.3 (C), 136.5 (C), 135.8 (C),
131.9 (C), 131.5 (C), 131.0 (C), 130.4 (CH), 129.3 (CH), 128.9 (CH), 128.8 (C),
128.5 (CH), 128.2 (2
× CH), 128.1 (CH), 127.6 (3 × CH), 127.5 (CH), 126.2
(CH), 125.9 (CH), 125.5 (CH), 125.3 (CH), 125.2 (C), 124.9 (CH), 124.9 (C),
125.9 (C), 122.1 (CH), 120.4 (C), 104.3 (CH), 70.5 (CH2); HRMS (ESI-TOF) m/z
[M+H]+ calcd. for C32H22NO 436.1696, found 436.1697.
4-(benzyloxy)-2-butylquinoline (10w): Reaction of azido aldehyde 7a (75 mg,
0.51 mmol), benzyl alcohol 8a (60
µL, 0.51 mmol) and hexyne 9f (90 µL, 0.765
mmol) with TMSOTf (74 L, 0.51 mmol) in dry CH2Cl2 (8.0 mL) at 0 °C as
µ
described for the 4-alkoxy quinoline 10a followed by purification on a silica gel
column using ethyl acetate-petroleum ether (2:98) as eluent furnished the 4-
alkoxy quinoline 10w (68 mg, 45%) as a sticky solid; IR (neat): 2852, 3018,
1592, 1557, 1493, 1445, 1422, 1338, 1215, 1160, 759, 668, 549 cm–1; H NMR
1
(400 MHz, CDCl3): δ 8.22 (d, J = 8.1 Hz, 1H), 8.05 (d, J = 8.1 Hz, 1H), 8.67 (t, J
= 8.1 Hz, 1H), 7.52-7.25 (m, 6H), 6.72 (s, 1H), 5.23 (s, 2H), 2.93 (t, J = 8.0 Hz,
2H), 1.80-1.72 (m, 2H), 1.44-1.38 (m, 2H), 0.95 (t, J = 7.2 Hz, 3H); 13C{1H}NMR
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(100 MHz, CDCl3, DEPT): δ 164.2 (C), 161.9 (C), 141.1 (C), 135.7 (C), 135.7
5
6
(CH), 128.8 (CH), 128.5 (CH), 128.4 (2
× CH), 127.6 (CH), 127.5 (2 × CH),
7
8
9
125.5 (CH), 117.6 (C), 101.06 (CH), 70.3 (CH2), 39.1 (CH2), 32.2 (CH2), 22.6
(CH2), 14.1 (CH3); HRMS (ESI-TOF) m/z [M+Na]+ calcd. for C20H21NNaO
314.1515, found 314.1513.
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4-(benzyloxy)-3-butyl-2-phenylquinoline (10x): Reaction of azido aldehyde 7a
(74.2 mg, 0.5 mmol), benzyl alcohol 8a (50
µL, 0.5 mmol) and alkyne 9g (98 mg,
0.6 mmol) with TMSOTf (92 L, 0.5 mmol) in dry CH2Cl2 (8.0 mL) at 0 °C as
µ
described for the 4-alkoxy quinoline 10a followed by purification on a silica gel
column using ethyl acetate-petroleum ether (2:98) as eluent furnished the 4-
alkoxy quinoline 10x (64 mg, 35%) as a pale yellow liquid; IR (neat): 3019, 2952,
2936, 1476, 1433, 1310, 1257, 1160, 1006, 658, 618 cm–1; 1H NMR (500 MHz,
CDCl3): d 8.16 (d, J = 8.3 Hz, 1H), 8.09 (dd, J = 8.3, 0.76 Hz, 1H), 7.68 (ddd, J = 8.4,
6.9, 1.45 Hz, 1H), 7.59-7.51 (m, 5H), 7.51-7.39 (m, 6H), 5.18 (s, 2H), 2.81-2.70 (m,
13
2H), 1.46-1.35 (m, 2H), 1.23-1.11 (m, 2H), 0.73 (t, J = 7.40 Hz, 3H); C{1H}NMR
(126 MHz, CDCl3, DEPT): d 162.8 (C), 160.8 (C), 148.2 (C), 141.3 (C), 136.9 (C),
129.9 (CH), 129.2 (CH), 128.8 (2 × CH), 128.7 (2 × CH), 128.5 (CH), 128.3 (2 ×
CH), 128.2 (CH), 127.8 (2 × CH), 126.6 (C), 126.3 (CH), 123.1 (C), 121.9 (CH), 76.8
(CH2), 32.4 (CH2), 26.8 (CH2), 22.9 (CH2), 13.7 (CH3); HRMS (ESI-TOF) m/z
[M+H]+ calcd. for C26H26NO 368.2009, found 368.2009.
4-(benzyloxy)-2,3-diphenylquinoline (10y): Reaction of azido aldehyde 7a (60
mg, 0.408 mmol), benzyl alcohol 8a (50
µL, 0.489 mmol) and alkyne 9h (72 mg,
0.408 mmol) with TMSOTf (75 L, 0.408 mmol) in dry CH2Cl2 (8.0 mL) at 0 °C
µ
as described for the 4-alkoxy quinoline 10a followed by purification on a silica
gel column using ethyl acetate-petroleum ether (2:98) as eluent furnished the 4-
alkoxy quinoline 10y (90 mg, 65%) as a colourless liquid; IR (neat): 2930, 1585,
1508, 1489, 1415, 1110, 939, 844, 762, 699 cm–1; 1H NMR (500 MHz, CDCl3): δ
8.24 (t, J = 7.0 Hz, 2H), 7.78 (t, J = 7.5 Hz, 1H), 7.59 (t, J = 7.5 Hz, 1H), 7.41-
7.26 (m, 13H), 7.13-7.12 (m, 2H), 4.60 (s, 2H); 13C{1H}NMR (125 MHz, CDCl3,
DEPT): δ 160.8 (C), 160.4 (C), 149.9 (C), 140.6 (C), 136.4 (C), 135.6 (C), 131.4
(2
×
CH), 130.1 (CH), 130.0 (2
×
CH), 129.7 (CH), 128.6 (2
×
CH), 128.5 (2
×
CH), 128.4 (CH), 128.3 (2
×
CH), 127.9 (CH), 127.8 (2 × CH), 127.4 (CH),
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126.6 (CH), 126.2 (C), 123.2 (C), 122.6 (CH), 75.8 (CH2); HRMS (ESI-TOF) m/z
[M+H]+ calcd. for C28H22NO 388.1696, found 388.1691.
7
8
4-(benzyloxy)-3-bromo-2-phenylquinoline (10z): Reaction of azido aldehyde 7a
(120 mg, 0.816 mmol), benzyl alcohol 8a (85
µ
L, 0.816 mmol) and bromo alkyne
L, 0.816 mmol) in dry CH2Cl2
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9i (147.8 mg, 0.816 mmol) with TMSOTf (148
µ
(8.0 mL) at 0 °C as described for the 4-alkoxy quinoline 10a followed by
purification on a silica gel column using ethyl acetate-petroleum ether (2:98) as
eluent furnished the 4-alkoxy quinoline 10z (187 mg, 72%) as a white solid; m.p.
122-125 oC; IR (neat): 3115, 2826, 1566, 1553, 1450, 1317, 1080, 1016, 678, 628
1
cm–1; H NMR (400 MHz, CDCl3): δ 8.14 (d, J = 8.4 Hz, 1H), 8.08 (d, J = 8.4
Hz, 1H), 7.76-7.71 (m, 3H), 7.61 (d, J = 7.2 Hz, 2H), 7.57-7.39 (m, 7H), 5.28 (s,
2H); 13C{1H}NMR (100 MHz, CDCl3, DEPT): δ 160.5 (C), 160.4 (C), 148.3 (C),
140.4 (C), 136.2 (C), 130.1 (CH), 129.8 (CH), 129.5 (2
(2 CH), 128.8 (2 CH), 128.5 (2 CH), 128.1 (CH), 127.2 (CH), 124.1 (C),
122.1 (CH), 110.9 (C), 76.3 (CH2)
HRMS (ESI-TOF) m/z [M+H]+ calcd. for
C22H17BrNO 390.0488, found 390.0485.
× CH), 128.9 (CH), 128.8
×
×
×
;
4-(2-azidoethoxy)-2-(4-propoxyphenyl)quinoline (10aa): Reaction of azido
aldehyde 7a (70 mg, 0.476 mmol), azido alcohol 8o (45 mg, 0.476 mmol) and
alkyne 9j (76 mg, 0.476 mmol) with TMSOTf (86
µL, 0.476 mmol) in dry
CH2Cl2 (8.0 mL) at 0 °C as described for the 4-alkoxy quinoline 9a followed by
purification on a silica gel column using ethyl acetate-petroleum ether (4:96) as
eluent furnished the 4-alkoxy quinoline 10aa (83 mg, 50%) as yellow liquid; IR
(neat): 2854, 2928, 2233, 1465, 1455, 1352, 1218, 1186, 1017, 697, 665 cm–1; 1H
NMR (500 MHz, CDCl3): δ 8.17 (d, J = 8.5 Hz, 1H), 8.15 (s, 1H), 8.06 (d, J = 9.0
Hz, 2H), 7.72 (td, J = 8.5, 1.0 Hz, 1H), 7.48 9(t, J = 7.5 Hz, 1H), 7.10 (s, 1H),
7.01 (d, J = 8.5 Hz, 2H), 4.45 (t, J = 5.0 Hz, 2H), 3.99 (t, J = 6.5 Hz, 2H), 3.78 (t,
5.0 Hz, 2H), 1.88-1.81 (m, 2H), 1.07 (t, J = 7.5 Hz, 3H); 13C{1H}NMR (125
MHz, CDCl3, DEPT): δ 161.8 (C), 160.7 (C), 158.2 (2
×
C), 130.5 (CH), 128.7
CH), 98.2 (CH),
(C), 129.1 (CH), 125.6 (CH), 121.8 (CH), 119.9 (C), 114.9 (3
×
69.8 (CH2), 67.6 (CH2), 50.3 (CH2), 22.7 (CH2), 10.6 (CH3); HRMS (ESI-TOF)
m/z [M+H]+ calcd. for C20H21N4O2 349.1659, found 349.1658.
4-(benzyloxy)-6-nitro-2-phenylquinoline (10ab): Reaction of azido aldehyde 6b
(100 mg, 0.52 mmol), benzyl alcohol 8a (55
µL, 0.52 mmol) and phenyl
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acetylene 9a (57
µ
L, 0.52 mmol) with TMSOTf (94 µL, 0.52 mmol) in dry
5
6
7
8
CH2Cl2 (8.0 mL) at 0 °C as described for the 4-alkoxy quinoline 10a followed by
purification on a silica gel column using ethyl acetate-petroleum ether (3:97) as
eluent furnished the 4-alkoxy quinoline 10ab (120 mg, 83%) as a yellow sticky
solid; IR (neat): 3153, 2834, 2863, 1627, 1492, 1409, 1367, 1253, 1122, 1015, 914,
768, 734, 695 cm–1; 1H NMR (400 MHz, CDCl3): δ 9.16 (d, J = 2.0 Hz, 1H), 8.43
(m, 1H), 8.17 (d, J = 9.2 Hz, 1H), 8.10 (d, J = 8.0 Hz, 1H), 7.56-7.41 (m, 8H),
7.36 (s, 1H), 5.43 (s, 2H); 13C{1H}NMR (100 MHz, CDCl3, DEPT): δ 163.1 (C),
162.4 (C), 151.6 (C), 144.7 (C), 139.2 (C), 134.9 (C), 131.8 (CH), 130.4 (CH),
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129.1 (2
× CH), 129.1 (CH), 128.9 (2 × CH), 127.8 (2 × CH), 127.7 (2 × CH),
119.7 (CH), 119.6 (CH), 100.5 (CH), 71.1 (CH2); HRMS (ESI-TOF) m/z [M+H]+
calcd. for C22H17N2O3 357.1234, found 357.1235.
4-(benzyloxy)-6-bromo-2-phenylquinoline (10ac): Reaction of azido aldehyde 7c
(100 mg, 0.442 mmol), benzyl alcohol 8a (46
µ
L, 0.442 mmol) and phenyl
L, 0.442 mmol) in dry
acetylene 9a (49 L, 0.442 mmol) with TMSOTf (80
µ
µ
CH2Cl2 (8.0 mL) at 0 °C as described for the 4-alkoxy quinoline 10a followed by
purification on a silica gel column using ethyl acetate-petroleum ether (3:97) as
eluent furnished the 4-alkoxy quinoline 10ac (143 mg, 83%) as a white sticky
solid; IR (neat): 3053, 2954, 2843, 1607, 1592, 1519, 1357, 1243, 1122, 1015, 918,
777, 731, 649 cm–1; 1H NMR (500 MHz, CDCl3): δ 8.37 (d, J = 2.5 Hz, 1H), 8.08-
8.06 (m, 2H), 7.98 (d, J = 6.5 Hz, 1H), 7.76 (dd, J = 7.2, 2.5 Hz, 1H), 7.54-7.51
(m, 4H), 7.49-7.46 (m, 3H), 7.43-7.40 (m, 1H), 7.25 (s, 1H), 5.34 (s, 2H);
13C{1H}NMR (125 MHz, CDCl3, DEPT): δ 161.0 (C), 159.1 (C), 147.8 (C), 139.8
(C), 135.5 (C), 131.0 (CH), 129.7 (CH), 129.0 (CH), 128.9 (2
× CH), 128.7 (2 ×
CH), 127.8 (CH), 127.7 (2 CH), 127.6 (2 CH), 124.4 (CH), 121.7 (C), 119.4
×
×
(C), 99.8 (CH), 70.6 (CH2); HRMS (ESI-TOF) m/z [M+H]+ calcd. for
C22H17BrNO 390.0488, found 390.0486.
8-(benzyloxy)-6-phenyl-[1,3]dioxolo[4,5-g]quinoline (10ad):
Reaction of azido aldehyde 7d (70 mg, 0.366 mmol), benzyl alcohol 8a (55
0.366 mmol) and phenyl acetylene 9a (50 L, 0.366 mmol) with TMSOTf (75
L, 0.366 mmol) in dry CH2Cl2 (8.0 mL) at 0 °C as described for the 4-alkoxy
µl,
µ
µ
quinoline 10a followed by purification on a silica gel column using ethyl acetate-
petroleum ether (3:97) as eluent furnished the 4-alkoxy quinoline 10ad (110 mg,
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83%) as a white solid; m.p. 108-110 C; IR (neat): 3133, 2984, 2863, 1627, 1542,
1519, 1347, 1323, 1212, 1165, 932, 759, 699 cm–1; 1H NMR (400 MHz, CDCl3): δ
8.03 (d, J = 7.2 Hz, 2H), 7.53-7.35 (m, 10H), 7.15 (s, 1H), 6.07 (s, 2H), 5.31 (s,
2H); 13C{1H}NMR (100 MHz, CDCl3, DEPT): δ 161.2 (C), 156.9 (C), 151.0 (C),
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147.5 (C), 147.2 (C), 140.2 (C), 136.0 (C), 129.5 (CH), 128.8 (2
× CH), 128.8 (2
×
CH), 128.4 (CH), 127.6 (2 CH), 127.4 (2 CH), 116.4 (C), 105.9 (CH),
×
×
101.7 (CH2), 98.5 (CH), 97.9 (CH), 70.2 (CH2); HRMS (ESI-TOF) m/z [M+H]+
calcd. for C23H18NO3 356.1281, found 356.1290.
2-phenylquinolin-4-ol (11):[18] Reaction of azido aldehyde 7a (50 mg, 0.34
mmol), (−)-Ethyl L-lactate 8j (42
µl, 0.34 mmol) and phenyl acetylene 9a (44 µL,
0.34 mmol) with TMSOTf (65 L, 0.34 mmol) in dry CH2Cl2 (8.0 mL) at 0 °C as
µ
described for the 4-alkoxy quinoline 10a followed by purification on a silica gel
column using ethyl acetate-petroleum ether (50:50) as eluent furnished the 4-
o
alkoxy quinoline 11 (50 mg, 65%) as a white solid; m.p. 205-207 C; IR (neat):
1
3533, 2952, 2926, 1466, 1453, 1350, 1217, 1180 cm–1; H NMR (500 MHz,
Acetone-d6): δ 8.34 (d, J = 8.0 Hz, 1H), 7.86 (d, J = 8.5 Hz, 1H), 7.69-7.64 (m,
3H), 7.51-7.42 (m, 3H), 7.26 (t, J = 7.5 Hz, 1H), 6.65 (s, 1H); 13C{1H}NMR (125
MHz, Acetone-d6, DEPT): δ 179.2 (C), 134.8 (C), 133.1 (CH), 131.5 (2
× CH),
129.9 (2 CH), 128.4 (CH), 126.1 (C), 125.6 (CH), 124.7 (C), 123.2 (CH), 119.5
×
(C), 118.1 (CH), 108.7 (CH); HRMS (ESI-TOF) m/z [M+Na]+ calcd. for
C15H11NaNO 244.0733, found 244.0728.
General procedure of intramolecular reaction for synthesis of cyclic ether-
fused quinoline derivatives:
4-phenyl-2, 3-dihydrofuro[3,2-c]quinoline (13a):[19]
To a magnetically stirred solution of azido aldehyde 7a (70 mg, 0.476 mmol),
alkynol 12a (70 mg, 0.476 mmol) in dry CH2Cl2 (8.0 ml) was added dropwise
o
TMSOTf (85
µ
L, 0.476 mmol) at 0 C. Reaction was monitored by TLC,
quenched with saturated aq. solution of NaHCO3 upon completion, extracted with
CH2Cl2 (3 × 5 mL) and dried over anhydrous Na2SO4. Evaporation of the solvent
and purification of the residue over a silica gel column using EtOAc-petroleum
ether as eluent furnished 4-alkoxy quinoline 13a (117 mg, 99%) as a white solid;
o
m.p. 64-66 C; IR (neat): 3052, 2926, 1566, 1473, 1360, 1207, 1190, 1006, 688,
1
658 cm–1; H NMR (500 MHz, CDCl3): δ 8.13 (d, J = 8.5 Hz, 1H), 7.90 (d, J =
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8.5 Hz, 1H), 7.86 (d, J = 7.5 Hz, 2H), 7.63 (t, J = 7.5 Hz, 1H), 7.47 (d, J = 7.5 Hz,
2H), 7.41 (d, J = 7.5 Hz, 2H), 4.71 (t, J = 9.0 Hz, 2H), 3.39 (t, J = 9.0 Hz, 2H);
13C{1H}NMR (125 MHz, CDCl3, DEPT): δ 164.2 (C), 155.3 (C), 149.0 (C), 139.7
(C), 129.6 (CH), 129.1 (CH), 128.7 (CH), 128.4 (2
× CH), 128.2 (2 × CH), 125.2
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(CH), 121.3 (CH), 115.9 (C), 115.0 (C), 72.9 (CH2), 29.9 (CH2); HRMS (ESI-
TOF) m/z [M+Na]+ calcd. for C17H13NNaO 270.0899, found 270.0877.
2-methyl-4-phenyl-2,3-dihydrofuro[3,2-c]quinoline (13b): Reaction of azido
aldehyde 7a (64 mg, 0.436 mmol), alkynol 12b (70 mg, 0.436 mmol) with
TMSOTf (80 µL, 0.436 mmol) in dry CH2Cl2 (8.0 mL) at 0 °C as described for
the quinoline 13a followed by purification on a silica gel column using ethyl
acetate-petroleum ether (5:95) as eluent furnished the quinoline 13b (109 mg,
o
96%) as a white solid; m.p. 68-70 C; IR (neat): 3059, 2975, 2927, 2857, 1630,
1592, 1554, 1505, , 703, 674 cm–1; 1H NMR (500 MHz, CDCl3): δ 8.13 (dd, J =
8.5, 1.0 Hz, 1H), 7.96 (dd, J = 8.5, 1.0 Hz, 1H), 7.91-7.89 (m, 2H), 7.68-7.64 (m,
1H), 7.52-7.48 (m, 2H), 7.46-7.42 (m, 2H), 5.25-5.18 (m, 1H), 3.66 (dd, J = 15.0,
9.5 Hz, 1H), 3.15 (dd, J = 15.0, 7.5 Hz, 1H), 1.58 (d, J = 6.0 Hz, 3H);
13C{1H}NMR (125 MHz, CDCl3, DEPT): δ 163.6 (C), 155.6 (C), 149.3 (C), 140.6
(C), 129.6 (CH), 129.3 (CH), 128.8 (CH), 128.5 (2
× CH), 128.3 (2 × CH), 125.3
(CH), 121.5 (CH), 116.1 (C), 114.9 (C), 82.1 (CH), 37.5 (CH2), 22.1 (CH3);
HRMS (ESI-TOF) m/z [M+H]+ calcd. for C18H16NO 262.1226, found 262.1228.
2-((benzyloxy)methyl)-4-phenyl-2,3-dihydrofuro[3,2-c]quinoline (13c): Reaction
of azido aldehyde 7a (70 mg, 0.476 mmol), alkynol 12c (152 mg, 0.476 mmol)
with TMSOTf (87 µL, 0.476 mmol) in dry CH2Cl2 (8.0 mL) at 0 °C as described
for the quinoline 13a followed by purification on a silica gel column using ethyl
acetate-petroleum ether (5:95) as eluent furnished the quinoline 13c (168 mg,
96%) as a pale yellow liquid; IR (neat): 3063, 2926, 1466, 1453, 1350, 1217,
1
1180, 1016, 698, 668 cm–1; H NMR (400 MHz, CDCl3): δ 8.26 (d, J = 8.1 Hz,
1H), 7.99 (d, J = 7.4 Hz, 1H), 7.90 (d, J = 7.4 Hz, 2H), 7.27-7.68 (m, 1H), 7.52-
7.45 (m, 4H), 7.32-7.26 (m, 5H), 5.32 (bs, 1H), 4.63 (AB, J = 12.4, 5.6 Hz, 2H),
3.83-3.75 (m, 2H), 3.66-3.59 (m, 1H), 3.39 (dd, J = 15.2, 6.8 Hz, 1H);
13C{1H}NMR (100 MHz, CDCl3, DEPT): δ 164.0 (C), 155.5 (C), 149.1 (C), 139.6
(C), 137.8 (C), 129.9 (CH), 129.1 (CH), 129.0 (CH), 128.7 (2
×
CH), 128.6 (2
×
CH), 128.5 (2
×
CH), 127.9 (CH), 127.9 (2 × CH), 125.6 (CH), 121.6 (CH),
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116.0 (C), 114.8 (C), 84.2 (CH), 73.7 (CH2), 71.7 (CH2), 32.6 (CH2); HRMS
(ESI-TOF) m/z [M+H]+ calcd. for C25H22NO2 368.1645, found 368.1644.
2-cyclohexyl-4-phenyl-2,3-dihydrofuro[3,2-c]quinoline (13d): Reaction of azido
aldehyde 7a (45 mg, 0.306 mmol), alkynol 12d (70 mg, 0.306 mmol) with
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TMSOTf (58 µL, 0.306 mmol) in dry CH2Cl2 (8.0 mL) at 0 °C as described for
the quinoline 13a followed by purification on a silica gel column using ethyl
acetate-petroleum ether (5:95) as eluent furnished the quinoline 13d (95 mg,
95%) as a white solid; m.p. 122-125 oC; IR (neat): 3022, 2936, 1456, 1433, 1356,
1267, 1160, 1026, 698, 666 cm–1; 1H NMR (500 MHz, CDCl3): δ 8.12 (d, J = 8.5
Hz, 1H), 7.98 (d, J = 8.0 Hz, 1H), 7.91 (d, J = 8.5 Hz, 2H), 7.65 (td, J = 7.0, 1.5
Hz, 1H), 7.51 (t, J = 7.5, Hz, 2H), 7.44 (td, J = 7.0, 1.5 Hz, 2H), 4.81 (dd, J =
16.2, 7.2 Hz, 1H), 3.53 (dd, J = 15.5, 9.0 Hz, 1H), 3.29 (dd, J = 15.5, 9.0 Hz, 1H),
2.05 (d, J = 13.0 Hz, 1H), 1.81-1.71 (m, 5H), 1.33-1.28 (m, 3H), 1.27-1.13 (m,
2H); 13C{1H}NMR (125 MHz, CDCl3, DEPT): δ 163.9 (C), 155.6 (C), 149.3 (C),
140.2 (C), 129.6 (CH), 129.3 (CH), 128.6 (2
× CH), 128.4 (3 × CH), 125.2 (CH),
121.6 (CH), 115.9 (C), 115.2 (C), 89.9 (CH), 43.3 (CH), 33.4 (CH2), 28.5 (CH2),
28.2 (CH2), 26.4 (CH2), 25.9 (CH2), 25.7 (CH2); HRMS (ESI-TOF) m/z [M+Na]+
calcd. for C23H23NNaO 352.1672, found 352.1675.
2,4-diphenyl-2,3-dihydrofuro[3,2-c]quinoline (13e): Reaction of azido aldehyde
7a (42 mg, 0.288 mmol), alkynol 12e (69 mg, 0.288 mmol) with TMSOTf (80
µ
L, 0.288 mmol) in dry CH2Cl2 (8.0 mL) at 0 °C as described for the quinoline
13a followed by purification on a silica gel column using ethyl acetate-petroleum
ether (5:95) as eluent furnished the quinoline 13e (97 mg, 93%) as a white solid;
o
m.p. 130-132 C; IR (neat): 3013, 2986, 1456, 1443, 1360, 1277, 1160, 1026,
678, 658 cm–1; 1H NMR (500 MHz, CDCl3): δ 8.18 (d, J = 8.5 Hz, 1H), 8.10 (d, J
= 8.0 Hz, 1H), 7.74 (t, J = 7.5 Hz, 1H), 7.68 (d, J = 8.0 Hz, 1H), 7.55 (t, J = 7.5
Hz, 1H), 7.49-7.37 (m, 7H), 7.30 (d, J = 8.0 Hz, 2H), 6.11 (t, J = 8.5 Hz, 1H),
3.76 (dd, J = 8.5, 7.5 Hz, 1H), 3.45 (dd, J = 8.5, 7.5 Hz, 1H); 13C{1H}NMR (125
MHz, CDCl3, DEPT): δ 163.0 (C), 156.4 (C), 149.2 (C), 141.1 (C), 141.0 (C),
132.9 (CH), 130.6 (CH), 130.1 (CH), 129.9 (CH), 129.5 (CH), 128.9 (2
× CH),
128.6 (CH), 127.7 (CH), 125.9 (CH), 125.9 (2 CH), 121.8 (CH), 121.7 (CH),
×
116.5 (C), 116.2 (C), 86.7 (CH), 37.5 (CH2); HRMS (ESI-TOF) m/z [M+H]+
calcd. for C23H18NO 324.1383, found 324.1382.
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4-ethyl-2,3-dihydrofuro[3,2-c]quinoline (13f): Reaction of azido aldehyde 7a (84
5
6
mg, 0.641 mmol), alkynol 12f (63 mg, 0.641 mmol) with TMSOTf (116
µL,
7
8
9
0.641 mmol) in dry CH2Cl2 (8.0 mL) at 0 °C as described for the quinoline 13a
followed by purification on a silica gel column using ethyl acetate-petroleum
ether (5:95) as eluent furnished the quinoline 13f (126 mg, 98%) as a yellow
liquid; IR (neat): 3013, 2998, 1566, 1463, 1370, 1237, 1120, 1036, 679, 669 cm–1;
1H NMR (400 MHz, CDCl3): δ 7.98 (d, J = 8.4 Hz, 1H), 7.86 (d, J = 8.0 Hz, 1H),
7.59 (t, J = 7.2 Hz, 1H), 7.38 (t, J = 7.2 Hz, 1H), 4.82 (t, J = 8.8 Hz, 2H), 3.31 (t,
J = 10.4 Hz, 2H), 2.86 (q, J = 7.6 Hz, 2H), 1.34 (t, J = 7.6 Hz, 3H); 13C{1H}NMR
(100 MHz, CDCl3, DEPT): δ 163.4 (C), 160.8 (C), 149.1 (C), 129.4 (CH), 128.5
(CH), 124.8 (CH), 121.4 (CH), 115.9 (C), 115.4 (C), 73.1 (CH2), 30.3 (CH2), 28.2
(CH2), 12.9 (CH3); HRMS (ESI-TOF) m/z [M+H]+ calcd. for C13H14NO
200.1070, found 200.1072.
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2-(tert-butyl)-4-(4-methoxyphenyl)-2,3-dihydrofuro[3,2-c]quinoline
Reaction of azido aldehyde 7a (42 mg, 0.288 mmol), alkynol 12g (67 mg, 0.288
mmol) with TMSOTf (52 L, 0.288 mmol) in dry CH2Cl2 (8.0 mL) at 0 °C as
(13g):
µ
described for the quinoline 13a followed by purification on a silica gel column
using ethyl acetate-petroleum ether (5:95) as eluent furnished the quinoline 13g
o
(88 mg, 92%) as a white solid; m.p. 140-142 C; IR (neat): 2999, 2986, 1476,
1433, 1310, 1207, 1090, 1036, 678, 658 cm–1; 1H NMR (400 MHz, CDCl3): δ
8.12 (d, J = 8.8 Hz, 1H), 7.97 (dd, J = 8.0, 0.8 Hz, 1H), 7.90 (dd, J = 6.8, 2.0 Hz,
2H), 7.67-7.63 (m, 1H), 7.46-7.42 (m, 1H), 7.04 (dd, J = 6.8, 2.0 Hz, 2H), 4.81 (t,
J = 8.8 Hz, 1H), 3.88 (s, 3H), 3.47 (dd, J = 15.6, 10.0 Hz, 1H), 3.32 (dd, J = 15.6,
8.6 Hz, 1H), 1.04 (s, 9H); 13C{1H}NMR (100 MHz, CDCl3, DEPT): δ 164.3 (C),
160.4 (C), 155.0 (C), 150.0 (C), 132.4(C), 129.9 (2
(CH), 125.0 (CH), 121.6 (CH), 115.7 (C), 114.9 (C), 114.1 (2
55.5 (CH), 34.8 (C), 31.5 (CH2), 25.1 (3
CH3); HRMS (ESI-TOF) m/z [M+H]+
×
CH), 129.8 (CH), 128.9
×
CH), 93.4 (CH),
×
calcd. for C22H24NO2 334.1820, found 334.1821.
4-(4-methoxyphenyl)-2-phenyl-2,3-dihydrofuro[3,2-c]quinoline (13h):
Reaction of azido aldehyde 7a (67 mg, 0.455 mmol), alkynol 12h (115 mg, 0.455
mmol) with TMSOTf (85 µL, 0.455 mmol) in dry CH2Cl2 (8.0 mL) at 0 °C as
described for the quinoline 13a followed by purification on a silica gel column
using ethyl acetate-petroleum ether (5:95) as eluent furnished the quinoline 13h
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(155 mg, 93%) as a white solid; m.p. 152-154 C; IR (neat): 3092, 2966, 1557,
1456, 1423, 1320, 1207, 1190, 1006, 658, 648 cm–1; H NMR (500 MHz, CDCl3):
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7
8
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δ 8.14 (d, J = 8.5 Hz, 1H), 8.03 (d, J = 8.0 Hz, 1H), 7.90 (d, J = 8.0 Hz, 2H), 7.68
(t, J = 7.5 Hz, 1H), 7.48-7.44 (m, 3H), 7.40 (t, J = 7.5 Hz, 2H), 7.35-7.33 (m, 1H),
7.01 (d, J = 8.0 Hz, 2H), 6.04 (dd, J = 8.0, 0.0 Hz, 1H), 4.40 (dd, J = 15.0, 9.5 Hz,
1H), 3.86 (s, 3H), 3.58 (dd, J = 15.0, 8.0 Hz, 1H); 13C{1H}NMR (125 MHz,
CDCl3, DEPT): δ 163.6 (C), 160.3 (C), 155.1 (C), 149.5 (C), 141.3 (C), 132.5
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(C), 129.8 (3
×
CH), 129.3 (CH), 128.9 (2
×
CH), 128.5 (CH), 125.8 (2
× CH),
125.3 (CH), 121.6 (CH), 115.8 (C), 114.1 (C), 114.0 (2
×
CH), 86.1 (CH), 55.4
(CH3), 39.3 (CH2); HRMS (ESI-TOF) m/z [M+H]+ calcd. for C24H20NO2
354.1489, found 354.1481.
2-methyl-4-(4-nitrophenyl)-2,3-dihydrofuro[3,2-c]quinoline (13i): Reaction of
azido aldehyde 7a (57 mg, 0.389 mmol), alkynol 13i (80 mg, 0.389 mmol) with
TMSOTf (75 µL, 0.389 mmol) in dry CH2Cl2 (8.0 mL) at 0 °C as described for
the quinoline 13a followed by purification on a silica gel column using ethyl
acetate-petroleum ether (5:95) as eluent furnished the quinoline 13i (110 mg,
93%) as a white sticky solid; IR (neat): 2952, 2936, 1456, 1423, 1390, 1297,
1
1150, 1026, 688, 648 cm–1; H NMR (400 MHz, CDCl3): δ 8.34-8.32 (m, 2H),
8.10-8.07 (m, 3H), 7.97 (dd, J = 8.5 Hz, 1H), 7.71-7.67 (m, 1H), 7.51-7.48 (m,
1H), 5.32-5.25 (m, 1H), 3.69 (dd, J = 15.0, 9.0 Hz, 1H), 3.18 (J = 15.0, 7.5 Hz,
1H), 1.62 (d, J = 6.5 Hz, 3H); 13C{1H}NMR (125 MHz, CDCl3, DEPT): δ 164.3
(C), 152.8 (C), 149.3 (C), 148.0 (C), 146.1 (C), 130.2 (CH), 129.5 (CH), 129.3 (2
×
CH), 126.2 (CH), 123.8 (2 × CH), 121.7 (CH), 116.4 (C), 115.2 (C), 82.4
(CH), 37.5 (CH2), 22.1 (CH3); HRMS (ESI-TOF) m/z [M+H]+ calcd. for
C18H15N2O3 307.1038, found 307.1036.
4-(2-bromophenyl)-2-phenyl-2,3-dihydrofuro[3,2-c]quinoline (13j): Reaction of
azido aldehyde 7a (50 mg, 0.332 mmol), alkynol 12j (100 mg, 0.332 mmol) with
TMSOTf (60 µL, 0.332 mmol) in dry CH2Cl2 (8.0 mL) at 0 °C as described for
the quinoline 13a followed by purification on a silica gel column using ethyl
acetate-petroleum ether (5:95) as eluent furnished the quinoline 13j (124 mg,
93%) as a white solid; m.p. 168-170 oC; IR (neat): 3012, 2986, 1416, 1403, 1360,
1
1207, 1120, 1006, 678, 658 cm–1; H NMR (500 MHz, CDCl3): δ 8.18 (d, J = 8.5
Hz, 1H), 8.10 (d, J = 8.0 Hz, 1H), 7.74 (t, J = 7.5 Hz, 1H), 7.68 (d, J = 8.0 Hz,
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1H), 7.55 (t, J = 7.5 Hz, 1H), 7.50-7.37 (m, 7H), 7.30 (t, J = 8.0 Hz, 1H), 6.11 (t,
J = 8.5 Hz, 1H), 3.76 (dd, J = 15.5, 10.0 Hz, 1H), 3.35 (dd, J = 15.5, 7.0 Hz, 1H);
13C{1H}NMR (125 MHz, CDCl3, DEPT): δ 163.0 (C), 156.4 (C), 149.2 (C), 141.1
(C), 141.0 (C), 132.9 (CH), 130.6 (CH), 130.1 (CH), 129.9 (CH), 129.5 (CH),
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128.9 (2
× CH), 128.6 (CH), 127.7 (CH), 125.9 (CH), 125.9 (2 × CH), 121.9 (C),
121.7 (CH), 116.5 (C), 116.2 (C), 86.7 (CH), 37.5 (CH2); HRMS (ESI-TOF) m/z
[M+H]+ calcd. for C23H17BrNO 402.0488, found 402.0489.
(6bS*,9aS*)-6-phenyl-6b,8,9,9a-tetrahydro-7H-cyclopenta[4,5]furo[3,2-
c]quinoline (13k): Reaction of azido aldehyde 7a (63 mg, 0.429 mmol), alkynol
12k (80 mg, 0.429 mmol) with TMSOTf (80 µL, 0.429 mmol) in dry CH2Cl2 (8.0
mL) at 0 °C as described for the quinoline 13a followed by purification on a silica
gel column using ethyl acetate-petroleum ether (5:95) as eluent furnished the
o
quinoline 13k (121 mg, 98%) as a white solid; m.p. 86-88 C; IR (neat): 3056,
2960, 1630, 1591, 1556, 1398, 1328, 1300, 1205, 1156, 1091, 1022, 991, 913,
760, 736, 700, 673 cm–1;1H NMR (500 MHz, CDCl3): δ 8.13 (d, J = 8.5, 1.0 Hz,
1H), 7.97 (dd, J = 8.5, 1.0 Hz, 1H), 7.91 (d, J = 7.0 Hz, 2H), 7.67-7.63 (m, 1H),
7.49 (t, J = 8.0 Hz, 2H), 7.45-7.42 (m, 2H), 5.52 (t, J = 6.5 Hz, 1H), 4.34-4.31 (m,
1H), 2.18 (dd, J = 11.6, 4.5 Hz, 1H), 1.87-1.81 (m, 1H), 1.75-1.68 (m, 1H), 1.61-
1.56 (m, 1H), 1.53-1.49 (m, 1H), 1.42-1.39 (m, 1H); 13C{1H}NMR (125 MHz,
CDCl3, DEPT): δ 164.2 (C), 156.1 (C), 149.1 (C), 139.7 (C), 129.5 (CH), 129.2
(CH), 128.6 (CH), 128.5 (2
× CH), 128.4 (2 × CH), 125.2 (CH), 121.7 (CH),
118.9 (C), 115.7 (C), 95.5 (CH), 46.4 (CH), 35.2 (CH2), 33.4 (CH2), 23.4 (CH2);
HRMS (ESI-TOF) m/z [M+Na]+ calcd. for C20H17NNaO 310.1202, found
310.1201.
4-(phenylethynyl)-2,3-dihydrofuro[3,2-c]quinoline (13l): Reaction of azido aldehyde
7a (60 mg, 0.411 mmol), alkynol 12l (70 mg, 0.411 mmol) with TMSOTf (90 µL,
0.411 mmol) in dry CH2Cl2 (8.0 mL) at 0 °C as described for the quinoline 13a
followed by purification on a silica gel column using ethyl acetate-petroleum
ether (5:95) as eluent furnished the quinoline 13l (108 mg, 93%) as a white solid;
m.p. 135-137 oC; IR (neat): 2984, 2102, 1466, 1383, 1263, 1037, 1027, 978, 877,
758, 608 cm–1;1H NMR (400 MHz, CDCl3): δ 8.02 (d, J = 8.4 Hz, 1H), 7.77 (d, J
= 8.0 Hz, 1H), 7.61-7.56 (m, 3H), 7.37 (t, J = 7.6 Hz, 1H), 77.31-7.28 (m, 3H),
4.76 (t, J = 9.2 Hz, 2H), 3.38 (t, J = 9.2 Hz, 2H); 13C{1H}NMR (100 MHz,
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