Efficient synthesis of functionalized dihydroquinolines, quinolines and dihydrobenzo[b]azepine via an iron(iii) chloride-catalyzed intramolecular alkyne-carbonyl metathesis of alkyne tethered 2-amino benzaldehyde/acetophenone derivatives

Article abstract of DOI:10.1039/c3ob42292e

In this study we have developed an efficient synthesis of 1,2-dihydroquinoline and dihydrobenzo[b]azepine derivatives involving the iron(iii) chloride intramolecular alkyne-carbonyl metathesis reaction for the first time. Various functionalized 1,2-dihydroquinolines and dihydrobenzo[b]azepines were prepared from easily accessible substrates in the presence of environmentally friendly and inexpensive iron(iii) chloride (10 mol%) under mild conditions. The method is applicable to a wide range of substrates containing different functional groups and furnishing products in good to excellent yields. This methodology was further extended to the one-pot synthesis of 3-acyl quinolines via alkyne-carbonyl metathesis/detosylation/ aromatization of N-propargyl-2-aminobenzaldehyde/acetophenone derivatives by the addition of NaOH/EtOH. While many Lewis acid and Bronsted acid catalysts were investigated, anhydrous iron(iii) chloride turned out to be the best catalyst for this transformation.

Full text of DOI:10.1039/c3ob42292e

Organic &
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PAPER
Efficient synthesis of functionalized
dihydroquinolines, quinolines and
dihydrobenzo[b]azepine via an iron(III)
chloride-catalyzed intramolecular
Cite this: Org. Biomol. Chem., 2014,
12, 1759
alkyne–carbonyl metathesis of alkyne tethered
2-amino benzaldehyde/acetophenone derivatives†
Swapnadeep Jalal, Krishnendu Bera, Soumen Sarkar, Kartick Paul and Umasish Jana*
In this study we have developed an efficient synthesis of 1,2-dihydroquinoline and dihydrobenzo[b]-
azepine derivatives involving the iron(III) chloride intramolecular alkyne–carbonyl metathesis reaction for
the first time. Various functionalized 1,2-dihydroquinolines and dihydrobenzo[b]azepines were prepared
from easily accessible substrates in the presence of environmentally friendly and inexpensive iron(III)
chloride (10 mol%) under mild conditions. The method is applicable to a wide range of substrates contain-
ing different functional groups and furnishing products in good to excellent yields. This methodology was
further extended to the one-pot synthesis of 3-acyl quinolines via alkyne–carbonyl metathesis/detosylation/
aromatization of N-propargyl-2-aminobenzaldehyde/acetophenone derivatives by the addition of NaOH/
EtOH. While many Lewis acid and Brønsted acid catalysts were investigated, anhydrous iron(III) chloride
turned out to be the best catalyst for this transformation.
Received 18th November 2013,
Accepted 7th January 2014
DOI: 10.1039/c3ob42292e
www.rsc.org/obc
Considering the importance of 1,2-dihydroquinoline deriva-
tives numerous synthetic strategies have been developed. In
Introduction
Nitrogen-containing heterocycles are ubiquitous structural general, traditional procedures are laborious, low yielding, and
motifs in many natural products and small molecules of bio- require special synthetic precursors.6 Recently, many new strat-
medical relevance.1 In this regard, quinolines and their fully egies towards the synthesis of 1,2-dihydroquinolines have been
or partially hydrogenated derivatives are widely found in many reported. For example, Brønsted and Lewis acid catalyzed
biologically active natural or synthetic products.2 In particular, tandem reactions of aniline with α-ketoesters,7 Michael-aldol
1,2-dihydroquinolines have received special attention because reactions,8 tandem reaction of aromatic amines with alkynes,9
of their numerous applications as pharmaceuticals and olefin metathesis reactions,10 intramolecular allylic amin-
agrochemicals, as well as their use as intermediates in the ation11 and many others have been reported.12 Despite these
synthesis of other heterocycles of biological significance.3 advances to obtain 1,2-dihydroquinolines, there still remain
For example, 1,2-dihydroquinoline moieties are potential some limitations such as low yields, expensive and toxic metal
therapeutics such as antibacterial,4a anti-inflammatory,4b anti- catalysts, poor atom economy, and harsh reaction conditions.
malarial,4c psychotropic,4d anti-allergic,4e lipid peroxidation
Similarly, nitrogen-containing medium ring heterocycles
inhibitors,4f HMG-CoA reductase,4g progesterone agonists4h such as the 1H-benzo[b]azepine ring constitute the core struc-
and antagonists.4i In addition they can be easily transformed ture of numerous pharmacologically important compounds.13
into corresponding 1,2,3,4-tetrahydroquinoline and quinoline Compounds having this skeleton have exhibited biological
derivatives.5
activity towards various targets such as enzymes, ion channels,
and G-protein-coupled receptors (GPCRs).14 Despite their
interesting biological activities, the synthesis of 1-benzazepine
derivatives has received little synthetic attention.15 Typical syn-
thetic routes are ring expansion,15c,i,k Dieckmann condensa-
tions,15j inter- and intramolecular metal-catalysed coupling15a,c,e
and metathesis reactions.15b Thus, developing general,
efficient and flexible synthetic strategies to prepare diverse
Department of Chemistry, Jadavpur University, Kolkata-700 032, West Bengal, India.
E-mail: jumasish2004@yahoo.co.in
†Electronic supplementary information (ESI) available. CCDC 961970.
For ESI and crystallographic data in CIF or other electronic format see DOI:
10.1039/c3ob42292e
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Scheme 2 Preparation of 2-(N-(prop-2-ynyl)-N-tosylamino)benzaldehydes/
acetophenone derivatives.
acetophenone derivatives by simple alkylation using aryl or
alkyl propargyl bromide in the presence of K2CO3, outlined in
Scheme 2.
Scheme 1 Strategy for the synthesis of 1,2-dihydroquinolines, quino-
lines and benzo[b]azepine derivatives.
After having synthesised a series of substrates 2a–2k, we
next investigated the alkyne–carbonyl metathesis reaction for
the synthesis of 1,2-dihydroquinolines. Our initial investi-
gation began by examining the intramolecular alkyne–carbonyl
metathesis of 2-(N-(3-phenylprop-2-ynyl)-N-tosylamino)benz-
aldehyde 2a utilizing a variety of Lewis and Brønsted acids to
develop the optimum reaction conditions.
These results are summarized in Table 1. In view of the
high catalytic activity of iron(III) chloride, we first examined the
intramolecular alkyne–carbonyl metathesis of 2a in the pres-
ence of anhydrous FeCl3 in different solvents such as toluene,
dichloromethane, 1,2-dichloroethane, acetonitrile and nitro-
methane (Table 1, entries 1 to 6). Gratifyingly, the desired
3-benzoyl-1-tosyl-1,2-dihydroquinoline 3a was furnished in 95%
yield as a sole product in the presence of anhydrous FeCl3
(10 mol%) in CH3CN at 85 °C in 4 h (Table 1, entry 4).
The other above mentioned solvents gave a lower yield of
the desired product 3a. Moreover, reduced yield of 3a to 60%
was observed when FeCl3 was reduced to 5 mol%. In contrast,
the same reaction with FeBr3 (10 mol%) was found to result
in 35% yield of the desired product 3a (Table 1, entry 7). It
also appeared that the reaction proceeded with other Lewis
and Brønsted acids such as AgOTf, InCl3, BF3·OEt2 and TfOH,
1,2-dihydroquinoline and 1H-benzo[b]azepine derivatives with
specific substitution patterns is still a highly desirable yet chal-
lenging task in organic synthesis.
In this regard, the alkyne–carbonyl metathesis reaction, i.e.
the cycloaddition of C–O double bonds to C–C triple bonds fol-
lowed by cycloreversion, has been recognized as an atom-econo-
mical alternative to the Wittig reaction for the construction of
α,β-unsaturated carbonyl compounds.16 The intramolecular
version of this reaction is very attractive as it allows the for-
mation of complex functionalized carbo- and heterocyclic com-
pounds from easily available starting materials.17 This reaction
is considered to be proceeding via a formal [2 + 2] cyclo-
addition and cycloreversion process. Generally, Lewis or strong
Brønsted acids or transition-metals such as TfOH, HBF4,
BF3·OEt2, In(OTf)3, AgSbF6, AuCl3, and the combination of
AuCl3/AgSbF6 acted as catalysts for this process.
In recent years, iron-catalyzed organic transformations have
attracted considerable attention because iron is one of the
most inexpensive, sustainable and environmentally benign
metals on earth. As part of our investigation on iron cata-
lysis,18a,b,c,19 we recently reported that FeCl3 can efficiently
perform an alkyne–carbonyl metathesis reaction.18a,b,c In con-
tinuation of our interest in this area, we thought that alkyne–
carbonyl metathesis of N-propargyl-2-aminobenzaldehyde/acet-
ophenone or N-homopropargyl-2-aminobenzaldehyde/aceto-
phenone derivatives would be a new and an efficient synthetic
route to access the libraries of 3-acyl 1,2-dihydroquinoline and
4-acyl benzo[b]azepine derivatives (Scheme 1). Herein, we wish
to report an iron(III)-chloride catalyzed intramolecular alkyne–
carbonyl metathesis strategy for the synthesis of 3-acyl 1,2-
dihydroquinoline and 4-acyl benzo[b]azepine derivatives under
mild conditions in good to excellent yields. Moreover, this
strategy also worked efficiently for the one-pot synthesis of
3-acyl quinolines in high yield.
Table 1 Optimisation of the reaction conditionsa
Catalyst
(mol%)
Time
(h)
Yield
(%)
Entry
Solvent
Temperature
1
2
3
4
5
6
7
8
FeCl3 (10)
FeCl3 (10)
FeCl3 (10)
FeCl3 (10)
FeCl3 (5)
FeCl3 (10)
FeBr3 (10)
AgOTf (10)
InCl3 (10)
BF3Et2O (10)
TfOH (10)
Toluene
DCE
DCM
85 °C
Reflux
Reflux
85 °C
85 °C
85 °C
85 °C
85 °C
85 °C
85 °C
85 °C
24
4
4
4
24
8
13
24
12
6
38
55
55
95
55
75
35
n.r.
70
80
65
CH3CN
CH3CN
CH3NO2
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
Results and discussion
First we attempted the synthesis of 3-acyl 1,2-dihydro-
quinolines from 2-(N-(prop-2-ynyl)-N-tosylamino)benzaldehyde/
acetophenone derivatives. The required substrates were
9
10
11
19
easily prepared in high yields from 2-aminobenzaldehyde or a Reaction conditions: substrates 2a (0.5 mmol) and solvent (2 mL).
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Table 2 Fe-catalyzed intramolecular alkyne–aldehyde metathesis for the synthesis of varieties of polyfunctional 1,2-dihydroquinolinea
Paper
Entry
1
Substrates
Products
Time (h)
4
Yield (%)
95
2
7
9
80
3
89
4
12
14
8
84
5
75
6
70
7
21
5
88
8
93
9
3
74b
75b
NR
10
11
3
—
12
a Reaction conditions: substrates (0.5 mmol), acetonitrile (2 mL), 85 °C. b Reaction was carried out in 1,2-dichloroethane (2 mL), at 65 °C.
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albeit in lower yield. AgOTf was totally inactive (Table 1,
entry 8), whereas InCl3, BF3·OEt2 and TfOH gave moderate
to good yields, 70%, 80% and 65%, respectively (Table 1,
entries 9–11). Thus the best reaction conditions for this coup-
ling process was found to be heating the substrate 2a in
acetonitrile at 85 °C in the presence of anhydrous FeCl3
(10 mol%).
Table 3 Fe-catalyzed intramolecular alkyne–ketone metathesis for
the synthesis of 3,4-substituted 1,2-dihydroquinolinesa
With these optimum conditions in hand, we next turned
to explore the scope of the reaction for a series of 2-(N-(prop-
2-ynyl)-N-tosylamino)benzaldehydes 2a–2k to synthesise a
variety of functionalised dihydroquinoline derivatives. The
results are summarized in Table 2. As shown in Table 2, a
series of functional groups such as –Cl, –Br and –CO2Et
groups in the alkyne terminus were well tolerated and corres-
ponding dihydroquinoline derivatives were obtained in good
to excellent yields (Table 2, entries 1–8). The presence of an
electron-donating group such as para-Me at the aryl ring of
the alkyne terminus (Table 2, entry 2) also gave a high yield
of 80%. Notably, thiophene substituted alkyne also worked
efficiently and gave the desired hybrid heterocyclic product 3f
in a good yield of 70% (Table 2, entry 6). Both tosyl and mesyl
protected 2-amino benzaldehyde survived under the reaction
conditions and gave a high yield of the desired products.
Free amine did not work as it reduced the reactivity of the
carbonyl group.
Importantly, para-bromo group on the benzene ring of the
alkyne unit and para-bromo with respect to aromatic amino
group containing substrate 2h afforded a high yield of the
desired product 3h (93%). It is noteworthy to mention that
halogen containing functional groups on the dihydroquinoline
derivatives could be utilized for further synthetic transform-
ation using transition-metal catalyzed cross-coupling reactions
to obtain a library of complex dihydroquinoline derivatives
that could be useful for their potential applications in medi-
cinal chemistry.
a Reaction conditions: substrates (0.5 mmol), nitromethane (2 mL),
heated at 85 °C.
reaction conditions and furnished a good yield of the desired
product.
Having successfully established suitable reaction con-
ditions for the synthesis of a diverse range of N-tosyldihydro-
quinoline derivatives, next we aimed to develop a one-pot
synthesis of 3-acyl substituted quinolines via alkyne–carbonyl
metathesis/detosylation and oxidation of the intermediate
products. N-Propargyl-2-aminobenzaldehyde/acetophenones
2a, 2c and 4a were first subjected to synthesis of 3-acyl di-
hydroquinoline derivatives via alkyne–carbonyl metathesis in
the presence of iron; then after completion of the reaction,
Next, we studied a few alkyl groups at the alkyne terminus
to show the versatility of this strategy (Table 2, entries 9 and
10). It appears that this strategy was also applicable to the
internal alkynes bearing an aliphatic alkyl group such as 2i
and 2j gave the desired dihydroquinoline derivatives 3i and 3j
in good yields, 74% and 75%, respectively. Unfortunately,
terminal alkyne containing the substrate did not work
(Table 3, entry 11), and only the starting material was left even
after 12 h of heating in acetonitrile.
Scheme 3 One-pot synthesis of 3-acyl quinoline via alkyne–carbonyl
metathesis/detosylation/aromatization.
In addition, we also tested 2-aminoacetophenone derivative
instead of a 2-aminobenzaldehyde derivative to show the
potentiality of this reaction for the preparation of a variety of
3,4-disubstituted dihydroquinoline derivatives such as 5a and
5b (Table 3). To our delight, the coupling of internal alkyne
with methylketones such as 4a and 4b also worked efficiently
within a short period of time in very good yields, 80% and
78%, respectively. However, in these cases the reaction in
acetonitrile medium gave slightly lower yields compared to
nitromethane. Possibly, less reactive substrate in more polar
solvent had a beneficial effect. Notably, N-acyl protected 2-amino-
acetophenone (Table 3, entry 5b) also survived under the Scheme 4 Preparation of substrates for benzo[b]azepines synthesis.
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NaOH/EtOH was added to the reaction mixture, and the
Finally, to expand the scope of this methodology we also
mixture was heated to 60 °C to obtain quinoline derivatives decided to explore the possibility of synthesising seven-mem-
(Scheme 3). To our delight, this one-pot strategy also worked bered nitrogen containing heterocycles such as benzo[b]aze-
efficiently for the synthesis of 3-acyl quinoline derivatives such pines, 8a–8d. The required substrates 7a–7d can be easily and
as 6a, 6b and 6c in high yields (85%, 70% and 65%). Therefore, efficiently prepared by a two-step transformation in good yield
this strategy of quinoline synthesis would be an important from N-tosyl-2-aminobenzaldehyde. That involves N-alkylation
alternative to recently developed strategies20 as the present with tosyl derivative of homopropargyl alcohol in the presence
route is highly efficient and environmentally friendly. Moreover, of K2CO3 in DMF followed by a palladium catalyzed Sono-
specific substituents could also be introduced into this method. gashira coupling with aryl iodide (Scheme 4).
Table 4 Fe-catalyzed alkyne–carbonyl metathesis for the synthesis of benzo[b]azepinea
Entry
1
Substrates
Products
Time (h)
8
Yield (%)
72
2
3
4
3
10
3
70
68
80b
a Reaction conditions: substrates (0.5 mmol), FeCl3 (10 mol%), and acetonitrile (2 mL), at 85 °C. b Reaction was carried out in 1,2-dichloroethane
(2 mL), at 65 °C.
Scheme 5 Possible mechanism for iron-catalyzed synthesis of 1,2-
dihydroquinolines and benzo[b]azepine derivatives.
Fig. 1 Representations of 3b showing 40% probability of thermal
ellipsoid.
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After having synthesised the substrates 7a–7c, these singlet. 13C NMR spectra were recorded in CDCl3 solution with
compounds were subjected to the alkyne–carbonyl metathesis complete proton decoupling. Chemical shifts are expressed
reaction. The desired benzo[b]azepines were successfully in parts per million (ppm, δ) and are referenced to CDCl3
synthesised using the same optimized reaction conditions in (δ = 77.0 ppm) as an internal standard. High-resolution
good yield. The electronic effects of alkyne terminus groups mass spectra (HRMS) were recorded in dichloromethane
have little influence on this reaction. Substrates with electron- solvent. The molecular fragments are quoted as the relation
rich and electron-deficient aryl rings at the alkyne terminus between mass and charge (m/z) ratio. Routine monitoring of
were reacted smoothly and gave 8a, 8b, 8c and 8d in 72%, reactions was performed with silica gel coated glass slides and
70%, 68% and 80% yields, respectively (Table 4). To our plea- pre-coated Al plates, which were analyzed with iodine, UV
sant surprise, alkynes bearing an alkyl group (Table 4, entry 4) light, and alkaline KMnO4, respectively. All reactions involving
such as substrate 7d also reacted smoothly and gave a high moisture-sensitive reactants were executed using oven-dried
yield 80% of the desired benzo[b]azepine 8d.
glassware.
A plausible mechanism for the iron(III) chloride alkyne–car-
Representative experimental procedure for the preparation
bonyl metathesis reaction is delineated in Scheme 5. This is of N-(2-formylphenyl)-4-methyl-N-(3-phenylprop-2-ynyl)benze-
very similar to our earlier study and those reported by nesulfonamide 2a.
others.17a,b,g,18b,c It is believed that the reaction may proceed
through a formal [2 + 2] cycloaddition via initial activation of
the carbonyl group by the iron(III) which lowers the LUMO
energy of the carbonyl group and hence accelerates the cyclo-
addition process producing an oxetene intermediate B′ which
upon ring opening leads to the desired cyclic α,β-carbonyl
derivative C′ and regenerates the catalyst for the next catalytic
cycle. All structures of 1,2-dihydroquinolines, quinolines and Aldehyde 1a (500 mg, 1.81 mmol) was dissolved in dry aceto-
benzo[b]azepine derivatives were confirmed by 1H NMR, 13C nitrile (10 mL) in a 50 mL round-bottom flask. To this solution
NMR and HRMS. The product 3b (CCDC no. 961970) was were added anhydrous K2CO3 (751.5 mg, 5.34 mmol) and
further proved using X-ray structure (Fig. 1).
phenyl propargyl bromide (276 mg, 2.34 mmol). The reaction
mixture was refluxed under an argon atmosphere for 4 h. Then
the mixture was cooled to room temperature and filtered
through the sintered glass crucible. The filtrate was concen-
trated under reduced pressure, and the residue was purified by
Conclusion
In summary, we have developed a general and flexible approach silica gel (mesh 60–120) column chromatography to obtain the
for the synthesis of six- and seven-membered nitrogen contain- product 2a21 (605 mg, 3.71 mmol, 86%) as an orange semi-
ing heterocycles such as 1,2-dihydroquinolines, quinolines and solid. 1H NMR (CDCl3, 300 MHz) δ 2.4 (s, 3H), 4.71 (s, 2H), 7.06
benzo[b]azepine derivatives. The strategy involved iron(III)-cata- (d, J = 7.41 Hz, 1H), 7.15 (d, J = 7.32 Hz, 2H), 7.22–7.27 (m,
lyzed alkyne–carbonyl metathesis reactions of alkyne tethered 5H), 7.50–7.52 (m, 2H), 7.58 (d, J = 8.0 Hz, 2H), 8.03 (q, J = 2.2 Hz,
2-aminobenzaldehyde/acetophenone derivatives. The reactions 2H), 10.44 (s, 1H) ppm. 13C NMR (CDCl3, 75 MHz) δ 21.6, 42.7,
are highly regioselective and worked under mild conditions 82.3, 86.5, 121.8, 128.1, 128.3, 128.5, 128.7, 129.2, 129.7, 131.4,
in good to excellent yield. Among various Lewis and Brønsted 134.3, 135.0, 136.0, 141.4, 144.4, 190.2 ppm. HRMS calcd for
acid catalysts, iron was found to be the most efficient. The C23H20NO3S [M + H] 390.1164, found 390.1160.
advantages of this new method are the ease of substrate prepa-
Compounds 2b, 2c, 2d, 2e, 2g, 2h, 2i, 2j, 2k and 4a were
ration, operational simplicity, high atom-economy, and use of also synthesized by a similar procedure.
inexpensive and environmentally friendly FeCl3 (10 mol%) as
N-(2-Formylphenyl)-4-methyl-N-(3-p-tolylprop-2-ynyl)benzene-
the catalyst. Thus this method may find application in the syn- sulfonamide 2b. Light yellow solid, m.p. 84 °C. 1H NMR
thesis of libraries of nitrogen containing biologically active (CDCl3, 300 MHz) δ 2.3 (s, 3H), 2.4 (s, 3H), 4.7 (s, 2H), 7.05 (s,
molecules to identify potential drug candidates.
5H), 7.26 (d, J = 8 Hz, 2H), 7.48–7.51 (m, 2H), 7.58 (d, J = 8.8
Hz, 2H), 8.0–8.03 (m, 1H), 10.46 (s, 1H) ppm. 13C NMR (CDCl3,
75 MHz) δ 21.4, 21.5, 42.8, 81.6, 86.7, 118.7, 128.1, 128.4,
128.7, 128.9, 129.1, 129.6, 131.3, 134.2, 135.9, 138.8, 141.4,
144.3, 190.1 ppm. HRMS calcd for C23H18ClNNaO3S [M + Na]
446.0594, found 446.0594.
Experimental section
General methods
1H NMR spectra were recorded in CDCl3 solvents. Chemical
N-(3-(4-Chlorophenyl)prop-2-ynyl)-N-(2-formylphenyl)-4-
shifts are expressed in parts per million (ppm, δ) and are refer- methylbenzenesulfonamide 2c. Light yellow solid, m.p. 94 °C,
enced to CHCl3 (δ = 7.26 ppm) as an internal standard. All 1H NMR (CDCl3, 300 MHz) δ 2.4 (s, 3H), 4.69 (s, 2H), 7.02 (d,
coupling constants are absolute values and are expressed in J = 7.6 Hz, 1H), 7.08 (d, J = 8.4 Hz, 2H), 7.20–7.32 (m, 4H),
hertz. Signal description: s = singlet, d = doublet, t = triplet, 7.46–7.53 (m, 2H), 7.57 (d, J = 8.1 Hz, 2H), 8.0–8.03 (m, 1H),
q = quartet, m = multiplet, dd = doublet of doublets, brs = broad 10.43 (s, 1H) ppm. 13C NMR (CDCl3, 75 MHz) δ 21.6, 42.8,
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83.4, 85.4, 120.3, 127.7, 128.0, 128.1, 128.4, 128.6, 128.7, 128.8, ppm. 13C NMR (CDCl3, 75 MHz) δ 13.2, 20.4, 21.5, 42.3, 73.1,
129.2, 129.3, 129.7, 129.8, 132.7, 134.3, 134.8, 136.0, 141.3, 87.3, 128.0, 128.1, 128.4, 129.0, 129.5, 134.1, 134.8, 136.0,
144.4, 190.1 ppm. HRMS calcd for C23H18ClNNaO3S [M + Na] 141.4, 144.2, 190.3 ppm. HRMS calcd for C20H21NNaO3S
446.0594, found 446.0594.
[M + Na] 378.1140, found 378.1145.
N-(3-(3-Bromophenyl)prop-2-ynyl)-N-(2-formylphenyl)-4-methyl-
N-(But-2-ynyl)-N-(2-formylphenyl)methanesulfonamide 2j.
benzenesulfonamide 2d. Yellow solid, m.p. 101 °C. 1H NMR Colorless semisolid. H NMR (CDCl3, 300 MHz) δ 1.82 (s, 3H),
(CDCl3, 300 MHz) δ 2.4 (s, 3H), 4.7 (s, 2H), 7.06–7.14 (m, 3H), 4.43 (brs, 2H), 7.52–7.57 (m, 1H), 7.67–7.70 (m, 2H), 8.0 (t, J =
7.26–7.28 (m, 3H), 7.43 (d, J = 4.5 Hz, 1H), 7.5–7.6 (m, 4H), 1.2 Hz, 1H), 10.34 (s, 1H) ppm. 13C NMR (CDCl3, 75 MHz)
8.03 (d, J = 0.6 Hz, 1H), 10.4 (s, 1H) ppm. 13C NMR (CDCl3, δ 28.7, 39.0, 42.3, 73.2, 83.2, 128.3, 129.1, 129.3, 134.8, 135.4,
75 MHz) δ 21.6, 24.6, 83.8, 84.9, 122.1, 123.8, 128.2, 128.7, 141.6, 190.1 ppm. HRMS calcd for C12H13NNaO3S [M + Na]
129.3, 129.7, 129.8, 130.1, 131.9, 134.2, 134.3, 135.1, 135.9, 274.0514, found 274.0517.
1
141.4, 144.5, 190.0 ppm. HRMS calcd for C23H18BrNNaO3S
[M + Na] 490.0088, found 490.0086.
N-(2-Acetylphenyl)-4-methyl-N-(3-phenylprop-2-ynyl)benzene-
sulfonamide 4a. Yellow solid, m.p. 132 °C. 1H NMR (CDCl3,
Ethyl [4-(3-(N-(2-formylphenyl)methylsulfonamido)prop-1- 300 MHz) δ 2.34 (s, 3H), 2.68 (s, 3H), 4.77 (brs, 2H), 7.03 (d, J =
yn-1-yl)]benzoate 2e. Orange solid, m.p. 100 °C. 1H NMR 7.8 Hz, 1H), 7.16–7.45 (m, 9H), 7.58 (d, J = 8.2 Hz, 2H), 7.62 (d,
(CDCl3, 300 MHz) δ 1.33 (t, J = 7.14 Hz, 3H), 3.1 (s, 3H), 4.32 J = 16.3 Hz, 1H) ppm. 13C NMR (CDCl3, 75 MHz) δ 21.5, 30.1,
(q, J = 7.8, Hz, 2H), 4.7 (brs, 2H), 7.37 (d, J = 7.9 Hz, 2H), 42.4, 83.4, 86.0, 122.3, 128.2, 128.3, 128.8, 128.9, 129.4, 129.5,
7.49–7.54 (m, 1H), 7.92 (s, 1H), 7.95–8.0 (m, 2H), 10.40 (s, 1H) 131.2, 131.5, 135.8, 136.6, 141.9, 143.9, 200.1 ppm. HRMS
ppm. 13C NMR (CDCl3, 75 MHz) δ 14.2, 39.1, 42.4, 61.2, 85.7, calcd for C24H21NNaO3S [M + Na] 426.1140, found 426.1138.
85.9, 126.1, 128.8, 129.5, 129.5, 130.6, 131.4, 134.9, 135.4,
141.0, 165.7, 190.0 ppm. HRMS calcd for C20H19NNaO5S brown semisolid, 1H NMR (CDCl3, 500 MHz) δ 1.85 (s, 3H),
[M + Na] 408.0882, found 408.0882. 2.32 (s, 3H), 2.6 (s, 1H), 4.42 (d, J = 10.5 Hz, 1H), 4.97 (d, J =
N-(2-Acetylphenyl)-N-(3-p-tolylprop-2-ynyl)acetamide 4b. Dark
N-(2-Formylphenyl)-N-(3-(thiophen-3-yl)prop-2-ynyl)methane- 10.5 Hz, 1H), 7.07 (d, J = 4.5 Hz, 2H), 7.17 (d, J = 4.5 Hz, 2H),
sulfonamide 2f. Black sticky solid. 1H NMR (CDCl3, 7.42 (d, J = 4.5 Hz, 1H), 7.52 (t, J = 4.5 Hz, 1H), 7.61 (t, J =
300 MHz) δ 3.1 (s, 3H), 4.70 (brs, 2H), 7.04 (d, J = 3.8 Hz, 1H), 4.5 Hz, 1H), 7.80–7.82 (m, 1H) ppm. 13C NMR (CDCl3,
7.27 (q, J = 2.9 Hz, 4.9 Hz, 1H), 7.43 (d, J = 1.8 Hz, 1H), 7.54 (t, 125 MHz) δ 21.5, 22.7, 29.9, 38.8, 85.2, 119.7, 129.0, 129.1,
J = 7.0 Hz, 1H), 7.66–7.75 (m, 2H), 8.01 (d, J = 6 Hz, 1H), 10.42 129.2, 130.0, 131.3, 131.5, 131.6, 132.9, 137.2, 139.5, 139.8,
(s, 1H) ppm. 13C NMR (CDCl3, 75 MHz) δ 39.1, 42.7, 82.1, 82.7, 170.1, 199.0 ppm. HRMS calcd for C20H19NNaO2 [M + Na]
120.7, 125.9, 128.6, 129.4, 129.6, 129.8, 134.9, 135.4, 141.4, 328.1313, found 328.1313.
190.1 ppm. HRMS calcd for C15H13NNaO3S2 [M
342.0235, found 342.0236.
+ Na]
General procedure for FeCl3-catalyzed synthesis of 1,2-
dihydroquinoline
N-(4-Chloro-2-formylphenyl)-4-methyl-N-(3-phenylprop-2-ynyl)-
benzenesulfonamide 2g. Brown semisolid, 1H NMR (CDCl3,
500 MHz) δ 2.42 (s, 3H), 4.69 (brs, 2H), 6.99 (d, J = 8.5 Hz, 1H),
7.14–7.17 (m, 2H), 7.19–7.37 (m, 5H), 7.47 (dd, J = 2.7, 8.6 Hz,
1H), 7.57 (d, J = 8.3 Hz, 2H), 7.98 (d, J = 2.6 Hz, 1H) ppm.
13C NMR (CDCl3, 125 MHz) δ 21.7, 42.8, 82.1, 87.0, 121.8,
127.9, 128.3, 128.4, 128.7, 128.8, 129.0, 129.9, 130.1, 130.4,
131.6, 134.2, 135.0, 135.9, 137.4, 139.8, 144.8, 188.9 ppm.
HRMS calcd for C23H18ClNNaO3S [M + Na] 446.0594, found
446.0594.
Representative experimental procedure for the synthesis of
phenyl(N-tosyl-1,2-dihydroquinolin-3-yl)methanone 3a.
Compound 2a (195 mg, 0.5 mmol) was taken in a dry 5 mL
N-(4-Bromo-2-formylphenyl)-N-(3-(2-bromophenyl)prop-2-ynyl)- round-bottom flask containing 2 mL of dry acetonitrile
4-methylbenzenesulfonamide 2h. Yellow solid, m.p. 134 °C. solvent. Anhydrous FeCl3 (8.11 mg, 0.05 mmol) was added,
1H NMR (CDCl3, 300 MHz) δ 2.39 (s, 3H), 4.72 (s, 2H), 7.01 and the reaction mixture was heated to reflux for 4 h under an
(d, J = 8.5 Hz, 1H), 7.12–7.16 (m, 1H), 7.19–7.26 (m, 4H), 7.5 (d, argon atmosphere. After complete conversion of the starting
J = 7.7 Hz, 1H), 7.55 (d, J = 8.3 Hz, 2H), 7.61 (q, J = 2.4, 8.5 Hz, material (monitoring by TLC), acetonitrile was removed under
1H), 8.13 (d, J = 2.4 Hz, 1H), 10.37 (s, 1H) ppm. 13C NMR reduced pressure and the residue was purified by silica gel
(CDCl3, 75 MHz) δ 21.5, 42.4, 85.1, 86.3, 123.5, 123.9, 125.2, (mesh 60–120) column chromatography to afford 3a (179 mg,
127.0, 128.1, 129.7, 129.9, 130.3, 131.6, 132.4, 133.4, 134.3, 0.46 mmol, 95%) as a white solid, m.p. 131 °C. 1H NMR
136.9, 137.3, 140.1, 144.7, 188.6 ppm. HRMS calcd for (CDCl3, 300 MHz) δ 2.34 (s, 3H), 4.82 (s, 2H), 6.65 (s, 1H), 7.08
C23H17Br2NNaO3S [M + Na] 567.9194, found 567.9198.
(d, J = 8.2 Hz, 3H), 7.22 (d, J = 7.2 Hz, 2H), 7.27–7.48 (m, 6H),
N-(2-Formylphenyl)-N-(hex-2-ynyl)-4-methylbenzenesulfon- 7.53 (t, J = 7.4 Hz, 1H), 7.81 (d, J = 8 Hz, 1H) ppm. 13C NMR
1
amide 2i. White solid, m.p. 48 °C. H NMR (CDCl3, 300 MHz) (CDCl3, 75 MHz) δ 21.5, 44.7, 127.0, 127.1, 127.5, 127.9, 128.0,
δ 0.75 (t, J = 7.3 Hz, 3H), 1.28 (q, J = 7.3, Hz, 2H), 1.91–1.96 (m, 128.4, 128.9, 129.0, 129.4, 129.8, 131.1, 132.0, 132.3, 136.5,
2H), 2.4 (s, 3H), 4.43 (brs, 2H), 6.90–6.93 (m, 1H), 7.26 (d, J = 137.0, 143.7, 193.4 ppm. HRMS calcd for C23H19NNaO3S [M +
8.4 Hz, 2H), 7.43–7.53 (m, 4H), 7.97–8.0 (m, 1H), 10.3 (s, 1H) Na] 412.0983, found 412.0980.
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1
p-Tolyl(1-tosyl-1,2-dihydroquinolin-3-yl)methanone 3b. The 70%). H NMR (CDCl3, 300 MHz) δ 2.75 (s, 1H), 4.79 (s, 2H),
general procedure was followed using 2b (202 mg, 0.5 mmol), 7.28–7.34 (m, 2H), 7.36 (s, 1H), 7.40–7.43 (m, 2H), 7.53 (d, J =
heating at reflux for 7 h. The product was purified by silica gel 3 Hz, 1H), 7.69 (d, J = 4.8 Hz, 1H), 7.97 (s, 1H) ppm. 13C NMR
(mesh 60–120) column chromatography to afford 3b as a (CDCl3, 75 MHz) δ 38.0, 44.6, 126.3, 126.8, 126.9, 127.3, 128.0,
1
yellow solid (161 mg, 0.4 mmol, 80%), m.p. 116 °C. H NMR 129.2, 129.7, 131.1, 132.5, 134.4, 134.8, 136.4, 140.2,
(CDCl3, 300 MHz) δ 2.34 (s, 3H), 2.40 (s, 1H), 4.80 (s, 2H), 6.63 187.1 ppm. HRMS calcd for C15H13NNaO3S2 [M
(s, 1H), 7.07 (d, J = 7.7 Hz, 3H), 7.12–7.16 (m, 4H), 7.19–7.28 342.0235, found 342.0235.
+ Na]
(m, 1H), 7.31 (d, J = 8.1 Hz, 2H), 7.44 (t, J = 7.6 Hz, 1H), 7.81
(6-Chloro-1-tosyl-1,2-dihydroquinolin-3-yl)(phenyl)methanone
(d, J = 8.1 Hz, 1H) ppm. 13C NMR (CDCl3, 75 MHz) δ 21.4, 44.8, 3g. The general procedure was followed using 2g (211 mg,
126.9, 127.0, 127.4, 127.9, 128.8, 129.0, 129.4, 130.8, 132.4, 0.5 mmol), heating at reflux for 21 h. The product was purified
134.2, 136.3, 136.4, 142.7, 143.6, 193.1 ppm. HRMS calcd for by silica gel (mesh 60–120) column chromatography to afford
C24H21NNaO3S [M + Na] 426.1141, found 426.1141.
3g as a yellow semi-solid (186.66 mg, 0.44 mmol, 88%).
(4-Chlorophenyl)(1-tosyl-1,2-dihydroquinolin-3-yl)methanone 1H NMR (CDCl3, 300 MHz) δ 2.4 (s, 3H), 4.81 (s, 2H), 6.21
3c. The general procedure was followed using 2c (s, 1H), 7.07–7.12 (m, 3H), 7.19–7.23 (m, 2H), 7.33–7.42
(212 mg, 0.5 mmol), heating at reflux for 9 h. The product was (m, 5H), 7.54 (t, J = 7.4 Hz, 1H), 7.76 (d, J = 8.61 Hz, 1H) ppm.
purified by silica gel (mesh 60–120) column chromatography 13C NMR (CDCl3, 75 MHz) δ 21.6, 44.6, 127.0, 127.7, 128.2,
to afford 3c as a light yellow solid (188 mg, 0.45 mmol, 89%), 128.3, 128.7, 128.8, 129.2, 129.6, 129.8, 130.1, 132.2, 132.5,
1
m.p. 170 °C. H NMR (CDCl3, 300 MHz) δ 2.35 (s, 3H), 4.80 (s, 133.3, 134.8, 135.4, 136.0, 136.6, 143.9, 193.1 ppm. HRMS
2H), 6.61 (s, 1H), 7.06–7.09 (m, 3H), 7.17 (dd, J = 1.8, 6.6 Hz, calcd for C23H18ClNNaO3S [M + Na] 446.0594, found 446.0593.
2H), 7.25–7.27 (m, 1H), 7.30–7.37 (m, 4H), 7.44–7.5 (m, 1H),
(6-Bromo-1-(p-tolyl)-1,2-dihydroquinolin-3-yl)(2-bromophenyl)-
7.81 (d, J = 8.0 Hz, 1H) ppm. 13C NMR (CDCl3, 75 MHz) δ 21.4, methanone 3h. The general procedure was followed using
44.5, 127.0, 127.4, 127.7, 128.5, 129.0, 129.3, 130.2, 131.2, 2h (272 mg, 0.5 mmol), heating at reflux for 5 h. The product
132.0, 135.2, 136.3, 136.5, 136.9, 138.4, 143.7, 192.1 ppm. was purified by silica gel (mesh 60–120) column chromato-
HRMS calcd for C23H18ClNNaO3S [M + Na] 446.0594, found graphy to afford 3h as a yellow solid (253 mg, 0.35 mmol,
1
446.0594.
93%), m.p. 120 °C. H NMR (CDCl3, 300 MHz) δ 2.37 (s, 3H),
(3-Bromophenyl)(1-tosyl-1,2-dihydroquinolin-3-yl)methanone 4.84 (s, 2H), 6.37 (s, 1H), 6.75–6.77 (m, 1H), 7.14 (d, J = 7.9 Hz,
3d. The general procedure was followed using 2d 1H), 7.21 (d, J = 1.9 Hz, 2H), 7.28–7.31 (m, 2H), 7.36 (d, J = 8.12
(233 mg, 0.5 mmol), heating at reflux for 12 h. The product Hz, 1H), 7.54–7.59 (m, 3H), 7.72 (d, J = 8.6 Hz, 1H) ppm.
was purified by silica gel (mesh 60–120) column chromato- 13C NMR (CDCl3, 75 MHz) δ 21.6, 43.3, 119.6, 120.2, 127.0,
graphy to afford 3d as a yellow solid (196 mg, 0.42 mmol, yield 127.1, 128.1, 128.6, 128.8, 129.4, 129.7, 131.6, 133.4, 133.8,
1
84%), m.p. 152 °C. H NMR (CDCl3, 300 MHz) δ 2.37 (s, 3H), 134.1, 135.7, 136.0, 136.9, 139.1, 144.1, 139.1 ppm. HRMS
4.7 (s, 2H), 6.64 (s, 1H), 7.01 (d, J = 4.8 Hz, 3H), 7.19 (d, J = 4.8 calcd for C23H17Br2NNaO3S [M
Hz, 2H), 7.25–7.29 (m, 3H), 7.32 (d, J = 4.8 Hz, 1H), 7.46–7.49 567.9191.
+ Na] 567.9194, found
(m, 1H), 7.65 (d, J = 4.5 Hz, 1H), 7.82 (d, J = 4.8 Hz, 1H) ppm.
1-(1-Tosyl-1,2-dihydroquinolin-3-yl)butan-1-one 3i. The
13C NMR (CDCl3, 75 MHz) δ 21.4, 44.8, 126.9, 127.0, 127.4, general procedure was followed using 2d (233 mg, 0.5 mmol),
127.9, 128.8, 129.0, 129.4, 130.9, 132.4, 134.2, 136.3, 136.4, heated to 65 °C for 3 h. The product was purified by silica gel
142.8, 143.6, 193.1 ppm. HRMS calcd for C23H18BrNNaO3S (mesh 60–120) column chromatography to afford 3i as a col-
[M + Na] 490.0088, found 490.0074.
ourless oil (132 mg, 0.37 mmol, 74%). 1H NMR (CDCl3,
Ethyl-4-(1-(methylsulfonyl)-1,2-dihydroquinoline-3-carbonyl)- 300 MHz) δ 0.87 (t, J = 7.2 Hz, 3H), 1.55 (q, J = 7.3 Hz, 2H),
benzoate 3e. The general procedure was followed using 2e 2.31–2.36 (m, 5H), 6.82 (s, 1H), 7.03 (d, J = 8 Hz, 2H), 7.15 (d,
(193 mg, 0.5 mmol), heating at reflux for 14 h. The product J = 7.5 Hz, 1H), 7.21 (s, 1H), 7.24–7.29 (m, 2H), 7.40–7.45 (m,
was purified by silica gel (mesh 60–120) column chromato- 1H), 7.76 (d, J = 8.1 Hz, 1H) ppm. 13C NMR (CDCl3, 75 MHz)
graphy to afford 3e as an orange semi-solid (144 mg, δ 14.0, 18.0, 21.6, 39.0, 43.6, 127.1, 127.2, 127.6, 128.8, 129.3,
0.375 mmol, 75%). 1H NMR (CDCl3, 300 MHz) δ 1.42 (t, J = 130.9, 132.8, 133.2, 136.2, 136.8, 134.7, 197.9 ppm. HRMS
7.11 Hz, 3H), 2.76 (s, 3H), 4.42 (q, J = 7.11 Hz, 2H), 4.82 (s, calcd for C20H21NNaO3S [M + Na] 378.1140, found 378.1142.
2H), 7.18 (s, 1H), 7.27 (d, J = 4.5 Hz, 2H), 7.40–7.45 (m, 1H),
1-(1-(Methylsulfonyl)-1,2-dihydroquinolin-3-yl)ethanone 3j.
7.69 (d, J = 8.1 Hz, 1H), 7.78 (d, J = 8.3 Hz, 2H), 8.16 (d, J = 8.3 The general procedure was followed using 2j (126 mg,
Hz, 2H) ppm. 13C NMR (CDCl3, 75 MHz) δ 14.3, 29.7, 38.2, 0.5 mmol), heated at 65 °C for 3 h. The product was purified
44.4, 61.5, 126.1, 126.8, 127.0, 129.0, 129.6, 129.7, 131.6, 133.2, by silica gel (mesh 60–120) column chromatography to afford
133.8, 136.6, 137.3, 140.5, 165.7, 193.2 ppm. HRMS calcd for 3j as a colorless solid (94 mg, 0.37 mmol, 75%), m.p. 145 °C.
C20H19NNaO5S [M + Na] 408.0882, found 408.0882.
1H NMR (CDCl3, 300 MHz) δ 2.46 (s, 3H), 2.67 (s, 3H), 4.67 (s,
(1-(Methylsulfonyl)-1,2-dihydroquinolin-3-yl)(thiophen-3-yl)- 2H), 7.3 (d, J = 7.28 Hz, 1H), 7.3–7.45 (m, 3H), 7.67 (d, J = 8.1
methanone 3f. The general procedure was followed using 2f Hz, 1H) ppm. 13C NMR (CDCl3, 75 MHz) δ 25.3, 38.1, 43.5,
(159 mg, 0.5 mmol), heating at reflux for 8 h. The product was 125.9, 126.8, 127.3, 129.4, 131.3, 134.4, 134.5, 136.6,
purified by silica gel (mesh 60–120) column chromatography 195.6 ppm. HRMS calcd for C12H13NNaO3S [M + Na] 274.0514,
to afford 3f as a dark brown semi-solid (112 mg, 0.35 mmol, found 274.0514.
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(4-Methyl-1-tosyl-1,2-dihydroquinolin-3-yl)(phenyl)metha- a similar method to that described for 6a. The residue was
none 5a. Compound 4a (202 mg, 0.5 mmol) was taken in an purified by silica gel (mesh 60–120) column chromatography
oven dried 5 mL round-bottom flask containing 2 mL of dry to afford 6c as a brown semi-solid (89 mg, 0.32 mmol, 65%).
nitromethane solvent. Anhydrous FeCl3 (8.11 mg, 0.05 mmol) 1H NMR (CDCl3, 300 MHz) δ 2.67 (s, 1H), 7.44–7.52 (m, 2H),
was added, and the reaction mixture was heated to 85 °C for 7.61–7.70 (m, 2H), 7.75–7.86 (m, 3H), 8.12–8.19 (m, 2H), 8.81
6 h under an inert atmosphere. After complete conversion of (s, 1H) ppm. HRMS calcd for C17H13NNaO [M + Na] 270.0895,
the starting material (monitoring by TLC), acetonitrile was found 270.0895.
removed under reduced pressure and the residue was purified
Preparation of N-(2-formylphenyl)-4-methyl-N-(4-phenylbut-
by silica gel (mesh 60–120) column chromatography to afford 3-ynyl)benzenesulfonamide 7a.
5a as a light yellow solid (161 mg, 0.40 mmol, 80%),
1
m.p. 144 °C. H NMR (CDCl3, 300 MHz) δ 1.47 (s, 3H), 2.32 (s,
3H), 4.61 (s, 2H), 7.07 (d, J = 8.1 Hz, 2H), 7.28–7.44 (m, 6H),
7.55 (d, J = 7.31 Hz, 2H), 7.62–7.65 (m, 2H), 7.8 (d, J = 7.78 Hz,
1H) ppm. 13C NMR (CDCl3, 75 MHz) δ 16.0, 21.5, 47.0, 124.5,
126.9, 127.2, 127.6, 128.8, 128.9, 129.0, 129.3, 130.1, 131.5,
133.3, 133.8, 135.4, 135.8, 137.7, 143.4, 196.1 ppm. HRMS
calcd for C24H21NNaO3S [M + Na] 426.1140, found 426.1144.
1-(4-Methyl-3-(4-methylbenzoyl)quinolin-1(2H)-yl)ethanone
Aldehyde 1a (500 mg, 1.81 mmol) was dissolved in dry DMF
(10 mL) in a 50 mL round-bottom flask. 5 mg KI was added; to
5b. The procedure of 4a was followed using 4b (153 mg, this solution were added anhydrous K2CO3 (1.25 g, 9 mmol)
0.5 mmol), heated at 85 °C for 4 h. The product was purified followed by but-3-ynyl 4-methylbenzenesulfonate (812 mg,
by silica gel (mesh 60–120) column chromatography to afford 3.62 mmol) and the reaction mixture was heated at 90 °C
1
5b a as yellow semi-solid (119 mg, 0.39 mmol, 78%). H NMR under an inert atmosphere for 18 h. The mixture was cooled to
(CDCl3, 400 MHz) δ 2.03 (s, 3H), 2.30 (s, 3H), 2.43 (s, 3H), 4.60 room temperature and filtered through the sintered glass cru-
(s, 2H), 7.26–7.35 (m, 5H), 7.46 (d, J = 6 Hz, 1H), 7.77 (d, J = 6.3 cible. After that, the solvent DMF was removed under reduced
Hz, 2H) ppm. 13C NMR (CDCl3, 100 MHz) δ 21.8, 22.5, 29.8, pressure, and the residue was purified by column chromato-
124.7, 124.9, 125.7, 128.5, 129.6, 129.7, 129.9, 130.5, 136.5, graphy using silica gel (mesh 60–120) to obtain the product D
144.7, 169.4, 196.6 ppm. HRMS calcd for C20H19NNaO2 (325 mg, 0.99 mmol, 55%) as a white solid.
[M + Na] 328.1313, found 328.1313.
To a mixture of compound D (327 mg, 1.0 mmol), 4-iodo-
Experimental procedure for the synthesis of phenyl(quino- anisole (281 mg, 1.2 mmol), and triethylamine (303 mg,
lin-3-yl)methanone 6a.22 Compound 2a (195 mg, 0.5 mmol) 3.0 mmol) in dry DMSO (5 mL) under an inert atmosphere at
was taken in an oven dried 5 mL round-bottom flask contain- room temperature were added Pd(PPh3)4 (11.55 mg,
ing 2 mL of dry acetonitrile solvent. Anhydrous FeCl3 (8.11 mg, 0.01 mmol) and CuI (5.75 mg, 0.03 mmol) successively. The
0.05 mmol) was added, and the reaction mixture was heated to reaction mixture was stirred at room temperature for 8 h. Then
reflux for 4 h under an argon atmosphere. After complete con- the mixture was diluted with saturated brine solution and
version of the starting material (monitoring by TLC), aceto- extracted with EtOAc. The compound was purified using silica
nitrile was removed under reduced pressure. Then 1 mL EtOH gel (mesh 60–120) column chromatography to afford com-
and NaOH (2.5 mmol, 100 mg) were added to the reaction pound 7a as a brown semisolid (320 mg, 74%). 1H NMR
mixture and heated to 60 °C for 2 h. The residue was purified (CDCl3, 300 MHz) δ 2.42 (s, 3H), 2.62–2.68 (m, 2H), 3.53 (brs,
by silica gel (mesh 60–120) column chromatography to afford 1H), 4.16 (brs, 1H), 6.77 (d, J = 7.2 Hz, 1H), 7.27 (brs, 7H),
1
6a as a yellow semi-solid (99.1 mg, 0.43 mmol, 85%). H NMR 7.42–7.51 (m, 4H), 8.0–8.03 (m, 1H), 10.5 (s, 1H) ppm. 13C
(CDCl3, 300 MHz) δ 7.54 (t, J = 8.03 Hz, 2H), 7.64–7.69 (m, 2H), NMR (CDCl3, 75 MHz) δ 20.3, 21.7, 42.0, 50.7, 83.1, 85.8, 123.1,
7.83–7.89 (m, 3H), 7.93 (d, J = 8.2 Hz, 1H), 8.19 (d, J = 8.5 Hz, 127.9, 128.0, 121.3, 128.7, 128.9, 129.8, 131.6, 132.1, 134.2,
1H), 8.56 (s, 1H), 9.3 (s, 1H) ppm. HRMS calcd for 134.4, 136.4, 141.6, 144.4, 190.1 ppm. HRMS calcd for
C16H11NNaO [M + Na] 256.0738, found 256.0738.
C25H23NNaO4S [M + Na] 426.1140, found 426.1143. Com-
(4-Chlorophenyl)(quinolin-3-yl)methanone 6b.22 Compound pounds 7b, 7c and 7d were also synthesized by a similar
6b was prepared using 2c (212 mg, 0.5 mmol) following a procedure.
similar method to that described for 6a. The product was puri-
N-(2-Formylphenyl)-N-(4-(4-methoxyphenyl)but-3-ynyl)-4-
fied by silica gel (mesh 60–120) column chromatography to methylbenzenesulfonamide 7b. Brown semi-solid, 1H NMR
1
afford 6b as a yellow semisolid (93 mg, 0.35 mmol, 70%). H (CDCl3, 300 MHz) δ 2.43 (s, 3H), 2.63 (d, J = 5.8 Hz, 2H), 3.5 (s,
NMR (CDCl3, 300 MHz) δ 7.53 (d, J = 8.4 Hz, 2H), 7.66 (d, J = 1H), 3.78 (s, 3H), 4.12 (s, 1H), 6.77–6.80 (m, 3H), 7.21 (d, J =
7.5 Hz, 1H), 7.81 (s, 1H), 7.85 (d, J = 2.6 Hz, 1H), 7.88–7.95 (m, 8.8 Hz, 2H), 7.27 (d, J = 6.32 Hz, 3H), 7.42–7.50 (m, 4H),
2H), 8.2 (d, J = 8.6 Hz, 1H), 8.55 (s, 1H), 9.3 (s, 1H) ppm. 8.0–8.03 (m, 1H), 10.53 (s, 1H) ppm. 13C NMR (CDCl3,
HRMS calcd for C16H10ClNNaO [M + Na] 290.0349, found 75 MHz) δ 20.4, 21.7, 50.8, 55.4, 83.0, 84.3, 114.0, 115.2, 127.9,
290.0344.
128.1, 128.8, 128.9, 129.9, 133.1, 134.3, 134.4, 136.4, 141.7,
(4-Methylquinolin-3-yl)(phenyl)methanone
6c.22 Com- 144.4, 159.6, 190.2 ppm. HRMS calcd for C25H23NNaO4S [M +
pound 6c was prepared using 4a (202 mg, 0.5 mmol) following Na] 456.1245, found 456.1245.
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Methyl[4-(4-(N-(2-formylphenyl)-4-methylphenylsulfonamido)- 60–120) column chromatography to afford 8c as a white solid
1
but-1-ynyl)]benzoate 7c. Brown solid, m.p. 156 °C. 1H (157 mg, 0.34 mmol, 68%). H NMR (CDCl3, 300 MHz) δ 2.38
NMR (CDCl3, 300 MHz) δ 2.43 (s, 3H), 2.64–2.72 (m, 2H), 3.55 (s, 1H), 3.04 (t, J = 5.8 Hz, 2H), 3.39 (s, 3H), 3.96–4.01 (m, 2H),
(d, J = 6.1 Hz, 1H), 3.9 (s, 3H), 4.16 (d, J = 6.6 Hz, 1H), 6.77 (d, 6.72 (s, 1H), 7.09 (d, J = 7.6 Hz, 1H), 7.17 (d, J = 8 Hz, 2H), 7.25
J = 7.6 Hz, 1H), 7.28–7.34 (m, 3H), 7.43–7.51 (m, 4H), 7.93 (d, J = (d, J = 5.9 Hz, 1H), 7.33 (q, J = 8.3 Hz, 2H), 7.42 (d, J = 8.1 Hz,
8.3 Hz, 2H), 8.01 (dd, J = 1.9, 7 Hz, 1H) ppm. 13C NMR (CDCl3, 3H), 7.73 (d, J = 8.1 Hz, 1H), 8.03 (d, J = 8 Hz, 2H) ppm. 13C
75 MHz) δ 20.4, 21.6, 50.4, 52.2, 82.4, 89.1, 127.7, 127.9, 128.6, NMR (CDCl3, 75 MHz) δ 21.5, 30.2, 48.7, 52.5, 127.0, 127.5,
128.8, 129.4, 129.7, 131.5, 134.1, 134.2, 136.2, 141.5, 144.4, 129.0, 129.3, 129.5, 129.6, 130.3, 130.9, 132.8, 134.0, 138.1,
166.5, 189.9 ppm. HRMS calcd for C26H23NNaO5S [M + Na] 139.5, 140.0, 141.1, 141.8, 143.4, 166.2, 197.3 ppm. HRMS
484.1195, found 484.1190.
calcd for C26H23NNaO5S [M + Na] 484.1195, found 484.1194.
N-(2-Formylphenyl)-4-methyl-N-(pent-3-yn-1-yl)benzenesul-
1-(1-Tosyl-2,3-dihydro-1H-benzo[b]azepin-4-yl)ethanone 8d.
fonamide 7d. Light yellow semi-solid. 1H NMR (CDCl3, Compound 8d was prepared using 7d (170.5 mg, 0.5 mmol)
400 MHz) δ 2.34 (s, 3H), 2.42 (s, 3H), 3.49 (brs, 1H), 4.17 (brs, following a similar procedure as described for 8a. The product
1H), 6.66 (d, J = 7.2 Hz, 1H), 7.26 (d, J = 8 Hz, 2H), 7.43–7.5 (M, was purified by silica gel (mesh 60–120) column chromato-
4H), 8.01 (d, J = 9.2 Hz, 1H), 10.5 (s, 1H) ppm. 13C NMR graphy to afford 8d as a white semisolid (136 mg, 0.40 mmol,
1
(CDCl3, 100 MHz) δ 19.5, 21.6, 21.7, 50.7, 75.3, 78.6, 127.3, 80%). H NMR (CDCl3, 300 MHz) δ 2.18 (s, 3H), 2.34 (s, 3H),
128.0, 128.4, 128.7, 129.8, 134.1, 134.2, 135.9, 136.3, 141.7, 2.87 (t, J = 5.7 Hz, 2H), 3.91 (t, J = 6 Hz, 2H), 7.02 (s, 1H), 7.1
144.3, 190.2 ppm. HRMS calcd for C19H19NNaO3S [M + Na] (d, J = 8.4 Hz, 2H), 7.28–7.39 (m, 5H), 7.64 (d, J = 7.8 Hz, 1H)
364.0983, found 364.0980.
Experimental procedure for the synthesis of phenyl(1-tosyl- 127.7, 129.4, 129.8, 130.2, 131.7, 133.8, 137.9, 140.4, 140.5,
2,3-dihydro-1H-benzo[b]azepin-4-yl)methanone 8a. Com- 143.4, 198.9 ppm. HRMS calcd for C19H19NaO3S [M + Na]
ppm. 13C NMR (CDCl3, 75 MHz) δ 21.6, 25.6, 29.0, 49.7, 127.2,
pound 7a (202 mg, 0.5 mmol) was taken in a 5 mL round- 364.0983, found 364.0983.
bottom flask containing 2 mL of dry acetonitrile solvent. Anhy-
drous FeCl3 (8.11 mg, 0.05 mmol) was added, and the reaction
mixture was heated to reflux for 8 h under an inert atmos-
phere. After complete conversion of the starting material
(monitoring by TLC), acetonitrile was removed under reduced
Acknowledgements
S. J., K. B., S. S. and K. P. are thankful to the CSIR, New Delhi,
pressure and the residue was purified by silica gel (mesh
60–120) column chromatography to afford 8a as a light yellow
semisolid (145 mg, 0.36 mmol, 72%). 1H NMR (CDCl3,
500 MHz) δ 2.3 (s, 3H), 3.03 (t, J = 3.6 Hz, 2H), 3.99 (t, J = 3.3
Hz, 2H), 6.75 (s, 1H), 7.11 (d, J = 4.8 Hz, 1H), 7.60 (d, J = 4.8
Hz, 2H), 7.26 (t, J = 4.3 Hz, 1H), 7.32 (d, J = 4.8 Hz, 2H),
7.36–7.43 (m, 5H), 7.50–7.53 (m, 1H), 7.73 (d, J = 4.8 Hz, 1H)
ppm. 13C NMR (CDCl3, 100 MHz) δ 21.6, 30.6, 48.9, 127.2,
127.5, 128.3, 129.4, 129.6, 129.7, 130.1, 131.3, 132.0, 133.9,
137.9, 138.3, 139.9, 140.0, 140.3, 143.4, 198.1 ppm. HRMS
calcd for C25H23NNaO4S [M + Na] 426.1140, found 426.1140.
(4-Methoxyphenyl)(1-tosyl-2,3-dihydro-1H-benzo[b]azepin-4-yl)-
methanone 8b. Compound 8b was prepared using 7b
(217 mg, 0.5 mmol) following a similar procedure to that
described for 8a. The residue was purified by silica gel (mesh
60–120) column chromatography to afford 8b as a white solid
(151.6 mg, 0.35 mmol, 70%), m.p. 197 °C. 1H NMR (CDCl3,
400 MHz) δ 2.36 (s, 3H), 3.05 (t, J = 3.4 Hz, 2H), 3.90 (s, 3H),
4.0 (s, 2H), 6.71 (s, 1H), 6.88 (d, J = 5.1 Hz, 2H), 7.14–7.17 (m,
3H), 7.28 (t, J = 4.8 Hz, 1H), 7.37–7.41 (m, 3H), 7.46 (d, J = 4.8
Hz, 2H), 7.75 (d, J = 4.8 Hz, 1H) ppm. 13C NMR (CDCl3,
100 MHz) δ 21.6, 29.8, 48.9, 55.6, 113.6, 127.2, 127.5, 129.5,
129.6, 129.7, 130.1, 131.4, 131.9, 133.7, 137.8, 138.3, 140.1,
140.3, 143.3, 163.1, 196.9 ppm. HRMS calcd for C25H23NNaO4S
[M + Na] 456.1245, found 456.1245.
India, for their fellowships.
References
1 (a) H. Fan, J. Peng, M. T. Hamann and J. F. Hu, Chem. Rev.,
2008, 108, 264; (b) S. Fustero, M. Sánchez-Roselló, P. Barrio
and A. Simón-Fuentes, Chem. Rev., 2011, 111, 6984;
(c) N. T. Patil and Y. Yamamoto, Chem. Rev., 2008, 108,
3395; (d) A. R. Katritzky, Chem. Rev., 2004, 104, 2125.
2 (a) V. R. Solomon and H. Lee, Curr. Med. Chem., 2011, 18,
1488; (b) V. Sridharan, P. A. Suryavanshi and C. Menendez,
Chem. Rev., 2011, 111, 7157; (c) K. Kaur, M. Jain,
R. P. Reddy and R. Jain, Eur. J. Med. Chem., 2010, 45, 3245;
(d) J. P. Michael, Nat. Prod. Rep., 2008, 25, 166; (e) G. Jones,
in Comprehensive Heterocyclic Chemistry II, ed. A. R. Katritzky,
C. W. Rees and E. F. V. Scriven, Pergamon Press, Oxford,
1996, vol. 5, p. 167; (f) S. Madapa and Z. T. S. Batra, Curr.
Org. Chem., 2008, 12, 1116–1183; (g) J. A. Joule and
K. Mills, in Heterocyclic Chemistry, Wiley, UK, 5th edn,
2010.
3 (a) H. Takahash, Y. Bekkali, A. J. Capolino, T. Gilmore,
S. E. Goldrick, P. V. Kaplita, L. Liu, R. M. Nelson,
D. Terenzio, J. Wang, L. Zuvela-Jelaska, J. Proudfoot,
G. Nabozny and D. Thomson, Bioorg. Med. Chem. Lett.,
2007, 17, 5091; (b) L. Zhi, C. M. Tegley, B. Pio, S. J. West,
K. B. Marschke, D. E. Mais and T. K. Jones, Bioorg. Med.
Chem. Lett., 2000, 10, 415.
Methyl [4-(1-tosyl-2,3-dihydro-1H-benzo[b]azepine-4-carbo-
nyl)]benzoate 8c. Compound 8c was prepared using 7c
(231 mg, 0.5 mmol) following a similar procedure to that
described for 8a. The product was purified by silica gel (mesh
1768 | Org. Biomol. Chem., 2014, 12, 1759–1770
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Paper
4 (a) J. V. Johnson, J. Med. Chem., 1989, 32, 1942;
(b) I. V. Ukrainets, L. V. Sidorenko, O. V. Gorokhova and
N. A. Jaradat, Chem. Heterocycl. Compd., 2006, 42, 475;
(c) J. C. Craig and P. E. Person, J. Med. Chem., 1971, 14,
1221; (d) N. Yamada, S. Kadowaki, K. Takahashi and
K. Umezu, Biochem. Pharmacol., 1992, 44, 1211; (e) B. Lockhart,
N. Bonhomme, A. Roger, G. Dorey, P. Casara and P. Lestage,
Eur. J. Pharmacol., 2001, 416, 59; (f) I. N. Nesterova,
L. M. Alekseeva, S. M. Golovira and V. G. Granik, Khim.-
Farm. Zh., 1995, 29, 31; (g) T. K. Jones, D. T. Winn, L. Zhi,
L. G. Hamann, C. M. Tegley and C. L. F. Pooley, U.S. Patent
5688808, 1997; (h) L. Zhi, C. M. Tegley, M. Christopher,
K. B. Marschke, D. E. Mais, T. K. Jones and K. Todd, J. Med.
Chem., 1999, 42, 1466; (i) M. J. Coughlan, S. W. Elmore,
8029; (d) K. A. Parker and T. L. Mindt, Org. Lett., 2002, 4,
4265; (e) C. S. Yi, S. Y. Yun and I. A. Guzei, J. Am. Chem.
Soc., 2005, 127, 5782; (f) R. Kamakshi and B. S. R. Reddy,
Catal. Commun., 2007, 8, 825; (g) M. E. Theoclitou and
L. A. Robinson, Tetrahedron Lett., 2002, 43, 3907;
(h) B. C. Ranu, A. Hajra, S. S. Dey and U. Jana, Tetrahedron,
2003, 59, 813–819; (i) K. Makino, O. Hara, Y. Takiguchi,
T. Katano, Y. Asakawa, K. Hatano and Y. Hamada, Tetra-
hedron Lett., 2003, 44, 8925–8929; ( j) R. H. F. Mansake and
M. Kulka, Org. React., 1953, 7, 59–70; (k) C. S. Yi and
S. Y. Yun, J. Am. Chem. Soc., 2005, 127, 17000–17006;
(l) X. Zhang, B. Liu, X. Shu, Y. Gao, H. Lv and J. Zhu, J. Org.
Chem., 2012, 77, 501; (m) M. M. Lorion, D. Gasperini,
J. Oble and G. Poli, Org. Lett., 2013, 15, 3050–3053.
M. E. Kort, P. R. Kym, J. L. Moore, J. K. Pratt, A. X. Wang, 13 Few selected examples: (a) T. Kametani and K. Fukumoto,
J. P. Edwards and T. K. Jones, Patent WO 9941256, 1999.
5 (a) P. Evans and A. O’Byrne, Tetrahedron, 2008, 64,
8067–8072; (b) R. D. Dillard, D. E. Pravey and D. N. Benslay,
J. Med. Chem., 1973, 16, 251–253; (c) S. Gurunathan and
P. T. Perumal, Tetrahedron Lett., 2011, 52, 1783–1787;
(d) J. A. Damavandi, M. A. Zolfigol and B. Karami, Synth.
Commun., 2001, 31, 3183–3187; (e) K. Nikham, B. Karami
and M. A. Zolfigol, Catal. Commun., 2007, 8, 1427–1430.
6 (a) Z. H. Skraup, Monatsh. Chem., 1880, 1, 316; (b) Z. H. Skraup,
Monatsh. Chem., 1881, 2, 587; (c) H. Skraup, Chem. Ber.,
1880, 13, 2086; (d) O. Doebner and W. V. Miller, Ber. Dtsch.
Chem. Ges., 1881, 14, 2812; (e) R. H. F. Mansake and
M. Kulka, Org. React., 1953, 7, 5912.
7 (a) X.-Y. Hu, J.-C. Zhang, W. Wie and J.-X. Ji, Tetrahedron
Lett., 2011, 52, 2903–2905 and references cited therein;
(b) H. Waldmann, G. V. Karunakar and K. Kumar, Org.
Lett., 2008, 10, 2159–2162; (c) J.-C. Zhang and J.-X. Ji, Cata-
lysis, 2011, 1360–1363; (d) J.-C. Zhang and J.-X. Ji, ACS
Catal., 2011, 1, 1360–1363; (e) Y.-W. Zhu, J.-L. Qian,
W.-B. Yi and C. Cai, Tetrahedron Lett., 2013, 54, 638–641.
8 (a) K. Makino, O. Hara, Y. Takiguchi, T. Katano,
Y. Asakawa, K. Hatano and Y. Hamada, Tetrahedron Lett.,
Heterocycles, 1975, 3, 931; (b) V. Kouznetsov, A. Palma and
C. Ewert, Curr. Org. Chem., 2001, 5, 519; (c) J.-P. K. Meigh,
Sci. Synth., 2004, 17, 825; (d) W. M. Kazmierski,
J. P. Peckham, M. Duan, T. P. Kenakin, S. Jenkinson,
K. S. Gudmundsson, S. C. Piscitelli and P. L. Feldman,
Curr. Med. Chem.: Anti-Infect. Agents, 2005, 4, 133;
(e) M. Thibonnier, P. Coles, A. Thibonnier and M. Shoham,
Annu. Rev. Pharmacol. Toxicol., 2001, 41, 175; (f) M. A. Xiang,
P. J. Rybczynski, M. Patel, R. H. Chen, D. F. McComsey,
H.-C. Zhang, J. W. Gunnet, R. Look, Y. Wang, L. K. Minor,
H. M. Zhong, F. J. Villani, K. T. Demarest, B. P. Damianob
and B. E. Maryanoff, Bioorg. Med. Chem. Lett., 2007, 17,
6623; (g) C. M. Yea, C. E. Allan, D. M. Ashworth, J. Barnett,
A. J. Baxter, J. D. Broadbridge, R. J. Franklin, S. L. Hampton,
P. Hudson, J. A. Horton, P. D. Jenkins, A. M. Penson,
G. R. W. Pitt, P. Riviére, P. A. Robson, D. P. Rooker,
G. Semple, A. Sheppard, R. M. Haigh and M. B. Roe, J. Med.
Chem., 2008, 51, 8124; (h) Y. Yamamura, S. Nakamura,
S. Ito, T. Hirano, T. Onogawa, T. Yamashita, Y. Yamada,
K. Tsujimae, M. Aoyama, K. Kotosai, H. Ogawa,
H. Yamashita, K. Kondo, M. Tominaga, G. Tsujimoto and
T. Mori, J. Pharmacol. Exp. Ther., 1998, 287, 860.
2003, 44, 8925–8929; (b) A. M. Wagner, C. E. Knezevic, 14 (a) J. D. Albright, M. F. Reich, E. G. Delos Santos,
J. L. Wall, V. L. Sun, J. A. Buss, L. A. T. Allen and
A. G. Wenzel, Tetrahedron Lett., 2012, 53, 833–836.
9 (a) Y. M. Luo, Z. G. Li and C. J. Li, Org. Lett., 2005, 7, 2675;
(b) X. Y. Liu, P. Ding, J. S. Huang and C. M. Che, Org. Lett.,
2007, 9, 2645; (c) Y. Zhou, E. Feng, G. Liu, D. Ye, J. Li,
H. Jiang and H. Liu, J. Org. Chem., 2009, 74, 7344–7348.
10 (a) P. Evans, R. Grigg and M. Monteith, Tetrahedron Lett.,
1999, 40, 5247; (b) M. Arisawa, C. Theeraladanon,
A. Nishida and M. Nakagawa, Tetrahedron Lett., 2001, 42,
8029–8033.
11 (a) Z. Wang, S. Li, B. Yu, H. Wu, Y. Wang and X. Sun, J. Org.
Chem., 2012, 77, 8615–8620; (b) P. Kothandraman, S. J. Foo
and P. W. H. Chan, J. Org. Chem., 2009, 74, 5947–
5952.
12 (a) Microreview: T. Kitamura, Eur. J. Org. Chem., 2009,
1111–1125; (b) X. Y. Liu and C. M. Che, Angew. Chem., Int.
Ed., 2008, 47, 3805; (c) M. Arisawa, C. Theeraladanon,
A. Nishida and M. Nakagawa, Tetrahedron Lett., 2001, 42,
J. P. Dusza, F.-W. Sum, A. M. Venkatesan, J. Coupet,
P. S. Chan, X. Ru, H. Mazandarani and T. Bailey, J. Med.
Chem., 1998, 41, 2442; (b) K. Kondo, H. Ogawa, T. Shinohara,
M. Kurimura, Y. Tanada, K. Kan, H. Yamashita,
S. Nakamura, T. Hirano, Y. Yamamura, T. Mori,
M. Tominaga and A. Itai, J. Med. Chem., 2000, 43, 4388;
(c) K. Kondo, K. Kan, Y. Tanada, M. Bando, T. Shinohara,
M. Kurimura, H. Ogawa, S. Nakamura, T. Hirano,
Y. Yamamura, M. Kido, T. Mori and M. Tominaga, J. Med.
Chem., 2002, 45, 3805; (d) A. A. Failli, J. S. Shumsky,
R. J. Steffan, T. J. Caggiano, D. K. Williams, E. J. Trybulski,
X. Ning, Y. Lock, T. Tanikella, D. Hartmann, P. S. Chan and
C. H. Park, Bioorg. Med. Chem. Lett., 2006, 16, 954;
(e) A. Martinez-Castelao, Curr. Opin. Invest. Drugs, 2001, 2,
525–530; (f) T. J. Caggiano, Drugs Future, 2002, 27, 248;
(g) M. Seto, N. Miyamoto, K. Aikawa, Y. Aramaki,
N. Kanzaki, Y. Iizawa, M. Baba and M. Shiraishi, Bioorg.
Med. Chem., 2005, 13, 363.
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Paper
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15 Selected examples: (a) E. M. L. Sze, M. J. Koh, Y. M. Tjia,
W. Rao and P. W. H. Chan, Tetrahedron, 2013, 69, 5558–
5565 and references cited therein; (b) T. A. Moss, Tetra-
hedron Lett., 2013, 54, 993–997; (c) C. Kothandaraman,
D. Huang, W. Susanti, P. Rao and W. H. Chan, Chem.–Eur.
L. Escalante, J. A. Varela, L. Castedo and C. Saá, Org. Lett.,
2009, 11, 1531; (f) T. Jin and Y. Yamamoto, Org. Lett., 2008,
10, 3137–3139; (g) For the Ag-catalyzed reaction, see:
J. U. Rhee and M. J. Krische, Org. Lett., 2005, 7, 2493–
2495.
J., 2011, 17, 10081–10088; (d) H. He, W.-B. Liu, L.-X. Dai 18 For the iron-catalyzed alkyne–carbonyl metathesis reaction,
and S.-L. You, Angew. Chem., Int. Ed., 2010, 49, 1496–1499;
(e) Á. González-Gómez, G. Domínguez and J. Pérez-Castells,
Eur. J. Org. Chem., 2009, 5057–5062; (f) S. Kotha and
V. R. Shah, Eur. J. Org. Chem., 2008, 1054; (g) R. Abonia,
P. Cuervo, B. Insuasty, J. Quiroga, M. Nogueras and J. Cobo,
Eur. J. Org. Chem., 2008, 4684; (h) D. Boeglin, D. Bonnet
and M. Hibert, J. Comb. Chem., 2007, 9, 487; (i) V. Singh
and S. Batra, Eur. J. Org. Chem., 2007, 2970;
see: (a) K. Bera, S. Jalal, S. Sarkar and U. Jana, Org. Biomol.
Chem., 2014, 12, 57; (b) K. Bera, S. Sarkar, S. Jalal and
U. Jana, J. Org. Chem., 2012, 77, 8780–8786; (c) K. Bera,
S. Sarkar, S. Biswas, S. Maiti and U. Jana, J. Org. Chem.,
2011, 76, 3539–3544; (d) For iron-catalyzed intramolecular
Prins cyclization of alkynyl-dimethylacetals, see: D. Zheng,
W. Gong;, Z. Ma, B. Ma, X. Zhao, Z. Xie and Y. Li, Tetra-
hedron Lett., 2011, 52, 314–317.
( j) H. Stukenbrock, R. Mussmann, M. Geese, Y. Ferandin, 19 (a) S. Sarkar, S. Maiti, K. Bera, S. Jalal and U. Jana, Tetra-
O. Lozach, T. Lemcke, S. Kegel, A. Lomow, U. Burk,
C. Dohrmann, L. Meijer, M. Austen and C. Kunick, J. Med.
Chem., 2008, 51, 2196; (k) G. L. Grunewald,
V. H. Dahanukar, P. Ching and K. R. Criscione, J. Med.
Chem., 1996, 39, 3539.
hedron Lett., 2012, 53, 5544–5547; (b) S. Maiti, S. Biswas
and U. Jana, J. Org. Chem., 2010, 75, 1674–1683; (c) U. Jana,
S. Biswas and S. Maiti, Eur. J. Org. Chem., 2008, 5798–5800;
(d) S. Biswas, S. Maiti and U. Jana, Eur. J. Org. Chem., 2009,
2354–2359; (e) S. Jalal, S. Sarkar, K. Bera, S. Maiti and
U. Jana, Eur. J. Org. Chem., 2013, 4823–4828; (f) S. Sarkar,
K. Bera, S. Jalal and U. Jana, Eur. J. Org. Chem., 2013, 6055–
6061.
16 For intermolecular alkyne–carbonyl metathesis, see:
(a) A. Hayashi, M. Yamaguchi and M. Hirama, Synlett,
1995, 195; (b) L.-W. Xu, L. Li, C.-Z. Xia and P.-Q. Zhao, Helv.
Chim. Acta, 2004, 87, 3080; (c) M. Curini, F. Epifano, 20 A few selected recent articles on the synthesis of quino-
F. Maltese and O. Rosati, Synlett, 2003, 552;
(d) K. C. M. Kurtz, R. P. Hsung and Y. Zhang, Org. Lett.,
2006, 8, 231–234; (e) A. Saito, M. Umakoshi, N. Yagyu and
Y. Hanazawa, Org. Lett., 2008, 10, 1783; (f) G. S. Viswanathan
and C.-J. Lee, Tetrahedron Lett., 2002, 43, 1613.
lines: (a) K. K. Toh, S. Sanjaya, S. Sahnoun, S. Y. Chong and
S. Chiba, Org. Lett., 2012, 14, 2290–2292; (b) C. Chowdhury,
B. Das, S. Mukherjee and B. Achari, J. Org. Chem., 2012, 77,
5108–5119; (c) S. Cai, J. Zeng, Y. Bai and X.-W. Liu, J. Org.
Chem., 2012, 77, 801–807; (d) Y. Zhang, M. Wang, P. Li and
L. Wang, Org. Lett., 2012, 14, 2206–2209; (e) S. Khong
and O. Kwon, J. Org. Chem., 2012, 77, 8257–8267;
(f) V. K. Tiwari, G. G. Pawar, R. Das, A. Adhikary and
M. Kapur, Org. Lett., 2013, 15, 3310–3313; (g) Z. Huo,
I. D. Gridnev and Y. Yamamoto, J. Org. Chem., 2010, 75,
1266–1270; (h) G.-L. Gao, Y.-N. Niu, Z.-Y. Yan, H.-L. Wang,
G.-W. Wang, A. Shaukat and Y.-M. Liang, J. Org. Chem.,
2010, 75, 1305–1308.
17 A few selected reports on intramolecular alkyne–carbonyl
metathesis: (a) For the HBF4-catalyzed reaction, see:
L. Escalante, C. González-Rodíguez, J. A. Varela and C. Saa,
Angew. Chem., Int. Ed., 2012, 51, 12316–12320; (b) For a
review on Au-catalysis, see: L. Liu, B. Xu and
G. B. Hammond, Beilstein J. Org. Chem., 2011, 7, 606–614
and references cited therein; (c) For the SbF5-MeOH cata-
lyzed reaction, see: A. Saito, J. Kasai, Y. Odaira, H. Fukaya
and Y. Hanzawa, J. Org. Chem., 2009, 74, 5644–5647; (d) For 21 T. A. Biju, N. E. Wurz and F. Glorius, J. Am. Chem. Soc.,
the TfOH-catalyzed reaction, see: T. Jin, F. Yang, C. Liu and 2010, 132, 5970.
Y. Yamamoto, Chem. Commun., 2009, 3533–3535; (e) For 22 H. Li, X. Xu, J. Yang, X. Xie, H. Huang and Y. Li, Tetra-
the TFA-catalyzed reaction, see: C. González-Rodríguez,
hedron Lett., 2011, 52, 530–533.
1770 | Org. Biomol. Chem., 2014, 12, 1759–1770
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