Access to quinolines through gold-catalyzed intermolecular cycloaddition of 2-aminoaryl carbonyls and internal alkynes

Article abstract of DOI:10.1021/jo202281x

A facile and general method leading to polyfunctionalized quinolines was developed. In the presence of a highly efficient combination encompassing (PPh)₃AuCl and AgOTf, the reactions between 2-aminocarbonyls and an array of internal alkynes pro

Full text of DOI:10.1021/jo202281x

Note
pubs.acs.org/joc
Access to Quinolines through Gold-Catalyzed Intermolecular
Cycloaddition of 2-Aminoaryl Carbonyls and Internal Alkynes
Shuting Cai, Jing Zeng, Yaguang Bai, and Xue-Wei Liu*
Division of Chemistry and Biological Chemistry, School of Physical and Mathematical Sciences, Nanyang Technological University,
Singapore 637371
S
* Supporting Information
ABSTRACT: A facile and general method leading to
polyfunctionalized quinolines was developed. In the presence
of a highly efficient combination encompassing (PPh)3AuCl
and AgOTf, the reactions between 2-aminocarbonyls and an
array of internal alkynes proceeded smoothly to afford
quinoline derivatives in good to excellent yields (up to 93%).
udging from the extensive reports surrounding quinolines,1
as they provide a convenient approach to the acquirement of
cyclic compounds.10 Our group has been actively developing
Jthe generation of an efficient platform for their expedient
synthesis has, indubitably, been of great interest for decades.
Apart from their wide presence in various natural products
(Figure 1) and pharmaceutical compounds,2 quinoline
new synthetic routes to heterocycles through efficacious
methodologies.11 One current example is the microwave-
assisted three-component synthesis of pyrimidinones, catalyzed
by copper(II) triflate.12 Inspired by the immense opportunities
presented by alkyne moieties and our growing interests in the
assembly of heterocycles, we envisioned the use of alkyne in the
construction of an array of quinoline derivatives.
Although there have been various reports on the synthesis of
quinolines using alkynes,9,13 the strategies often employ
terminal alkynes with a rather limited substrate applicability.
Internal alkynes, in contrast to terminal alkynes, allow
integration of more functional groups into quinolines,
increasing their possible applications and employability.
Encouraged by the seemingly sparse report on using internal
alkynes to construct quinolines, we sought to develop a novel
method for the reaction of internal ynoates report successful
applications of a variety of 2-aminoaryl carbonyls and internal
alkynes in the synthesis of quinoline derivatives.
Preliminary studies were conducted with the aim to locate a
suitable catalyst to promote the reaction between 2-amino-
benzaldehyde 1a and ethyl 3-phenylpropiolate 2a. Ni(cod)2 was
chosen as the initial experimental catalyst due to reports
demonstrating nickel’s successful applications in such addition
reactions.14 However, the catalyst failed to produce the desired
product. On top of that, no reaction was observed for Sc(OTf)3
after heating at 100 °C for 24 h (Table 1, entries 1 and 2).
Following the failure of preceding catalysts, attention was then
directed to gold catalysts. Gold catalysts provide huge
possibilities in organic reactions and ubiquitous reports have
acknowledged their potentials, especially in cycloaddition
reactions of alkyne as they preferentially coordinates to alkyne
bonds.15 In addition, gold catalysts have also been reported to
aid substantially to the synthesis of quinolines16 and isoquino-
Figure 1. Examples of quinoline-containing natural products.
derivatives have been reported to possess biological properties
such as antibacterial,3a anti-inflammatory,3b and antimicrobial
activities.3c Therefore, the benefits associated with them justify
the continual search for strategies to develop their synthesis.
Pioneering work on the construction of quinolines by
Koenigs4 in 1879 drew the attention of researchers and
prompted a widespread search to increase the preparative value
as the initial method required harsh conditions.5
Among the methods described over the years, prominent
conventional examples include Friedlander synthesis, Skarup
̈
reactions, as well as Doebner−Miller reactions.6 However, a
recent upsurge of reports on synthesizing quinolines has
demonstrated that new cycloadditions of suitable precursors
through acid catalysis7 and novel metal-catalyzed coupling−
cyclization reactions8 could compete and surpass conventional
strategies in terms of celerity and efficacy. One prominent
example is the recent work done by Li and co-workers, in which
they reported an elegant work on the use of terminal ynones
with aminoaryls to synthesize 3-carbonyl quinolines through
Fe-catalyzed Michael addition−cycloaddition approach.9
Alkyne moieties have been ubiquitously employed in many
organic syntheses. In particular, metal-catalyzed intermolecular
alkyne reactions have been extremely popular in cycloadditions
Received: November 14, 2011
Published: December 12, 2011
© 2011 American Chemical Society
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Note
Table 1. Optimization of Quinoline 3a
a
entry
catalyst
ligand/additive
PPh3
solvent
temp (°C)
time (h)
yield (%)
1
2
3
4
Ni(cod)2
DMF
DMF
DMF
DMF
DMF
DMF
DMF
ACN
THF
100
100
100
100
100
100
100
reflux
60
24
24
4
Sc(OTf)3
nr
30
AuCl3
(Ph3P)AuCl
RAuCl
AgOTf
AgOTf
AgNO3
Ag2CO3
AgOTf
AgOTf
AgOTf
AgOTf
AgOTf
AgOTf
2
88
b
5
3
72
c
6
(Ph3P)AuCl
(Ph3P)AuCl
(Ph3P)AuCl
(Ph3P)AuCl
(Ph3P)AuCl
(Ph3P)AuCl
(Ph3P)AuCl
(Ph3P)AuCl
24
24
12
12
24
5
<10
nr
7
8
9
58
47
c
10
CH2Cl2
DMF
DMF
DMF
reflux
50
<10
66
11
d
12
100
100
8
82
e
13
1
80
a
Unless specified, reactions were carried out by treating 1a (1 equiv) and 2a (1.5 equiv) with catalyst (10 mol %) and ligand/additive (10 mol %) in
b
c
d
solvent (2 mL). R = [P(t-Bu)2(o-biphenyl)]. More than 80% of the starting materials were recovered. Reaction was carried out with catalyst (5
mol %) and additive (5 mol %). Reaction was carried out with catalyst (20 mol %) and additive (20 mol %).
e
lines.17 To our delight, successful acquirement of the desired
product when catalytic amount of AuCl3 was employed
validated our prediction, albeit the yield was only 30% (Table
1 entry 3). Silver additives have been known to complement
gold catalysts by increasing the electrophilicity of the gold
center through halide abstraction.18 Hence, the reaction was
further examined by the incorporation of silver additive.
Interestingly, the yield was raised significantly to 88% and the
time was shortened to 2 h when AuCl3 was replaced by
(Ph3P)AuCl, with AgOTf as additive. Further attempt to
alternate the catalyst to [P(t-Bu)2(o-biphenyl)]AuCl gave a less
satisfactory result (72% yield, Table 1 entry 5). These outcomes
showcases the suitability of (Ph3P)AuCl for this reaction and
prompted a search for an additive most compatible with
(Ph3P)AuCl. After screening various additives including
AgNO3 and Ag2CO3, it was apparent that the combination of
(Ph3P)AuCl with AgOTf gave the best yield (Table 1, entries 4,
6, and 7). Subsequent examination of the solvent effect reveals
DMF to be the optimal solvent in comparison to ACN, THF
and CH2Cl2 (Table 1, entries 8−10). The reaction temperature
was fixed at 100 °C as longer reaction times were required and
lower yields were obtained when the temperature was reduced
to 50 °C (Table 1, entry 11). In the final part of the studies, the
catalyst and additive loadings were investigated. Although there
were no significant effects of the loadings on the yields,
observable changes in the reaction times were documented
(Table 1, entries 12−13). When the loadings were decreased to
5 mol %, the reaction time was prolonged to 8 h. Increase of
the loadings to 20 mol % did not shorten the reaction time
significantly, therefore 10 mol % of catalyst loading and additive
loading were chosen as the most favorable loading amounts.
Through the optimization studies, a set of optimal conditions
was defined. With 10 mol % (Ph3P)AuCl, 10 mol % AgOTf in
DMF at 100 °C, the reaction proceeded smoothly, providing a
high yield of 88% in 2 h.
worthy of note that most of the 2-aminoaryl carbonyls 1
provided the desired compound in good to excellent yields
(80−91%). A closer examination of the results revealed that in
contrast to the 5-Cl-, 5-NO2-, 4′-Cl-, and 4′-Br-substituted 2-
aminobenzophenones, the 4-Me- and 4′-Me-substituted
benzophenones produced observable higher yields (Table 2,
entries 4−9, 3d−i). This led to the speculation that electron-
donating substituents perform better than electron-withdrawing
substituents. In particular, when strong electron-withdrawing 5-
NO2-substituted 2-aminobenzophenone was subjected to the
same conditions, the reaction could not be completed even
after 48 h and the 38% yield (3f) obtained was comparatively
inferior to other products (Table 2, entry 6). In addition, when
2-aminobenzophenone was substituted with 5-Cl and 2′-F, the
yield was slightly lower (80%), presumably due to the presence
of two electron-withdrawing substituents (Table 2, entry 10).
Encouraged by the success of aryl substituents, the focus was
directed to the possibility of incorporating alkyl substituents in
the system. Notably, the reaction proceeded smoothly in the
presence of 2-aminoacetophenone, providing an excellent yield
of 91% (Table 2, entry 2, 3b). Increasing the alkyl chain did not
affect the yield, and compound 3k was also produced with an
exceptional yield (Table 2, entry 11).
Extension of the preliminary studies on the substrate scope
(Table 3) was essential, and exploration using a range of alkyne
substituents 2 was therefore crucial. Gratifyingly, good to
excellent yields (80−90%) were obtained in the presence of
electron-donating or electron-withdrawing substituents on the
aryl ring of the alkyne (Table 3, entries 1−4, 3l−o). Although
there was a slight decrease in the yields for electron-
withdrawing substituents as compared to electron-donating
substituents, the difference is less significant and good yields
were acquired even for NO2-substituted aryl alkynes.
Furthermore, bulky substituent (naphthalene) on the aryl
alkyne did not hinder the reaction and 3p was obtained in high
yield of 88% (Table 3, entry 5). Smooth progression of the
reaction also occurred for alkyl alkyne, providing excellent
yields between 88% to 91% (Table 3, entries 6−8, 3q−s).
Subsequently, the ethoxy group in the alkyne was replaced with
Elucidation of the optimal set of conditions allowed
continual investigation of the reaction scope and flexibility.
To examine the adaptability of the reaction, a wide array of 2-
aminoaryl carbonyls 1 were employed. From Table 2, it was
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Note
Table 2. Substrate Scope: An Insight to the Flexibility of the Reaction through Various 2-Aminoaryl Carbonyls 1
Table 3. Substrate Scope: An Insight to the Flexibility of the Reaction through Various Internal Alkyne Substituents 2
a
entry
1
2
3
yield (%)
1
2
3
4
5
1a
1a
1a
1a
1a
1c
1c
1c
1a
1a
2b
2c
2d
2e
2f
R1 = 4- CH3Ph, R2 = CO2Et
R1 = 4-OCH3Ph, R2 = CO2Et
R1 = 4-BrPh, R2 = CO2Et
R1 = 4-NO2Ph, R2 = CO2Et
R1 = naphthalene, R2 = CO2Et
R1 = CH3, R2 = CO2Et
3l
90
93
85
80
88
90
91
88
75
65
3m
3n
3o
3p
3q
3r
b
6
2g
2h
2i
b
7
b
R1 = CH2CH2CH3, R2 = CO2Et
R1 = (CH2)5CH3, R2 = CO2Et
R1 = Ph, R2 = piperidine
8
3s
9
2j
3t
10
2k
R1 = Ph, R2 = CH3
3u
a
Reactions carried out by treating 1a (1 equiv) and 2 (1.5 equiv) with (Ph3P)AuCl (10 mol %) and AgOTf (10 mol %) in DMF (2 mL) at 100 °C.
Reactions with 1c (1 equiv).
b
803
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Note
Ethyl 4-Methyl-2-phenylquinoline-3-carboxylate (3b). The crude
residue was then purified by flash column chromatography on silica gel
(10% EtOAc in hexanes) to afford compound 3b (19.6 mg, 0.07
piperidine, and a relatively good yield of 75% was obtained for
3t (Table 3, entry 9). Rounding up on investigation of the
substrate scope, a ketone-substituted alkyne was employed and
the reaction was able to give a reasonable yield of 65% (Table 3,
entry 10, 3u). This further exemplifies the diversity of the
reaction and provides a favorable conclusion to our
investigations.
In summary, an expedient methodology for the facile
synthesis of quinolines was demonstrated with the aid of
(PPh3)AuCl catalyst and AgOTf additive. This intermolecular
cyclization of internal alkynes allowed the efficient integration
of more functional groups into quinolines. In addition, the
adaptability of this strategy was displayed by the good to
excellent yields obtained for a large array of substrates. The
importance of quinolines extends beyond being components of
natural products; they have also been acknowledged for their
wide applications in biological and pharmaceutical fields.1−3
Therefore, the success of this strategy provides immediate
access to an extensive library of quinolines, contributing
significantly to the research sector.
1
mmol, 91% yield) as a yellow oil. Rf = 0.34 (EtOAc/Hex 20/80). H
NMR (400 MHz, CDCl3): δ 8.17 (d, J = 8.4 Hz, 1H), 8.07 (d, J = 8.4
Hz, 1H), 7.76 (t, J = 7.5 Hz, 1H), 7.70−7.68 (m, 2H), 7.61 (t, J = 7.5
Hz, 1H), 7.48−7.43 (m, 3H), 4.15 (q, J = 7.2 Hz, 2H), 2.76 (s, 3H),
1.01 (t, J = 7.2 Hz, 3H). 13C NMR (100 MHz, CDCl3): δ 169.1, 156.2,
147.2, 142.7, 140.6, 130.3, 128.6, 128.3, 127.4, 126.9, 126.0, 124.1,
61.5, 15.6, 13.6. FT-IR (neat): νmax 3063, 2986, 1721, 1644, 1582,
1497, 1450, 1296, 1234 cm−1. HRMS (ESI): m/z calcd for C19H17NO2
[M + H]+ 292.1259, found 292.1338.
Ethyl 2,4-Diphenylquinoline-3-carboxylate (3c). The crude resi-
due was then purified by flash column chromatography on silica gel
(10% EtOAc in hexanes) to afford compound 3c (16.3 mg, 0.05 mmol,
91% yield) as a yellow solid. Rf = 0.34 (EtOAc/Hex 20/80). Mp: 89−
1
91 °C. H NMR (400 MHz, CDCl3): δ 8.23 (d, J = 8.3 Hz, 1H),
7.79−7.75 (m, 3H), 7.62 (d, J = 8.3 Hz, 1H), 7.52−7.41 (m, 9H), 3.87
(q, J = 7.2 Hz, 2H), 0.82 (t, J = 7.2 Hz, 3H). 13C NMR (100 MHz,
CDCl3): δ 168.2, 156.0, 147.8, 147.1, 140.2, 135.5, 130.4, 129.8, 129.4,
129.1, 128.8, 128.6, 128.5, 128.4, 128.2, 127.2, 127.0, 126.5, 125.5,
61.2, 13.4. FT-IR (neat): νmax 3063, 2978, 2893, 1728, 1612, 1551,
1481, 1443, 1296, 1227, 1103 cm−1. HRMS (ESI): m/z calcd for
C24H19NO2 [M + H]+ 354.1416, found 354.1494.
EXPERIMENTAL SECTION
Ethyl 7-Methyl-2,4-diphenylquinoline-3-carboxylate (3d). The
crude residue was then purified by flash column chromatography on
silica gel (10% EtOAc in hexanes) to afford compound 3d (15.7 mg,
0.04 mmol, 90% yield) as a yellow oil. Rf = 0.34 (EtOAc/Hex 20/80).
1H NMR (400 MHz, CDCl3): δ 8.00 (s, 1H), 7.75−7.73 (m, 2H),
7.51−7.40 (m, 9H), 7.31 (d, J = 8.7 Hz, 1H), 3.86 (q, J = 7.2 Hz, 2H),
2.57 (s, 3H), 0.81 (t, J = 7.2 Hz, 3H). 13C NMR (100 MHz, CDCl3): δ
168.3, 156.0, 148.1, 146.9, 141.0, 140.4, 135.8, 129.4, 129.3, 128.8,
128.7, 128.5, 128.4(2), 128.2, 126.4, 126.2, 123.5, 61.2, 21.8, 13.4. FT-
IR (neat): vmax 3063, 2978, 2932, 2870, 1728, 1620, 1551, 1489, 1450,
1412, 1288, 1227, 1173 cm−1. HRMS (ESI): m/z calcd for C25H21NO2
[M + H]+ 368.1572, found 368.1650.
Ethyl 6-Chloro-2,4-diphenylquinoline-3-carboxylate (3e). The
crude residue was then purified by flash column chromatography on
silica gel (10% EtOAc in hexanes) to afford compound 3e (13.8 mg,
0.04 mmol, 83% yield) as a yellow oil. Rf = 0.35 (EtOAc/Hex 20/80).
1H NMR (400 MHz, CDCl3): δ 8.16 (d, J = 9.0 Hz, 1H), 7.76−7.73
(m, 2H), 7.70 (dd, J = 2.2, 9.0 Hz, 1H), 7.58 (d, J = 2.2 Hz, 1H),
7.52−7.46 (m, 6H), 7.46−7.39 (m, 2H), 3.88 (q, J = 7.2 Hz, 2H), 0.82
(t, J = 7.2 Hz, 3H). 13C NMR (100 MHz, CDCl3): δ 167.8, 156.2,
146.3, 146.2, 139.8, 134.8, 133.0, 131.4, 129.3, 129.1, 128.8, 128.5(2),
128.4, 127.9, 126.3, 125.3, 61.4, 13.4. FT-IR (neat): νmax 3063, 2986,
2932, 1728, 1643, 1551, 1474, 1443, 1296, 1219, 1111, 756, 702 cm−1.
HRMS (ESI): m/z calcd for C24H18ClNO2 [M + H]+ 388.1026, found
388.1104.
■
All reactions were conducted under an atmosphere of nitrogen, unless
otherwise indicated. All reagents and solvents were obtained from
commercial suppliers and used without further purification. Product
purification by flash column chromatography was accomplished using
silica gel (0.010−0.063 mm). Technical grade solvents were used for
chromatography and distilled prior to use. IR spectra were recorded
and reported in cm−1. High-resolution mass spectra (HRMS) were
obtained on an ion trap mass spectrometer, coupled with the HPLC
system and the CE system. Accurate masses are reported for the
molecular ion [M + H]+ or a suitable fragment ion. NMR spectra were
recorded at room temperature on a 400 MHz NMR spectrometer. The
1
residual solvent signals were taken as the reference (7.26 ppm for H
NMR spectroscopy and 77.0 ppm for 13C NMR spectroscopy).
Chemical shifts are reported in delta (δ) units, parts per million (ppm)
downfield from triethylsilane. Chemical shift (δ) is referred in terms of
ppm, coupling constants (J) are given in Hz. Following abbreviations
classify the multiplicity: s = singlet, d = doublet, t = triplet, q = quartet,
m = multiplet, or unresolved.
2-Aminoaryl carbonyls 1b−j and internal alkynes 2a,g−i were
obtained from commercial suppliers and used without further
purification. Other 2-aminoaryl carbonyls 1a19a and 1k19b and internal
alkynes 2b−f,20a 2j,20b 2k20c were prepared from the standard
literature procedures.
General Procedure for the Synthesis of Quinolines. To a
solution of 2-aminobenzaldehyde 1a (10.0 mg, 0.08 mmol, 1.0 equiv),
(PPh3)AuCl (0.4 mg, 0.008 mmol, 0.1 equiv), and AgOTf (0.2 mg,
0.008 mmol, 0.1 equiv) in DMF (2 mL) was added ethyl 3-
phenylpropiolate 2a (15.0 μL, 0.09 mmol, 1.1 equiv). The reaction
mixture was stirred at 100 °C for 2 h (TLC monitored). The resulting
mixture was then diluted with EtOAc and filtered through Celite. The
filtrate was washed with water (2 × 20 mL) and brine (2 × 20 mL),
and the organic layers were dried over Na2SO4, filtered, and
concentrated under reduced pressure to yield the crude residue as a
dark yellow oil. The crude residue was then purified by flash column
chromatography on silica gel (10% EtOAc in hexanes) to afford
compound 3a (20.1 mg, 0.07 mmol, 88% yield) as a yellow oil.
Ethyl 2-Phenylquinoline-3-carboxylate (3a). Rf = 0.34 (EtOAc/
Hex 20/80). 1H NMR (400 MHz, CDCl3): δ 8.65 (s, 1H), 8.19 (d, J =
8.5 Hz, 1H), 7.93 (d, J = 7.9 Hz, 1H), 7.83−7.79 (m, 1H), 7.65−7.59
(m, 3H), 7.50−7.44 (m, 3H), 4.19 (q, J = 7.2 Hz, 2H), 1.07 (t, J = 7.2
Hz, 3H). 13C NMR (100 MHz, CDCl3): δ 168.0, 158.1, 148.4, 140.8,
139.0, 131.5, 129.5, 128.6, 128.5, 128.2(2), 127.2, 125.8, 125.5, 61.5,
13.7. FT-IR (neat):: νmax 3063, 2986, 2901, 1721, 1620, 1597, 1451,
1234, 1096, 833 cm−1. HRMS (ESI): m/z calcd for C18H15NO2 [M +
H]+ 278.1103, found 278.1181.
Ethyl 6-Nitro-2,4-diphenylquinoline-3-carboxylate (3f). The
crude residue was then purified by flash column chromatography on
silica gel (20% EtOAc in hexanes) to afford compound 3f (6.2 mg,
0.02 mmol, 38% yield) as a yellow solid. Rf = 0.31 (EtOAc/Hex 20/
1
80). Mp: 126−128 °C. H NMR (400 MHz, CDCl3): δ 8.56 (d, J =
2.4 Hz, 1H), 8.53 (dd, J = 2.4, 9.2 Hz, 1H), 8.34 (d, J = 9.2 Hz, 1H),
7.79−7.77 (m, 2H), 7.57−7.56 (m, 3H), 7.51−7.49 (m, 3H), 7.43−
7.41 (m, 2H), 3.91 (q, J = 7.1 Hz, 2H), 0.84 (t, J = 7.1 Hz, 3H). 13C
NMR (100 MHz, CDCl3): δ 167.3, 159.4, 149.8, 149.1, 145.9, 138.3,
134.0, 131.7, 129.7, 129.4, 129.3, 128.9, 128.7, 128.6(2), 124.9, 123.9,
123.6, 61.7, 13.3. FT-IR (neat): νmax 1728, 1643, 1558, 1528, 1481,
1443, 1342, 1288, 1219, 1111, 1088 cm−1. HRMS (ESI): m/z calcd for
C24H18N2O4 [M + H]+ 399.1267, found 399.1345.
Ethyl 2-Phenyl-4-p-tolylquinoline-3-carboxylate (3g). The crude
residue was then purified by flash column chromatography on silica gel
(10% EtOAc in hexanes) to afford compound 3g (15.3 mg, 0.04
1
mmol, 88% yield) as a yellow oil. Rf = 0.34 (EtOAc/Hex 20/80). H
NMR (400 MHz, CDCl3): δ 8.22 (d, J = 8.4 Hz, 1H), 7.78−7.74 (m,
3H), 7.65 (d, J = 8.4 Hz, 1H), 7.50−7.45 (m, 4H), 7.31 (s, 4H), 3.88
(q, J = 7.1 Hz, 2H), 2.46 (s, 3H), 0.83 (t, J = 7.1 Hz, 3H). 13C NMR
(100 MHz, CDCl3): δ 168.3, 156.0, 147.8, 147.3, 140.3, 138.3, 132.5,
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Note
130.4, 129.8, 129.3, 128.9, 128.8, 128.6, 128.4, 126.9, 126.6, 125.7,
61.2, 21.4, 13.4. FT-IR (neat): νmax 2978, 2924, 1728, 1636, 1551,
1489, 1458, 1296, 1227, 1103 cm−1. HRMS (ESI): m/z calcd for
C25H21NO2 [M + H]+ 368.1572, found 368.1650.
Ethyl 2-(4-Methoxyphenyl)quinoline-3-carboxylate (3m). The
crude residue was then purified by flash column chromatography on
silica gel (20% EtOAc in hexanes) to afford compound 3m (23.6 mg,
0.08 mmol, 93% yield) as a yellow oil. Rf = 0.21 (EtOAc/Hex 20/80).
1H NMR (400 MHz, CDCl3): δ 8.60 (s, 1H), 8.16 (d, J = 8.4 Hz, 1H),
7.90 (d, J = 8.4 Hz, 1H), 7.80 (t, J = 7.7 Hz, 1H), 7.61 (d, J = 8.6 Hz,
2H), 7.60−7.56 (m, 1H), 7.00 (d, J = 8.6 Hz, 2H), 4.24 (q, J = 7.2 Hz,
2H), 3.87 (s, 3H), 1.16 (t, J = 7.2 Hz, 3H). 13C NMR (100 MHz,
CDCl3): δ 168.3, 160.2, 157.7, 148.4, 138.9, 133.2, 131.4, 130.1, 129.4,
128.2, 127.0, 125.7, 125.5, 113.7, 61.6, 55.4, 13.9. FT-IR (neat): νmax
3017, 2978, 2940, 2839, 1721, 1612, 1558, 1512, 1458, 1420, 1250,
1219, 1096, 1034 cm−1. HRMS (ESI): m/z calcd for C19H17NO3 [M +
H]+ 308.1208, found 308.1287.
Ethyl 4-(4-Chlorophenyl)-2-phenylquinoline-3-carboxylate (3h).
The crude residue was then purified by flash column chromatography
on silica gel (10% EtOAc in hexanes) to afford compound 3h (13.7
mg, 0.04 mmol, 82% yield) as a yellow solid. Rf = 0.35 (EtOAc/Hex
20/80). Mp: 107−109 °C. 1H NMR (400 MHz, CDCl3): δ 8.23 (d, J
= 8.4 Hz, 1H), 7.80−7.73 (m, 3H), 7.57−7.56 (m, 1H), 7.52−7.45 (m,
6H), 7.37 (d, J = 8.4 Hz, 2H), 3.90 (q, J = 7.1 Hz, 2H), 0.85 (t, J = 7.1
Hz, 3H). 13C NMR (100 MHz, CDCl3): δ 168.0, 156.0, 147.8, 156.8,
140.1, 134.8, 133.9, 130.8, 130.6, 129.9, 128.9, 128.5(2), 128.4, 127.3,
127.2, 126.2, 125.3, 61.4, 13.4. FT-IR (neat): νmax 3017, 2986, 1721,
1636, 1574, 1551, 1481, 1404, 1219, 1103, 756, 664 cm−1. HRMS
(ESI): m/z calcd for C24H18ClNO2 [M + H]+ 388.1026, found
388.1104.
Ethyl 2-(4-Bromophenyl)quinoline-3-carboxylate (3n). The crude
residue was then purified by flash column chromatography on silica gel
(10% EtOAc in hexanes) to afford compound 3n (24.9 mg, 0.07
mmol, 85% yield) as a pale yellow solid. Rf = 0.35 (EtOAc/Hex 20/
1
80). Mp: 86−88 °C. H NMR (400 MHz, CDCl3): δ 8.68 (s, 1H),
Ethyl 4-(4-Bromophenyl)-2-phenylquinoline-3-carboxylate (3i).
The crude residue was then purified by flash column chromatography
on silica gel (10% EtOAc in hexanes) to afford compound 3i (13.0 mg,
0.03 mmol, 83% yield) as a yellow solid. Rf = 0.35 (EtOAc/Hex 20/
8.16 (d, J = 8.3 Hz, 1H), 7.93 (d, J = 8.3 Hz, 1H), 7.83 (t, J = 8.3 Hz,
1H), 7.64−7.60 (m, 3H), 7.52 (d, J = 8.3 Hz, 2H), 4.23 (q, J = 7.2 Hz,
2H), 1.16 (t, J = 7.2 Hz, 3H). 13C NMR (100 MHz, CDCl3): δ 167.5,
157.0, 148.4, 139.7, 139.4, 131.8, 131.3, 130.3, 129.5, 128.3, 127.5,
125.9, 125.0, 123.0, 61.7, 13.8. FT-IR (neat): νmax 3017, 2986, 1721,
1620, 1597, 1558, 1481, 1450, 1420, 1265, 1227, 1096 cm−1. HRMS
(ESI): m/z calcd for C18H14BrNO2 [M + H]+ 356.0208, found
356.0286.
1
80). Mp: 138−140 °C. H NMR (400 MHz, CDCl3): δ 8.23 (d, J =
8.4 Hz, 1H), 7.80−7.73 (m, 3H), 7.65 (d, J = 8.4 Hz, 2H), 7.58−7.45
(m, 5H), 7.30 (d, J = 8.4 Hz, 2H), 3.90 (q, J = 7.1 Hz, 2H), 0.85 (t, J =
7.1 Hz, 3H). 13C NMR (100 MHz, CDCl3): δ 168.0, 156.0, 147.8,
145.8, 140.1, 134.4, 131.5, 131.1, 130.6, 129.9, 128.9, 128.5, 128.4,
127.3, 127.1, 126.2, 125.2, 123.0, 61.4, 13.4. FT-IR (neat): νmax 3071,
2986, 2932, 1728, 1636, 1551, 1481, 1443, 1296, 1227, 1103, 694, 664
cm−1. HRMS (ESI): m/z calcd for C24H18BrNO2 [M + H]+ 432.0521,
found 432.0599.
Ethyl 2-(4-Nitrophenyl)quinoline-3-carboxylate (3o). The crude
residue was then purified by flash column chromatography on silica gel
(20% EtOAc in hexanes) to afford compound 3o (21.3 mg, 0.07
mmol, 80% yield) as a yellow solid. Rf = 0.23 (EtOAc/Hex 20/80).
Mp: 146−148 °C. 1H NMR (400 MHz, CDCl3): δ 8.80 (s, 1H), 8.34
(d, J = 8.5 Hz, 2H), 8.18 (d, J = 8.5 Hz, 1H), 7.98 (d, J = 8.0 Hz, 1H),
7.88 (t, J = 8.0 Hz, 1H), 7.79 (d, J = 8.5 Hz, 2H), 7.68 (t, J = 8.0 Hz,
1H), 4.25 (q, J = 7.2 Hz, 2H), 1.17 (t, J = 7.2 Hz, 3H). 13C NMR (100
MHz, CDCl3): δ 166.7, 156.2, 148.4, 147.8, 147.3, 140.0, 132.2, 129.7,
129.6, 128.4, 128.1, 126.2, 124.4, 123.3, 61.8, 13.9. FT-IR (neat): νmax
3017, 2986, 1721, 1620, 1597, 1558, 1481, 1450, 1420, 1373, 1265,
1227, 1096 cm−1. HRMS (ESI): m/z calcd for C18H14N2O4 [M + H]+
323.0954, found 323.1032.
Ethyl 6-Chloro-4-(2-fluorophenyl)-2-phenylquinoline-3-carboxy-
late (3j). The crude residue was then purified by flash column
chromatography on silica gel (10% EtOAc in hexanes) to afford
compound 3j (13.0 mg, 0.03 mmol, 80% yield) as a yellow oil. Rf =
1
0.35 (EtOAc/Hex 20/80). H NMR (400 MHz, CDCl3): δ 8.17 (d, J
= 9.0 Hz, 1H), 7.76−7.70 (m, 3H), 7.54−7.46 (m, 5H), 7.34−7.25 (m,
3H), 3.90 (q, J = 7.1 Hz, 2H), 0.85 (t, J = 7.1 Hz, 3H). 13C NMR (100
MHz, CDCl3): δ 167.5, 160.9, 158.5, 156.5, 146.1, 140.9, 139.8, 133.4,
131.7, 131.5, 131.3, 131.2, 129.1, 128.5(2), 126.2, 124.8, 124.3(2),
122.6, 116.0, 115.8, 61.5, 13.4. FT-IR (neat): νmax 3017, 2986, 2940,
1728, 1636, 1574, 1551, 1474, 1450, 1296, 1219, 1111, 756, 664 cm−1.
HRMS (ESI): m/z calcd for C24H17FClNO2 [M + H]+ 406.0932,
found 406.1010.
Ethyl 2-(Naphthalen-2-yl)quinoline-3-carboxylate (3p). The
crude residue was then purified by flash column chromatography on
silica gel (10% EtOAc in hexanes) to afford compound 3p (23.8 mg,
0.07 mmol, 88% yield) as a pale yellow oil. Rf = 0.34 (EtOAc/Hex 20/
80). 1H NMR (400 MHz, CDCl3): δ 8.87 (s, 1H), 8.22 (d, J = 8.4 Hz,
1H), 8.02 (d, J = 8.4 Hz, 1H), 7.94−7.84 (m, 3H), 7.67 (t, J = 7.6 Hz,
1H), 7.60−7.52 (m, 3H), 7.46 (t, J = 7.0 Hz, 1H), 7.37 (t, J = 7.6 Hz,
1H), 3.85 (q, J = 7.1 Hz, 2H), 0.60 (t, J = 7.1 Hz, 3H). 13C NMR (100
MHz, CDCl3): δ 166.8, 158.1, 148.7, 139.5, 139.1, 133.4, 131.9, 131.8,
129.6, 128.5(2), 128.3, 127.5, 126.4, 126.3(2), 125.7, 125.2, 125.1,
61.1, 13.1. FT-IR (neat): νmax 3055, 2978, 2932, 1721, 1620, 1597,
1558, 1489, 1458, 1427, 1250, 1234, 1204, 1072 cm−1. HRMS (ESI):
m/z calcd for C22H17NO2 [M + H]+ 328.1259, found 328.1338.
Ethyl 2-Methyl-4-phenylquinoline-3-carboxylate (3q). The crude
residue was then purified by flash column chromatography on silica gel
(10% EtOAc in hexanes) to afford compound 3q (13.3 mg, 0.05
mmol, 90% yield) as a yellow solid. Rf = 0.42 (EtOAc/Hex 20/80).
Ethyl 4-Butyl-2-phenylquinoline-3-carboxylate (3k). The crude
residue was then purified by flash column chromatography on silica gel
(10% EtOAc in hexanes) to afford compound 3k (17.1 mg, 0.05
1
mmol, 91% yield) as a yellow oil. Rf = 0.42 (EtOAc/Hex 20/80). H
NMR (400 MHz, CDCl3): δ 8.17 (d, J = 8.4 Hz, 1H), 8.09 (d, J = 8.4
Hz, 1H), 7.76 (t, J = 7.6 Hz, 1H), 7.69−7.67 (m, 2H), 7.60 (t, J = 7.6
Hz, 1H), 7.48−7.42 (m, 3H), 4.13 (q, J = 7.1 Hz, 2H), 3.15−3.11 (m.
2H), 1.80−1.73 (m, 2H), 1.52 (sext, J = 7.4 Hz, 2H), 1.03−0.97 (m,
6H). 13C NMR (100 MHz, CDCl3): δ 169.1, 156.4, 147.7, 147.4,
140.7, 130.5, 130.2, 128.6, 128.4, 128.3, 126.9(2), 125.3, 124.1, 61.4,
33.2, 29.7, 23.3, 13.8, 13.6. FT-IR (neat): νmax 3063, 2955, 2924, 2870,
1721, 1620, 1574, 1497, 1458, 1404, 1288, 1234, 1165, 1103 cm−1.
HRMS (ESI): m/z calcd for C22H23NO2 [M + H]+ 334.1729, found
334.1807.
1
Mp: 85−87 °C. H NMR (400 MHz, CDCl3): δ 8.07 (d, J = 8.4 Hz,
1H), 7.74−7.70 (m, 1H), 7.58 (d, J = 8.4 Hz, 1H), 7.50−7.47 (m,
3H), 7.45−7.41 (m, 1H), 7.38−7.35 (m, 2H), 4.06 (q, J = 7.1 Hz,
2H), 2.79 (s, 3H), 0.95 (t, J = 7.1 Hz, 3H). 13C NMR (100 MHz,
CDCl3): δ 168.5, 154.6, 147.7, 146.2, 135.7, 130.2, 129.4, 128.9, 128.4,
128.2, 127.4, 126.5, 126.4, 125.2, 31.3, 23.8, 13.6. FT-IR (neat): νmax
2978, 2932, 1728, 1566, 1489, 1443, 1404, 1296, 1227, 1180, 1065
cm−1. HRMS (ESI): m/z calcd for C19H17NO2 [M + H]+ 292.1259,
found 292.1338.
Ethyl 2-p-Tolylquinoline-3-carboxylate (3l). The crude residue
was then purified by flash column chromatography on silica gel (10%
EtOAc in hexanes) to afford compound 3l (21.6 mg, 0.07 mmol, 90%
1
yield) as a yellow oil. Rf = 0.34 (EtOAc/Hex 20/80). H NMR (400
MHz, CDCl3): δ 8.62 (s, 1H), 8.17 (d, J = 8.4 Hz, 1H), 7.91 (d, J = 8.4
Hz, 1H), 7.80 (t, J = 7.6 Hz, 1H), 7.59 (t, J = 7.6 Hz, 1H), 7.54 (d, J =
8.0 Hz, 2H), 7.28−7.26 (m, 1H), 4.22 (q, J = 7.1 Hz, 2H), 2.42 (s,
3H), 1.13 (t, J = 7.1 Hz, 3H). 13C NMR (100 MHz, CDCl3): δ 168.1,
158.1, 148.5, 138.9, 138.5, 137.8, 131.4, 129.5, 128.9, 128.5, 128.2,
127.0, 125.8, 125.5, 61.5, 21.3, 13.8. FT-IR (neat): νmax 3017, 2932,
1721, 1620, 1458, 1427, 1219, 1096 cm−1. HRMS (ESI): m/z calcd for
C19H17NO2 [M + H]+ 292.1259, found 292.1338.
Ethyl 4-Phenyl-2-propylquinoline-3-carboxylate (3r). The crude
residue was then purified by flash column chromatography on silica gel
(10% EtOAc in hexanes) to afford compound 3r (14.7 mg, 0.05 mmol,
91% yield) as a pale yellow solid. Rf = 0.42 (EtOAc/Hex 20/80). Mp:
85−87 °C. 1H NMR (400 MHz, CDCl3): δ 8.10 (d, J = 8.4 Hz, 1H),
805
dx.doi.org/10.1021/jo202281x | J. Org. Chem. 2012, 77, 801−807

The Journal of Organic Chemistry
Note
7.73−7.69 (m, 1H), 7.57 (d, J = 8.4 Hz, 1H), 7.50−7.35 (m, 6H), 4.04
(q, J = 7.2 Hz, 2H), 3.02−2.98 (m, 2H), 1.88 (sext, J = 7.4 Hz, 3H),
1.05 (t, J = 7.4 Hz, 3H), 0.95 (t, J = 7.2 Hz, 3H). 13C NMR (100 MHz,
CDCl3): δ 168.5, 158.3, 147.8, 146.3, 135.8, 130.1, 129.4, 129.0, 128.4,
128.2, 127.4, 126.4, 126.3, 125.1, 61.2, 39.2, 23.1, 14.2, 13.6. FT-IR
(neat): νmax 3017, 2963, 2870, 1721, 1566, 1481, 1458, 1404, 1219,
1065 cm−1. HRMS (ESI): m/z calcd for C21H21NO2 [M + H]+
320.1572, found 320.1650.
Chem. Soc. 2009, 131, 13888. (c) Dinakaran, M.; Senthilkumar, P.;
Yogeswari, P.; China, A.; Nagaraja, V.; Sriram, D. Med. Chem. 2008, 4,
482.
(2) (a) Lovely, C. J.; Bararinayana, V. Curr. Org. Chem. 2008, 12,
1431. (b) Behenna, D. C.; Stockdill, J. L.; Stoltz, B. M. Angew. Chem.,
Int. Ed. 2008, 47, 2365. (c) Andries, K.; Verhasselt, P.; Guillemont, J.;
Gohlmann, H. W. H.; Neefs, J.-M.; Winkler, H.; Van Gestel, J.;
̈
Timmerman, P.; Zhu, M.; Lee, E.; Williams, P.; de Chaffoy, D.;
Huitric, E.; Hoffner, S.; Cambau, E.; Truffot-Pernot, C.; Lounis, N.;
Jarlier, V. Science 2005, 307, 223.
Ethyl 2-Hexyl-4-phenylquinoline-3-carboxylate (3s). The crude
residue was then purified by flash column chromatography on silica gel
(10% EtOAc in hexanes) to afford compound 3s (16.1 mg, 0.04 mmol,
(3) (a) Bax, B. D.; Chan, P. F.; Eggleston, D. S.; Fosberry, A.; Gentry,
D. R.; Gorrec, F.; Giordano, I.; Hann, M. M.; Hennessy, A.; Hibbs, M.;
Huang, J.; Jones, E.; Jones, J.; Brown, K. K.; Lewis, C. J.; May, E. W.;
Saunders, M. R.; Singh, O.; Spitzfaden, C. E.; Shen, C.; Shillings, A.;
Theobald, A. J.; Wohlkonig, A.; Pearson, N. D.; Gwynn, M. N. Nature
2010, 466, 935. (b) El-Gazzar, A. B. A.; Hafez, H. N.; Nawwar, G. A.
M. Eur. J. Med. Chem. 2009, 44, 1427. (c) Kumar, S.; Bawa, S.; Gupta,
H. Mini Rev. Med. Chem. 2009, 9, 1648.
1
88% yield) as a pale yellow oil. Rf = 0.42 (EtOAc/Hex 20/80). H
NMR (400 MHz, CDCl3): δ 8.10 (d, J = 8.4 Hz, 1H), 7.73−7.69 (m,
1H), 7.57 (d, J = 8.4 Hz, 1H), 7.49−7.35 (m, 6H), 4.04 (q, J = 7.2 Hz,
2H), 3.04−3.00 (m, 2H), 1.89−1.81 (m, 2H), 1.45 (t, J = 7.2 Hz, 2H),
1.34−1.30 (m, 4H), 0.95 (t, J = 7.2 Hz, 3H), 0.89 (t, J = 7.0 Hz, 3H).
13C NMR (100 MHz, CDCl3): δ 168.5, 158.5, 147.8, 146.3, 135.9,
130.1, 129.4, 129.0, 128.4, 128.2, 127.3, 126.4, 126.3, 125.1, 61.2, 37.3,
31.7, 29.8, 29.4, 22.5, 14.0, 13.6. FT-IR (neat): νmax 3024, 2955, 2932,
2862, 1721, 1643, 1556, 1489, 1458, 1404, 1219, 1173, 1065 cm−1.
HRMS (ESI): m/z calcd for C24H27NO2 [M + H]+ 362.2042, found
362.2120.
(2-Phenylquinolin-3-yl)(piperidin-1-yl)methanone (3t). The
crude residue was then purified by flash column chromatography on
silica gel (10% EtOAc in hexanes) to afford compound 3t (19.6 mg,
0.06 mmol, 75% yield) as a yellow oil. Rf = 0.03 (EtOAc/Hex 20/80).
1H NMR (400 MHz, CDCl3): δ 8.24 (s, 1H), 8.18 (d, J = 8.4 Hz, 1H),
7.90−7.85 (m, 3H), 7.77 (t, J = 7.2 Hz, 1H), 7.58 (t, J = 7.2 Hz, 1H),
7.51−7.45 (m, 3H), 3.72−3.66 (m, 1H), 3.53−3.47 (m, 1H), 2.93−
2.86 (m, 1H), 2.73−2.67 (m, 1H), 1.58−1.50 (m, 1H), 1.44−1.30 (m,
3H), 1.18−1.09 (m, 1H), 0.62−0.53 (m, 1H). 13C NMR (100 MHz,
CDCl3): δ 168.4, 155.2, 148.0, 139.4, 136.0, 130.5, 130.1, 129.6,
129.2(2), 128.5, 127.7, 127.1, 126.5, 47.7, 42.5, 25.2, 24.9, 24.1. FT-IR
(neat): νmax 3017, 2947, 2862, 1620, 1474, 1443, 1219, 1026 cm−1.
HRMS (ESI): m/z calcd for C21H20N2O [M + H]+ 317.1576, found
317.1654.
(4) Koenigs, W. Chem. Ber. 1879, 12, 453.
(5) Ahmad, N. M.; Li, J. J. Adv. Heterocycl. Chem. 2003, 84, 1.
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Kleinberg, A.; Laufer, R.; Mulvihill, K. M.; Nigro, A.; Rastogi, P.;
Sherman, D.; Siu, K. W.; Steinig, A. G.; Wang, T.; Werner, D.; Crew,
A. P.; Mulvihill, M. J. Synthesis 2010, 1678. (b) Yang, D.; Jiang, K.; Li,
J.; Xu, F. Tetrahedron 2007, 63, 7654. (c) Doebner, O.; Miller, W.
Chem. Ber. 1881, 14, 2812. (d) Skraup, Z. H. Chem. Ber. 1880, 13,
2086.
(7) (a) De Paolis, O.; Teixeira, L.; Torok, B. Tetrahedron Lett. 2009,
̈
̈
50, 2939. (b) Guo, Q.-S.; Du, D.-M.; Xu, J. Angew. Chem., Int. Ed.
2008, 47, 759. Shindoh, N.; Tokuyama, H.; Takemoto, Y.; Takasu, K.
J. Org. Chem. 2008, 73, 7451.
(8) (a) C. Majumdar, K.; Debnath, P.; De, N.; Roy, B. Curr. Org.
Chem. 2011, 15, 1760. (b) Yamazaki, S.; Morikawa, S.; Miyazaki, K.;
Takebayashi, M.; Yamamoto, Y.; Morimoto, T.; Kakiuchi, K.; Mikata,
Y. Org. Lett. 2009, 11, 2796. (c) Campeau, L.-C.; Stuart, D. R.; Leclerc,
J.-P.; Bertrand-Laperle, M. g.; Villemure, E.; Sun, H.-Y.; Lasserre, S.;
Guimond, N.; Lecavallier, M.; Fagnou, K. J. Am. Chem. Soc. 2009, 131,
1-(2-Phenylquinolin-3-yl)ethanone (3u). The crude residue was
then purified by flash column chromatography on silica gel (10%
EtOAc in hexanes) to afford compound 3u (15.2 mg, 0.06 mmol, 65%
3291. (d) Kouznetsov, V. V.; Men
Org. Chem. 2005, 9, 141.
́ ́
dez, L. Y. V.; Gomez, C. M. M. Curr.
1
yield) as a yellow oil. Rf = 0.17 (EtOAc/Hex 20/80). H NMR (400
(9) Li, H.; Xu, X.; Yang, J.; Xie, X.; Huang, H.; Li, Y. Tetrahedron Lett.
2011, 52, 530.
(10) (a) Boren, B. C.; Narayan, S.; Rasmussen, L. K.; Zhang, L.;
Zhao, H.; Lin, Z.; Jia, G.; Fokin, V. V. J. Am. Chem. Soc. 2008, 130,
8923. (b) Chen, W.; Cao, J.; Huang, X. Org. Lett. 2008, 10, 5537.
(c) Xi, Z.; Li, P. Angew. Chem., Int. Ed. 2000, 39, 2950.
(11) (a) Cai, S.; Xiang, S.; Zeng, J.; Gorityala, B. K.; Liu, X.-W. Chem.
Commun. 2011, 47, 8676. (b) Cai, S.; Kishan Gorityala, B.; Ma, J.;
Leow, M. L.; Liu, X.-W. Org. Lett. 2011, 13, 1072. (c) Vedachalam, S.;
Wong, Q.-L.; Maji, B.; Zeng, J.; Ma, J.; Liu, X.-W. Adv. Synth. Catal.
2011, 353, 219. (d) Bai, Y.; Zeng, J.; Ma, J.; Gorityala, B. K.; Liu, X.-W.
J. Comb. Chem. 2010, 12, 696. (e) Vedachalam, S.; Zeng, J.; Gorityala,
B. K.; Antonio, M.; Liu, X.-W. Org. Lett. 2009, 12, 352.
MHz, CDCl3): δ 8.11 (s, 1H), 8.08 (d, J = 8.4 Hz, 1H), 7.84 (d, J = 7.3
Hz, 2H), 7.79−7.75 (m, 2H), 7.63 (t, J = 7.3 Hz, 1H), 7.56−7.47 (m,
3H), 2.74 (s, 3H). 13C NMR (100 MHz, CDCl3): δ 196.7, 156.6,
148.0, 137.2, 136.7, 133.7, 132.2, 131.0, 130.1, 128.7, 128.6, 128.1,
126.6, 125.2, 24.2. FT-IR (neat): νmax 3061, 3019, 2958, 1663, 1568
cm−1. HRMS (ESI): m/z calcd for C17H13NO [M + H]+ 248.0997,
found 248.1075.
ASSOCIATED CONTENT
■
S
* Supporting Information
1H and 13C NMR spectra for compounds 3a−u. This material
is available free of charge via the Internet at http://pubs.acs.org.
(12) Pasunooti, K. K.; Chai, H.; Jensen, C. N.; Gorityala, B. K.;
Wang, S.; Liu, X.-W. Tetrahedron Lett. 2011, 52, 80.
AUTHOR INFORMATION
Corresponding Author
*E-mail: xuewei@ntu.edu.sg.
■
(13) (a) Patil, N. T.; Raut, V. S. J. Org. Chem. 2010, 75, 6961.
(b) Lekhok, K. C.; Prajapati, D.; Boruah, R. C. Synlett 2008, 655.
(14) Korivi, R. P.; Cheng, C.-H. J. Org. Chem. 2006, 71, 7079.
(15) (a) Rudolph, M.; Hashmi, A. S. K. Chem. Commun. 2011, 47,
6536 and references cited therein. (b) Praveen, C.; Kalyanasundaram,
ACKNOWLEDGMENTS
■
A.; Perumal, P. T. Synlett 2010, 777. (c) Trillo, B.; Lop
Montserrat, S.; Ujaque, G.; Castedo, L.; Lledos, A.; Mascarenas, J. L.
Chem.Eur. J. 2009, 15, 3336. (d) Barluenga, J.; Fernan
Rodríguez, M. A.; García-García, P.; Aguilar, E. J. Am. Chem. Soc.
2008, 130, 2764. (e) Hashmi, A. S. K.; Wolfle, M.; Ata, F.; Hamzic,
́
ez, F.;
Financial support from Nanyang Technological University
(NTU RG50/08), Ministry of Education, Singapore
(MOE2009-T2-1-030), and scholarship support from the
Agency for Science, Technology and Research (A*STAR) are
gratefully acknowledged.
́
̃
́
dez-
̈
́
M.; Salathe, R.; Frey, W. Adv. Synth. Catal. 2006, 348, 2501.
(16) Arcadi, A.; Chiarini, M.; Di Giuseppe, S.; Marinelli, F. Synlett
2003, 203.
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The Journal of Organic Chemistry
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