Bismuth triflate-L(-)-proline catalyzed synthesis of chiral 2,5-diaryl-2,3-dihydropyrano[2,3-b]quinolin-4-ones

Article abstract of DOI:10.1002/jhet.762

The synthesis of chiral (2R) 2,5-diaryl-2,3-dihydropyrano[2,3-b]quinolin-4- ones, was achieved, at ambient temperature, by the reaction of 3-acetyl-4-aryl-carbostyril and an aldehyde, in the presence of bismuth triflate-L(-)-proline complex, formed in situ. The products were obtained in 62-78% yield with high enantioselectivity (72-96% ee). Copyright

Full text of DOI:10.1002/jhet.762

1302
Bismuth Triflate–L(ꢀ)-Proline Catalyzed Synthesis of Chiral
Vol 48
2,5-Diaryl-2,3-dihydropyrano[2,3-b]quinolin-4-ones
Nitu Mahajan,a Surrinder Koul,b and Tej K. Razdana*
aDepartment of Chemistry, University of Jammu, Ambedkar Road, Jammu 180006, India
bIndian Institute of Integrated Medicine, Canal Road, Jammu 180006, India
*E-mail: tk_razdan@rediffmail.com
Received June 22, 2010
DOI 10.1002/jhet.762
Published online 4 August 2011 in Wiley Online Library (wileyonlinelibrary.com).
The synthesis of chiral (2R) 2,5-diaryl-2,3-dihydropyrano[2,3-b]quinolin-4-ones, was achieved, at am-
bient temperature, by the reaction of 3-acetyl-4-aryl-carbostyril and an aldehyde, in the presence of bis-
muth triflate–L(ꢀ)-proline complex, formed in situ. The products were obtained in 62–78% yield with
high enantioselectivity (72–96% ee).
J. Heterocyclic Chem., 48, 1302 (2011).
complicated by one or other drawback, such as multi-
stage processes and operational difficulty, harsh reaction
conditions, low to moderate yield, difficult availability
of substrates, and difficult stereochemical control. There-
fore, there is ample scope for the development of effi-
cient synthetic methodologies for the preparation of
these biologically important compounds.
INTRODUCTION
Pyranoquinoline nucleus constitutes the core moiety of
a small group of naturally occurring bioactive alkaloids
[1], mostly found in the plants belonging to family Ruta-
ceae [2]. These alkaloids display a wide array of biologi-
cal activity [3], such as antimicrobial [4], antiasthmatic
[5], anti-inflammatory [6], psychotropic [7], immune-
modulating [8], protein glysomal GAPDH enzyme inhibi-
ting [9], and insect antifeedant [10] activity. They are
believed to be useful in the treatment of rheumatoid ar-
thritis, cirrhosis, fibrosis, prevention of graft rejection,
and diabetic complications [11]. Additionally, these com-
pounds may also find use in the photochemical applica-
tions [12]. With all these potential pharmacological
properties, the synthesis of pyranoquinoline derivatives
continues to receive significant attention.
2-Arylpyrano[2,3-b]quinolin-4-ones are the structural
analogues of the privileged naturally occurring flavones
[21]. Therefore, these compounds are expected to exhibit
interesting biological properties. Normally, an enantiose-
lective synthesis of pyranone derivatives possessing C-2
chiral centre is a difficult process. A few strategies known
for the asymmetric synthesis of chiral pyranone deriva-
tives include resolution of the related alcohols [22], sub-
stitution reactions [23] and addition reactions of 2-chro-
menes [24], using Cu (I) and Et2Zn. During our studies
on the exploration of the catalyst potential and limitations
of the nontoxic and readily available bismuth salts, in the
preparation of heterocyclic compounds, we got interested
in the development of a suitable methodology for the
preparation of chiral pyranoquinoline derivatives. We
opined that asymmetrical catalysis would be an ideal
approach for the preparation of optically active pyrano-
quinolines. In this article, we report a simple and efficient
two-step synthesis of 2,5-diaryl-2,3-dihydropyrano[2,3-
b]quinolin-4-ones, from carbostyril derivatives, under
ambient reaction conditions, using a chiral Bi3þ-L(ꢀ)
Several synthetic protocols, involving cycloaddition
reactions, such as Diel’s–Alder reaction [13] and 1,3-
dipolar addition of nitrile amines, nitrones, and nitrile
oxides [14], for the preparation of pyranoquinoline
derivatives are known. These compounds have also been
prepared by the oxidative cyclization with DDQ [15],
Provost reaction [16], FeCl3-NaI reductive cyclization
[17], organolithiation of dihyropyrans and furans [18],
cyclization with PPA [19], and ring cleavage of cyclo-
pentanone carboxamides [20]. Despite their attractive-
ness, most of the known synthetic methodologies are
C
V
2011 HeteroCorporation

November 2011
Bismuth Triflate–L(ꢀ)-Proline Catalyzed Synthesis of Chiral
1303
2,5-Diaryl-2,3-dihydropyrano[2,3-b]quinolin-4-ones
Table 1
Percent yield of 3a–3k.
Compounds
R1
R2
R3
R4
% Yield
M.P (ꢁC)
[a]D
Time (h)
ee (%)a
3a
3b
3c
3d
3e
3f
3g
3h
3i
H
H
H
H
H
Cl
H
H
H
H
Br
H
H
H
H
H
H
H
H
H
H
H
H
OCH3
Cl
F
Br
H
H
H
H
H
H
70
76
72
68
70
64
67
78
69
62
74
205
195
þ55ꢁ
þ58ꢁ
þ52ꢁ
þ50ꢁ
þ51ꢁ
þ52ꢁ
þ54ꢁ
þ54ꢁ
þ53ꢁ
þ45ꢁ
þ52ꢁ
25
28
24
25
24
26
24
24
28
38
26
90
89
91
96
91
88
72
90
92
87
89
176
165
215
188
199
173
Cl
AOACH2AOA
OCH3
CH3
NO2
H
OCH3
H
H
H
218 (dec.)
225 (dec.)
210
3j
3k
a The ee were determined by HPLC, using Diacel OD-H column; solvent: hexane-isoPrOH.
proline complex. It is pertinent to mention here that only
few examples of the enantioselective reactions involving
a chiral bismuth catalyst [25] are known.
pyrano[2,3-b]quinolones, 3a, in good yield (Table 1).
Optimization of the catalyst composition revealed that,
for the maximum yield of 3a, the ideal composition of
the catalyst was 10 mol % of bismuth triflate, 15 mol %
of L(ꢀ)-proline and 15 mol % of Et3N. We also
observed that the presence of moisture was detrimental
to intramolecular conjugate addition.
RESULTS AND DISCUSSION
Our strategy for the preparation of optically active 2,5-
diaryl-2,3-dihydropyrano[2,3-b]quinolin-4-ones,
from
With optimized conditions in hand, we prepared com-
pounds 3a–3k (Scheme 1) by stirring compound 1, alde-
hyde 2a–2k (1:1.4 mol), and the catalyst mixture at
room temperature. The reactions were monitored by
TLC. On completion of the reaction (24–28 h) and usual
work up, the products 3a–3k were obtained in 62–78%
yield (Table 1); the lowest yield was obtained when
4-nitrobenzaldehyde was used in the reaction. The prod-
ucts were purified by column chromatography on silica
gel, followed by crystallization, and analyzed by spectral
carbostyril derivatives, involved the introduction of an
unsaturated carbonyl side chain, adjacent to the imido car-
bonyl, of the compound. This side chain may provide the
basic site for interaction with a chiral Bi3þ catalyst and
permit intramolecular carbon–oxygen bond formation, via
enolization of the carbostyril imido carbonyl group.
Accordingly, our protocol consisted of 3-acetyl-4-arylcar-
bostyril, an aldehyde, and a suitable Bi3þ ion-based chiral
catalyst. 3-Acetyl-4-(3-carboxyphenyl)carbostyril 1, was
used as a model substrate for the present reaction.
13
methods (IR, 1H NMR, C NMR, DEPT 135ꢁ, and
1
HRMS) and elemental analysis. In their H NMR spec-
For the asymmetric synthesis of the desired pyrano-
quinolines, we surveyed bismuth salts, which could be
used in the presence of L(ꢀ) proline to provide a suita-
ble catalyst for the one-pot condensation-intramolecular
conjugate addition reaction of 3-acetyl-4-(3-carboxy-
phenyl) carbostyril 1 and an aldehyde. After a few
experiments, we observed that bismuth triflate–L(ꢀ)-
proline was the catalyst of choice and dry acetonitrile
was the appropriate solvent for the preparation of 2-phe-
nyl-5-(3-carboxyphenyl)-2,3-dihydropyrano[2,3-b]quino-
lin-4-one at room temperature. However, the yield of
the products was not encouraging. This could be attrib-
uted to the possible coordination of carbostyril nitrogen
to the catalyst, under the reaction conditions, and the
difficulty in the enolization of the amido carbonyl. We
assumed that this difficulty may be surmounted by mod-
ifying the reaction conditions such that the abstraction
of hydrogen from the amido nitrogen of the carbostyril
is facilitated. In fact, bismuth triflate–L(ꢀ)-proline
and Et3N in a single catalyst provided the desired
tra (See Experimental section), compounds 3a–3k dis-
played a typical ABX pattern with resonance signals
near d 2.80 (1H, dd, J ¼ 16.5, 13.2 Hz), 3.08 (1H, dd, J
¼ 16.5, 3.2 Hz) and 5.06 (1H, dd, J ¼ 13.2, 3.2 Hz),
besides the expected aromatic proton signals and car-
boxylic proton signal, d 11.2. The 13C NMR coupled
with DEPT 135ꢁ placed the C-3 CH2 near dC 44.5. In
addition to the expected aromatic carbon signals, the
13C NMR displayed resonance signals near dC 78.3–80.1
(C-2), 198.1 (C-4), and 167.5 (COOH). The mass frag-
mentation agreed with the assigned structures. The com-
pounds showed optical rotation [a]D (20ꢁC) ¼ þ45ꢁ to
þ58ꢁ (c. 0.5, EtOH; Table 1). The enentioselective
excess (Table 1) was determined by HPLC, using Diacel
OD-H column and hexane-isoPrOH as eluent. The ster-
eochemistry at C-2 was fixed on the basis of the com-
parison of the multiplicity and coupling constant of the
carbinylic proton (H-2) with the reported data for 2-aryl
chromanans[26c].
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

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N. Mahajan, S. Koul, and T. K. Razdan
Vol 48
Scheme 1. Preparation of 2,5-diaryl-2,3-dihydropyrano[2,3-b]quinolin-4-ones.
The most plausible mechanism (Scheme 2) for the
intramolecular oxa-Micheal addition [27], probably via
the formation of a transition state T-1 with the catalyst
[27a], to form chiral 2,5-diaryl-2,3-dihydropyrano[2,3-
b]quinolin-4-ones. Triethylamine may be facilitating the
enolization of the carbostyril amido group by the facile
removal of proton from the ring nitrogen.
reaction may involve the Lewis acid-catalyzed Claisen–
Schmidt condensation [27] of 3-acetyl-4-aryl-carbostyril,
such as compound 1, with an arylaldehyde, to generate
a a,b-unsaturated ketone. Subsequent enolization of the
activated carbonyl as also the carbostyril amido group,
in the presence of the catalyst Bi3þ-L(ꢀ) proline
complex, formed in situ, may bring about asymmetric
In conclusion, we have developed an efficient and
simple catalytic asymmetric method for the preparation
Scheme 2. Probable mechanism for the formation of (2R) 2,5-diaryl-2,3-dihydropyrano [2,3-b]quinolin-4-ones.
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

November 2011
Bismuth Triflate–L(ꢀ)-Proline Catalyzed Synthesis of Chiral
1305
2,5-Diaryl-2,3-dihydropyrano[2,3-b]quinolin-4-ones
119.5, 123.4, 124.8, 126.0 (2C), 127.9, 128.0, 128.2, 128.5,
128.9, 129.0 (2C), 129.5, 131.5, 132.2, 132.5, 138.3, 140.1,
148.2, 151.5, 168.6, 179.9, 194.6. HRMS: m/z (rel.int.)
395.1166 (Mþ) (48) (Calc. for C25H17NO4, 395.1158), 394
(62), 351 (100), 350 (78), 248 (62), 220 (48), 154 (43), 116
(65), 91 (66), 77 (80). Anal.: CHN (%): Found; C, 75.90; H,
4.38; N, 3.59; Calc.; C, 75.94; H, 4.33; N, 3.54. HPLC: sol-
vent, n-hexane-isoPrOH (8:2 v/v); tr (minor), 8.58 min; tr
(major), 10.65 min.
of optically active (2R) 2-phenyl-5-(3-carboxyphenyl)-
2,3-dihydropyrano[2,3-b]quinolin-4-ones, from easily ac-
cessible 3-acetyl-4-arylcarbostyrils, using chiral Bi3þ
-
L(ꢀ) proline complex, formed in situ, as catalyst. Cur-
rent research efforts are directed toward the scope of
this process in the synthesis of other optically active
nitrogen heterocyclic compounds.
5-(3-Carboxyphenyl)-2-(4-methoxyphenyl)-2H-pyrano[2,3-
b]quinolin-4(3H)-one, (3b). IR: umax cmꢀ1 3150, 1713, 1685,
1595, 1460, 1440, 1410, 1360, 1280, 1255, 1215, 976, 930. H
EXPERIMENTAL
1
Melting points are uncorrected and were determined on Per-
fit melting point apparatus. IR spectra were recorded on
Brucker 4800 IR spectrometer. 1H NMR (200 MHz) and 13C
NMR (50.3 MHz) spectra were recorded in CDCl3, using a
Brucker AcDPX-200 spectrometer; some spectra were
recorded on Varian Gemini 300 MHz instrument, using TMS
as standard. HRMS were recorded at 70 eV on JEOL D-300
mass spectrometer; CHN analysis was done on Fison Model
EA 1108 elemental analyzer. [a]D was measured on Perkin-
Elmer 241 polarimeter. TLC was performed on 0.5-mm thick
plates, using silica gel-G (BDH) adsorbent. Column chroma-
tography was performed on silica gel (mesh size 60–120
BDH). The enantiomeric excess (ee) of the products were
determined by HPLC, using Diacel OD-H column and solvent
system n-hexane-isoPrOH as eluant; retention times are given
with the spectral data of individual compounds. The calculated
mass values are based on the values obtained by Chem 4-D
Draw (Chemical Innovation) software.
NMR(CDCl3): d 2.81 (1H, dd, J ¼ 16.8, 2.7 Hz), 3.04 (1H,
dd, J ¼ 16.7, 13.3 Hz), 3.73 (3H, s), 5.20 (1H, dd, J ¼ 13.3,
2.7 Hz), 6.88 (2H, d, J ¼ 8.8 Hz), 7.16 (2H, d, J ¼ 8.8 Hz),
7.28 (1H, m), 7.32 (1H, dd, J ¼ 8.2, 2.6 Hz), 7.38 (1H, d, J ¼
7.8 Hz), 7.52 (1H, d, J ¼ 8.1 Hz), 7.66 (1H, dd, J ¼ 7.8, 2.1
Hz), 8.02 (1H, dd, J ¼ 8.1, 2.1 Hz), 8.20 (1H, dd, J ¼ 7.8, 2.1
Hz), 8.36 (1H, d, J ¼ 2.1 Hz), 11.23 (1H, s br exch. D2O).
13C NMR (CDCl3): dC 44.8, 56.1, 78.9, 107.5, 113.8 (2C),
123.7, 126.4, 126.6, 126.7, 127.6 (2C), 127.7, 128.4, 128.5,
129.6, 130.5, 132.5, 135.3, 136.7, 146.3, 148.5, 158.5, 168.1,
178.4, 194.7. HRMS: m/z at (rel.int.) 425.1272 (Mþ) (45),
(Calc. for C26H19NO5, 425.1263), 424 (60), 381 (83), 380
(100), 248 (71), 220 (53), 154 (36), 132 (76), 118 (53), 107
(61), 93 (88). Anal.: CHN (%): Found; C, 73.46; H, 4.58;
N, 3.22; Calc.; C, 73.40; H, 4.50; N, 3.29. HPLC: solvent,
n-hexane-isoPrOH (8:2 v/v); tr (minor), 6.85 min; tr (major),
7.49 min.
5-(3-Carboxyphenyl)-2-(4-chlorophenyl)-2H-pyrano[2,3-
b]quinolin-4(3H)-one, (3c). IR: umax cmꢀ1 3154, 1716, 1686,
1595, 1460, 1440, 1410, 1360, 1280, 1255, 1215, 976, 930. H
General method for the preparation of 2,5-diaryl-2,3-
dihydropyrano[2,3-b]quinolin-4-ones. To a mixture of 3-ace-
tyl-4-(3-carboxy)phenylcarbostyril, compound 1 (1 ꢂ 10ꢀ3
mol) and aldehyde 2a–2k (1.4 ꢂ 10ꢀ3 mol) in dry acetonitrile
(10 mL) were added with a mixture of bismuth triflate (10 mol
%) and L(ꢀ)-proline (15 mol %) in dry acetonitrile (5 mL),
stirred separately at ice-salt bath temperature for 1 h. The reac-
tion mixture was stirred further for 1.5 h, under similar condi-
tions, and Et3N (15 mol %) was added. After stirring for
another 3 h, at the same temperature, the reaction mixture was
brought to room temperature and stirred further for 20–23 h.
The reaction was monitored by TLC on silica gel G plates
using CHCl3-EtOAc (9:1 v/v). On completion of the reaction,
the solvent was removed under vacuum. The residue was
diluted with water and extracted with ethyl acetate. The or-
ganic layer was washed with brine solution and water, dried
over anhydrous Na2SO4, filtered, concentrated, and subjected
to column chromatography over silica gel, using graded sol-
vent system of CH2Cl2-EtOAc (9:1, 7:3, 1:1 v/v). The com-
pounds 3a–3k were obtained with CH2Cl2-EtOAc (1:1 v/v).
The compounds were further purified by crystallization from
hot methanol.
5-(3-Carboxyphenyl)-2-phenyl-2H-pyrano[2,3-b]quinolin-
4(3H)-one, (3a). IR: umax cmꢀ1 3125, 1710, 1685, 1597,
1460, 1440, 1410, 1360, 1282, 1262, 1210, 1158, 1040, 930.
1H NMR: d 2.83 (1H, dd, J ¼ 16.8, 2.7 Hz), 3.06 (1H, dd, J
¼ 16.8, 13.4 Hz), 5.27 (1H, dd, J ¼ 13.4, 2.7 Hz), 7.28–7.30
(5H, m), 7.33 (1H, dd, J ¼ 8.2, 2.0 Hz), 7.38 (1H, d, J ¼ 7.8
Hz), 7.52 (1H, d, J ¼ 8.1 Hz), 7.66 (1H, dd, J ¼ 7.8, 2.1 Hz),
7.80 (1H, dd, J ¼ 8.1, 2.0 Hz), 8.01 (1H, dd, J ¼ 8.1, 2.1 Hz),
8.23 (1H, dd, J ¼ 7.8, 2.1 Hz), 8.28 (1H, d, J ¼ 2.1 Hz),
11.23 (1H, s br, CO2H). 13C NMR (CDCl3): dC 44.5, 79.2,
1
NMR: d 2.84 (1H, dd, J ¼ 16.8, 2.6 Hz), 3.06 (1H, dd, J ¼
16.8, 13.4 Hz), 5.18 (1H, dd, J ¼ 13.4, 2.6 Hz), 7.23 (2H, d, J
¼ 8.5 Hz), 7.28 (1H, d, J ¼ 7.6 Hz), 7.33 (1H, dd, J ¼ 8.2,
2.0 Hz), 7.38 (2H, d, J ¼ 8.5 Hz), 7.52 (1H, dd, J ¼ 8.1, 2.0
Hz), 7.65 (1H, dd, J ¼ 7.6, 2.1 Hz), 7.80 (1H, m), 8.01 (1H,
dd, J ¼ 8.1, 2.1 Hz), 8.20 (1H, dd, J ¼ 7.8, 2.1 Hz), 8.34 (1H,
d, J ¼ 2.1 Hz), 11.23 (1H, s br exch. D2O, CO2H). 13C NMR
(CDCl3): dC 44.7, 78.6, 107.4, 123.7, 126.4, 126.7, 127.7 (2C),
128.1, 128.3, 128.5, 128.7, 129.1 (2C), 129.5, 130.5, 132.7,
133.1, 135.1, 139.1, 147.9, 148.8, 167.9, 178.5, 194.5. HRMS:
m/z at 431.0776, 429.0775 (Calc. for C25H16ClNO4, 429.0768,
431.0768) (Mþ) (35), 387 (48), 385 (52), 384 (86), 384 (100),
248 (62), 220 (49), 154 (62), 136 (49), 113 (64), 111 (61), 107
(64). Anal.: CHN (%): Found; C, 69.89; H, 3.78; N, 3.21;
Calc.; C, 69.85; H, 3.75; N, 3.26. HPLC: solvent, n-hexane-
isoPrOH (7.5:2.5 v/v); tr (minor), 8.45 min; tr (major),
9.69 min.
5-(3-Carboxyphenyl)-2-(4-fluorophenyl)-2H-pyrano[2,3-
b]quinolin-4(3H)-one, (3d). IR: umax cmꢀ1 3150, 1710,
1680, 1599, 1460, 1440, 1410, 1360, 1282, 1262, 1206, 936.
1H NMR: d 2.84 (1H, dd, J ¼ 16.8, 2.8 Hz), 3.10 (1H, dd, J
¼ 16.8, 13.4 Hz), 5.20 (1H, dd, J ¼ 13.4, 2.8 Hz), 6.80 (2H,
d, J ¼ 7.5 Hz), 7.18 (2H, d, J ¼ 7.5 Hz), 7.33 (1H, dd, J ¼
8.1, 2.3 Hz), 7.36 (1H, d, J ¼ 7.8 Hz), 7.53 (2H, d, J ¼ 8.1
Hz), 7.63 (1H, dd, J ¼ 7.8, 1.9 Hz), 8.01 (1H, dd, J ¼ 8.1, 2.3
Hz), 8.22 (1H, dd, J ¼ 7.8, 2.1 Hz), 8.3 (1H, d, J ¼ 2.1 Hz),
11.18 (1H, s br, CO2H). 13C NMR (CDCl3): dC 48.8, 72.9,
115.2 (2C), 119.9, 123.4, 124.8, 128.2, 128.3, 128.5, 128.7,
128.9, 130.6 (2C), 131.1, 132.0, 132.5, 136.5, 138.0, 148.2,
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

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N. Mahajan, S. Koul, and T. K. Razdan
Vol 48
151.5, 162.9, 172.0, 179.9, 197.6. HRMS: m/z (rel. int.) at
413.1072, (Mþ) (46) (Calc. for C25H16FNO4, 413.1063), 412
(59), 369 (100) (Mþ-CO2), 248 (65), 220 (54), 154 (48), 120
(35), 105 (59), 93 (72). Anal.: CHN (%): Found; C, 72.65; H,
3.85; N, 3.36; Calc.; C, 72.63; H, 3.90; N, 3.39. HPLC sol-
vent, n-hexane-isoPrOH (8:2 v/v); tr (minor), 9.48 min; tr
(major), 11.46 min.
(41), 179 (48), 102 (53). Anal.: CHN (%): Found; C, 71.01; H,
3.12; N, 3.27; Calc.; C, 71.07; H, 3.90; N, 3.19. HPLC: sol-
vent, n-hexane-isoPrOH (7.5:2.5 v/v); tr (minor), 9.25 min; tr
(major), 11.35 min.
5-(3-Carboxyphenyl)-2-(3,4-dimethoxyphenyl)-2H-pyr-
ano[2,3-b]quinolin-4(3H)-one, (3h). IR: umax cmꢀ1 3155,
1715, 1685, 1597, 1460, 1440, 1360, 1282, 1260, 1240, 1210,
930. 1H NMR: d 2.81 (1H, dd, J ¼ 16.7, 2.7 Hz), 3.08 (1H,
dd, J ¼ 16.7, 13.4 Hz), 3.75 (3H, s), 3.77 (3H, s), 5.19 (1H,
dd, J ¼ 13.4, 2.7 Hz), 6.38 (1H, d, J ¼ 2.0 Hz), 6.59 (1H, d,
J ¼ 8.1 Hz), 6.64 (1H, dd, J ¼ 8.1, 2.0 Hz), 7.32 (1H, dd, J
¼ 8.2, 2.1 Hz), 7.38 (1H, d, J ¼ 7.8 Hz), 7.52 (1H, d, J ¼ 8.1
Hz), 7.66 (1H, dd, J ¼ 7.6, 2.1 Hz), 7.78 (1H, m), 8.12 (1H,
dd, J ¼ 8.1, 2.1 Hz), 8.20 (1H, dd, J ¼ 7.8, 2.1 Hz), 8.36 (1H,
s), 11.30 (1H, s br). 13C NMR (CDCl3) : dC 46.8, 55.7, 55.9,
73.5, 107.5, 115.3, 115.5, 123.7, 126.4, 126.6, 126.8, 127.3,
127.6, 128.3, 128.5, 129.6, 130.5, 132.3, 134.2, 136.7, 146.2,
148.3, 158.2, 158.5, 168.0, 177.9, 194.6. HRMS: m/z at
455.1362 (Mþ) (36) (Calc. for C27H21NO6, 455.1369), 454
(32), 410 (100), 248 (69), 220 (58), 162 (48), 148 (68), 134
(36), 123 (58), 77 (71). Anal.: CHN (%): Found; C, 71.29; H,
4.61; N, 3.03; Calc.; C, 71.20; H, 4.65; N, 3.08. HPLC: sol-
vent, n-hexane-isoPrOH (8:2 v/v); tr (minor), 7.56 min; tr
(major), 10.53 min.
5-(3-Carboxyphenyl)-2-(4-bromophenyl)-2H-pyrano[2,3-
b]quinolin-4(3H)-one, (3e). IR: umax cmꢀ1 3158, 1713, 1680,
1595, 1460, 1442, 1412, 1360, 1280, 1242, 1210, 1050, 980.
1H NMR: d 2.79 (1H, dd, J ¼ 16.8, 2.6 Hz), 3.00 (1H, dd, J
¼ 16.8, 13.4 Hz), 5.30 (1H, dd, J ¼ 13.4, 2.6 Hz), 7.18 (2H,
d, J ¼ 8.5 Hz), 7.26 (2H, d, J ¼ 8.5 Hz), 7.28 (1H, m), 7.33
(1H, dd, J ¼ 8.1, 2.3 Hz), 7.36 (1H, d, J ¼ 7.8 Hz), 7.53 (1H,
d, J ¼ 8.1 Hz), 7.63 (1H, dd, J ¼ 7.8, 1.9 Hz), 8.01 (1H, dd,
J ¼ 8.1, 2.3 Hz), 8.22 (1H, dd, J ¼ 7.8, 2.1 Hz), 8.3 (1H, d, J
¼ 2.1 Hz), 11.18 (1H, s br, CO2H). 13C NMR (CDCl3): dC
44.9, 78.9, 107.3, 123.5, 126.5, 126.7, 127.6, 128.2 (2C),
128.5, 128.7, 128.9 (2C), 129.5, 129.8 (2C), 130.5, 132.5,
135.5, 136.9, 146.7, 148.7, 167.8, 177.9, 194.6. HRMS: m/z at
475.0270, (44), 473.0270 (Mþ) (46) (Calc. for C25H16BrNO4,
473.0263, 475.0263), 431 (55), 429 (52), 428 (61), 248 (68),
220 (50), 180 (54), 155 (66), 154 (63), 74 (62). Anal.: CHN
(%): Found; C, 63.39; H, 3.44; N, 2.98; Calc.; C, 63.31; H,
3.40; N, 2.95 . HPLC: solvent, n-hexane-isoPrOH (7.5:2.5 v/
v); tr (minor), 9.29 min; tr (major), 12.06 min.
5-(3-Carboxyphenyl)-2-(4-methylphenyl)-2H-pyrano[2,3-
b]quinolin-4(3H)-one, (3i). IR: umax cmꢀ1 3155, 1710, 1683,
1597, 1460, 1440, 1410, 1360, 1280, 1250, 1210, 970, 930. H
1
5-(3-Carboxyphenyl)-2-(2,4-dichlorophenyl)-2H-pyrano[2,3-
b]quinolin-4(3H)-one, (3f). IR: umax cmꢀ1 3155, 1715, 1685,
1595, 1460, 1440, 1420, 1410, 1370, 1360, 1280, 1265, 1255,
NMR: d 2.35 (3H, s), 2.80 (1H, dd, J ¼ 16.8, 2.7 Hz), 3.11
(1H, dd, J ¼ 16.8, 13.4 Hz), 5.20 (1H, dd, J ¼ 13.4, 2.7 Hz),
6.99 (2H, d, J ¼ 8.5 Hz), 7.17 (2H, d, J ¼ 8.5 Hz), 7.33 (1H,
dd, J ¼ 8.5, 2.1 Hz), 7.38 (1H, d, J ¼ 7.8 Hz), 7.52 (1H, d, J
¼ 8.5 Hz), 7.66 (1H, dd, J ¼ 7.6, 2.1 Hz), 7.80 (1H, dd, J ¼
8.5, 2.0 Hz), 8.10 (1H, dd, J ¼ 8.1, 2.1 Hz), 8.23 (1H, dd, J ¼
7.8, 2.1 Hz), 8.36 (1H, d, J ¼ 2.1 Hz), 11.22 (1H, s br, exch
D2O). 13C NMR (CDCl3): dC 20.9, 44.6, 78.3, 107.5, 123.9,
126.4, 126.5, 126.6, 127.2 (2C), 127.8, 128.1, 128.5, 129.4
(2C), 129.7, 130.4, 132.5, 135.2, 136.6, 137.9, 146.2, 148.7,
168.5, 178.3, 195.0. HRMS: m/z at 409.1322, (100), (Calc. for
C26H19NO4, 409.1314), (56), 408 (Mþ) (67), 365 (100), 364
(82), 248 (66), 220 (53), 154 (45), 116 (76), 91 (63), 77 (88).
Anal.: CHN (%): Found; C, 76.22; H, 4.65; N, 3.48; Calc.; C,
76.27; H, 4.68; N, 3.42. HPLC: solvent, n-hexane-isoPrOH
(8:2 v/v); tr (minor), 6.55 min; tr (major), 9.46 min.
5-(3-Carboxyphenyl)-2-(4-nitrophenyl)-2H-pyrano[2,3-
b]quinolin-4(3H)-one, (3j). IR: umax cmꢀ1 3158, 1712,
1687, 1598, 1465, 1440, 1365, 1286, 1262, 1210, 1205, 930.
1H NMR: d 2.83 (1H, dd, J ¼ 16.7, 2.8 Hz), 3.10 (1H, dd, J
¼ 16.7, 13.2 Hz), 5.48 (1H, dd, J ¼ 13.2, 2.8 Hz), 7.32 (1H,
dd, J ¼ 8.1, 2.7 Hz), 7.36 (1H, d, J ¼ 7.8 Hz), 7.52 (1H, d, J
¼ 8.1 Hz), 7.60 (2H, d, J ¼ 8.2 Hz), 7.62 (1H, dd, J ¼ 7.6,
2.1 Hz), 7.78 (1H, m), 8.0 (1H, dd, J ¼ 8.1, 2.0 Hz), 8.18
(2H, d, J ¼ 8.2 Hz), 8.24 (1H, dd, J ¼ 7.8, 2.1 Hz), 8.32 (1H,
d, J ¼ 2.1 Hz), 11.20 (1H, s br, exch D2O). 13C NMR
(CDCl3): dC 48.8, 71.9, 108.0, 122.4, 122.8, 123.6 (2C), 126.1,
126.5, 127.8, 128.3 (2C), 128.7, 129.4, 130.6, 132.4, 133.8
(2C), 136.9, 141.3, 146.3, 148.4, 167.8, 178.6, 195.3. HRMS:
m/z (rel. int.) at 440.4053, (Mþ) (36) (Calc. for C25H16N2O6,
440.1008), 439 (42), 396 (55), 395 (48), 273 (49), 272 (58),
247 (62), 245 (33), 219 (38), 191 (62), 77 (67). Anal.: CHN
(%): Found; C, 68.11; H, 3.63; N, 6.39; Calc.; C, 68.18; H,
3.66; N, 6.36. HPLC: solvent, n-hexane-isoPrOH (6:4 v/v); tr
(minor), 14.45 min; tr (major), 15.46 min.
1
1215, 976. H NMR: d 2.80 (1H, dd, J ¼ 16.8, 2.7 Hz), 3.06
(1H, dd, J ¼ 16.8, 13.4 Hz), 5.54 (1H, dd, J ¼ 13.4, 2.7 Hz),
7.27 (1H, d, J ¼ 8.2 Hz), 7.33 (1H, dd, J ¼ 8.2, 2.0 Hz), 7.37
(1H, d, J ¼ 7.6 Hz), 7.40 (1H, dd, J ¼ 8.4, 1.6 Hz), 7.53 (1H,
d, J ¼ 8.2 Hz), 7.56 (1H, d, J ¼ 1.6 Hz), 7.66 (1H, dd, J ¼
7.6, 2.1 Hz), 7.80 (1H, m), 8.10 (1H, d, J ¼ 8.1 Hz), 8.22
(1H, dd, J ¼ 7.5, 2.1 Hz), 8.36 (1H, s), 11.23 (1H, s br, exch.
D2O). 13C NMR (CDCl3): dC 46.3, 68.8, 119.9, 124.0, 126.6,
127.8, 128.1, 128.3 (2C), 128.5, 129.4, 129.6, 130.4, 130.7,
131.8, 132.6, 134.1, 134.3, 135.3, 139.4, 146.2, 151.2, 168.4,
180.1, 197.6. HRMS: m/z at 467.0378, (34), 463.0376 (33)
(Mþ) (Calc. for C25H15Cl2NO4, 463.0378, 467.0378), 466
(20), 462 (23), 422 (90), 418 (100), 248 (66), 220 (48), 174
(60), 170 (68), 145 (33), 154 (38), 91 (42). Anal.: CHN (%):
Found; C, 64.63; H, 3.21; N, 3.11; Calc.; C, 64.67; H, 3.26;
N, 3.16. HPLC: solvent, n-hexane-isoPrOH (8:2 v/v); tr
(minor), 10.25 min; tr (major), 13.20 min.
5-(3-Carboxyphenyl)-2-(benzo[d][1,3]dioxol-6-yl)-2H-pyr-
ano[2,3-b]quinolin-4(3H)-one, (3g). IR: umax cmꢀ1 3165,
1710, 1680, 1590, 1460, 1450, 1440, 1355, 1270, 1240, 1210,
1
1205, 1040, 980, 785. H NMR: d 2.81 (1H, dd, J ¼ 16.7, 2.7
Hz), 3.04 (1H, dd, J ¼ 16.7, 13.4 Hz), 5.10 (1H, dd, J ¼ 13.4,
2.7 Hz), 6.01 (2H, s), 6.79 (2H, s), 6.94 (1H, d, J ¼ 2.1 Hz),
7.26 (1H, m), 7.32 (1H, dd, J ¼ 8.2, 2.6 Hz), 7.36 (1H, dd, J
¼ 7.6, 2.1 Hz), 7.54 (1H, d, J ¼ 8.2 Hz), 7.66 (1H, dd, J ¼
7.6, 2.1 Hz), 8.08 (1H, dd, J ¼ 8.1, 2.2 Hz), 8.22 (1H, dd, J ¼
7.6, 2.1 Hz), 8.32 (1H, d, J ¼ 2.1 Hz), 11.23 (1H, s br, exch.
D2O). 13C NMR (CDCl3): dC 44.9, 76.8, 100.7, 107.6, 115.3,
123.6, 123.9, 126.5 (2C), 126.9, 127.4, 127.6, 128.3, 128.5,
129.6, 130.5, 132.4, 134.2, 136.7, 146.2, 148.3, 149.5, 149.8,
176.8, 167.6, 194.6. HRMS: m/z at 439.1064, (100), (Mþ)
(Calc. for C26H17NO6, 439.1056), 438 (54), 409 (45), 381
(32), 337 (38), 317 (54), 273 (65), 245 (23), 243 (62), 215
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

November 2011
Bismuth Triflate–L(ꢀ)-Proline Catalyzed Synthesis of Chiral
1307
2,5-Diaryl-2,3-dihydropyrano[2,3-b]quinolin-4-ones
[8] Deshmukh-Phadke, K.; Lawrence, M.; Nanda, S. Biochem
Biophys Res Commun 1978, 85, 490.
5-(3-Carboxyphenyl)-2-(2-bromophenyl)-2H-pyrano[2,3-
b]quinolin-4(3H)-one, (3k). IR: umax cmꢀ1 3158, 1715, 1680,
1595, 1460, 1440, 1410, 1360, 1280, 1240, 1210, 1050, 980. 1H
NMR: d 2.80 (1H, dd, J ¼ 16.7, 2.6 Hz), 3.11 (1H, dd, J ¼
16.8, 13.4 Hz), 5.30 (1H, dd, J ¼ 13.4, 2.6 Hz), 7.18 (2H, dd, J
¼ 8.5, 1.8 Hz), 7.32 (1H, d, J ¼ 8.5 Hz), 7.33 (1H, dd, J ¼ 8.2,
2.0 Hz), 7.38 (2H, ddd, J ¼ 7.8, 8.5, 1.8 Hz), 7.50 (1H, d, J ¼
8.1 Hz), 7.66 (1H, d, J ¼ 7.6, 2.1 Hz), 7.80 (1H, m), 8.11 (1H,
dd, J ¼ 8.1, 2.1 Hz), 8.22 (1H, dd, J ¼ 7.6, 2.1 Hz), 8.35 (1H,
s), 11.23 (1H, s br, exch D2O). 13C NMR (CDCl3): dC 46.3,
70.2, 119.9, 122.3, 126.4, 126.8, 127.6, 128.0, 128.2, 128.4,
128.5, 128.7 (2C), 128.9, 129.4, 129.7, 130.1, 132.1, 132.6,
135.0, 146.7, 148.6, 167.9, 178.1, 195.6. HRMS: m/z at
475.0268, (42), 473.0669 (45) (Mþ) (Calc. for C25H16BrNO4,
473.0263, 475.0263), 431 (59), 429 (60), 428 (65), 248 (66),
220 (50), 180 (59), 155 (63), 154 (60), 74 (68). Anal.: CHN
(%): Found; C, 68.38; H, 3.46; N, 2.91; Calc.; C, 68.31; H,
3.40; N, 2.95. HPLC: solvent, n-hexane-isoPrOH (8:2 v/v); tr
(minor), 9.29 min; tr (major),12.46 min.
[9] Moraes, V. R. S.; Tomazela, D. M.; Ferracin, R. J.; Garcia,
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Acknowledgments. The authors are thankful to T.S. Banipal
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Journal of Heterocyclic Chemistry
DOI 10.1002/jhet