Quinoline-Fused Lactones via Tandem Oxidation Cyclization: Metal-Free sp3C-H Functionalization

Article abstract of DOI:10.1021/acs.joc.0c02238

A unique lactonization of 2-methyl-3-acyl-4-phenylquinolines using PhIO as the oxidant and selectfluor as an additive is reported. The reaction occurs under ambient conditions through tandem oxidation and cyclization of sp3 C-H bonds under metal-free conditions. The heterocycle-fused lactones are obtained in moderate to good yield.

Full text of DOI:10.1021/acs.joc.0c02238

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Quinoline-Fused Lactones via Tandem Oxidation Cyclization: Metal-
Free sp3 C−H Functionalization
Alankrita Garia, Parul Chauhan, Riya Halder, and Nidhi Jain*
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ABSTRACT: A unique lactonization of 2-methyl-3-acyl-4-phenylquinolines using PhIO as the oxidant and selectfluor as an additive
is reported. The reaction occurs under ambient conditions through tandem oxidation and cyclization of sp3 C−H bonds under
metal-free conditions. The heterocycle-fused lactones are obtained in moderate to good yield.
process13 or oxidative strategy using hypervalent iodine
INTRODUCTION
Aryl- and heteroaryl-fused lactones are useful scaffolds that
■
reagents.14 As shown in (Scheme 1B(ii)), quinoline lactones
display a range of biological properties.1 Generally, the
serve as key synthetic intermediates for aza-podophyllotoxin
derivatives. 1,4-Dihydroquinoline lactones (I), derived by
synthesis of these molecules is carried out in multiple steps
using metal, ligand, or acid. Scheme 1A(i−viii) enlists some of
reduction of 9-phenylfuro[3,4-b]quinolin-1(3H)-one, are
known for their anti-leishmanial and anti-leukemic properties.
the classical prefunctionalized starting materials that enable
Another biologically important molecule, 3-fluoromethylquino-
access to benzolactones. The methodologies involve (i) metal-
line-2-carboxamide ([18F]-AB5186) (II), known as a positron
emission tomography imaging agent can be derived from 9-
phenylfuro[3,4-b]quinolin-1(3H)-one.15
mediated oxidative lactonization of benzene-1,2-dimethanol,2
(ii) Tishchenko reaction of phthalaldehyde with actinide
coordination complexes,3 (iii) Zn/ligand-mediated lactoniza-
tion of 2-formylbenzoates,4 and (iv) lactonization of 2-
(halomethyl)benzoic acid.5 Alternatively, benzolactone for-
mation has also been achieved via metal-catalyzed and
directing group-assisted C−H activation/C−O bond forma-
tion in (v) o-toluic acid6a,b and aliphatic carboxylic acid,6c (vi)
(Z)-2-(3-hydroxyprop-1-en-1-yl)benzoic acid,7 (vii) γ-(2-
methoxycarbonylphenyl)propargylic alcohol,8 and (viii) benzyl
alcohol and CO2.9 Pyridine-fused lactones (Scheme 1B) have
been synthesized from pyridine-2,3-dimethanol or pyridine-
3,4-dimethanol in the presence of metal and ligand (i),10 while
quinoline-fused lactones have been prepared from 2-amino-
benzophenone in multiple steps using metal and/or acid at
high temperature (ii).11 In general, most of these methods
suffer from limitations of prefunctionalized substrates, harsh
reagents, multiple steps, high temperature, and toxicity.
Therefore, seeking efficient, atom economical, and mild
strategies for synthesizing heteroaryl-fused lactones is highly
desirable. Direct sp3 C−H functionalization has emerged as a
powerful tool for construction of C−C, C−N, and C−O
bonds.12 Because of the inertness of the C(sp3)−H bond, its
late-stage functionalization is challenging, though attractive.
Recent approaches for C(sp3)−H functionalization describe
the use of metal/oxidant via ionic pathway/free-radical
In view of the immense biological significance of heteroaryl-
fused lactones and limited synthetic procedures, we delved into
hypervalent iodine-assisted protocols to access them. In this
work, we report an unprecedented synthesis of quinoline and
quinoxaline lactones via oxidative cyclization of sp3 C−H
bonds using PhIO (iodosobenzene) and selectfluor under
room temperature (RT) conditions (Scheme 1C).
RESULTS AND DISCUSSION
■
The study initiated with the reaction of 1-(2-methyl-6-nitro-4-
phenylquinolin-3-yl)ethan-1-one (1a) using PhIO and select-
fluor (1:1) at RT. After 24 h, a cyclic product, 7-nitro-9-
phenylfuro[3,4-b]quinolin-1(3H)-one (2a) was isolated in
31% yield along with the formation of 7-nitro-5-phenyl-1H-
pyrano[3,4-b]quinolin-4(3H)-one (2a′) in 17% yield (Table 1,
Received: September 17, 2020
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© XXXX American Chemical Society
J. Org. Chem. XXXX, XXX, XXX−XXX
A

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Scheme 1. Synthetic Routes for Benzolactone and Heteroaryl-Fused Lactones
a
Table 1. Optimization Table
b
s. no
hypervalent iodine
additive
selectfluor (1)
solvent
yield (%)
c
1
2
3
4
5
6
7
8
PhIO (1)
PhIO (1)
PhIO (2)
PhIO (3)
PhIO (3)
DPIB (3)
PIDA (3)
PIFA (3)
HTIB (3)
PhIO (3)
PhIO (3)
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
31, 17
40, 13
58, 7
c
selectfluor (2)
selectfluor (1)
selectfluor (2)
selectfluor (2)
selectfluor (2)
selectfluor (2)
selectfluor (2)
selectfluor (2)
PTSA/BF3·OEt/NFSI (2)
selectfluor (2)
c
86
d
e
69 , 56
67
61
53
49
9
10
11
51/53/8
f gh
solvent ,
,
0
a
b
c
d
e
Reaction conditions: 1a (1.0 equiv), hypervalent iodine, additive, solvent (3 mL) at RT for 24 h. Yields of 2a. 2a′ are isolated yields. 50 °C. 80
f
g
h
°C. DCE. Dioxane. THF.
entry 1). To improve the yield, optimization studies were
carried out (Table 1, entries 2−4). On changing the
stoichiometry of PhIO and selectfluor to 1:2 (Table 1, entry
2), the yield of 2a increased slightly (40%) and 2a′ was formed
in 13% yield (Table 1, entry 2). With a 2:1 stoichiometry, 2a
increased to 58% and 2a′ got reduced to 7% (Table 1, entry 3).
Changing the ratio to 3:2 helped in driving the reaction to
completion, and 2a was isolated in 86% yield (Table 1, entry
4). Raising the temperature to 50 and 80 °C reduced the yield
to 69 and 56%, respectively, because of the formation of
unknown polar products (Table 1, entry 5). Use of other
hypervalent iodine reagents such as dipivaloyloxyiodobenzene
(DPIB), phenyliodine(III) diacetate (PIDA), [bis-
(trifluoroacetoxy)iodo]benzene (PIFA), and hydroxy-
(tosyloxy)iodobenzene (HTIB) did not help, and lower yields
were obtained in all cases (Table 1, entries 6−9).
B
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a
Scheme 2. Substrate Scope
a
Reaction conditions: 1 (1.0 equiv), PhIO (3.0 equiv), selectfluor (2.0 equiv), CH3CN, RT, 24 h. Yields are isolated yields. bReaction carried on a
gram scale with 1 g of 1a.
Scheme 3. Control Experiments for Mechanistic Investigation
On substituting selectfluor with N-fluorobenzenesulfoni-
mide, the yield of 2a dropped considerably (8%). With acid
additives such as p-toluenesulfonic acid (PTSA) and BF3·OEt2,
2a was obtained in 51 and 53% yields, respectively (Table 1,
entry 10). No reaction took place in dichloroethene (DCE),
dioxane, and tetrahydrofuran (THF) (Table 1, entry 11), and
acetonitrile was found to be the best solvent for the reaction.
With the optimized reaction conditions in hand, the
generality of the reaction was examined. Quinoline derivatives
with electron-withdrawing substituents such as NO2, F, Cl, and
Br at 5, 6, and 8 positions afforded the corresponding lactones
in 61−86% yields (Scheme 2, entries 2a−2d). However,
unsubstituted and 7-methyl-substituted quinolines gave lower
yield (Scheme 2, entries 2e and 2f), suggesting higher
reactivity of methyl sp3 C−H under the influence of
electron-withdrawing groups. Next, the effect of substituents
on 4-phenyl ring was examined. F, Cl, Br, and CF3 groups at
the para position showed good compatibility and afforded the
C
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Scheme 4. Proposed Mechanism
corresponding products in moderate yields (Scheme 2, entries
2g−2j). Lower yield was obtained with electron-donating p-
methoxy and p-benzyloxy substituted derivatives as a
substantial amount of starting material was left unreacted
(Scheme 2, entries 2k−2l). Next, disubstituted derivates with
halo-/nitrosubstituents on both the phenyl rings were
explored, and moderate-to-good product yields were obtained
(Scheme 2, entries 2m−2s). Interestingly, with 1-(3-methyl-
quinoxalin-2-yl)ethanone, the desired lactone furo[3,4-b]-
quinoxalin-1(3H)-one (2t) was obtained in 39% yield with
considerable amount of unreacted 1t.
Notably, it was found that the desired reaction did not take
place with 1-(2-methylquinolin-3-yl)ethan-1-one (1u) and 1-
(2,4-dimethylquinolin-3-yl)ethan-1-one (1v) (Scheme 2), and
a mixture of polar products was formed in either case
suggesting the importance of electron-withdrawing effect of
4-phenyl group in the reaction. The results indicated that the
electron-withdrawing effect played a dominant role in
activating the sp3-C−H bond and enabling lactonization.
Reaction was carried out on a gram scale, and 2a was isolated
in 67% yield (670 mg) under optimized reaction conditions
(Scheme 2).
To gain insight into the reaction mechanism, some control
experiments were carried out. The role of PhIO and selectfluor
was studied by carrying out the reaction of 1a in the presence
of PhIO alone (Scheme 3(i)) and then in the presence of
selectfluor alone (Scheme 3(ii)). In both the cases, 2a was not
formed. Interestingly, with selectfluor alone, fluorination of 2-
methyl group took place, and 1-(2-(fluoromethyl)-6-nitro-4-
phenylquinolin-3-yl)ethanone (3a) was obtained in 30% yield
(Scheme 3(ii)). Few other substituted quinolines were also
subjected to the reaction with selectfluor. However, small
amounts of fluorinated products were obtained in all cases
(Scheme 3(ii), 3a−3d).16 The involvement of methyl free
radical in the reaction was ascertained by carrying out the
reaction in the presence of 2,2,6,6-tetramethylpiperidine-N-
oxyl (TEMPO) (2 equiv). It was found that the desired
lactone 2a did not form under these conditions, and a TEMPO
adduct 2a″ was isolated in 69% yield (Scheme 3(iii)).
Based on the experimental results, a reaction mechanism has
been proposed as shown in Scheme 4. The reaction is believed
to initiate via in situ generation of fluorine radical and radical
cation intermediate [A] by the reaction of 1a with
selectfluor.17a [A] reacts with fluorine radical and forms
intermediate [B], which subsequently loses the fluorine radical
to generate a methylene radical intermediate [C] at the C-2
position. The formation of [C] is supported by the formation
of 2a″ (TEMPO adduct) and 3a (Scheme 3(ii)). [C]
undergoes intramolecular cyclization by radical coupling with
carbonyl oxygen and yields intermediate [E] (m/z 305.0936,
Figure S1, Supporting Information) via [D]. [E] undergoes
ring opening reaction with protonated PhIO, and the cationic
site is attacked by the amine nucleophile derived from
selectfluor17b to form [F]. It is noteworthy to mention that
selectfluor plays a dual role. First, it activates the substrate (1a-
[A]), and second the diazoniabicyclo[2.2.2]octane moeity acts
as a nucleophile and facilitates the ring-opening step ([E]−
[F]).17c Further, [F] undergoes reductive elimination of
hypervalent iodine followed by hydroxide attack resulting in
the formation of [G]. On reaction with protonated PhIO, [G]
forms [H], while in it’s absence, 2a′ is formed as a side product
(Table 1). [H] undergoes reductive elimination of hypervalent
iodine and loss of formaldehyde to give [I], which eventually
yields 2a after elimination of ammonia.
CONCLUSIONS
■
In conclusion, we report an unprecedented, metal-free sp3 C−
H functionalization of methyl group in 2-methyl-3-acyl-4-
phenylquinolines. The reaction occurs under ambient con-
ditions via oxidative cyclization using PhIO and selectfluor.
The protocol offers metal- and ligand-free conditions, smooth
scalability, and good functional group tolerance and provides
quinoline-fused lactones in moderate to good yields.
EXPERIMENTAL SECTION
■
General Information. All reagents and solvents were of pure
analytical grade. Thin-layer chromatography (TLC) was performed
on 60 F254 silica gel, precoated on aluminum plates, and revealed
with a UV lamp (λmax = 254 nm). The products were purified by
D
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1
column chromatography on silica gel 230−400 mesh. H and 13C
NMR spectra were recorded on 300 MHz (1H 300 MHz, 13C 75
MHz), 400 MHz (1H 400 MHz, 13C 100 MHz, 19F 376 MHz,) and
500 MHz spectrometers (1H 500 MHz, 13C 125 MHz) using CDCl3
as the solvent with tetramethylsilane (TMS) as the internal standard
at RT. Chemical shifts are in δ (ppm) relative to TMS. The coupling
constants (J) are in Hz. High-resolution mass spectra (HRMS) were
recorded on a mass spectrometer using electrospray ionization time-
of-flight (ESI-TOF) reflectron experiments.
1-(8-Bromo-6-chloro-2-methyl-4-phenylquinolin-3-yl)ethan-1-
one (1d). White solid, yield 89% (165.5 mg), hexane/EtOAc (92:7);
1H NMR (500 MHz, CDCl3): δ 8.02 (d, J = 2.25 Hz, 1H), 7.54−7.53
(m, 4H), 7.32−7.30 (m, 2H), 2.73 (s, 3H), 1.99 (s, 3H); 13C{1H}
NMR (125 MHz, CDCl3): δ 204.7, 155.0, 143.5, 143.1, 136.2, 134.1,
133.9, 132.0, 129.9, 129.4, 129.0, 126.7, 125.6, 124.8, 31.7, 24.1;
HRMS (ESI-TOF) m/z: [M + H]+ calcd for C18H14 BrClNO+,
373.9942; found, 373.9872.
1-(2,7-Dimethyl-4-phenylquinolin-3-yl)ethan-1-one (1f). White
1
solid, yield 87% (119.6 mg), hexane/EtOAc (93:7); H NMR (500
General Procedure for Synthesis of Compounds (1a−1s). A
mixture of 2-aminoaryl ketones (0.50 mmol, 1 equiv), β-ketoesters/
ketones (1.0 mmol, 2 equiv), and 4-toluenesulfonic acid (0.10 mmol,
0.2 equiv) in EtOH (3 mL) was added into a Schlenk flask (25 mL),
and the mixture was stirred at 80 °C using oil bath and stirred until
the reaction was complete. The solvent was evaporated under reduced
pressure, and the residue was purified by column chromatography on
silica gel using ethyl acetate-hexane.18a Isolated yields: 1a18c (97%),
1b18c (93%), 1c (92)%, 1d (89)%, 1e18a (99%), 1f (87%), 1g18c
(77%), 1h18a (81%), 1i18c (80%), 1j (81%), 1k (85%), 1l18c (86%),
1m (71%), 1n18a (75%), 1o18a (61%), 1p18a (72%), 1q (69%), 1r
(70%), 1s (71%).
General Procedure for Synthesis of Compound 1t. To a round-
bottom flask containing water (15 mL), acetyl acetone (185 mg, 1
mmol) was added followed by N-bromo succinimide (393 mg, 1.2
mmol) and stirred for 20 min at 70 °C using oil bath. To this reaction
mixture, 1,2-phenylene diamine (200 mg, 1.0 mmol) was added, and
the contents were stirred until completion of the reaction as indicated
by TLC.18b The reaction mixture was then cooled to RT and poured
onto ice and extracted with ethyl acetate. The organic extract was
washed successively with brine, dried over Na2SO4, and concentrated
under reduced pressure. The product was purified by column
chromatography on silica gel using ethyl acetate-hexane.
General Procedure for Synthesis of Lactone-Fused Quinoline
and Quinoxaline (2a−2t). To a 25 mL round-bottom flask was
added 1a (60 mg, 1 equiv), PhIO (128 mg, 3 equiv), selectfluor (138
mg, 2 equiv), and CH3CN (4 mL). The reaction mixture was stirred
for 24 h at RT, and the reaction was monitored through TLC. After
reaction completion, the contents were diluted with water, extracted
with ethyl acetate, and concentrated at reduced pressure. The product
was purified by column chromatography on silica gel using ethyl
acetate-hexane.
General Procedure for Synthesis of Fluorinated Compounds
3a−3d. To a 25 mL round-bottom flask was added 1a (60 mg, 1
equiv), selectfluor (138 mg, 2 equiv), and CH3CN (3 mL). The
reaction mixture was stirred for 24 h at RT, and the reaction was
monitored through TLC. After reaction completion, the contents
were diluted with water, extracted with ethyl acetate, and
concentrated at reduced pressure. The product was purified by
column chromatography on silica gel using ethyl acetate-hexane.
General Procedure for Preparation of TEMPO Adduct 2a″. To a
25 mL round-bottom flask was added 1a (60 mg, 1 equiv), PhIO (128
mg, 3 equiv), selectfluor (138 mg, 2 equiv), TEMPO (61.1 mg, 2
equiv), and CH3CN (3 mL). The reaction mixture was stirred for 24
h at RT, and the reaction was monitored through TLC. After reaction
completion, the contents were diluted with water, extracted with ethyl
acetate, and concentrated at reduced pressure. The product was
purified by column chromatography on silica gel using ethyl acetate-
hexane.
MHz, CDCl3): δ 7.86 (s, 1H), 7.51−7.49 (m, 4H), 7.35−7.33 (m,
2H), 7.283−7.280 (m, 1H), 2.67 (s, 3H), 2.55 (s, 3H), 1.98 (s, 3H);
13C{1H} NMR (125 MHz, CDCl3): δ 205.9, 153.3, 147.7, 143.8,
140.6, 135.4, 134.1, 130.0, 128.8, 128.7, 128.6, 127.9, 125.8, 123.0,
32.0, 23.8, 21.7; HRMS (ESI-TOF) m/z: [M + H]+ calcd for
C19H18NO+, 276.1383; found, 276.1392.
1-(2-Methyl-4-(4-(trifluoromethyl)phenyl)quinolin-3-yl)ethan-1-
one (1j). White solid, yield 81% (133.2 mg), hexane/EtOAc (92:8);
1H NMR (500 MHz, CDCl3): δ 8.09 (d, J = 8.30 Hz, 1H), 7.79 (d, J
= 8.10 Hz, 2H), 7.76−7.73 (m, 1H), 7.51−7.46 (m, 4H), 2.71 (s,
3H), 2.06 (s, 3H); 13C{1H} NMR (125 MHz, CDCl3): δ 205.1,
153.4, 147.5, 142.1, 139.0, 134.9, 130.5, 130.3, 129.1, 126.9, 125.7,
1
125.6 (2C), 124.5, 123.8 (q, JC−F = 270.62 Hz), 32.2, 23.8; HRMS
(ESI-TOF) m/z: [M + H]+; calcd for C19H15F3NO+, 330.1100;
found, 330.1036.
1-(4-(4-(Benzyloxy)phenyl)-2-methylquinolin-3-yl)ethan-1-one
1
(1k). White solid, yield 85% (155.9 mg), hexane/EtOAc (93:7); H
NMR (400 MHz, CDCl3): δ 8.07 (d, J = 8.48 Hz, 1H), 7.70−7.67
(m, 2H), 7.47−7.44 (m, 2H), 7.42−7.38 (m, 3H), 7.35−7.33 (m,
1H), 7.29−7.26 (m, 2H), 7.12−7.10 (m, 2H) 5.12 (s, 2H), 2.69 (s,
3H), 2.00 (m, 3H); 13C{1H} NMR (100 MHz, CDCl3): δ 205.9,
159.3, 153.3, 147.5, 143.7, 136.5, 134.9, 131.4, 130.0, 128.8, 128.6,
128.1, 127.5, 127.4, 126.4, 126.1, 125.3, 115.1, 70.1, 31.9, 23.8;
+
HRMS (ESI-TOF) m/z: [M + H]+ calcd for C25H22NO2 , 368.1645;
found, 368.1647.
1-(4-(3-Chloro-4-fluorophenyl)-2-methylquinolin-3-yl)ethan-1-
one (1m). White solid, yield 71% (111.1 mg), hexane/EtOAc (93:7);
1H NMR (500 MHz, CDCl3): δ 8.10 (d, J = 8.40 Hz, 1H), 7.77−7.74
(m, 1H), 7.55−7.54 (m, 1H), 7.51−7.48 (m, 1H), 7.46−7.45 (m,
1H), 7.33−7.30 (m, 1H), 7.28−7.25 (m, 1H), 2.71 (s, 3H), 2.13 (s,
1
3H); 13C{1H} NMR (125 MHz, CDCl3): δ 205.0, 158.4 (d, JC−F
=
250.48 Hz), 153.4, 147.5, 141.2, 135.0, 132.18, 132.12, 130.3, 130.0
3
2
(d, JC−F = 7.22 Hz), 129.1, 127.0, 125.5, 124.7, 121.7 (d, JC−F
=
2
18.18 Hz), 117.1 (d, JC−F = 21.05 Hz), 32.2, 23.8; HRMS (ESI-
TOF) m/z: [M + H]+ calcd for C18H14ClFNO+, 314.0742; found,
314.0680.
1-(5-Fluoro-4-(4-fluorophenyl)-2-methylquinolin-3-yl)ethan-1-
one (1q). White solid, yield 69% (104.6 mg), hexane/EtOAc (92:8);
1H NMR (500 MHz, CDCl3): δ 7.89 (d, J = 8.45 Hz, 1H), 7.67−7.63
(m, 1H), 7.31−7.28 (m, 2H), 7.15−7.12 (m, 2H), 7.10−7.08 (m,
1H), 2.65 (s, 3H), 1.99 (s, 3H); 13C{1H} NMR (125 MHz, CDCl3):
1
δ 205.1, 162.8 (d, 1JC−F = 247.05 Hz), 158.6 (d, JC−F = 257.52 Hz),
154.1, 148.8, 140.0, 136.8, 132.9, 130.9 (d, 4JC−F = 3.60 Hz), 130.8 (d,
3
4
4JC−F = 3.55 Hz), 129.9 (d, JC−F = 9.57 Hz), 125.3 (d, JC−F = 4.37
2
2
Hz), 115.1 (d, JC−F = 26.60 Hz), 112.0 (d, JC−F = 21.71 Hz), 32.0,
23.7; HRMS (ESI-TOF) m/z: [M + H]+ calcd for C18H14F2NO+,
298.1038; found, 298.1042.
1-(4-(4-Bromophenyl)-5-fluoro-2-methylquinolin-3-yl)ethan-1-
one (1r). White solid, yield 70% (124.9 mg), hexane/EtOAc (93:7);
1H NMR (500 MHz, CDCl3): δ 7.88 (d, J = 8.50 Hz, 1H), 7.64−7.60
Physical Properties and Characterization Data of the
Synthesized Compounds. 1-(5-Fluoro-2-methyl-4-phenylquino-
lin-3-yl)ethan-1-one (1c). White solid, yield 92% (128.34 mg),
(m, 1H), 7.55 (d, J = 8.20 Hz, 2H), 7.18 (d, J = 8.10 Hz, 2H), 7.09−
1
7.05 (m, 1H), 2.63 (s, 3H), 2.00 (s, 3H); 13C{1H} NMR (100 MHz,
hexane/EtOAc (92:8); H NMR (400 MHz, CDCl3): δ 7.89 (d, J =
1
8.48 Hz, 1H), 7.64−7.58 (m, 1H), 7.43−7.42 (m, 3H), 7.32−7.31
CDCl3): δ 204.9, 158.5 (d, JC−F = 257.50 Hz), 154.1, 148.7, 139.6,
(m, 2H), 7.08−7.03 (m, 1H), 2.66 (s, 3H), 1.95 (s, 3H); 13C{1H}
136.5, 135.9, 131.1, 130.6 (d, 4JC−F = 3.55 Hz), 129.9 (d, 3JC−F = 9.55
1
4
3
NMR (100 MHz, CDCl3): δ 205.1, 158.6 (d, JC−F = 257.90 Hz),
Hz), 125.3 (d, JC−F = 4.18 Hz), 122.9, 115.1 (d, JC−F = 9.13 Hz),
112.0 (d, 2JC−F = 21.71 Hz), 32.1, 23.6; HRMS (ESI-TOF) m/z: [M
+ H]+ calcd for C18H14BrFNO+, 358.0237; found, 358.0238.
154.1, 148.7, 141.0, 137.0 (d, 4JC−F = 3.54 Hz), 136.5, 129.7 (d, 3JC−F
= 9.58 Hz), 129.0 (d, 4JC−F = 3.45 Hz), 128.4, 127.9, 125.2 (d, 4JC−F
=
3
2
4.15 Hz), 115.3 (d, JC−F = 9.15 Hz), 111.8 (d, JC−F = 21.65 Hz),
31.8, 23.7; HRMS (ESI-TOF) m/z: [M + H]+ calcd for C18H15FNO+,
280.1132; found, 280.1080.
1-(4-(4-Chlorophenyl)-2-methyl-6-nitroquinolin-3-yl)ethan-1-
one (1s). White solid, yield 71% (120.7 mg), hexane/EtOAc (93:7);
1H NMR (500 MHz, CDCl3): δ 8.51−8.48 (m, 2H), 8.20 (d, J = 9.05
E
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Article
Hz, 1H), 7.57 (d, J = 8.35 Hz, 2H), 7.31 (d, J = 8.35 Hz, 2H), 2.73 (s,
3H), 2.07 (s, 3H); 13C{1H} NMR (125 MHz, CDCl3): δ 204.2,
157.8, 149.5, 145.7, 144.1, 136.4, 136.3, 131.9, 131.2, 130.9, 129.6,
124.1, 123.7, 122.7, 31.9, 24.2; Anal. Calcd for C18H13ClN2 O3: C,
63.45; H, 3.85; N, 8.22. Found: C, 61.61; H, 3.52; N, 7.62%.
7-Nitro-9-phenylfuro[3,4-b]quinolin-1(3H)-one (2a). White solid,
163.5, 151.3, 150.0, 135.9, 132.7, 131.2, 129.9, 129.5, 128.6, 127.7,
127.6, 126.7, 113.4, 69.6; HRMS (ESI-TOF) m/z: [M + Na]+ calcd
+
for C17H10ClNNaO2 , 318.0292; found, 318.0275.
9-(4-Bromophenyl)furo[3,4-b]quinolin-1(3H)-one (2i). White
1
solid, yield 57% (34.2 mg), hexane/EtOAc (92:8); H NMR (500
MHz, CDCl3): δ 8.22 (d, J = 8.52 Hz, 1H), 7.94−7.87 (m, 2H),
7.73−7.71 (d, J = 6.4 Hz, 2H), 7.63−7.59 (d, J = 6.2 Hz, 1H), 7.36−
7.33 (m, 2H), 5.46 (s, 2H); 13C{1H} NMR (125 MHz, CDCl3): δ
167.8, 163.5, 151.3, 149.9, 132.7, 131.6, 131.4, 130.4, 129.5, 127.6
(2C), 126.7, 124.1, 113.4, 69.6; HRMS (ESI-TOF) m/z: [M + H]+
1
yield 86% (51.5 mg), hexane/EtOAc (83:17); H NMR (300 MHz,
CDCl3): δ 8.86 (d, J = 2.52 Hz, 1H), 8.64 (dd, J1 = 9.21 Hz, J2 = 2.40
Hz, 1H), 8.35 (d, J = 9.30 Hz, 1H), 7.68−7.64 (m, 3H), 7.50−7.47
(m, 2H), 5.51 (s, 2H); 13C{1H} NMR (100 MHz, CDCl3): δ 167.1,
166.7, 153.6, 153.1, 146.1, 131.3, 130.5, 130.0, 129.9, 128.7, 126.3,
125.7, 124.9, 115.1, 69.6; HRMS (ESI-TOF) m/z: [M + H]+ calcd for
+
calcd for C17H11BrNO2 , 339.9967; found, 339.9961.
9-(4-(Trifluoromethyl)phenyl)furo[3,4-b]quinolin-1(3H)-one (2j).
+
1
C17H11N2O4 , 307.0713; found, 307.0714.
White solid, yield 60% (36.0 mg), hexane/EtOAc (92:8); H NMR
7-Chloro-9-phenylfuro[3,4-b]quinolin-1(3H)-one (2b).11e White
(500 MHz, CDCl3): δ 8.24 (d, J = 8.45 Hz, 1H), 7.95−7.91 (m, 1H),
7.84 (d, J = 8.0 Hz, 2H), 7.81 (d, J = 8.5 Hz, 1H), 7.63 (d, J = 8.05
Hz, 1H), 7.59 (d, J = 7.95 Hz, 2H), 5.47 (s, 2H); 13C{1H} NMR (125
1
solid, yield 61% (36.6 mg), hexane/EtOAc (92:8); H NMR (500
MHz, CDCl3): δ 8.14 (d, J = 8.95 Hz, 1H), 7.86 (d, J = 2.25 Hz, 1H),
7.83 (dd, J1 = 8.95 Hz, J2 = 2.35 Hz, 1H), 7.60−7.59 (m, 3H), 7.44−
7.42 (m, 2H), 5.44 (s, 2H); 13C{1H} NMR (125 MHz, CDCl3): δ
167.4, 163.8, 150.5, 149.6, 133.6, 133.4, 130.9, 130.9, 129.8, 129.7,
128.4, 127.8, 126.6, 114.2, 69.5; HRMS (ESI-TOF) m/z: [M + Na]+
MHz, CDCl3): δ 167.7, 163.4, 151.3, 149.4, 135.3, 132.8, 131.5 (d,
4
2JC−F = 32.5 Hz), 130.2, 129.6, 127.9, 127.4, 126.5, 125.3 (d, JC−F
=
1
3.76 Hz), 123.94 (d, JC−F = 270.62 Hz), 113.5, 69.7; HRMS (ESI-
TOF) m/z: [M + Na]+ calcd for C18H10F3NNaO2 , 352.0555; found,
+
+
calcd for C17H10ClNNaO2 , 318.0292; found, 318.0303.
352.0548.
8-Fluoro-9-phenylfuro[3,4-b]quinolin-1(3H)-one (2c). White
9-(4-(Benzyloxy)phenyl)furo[3,4-b]quinolin-1(3H)-one (2k).
1
solid, yield 69% (41.3 mg), hexane/EtOAc (91:9); H NMR (500
1
White solid, yield 52% (31.2 mg), hexane/EtOAc (93:7); H NMR
MHz, CDCl3): δ 8.06 (d, J = 8.50 Hz, 1H), 7.88−7.83 (m, 1H),
7.53−7.52 (m, 3H), 7.39−7.38 (m, 2H), 7.27−7.28 (m, 1H), 5.43 (s,
2H); 13C{1H} NMR (125 MHz, CDCl3): δ 167.0, 164.1, 160.07 (d,
(500 MHz, CDCl3): δ 8.19 (d, J = 7.40 Hz, 1H), 8.00 (d, J = 7.20 Hz,
1H), 7.91−7.89 (m, 1H), 7.61−7.57 (m, 1H), 7.51−7.49 (m, 2H),
7.44−7.43 (m, 4H), 7.38−7.35 (m, 1H) 7.19−7.17 (m, 2H), 5.44 (s,
2H), 5.17 (s, 2H); 13C{1H} NMR (125 MHz, CDCl3): δ 168.1,
163.7, 160.0, 151.5, 151.3, 136.6, 132.4, 131.7, 129.3, 128.7, 128.6,
128.19, 128.17, 127.6, 127.2, 123.8, 114.6, 113.3, 70.2, 69.4; HRMS
4
1JC−F = 260.37 Hz), 152.2, 149.7, 134.0 (d, JC−F = 4.56 Hz), 132.7
3
4
(d, JC−F = 9.67 Hz), 128.9, 127.9 (d, JC−F = 3.38 Hz), 127.6, 125.7
4
3
(d, JC−F = 4.55 Hz), 117.8 (d, JC−F = 9.27 Hz), 115.0, 112.9 (d,
2JC−F = 21.67 Hz), 69.1; HRMS (ESI-TOF) m/z: [M + Na]+ calcd for
+
(ESI-TOF) m/z: [M + Na]+ calcd for C24H17NNaO3 , 390.1106;
+
C17H10FNNaO2 , 302.0587; found, 302.0594.
found, 390.1081.
5-Bromo-7-chloro-9-phenylfuro[3,4-b]quinolin-1(3H)-one (2d).
9-(4-Methoxyphenyl)furo[3,4-b]quinolin-1(3H)-one (2l). White
1
White solid, yield 65% (39 mg), hexane/EtOAc (92:8); H NMR
1
solid, yield 50% (30.0 mg), hexane/EtOAc (91:9); H NMR (500
(500 MHz, CDCl3): δ 8.20 (d, J = 2.25 Hz, 1H), 7.83 (d, J = 2.25 Hz,
1H), 7.61 (d, J = 1.85 Hz, 2H), 7.60 (d, J = 2.35 Hz, 1H), 7.42 (d, J =
1.85 Hz, 1H), 7.41−7.40 (m, 1H), 5.52 (s, 2H); 13C{1H} NMR (125
MHz, CDCl3): δ 166.8, 164.5, 151.2, 146.9, 136.4, 133.2, 130.6,
130.0, 129.6, 128.8, 128.5, 126.4, 125.7, 115.0, 69.7; HRMS (ESI-
MHz, CDCl3): δ 8.18 (d, J = 8.40 Hz, 1H), 8.00 (d, J = 8.15 Hz, 1H),
7.90−7.87 (m, 1H), 7.58 (t, J = 7.25 Hz, 1H), 7.43 (d, J = 8.65 Hz,
2H), 7.10 (d, J = 8.65 Hz, 2H), 5.43 (s, 2H), 3.92 (s, 3H); 13C{1H}
NMR (125 MHz, CDCl3): δ 168.2, 163.7, 160.7, 151.6, 151.3, 132.5,
131.6, 129.3, 128.2, 127.29, 127.24, 123.4, 113.7, 113.3, 69.4, 55.3;
+
TOF) m/z: [M + H]+ calcd for C17H10BrClNO2 , 373.9577; found,
+
HRMS (ESI-TOF) m/z: [M + H]+ calcd for C18H14NO3 , 292.0968;
373.9588.
found, 292.0975.
9-Phenylfuro[3,4-b]quinolin-1(3H)-one (2e)11. White solid, yield
53% (31.7 mg), hexane/EtOAc (93:7); 1H NMR (400 MHz,
CDCl3): δ 8.21 (d, J = 8.24 Hz, 1H), 7.93−7.89 (m, 2H), 7.61−
7.57 (m, 4H), 7.47−7.45 (m, 2H), 5.46 (s, 2H); 13C{1H} NMR (125
MHz, CDCl3): δ 167.8, 163.6, 151.4, 151.3, 132.5, 131.6, 129.8,
129.5, 129.3, 128.2, 128.0, 127.4, 127.0, 113.5, 69.5; HRMS (ESI-
9-(3-Chloro-4-fluorophenyl)furo[3,4-b]quinolin-1(3H)-one (2m).
White solid, yield 70% (70.0/42 mg), hexane/EtOAc (92:8); 1H
NMR (500 MHz, CDCl3): δ 8.22 (d, J = 8.50 Hz, 1H), 7.95−7.91
(m, 1H), 7.87 (d, J = 8.60 Hz, 1H), 7.66−7.62 (m, 1H), 7.51 (d, J =
6.80 Hz, 1H), 7.36 (d, J = 6.80 Hz, 2H), 5.46 (s, 2H); 13C{1H} NMR
1
(125 MHz, CDCl3): δ 167.7, 163.5, 158.8 (d, JC−F = 250.8 Hz),
+
TOF) m/z: [M + Na]+ calcd for C17H11NNaO2 , 284.0681; found,
151.3, 148.5, 132.8, 132.0, 129.9 (d, 3JC−F = 7.5 Hz), 129.6, 128.5 (d,
284.0680.
2
4JC−F = 4.2 Hz), 127.9, 127.3, 126.6, 121.4 (d, JC−F = 17.10 Hz),
6-Methyl-9-phenylfuro[3,4-b]quinolin-1(3H)-one (2f). White
116.7 (d, 2JC−F = 21.50 Hz), 113.6, 69.6; HRMS (ESI-TOF) m/z: [M
1
solid, yield 51% (30.6 mg), hexane/EtOAc (93:7); H NMR (400
+
+ H]+ calcd for C17H10ClFNO2 , 314.0378; found, 314.0370.
MHz, CDCl3): δ 7.97 (s, 1H), 7.79 (d, J = 8.68 Hz, 1H), 7.59−7.56
(m, 3H), 7.45−7.44 (m, 2H), 7.42−7.40 (m, 1H) 5.43 (s, 2H), 2.62
(s, 3H); 13C{1H} NMR (100 MHz, CDCl3): δ 168.1, 163.8, 151.6,
151.2, 143.7, 131.8, 129.8, 129.7, 129.4, 128.3, 128.2, 127.7, 125.1,
112.7, 69.8, 22.0 HRMS (ESI-TOF) m/z: [M + H]+ calcd for
7-Chloro-9-(2-chlorophenyl)furo[3,4-b]quinolin-1(3H)-one (2n).
1
White solid, yield 70% (42.0 mg), hexane/EtOAc (92:8); H NMR
(500 MHz, CDCl3): δ 8.17 (d, J = 9.05 Hz, 1H), 7.83 (dd, J1 = 9.0
Hz, J2 = 2.3 Hz, 1H), 7.63−7.61 (m, 2H), 7.55 (td, J1 = 7.60 Hz, J2 =
1.70 Hz, 1H), 7.48 (td, J1 = 7.45 Hz, J2 = 1.30 Hz, 1H), 7.28 (dd, J1 =
7.60 Hz, J2 = 1.75 Hz, 1H), 5.46 (s, 2H); 13C{1H} NMR (125 MHz,
CDCl3): δ 167.0, 163.6, 149.7, 146.9, 133.9, 133.6, 132.9, 131.1,
131.0, 130.6, 130.5, 130.0, 127.5, 126.9, 126.0, 115.3, 69.8; HRMS
+
C18H14NO2 , 276.1019; found, 276.1011.
9-(4-fluorophenyl)furo[3,4-b]quinolin-1(3H)-one (2g).11e White
1
solid, yield 61% (36.6 mg), hexane/EtOAc (92:8); H NMR (400
MHz, CDCl3): δ 8.22 (d, J = 8.40 Hz, 1H), 7.94−7.89 (m, 2H),
+
(ESI-TOF) m/z: [M + Na]+ calcd for C17H9Cl2NNaO2 , 351.9902;
7.63−7.59 (m, 1H), 7.48−7.44 (m, 2H), 7.30−7.29 (m, 2H), 5.46 (s,
1
2H); 13C{1H} NMR (125 MHz, CDCl3): δ 167.8, 163.5 (d, JC−F
=
found, 351.9903.
3
9-(2-Chlorophenyl)-7-nitrofuro[3,4-b]quinolin-1(3H)-one (2o).
248.26 Hz), 163.6, 151.3, 150.3, 132.6, 131.8 (d, JC−F = 8.45 Hz),
1
129.5, 127.64 (d, 2JC−F = 20.37 Hz) (2C), 127.01, 115.55 (d, 2JC−F
=
White solid, yield 74% (74.0/44.3 mg), hexane/EtOAc (90:10); H
21.76 Hz) (2C), 113.57, 69.5; HRMS (ESI-TOF) m/z: [M + H]+
NMR (500 MHz, CDCl3): δ 8.17 (d, J = 9.0 Hz, 1H), 7.83 (dd, J1 =
9.05 Hz, J2 = 2.40 Hz, 1H), 7.64−7.61 (m, 2H), 7.57−7.53 (m, 1H),
7.50−7.47 (m, 1H), 7.29 (dd, J1 = 7.55 Hz, J2 = 1.65 Hz, 1H), 5.48 (s,
2H); 13C{1H} NMR (125 MHz, CDCl3): δ 167.0, 163.6, 149.7,
146.9, 133.9, 133.6, 132.9, 131.1, 131.0, 130.6, 130.5, 130.0, 127.4,
126.9, 126.0, 115.3, 69.8; HRMS (ESI-TOF) m/z: [M + H]+ calcd for
+
calcd for C17H11FNO2 , 280.0768; found, 280.0770.
9-(4-Chlorophenyl)furo[3,4-b]quinolin-1(3H)-one (2h). White
1
solid, yield 59% (35.4 mg), hexane/EtOAc (92:8); H NMR (500
MHz, CDCl3): δ 8.21 (d, J = 8.45 Hz, 1H), 7.93−7.87 (m, 2H),
7.62−7.59 (m, 2H), 7.56 (d, J = 8.45 Hz, 1H), 7.40 (d, J = 8.40 Hz,
2H), 5.45 (s, 2H); 13C{1H} NMR (125 MHz, CDCl3): δ 167.8,
+
C17H10ClN2O4 , 341.0323; found, 341.0328.
F
https://dx.doi.org/10.1021/acs.joc.0c02238
J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
pubs.acs.org/joc
Article
7-Chloro-9-(2-fluorophenyl)furo[3,4-b]quinolin-1(3H)-one (2p).
White solid, yield 71% (42.6 mg), hexane/EtOAc (93:7); H NMR
145.0, 134.8, 133.6, 130.5, 129.9 (2C), 129.6, 129.1, 128.8, 127.8,
1
1
126.2, 85.06 (d, JC−F = 166.55 Hz), 31.8; 19F NMR (376 MHz,
CDCl3): δ −113.9; HRMS (ESI-TOF) m/z: [M + H]+ calcd for
(500 MHz, CDCl3): δ 8.17 (d, J = 9.0 Hz, 1H), 7.85 (dd, J1 = 9.05
Hz, J2 = 2.35 Hz, 1H), 7.79 (s, 1H), 7.63−7.59 (m, 1H), 7.39−7.36
(m, 2H), 7.34−7.31 (m, 1H), 5.47 (s, 2H); 13C{1H} NMR (125
C18H15FNO+, 280.1132; found: 280.1125.
1-(4-(4-Bromophenyl)-2-(fluoromethyl)quinolin-3-yl)ethan-1-
one (3c). White solid, yield 20% (12.6 mg), hexane/EtOAc (95:5);
1H NMR (500 MHz, CDCl3): δ 8.16 (d, J = 8.45 Hz, 1H), 7.80−7.77
(m, 1H), 7.69 (d, J = 3.3 Hz, 2H), 7.63 (dd, J1 = 7.63 Hz, J21= 1.45
1
MHz, CDCl3): δ 167.0, 163.5, 159.60 (d, JC−F = 247.50 Hz), 149.7,
3
4
143.8, 133.9, 133.5, 132.07 (d, JC−F = 8.15 Hz), 131.24 (d, JC−F
=
2.47 Hz), 131.0, 127.6, 126.0, 124.27 (d, 4JC−F = 3.60 Hz), 118.98 (d,
2JC−F = 15.9 Hz), 116.19 (, JC−F = 21.2 Hz), 115.3, 69.6; HRMS
2
Hz, 1H), 7.56−7.53 (m, 1H), 7.26−7.25 (m, 2H), 5.72 (d, JH−F
=
+
(ESI-TOF) m/z: [M + H]+ calcd for C17H10ClFNO2 , 314.0378;
46.65 Hz, 2H), 2.05 (s, 3H); 13C{1H} NMR (125 MHz, CDCl3): δ
2
found, 314.0370.
204.5, 151.6 (d, JC−F = 18.65 Hz), 146.9, 143.5, 133.6, 132.1 (2C),
1
8-Fluoro-9-(4-fluorophenyl)furo[3,4-b]quinolin-1(3H)-one (2q).
131.5, 130.6 (2C), 129.7, 128.0, 125.9, 125.8, 123.7, 85.0 (d, JC−F
=
1
White solid, yield 78% (46.8 mg), hexane/EtOAc (92:8); H NMR
166.8 Hz), 32.0; 19F NMR (376 MHz, CDCl3): δ −113.5; HRMS
(ESI-TOF) m/z: [M + H]+ calcd for C18H14BrFNO+, 358.0237;
found, 358.0247.
(500 MHz, CDCl3): δ 8.05−8.03 (m, 1H), 7.87−7.83 (m, 1H),
7.37−7.34 (m, 2H), 7.26−7.23 (m, 1H), 7.22−7.20 (m, 1H), 7.19−
7.17 (m, 1H), 5.42 (s, 2H); 13C{1H} NMR (100 MHz, CDCl3): δ
1-(4-(4-Chlorophenyl)-2-(fluoromethyl)-6-nitroquinolin-3-yl)-
ethan-1-one (3d). White solid, yield 28% (17.6 mg), hexane/EtOAc
(95:5); 1H NMR (500 MHz, CDCl3): δ 8.56−8.53 (m, 1H), 8.52 (d,
J = 2.28 Hz, 1H), 8.29 (d, J = 9.04 Hz, 1H), 7.61−7.59 (m, 2H),
1
1
167.1, 164.0, 163.6 (d, JC−F = 246.81 Hz), 159.9 (d, JC−F = 261.03
3
4
Hz), 152.3, 148.7, 132.8 (d, JC−F = 9.81 Hz), 130.0 (d, JC−F = 3.6
Hz), 129.9 (d, JC−F = 3.53 Hz), 125.8 (d, JC−F = 4.35 Hz), 114.9
4
4
1
1
(2C) (d, JC−F = 28.7 Hz), 113.0 (2C) (d, JC−F = 21.7 Hz), 69.2;
1
7.33−7.32 (m, 2H), 5.73 (d, JH−F = 46.44 Hz, 2H), 2.05 (s, 3H);
+
HRMS (ESI-TOF) m/z: [M + Na]+ calcd for C17H9F2NNaO2 ,
13C{1H} NMR (100 MHz, CDCl3): δ 202.2, 154.58 (d, 2JC−F = 18.88
320.0493; found, 320.0476.
Hz), 147.8, 145.5, 144.3, 135.5, 134.0, 130.7, 130.5, 130.1, 128.7,
9-(4-Bromophenyl)-8-fluorofuro[3,4-b]quinolin-1(3H)-one (2r).
1
124.3, 123.0, 121.6, 83.64 (d, JC−F = 168.53 Hz), 30.7; 19F NMR
1
White solid, yield 75% (45 mg), hexane/EtOAc (92:8); H NMR
(376 MHz, CDCl3): δ −114.5. HRMS (ESI-TOF) m/z: [M + H]+
(500 MHz, CDCl3): δ 8.05 (d, J = 8.55 Hz, 1H), 7.89−7.84 (m, 1H),
7.65−7.63 (m, 2H), 7.27−7.26 (m, 1H), 7.25−7.23 (s, 2H), 5.44 (s,
2H); 13C{1H} NMR (100 MHz, CDCl3): δ 167.0, 164.5, 159.6 (d,
1JC−F = 277.65 Hz), 152.3, 148.3, 132.9, 132.88, 132.81, 131.0, 129.6
+
calcd for C18H13ClFN2O3 , 359.0593; found, 359.0600.
1-(6-Chloro-4-phenyl-2-(((2,2,6,6-tetramethylpiperidin-1-yl)oxy)-
methyl)quinolin-3-yl)ethan-1-one (2a″). White solid, yield 69%
1
4
4
(62.37 mg), hexane/EtOAc (98:2); H NMR (500 MHz, CDCl3): δ
(d, JC−F = 3.53 Hz), 125.9 (d, JC−F = 4.31 Hz), 123.4, 115.6, 113.1
(d, 4JC−F = 4.31 Hz), 69.2; HRMS (ESI-TOF) m/z: [M + Na]+ calcd
for C17H9BrFNNaO2 , 379.9692; found, 379.9693.
8.59 (d, J = 2.40 Hz, 1H), 8.47 (d, J = 2.45 Hz, 1H), 8.26 (d, J = 9.20
Hz, 1H), 7.60−7.58 (m, 3H), 7.39−7.38 (m, 2H), 5.23 (s, 2H), 2.05
(s, 3H), 1.53−1.51 (m, 3H), 1.48−1.46 (m, 3H), 1.22 (s, 6H), 1.05
(s, 6H); 13C{1H} NMR (125 MHz, CDCl3): 203.3, 157.4, 149.2,
146.0 (2C), 135.6, 133.7, 131.6, 129.9, 129.8, 129.2, 125.3, 123.3,
123.0, 80.3, 60.1, 39.9, 32.8, 32.1, 20.6, 17.0; HRMS (ESI-TOF) m/z:
+
9-(4-Chlorophenyl)-7-nitrofuro[3,4-b]quinolin-1(3H)-one (2s).
1
White solid, yield 75% (45 mg), hexane/EtOAc (90:10); H NMR
(500 MHz, CDCl3): δ 8.83 (d, J = 2.55 Hz, 1H), 8.66 (dd, J1 = 9.25
Hz, J2 = 2.55 Hz, 1H), 8.37 (d, J = 9.25 Hz, 1H), 7.63 (d, J = 7.90,
2H), 7.44 (d, J = 8.35, 2H), 5.51 (s, 2H); 13C{1H} NMR (125 MHz,
CDCl3): δ 167.1, 166.6, 153.1, 152.2, 146.3, 137.1, 131.5, 131.3,
129.2, 128.3, 126.1, 125.8, 124.4, 115.2, 69.6; HRMS (ESI-TOF) m/
+
[M + H]+ calcd for C27H32N3O4 , 462.2387; found, 462.2309.
ASSOCIATED CONTENT
+
z: [M + H]+ calcd for C17H10ClN2O4 , 341.0323; found, 341.0324.
■
Furo[3,4-b]quinoxalin-1(3H)-one (2t). White solid, yield 39%
sı
* Supporting Information
1
(23.4 mg), hexane/EtOAc (92:8); H NMR (500 MHz, CDCl3): δ
The Supporting Information is available free of charge at
https://pubs.acs.org/doi/10.1021/acs.joc.0c02238.
8.41 (dd, J1 = 8.45 Hz, J2 = 1.7 Hz, 1H), 8.24 (dd, J1 = 8.42 Hz, J2 =
1.45 Hz, 1H), 8.04−8.00 (m, 1H), 7.98−7.95 (m, 1H), 5.61 (s, 2H);
13C{1H} NMR (125 MHz, CDCl3): δ 166.3, 156.5, 144.2 (2C),
138.4, 133.6, 131.5, 131.3, 129.3, 69.0; HRMS (ESI-TOF) m/z: [M +
1
Copies of H NMR, 13C NMR, and HRMS for all
synthesized compounds and mechanistic investigation
(PDF)
+
H]+ calcd for C10H7N2O2 , 187.0502; found, 187.0491.
7-Nitro-5-phenyl-1H-pyrano[3,4-b]quinolin-4(3H)-one (2a′).
1
White solid, hexane/EtOAc (85:15), H NMR (400 MHz, CDCl3):
δ 8.56 (dd, J1 = 9.20 Hz, J2 = 2.44 Hz, 1H), 8.51 (d, J = 2.44 Hz, 1H),
8.23 (d, J = 9.20 Hz, 1H), 7.60−7.58 (m, 3H), 7.25−7.23 (m, 2H),
5.16 (s, 2H), 4.41 (s, 2H); 13C{1H} NMR (125 MHz, CDCl3): δ
192.7, 162.6, 153.5, 150.6, 146.0, 134.5, 130.8, 129.1, 128.7, 128.2,
127.0, 125.4, 125.0, 122.1, 74.3, 71.2; HRMS (ESI-TOF) m/z: [M +
AUTHOR INFORMATION
■
Corresponding Author
Nidhi Jain − Department of Chemistry, Indian Institute of
Technology, New Delhi 110016, India; orcid.org/0000-
0001-8645-430X; Email: njain@chemistry.iitd.ac.in
+
H]+ calcd for C18H13N2O4 , 321.0869; found, 321.0880.
1-(2-(Fluoromethyl)-6-nitro-4-phenylquinolin-3-yl)ethan-1-one
1
(3a). White solid, yield 30% (19.05 mg), hexane/EtOAc (94:6); H
NMR (400 MHz, CDCl3): δ 8.62 (d, J = 2.44 Hz, 1H), 8.53 (dd, J1 =
9.16 Hz, J2 = 2.52 Hz, 1H), 8.28 (d, J = 9.20 Hz, 1H), 7.62−7.60 (m,
Authors
Alankrita Garia − Department of Chemistry, Indian Institute
of Technology, New Delhi 110016, India
Parul Chauhan − Department of Chemistry, Indian Institute of
Technology, New Delhi 110016, India
Riya Halder − Department of Chemistry, Indian Institute of
Technology, New Delhi 110016, India
1
3H), 7.38−7.36 (m, 2H), 5.74 (d, JH−F = 46.44 Hz, 2H), 1.99 (s,
2
3H); 13C{1H} NMR (100 MHz, CDCl3): δ 203.7, 155.6 (d, JC−F
=
18.6 Hz), 148.9, 146.8, 146.4, 134.9, 133.2, 131.6, 130.1, 129.8, 129.4,
125.6, 123.9, 123.1, 84.7 (d, 1JC−F = 168.41 Hz), 31.5; 19F NMR (376
MHz, CDCl3): δ −115.0; HRMS (ESI-TOF) m/z: [M + H]+ calcd
+
for C18H14FN2O3 , 325.0982; found, 325.0990.
1-(2-(Fluoromethyl)-4-phenylquinolin-3-yl)ethan-1-one (3b).
White solid, yield 16% (10.2 mg), hexane/EtOAc (95:5); H NMR
Complete contact information is available at:
https://pubs.acs.org/10.1021/acs.joc.0c02238
1
(500 MHz, CDCl3): δ 8.15 (d, J = 8.35 Hz, 1H), 7.79−7.76 (m, 1H),
7.69−7.68 (d, J = 8.35 Hz, 1H), 7.54−7.51 (m, 4H), 7.38−7.36 (m,
1
2H), 5.72 (d, JH−F = 46.70 Hz, 2H), 1.98 (s, 3H); 13C{1H} NMR
Notes
2
(125 MHz, CDCl3): δ 204.9, 151.65 (d, JC−F = 18.43 Hz), 146.9,
The authors declare no competing financial interest.
G
https://dx.doi.org/10.1021/acs.joc.0c02238
J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
pubs.acs.org/joc
Article
(3H,5H)-Furandione: Heteroannulations with Aromatic o-Amino
Carbonyl Compounds and Condensations with Some Vic-Polyones. J.
Org. Chem. 1983, 48, 1914−1916.
ACKNOWLEDGMENTS
■
A.G. thanks the UGC for her graduate fellowship. The authors
thank the DST-FIST for funding the ESI-HRMS facility at IIT
Delhi.
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