Zn(OTf)2-Catalyzed Formal [3 + 3] Cascade Annulation of Propargylic Alcohols with 2-Aminochromones: Accessing the Chromeno[2,3- b]pyridines

Article abstract of DOI:10.1021/acs.joc.9b02120

A Zn(OTf)₂-catalyzed formal [3 + 3] cascade annulation strategy for the synthesis of functionalized chromeno[2,3-b]pyridines has been developed using propargylic alcohols and 2-aminochromones as the substrates. The protocol provides a convenien

Full text of DOI:10.1021/acs.joc.9b02120

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Article
Zn(OTf)2-Catalyzed Formal [3+3] Cascade Annulation of Propargylic
Alcohols with 2-Aminochromones: Accessing to Chromeno[2,3-b]pyridines
Pei Tong, Zhou Sun, Shutao Wang, Yuan Zhang, and Ying Li
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.9b02120 • Publication Date (Web): 25 Sep 2019
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Zn(OTf)2-Catalyzed Formal [3+3] Cascade Annulation of
Propargylic Alcohols with 2-Aminochromones: Accessing to
Chromeno[2,3-b]pyridines
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Pei Tong,†, § Zhou Sun,†, ‡, § Shutao Wang,† Yuan Zhang,*, † and Ying Li*, †
†State Key Laboratory of Applied Organic Chemistry, College of Chemistry and Chemical Engineering, Lanzhou
University, Lanzhou 730000, People’s Republic of China
‡Institute for Advanced Interdisciplinary Research, Qilu University of Technology, Daxue Road No.3501, Jinan,
Shandong 250353, People’s Republic of China
Abstract:
A Zn(OTf)2-catalyzed formal [3+3] cascade annulation strategy for the synthesis of
functionalized chromeno[2,3-b]pyridines has been developed using propargylic alcohols and
2-aminochromones as the substrates. The protocol provides a convenient and atom-economical
method of accessing a broad range of chromeno[2,3-b]pyridine derivatives in excellent yields with
good functional-group tolerance. The method is also effective on gram scale, which highlights the
inherent practicality of this synthetic transformation.
Introduction
Functionalized 4-oxo-4H-chromones are of particular utility since they belong to privileged
medicinal scaffolds,1 and serve as key intermediates for the construction of a variety of novel
heterocycles possessing diverse biological activities.2 Among the family of 4-oxo-4H-chromones,
the chromeno[2,3-b]pyridine scaffold is a key skeleton that exists in many pharmacologically
active molecules. The derivatives of these compounds have been found to show diverse
biological activities, such as glucocorticoid receptor (GR) agonists,3a antiinflammatory,3b,3c
antiproliferative,3d antiasthmatic,3e antitumor,3f antirheumatic,4a antimyopic,4a antihistaminic,4a
hypotensive,4a and antibacterial activities;3g,3h some chromeno[2,3-b]pyridine derivatives show
potential application prospect for the treatment of Alzheimer’s disease.3i,3j Owing to their
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intriguing pharmaceutical and biological activities, the development of practical and efficient
approaches for the synthesis of chromeno[2,3-b]pyridine derivatives has attracted considerable
attention. In 2007, Kornienko and co-workers showed a noteworthy single-step multicomponent
reaction of salicylic aldehydes with various thiols and malononitrile, delivered
chromeno[2,3-b]pyridine derivatives (Scheme 1a).4a In 2008, Kumaret al. reported a gold
catalyzed condensation reaction, leading to aza-xanthone frameworks from aryl alkyl ketones
(Scheme 1b).4b Lawson and co-workers developed an efficient one-pot domino process through a
1,6-aza-Michael addition-triggered sequence and an original Mitsunobu-type concerted sequence
for the synthesis of chromenopyridine systems containing a bis-N,O-acetal junction (Scheme 1c).4c
Although these methods are effective for certain substrates,5 the development of more versatile,
convenient and efficient methods starting from easily available substrates is still highly desirable
for the generation of chromeno[2,3-b]pyridine derivatives.
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Scheme 1. Strategy for the Synthesis of Chromeno[2,3-b]pyridine derivatives
Recently, propargyl alcohols have been widely used as unique synthons in organic synthesis.6
Upon treatment with Lewis acids, propargyl alcohols would readily undergo the Meyer-Schuster
rearrangement to form allenic carbocations, which can participate in several [3+n] (n = 2, 3, 4)
annulation reactions with apt partners to give a range of carbocycles and heterocycles.7 In
particular, this phenomenon has been exploited with 1,3-bis-nucleophilic enamines for the
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synthesis of five,8a six8b-d and seven-membered8e rings. However, to the best of our knowledge, the
annulation reaction involving propargylic alcohols and chromone derivatives has not been
properly explored. Inspired by these intriguing discoveries for propargylic alcohols, we herein
describe a Zn(OTf)2-catalyzed formal [3+3] cascade annulation of propargylic alcohols with
2-aminochromones containing nonprotected free NH2, leading to the facile formation of
chromeno[2,3-b]pyridine derivatives in excellent yields.
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Results and Discussion
Initially, propargylic alcohol 1a and 2-aminochromone 2a were selected as the model substrates
to screen the optimal experimental conditions (Table 1). We first screened various Lewis acids, to
our delight, the expected transformation could occur in the presence of AgOTf or Cu(OTf)2 in
PhCH3 at 100 °C , and the desired compound 3a was obtained in 56% and 18% yield, respectively
(Table 1, entries 5–6). The structure of 3a was further identified by the X-ray crystal structure
analysis (for details see the Supporting Information).9 Gratifyingly, the yield was notably
increased when Zn(OTf)2 was chosen as the catalyst (Table 1, entry 7). Among several solvents
screened, DCE was found to be the best in terms of product yield (Table 1, entries 8–12).
Temperature screening showed that 100 °C was optimal to give an 89% yield of the desired
product (Table 1, entries 9, 13–15). By decreasing the catalyst loading to 10 mol %, the yield of
the product slightly reduced to 80% (Table 1, entry 16). Ultimately, the optimal reaction
conditions for the construction of the expected product 3a were chosen as: the use of propargylic
alcohol 1a (0.1 mmol) and 2-aminochromone 2a (0.15 mmol) in the presence of Zn(OTf)2 (20
mol %) in DCE (2.0 mL) at 100 °C.
Table 1. Optimization of the Reaction Conditionsa
entry catalyst
solvent
temp. (°C) yield (%)b
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Sc(OTf)3 PhCH3
La(OTf)3 PhCH3
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100
100
0
0
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Y(OTf)3
PhCH3
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Yb(OTf)3 PhCH3
AgOTf PhCH3
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Cu(OTf)2 PhCH3
Zn(OTf)2 PhCH3
Zn(OTf)2 THF
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Zn(OTf)2 DCE
Zn(OTf)2 CH3NO2
Zn(OTf)2 CH3CN
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Zn(OTf)2 1,4-dioxane 100
Zn(OTf)2 DCE
Zn(OTf)2 DCE
Zn(OTf)2 DCE
Zn(OTf)2 DCE
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80
120
100
aUnless otherwise indicated, all reactions were carried out with 1a (0.1 mmol),
2a (0.15 mmol) and catalyst (20 mol %) in solvent (2.0 mL) in a sealed tube.
bYield of the isolated product. The reaction was performed with 10 mol %
c
catalyst.
With the optimal conditions in hand, we next examined the scope of propargylic alcohols in this
annulation reaction. We first investigated the electronic effects of the aromatic substituents (R3) of
propargylic alcohols 1 (Scheme 2). Propargylic alcohols 1 bearing either electron donating or
electron withdrawing groups in their aryl moiety (R3) showed moderate to good reactivity toward
the desired products (3a–3l, 71%–97%). Symmetrical propargylic alcohols containing either
electron donating (3m, 3n) or withdrawing (3o–3q) groups on the phenyl rings (R1, R2) gave high
yields of the expected products (3m–3q, 75%–97%). Moreover, the unsymmetrical propargylic
alcohols with a series of substituents at the ortho-, meta- and para-positions of the phenyl ring
reacted readily with 2a to provide the desired products in moderate to good yields (3r–3w, 79%–
97%). Regrettably, the alkyl-substituted (R1 = Me or cyclohexyl) propargylic alcohols led to no
reaction due to their less reactivity.
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Scheme 2. Scope with Respect to Propargylic Alcoholsa,b
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aUnless otherwise indicated, all reactions were carried out with 1 (0.1 mmol), 2a (0.15 mmol), and Zn(OTf)2 (20
mol %) in DCE (2.0 mL) at 100 °C in a sealed tube. bYield of the isolated product.
The scope of 2-aminochromones 2 was subsequently investigated with propargylic alcohols 1a
as partners (Scheme 3). Halogen-containing substrates (2b–2d) were well tolerated, and the
annulated products (3ab–3ad) were obtained in good yields (80–87%). Likewise,
2-aminochromones (2e–2g) possessing 6-Me, 6-MeO and 7-MeO groups efficiently cyclized into
the corresponding products (3ae–3ag) in 72–90% yields. Moreover, 2-amino-
7,8-dimethoxy-4H-chromen-4-one 2h and 2-amino-5-methoxy-7-methyl-4H-chromen-4-one 2i led
to the formation of expected products 3ah and 3ai in good yields respectively.
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Scheme 3. Scope with Respect to 2-Aminochromonesa,b
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aUnless otherwise indicated, all reactions were carried out with 1a (0.1 mmol), 2 (0.15 mmol), and Zn(OTf)2 (20
mol %) in DCE (2.0 mL) at 100 °C in a sealed tube. bYield of the isolated product.
In order to expand the synthetic competence of our strategy, a gram-scale synthesis of 3a was
performed under the standard conditions. The desired chromeno[2,3-b]pyridine 3a was isolated in
81% yield, which demonstrated the potential applicability of our strategy (Scheme 4).
Scheme 4. Large-Scale Synthesis of 3a
A plausible mechanism based on the precedent literatures is illustrated in Scheme 5.10 Initially,
the Lewis acid catalyst Zn(OTf)2 promotes the formation of active propargyl intermediate A from
propargylic alcohol 1, which could afford the allenic carbocation B formed in situ through the
Meyer-Schuster rearrangement. Subsequently, the allenic carbocation B undergoes a nucleophilic
attack by the 2-aminochromone 2 to furnish iminium intermediate C, which could readily
transform to intermediate D by the removal of a proton. Finally, the protonation of intermediate D
delivers intermediate E, which could undergo an intramolecular nucleophilic attack to afford the
desired product 3.8b
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Scheme 5. Proposed Mechanism for the Formation of Chromeno[2,3-b]pyridine Derivatives
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Conclusion
In summary, we have developed a Zn(OTf)2 catalyzed formal [3+3] cascade annulation of
propargylic alcohols with 2-aminochromones that provides a practical, convenient and efficient
method for the formation of chromeno[2,3-b]pyridine derivatives in good to excellent yields. The
reaction conditions tolerate a wide scope of typical organic functional groups. The highly efficient
catalytic system, operational simplicity and good functional group compatibility of this strategy
can be ranked the sustainable and convenient alternatives for the synthesis of
chromeno[2,3-b]pyridine derivatives.
EXPERIMENTAL SECTION
General Experimental Procedures
All reactions under standard conditions were monitored by thin-layer chromatography (TLC) on
GF254 plates. Silica gel (200−300 mesh) was used for column chromatography. Unless otherwise
noted, commercially available reagents and solvents were used without any purification. The
distillation range of petroleum ether was 60–90 °C. Liquid 1H NMR, 13C NMR and 19F NMR
spectra were recorded on a 400 MHz spectrometer. The data were reported as follows: chemical
shift on the δ scale using the residual proton solvent as the internal standard [δ 0.00 (TMS)],
multiplicity (br = broad, s = singlet, d = doublet, t = triplet, q = quartet, m = multiplet), integration,
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and coupling constant(s) J in hertz. High-resolution mass spectras (HRMS) were obtained on a
mass spectrometer using electrospray ionization (ESI) analyzed by quadrupole time-of-flight
(QToF). Melting points were determined on a microscopic apparatus and were uncorrected. The
required propargyl alcohols were prepared by following the literature procedure.11
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General Procedure for the synthesis of 2-aminochromones 2. The required 2-aminochromones
were prepared by following the literature procedure.12 o-Hydroxyacetophenone (10 mmol) and
dimethylformamide dimethyl acetal (DMFDA, 15 mmol, 1.5 equiv) were heated at 90–100 °C for
2h. The reaction mixture was cooled to room temperature and excess methanol and DMFDA were
removed in vacuo to leave a light brown solid. This solid was purified by column chromatography
on silica gel using petroleum ether/ethyl acetate to obtain the desired enamino ketones.
To an EtOH solution (50 mL) of enamino ketone (5 mmol), NH2OH·HCl (7.5 mmol, 1.5 equiv)
was added. The reaction mixture was heated under reflux for 30 min. Solvent was removed under
reduced pressure. Ice-cold H2O (50 mL) was added to the residue, the precipitated solid was
filtered off, washed with H2O, dried in air and recrystallized (ethyl acetate–light petroleum) to
afford crystalline isoxazole solids.
Et3N (5 mmol, 1.0 equiv) was added to a solution of isoxazole (5 mmol) in DMF (30 mL). The
reaction mixture was heated in an oil bath at 140–150 °C for 8 h. DMF was removed under
reduced pressure and ice-cold H2O was added to the residue. The separated solid was filtered off
and recrystallized from MeOH to get crystalline compounds 2.
1
2-Amino-4H-chromen-4-one (2a). Pale yellow solid, mp 254–255 °C , 0.65 g, 81% yield. H
NMR (400 MHz, DMSO-d6) δ 7.91 (d, J = 7.5 Hz, 1H), 7.65 – 7.54 (m, 3H), 7.43 – 7.28 (m, 2H),
5.21 (s, 1H). 13C{1H} NMR (101 MHz, DMSO-d6) δ 175.0, 165.4, 153.7, 132.5, 25.1, 124.9,
123.4, 116.9, 85.5. HRMS (ESI): calcd for C9H8NO2 (M+H)+ 162.0550, found 162.0551.
1
2-Amino-6-fluoro-4H-chromen-4-one (2b). Brown solid, mp257–258 °C , 0.54 g, 60% yield. H
NMR (400 MHz, DMSO-d6) δ 7.63 (s, 2H), 7.55 (d, J = 5.5 Hz, 1H), 7.45 (s, 2H), 5.19 (s, 1H).
13C{1H} NMR (101 MHz, DMSO-d6) δ 173.9, 165.5, 159.1 (d, J(C, F) = 243.4 Hz), 149.9, 124.9,
119.9 (d, J(C, F) = 25.3 Hz), 119.3 (d, J(C, F) = 8.1 Hz), 110.1 (d, J(C, F) = 24.2 Hz), 85.2.
19F{1H} NMR (376 MHz, DMSO-d6) δ -117.4. HRMS (ESI): calcd for C9H7FNO2 (M+H)+
180.0455, found 180.0459.
2-Amino-6-chloro-4H-chromen-4-one (2c). Pale grey solid, mp 284–285 °C , 0.76 g, 78% yield.
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1H NMR (400 MHz, DMSO-d6) δ 7.81 (s, 1H), 7.75 – 7.58 (m, 3H), 7.42 (d, J = 8.7 Hz, 1H), 5.19
(s, 1H). 13C{1H} NMR (101 MHz, DMSO-d6) δ 173.4, 165.5, 152.2, 132.3, 129.3, 124.9, 124.2,
119.3, 85.5. HRMS (ESI): calcd for C9H7ClNO2 (M+H)+ 196.0160, found 196.0163.
2-Amino-6-bromo-4H-chromen-4-one (2d). Pale grey solid, mp 282–283 °C , 0.80 g, 67% yield.
1H NMR (400 MHz, DMSO-d6) δ 7.95 (s, 1H), 7.78 – 7.61 (m, 3H), 7.36 (d, J = 8.0 Hz, 1H), 5.19
(s, 1H). 13C{1H} NMR (101 MHz, DMSO-d6) δ 173.3, 165.4, 152.6, 135.0, 127.3, 125.2, 119.6,
117.2, 85.5. HRMS (ESI): calcd for C9H7BrNO2 (M+H)+ 239.9655, found 239.9658.
2-Amino-6-methyl-4H-chromen-4-one (2e). Pale yellow solid, mp 281–283 °C , 0.67 g, 77%
yield. 1H NMR (400 MHz, DMSO-d6) δ 7.68 (s, 1H), 7.48 (s, 2H), 7.40 (d, J = 8.1 Hz, 1H), 7.25
(d, J = 8.3 Hz, 1H), 5.14 (s, 1H), 2.36 (s, 3H). 13C{1H} NMR (101 MHz, DMSO-d6) δ 175.0,
165.3, 151.9, 134.1, 133.3, 124.7, 123.1, 116.7, 85.5, 20.9. HRMS (ESI): calcd for C10H10NO2
(M+H)+ 176.0706, found 176.0709.
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2-Amino-6-methoxy-4H-chromen-4-one (2f). Yellow solid, mp 250–252 °C , 0.74 g, 77% yield.
1H NMR (400 MHz, DMSO-d6) δ 7.49 (s, 2H), 7.35 – 7.29 (m, 2H), 7.16 (dd, J = 8.9, 2.8 Hz, 1H),
5.17 (s, 1H), 3.80 (s, 3H). 13C{1H} NMR (101 MHz, DMSO-d6) δ 174.7, 165.3, 156.3, 148.0,
124.1, 120.4, 118.3, 106.3, 85.3, 56.0. HRMS (ESI): calcd for C10H10NO3 (M+H)+ 192.0655,
found 192.0660.
2-Amino-7-methoxy-4H-chromen-4-one (2g). Yellow solid, mp 254–256 °C , 0.72 g, 75% yield.
1H NMR (400 MHz, DMSO-d6) δ 7.80 (d, J = 8.7 Hz, 1H), 7.40 (s, 2H), 6.94 – 6.87 (m, 1H), 6.83
(s, 1H), 5.10 (s, 1H), 3.83 (s, 3H). 13C{1H} NMR (101 MHz, DMSO-d6) δ 175.0, 165.3, 162.7,
155.2, 126.4, 117.0, 112.7, 100.7, 84.9, 56.2. HRMS (ESI): calcd for C10H10NO3 (M+H)+
192.0655, found 192.0659.
2-Amino-7,8-dimethoxy-4H-chromen-4-one (2h). Yellow solid, mp 212–213 °C , 0.72 g, 65%
1
yield. H NMR (400 MHz, DMSO-d6) δ 7.74 – 7.42 (m, 3H), 7.08 (s, 1H), 5.08 (s, 1H), 3.84 (s,
6H). 13C{1H} NMR (101 MHz, DMSO-d6) δ 174.9, 165.2, 155.3, 147.6, 136.0, 119.9, 117.9, 109.5,
84.6, 61.3, 56.6. HRMS (ESI): calcd for C11H12NO4 (M+H)+ 222.0761, found 222.0765.
2-Amino-5-methoxy-7-methyl-4H-chromen-4-one (2i). Brown solid, mp >350 °C , 0.75 g, 73%
yield. 1H NMR (400 MHz, DMSO-d6) δ 7.11 (s, 2H), 6.69 (s, 2H), 4.94 (s, 1H), 3.75 (s, 3H), 2.33
(s, 3H). 13C{1H} NMR (101 MHz, DMSO-d6) δ 175.5, 163.3, 159.1, 155.9, 143.1, 111.0, 109.3,
108.8, 86.6, 56.4, 21.9. HRMS (ESI): calcd for C11H12NO3 (M+H)+ 206.0812, found 206.0817.
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General Procedure for the synthesis of chromeno [2,3-b]pyridine derivatives 3. A mixture of
of propargylic alcohols 1 (0.1 mmol), substituted 2-aminochromones 2 (0.15 mmol, 1.5 equiv),
and Zn(OTf)2 (20 mol %) in dry DCE (2.0 mL) was stirred in a sealed tube under an air
atmosphere at 100 °C for 24 h (monitored by TLC). The resulting mixture was cooled down to
room temperature. The solvent was evaporated under reduced pressure, and the residues were
further purified by chromatography on silica gel (column chromatography eluent, petroleum
ether/ethyl acetate = 2/1) to afford the corresponding products 3.
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2,2,4-Triphenyl-1,2-dihydro-5H-chromeno[2,3-b]pyridin-5-one (3a). Pale yellow solid, mp
243 – 244 °C , 38.3 mg, 89% yield. 1H NMR (400 MHz, DMSO-d6) δ 9.75 (s, 1H), 7.83 (d, J = 6.7
Hz, 1H), 7.62 (t, J = 7.7 Hz, 1H), 7.44 – 7.38 (m, 9H), 7.37 – 7.29 (m, 3H), 7.28 – 7.24 (m, 5H),
5.48 (s, 1H). 13C{1H} NMR (101 MHz, DMSO-d6) δ 169.6, 161.5, 152.8, 146.5, 140.2, 134.3,
132.7, 128.8, 128.1, 127.7, 127.6, 127.5, 127.0, 125.8, 125.2, 124.1, 123.1, 116.9, 93.4, 65.3.
HRMS (ESI): calcd for C30H22NO2 (M+H)+ 428.1645, found 428.1649.
2,2-Diphenyl-4-(p-tolyl)-1,2-dihydro-5H-chromeno[2,3-b]pyridin-5-one (3b). Pale yellow solid,
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mp 232 – 234 °C , 38.6 mg, 87% yield. H NMR (400 MHz, CDCl3) δ 8.06 (dd, J = 7.8, 1.3 Hz,
1H), 7.47 (dd, J = 11.2, 4.2 Hz, 1H), 7.35 (d, J = 4.2 Hz, 7H), 7.31 – 7.26 (m, 3H), 7.26 – 7.22 (m,
3H), 7.18 (d, J = 8.3 Hz, 1H), 7.12 (d, J = 7.9 Hz, 2H), 5.83 (s, 1H), 5.52 (d, J = 1.8 Hz, 1H), 2.33
(s, 3H). 13C{1H} NMR (101 MHz, CDCl3) δ 171.1, 160.0, 152.7, 145.6, 137.0, 136.6, 134.5, 131.7,
128.6, 128.1, 127.6, 127.6, 127.0, 126.4, 124.7, 124.4, 121.6, 116.0, 94.7, 65.6, 21.3. HRMS (ESI):
calcd for C31H24NO2 (M+H)+ 442.1802, found 442.1807.
2,2-Diphenyl-4-(m-tolyl)-1,2-dihydro-5H-chromeno[2,3-b]pyridin-5-one (3c). Pale yellow
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solid, mp 227 – 228 °C , 42.0 mg, 95% yield. H NMR (400 MHz, CDCl3) δ 8.08 (dd, J = 7.9, 1.6
Hz, 1H), 7.51 – 7.46 (m, 1H), 7.39 – 7.35 (m, 7H), 7.34 – 7.20 (m, 6H), 7.17 – 7.07 (m, 3H), 5.62
(s, 1H), 5.52 (d, J = 2.0 Hz, 1H), 2.35 (s, 3H). 13C{1H} NMR (101 MHz, CDCl3) δ 171.1, 159.9,
152.8, 145.6, 139.9, 136.9, 134.8, 131.8, 128.7, 128.2, 127.9, 127.7, 127.3, 127.0, 126.5, 125.0,
124.8, 124.4, 121.8, 116.0, 94.9, 65.7, 21.6. HRMS (ESI): calcd for C31H24NO2 (M+H)+ 442.1802,
found 442.1815.
4-(4-Ethylphenyl)-2,2-diphenyl-1,2-dihydro-5H-chromeno[2,3-b]pyridin-5-one (3d). White
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solid, mp 131 – 132 °C , 42.9 mg, 94% yield. H NMR (400 MHz, CDCl3) δ 8.06 (dd, J = 7.9, 1.5
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Hz, 1H), 7.48 – 7.43 (m, 1H), 7.36 – 7.33 (m, 6H), 7.29 – 7.23 (m, 7H), 7.16 (t, J = 8.2 Hz, 3H),
5.95 (s, 1H), 5.51 (d, J = 1.9 Hz, 1H), 2.64 (q, J = 7.6 Hz, 2H), 1.23 (t, J = 7.6 Hz, 3H). 13C{1H}
NMR (101 MHz, CDCl3) δ 171.1, 160.1, 152.7, 145.7, 142.8, 137.2, 134.5, 131.7, 128.8, 128.7,
128.6, 127.6, 127.6, 127.0, 126.9, 124.7, 121.8, 116.0, 94.7, 65.7, 28.6, 15.3. HRMS (ESI): calcd
for C32H26NO2 (M+H)+ 456.1958, found 456.1971.
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4-(4-Methoxyphenyl)-2,2-diphenyl-1,2-dihydro-5H-chromeno[2,3-b]pyridin-5-one
(3e).
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Yellow solid, mp 222 – 223 °C , 44.5 mg, 97% yield. H NMR (400 MHz, CDCl3) δ 8.03 (dd, J =
7.9, 1.4 Hz, 1H), 7.45 (dd, J = 11.2, 4.2 Hz, 1H), 7.37 – 7.31 (m, 8H), 7.30 – 7.25 (m, 4H), 7.24 –
7.20 (m, 1H), 7.16 (d, J = 8.2 Hz, 1H), 6.85 (d, J = 8.7 Hz, 2H), 6.03 (s, 1H), 5.49 (d, J = 1.9 Hz,
1H), 3.77 (s, 3H). 13C{1H} NMR (101 MHz, CDCl3) δ 171.1, 160.1, 158.6, 152.7, 145.6, 134.1,
132.3, 131.7, 128.8, 128.6, 127.6, 127.0, 126.4, 124.7, 124.3, 121.4, 116.0, 112.8, 94.6, 65.6, 55.1.
HRMS (ESI): calcd for C31H24NO3 (M+H)+ 458.1751, found 458.1762.
4-([1,1'-Biphenyl]-4-yl)-2,2-diphenyl-1,2-dihydro-5H-chromeno[2,3-b]pyridin-5-one
(3f).
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White solid, mp 246 – 247 °C , 48.4 mg, 96% yield. H NMR (400 MHz, CDCl3) δ 8.09 (dd, J =
7.9, 1.6 Hz, 1H), 7.63 – 7.58 (m, 2H), 7.57 – 7.53 (m, 2H), 7.51 – 7.46 (m, 1H), 7.44 – 7.40 (m,
3H), 7.39 – 7.34 (m, 8H), 7.33 – 7.24 (m, 5H), 7.21 (d, J = 7.8 Hz, 1H), 5.78 (s, 1H), 5.59 (d, J =
2.0 Hz, 1H). 13C{1H} NMR (101 MHz, CDCl3) δ 171.2, 160.1, 152.8, 145.6, 141.2, 139.8, 139.0,
134.3, 131.9, 128.7, 128.6, 128.2, 127.7, 127.1, 127.0, 127.0, 126.5, 126.2, 124.8, 124.3, 122.2,
116.1, 94.6, 65.7. HRMS (ESI): calcd for C36H26NO2 (M+H)+ 504.1958, found 504.1973.
4-(4-Fluorophenyl)-2,2-diphenyl-1,2-dihydro-5H-chromeno[2,3-b]pyridin-5-one (3g). Yellow
solid, mp 237 – 239 °C , 41.2 mg, 92% yield. 1H NMR (400 MHz, CDCl3) δ 8.03 (d, J = 7.9, 1H),
7.48 – 7.43 (m, 1H), 7.39 – 7.32 (m, 8H), 7.32 – 7.22 (m, 5H), 7.17 (d, J = 8.3 Hz, 1H), 6.98 (t, J
= 8.7 Hz, 2H), 6.02 (s, 1H), 5.49 (d, J = 1.9 Hz, 1H). 13C{1H} NMR (101 MHz, CDCl3) δ 171.1,
162.0 (d, J(C, F) = 245.4 Hz), 160.1, 152.7, 145.5, 135.8 (d, J(C, F) = 3.0 Hz), 133.7, 131.9, 129.3
(d, J(C, F) = 8.1 Hz), 128.6, 127.7, 127.0, 126.3, 124.8, 124.2, 122.0, 116.0, 114.2 (d, J(C, F) =
21.2 Hz), 94.4, 65.7. 19F{1H} NMR (376 MHz, CDCl3) δ -115.7. HRMS (ESI): calcd for
C30H21FNO2 (M+H)+ 446.1551, found 446.1560.
4-(4-Chlorophenyl)-2,2-diphenyl-1,2-dihydro-5H-chromeno[2,3-b]pyridin-5-one (3h). Pale
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yellow solid, mp 223 – 224 °C , 43.8 mg, 95% yield. H NMR (400 MHz, CDCl3) δ 8.05 (dd, J =
7.9, 1.5 Hz, 1H), 7.50 – 7.45 (m, 1H), 7.39 – 7.33 (m, 8H), 7.32 – 7.24 (m, 7H), 7.20 (d, J = 8.3
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Hz, 1H), 5.83 (s, 1H), 5.51 (d, J = 1.7 Hz, 1H). 13C{1H} NMR (101 MHz, CDCl3) δ 171.1, 160.0,
152.8, 145.4, 138.4, 133.7, 132.8, 131.9, 129.1, 128.7, 127.8, 127.5, 126.9, 126.5, 124.9, 124.2,
122.2, 116.1, 94.3, 65.7. HRMS (ESI): calcd for C30H21ClNO2 (M+H)+ 462.1255, found 462.1267.
4-(4-Bromophenyl)-2,2-diphenyl-1,2-dihydro-5H-chromeno[2,3-b]pyridin-5-one (3i). Yellow
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solid, mp 235 – 236 °C , 36.2 mg, 71% yield. H NMR (400 MHz, CDCl3) δ 8.07 (dd, J = 7.9, 1.4
Hz, 1H), 7.53 – 7.48 (m, 1H), 7.44 (d, J = 8.3 Hz, 2H), 7.41 – 7.35 (m, 7H), 7.34 – 7.28 (m, 4H),
7.24 – 7.19 (m, 3H), 5.71 (s, 1H), 5.52 (d, J = 1.7 Hz, 1H). 13C{1H} NMR (101 MHz, CDCl3) δ
171.2, 160.0, 152.8, 145.4, 138.8, 133.7, 132.0, 130.5, 129.5, 128.7, 127.8, 126.9, 126.4, 124.9,
124.2, 122.1, 121.0, 116.0, 94.3, 65.7. HRMS (ESI): calcd for C30H21BrNO2 (M+H)+ 506.0750,
found 506.0766.
4-(4-Nitrophenyl)-2,2-diphenyl-1,2-dihydro-5H-chromeno[2,3-b]pyridin-5-one (3j). Red solid,
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mp 161 – 162 °C , 33.7 mg, 71% yield. H NMR (400 MHz, CDCl3) δ 8.17 (d, J = 8.5Hz, 2H),
8.04 (d, J = 7.6 Hz, 1H), 7.57 – 7.49 (m, 1H), 7.48 – 7.45 (m, 2H), 7.41 – 7.33 (m, 11H), 7.24 –
7.23 (m, 1H), 5.84 (s, 1H), 5.59 (d, J = 1.5 Hz, 1H). 13C{1H} NMR (101 MHz, CDCl3) δ 171.1,
160.0, 152.8, 146.9, 146.8, 145.1, 133.1, 132.3, 128.9, 128.6, 128.0, 126.9, 126.3, 125.1, 123.9,
123.2, 122.8, 116.2, 93.9, 65.9. HRMS (ESI): calcd for C30H21N2O4 (M+H)+ 473.1496, found
473.1511.
4-(5-Oxo-2,2-diphenyl-1,5-dihydro-2H-chromeno[2,3-b]pyridin-4-yl) benzonitrile (3k). Pale
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yellow solid, mp 157 – 158 °C , 43.5 mg, 96% yield. H NMR (400 MHz, CDCl3) δ 8.04 (dd, J =
7.8, 1.2 Hz, 1H), 7.59 (d, J = 8.2 Hz, 2H), 7.54 – 7.47 (m, 2H), 7.43 – 7.32 (m, 11H), 7.24 – 7.21
(m, 2H), 5.89 (s, 1H), 5.55 (d, J = 1.8 Hz, 1H). 13C{1H} NMR (101 MHz, CDCl3) δ 171.1, 160.0,
152.8, 145.2, 144.9, 133.4, 132.2, 131.2, 128.8, 128.6, 128.0, 126.9, 126.3, 125.1, 124.0, 123.0,
119.2, 116.1, 110.6, 93.9, 65.9. HRMS (ESI): calcd for C31H21N2O2 (M+H)+ 453.1598, found
453.1606.
Methyl 4-(5-oxo-2,2-diphenyl-1,5-dihydro-2H-chromeno[2,3-b]pyridin-4-yl) benzoate (3l).
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Pale yellow solid, mp 220 – 221 °C , 46.1 mg, 95% yield. H NMR (400 MHz, CDCl3) δ 8.04 –
8.00 (m, 1H), 7.98 (d, J = 8.3 Hz, 2H), 7.48 – 7.45 (m, 1H), 7.38 (d, J = 8.4 Hz, 2H), 7.36 – 7.33
(m, 7H), 7.31 – 7.26 (m, 2H), 7.26 – 7.20 (m, 2H), 7.18 – 7.14 (m, 1H), 6.31 (br, 1H), 5.55 (d, J =
1.9 Hz, 1H), 3.85 (s, 3H). 13C{1H} NMR (101 MHz, CDCl3) δ 171.0, 167.1, 160.1, 152.7, 145.4,
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145.0, 134.0, 131.9, 128.8, 128.7, 128.6, 128.5, 127.7, 127.0, 126.3, 124.8, 124.1, 122.6, 116.1,
94.2, 65.7, 51.9. HRMS (ESI): calcd for C32H24NO4 (M+H)+ 486.1700, found 486.1705.
4-Phenyl-2,2-di-p-tolyl-1,2-dihydro-5H-chromeno[2,3-b]pyridin-5-one (3m). White solid, mp
236 – 237 °C , 44.2 mg, 97% yield. 1H NMR (400 MHz, CDCl3) δ 8.08 – 8.02 (m, 1H), 7.49 – 7.43
(m, 1H), 7.37 – 7.28 (m, 5H), 7.26 – 7.23 (m, 5H), 7.17 (t, J = 9.9 Hz, 5H), 5.68 (s, 1H), 5.49 (d, J
= 1.6 Hz, 1H), 2.34 (s, 6H). 13C{1H} NMR (101 MHz, CDCl3) δ 171.0, 160.0, 152.7, 142.9, 140.0,
137.4, 134.3, 131.7, 129.3, 127.7, 127.3, 126.9, 126.9, 126.5, 124.7, 124.4, 122.3, 116.0, 94.6,
65.3, 21.0. HRMS (ESI): calcd for C32H26NO2 (M+H)+ 456.1958, found 456.1965.
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2,2-Bis(4-methoxyphenyl)-4-phenyl-1,2-dihydro-5H-chromeno[2,3-b]pyridin-5-one
(3n).
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Yellow solid, mp 230 – 231 °C , 46.8 mg, 96% yield. H NMR (400 MHz, CDCl3) δ 8.05 (dd, J =
7.9, 1.5 Hz, 1H), 7.49 – 7. 43 (m, 1H), 7.36 – 7.24 (m, 10H), 7.18 (d, J = 8.3 Hz, 1H), 6.90 – 6.84
(m, 4H), 5.75 (s, 1H), 5.47 (d, J = 1.5 Hz, 1H), 3.79 (s, 6H). 13C{1H} NMR (101 MHz, CDCl3) δ
171.1, 160.0, 158.9, 152.8, 140.0, 138.0, 134.1, 131.7, 128.2, 127.7, 127.4, 127.0, 126.5, 124.7,
124.4, 122.5, 116.0, 113.9, 94.6, 64.9, 55.3. HRMS (ESI): calcd for C32H26NO4 (M+H)+ 488.1856,
found 488.1866.
2,2-Bis(4-fluorophenyl)-4-phenyl-1,2-dihydro-5H-chromeno[2,3-b]pyridin-5-one (3o). Pale
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yellow solid, mp 244 – 245 °C , 41.8 mg, 90% yield. H NMR (400 MHz, CDCl3) δ 7.99 (dd, J =
7.8, 1.2 Hz, 1H), 7.49 – 7.44 (m, 1H), 7.35 – 7.27 (m, 9H), 7.26 – 7.21 (m, 1H), 7.16 (d, J = 8.3
Hz, 1H), 7.06 – 6.98 (m, 4H), 6.05 (s, 1H), 5.45 (d, J = 1.7 Hz, 1H). 13C{1H} NMR (101 MHz,
CDCl3) δ 171.2, 162.1 (d, J(C, F) = 249.5 Hz), 159.9, 152.7, 141.3 (d, J(C, F) = 3.0 Hz), 139.6,
135.0, 131.9, 128.8 (d, J(C, F) = 8.1 Hz), 127.7, 127.4, 127.2, 126.4, 124.9, 124.2, 121.6, 116.0,
115.6 (d, J(C, F) = 21.2 Hz), 94.7, 64.8. 19F{1H} NMR (376 MHz, CDCl3) δ -114.1. HRMS (ESI):
calcd for C30H20F2NO2 (M+H)+ 464.1457, found 464.1467.
2,2-Bis(4-chlorophenyl)-4-phenyl-1,2-dihydro-5H-chromeno[2,3-b]pyridin-5-one (3p). Pale
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yellow solid, mp 235 – 236 °C , 44.3 mg, 89% yield. H NMR (400 MHz, CDCl3) δ 8.04 (dd, J =
7.9, 1.5 Hz, 1H), 7.52 – 7.47 (m, 1H), 7.35 – 7.31 (m, 8H), 7.30 – 7.26 (m, 6H), 7.19 (d, J = 8.9
Hz, 1H), 5.75 (s, 1H), 5.42 (d, J = 1.4 Hz, 1H). 13C{1H} NMR (101 MHz, CDCl3) δ 171.2, 159.8,
152.8, 143.7, 139.5, 135.5, 134.0, 132.0, 130.0, 128.9, 128.4, 127.6, 127.5, 127.3, 126.5, 125.0,
120.9, 116.1, 94.8, 65.0. HRMS (ESI): calcd for C30H20Cl2NO2 (M+H)+ 496.0866, found
496.0878.
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2,2-Bis(4-bromophenyl)-4-phenyl-1,2-dihydro-5H-chromeno[2,3-b]pyridin-5-one (3q). White
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solid, mp 245 – 246 °C , 43.8 mg, 75% yield. H NMR (400 MHz, CDCl3) δ 8.05 (dd, J = 7.8, 1.3
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Hz, 1H), 7.52 – 7.45 (m, 5H), 7.34 – 7.27 (m, 6H), 7.24 – 7.17 (m, 5H), 5.69 (s, 1H), 5.41 (d, J =
1.5 Hz, 1H). 13C{1H} NMR (101 MHz, CDCl3) δ 171.3, 159.8, 152.8, 144.1, 139.4, 135.5, 132.1,
131.9, 128.7, 127.6, 127.5, 127.3, 126.5, 125.0, 124.2, 122.2, 120.8, 116.1, 94.8, 65.1. HRMS
(ESI): calcd for C30H20Br2NO2 (M+H)+ 583.9855, found 583.9868.
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2,4-Diphenyl-2-(p-tolyl)-1,2-dihydro-5H-chromeno[2,3-b]pyridin-5-one (3r). Yellow solid, mp
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247 – 248 °C , 42.9 mg, 97% yield. H NMR (400 MHz, CDCl3) δ 8.04 (dd, J = 7.8, 1.1 Hz, 1H),
7.49 – 7.43 (m, 1H), 7.38 – 7.27 (m, 10H), 7.26 – 7.22 (m, 3H), 7.21 – 7.13 (m, 3H), 5.76 (s, 1H),
5.51 (d, J = 1.7 Hz, 1H), 2.34 (s, 3H). 13C{1H} NMR (101 MHz, CDCl3) δ 171.1, 160.0, 152.8,
145.8, 142.8, 140.0, 137.5, 134.5, 131.7, 129.3, 128.6, 127.7, 127.6, 127.4, 127.0, 126.9, 126.5,
124.7, 124.4, 122.1, 116.0, 94.6, 65.5, 21.0. HRMS (ESI): calcd for C31H24NO2 (M+H)+ 442.1802,
found 442.1810.
2,4-Diphenyl-2-(m-tolyl)-1,2-dihydro-5H-chromeno[2,3-b]pyridin-5-one (3s). Pale yellow
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solid, mp 218 – 219 °C , 35.0 mg, 79% yield. H NMR (400 MHz, CDCl3) δ 8.03 (dd, J = 7.9, 1.5
Hz, 1H), 7.47 – 7.42 (m, 1H), 7.36 – 7.33 (m, 6H), 7.31 (s, 1H), 7.30 – 7.20 (m, 5H), 7.19 – 7.16
(m, 2H), 7.10 (t, J = 8.5 Hz, 2H), 5.94 (d, J = 1.5 Hz, 1H), 5.51 (d, J = 2.0 Hz, 1H), 2.32 (s, 3H).
13C{1H} NMR (101 MHz, CDCl3) δ 171.0, 160.0, 152.7, 145.7, 145.6, 139.9, 138.3, 134.4, 131.7,
128.6, 128.5, 128.4, 127.7, 127.7, 127.5, 127.3, 126.9, 126.4, 124.7, 124.3, 124.1, 122.1, 116.0,
94.5, 65.6, 21.6. HRMS (ESI): calcd for C31H24NO2 (M+H)+ 442.1802, found 442.1808.
2-(4-Methoxyphenyl)-2,4-diphenyl-1,2-dihydro-5H-chromeno[2,3-b]pyridin-5-one (3t). Pale
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yellow solid, mp 248 – 249 °C , 43.5 mg, 95% yield. H NMR (400 MHz, DMSO-d6) δ 9.69 (s,
1H), 7.83 (d, J = 7.4 Hz, 1H), 7.62 (t, J = 7.6 Hz, 1H), 7.44 – 7.36 (m, 5H), 7.35 (d, J = 7.8 Hz,
1H), 7.32 – 7.28 (m, 3H), 7.28 – 7.22 (m, 5H), 6.95 (d, J = 8.6 Hz, 2H), 5.44 (s, 1H), 3.73 (s, 3H).
13C {1H} NMR (101 MHz, DMSO-d6) δ 169.6, 161.5, 158.8, 152.8, 146.7, 140.3, 138.6, 134.0,
132.7, 128.8, 128.7, 128.1, 127.6, 127.5, 127.4, 127.0, 125.8, 125.2, 124.1, 123.3, 116.8, 114.1,
93.4, 64.9, 55.6. HRMS (ESI): calcd for C31H24NO3 (M+H)+ 458.1751, found 458.1761.
2-(2-Chlorophenyl)-4-(4-methoxyphenyl)-2-phenyl-1,2-dihydro-5H-chromeno[2,3-b]pyridin-
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5-one (3u). White solid, mp 141– 142 °C , 95% yield. H NMR (400 MHz, CDCl3) δ 8.10 (dd, J =
7.8, 1.5 Hz, 1H), 7.91– 7.83 (m, 1H), 7.53 – 7.47 (m, 1H), 7.41 – 7.35 (m, 2H), 7.34 – 7.24 (m,
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10H), 6.88 (d, J = 8.6 Hz, 2H), 6.60 (s, 1H), 5.38 (d, J = 1.9 Hz, 1H), 3.81 (s, 3H). 13C{1H} NMR
(101 MHz, CDCl3) δ 171.4, 160.7, 158.9, 152.8, 145.5, 141.0, 134.5, 132.0, 131.9, 131.9, 131.7,
130.5, 129.6, 128.8, 128.7, 127.3, 127.1, 126.5, 125.9, 124.8, 124.4, 120.3, 116.1, 113.0, 94.8,
65.6, 55.2. HRMS (ESI): calcd for C31H23ClNO3 (M+H)+ 492.1361, found 492.1374.
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2-(3-Chlorophenyl)-4-(4-methoxyphenyl)-2-phenyl-1,2-dihydro-5H-chromeno[2,3-b]pyridin-
5-one (3v). Off white solid, mp 151 – 152 °C , 45.8 mg, 93% yield. 1H NMR (400 MHz, CDCl3) δ
8.07 (dd, J = 7.9, 1.6 Hz, 1H), 7.48 – 7.43 (m, 1H), 7.39 – 7.23 (m, 12H), 7.21 (d, J = 8.5 Hz, 1H),
6.86 (d, J = 8.6 Hz, 2H), 5.75 (s, 1H), 5.45 (d, J = 1.5 Hz, 1H), 3.79 (s, 3H). 13C{1H} NMR (101
MHz, CDCl3) δ 171.3, 160.1, 158.8, 152.7, 147.8, 145.0, 134.7, 134.6, 132.1, 131.8, 129.9, 128.8,
128.7, 127.9, 127.8, 127.2, 127.0, 126.4, 125.3, 124.8, 124.3, 120.7, 116.1, 112.9, 94.1, 65.4, 55.1.
HRMS (ESI): calcd for C31H23ClNO3 (M+H)+ 492.1361, found 492.1375.
(4-Chlorophenyl)-4-(4-methoxyphenyl)-2-phenyl-1,2-dihydro-5H-chromeno[2,3-b]pyridin-5-
one (3w). Pale yellow solid, mp 234 – 235 °C , 42.7 mg, 87% yield. 1H NMR (400 MHz, CDCl3) δ
8.05 (dd, J = 7.9, 1.5 Hz, 1H), 7.51 – 7.46 (m, 1H), 7.38 – 7.30 (m, 8H), 7.30 – 7.26 (m, 2H), 7.26
– 7.23 (m, 2H), 7.19 (d, J = 8.2 Hz, 1H), 6.86 (d, J = 8.7 Hz, 2H), 5.88 (s, 1H), 5.45 (s, 1H), 3.79
(s, 3H).13C{1H} NMR (101 MHz, CDCl3) δ 171.3, 160.1, 158.8, 152.7, 145.2, 144.2, 134.6, 133.7,
132.0, 131.9, 128.8, 128.8, 128.5, 127.9, 126.9, 126.5, 124.9, 124.3, 121.0, 116.0, 112.9, 94.9,
65.3, 55.2. HRMS (ESI): calcd for C31H23ClNO3 (M+H)+ 492.1361, found 492.1375.
7-Fluoro-2,2,4-triphenyl-1,2-dihydro-5H-chromeno[2,3-b]pyridin-5-one (3ab). Yellow solid,
1
mp 235 – 236 °C , 38.4 mg, 86% yield. H NMR (400 MHz, CDCl3) δ 7.74 – 7.65 (m, 1H), 7.39 –
7.27 (m, 15H), 7.19 – 7.13 (m, 2H), 5.93 (s, 1H), 5.54 (d, J = 1.9 Hz, 1H). 13C{1H} NMR (101
MHz, CDCl3) δ 170.2, 160.3, 159.5 (d, J(C, F) = 245.4 Hz), 148.8, 145.5, 139.8, 134.4, 128.7,
127.8, 127.8, 127.5, 127.2, 127.1, 125.8 (d, J(C, F) = 7.1 Hz), 122.4, 119.4(d, J(C, F) = 28.3 Hz),
117.9 (d, J(C, F) = 8.1 Hz), 111.9 (d, J(C, F) = 24.2 Hz), 94.4, 65.9. 19F{1H} NMR (376 MHz,
CDCl3) δ -116.3. HRMS (ESI): calcd for C30H21FNO2 (M+H)+ 446.1551, found 446.1561.
7-Chloro-2,2,4-triphenyl-1,2-dihydro-5H-chromeno[2,3-b]pyridin-5-one (3ac). Pale yellow
1
solid, mp 237 – 238 °C , 40.3 mg, 87% yield. H NMR (400 MHz, CDCl3) δ 8.03 (d, J = 2.3 Hz,
1H), 7.43 – 7.39(m, 1H), 7.38 – 7.26 (m, 15H), 7.16 (d, J = 8.8 Hz, 1H), 5.79 (s, 1H), 5.55 (d, J =
1.5 Hz, 1H). 13C{1H} NMR (101 MHz, CDCl3) δ 169.8, 160.1, 151.0, 145.4, 139.6, 134.3, 131.8,
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130.6, 128.7, 127.8, 127.7, 127.4, 127.1, 127.0, 126.0, 125.5, 122.3, 117.7, 94.6, 65.8. HRMS
(ESI): calcd for C30H21ClNO2 (M+H)+ 462.1255, found 462.1266.
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7-Bromo-2,2,4-triphenyl-1,2-dihydro-5H-chromeno[2,3-b]pyridin-5-one (3ad). Pale yellow
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solid, mp 240 – 241 °C , 40.4 mg, 80% yield. H NMR (400 MHz, CDCl3) δ 8.20 (d, J = 1.9 Hz,
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1H), 7.56 (dd, J = 8.8, 2.4 Hz, 1H), 7.39 – 7.35 (m, 7H), 7.34 – 7.29 (m, 8H), 7.10 (d, J = 8.7 Hz,
1H), 5.74 (s, 1H), 5.55 (d, J = 1.9 Hz, 1H). 13C{1H} NMR (101 MHz, CDCl3) δ 169.7, 160.0,
151.5, 145.4, 139.5, 134.6, 134.3, 129.2, 128.7, 127.8, 127.7, 127.4, 127.2, 127.0, 125.8, 122.3,
118.1, 117.9, 94.7, 65.8. HRMS (ESI): calcd for C30H21BrNO2 (M+H)+ 506.0750, found
506.0762.
7-Methyl-2,2,4-triphenyl-1,2-dihydro-5H-chromeno[2,3-b]pyridin-5-one (3ae). Yellow solid,
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mp 238 – 239 °C , 36.1 mg, 82% yield. H NMR (400 MHz, DMSO-d6) δ 9.69 (s, 1H), 7.61 (s,
1H), 7.46 – 7.35 (m, 10H), 7.32 – 7.28 (m, 3H), 7.26 – 7.23 (m, 4H), 5.47 (s, 1H), 2.34 (s, 3H).
13C{1H} NMR (101 MHz, DMSO-d6) δ 169.8, 161.5, 151.0, 146.6, 140.2, 134.5, 133.4, 128.8,
128.1, 127.7, 127.5, 127.0, 125.5, 123.8, 123.0, 116.7, 93.4, 65.2, 20.9. HRMS (ESI): calcd for
C31H24NO2 (M+H)+ 442.1802, found 442.1809.
7-Methoxy-2,2,4-triphenyl-1,2-dihydro-5H-chromeno[2,3-b]pyridin-5-one (3af). Pale yellow
1
solid, mp 232 – 234 °C , 41.2 mg, 90% yield. H NMR (400 MHz, CDCl3) δ 7.51 (d, J = 3.0 Hz,
1H), 7.38 – 7.33 (m, 10H), 7.33 – 7.24 (m, 5H), 7.11 (d, J = 9.0 Hz, 1H), 7.04 (dd, J = 9.0, 3.0 Hz,
1H), 5.76 (s, 1H), 5.53 (d, J = 1.9 Hz, 1H), 3.75 (s, 3H). 13C{1H} NMR (101 MHz, CDCl3) δ
171.0, 160.0, 156.6, 147.2, 145.6, 140.0, 134.7, 128.6, 127.7, 127.6, 127.4, 127.0, 124.9, 122.0,
120.9, 117.2, 106.7, 94.4, 65.7, 55.8. HRMS (ESI): calcd for C31H24NO3 (M+H)+ 458.1751, found
458.1759.
8-Methoxy-2,2,4-triphenyl-1,2-dihydro-5H-chromeno[2,3-b]pyridin-5-one (3ag). Yellow solid,
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mp 231 – 232 °C , 33.1 mg, 72% yield. H NMR (400 MHz, CDCl3) δ 7.95 (d, J = 8.8 Hz, 1H),
7.38 – 7.25 (m, 15H), 6.81 (dd, J = 8.8, 2.3 Hz, 1H), 6.65 (d, J = 2.3 Hz, 1H), 5.73 (s, 1H), 5.50 (d,
J = 1.9 Hz, 1H), 3.82 (s, 3H). 13C{1H} NMR (101 MHz, CDCl3) δ 171.1, 162.7, 160.0, 154.1,
145.7, 140.0, 134.8, 128.6, 127.7, 127.6, 127.3, 127.0, 127.0, 121.7, 117.9, 112.4, 100.1, 94.2,
65.7, 55.7. HRMS (ESI): calcd for C31H24NO3 (M+H)+ 458.1751, found 458.1759.
8,9-Dimethoxy-2,2,4-triphenyl-1,2-dihydro-5H-chromeno[2,3-b]pyridin-5-one (3ah). Pale
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yellow solid, mp 202 – 203 °C , 34.3 mg, 70% yield. H NMR (400 MHz, DMSO-d6) δ 9.71 (s,
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1H), 7.52 (d, J = 8.9 Hz, 1H), 7.43 – 7.35 (m, 9H), 7.33 – 7.28 (m, 2H), 7.26 – 7.22 (m, 4H), 7.08
(d, J = 8.9 Hz, 1H), 5.45 (s, 1H), 3.91 (s, 3H), 3.88 (s, 3H). 13C{1H} NMR (101 MHz, DMSO-d6)
δ 169.7, 161.4, 155.5, 146.8, 146.6, 140.4, 136.0, 134.4, 128.8, 128.1, 127.7, 127.6, 127.5, 127.0,
122.7, 120.6, 118.5, 109.9, 92.6, 65.3, 61.6, 56.8. HRMS (ESI): calcd for C32H26NO4 (M+H)+
488.1856, found 488.1866.
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6-Methoxy-8-methyl-2,2,4-triphenyl-1,2-dihydro-5H-chromeno[2,3-b]pyridin-5-one
(3ai).
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Yellow solid, mp 236 – 237 °C , 38.2 mg, 81% yield. H NMR (400 MHz, CDCl3) δ 7.36 – 7.31
(m, 10H), 7.29 – 7.21 (m, 5H), 6.58 (s, 1H), 6.51 (s, 1H), 5.48 (s, 1H), 5.44 (d, J = 1.5 Hz, 1H),
3.78 (s, 3H), 2.35 (s, 3H). 13C{1H} NMR (101 MHz, CDCl3) δ 171.6, 160.0, 158.4, 154.8, 145.9,
142.8, 140.5, 135.2, 128.5, 127.6, 127.5, 127.3, 127.0, 126.7, 121.9, 111.9, 108.8, 108.3, 95.4,
65.4, 56.2, 21.9. HRMS(ESI): calcd for C32H26NO3 (M+H)+ 472.1907, found 472.1917.
ASSOCIATED CONTENT
Supporting Information
The Supporting Information is available free of charge via the Internet at http://pubs.acs.org.
1
X-Ray Single Crystal Diffraction Data for 3a; Copies of H and 13C NMR spectra of synthetic
compounds.
AUTHOR INFORMATION
Corresponding Authors
*E-mail: liying@lzu.edu.cn
*E-mail: zhangyuan@lzu.edu.cn
ORCID
Ying Li: 0000-0001-7608-4165
Author Contributions
§Pei Tong and Zhou Sun contributed equally to this work.
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
We gratefully acknowledge the National Natural Science Foundation of China (No. 21772079 and
21572092) and Science and Technology Program of Gansu Province (18JR4RA003) for financial
support.
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