Visible-Light-Induced C(sp2)-C(sp3) Coupling Reaction for the Regioselective Synthesis of 3-Functionalized Coumarins

Article abstract of DOI:10.1021/acs.joc.1c00848

A photocatalysis strategy for the regioselective synthesis of 3-functionalized coumarins is reported. With visible light irradiation, a direct and regioselective C(sp2)-C(sp3) coupling reaction of 3-(2-hydroxyphenyl)acrylates with ethers or thioethers occurs by using Ru(bpy)3Cl2·6H2O as a photocatalyst and TBHP as an oxidant. The cascade process involves alkenylation of the C(sp3)-H bond of ethers and lactonization, furnishing 3-alkylated coumarins as the final products. This approach is characterized by a broad substrate scope, mild reaction conditions, and simplified operation. The synthesis of 3-alkylated coumarins could be realized by a one-pot procedure, starting from commercially available salicylaldehyde.

Full text of DOI:10.1021/acs.joc.1c00848

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Visible-Light-Induced C(sp2)−C(sp3) Coupling Reaction for the
Regioselective Synthesis of 3‑Functionalized Coumarins
Ke Zhang, Li Qiao, Jianwei Xie, Zhenwei Lin, Hanjie Li, Ping Lu,* and Yanguang Wang*
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ABSTRACT: A photocatalysis strategy for the regioselective
synthesis of 3-functionalized coumarins is reported. With visible
light irradiation, a direct and regioselective C(sp2)−C(sp3)
coupling reaction of 3-(2-hydroxyphenyl)acrylates with ethers or
thioethers occurs by using Ru(bpy)3Cl2·6H2O as a photocatalyst
and TBHP as an oxidant. The cascade process involves
alkenylation of the C(sp3)−H bond of ethers and lactonization,
furnishing 3-alkylated coumarins as the final products. This approach is characterized by a broad substrate scope, mild reaction
conditions, and simplified operation. The synthesis of 3-alkylated coumarins could be realized by a one-pot procedure, starting from
commercially available salicylaldehyde.
INTRODUCTION
RESULTS AND DISCUSSION
■
■
To validate the conceptual framework outlined in Scheme 1c,
the coupling of ethyl 3-(2-hydroxyphenyl)acrylate (1a) and
THF (2a) was explored (Table 1). Primarily, Ru(bpy)3Cl2·
6H2O (0.5 mol %) as a photocatalyst and tert-butyl
hydroperoxide (TBHP, 5.5 M in decane, 3.0 equiv) as an
oxidant were used for this model reaction. When the reaction
mixture was irradiated with 10 W LED (450−455 nm) for 20
h, 3-(tetrahydrofuran-2-yl)coumarin 3a was isolated in 45%
yield (Table 1, entry 1). Ru(bpy)3Cl2 and Ru(bpy)3(PF6)2
were also tested, but lower yields were obtained (Table 1,
entries 2 and 3). We then fixed Ru(bpy)3Cl2·6H2O as a
photocatalyst and screened several other oxidants, such as di-
tert-butyl peroxide (DTBP), dicumyl peroxide (DCP), and
dibenzoyl peroxide (BPO). In these cases, 3a was obtained in
very lower yields (Table 1, entries 4−7). Using 70% TBHP (in
water) instead of 5.5 M TBHP (in decane) did not improve
the reaction (Table 1, entry 8). To our surprise, the addition of
an appropriate base remarkably increased the yield of 3a
(Table 1, entries 9−13). The best result was obtained in the
case where 2 equiv of 1,4-diazabicyclo[2.2.2]octane (DABCO)
was added to the reaction mixture (Table 1, entry 13).
Subsequently, several solvents, such as EtOH, DMF, and
dichloromethane (DCM), were screened. In these cases, a
trace of or lower yield of 3a was observed (Table 1, entries
14−16). In the case where MeOH was used as a solvent,
Coumarin and its derivatives are a huge class of compounds
occurring in the structures of biologically active natural
products and pharmaceuticals,1 small-molecule fluorescent
chemosensors,2 as well as functional materials.3 Consequently,
the development of numerous strategies for the synthesis of
these compounds has been stimulated in the past decade.4
Among various coumarins, 3-substituted coumarins have
attracted significant attention due to their important
applications in medicine and chemical biology. Pertinent
examples for the 3-substituted coumarins are illustrated in
Figure 1.
The direct C−H functionalization through oxidative cross-
coupling reactions is a powerful tool for the synthesis of 3-
substituted coumarins. The published methods include
palladium-catalyzed C−H olefination and arylation of coumar-
in5 and C(sp2)−C(sp3) oxidative coupling reactions of
coumarin with ethers or alkanes under metal catalysts6 or
metal-free conditions (Scheme 1a).7 In 2019, Jin and co-
workers reported a photocatalyzed C-3 alkylation of coumarins
via decarboxylative coupling with N-hydroxyphthalimide esters
(Scheme 1b).8 However, the approaches require preparation of
coumarins prior to functionalization, which often erodes step
economy and sometimes suffers from the loss in regioselec-
tivity. To complement existing methodology, efforts to devise a
more efficient route were investigated. Herein, we reported a
concise, regioselective synthesis of 3-alkyl coumarins from 3-
(2-hydroxyphenyl)acrylates and ethers based on the visible-
light-induced strategy combining direct C(sp2)−C(sp3)
coupling and cyclization in one cascade process (Scheme 1c).
Received: April 12, 2021
Published: June 30, 2021
https://doi.org/10.1021/acs.joc.1c00848
© 2021 American Chemical Society
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Figure 1. Pharmaceuticals and chemosensors containing a coumarin core.
coumarin (4a) was isolated (Table 1, entry 14). Decreasing or
increasing the amount of oxidant TBHP led to a reduction in
the yield (Table 1, entries 17 and 18). Finally, several control
experiments were conducted. When the reaction was
performed under an air atmosphere, without irradiation, or
in the absence of photocatalyst, only coumarin, instead of the
desired 3a, was isolated (Table 1, entries 19−21).
Scheme 1. Synthesis of 3-Substituted Coumarins via the
C(sp2)−C(sp3) Coupling Strategies
Having identified optimized reaction conditions for the
cascade C−C coupling/cyclization, the scope and limitations
were investigated using a range of structurally modified 3-(2-
hydroxyphenyl)acrylates (Scheme 2). Systematically altering
the electron demand of substituent R1 of the phenol moiety
from methyl (3b) to methoxy (3c), fluoro (3d), chloro (3e),
and bromo (3f) was well tolerated (51−71% yields). The
structure of 3c was unambiguously characterized by X-ray
single-crystal analysis.9 The addition of substituent R2 was also
well tolerated, enabling the formation of the desired products
3g−k. In these cases, the electron-donating group (Me)
substituted 3-(2-hydroxyphenyl)acrylate (product 3g, 74%
yield) gave a higher yield than the electron-withdrawing
a
Table 1. Reaction Optimization
b
entry
PC
oxidant (equiv)
solvent
base
yield (%)
1
2
3
4
5
6
7
8
Ru(bpy)3Cl2·6H2O
Ru(bpy)3Cl2
Ru(bpy)3(PF6)2
TBHP (3)
TBHP (3)
TBHP (3)
DTBP (3)
TBPB (3)
DCP (3)
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
EtOH
45
23
23
24
24
18
13
19
0
21
52
25
67
Ru(bpy)3Cl2·6H2O
Ru(bpy)3Cl2·6H2O
Ru(bpy)3Cl2·6H2O
Ru(bpy)3Cl2·6H2O
Ru(bpy)3Cl2·6H2O
Ru(bpy)3Cl2·6H2O
Ru(bpy)3Cl2·6H2O
Ru(bpy)3Cl2·6H2O
Ru(bpy)3Cl2·6H2O
Ru(bpy)3Cl2·6H2O
Ru(bpy)3Cl2·6H2O
Ru(bpy)3Cl2·6H2O
Ru(bpy)3Cl2·6H2O
Ru(bpy)3Cl2·6H2O
Ru(bpy)3Cl2·6H2O
Ru(bpy)3Cl2·6H2O
Ru(bpy)3Cl2·6H2O
BPO (3)
c
TBHP (3)
TBHP (3)
TBHP (3)
TBHP (3)
TBHP (3)
TBHP (3)
TBHP (3)
TBHP (3)
TBHP (3)
TBHP (2)
TBHP (4)
TBHP (3)
TBHP (3)
TBHP (3)
9
K2CO3
10
11
12
13
14
15
16
17
18
19
20
LiOtBu
DBU
quinuclidine
DABCO
DABCO
DABCO
DABCO
DABCO
DABCO
DABCO
DABCO
DABCO
d
trace
DMF
DCM
37
45
43
54
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
e
trace
f
0
g
21
0
a
Reaction conditions: 1a (0.1 mmol), 2a (1.0 mL), photocatalyst (5.0 mol %), oxidant (3.0 equiv), base (2.0 equiv), CH3CN (0.6 mL), ambient
b
c
d
e
f
temperature, Ar, 10 W LED (450−455 nm), 20 h. Isolated yield. 70% TBHP in water. Coumarin (4a) was isolated. Air atmosphere. Without
visible light. In the absence of a photocatalyst.
g
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Scheme 2. Substrate Scope and Limitation of O-Hydroxycinnamates 1
Scheme 3. Scope and Limitation of Substrates 2
group (F, Cl, Br, CF3) substituted substrates (products 3h−k,
54−58% yields). The substituent R3 of the phenol moiety
could be electron-donating t-Bu (3l, 42% yield) or electron-
withdrawing F (3m, 69% yield) or Cl (3n, 50% yield). The
influence of substituent R4 of the phenol moiety on the
reaction was also examined. Thus, methyl- (3o), methoxy-
(3p), and chloro- (3r) substituted substrates gave the
corresponding products in higher yields (60−70%) compared
with the fluoro-substituted substrate (3q, 49% yield). Ethyl 3-
(3,5-dichloro-2-hydroxyphenyl)acrylate (3s) and ethyl 3-(3-
hydroxyanthracen-2-yl)acrylate (3t) provided good yields
(55% and 56%, respectively). When ethyl (E)-3-(2-hydroxy-
5-nitrophenyl)acrylate (1u) was used as the substrate,
however, we did not obtain any isolable products (Scheme 3).
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Encouraged by these results, we extended our strategy to
install 3-functionalized coumarins by simply replacing THF
with tetrahydrothiophene or various commercially available
ethers as alkyl radical sources. As shown in Scheme 3,
tetrahydrothiophene could work to give the desired products
3u−3w in satisfactory yields (51−65%). In the cases where
tetrahydro-2H-pyran, ethyl ether, or 1,3-dioxolane was used,
the reaction also proceeded smoothly to provide the
corresponding products 3x−3z in 50−62% yields with
excellent site selectivity. However, 1,4-dioxane, 1,2-dimethoxy-
ethane, and anisole only rendered a fairly complex reaction,
and the desired products were undetected.
Scheme 5. Kinetic Isotope Effect Experiment
Scheme 6. Plausible Mechanism for the Formation of 3a and
4a
To gain mechanistic insights into this transformation, several
control experiments were subsequently conducted (Scheme 4).
Scheme 4. Control Experiments
First, coumarin (4a) was submitted to the standard reaction
conditions. The desired 3-alkylated coumarin 3a and its 4-
alkylated isomer 5 were isolated in 52% and 22% yields,
respectively (Scheme 4, eq 1). When the 2-position of acrylate
substrate was blocked by a group, e.g., ethyl (E)-3-(2-
hydroxyphenyl)-2-methylacrylate (1v) was used as the
substrate, we just isolated coumarin 4b but did not obtain
any cross-coupling products (Scheme 4, eq 2). When 2,2,6,6-
tetramethylpiperidine N-oxide (TEMPO, 2 equiv) was used as
a radical trapping reagent into the model reaction system, the
transformation was totally suppressed and no C-3 alkylated
product 3a was obtained. However, coumarin was isolated in
58% yield, while TEMPO-tetrahydrofuran-2-yl adduct 6 was
detected by HRMS analysis of the reaction mixture (Scheme 4,
eq 3). These results indicated that this reaction proceeded via a
free radical pathway, and tetrahydrofuran-2-yl radical was a key
intermediate.
−0.81 V vs SCE) under the irradiation of blue light. Then, the
single electron transfer (SET) from *[Ru(ppy)3]2+ to oxidant
t-BuOOH forms radical t-BuO·, accompanied by the oxidation
of *[Ru(ppy)3]2+ to [Ru(ppy)3]3+. The radical t-BuO·
abstracts a hydrogen from THF to form a carbon radical A.
Subsequently, the radical A regioselectively attacks the most
electron-rich position of the double bond in cinnamate 1a to
form carbon radical B−I (Path I), which is further oxidized to
carbocation C−I by [Ru(ppy)3]3+ (E1/2[Ru(III)/Ru(II)] = +1.29 V
vs SCE) via SET process, completing the photocatalytic cycle
and regenerating the ground state [Ru(ppy)3]2+. In the
presence of a base, the carbocation C−I undergoes
deprotonation to form intermediate D, which provides the
final product 3a through lactonization. Alternatively, an
isomerization/cyclization/alkylation sequence may take place.
Thus, the energy transfer (EnT) from *[Ru(ppy)3]2+ to 1a
leads to the formation of coumarin 4a as shown in Scheme 6b.
Subsequently, a kinetic isotope effect (KIE) experiment was
conducted (Scheme 5). A kinetic isotope effect (kH/kD = 3.2)
was observed when 1a was treated with an equal mixture (1:1)
of THF (2a) and THF-d8 (D8−2a) under identical conditions.
Thus, the C(sp3)−H cleavage of THF is the rate-determining
step in this process (see Supporting Information).
Based on our observations and previous literature reports,10
a plausible mechanism for the formation of 3 is proposed in
Scheme 6. Initially, photocatalyst [Ru(ppy)3]2+ generates the
highly reducing excited *[Ru(ppy)3]2+ (E1/2[
*
=
Ru(II)/Ru(III)]
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Scheme 7. Experiment in a mmol Scale and One-Pot Synthesis
values were reported in hertz (Hz). Chemical shifts (in ppm) were
referenced to TMS (δ = 0 ppm) in CDCl3 or the center line of a
quintet at 3.30 ppm of MeOH-d4 as an internal standard. 13C{1H}
NMR spectra were obtained by using the same NMR spectrometers
and chemical shifts were referenced to the center line of a triplet at
77.00 ppm of CDCl3 or the center line of a heptet at 48.80 ppm of
MeOH-d4. High-resolution mass spectra (HRMS) were recorded on a
Q-TOF-MS instrument (ESI). The fluorescence spectra were
recorded on a fluorescence spectrophotometer with a xenon lamp
excitation source.
The process might include an isomerization of (E)-cinnamate
1a to its (Z)-isomer E and base-promoted lactonization.4c,11
The Stern−Volmer experiment exhibited that the excited
photocatalyst *[Ru(ppy)3]2+ could be oxidatively quenched by
cinnamate 1a (see Figure S2), supporting the EnT mechanism.
The addition of carbon radical A to 4a generates carbon radical
B−II (path II). The subsequent SET oxidation results in the
carbocation intermediate C−II, which undergoes elimination
to provide 3a.
To demonstrate the practicality and scalability of this
protocol, we performed the reaction of 1a with THF on a 1
mmol scale under standard reaction conditions and obtained a
47% yield of 3a (Scheme 7A). Furthermore, a one-pot
synthesis of the desired product 3a by starting from
salicylaldehyde (7) and ethyl 2-(triphenylphosphoranylidene)-
acetate (8) was developed, and 54% yield was obtained
(Scheme 7B), indicating that the synthetic operation could be
simplified.
General Procedures for the Synthesis of Compounds 1.11
To an oven-dried 100 mL sealing tube equipped with a magnetic
stirring bar were added sequentially salicylaldehyde (10.0 mmol),
ethyl 2-(triphenylphosphoranylidene) acetate (12.0 mmol), and dry
CH2Cl2 (40 mL). The reaction mixture was stirred at room
temperature for 2−8 h. The conversion of the starting materials
was monitored by TLC. Then, the reaction solution was concentrated
in vacuo to remove the solvent. The crude product was purified by
silica gel column chromatography [petroleum ether (PE)/ethyl
acetate (EA) = 30:1−8:1, v/v].
((E)-Ethyl 3-(2-Hydroxyphenyl)acrylate (1a). Known compoun-
CONCLUSION
d.12a White solid; column chromatography (PE/EA = 5:1). Yield:
■
1
1.23 g, 64%. H NMR (400 MHz, CDCl3): δ 8.11−8.06 (m, 1H),
In summary, we have demonstrated a regioselective synthesis
of 3-functionalized coumarins by photocatalysis strategy using
Ru(bpy)3Cl2·6H2O as photocatalyst and TBHP as oxidant.
With visible light irradiation, direct and regioselective C(sp2)-
C(sp3) coupling reaction of 3-(2-hydroxyphenyl)acrylates with
ethers or thioethers furnished 3-alkylated coumarins. The
cascade process involves alkenylation of α-C(sp3)-H bond of
ethers/thioethers and lactonization. The features of this
method include broad substrate scope, mild reaction
conditions, and simplified operation. Additionally, the syn-
thesis of 3-alkylated coumarins could be realized by a one-pot
procedure starting from commercially available salicylaldehyde.
7.47−7.45 (m, 2H), 7.25−7.20 (m, 1H), 6.91−6.88 (m, 2H), 6.68 (d,
J = 16.2 Hz, 1H), 4.30 (q, J = 7.2 Hz, 2H), 1.35 (t, J = 7.2 Hz, 3H).
13C{1H} NMR (100 MHz, CDCl3): δ 169.0 155.8, 141.1, 131.5,
129.2, 121.6, 120.5, 118.0, 116.4, 60.8, 14.3. HRMS (ESI) m/z: [M +
+
H] calcd for C11H12O3H+ 193.0859, found: 193.0860.
(E)-Ethyl 3-(2-Hydroxy-3-methylphenyl)acrylate (1b). Known
compound.12b White solid; column chromatography (PE/EA =
5:1). Yield: 1.45 g, 70%. 1H NMR (400 MHz, CDCl3): δ 8.26−
8.20 (m, 1H), 7.36 (d, J = 7.6 Hz, 1H), 7.14 (d, J = 7.4 Hz, 1H), 6.83
(t, J = 7.6 Hz, 1H), 6.53 (d, J = 16.0 Hz, 2H), 4.27 (q, J = 7.2 Hz,
2H), 2.32 (s, 3H), 1.34 (t, J = 7.2 Hz, 3H). 13C{1H} NMR (100
MHz, CDCl3): δ 168.3, 153.70, 140.8, 132.8, 126.1, 124.1, 121.6,
120.3, 117.8, 60.6, 16.0, 14.3. HRMS (ESI) m/z: [M + H] + calcd for
C12H14O3H+ 207.1016, found: 207.1016.
((E)-Ethyl 3-(2-Hydroxy-3-methoxyphenyl)acrylate (1c). Known
compound.12a White solid; column chromatography (PE/EA = 5:1).
Yield: 1.74 g, 78%. 1H NMR (400 MHz, CDCl3): δ 7.95 (d, J = 16.2
Hz, 1H), 7.09−7.07(m, 1H), 6.87−6.81 (m, 2H), 6.60 (d, J = 16.2
Hz, 1H), 6.22 (s, 1H), 4.26 (q, J = 7.2 Hz, 2H), 3.90 (s, 3H), 1.34 (t,
J = 7.2 Hz, 3H). 13C{1H} NMR (100 MHz, CDCl3): δ 167.55,
146.81, 145.3, 139.5, 120.9, 120.8, 119.6, 119.3, 111.7, 60.4, 56.2,
14.4. HRMS (ESI) m/z: [M + H] + calcd for C12H14O4H+ 223.0965,
found: 223.0966.
EXPERIMENTAL SECTION
■
General Information. Unless otherwise mentioned, solvents,
compounds 2, and reagents were purchased from commercial sources
and used as received. The photochemical reactions were irradiated at
room temperature using a 10 W blue LED lamp (450−455 nm)
equipped with ten 20 mL quartz tubes (Figure S1). The distance from
the light source to the irradiation container was about 2 cm. Flash
column chromatography was performed using 300−400 mesh silica
gel. Melting points were recorded on a SGW X-4. NMR spectra were
1
obtained at 400 or 600 MHz for H NMR, 100 or 150 MHz for
((E)-Ethyl 3-(3-Fluoro-2-hydroxyphenyl)acrylate (1d). Known
compound.12b White solid; column chromatography (PE/EA =
5:1). Yield: 1.46 g, 69%. 1H NMR (400 MHz, CDCl3): δ 8.03−
7.98 (m, 1H), 7.27−7.23 (m, 1H), 7.15−7.05 (m, 1H), 6.86−6.81
13C{1H} NMR, and 376 or 564 MHz for 19F{1H} NMR. The
following abbreviations were used to describe peak splitting patterns
when appropriate: s = singlet, d = doublet, t = triplet, m = multiplet. J
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(m, 1H), 6.79−6.58 (m, 2H), 4.30 (q, J = 7.2 Hz, 2H), 1.35 (t, J = 7.2
Hz, 3H). 13C{1H} NMR (100 MHz, CDCl3): δ 167.8, 151.4 (d, J =
235.0 Hz), 143.5 (d, J = 13.0 Hz), 139.1, 124.2 (d, J = 3.0 Hz),
123.67, 119.9 (d, J = 7.0 Hz), 119.8, 116.6 (d, J = 18.0 Hz), 60.7,
14.3. HRMS (ESI) m/z: [M + H]+ calcd for C11H11FO3H+ 211.0765,
found: 211.0765.
14.23. HRMS (ESI) m/z: [M + H]+ calcd for C12H11F3O3H+
261.0733, found: 261.0735.
((E)-Ethyl 3-(5-(tert-Butyl)-2-hydroxyphenyl)acrylate (1l). Known
compound.12d White solid; column chromatography (PE/EA = 5:1).
1
Yield: 1.50 g, 60%. H NMR (400 MHz, CDCl3): δ 8.05−8.00 (m,
1H), 7.46 (d, J = 2.4 Hz, 1H), 7.28−7.25 (m, 1H), 6.81−6.78 (m,
1H), 6.69−6.64 (m, 1H), 6.55 (s, 1H), 4.30 (q, J = 7.2 Hz, 2H), 1.36
(t, J = 7.2 Hz, 3H), 1.29 (s, 9H). 13C{1H} NMR (100 MHz, CDCl3):
δ 168.6, 153.2, 143.4, 141.3, 128.7, 126.0, 120.9, 118.1, 116.1, 60.7,
34.1, 31.4, 14.4. HRMS (ESI) m/z: [M + H]+ calcd for C15H20O3H+
249.1485, found: 249.1487.
((E)-Ethyl 3-(3-Chloro-2-hydroxyphenyl)acrylate (1e). Known
compound.12b White solid; column chromatography (PE/EA =
1
5:1). Yield: 1.45 g, 64%. H NMR (400 MHz, CDCl3): δ 7.94 (d, J
= 16.2 Hz, 1H), 7.41−7.41 (m, 1H), 7.39−7.39 (m, 1H), 6.91−6.87
(m, 1H), 6.60 (d, J = 16.2 Hz, 1H), 6.15 (s, 1H), 4.28 (q, J = 7.1 Hz,
2H), 1.34 (t, J = 7.2 Hz, 3H). 13C{1H} NMR (100 MHz, CDCl3): δ
((E)-Ethyl 3-(5-Fluoro-2-hydroxyphenyl)acrylate (1m). Known
compound.11 White solid; column chromatography (PE/EA = 5:1).
Yield: 1.39 g, 66%. 1H NMR (400 MHz, CDCl3): δ 8.04 (d, J = 16.2
Hz, 1H), 7.17−7.14 (m, 1H), 6.96−6.91 (m, 1H), 6.86−6.82 (m,
1H), 6.59 (d, J = 16.2 Hz, 1H), 4.30 (q, J = 7.2 Hz, 2H), 1.36 (t, J =
7.2 Hz, 3H). 13C{1H} NMR (100 MHz, CDCl3): δ 168.6, 156.7 (d, J
= 237 Hz), 155.50, 151.9 (d, J = 2.0 Hz, 1H), 139.9 (d, J = 2.0 Hz),
122.5 (d, J = 8.0 Hz), 118.86 (d, J = 23.0 Hz), 117.4 (d, J = 8.0 Hz),
114.27 (d, J = 23.0 Hz), 61.04, 14.28. HRMS (ESI) m/z: [M + H]+
calcd for C11H11FO3H+ 211.0765, found: 211.0766.
167.2, 150.4, 139.0, 130.2, 127.8, 122.9, 121.0, 120.9, 120.3, 60.6,
+
14.3. HRMS (ESI) m/z: [M + H]
calcd for C11H11ClO3H+
227.0468, found: 227.0469.
((E)-Ethyl 3-(3-Bromo-2-hydroxyphenyl)acrylate (1f). Known
compound.12b White solid; column chromatography (PE/EA =
1
5:1). Yield: 1.68 g, 62%. H NMR (400 MHz, CDCl3): δ 7.93 (d, J
= 16.2 Hz, 1H), 7.49−7.47 (m, 1H), 7.46−7.41 (m, 1H), 6.85−6.81
(m, 1H), 6.58 (d, J = 16.2 Hz, 1H), 6.03 (s, 1H), 4.27 (q, J = 7.2 Hz,
2H), 1.34 (t, J = 7.2 Hz, 3H). 13C{1H} NMR (100 MHz, CDCl3): δ
((E)-Ethyl 3-(5-Chloro-2-hydroxyphenyl)acrylate (1n). Known
compound.11 White solid; column chromatography (PE/EA = 5:1).
Yield: 1.66 g, 73%. 1H NMR (400 MHz, CDCl3): δ 8.00 (d, J = 16.2
Hz, 1H), 7.59 (s, 1H), 7.43 (d, J = 2.5 Hz, 1H), 7.19−7.17 (m, 1H),
6.83 (d, J = 8.6 Hz, 1H), 6.65 (d, J = 16.2 Hz, 1H), 4.31 (q, J = 7.2
Hz, 2H), 1.36 (t, J = 7.2 Hz, 3H). 13C{1H} NMR (100 MHz,
CDCl3): δ 168.7, 154.2, 139.7, 131.0, 128.3, 125.4, 123.0, 119.1,
117.7, 61.1, 14.2. HRMS (ESI) m/z: [M + H]+ calcd for
C11H11ClO3H+ 227.0469, found: 227.0471.
167.2, 150.4, 139.0, 130.2, 127.8, 122.9, 121.0, 120.9, 120.3, 60.6,
14.3. HRMS (ESI) m/z: [M + H]
270.9964, found: 270.9964.
+
calcd for C11H11ClO3H+
((E)-Ethyl 3-(2-Hydroxy-4-methylphenyl)acrylate (1g). Known
compound.12b White solid; column chromatography (PE/EA =
5:1). Yield: 1.45 g, 70%. 1H NMR (400 MHz, CDCl3): δ 8.02−
7.98 (m, 1H), 7.35 (d, J = 7.9 Hz, 1H), 6.73 (d, J = 8.0 Hz, 1H), 6.67
(s, 1H), 6.63−6.58 (m, 1H), 4.29 (q, J = 7.2 Hz, 2H), 2.30 (s, 3H),
1.35 (t, J = 7.2 Hz, 3H). 13C{1H} NMR (100 MHz, CDCl3): δ 168.7,
155.3, 142.3, 140.5, 129.1, 121.8, 119.0, 117.4, 117.0, 60.6, 21.4, 14.3.
((E)-Ethyl 3-(2-Hydroxy-6-methylphenyl)acrylate (1o). Known
compound.12e White solid; column chromatography (PE/EA =
+
HRMS (ESI) m/z: [M + H] calcd for C12H14O3H+ 207.1016,
1
5:1). Yield: 1.47 g, 71%. H NMR (400 MHz, CDCl3): δ 7.89 (d, J
found: 207.1015.
= 16.4 Hz, 1H), 7.10 (t, J = 7.8 Hz, 1H), 6.79 (d, J = 7.6 Hz, 1H),
6.76−6.69 (m, 2H), 5.98 (s, 1H), 4.29 (q, J = 7.2 Hz, 2H), 2.41 (s,
3H), 1.35 (t, J = 7.2 Hz, 3H). 13C{1H} NMR (100 MHz, CDCl3): δ
168.1, 155.2, 139.7, 139.1, 130.1, 122.9, 122.4, 120.6, 114.0, 60.6,
20.7, 14.3. HRMS (ESI) m/z: [M + H]+ calcd for C12H14O3H+
207.1016, found: 207.1016.
((E)-Ethyl 3-(2-Hydroxy-6-methoxyphenyl)acrylate (1p). Known
compound.12e White solid; column chromatography (PE/EA = 5:1).
Yield: 1.45 g, 65%. 1H NMR (400 MHz, CDCl3): δ 8.18 (d, J = 16.4
Hz, 1H), 7.16 (t, J = 8.0 Hz, 1H), 7.05 (s, 1H), 6.98 (d, J = 16.4 Hz,
1H), 6.51 (d, J = 8.0 Hz, 1H), 6.47 (d, J = 8.0 Hz, 1H), 4.30 (q, J =
7.2 Hz, 2H), 3.87 (s, 3H), 1.36 (t, J = 7.2 Hz, 3H). 13C{1H} NMR
(100 MHz, CDCl3): δ 169.5, 160.1, 157.0, 136.4, 131.2, 120.2, 111.1,
108.8, 102. 8, 60.5, 55.7, 14.4. HRMS (ESI) m/z: [M + H] + calcd for
C12H14O4H+ 223.0965, found: 223.0963.
((E)-Ethyl 3-(4-Fluoro-2-hydroxyphenyl)acrylate (1h). Known
compound.12b White solid; column chromatography (PE/EA =
1
5:1). Yield: 1.58 g, 75%. H NMR (400 MHz, CDCl3): δ 8.02 (d, J
= 16.2 Hz, 1H), 7.84 (s, 1H), 7.46−7.42 (m, 1H), 6.66−6.06 (m,
3H), 4.31 (q, J = 7.2 Hz, 2H), 1.36 (t, J = 7.2 Hz, 3H). 13C{1H}
NMR (100 MHz, CDCl3): δ 169.1, 164.5 (d, J = 250.0 Hz), 157.2 (d,
J = 11.0 Hz), 140.2, 130.6 (d, J = 10.0 Hz), 118.2 (d, J = 3.0 Hz),
117.4 (d, J = 2.0 Hz), 107.9 (d, J = 22.0 Hz), 103.9 (d, J = 24.0 Hz),
+
60.9, 14.3. HRMS (ESI) m/z: [M + H] calcd for C11H11FO3H+
211.0765, found: 211.0764.
((E)-Ethyl 3-(4-Chloro-2-hydroxyphenyl)acrylate (1i). Known
compound.12b White solid; column chromatography (PE/EA =
1
5:1). Yield: 1.66 g, 73%. H NMR (400 MHz, CDCl3) 8.01 (d, J =
16.2 Hz, 2H), 7.38 (d, J = 8.4 Hz, 1H), 6.93 (d, J = 2.0 Hz, 1H),
6.90−6.87 (m, 1H), 6.67 (d, J = 16.2 Hz, 1H), 4.32 (q, J = 7.2 Hz,
2H), 1.37 (t, J = 7.2 Hz, 3H). 13C{1H} NMR (100 MHz, CDCl3): δ
((E)-Ethyl 3-(2-Fluoro-6-hydroxyphenyl)acrylate (1q). Known
compound.10 White solid; column chromatography (PE/EA = 5:1).
Yield: 1.39 g, 66%. 1H NMR (600 MHz, CDCl3): δ 8.03 (d, J = 16.4
Hz, 1H), 7.87 (s, 1H), 7.16 (q, J = 8.0 Hz, 1H), 6.98 (d, J = 16.4 Hz,
1H), 6.69 (d, J = 8.2 Hz, 1H), 6.67−6.63 (m, 1H), 4.32 (q, J = 7.2
Hz, 2H), 1.37 (t, J = 7.2 Hz, 3H). 13C{1H} NMR (150 MHz,
CDCl3): δ 169.4, 162.7 (d, J = 252.0 Hz), 157.2 (d, J = 6.0 Hz),
134.3, 131.2 (d, J = 12.0 Hz), 121.6 (d, J = 9.0 Hz), 111.9 (d, J = 3.0
Hz), 111.0 (d, J = 13.5 Hz), 107.4 (d, J = 22.5 Hz), 63.63, 16.93.
169.1, 156.4, 140.2, 136.7, 130.0, 120.9, 120.4, 118.2, 116.7, 61.1,
+
14.3. HRMS (ESI) m/z: [M + H]
calcd for C11H11ClO3H+
227.0469, found: 227.0470.
((E)-Ethyl 3-(4-Bromo-2-hydroxyphenyl)acrylate (1j). Known
compound.12c White solid; column chromatography (PE/EA =
1
5:1). Yield: 3.0 g, 74%. H NMR (400 MHz, CDCl3): δ 7.99 (d, J
= 16.2 Hz, 1H), 7.76 (s, 1H), 7.32 (d, J = 8.4 Hz, 1H), 7.08 (d, J = 1.8
Hz, 1H), 7.06−7.03 (m, 1H), 6.67 (d, J = 16.2 Hz, 1H), 4.32 (q, J =
7.2 Hz, 2H), 1.37 (t, J = 7.2 Hz, 3H). 13C{1H} NMR (100 MHz,
CDCl3): δ 169.1, 156.4, 140.2, 136.7, 130.0, 120.9, 120.4, 118.2,
116.7, 61.1, 14.3. HRMS (ESI) m/z: [M + H]+ calcd for
C11H11BrO3H+ 270.9964, found: 270.9966.
((E)-Ethyl 3-(2-Hydroxy-4-(trifluoromethyl)phenyl)acrylate (1k).
Known compound.12b White solid; column chromatography (PE/EA
= 5:1). Yield: 1.65 g, 63%. 1H NMR (400 MHz, CDCl3): δ 8.06 (d, J
= 16.2 Hz, 1H), 7.67 (s, 1H), 7.57 (d, J = 8.0 Hz, 1H), 7.17 (d, J = 8.2
Hz, 1H), 7.13 (s, 1H), 6.75 (d, J = 16.2 Hz, 1H), 4.34 (q, J = 7.2 Hz,
2H), 1.38 (t, J = 7.2 Hz, 3H). 13C{1H} NMR (100 MHz, CDCl3): δ
168.5, 155.4, 139.4, 132.8 (q, J = 33.0 Hz), 129.6, 125.0, 123.6 (q, J =
270.0 Hz), 120.45, 117.2 (q, J = 4.0 Hz), 113.4 (q, J = 4.0 Hz), 61.23,
+
HRMS (ESI) m/z: [M + H] calcd for C11H11FO3H+ 211.0765,
found: 211.0765.
((E)-Ethyl 3-(2-Chloro-6-hydroxyphenyl)acrylate (1r). Known
compound.10 White solid; column chromatography (PE/EA = 5:1).
Yield: 1.45 g, 64%. 1H NMR (400 MHz, CDCl3): δ 8.04 (d, J = 16.0
Hz, 1H), 7.29 (s, 1H), 7.13 (t, J = 8.0 Hz, 1H), 7.07−6.98 (m, 2H),
6.82 (d, J = 8.2 Hz, 1H), 4.33 (q, J = 7.2 Hz, 2H), 1.38 (t, J = 7.2 Hz,
3H). 13C{1H} NMR (100 MHz, CDCl3): δ 168.4, 156.8, 137.9, 136.2,
130.6, 123.4, 122.0, 119.9, 115.0, 61.0, 14.3. HRMS (ESI) m/z: [M +
H]+ calcd for C11H11ClO3H+ 227.0469, found: 227.0470.
((E)-Ethyl 3-(3,5-Dichloro-2-hydroxyphenyl)acrylate (1s). Known
compound.10 White solid; column chromatography (PE/EA = 5:1).
Yield: 1.25 g, 48%. 1H NMR (400 MHz, CDCl3): δ 7.86 (d, J = 16.2
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Hz, 1H), 7.39 (d, J = 2.4 Hz, 1H), 7.35 (d, J = 2.4 Hz, 1H), 6.57 (d, J
= 16.2 Hz, 1H), 6.08 (s, 1H), 4.28 (q, J = 7.2 Hz, 2H), 1.34 (t, J = 7.2
Hz, 3H). 13C{1H} NMR (100 MHz, CDCl3): δ 166.8, 149.0, 137.6,
129.5, 127.3, 125.6, 123.9, 121.5, 121.4, 60.7, 14.3. HRMS (ESI) m/z:
2.00 (m, 1H), 1.97−1.92 (m, 1H), 1.79−1.75 (m, 1H). 13C{1H}
NMR (100 MHz, CDCl3): δ 160.5, 153.1, 136.4, 131.1, 130.9, 127.8,
124.4, 119.3, 116.4, 75.9, 68.9, 32.2, 25.7. IR (film): 3097, 2951, 2925,
2877, 1716, 1634, 1608, 1489, 1457, 1399, 1284, 1170, 1045 cm−1.
HRMS (ESI) m/z: [M + Na]+ calcd for C13H12O3Na+, 239.0679;
found, 239.0680.
−
−
[M-H] calcd for C11H9Cl2O3 258.9934, found: 258.9934.
((E)-Ethyl 3-(3-Hydroxynaphthalen-2-yl)acrylate (1t). Known
compound.12f Yellow solid; column chromatography (PE/EA =
5:1). Yield: 1.46 g, 60%. 1H NMR (400 MHz, CDCl3): δ 8.36 (d, J =
16.0 Hz, 1H), 8.05 (d, J = 8.4 Hz, 1H), 7.78−7.74 (m, 2H), 7.54−
7.50 (m, 1H), 7.40−7.35 (m, 1H), 7.17 (d, J = 9.2 Hz, 1H), 6.84 (d, J
= 16.4 Hz, 2H), 4.36 (q, J = 7.2 Hz, 2H), 1.40 (t, J = 7.2 Hz, 3H).
13C{1H} NMR (100 MHz, CDCl3): δ 168.1, 153.3, 138.5, 132.8,
131.6, 128.9, 128.7, 127.4, 123.8, 123.2, 123.0, 118.1, 113.8, 60.9,
14.4. HRMS (ESI) m/z: [M + H] + calcd for C15H14O3H+ 243.1016,
found: 243.1017.
8-Methyl-3-(tetrahydrofuran-2-yl)-2H-chromen-2-one (3b).
White solid; column chromatography (PE/EA = 40:1−30:1). Yield:
1
11.7 mg, 51%. Mp: 71−72 °C. H NMR (400 MHz, CDCl3): δ 7.79
(d, J = 1.6 Hz, 1H), 7.34 (d, J = 8.0 Hz, 2H), 7.19−7.15 (m, 1H),
4.98 (t, J = 6.8 Hz, 1H), 4.14−4.09 (m, 1H), 3.99−3.93 (m, 1H),
2.58−2.49 (m, 1H), 2.46 (s, 3H), 2.07−1.99 (m, 1H), 1.97−1.89 (m,
1H), 1.81−1.72 (m, 1H). 13C{1H} NMR (100 MHz, CDCl3): δ
160.7, 151.5, 136.8, 132.3, 130.6, 125.9, 125.5, 124.0, 119.0, 75.9,
68.9, 32.3, 25.6, 15.5. IR (film): 3041, 2963, 2923, 2847, 1737, 1598,
1557, 1444, 1399, 1257, 1235, 1222, 1171, 1111, 1070, 952, 917, 832,
742, 649 cm−1. HRMS (ESI) m/z: [M + Na]+ calcd for C14H14O3Na+,
253.0835; found, 253.0836.
((E)-Ethyl 3-(2-Hydroxy-5-nitrophenyl)acrylate (1u). Known
compound.11 Yellow solid; column chromatography (PE/EA = 5:1).
Yield: 1.02 g, 90%. 1H NMR (400 MHz, CD3OD): δ 7.96 (d, J = 16.2
Hz, 1H), 7.78−7.72 (m, 2H), 7.71 (d, J = 1.2 Hz, 1H), 6.77 (d, J =
16.2 Hz, 1H), 4.28 (q, J = 7.2 Hz, 2H), 1.35 (t, J = 7.2 Hz, 3H).
13C{1H} NMR (100 MHz, CD3OD): δ 168.3, 158.3, 150.4, 139.2,
130.6, 128.8, 122.5, 115.1, 111.2, 61.6, 14.4. HRMS (ESI) m/z: [M-
8-Methoxy-3-(tetrahydrofuran-2-yl)-2H-chromen-2-one (3c).
Known compound.7 Colorless crystal; column chromatography
(PE/EA = 40:1−30:1). Yield: 12.8 mg, 52%. Mp: 112−113 °C (lit.
109−111 °C).7 1H NMR (400 MHz, CDCl3): δ 7.78 (d, J = 1.6 Hz,
1H), 7.22−7.19 (m, 1H), 7.09−7.04 (m, 2H), 5.00−4.96 (m, 1H),
4.14−4.09 (m, 1H), 3.98−3.93 (m, 1H), 3.97 (s, 3H), 2.56−2.51 (m,
1H), 2.03−1.98 (m, 1H), 1.96−1.91 (m, 1H), 1.79−1.75 (m, 1H).
13C{1H} NMR (100 MHz, CDCl3): δ 159.9, 147.0, 142.8, 136.5,
131.3, 124.2, 119.9, 119.3, 112.8, 75.9, 68.9, 56.2, 32.2, 25.6. IR
(film): 3085, 2955, 2924, 2851, 1722, 1621, 1568, 1461, 1378, 1276,
1181, 1144, 1089, 1051, 1025 cm−1. HRMS (ESI) m/z: [M + Na]+
calcd for C14H14O4Na+, 269.0784; found, 269.0785.
−
−
H] calcd for C11H10NO5 236.0564, found: 236.0566.
((E)-ethyl 3-(2-Hydroxyphenyl)-2-methylacrylate (1v). Known
compound.12g White solid; column chromatography (PE/EA =
1
5:1). Yield: 1.43 g, 69%. H NMR (400 MHz, CDCl3): δ 7.81 (s,
1H), 7.26−7.19 (m, 2H), 6.95−6.91 (m, 2H), 6.25 (s, 1H), 4.28 (q, J
= 7.2 Hz, 2H), 2.03 (s, 3H), 1.34 (t, J = 7.2 Hz, 3H). 13C{1H} NMR
(100 MHz, CDCl3): δ 169.1, 154.0, 134.4, 130.0, 130.0, 122.8, 120.3,
120.2, 115.8, 61.2, 14.3, 14.2. HRMS (ESI) m/z: [M + H]+ calcd for
C12H14O3H+ 207.1018, found: 207.1016.
General Procedure for the Preparation of Compounds 3. To
an oven-dried test tube equipped with a magnetic stirring bar was
added sequentially ortho-hydroxycinnamates 1 (0.10 mmol), DABCO
(0.20 mmol, 2.0 equiv), Ru(bpy)3Cl2·6H2O (5.0 mol %), TBHP (5.5
M in decane, 55 μL, 3.0 equiv), ether (2, 1.0 mL) and MeCN (0.6
mL). The reaction mixture was irradiated with 10 W LED (450−455
nm) under argon atmosphere at 25 °C for 20 h. The resulting mixture
was evaporated under reduced pressure, the residue was purified by
flash column chromatography on silica gel (PE/EA = 30:1−20:1, v/v)
to give pure product 3.
Preparation of 3a in a 1 mmol Scale. To an oven-dried 100 mL
round-bottom flask equipped with a magnetic stirring bar were added
sequentially 1a (1.0 mmol), DABCO (2.0 mmol, 2.0 equiv),
Ru(bpy)3Cl2·6H2O (5.0 mol %), TBHP (5.5 M in decane, 550 μL,
3.0 equiv), THF (3.0 mL) and MeCN (1.8 mL). The reaction
mixture was irradiated with 10 W LED (450−455 nm) under argon
atmosphere at 25 °C for 20−24 h. The conversion of the starting
materials was followed by TLC. Then, the reaction concentrated in
vacuo to remove solvent. The crude product was purified by column
chromatography on silica gel (PE/EA = 30:1- 20:1, v/v) to give 102
mg of pure 3a (47% yield).
Preparation of 3a in One-Pot. To an oven-dried test tube
equipped with a magnetic stirring bar was added sequentially
salicylaldehyde (0.1 mmol, 1.0 equiv), (carbethoxymethylene)-
triphenyl phosphorane (0.12 mmol, 1.2 equiv), dry CH3CN (0.6
mL). The mixture was stirred at 25 °C for 4 h. Then, DABCO (0.20
mmol, 2.0 equiv), Ru(bpy)3Cl2·6H2O (5.0 mol %), TBHP (5.5 M in
decane, 55 μL, 3.0 equiv), THF (1.0 mL) and CH3CN (0.6 mL) were
add. The reaction mixture was irradiated with 10 W LED (450−455
nm) under argon atmosphere at 25 °C for 20 h. The conversion of the
starting materials was followed by TLC. After removal of solvent in
vacuo, the crude product was purified by column chromatography on
silica gel (PE/EA = 30:1−20:1, v/v) to give 11.7 mg of pure 3a (54%
yield).
8-Fluoro-3-(tetrahydrofuran-2-yl)-2H-chromen-2-one (3d). Col-
orless crystal; column chromatography (PE/EA = 40:1−30:1). Yield:
1
12.7 mg, 54%. Mp: 115−116 °C. H NMR (400 MHz, CDCl3): δ
7.82 (d, J = 1.6 Hz, 1H), 7.35−7.29 (m, 1H), 7.25−7.19 (m, 2H),
4.96 (t, J = 7.0 Hz, 1H), 4.14−4.09 (m, 1H), 3.96 (q, J = 7.4 Hz, 1H),
2.57−2.50 (m, 1H), 2.05−2.00 (m, 1H), 1.98−1.91 (m, 1H), 1.81−
1.74 (m, 1H). 13C{1H} NMR (100 MHz, CDCl3): δ 159.1, 149.3 (d,
J = 250.0 Hz), 142.9, 141.2(d, J = 12.0 Hz), 135.9 (d, J = 3.0 Hz),
132.1, 124.2 (d, J = 7.0 Hz), 122.9 (d, J = 4.0 Hz), 117.3 (d, J = 17.0
Hz), 75.8, 68.9, 32.2, 25.6. 19F{1H} NMR (376 MHz, CDCl3): δ
−119.3 (s, 1F). IR (film): 3097, 2955, 2916, 2856, 1730, 1646, 1485,
1403, 1268, 1182, 1139, 1081, 1021 cm−1. HRMS (ESI) m/z: [M +
+
H]+ calcd for C13H12FO3 , 235.0765; found, 235.0765.
8-Chloro-3-(tetrahydrofuran-2-yl)-2H-chromen-2-one (3e). Yel-
low solid; column chromatography (PE/EA = 40:1−30:1). Yield: 16.5
1
mg, 66%. Mp: 97−98 °C. H NMR (400 MHz, CDCl3): δ 7.80 (s,
1H), 7.55 (d, J = 8.0 Hz, 1H), 7.41 (d, J = 7.6 Hz, 1H), 7.24−7.20
(m, 1H), 4.97 (t, J = 7.0 Hz, 1H), 4.14−4.09 (m, 1H), 3.96 (q, J = 7.4
Hz, 1H), 2.60−2.51 (m, 1H), 2.08−2.00 (m, 1H), 1.99−1.89 (m,
1H), 1.80−1.72 (m, 1H). 13C{1H} NMR (100 MHz, CDCl3): δ
159.4, 148.8, 136.0, 132.0, 131.3, 126.2, 124.6, 121.3, 120.5, 75.8,
68.9, 32.2, 25.6. IR (film): 3054, 2925, 2954, 2865, 1722, 1606, 1466,
1384, 1270, 1177, 1160, 1089, 1077, 1057, 1019 cm−1. HRMS (ESI)
m/z: [M + Na]+ calcd for C13H11ClO3Na+, 273.0289; found,
273.0291.
8-Bromo-3-(tetrahydrofuran-2-yl)-2H-chromen-2-one (3f).
White solid; column chromatography (PE/EA = 40:1−30:1). Yield:
1
20.9 mg, 71%. Mp: 114−115 °C. H NMR (400 MHz, CDCl3): δ
7.77 (d, J = 1.6 Hz, 1H), 7.73−7.70 (m, 1H), 7.46−7.44 (m, 1H),
7.18−7.14 (m, 1H), 4.97 (t, J = 7.0 Hz, 1H), 4.14−4.09 (m, 1H),
4.00−3.94 (m, 1H), 2.59−2.50 (m, 1H), 2.08−1.99 (m, 1H), 1.98−
1.89 (m, 1H), 1.80−1.72 (m, 1H). 13C{1H} NMR (100 MHz,
CDCl3): δ 159.4, 149.8, 136.0, 134.4, 131.9, 127.0, 125.1, 120.5,
109.9, 75.8, 68.9, 32.2, 25.6. IR (film): 3092, 2967, 2925, 2873, 1725,
1637, 1597, 1447, 1384, 1266, 1168, 1066, 1044, 1021, 928 cm−1.
+
HRMS (ESI) m/z: [M + Na] calcd for C13H11BrO3Na+, 316.9784;
3-(Tetrahydrofuran-2-yl)-2H-chromen-2-one (3a). Colorless oil;
column chromatography (PE/EA = 40:1−30:1). Yield: 14.5 mg, 67%.
1H NMR (400 MHz, CDCl3): δ 7.80 (s, 1H), 7.50−4.7 (m, 2H), 7.33
(d, J = 5.6 Hz, 1H), 7.29−7.26 (m, 1H), 4.96 (t, J = 4.8 Hz, 1H),
4.13−4.10 (m, 1H), 3.98−3.94 (m, 1H), 2.55−2.50 (m, 1H), 2.04−
found, 316.9786.
7-Methyl-3-(tetrahydrofuran-2-yl)-2H-chromen-2-one (3g).
Known compound.13 White solid; column chromatography (PE/EA
= 40:1−30:1). Yield: 17.0 mg, 74%. Mp: 61−62 °C (lit. 61.6−62.2
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°C).13 1H NMR (400 MHz, CDCl3): δ 7.77 (s, 1H), 7.37 (d, J = 8.0
Hz, 1H), 7.14 (s, 1H), 7.09 (d, J = 8.0 Hz, 1H), 4.97−4.93 (m, 1H),
4.14−4.08 (m, 1H), 3.98−3.92 (m, 1H), 2.55−2.47 (m, 1H), 2.45 (s,
3H), 2.07−1.99 (m, 1H), 1.97−1.89 (m, 1H), 1.81−1.72 (m, 1H).
13C{1H} NMR (100 MHz, CDCl3): δ 160.7, 153.2, 142.0, 136.4,
129.7, 127.4, 125.6, 116.8, 116.6, 75.9, 68.8, 32.2, 25.6, 21.7. IR
(film): 3051, 2925, 2872, 1721, 1621, 1569, 1455, 1384, 1328, 1281,
1181, 1144, 1100, 1051, 1026 cm−1. HRMS (ESI) m/z: [M + Na]+
calcd for C14H14O3Na+, 253.0835; found, 253.0835.
5-Fluoro-3-(tetrahydrofuran-2-yl)-2H-chromen-2-one (3m).
White solid; column chromatography (PE/EA = 40:1−30:1). Yield:
1
16.2 mg, 69%. Mp: 81−82 °C. H NMR (400 MHz, CDCl3): δ 7.76
(d, J = 1.6 Hz, 1H), 7.33−7.29 (m, 1H), 7.23−7.17 (m, 2H), 4.97−
4.94 (m, 1H), 4.14−4.08 (m, 1H), 3.99−3.94 (m, 1H), 2.56−2.51
(m, 1H), 2.05−2.00 (m, 1H), 1.97−1.94 (m, 1H) 1.79−1.75 (m,
1H). 13C{1H} NMR (100 MHz, CDCl3): δ 160.1, 158.8 (d, J = 243.0
Hz), 149.2 (d, J = 2.0 Hz), 135.4 (d, J = 2.0 Hz), 132.4, 120.0 (d, J =
10.0 Hz), 118.3 (d, J = 24.0 Hz), 117.9 (d, J = 8.0 Hz), 113.0 (d, J =
24.0 Hz), 75.9, 68.9, 32.2, 25.7. 19F{1H} NMR (376 MHz, CDCl3): δ
−117.6 (s, 1F). IR (film): 3071, 2951, 2925, 2865, 1731, 1582, 1490,
1439, 1403, 1266, 1181, 1049 cm−1. HRMS (ESI) m/z: [M + Na]+
calcd for C13H11FO3Na+, 257.0584; found, 257.0584.
7-Fluoro-3-(tetrahydrofuran-2-yl)-2H-chromen-2-one (3h).
White solid; column chromatography (PE/EA = 40:1−30:1). Yield:
1
12.7 mg, 54%. Mp: 73−74 °C. H NMR (400 MHz, CDCl3): δ 7.78
(d, J = 1.2 Hz, 1H), 7.50−7.46 (m, 1H), 7.07−6.99 (m, 2H), 4.94 (t,
J = 6.8 Hz, 1H), 4.13−4.08 (m, 1H), 3.98−3.93 (m, 1H), 2.56−2.48
(m, 1H), 2.08−1.99 (m, 1H), 1.97−1.89 (m, 1H), 1.80−1.72 (m,
1H). 13C{1H} NMR (100 MHz, CDCl3): δ 163.9 (d, J = 251.0 Hz),
160.1, 154.1 (d, J = 13.0 Hz), 135.9, 129.8(d, J = 3.0 Hz), 129.2 (d, J
= 10.0 Hz), 115.9, 112.5 (d, J = 23.0 Hz), 104.1 (d, J = 25.0 Hz),
75.8, 68.9, 32.2, 25.7. 19F{1H} NMR (376 MHz, CDCl3): δ −106.4
(s, 1F). IR (film): 3082, 2955, 2925, 2865, 1729, 1619, 1586, 1505,
1431, 1385, 1273, 1251, 1180, 1141, 1110, 1045, 1021 cm−1. HRMS
6-Chloro-3-(tetrahydrofuran-2-yl)-2H-chromen-2-one (3n).
Known compound.6b White crystal; column chromatography (PE/
EA = 40:1−30:1). Yield: 12.5 mg, 50%. Mp: 124−125 °C (lit. 80−81
°C).6b 1H NMR (400 MHz, CDCl3): δ 7.74 (d, J = 1.6 Hz, 1H),
7.48−7.42 (m, 2H), 7.29 (s, 1H), 4.97−4.93 (m, 1H), 4.13−4.08 (m,
1H), 3.99−3.93 (m, 1H), 2.58−2.49 (m, 1H), 2.06−1.99 (m, 1H),
1.98−1.90 (m, 1H), 1.80−1.71 (m, 1H). 13C{1H} NMR (100 MHz,
CDCl3): δ 159.9, 151.5, 135.2, 132.4, 130.8, 129.6, 127.0, 120.3,
117.9, 75.9, 68.9, 32.2, 25.6. IR (film): 3092, 2955, 2920, 2847, 1715,
1564, 1480, 1403, 1381, 1268, 1244, 1180, 1080, 1048 cm−1. HRMS
+
(ESI) m/z: [M + Na] calcd for C13H11FO3Na+, 257.0584; found,
257.0585.
+
(ESI) m/z [M + Na] calcd for C13H11ClO3Na+, 273.0289; found,
7-Chloro-3-(tetrahydrofuran-2-yl)-2H-chromen-2-one (3i). Yel-
low solid; column chromatography (PE/EA = 40:1−30:1). Yield: 14.0
mg, 56%. Mp: 65−67 °C. 1H NMR (400 MHz, CDCl3): δ 7.77 (d, J =
1.6 Hz, 1H), 7.42 (d, J = 8.4 Hz, 1H), 7.34 (d, J = 2.0 Hz, 1H), 7.27−
7.24 (m, 1H), 4.95−4.91 (m, 1H), 4.13−4.08 (m, 1H), 3.98−3.93
(m, 1H), 2.57−2.48 (m, 1H), 2.08−1.99 (m, 1H), 1.94−1.89 (m,
1H), 1.80−1.71 (m, 1H). 13C{1H} NMR (100 MHz, CDCl3): δ
159.8, 153.3, 136.7, 135.6, 131.1, 128.5, 125.0, 117.8, 116.7, 75.8,
68.9, 32.2, 25.6. IR (film): 3085, 2925, 1724, 1633, 1062, 1567, 1488,
1461, 1411, 1180, 1076, 1047, 1021, 952 cm−1. HRMS (ESI) m/z:
[M + Na]+ calcd for C13H11ClO3Na+, 273.0289; found, 273.0289.
7-Bromo-3-(tetrahydrofuran-2-yl)-2H-chromen-2-one (3j). White
solid; column chromatography (PE/EA = 40:1−30:1). Yield: 17.0
mg, 58%. Mp: 103−104 °C. 1H NMR (400 MHz, CDCl3): δ 7.76 (s,
1H), 7.50 (d, J = 2.0 Hz, 1H), 7.42−7.39 (m, 1H), 7.35 (d, J = 8.0
Hz, 1H), 4.94−4.90 (m, 1H), 4.13−4.08 (m, 1H), 3.98−3.93 (m,
1H), 2.55−2.50 (m, 1H), 2.05−1.99 (m, 1H), 1.97−1.94 (m, 1H),
1.78−1.75 (m, 1H). 13C{1H} NMR (100 MHz, CDCl3): δ 159.7,
153.3, 135.8, 131.4, 128.7, 127.9, 124.7, 119.7, 118.2, 75.9, 68.9, 32.2,
25.6. IR (film): 3095, 2968, 2926, 2856, 1721, 1632, 1605, 1468,
1379, 1270, 1184, 1155, 1056, 1021, 784 cm−1. HRMS (ESI) m/z:
[M + Na]+ calcd for C13H11BrO3Na+, 316.9784; found, 316.9783.
3-(Tetrahydrofuran-2-yl)-7-(trifluoromethyl)-2H-chromen-2-one
(3k). White solid; column chromatography (PE/EA = 40:1−30:1).
Yield: 16.2 mg, 57%. Mp: 87−88 °C. 1H NMR (600 MHz, CDCl3): δ
7.84 (d, J = 1.8 Hz, 1H), 7.62 (d, J = 8.4 Hz, 1H), 7.58 (s, 1H), 7.52
(d, J = 7.8 Hz, 1H), 4.97−4.95 (m, 1H), 4.14−4.10 (m, 1H), 3.97 (q,
J = 7.4 Hz, 1H), 2.59−2.53 (m, 1H), 2.07−2.01 (m, 1H), 1.99−1.93
(m, 1H), 1.79−1.74 (m, 1H). 13C{1H} NMR (150 MHz, CDCl3): δ
159.5, 152.6, 135.1, 133.7, 132.6 (q, J = 33.0 Hz), 128.4, 123.3 (q, J =
270.0 Hz), 121.9, 121.0 (q, J = 4.5 Hz), 113.9 (q, J = 4.5 Hz), 75.9,
69.0, 32.2, 25.7. 19F{1H} NMR (564 MHz, CDCl3): δ −62.8 (s, 3F).
IR (film): 2956, 3087, 2956, 2943, 2910, 1738, 1635, 1511, 1429,
1334, 1320, 1267, 1210, 1267, 1170, 1130, 1064, 1047, 1022 cm−1.
273.0290.
5-Methyl-3-(tetrahydrofuran-2-yl)-2H-chromen-2-one (3o).
White solid; column chromatography (PE/EA = 40:1−30:1). Yield:
13.8 mg, 60%. Mp: 124−125 °C. H NMR (400 MHz, CDCl3): δ
1
7.99 (d, J = 0.8 Hz, 1H), 7.39−7.35 (m, 1H), 7.18 (d, J = 8.0 Hz,
1H), 7.10 (d, J = 7.2 Hz, 1H), 4.98−4.95 (m, 1H), 4.14−4.11 (m,
1H), 4.00−3.96 (m, 1H), 2.57−2.53 (m, 3H), 2.55 (s, 1H), 2.04−
2.02 (m, 1H), 2.00−1.96 (m, 1H), 1.82−1.71 (m, 1H). 13C{1H}
NMR (100 MHz, CDCl3): δ 160.5, 153.6, 136.0, 133.2, 130.6, 130.1,
125.6, 118.0, 114.4, 76.1, 68.8, 32.3, 25.7, 18.5. IR (film): 3075, 2952,
1722, 1629, 1481, 1401, 1282, 1262, 1180, 1155, 1086, 1047, 1022,
786 cm−1. HRMS (ESI) m/z: [M + Na]+ calcd for C14H14O3Na+,
253.0835; found, 253.0837.
5-Methoxy-3-(tetrahydrofuran-2-yl)-2H-chromen-2-one (3p).
White solid; column chromatography (PE/EA = 40:1−30:1). Yield:
16.0 mg, 65%. Mp: 60−61 °C. H NMR (400 MHz, CDCl3): δ 8.16
1
(d, J = 1.2 Hz, 1H), 7.42−7.38 (m, 1H), 6.92 (d, J = 8.4 Hz, 1H),
6.71 (d, J = 8.0 Hz, 1H), 4.98−4.95 (m, 1H), 4.17−4.11 (m, 1H),
3.98−3.93 (m, 1H), 3.94 (s, 3H), 2.52−2.47 (m, 1H), 2.01−1.94 (m,
2H), 1.79−1.74 (m, 1H). 13C{1H} NMR (100 MHz, CDCl3): δ
160.6, 156.1, 154.1, 131.7, 131.4, 129.0, 109.9, 108.8, 105.1, 76.1,
68.8, 55.9, 32.3, 25.6. IR (film): 3131, 2897, 1732, 1608, 1471, 1398,
1285, 1256, 1181, 1109, 1090 cm−1. HRMS (ESI) m/z: calcd for
C14H14O4Na+ [M + Na]+, 269.0784; found, 269.0785.
5-Fluoro-3-(tetrahydrofuran-2-yl)-2H-chromen-2-one (3q).
White solid; column chromatography (PE/EA = 40:1−30:1). Yield:
11.5 mg, 49%. Mp: 101−102 °C. H NMR (400 MHz, CDCl3): δ
1
8.04−8.03 (m, 1H), 7.47−7.41 (m, 1H), 7.14 (d, J = 8.8 Hz, 1H),
7.02−6.93 (m, 1H), 4.99−4.95 (m, 1H), 4.16−4.11 (m, 1H), 3.99−
3.94 (m, 1H), 2.55−2.51 (m, 1H), 2.08−2.00 (m, 1H), 1.99−1.90
(m, 1H), 1.80−1.77 (m, 1H). 13C{1H} NMR (100 MHz, CDCl3): δ
159.8, 158.5 (d, J = 252.0 Hz), 153.7 (d, J = 6.0 Hz), 131.4 (d, J = 2.0
Hz), 131.1 (d, J = 10.0 Hz), 129.3 (d, J = 4.0 Hz), 112.2 (d, J = 4.0
Hz), 110.3 (d, J = 19.0 Hz), 109.4 (d, J = 19.0 Hz), 75.9, 68.9, 32.2,
25.6. 19F{1H} NMR (376 MHz, CDCl3): δ −119.3 (s, 1F). IR (film):
3084, 2955, 2923, 2856, 1716, 1619, 1467, 1247, 1181, 1143, 1066,
1053, 1036, 1019 cm−1. HRMS (ESI) m/z: [M + Na]+ calcd for
C13H11FO3Na+, 257.0584; found, 257.0585.
+
HRMS (ESI) m/z: [M + H] calcd for C14H11F3O3H+, 285.0733,
found: 285.0733.
6-(tert-Butyl)-3-(tetrahydrofuran-2-yl)-2H-chromen-2-one (3l).
White solid; column chromatography (PE/EA = 40:1−30:1). Yield:
1
11.4 mg, 42%. Mp: 91−92 °C. H NMR (400 MHz, CDCl3): δ 7.81
(d, J = 1.6 Hz, 1H), 7.55−7.52 (m, 1H), 7.47 (d, J = 2.4 Hz, 1H),
7.28 (s, 1H), 4.99−4.95 (m, 1H), 4.14−4.09 (m, 1H), 3.99−3.93 (m,
1H), 2.54−2.49 (m, 1H), 2.04−1.99 (m, 1H), 1.97−1.92 (m, 1H),
1.79−1.74 (m, 1H), 1.35 (s, 9H). 13C{1H} NMR (100 MHz, CDCl3):
δ 160.8, 151.1, 147.5, 136.9, 130.7, 128.6, 124.1, 118.6, 116.0,76.0,
68.9, 34.5, 32.3, 31.4, 25.6. IR (film): 3092, 2957, 2318, 1717, 1631,
1465, 1397, 1384, 1261, 1175, 1070 cm−1. HRMS (ESI) m/z: [M +
Na]+ calcd for C17H20O3Na+, 295.1305; found, 295.1306.
5-Chloro-3-(tetrahydrofuran-2-yl)-2H-chromen-2-one (3r). Col-
orless solid; column chromatography (PE/EA = 40:1−30:1). Yield:
17.5 mg, 70%. Mp: 95−96 °C. H NMR (400 MHz, CDCl3): δ 8.16
(d, J = 1.6 Hz, 1H), 7.43−7.39 (m, 1H), 7.33−7.31 (m, 1H), 7.25 (d,
J = 8.0 Hz, 1H), 4.99−4.95 (m, 1H), 4.18−4.13 (m, 1H), 4.01−3.95
(m, 1H), 2.56−2.51 (m, 1H), 2.06−1.97 (m, 2H), 1.80−1.75 (m,
1H). 13C{1H} NMR (100 MHz, CDCl3): δ 159.7, 153.8, 132.7, 132.3,
132.1, 130.9, 125.0, 117.8, 115.3, 76.0, 68.9, 32.2, 25.6. IR (film):
1
9559
https://doi.org/10.1021/acs.joc.1c00848
J. Org. Chem. 2021, 86, 9552−9562

The Journal of Organic Chemistry
pubs.acs.org/joc
Article
3071, 2946, 2921, 2852, 1731, 1646, 1599, 1569, 1452, 1399, 1205,
1161, 1048, 1021, 964 cm−1. HRMS (ESI) m/z: [M + Na]+ calcd for
C13H11ClO3Na+, 273.0289; found, 273.0291.
(100 MHz, CDCl3): δ 160.3, 153.0, 137.4, 130.9, 130.9, 127.9, 124.4,
119.4, 116.4, 74.5, 69.1, 32.2, 25.9, 23.5. IR (film): 3062, 2936, 2853,
1717, 1634, 1609, 1457, 1398, 1308, 1285, 1207, 1181, 1087, 1074,
1040, 987 cm−1. HRMS (ESI) m/z: [M + Na]+ calcd for
C14H14O3Na+, 253.0835; found, 253.0835.
6,8-Dichloro-3-(tetrahydrofuran-2-yl)-2H-chromen-2-one (3s).
Yellow solid; column chromatography (PE/EA = 40:1−30:1).
Yield: 15.6 mg, 55%. Mp: 133−134 °C. 1H NMR (400 MHz,
CDCl3): δ 7.72 (d, J = 1.6 Hz, 1H), 7.54 (d, J = 2.4 Hz, 1H), 7.39 (d,
J = 2.4 Hz, 1H), 4.97−4.93 (m, 1H), 4.12−4.07 (m, 1H), 3.99−3.94
(m, 1H), 2.59−2.51 (m, 1H), 2.08−1.98 (m, 1H), 1.96−1.88 (m,
1H), 1.79−1.70 (m, 1H). 13C{1H} NMR (100 MHz, CDCl3): δ
158.8, 147.5, 134.9, 133.3, 130.9, 129.5, 125.6, 122.3, 121.1, 75.8,
69.0, 32.2, 25.7. IR (film): 3071, 2955, 2918, 2850, 1723, 1564, 1455,
1402, 1376, 1250, 1190, 1072, 1099, 1042, 1021 cm−1. HRMS (ESI)
m/z: [M + Na]+ calcd for C13H10Cl2O3Na+, 306.9899; found,
306.9901.
3-(Tetrahydrofuran-2-yl)-2H-benzo[g]chromen-2-one (3t).
Known compound.6b Yellow solid; column chromatography (PE/
EA = 40:1−30:1). Yield: 14.9 mg, 56%. Mp: 95−96 °C (lit. 89−91
°C).6b 1H NMR (400 MHz, CDCl3): δ 8.61 (s, 1H), 8.34 (d, J = 8.4
Hz, 1H), 7.97−7.87 (m, 2H), 7.71−7.67 (m, 1H), 7.59−7.56 (m,
1H), 7.47 (d, J = 8.8 Hz, 1H), 5.07−5.03 (m, 1H), 4.24−4.18 (m,
1H), 4.05−4.00 (m, 1H), 2.62−2.58 (m, 1H), 2.09−2.04 (m, 1H),
2.03−1.99 (m, 1H), 1.85−1.80 (m, 1H). 13C{1H} NMR (100 MHz,
CDCl3): δ 160.6, 152.5, 132.2, 132.1, 130.3, 130.1, 129.1, 128.9,
128.0, 125.9, 121.8, 116.7, 113.4, 76.2, 68.9, 32.3, 25.8. IR (film):
3049, 2952, 2869, 1716, 1635, 1575, 1516, 1438, 1384, 1209, 1182,
1092, 1050, 1019, 992 cm−1. HRMS (ESI) m/z: [M + Na]+ calcd for
C17H14O3Na+, 289.0835; found, 289.0836.
3-(1-Ethoxyethyl)-2H-chromen-2-one (3y). Known compound.6b
Colorless oil; column chromatography (PE/EA = 20:1−10:1). Yield:
1
11.8 mg, 54%. H NMR (400 MHz, CDCl3): δ 7.80 (s, 1H), 7.53−
7.49 (m, 2H), 7.35−7.29 (m, 2H), 4.62 (q, J = 6.4 Hz, 1H), 3.57−
3.51 (m, 2H), 1.44 (d, J = 6.4 Hz, 3H), 1.27 (t, J = 6.8 Hz, 3H).
13C{1H} NMR (100 MHz, CDCl3): δ 160.8, 153.1, 137.2, 131.7,
131.1, 127.9, 124.4, 119.4, 116.5, 72.2, 64.7, 21.5, 15.5. IR (film):
3097, 2955, 2919, 2850, 1738, 1463, 1399, 1378 cm−1. HRMS (ESI)
m/z: [M + Na]+ calcd for C13H14O3Na+, 241.0835; found, 241.0836.
3-(1,3-Dioxolan-2-yl)-2H-chromen-2-one (3z). Known com-
pound.6b White solid; column chromatography (PE/EA = 5:1−3:1).
Yield: 10.9 mg, 50%. Mp: 78−79 °C (lit. 73−75 °C).6b 1H NMR
(400 MHz, CDCl3): δ 7.96 (s, 1H), 7.57−7.53 (m, 2H), 7.35 (d, J =
8.2 Hz, 1H), 7.32−7.28 (m, 1H), 5.95 (s, 1H), 4.17−4.12 (m, 2H),
4.11−4.07 (m, 2H). 13C{H} NMR (100 MHz, CDCl3): δ 160.0,
153.9, 139.8, 132.2, 128.5, 125.1, 124.6, 118.6, 116.7, 99.0, 65.5. IR
(film): 3097, 2955, 2923, 2851, 1716, 1608, 1457, 1402, 1173, 1114,
1036, 753, 668 cm−1. HRMS (ESI) m/z: [M + Na]+ calcd for
C12H10O4Na+, 241.0471; found, 241.0471.
2H-Chromen-2-one (4a). White solid; column chromatography
(PE/EA = 40:1−30:1). Yield: 8.5 mg, 58%. Mp: 70−71 °C. 1H NMR
(400 MHz, CDCl3): δ 7.72 (d, J = 9.6 Hz, 1H), 7.56−7.49 (m, 2H),
7.35−7.27 (m, 2H), 6.43 (d, J = 9.6 Hz, 1H). 13C{1H} NMR (100
MHz, CDCl3): δ 160.8, 154.0, 143.4, 131.8, 127.8, 124.4, 118.8,
116.9, 116.7. IR (film): 1707, 1619, 1606, 1561, 1453, 1399, 1275,
1259, 1229, 1178, 1120, 1108 cm−1. HRMS (ESI) m/z: [M + H]+
3-(Tetrahydrothiophen-2-yl)-2H-chromen-2-one (3u). Known
compound.14 Yellow solid; column chromatography (PE/EA =
1
40:1−30:1). Yield: 11.8 mg, 51%. Mp: 69−70 °C. H NMR (400
+
MHz, CDCl3): δ 8.03 (s, 1H), 7.52−7.47 (m, 2H), 7.34−7.32 (m,
1H), 7.30−7.26 (m, 1H), 4.69 (t, J = 6.4 Hz, 1H), 3.09−3.08 (m,
1H), 2.99−2.96 (m, 1H), 2.45−2.41 (m, 1H), 2.10−2.07 (m, 1H),
2.06−2.00 (m, 1H), 1.99−1.93 (m, 1H). 13C{1H} NMR (100 MHz,
CDCl3): δ 161.2, 152.9, 139.0, 131.1, 130.8, 127.8, 124.4, 119.3,
116.4, 46.9, 37.1, 32.8, 30.0. IR (film): 2977, 2924, 2851, 1715, 1608,
1456, 1399, 1168 cm−1. HRMS (ESI) m/z: [M + Na]+ calcd for
C13H12O2SNa+, 255.0450; found, 255.0451.
calcd for C9H7O2 , 147.0446; found, 147.0443.
3-Methyl-2H-chromen-2-one (4b). White solid; column chroma-
tography (PE/EA = 50:1−40:1). Yield: 10.2 mg, 64%. Mp: 93−94 °C.
1H NMR (400 MHz, CDCl3): δ 7.53 (s, 1H), 7.49−7.41 (m, 2H),
7.32 (d, J = 8.0 Hz, 1H), 7.27−7.23 (m, 1H), 2.22 (s, 3H). 13C{1H}
NMR (100 MHz, CDCl3): δ 162.2, 153.2, 139.2, 130.4, 126.9, 125.8,
124.2, 119.6, 116.5, 17.2. IR (film): 3041, 2981, 2952, 2925, 2843,
1705, 1635, 1610, 1489, 1463, 1449, 1295, 1192, 1125, 1004, 947,
919, 853, 767, 753, 723 cm−1. HRMS (ESI) m/z: [M + H]+ calcd for
7-Methyl-3-(tetrahydrothiophen-2-yl)-2H-chromen-2-one (3v).
Yellow solid; column chromatography (PE/EA = 40:1−30:1).
Yield: 13.3 mg, 54%. Mp: 75−76 °C. 1H NMR (400 MHz,
CDCl3): δ 7.99 (s, 1H), 7.38 (d, J = 8.0 Hz, 1H), 7.13 (s, 1H),
7.09 (d, J = 7.6 Hz, 1H) 4.68 (t, J = 6.2 Hz, 1H), 3.11−3.06 (m, 1H),
3.00−2.94 (m, 1H), 2.45 (s, 3H), 2.42−2.37 (m, 1H), 2.11−2.01 (m,
2H), 2.00−1.92 (m, 1H). 13C{1H} NMR (150 MHz, CDCl3): δ
161.5, 153.1, 142.3, 138.9, 129.5, 127.4, 125.6, 116.8, 116.5, 46.9,
37.2, 32.8, 30.0, 21.7. IR (film): 2954, 2927, 2859, 2714, 1722, 1621,
1567, 1502, 1457, 1441, 1418, 1378, 1316, 1235, 1260, 1174, 1143,
1113, 1033, 967, 890, 860, 810, 781 cm−1. HRMS (ESI) m/z: [M +
Na]+ calcd for C14H14O2SNa+, 269.0606; found, 269.0607.
+
C10H9O2 , 161.0597; found, 161.0597.
4-(Tetrahydrofuran-2-yl)-2H-chromen-2-one (5). Colorless oil;
column chromatography (PE/EA = 50:1−40:1). Yield: 4.7 mg, 22%.
1H NMR (400 MHz, CDCl3): δ 7.52 (d, J = 7.6 Hz, 2H), 7.37 (d, J =
7.6 Hz, 1H), 7.30−7.26 (m, 1H), 6.60 (d, J = 1.2 Hz, 1H), 5.26−5.22
(m, 1H), 4.17−4.12 (m, 1H), 4.03−3.97 (m, 1H), 2.57−2.50 (m,
1H), 2.09−2.15 (m, 1H), 2.03−1.96 (m, 1H), 1.92−1.86 (m, 1H).
13C{1H} NMR (100 MHz, CDCl3): δ 161.16, 156.82, 153.89, 131.52,
124.09, 124.01, 117.58, 117.45, 110.93, 75.77, 69.16, 32.89, 25.71. IR
(film): 3086, 2956, 2930, 2867, 1717, 1639, 1483, 1455, 1275, 1171,
1043 cm−1. HRMS (ESI) m/z: [M + Na]+ calcd for C13H12O3Na+,
239.0679; found, 239.0679.
5-Chloro-3-(tetrahydrothiophen-2-yl)-2H-chromen-2-one (3w).
White solid; column chromatography (PE/EA = 40:1−30:1). Yield:
1
17.3 mg, 65%. Mp: 114−115 °C. H NMR (400 MHz, CDCl3): δ
ASSOCIATED CONTENT
8.36 (s, 1H), 7.43−7.39 (m, 1H), 7.34−7.31 (m, 1H), 7.25 (d, J = 8.0
Hz, 1H), 4.69 (t, J = 6.4 Hz, 1H), 3.15−3.09 (m, 1H), 3.02−2.96 (m,
1H), 2.48−2.40 (m, 1H), 2.12−2.05 (m, 2H), 2.02−1.95 (m, 1H).
13C{1H} NMR (100 MHz, CDCl3): δ 160.5, 153.6, 135.0, 132.2,
131.9, 131.1, 125.0, 117.7, 115.2, 47.0, 36.8, 32.9, 30.2. IR (film):
3080, 2956, 2924, 2869, 2847, 1753, 1726, 1569, 1483, 1463, 1443,
1380, 1339, 1260, 1189, 1155, 1122, 1100, 973, 914, 886, 816, 749,
680 cm−1. HRMS (ESI) m/z: [M + H]+ calcd for C13H11ClO2SH+,
267.0247; found, 267.0243.
■
sı
* Supporting Information
The Supporting Information is available free of charge at
https://pubs.acs.org/doi/10.1021/acs.joc.1c00848.
1
Copies of H NMR and 13C NMR spectra for all new
compounds; light reaction device; structures of sub-
strates; mechanistic experiments; X-ray crystal structures
and crystal data of compounds 3c (PDF)
3-(Tetrahydro-2H-pyran-2-yl)-2H-chromen-2-one (3x). Known
compound.6b Colorless oil; column chromatography (PE/EA =
Accession Codes
1
40:1−30:1). Yield: 14.3 mg, 62%. H NMR (400 MHz, CDCl3): δ
CCDC 2054357 contains the supplementary crystallographic
data for this paper. These data can be obtained free of charge
via www.ccdc.cam.ac.uk/data_request/cif, or by emailing
data_request@ccdc.cam.ac.uk, or by contacting The Cam-
7.83 (s, 1H), 7.51−7.47 (m, 2H), 7.33 (d, J = 8.0 Hz, 1H), 7.29−7.25
(m, 1H), 4.47 (d, J = 10.8 Hz, 1H), 4.19−4.16 (m, 1H), 3.69−3.62
(m, 1H), 2.22 (d, J = 13.4 Hz, 1H), 1.94−1.91 (m, 1H), 1.74−1.71
(m, 1H), 1.71−1.65 (m, 1H), 1.31−1.22 (m, 2H). 13C{1H} NMR
9560
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J. Org. Chem. 2021, 86, 9552−9562

The Journal of Organic Chemistry
pubs.acs.org/joc
Article
M.; Molloy, J. J.; Daniliuc, C. G.; Gilmour, R. Coumarins by Direct
Annulation: β-Borylacrylates as Ambiphilic C3-Synthons. Angew.
Chem., Int. Ed. 2021, 60, 685−689. (c) Metternich, J. B.; Gilmour, R.
One Photocatalyst, n Activation Modes Strategy for Cascade
Catalysis: Emulating Coumarin Biosynthesis with (−)-Riboflavin. J.
Am. Chem. Soc. 2016, 138, 1040−1045. (d) Chen, J. M.; Liu, W.;
Zhou, L. D.; Zhao, Y. L. Palladium catalyzed Heck-arylation/
cyclization cascade: An environmentally benign and efficient synthesis
of 4-arylcoumarins in Water. Tetrahedron Lett. 2018, 59, 2526−2531.
(5) For selected examples, see: (a) Min, M.; Kim, Y.; Hong, S.
Regioselective palladium-catalyzed olefination of coumarins via
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198. (b) Jafarpour, F.; Hazrati, H.; Mohasselyazdi, N.; Khoobi, M.;
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bridge Crystallographic Data Centre, 12 Union Road,
Cambridge CB2 1EZ, UK; fax: +44 1223 336033.
AUTHOR INFORMATION
Corresponding Authors
■
Ping Lu − Department of Chemistry, Zhejiang University,
Hangzhou 310027, People’s Republic of China;
orcid.org/0000-0002-3221-3647; Email: pinglu@
zju.edu.cn
Yanguang Wang − Department of Chemistry, Zhejiang
University, Hangzhou 310027, People’s Republic of China;
orcid.org/0000-0002-5096-7450; Email: orgwyg@
zju.edu.cn
Authors
Ke Zhang − Department of Chemistry, Zhejiang University,
Hangzhou 310027, People’s Republic of China
Li Qiao − Department of Chemistry, Zhejiang University,
Hangzhou 310027, People’s Republic of China
Jianwei Xie − Department of Chemistry, Zhejiang University,
Hangzhou 310027, People’s Republic of China
Zhenwei Lin − Department of Chemistry, Zhejiang University,
Hangzhou 310027, People’s Republic of China
Hanjie Li − Department of Chemistry, Zhejiang University,
Hangzhou 310027, People’s Republic of China
(6) For selected examples, see: (a) Niu, B.; Zhao, W. N.; Ding, Y.
C.; Bian, Z. G.; Pittman, C. U., Jr.; Zhou, A. H.; Ge, H. B.
Regioselective Cross-Couplings of Coumarins and Flavones with
Ethers via C(sp3)-H Functionalization. J. Org. Chem. 2015, 80, 7251−
7257. (b) Dian, L. Y.; Zhao, H.; Zhang-Negrerie, D.; Du, Y. F. Cobalt-
Catalyzed Twofold Direct C(sp2)-C(sp3) Bond Coupling: Regiose-
lective C-3 Alkylation of Coumarins with (Cyclo)alkyl Ethers. Adv.
Synth. Catal. 2016, 358, 2422−2426. (c) Banerjee, A.; Santra, S. K.;
Khatun, N.; Ali, W.; Patel, B. K. Oxidant controlled regioselective
mono- and difunctionalization reactions of coumarins. Chem.
Commun. 2015, 51, 15422−15425.
Complete contact information is available at:
https://pubs.acs.org/10.1021/acs.joc.1c00848
(7) Jafarpour, F.; Darvishmolla, M. Peroxy mediated Csp2-Csp3
dehydrogenative coupling: regioselective functionalization of coumar-
ins and coumarin-3-carboxylic acids. Org. Biomol. Chem. 2018, 16,
3396−3401.
Notes
The authors declare no competing financial interest.
(8) Jin, C.; Yan, Z. Y.; Sun, B.; Yang, J. Visible-Light-Induced
Regioselective Alkylation of Coumarins via Decarboxylative Coupling
with N-Hydroxyphthalimide Esters. Org. Lett. 2019, 21, 2064−2068.
(9) CCDC no. 2054357 (3c) contains supplementary crystallo-
graphic data for this paper.
ACKNOWLEDGMENTS
This work was financially supported by the National Natural
Science Foundation of China (21632003 and 21871229).
■
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