Visible-Light-Induced Direct Csp2-H Radical Trifluoroethylation of Coumarins with 1,1,1-Trifluoro-2-iodoethane (CF3CH2I)

Article abstract of DOI:10.1021/acs.joc.0c02739

Herein, we developed the first visible-light-induced direct Csp2-H radical 2,2,2-trifluoroethylation of coumarins with commercially available and cheap reagent CF3CH2I at room temperature. This transformation proceeded smoothly under mild conditions and showed excellent functional group compatibility. The synthetic value of the protocol was also demonstrated by the successful functionalization of several pharmaceuticals.

Full text of DOI:10.1021/acs.joc.0c02739

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Article
Visible-Light-Induced Direct Csp2‑H Radical Trifluoroethylation of
Coumarins with 1,1,1-Trifluoro-2-iodoethane (CF3CH2I)
Xiaoyu Chen, Linlin Li, Congcong Pei, Jingya Li, Dapeng Zou,* Yangjie Wu,* and Yusheng Wu*
Cite This: J. Org. Chem. 2021, 86, 2772−2783
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ABSTRACT: Herein, we developed the first visible-light-induced
direct Csp2-H radical 2,2,2-trifluoroethylation of coumarins with
commercially available and cheap reagent CF3CH2I at room
temperature. This transformation proceeded smoothly under mild
conditions and showed excellent functional group compatibility. The
synthetic value of the protocol was also demonstrated by the
successful functionalization of several pharmaceuticals.
using tert-butyl hydroperoxide (TBHP) as an oxidant and
easily prepared zinc sulphinate salts as different fluoroalkyl
radical sources (Scheme 1a).2a Based on this study, a number
of synthetic methods for (2,2,2-trifluoroethyl)arenes have been
intensively studied.2d For instance, Fu and Xu developed a
visible-light-induced C-3 selective trifluoroethylation of
INTRODUCTION
■
The introduction of fluorinated moieties into organic
compounds can have a profound influence on their chemical
and bioactive properties, such as lipophilicity, metabolic
stability, and bioavailability.1 Like various other fluorine-
containing functional groups, the 2,2,2-trifluoroethyl group
(CF3CH2) has also attracted increasing attention of synthetic
chemists owing to its potential utilities in medicinal chemistry
and related fields (Figure 1).2 To the best of our knowledge,
Scheme 1. Fluorine-Containing Functionalization of
Coumarins
Figure 1. CF3CH2-containing bioactive molecules.
the commercially available and cheap reagent 1,1,1-trifluoro-2-
iodoethane (CF3CH2I) as the source of CF3CH2 group has
been widely studied.3 Initially, it was believed that cross-
coupling reactions between 1,1,1-trifluoro-2-iodoethane
(CF3CH2I) and aromatic compounds remain a great challenge
because of (1) the slow oxidative addition of inactivated
CF3CH2I to a transition-metal (M) catalyst, (2) the difficulty
of reductive elimination from the CF3CH2−M−aryl complex,
and (3) the high tendency of β elimination of a fluoride ion
from this complex, which leads to the formation of undesired
side products.4 In 1969, McLoughlin and Thrower reported
copper(0)-promoted 2,2,2-trifluo-roethylation of iodobenzene
with 1,1,1-trifluoro-2-iodoethane (CF3CH2I) with a low
efficiency.5 In 2012, Baran and coworkers reported direct
C−H fluoroalkylation of nitrogen-rich heterocyclic compounds
Received: November 16, 2020
Published: January 25, 2021
https://dx.doi.org/10.1021/acs.joc.0c02739
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a
imidazoheterocycles using CF3CH2I as the trifluoroethyl
radical source in 2016 (Scheme 1b).6 Further, transition-
metal-catalyzed 2,2,2-trifluoroethylation reactions starting from
aryl halides,7 boronic acids,8 organoboronic esters,9 alkenes,10
alkynes,11 and alkynyl carboxylic acids12 have emerged as
efficient methods for C(sp2/sp)−CH2CF3 bond formation.
Despite this elegant progress, further expansion for the
synthetic approach of CF3CH2-substituted (hetero)arenes
under mild conditions is still highly desirable.
Table 1. Reaction Optimization
b
entry
photocatalysts
base
solvent
yield (%)
1
2
3
4
Ir(ppy)3
Ir(ppy)3
Ir(ppy)3
Ir(ppy)3
Ir(ppy)3
Ir(ppy)3
Ir(ppy)3
Ir(ppy)3
Ir(ppy)3
Ir(ppy)3
Eosin Y
Eosin B
Rose bengal
Ir(ppy)3
Ir(ppy)3
Ir(ppy)3
Ir(ppy)3
Ir(ppy)3
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
dioxane
DMF
NR
18
39
trace
12
61
81
56
45
21
NR
NR
NR
NR
NR
NR
73
Et3N
DBU
Coumarin and its derivatives, as an important class of
oxygen-containing heterocycle units, are widely found in
natural products and pharmaceutical molecules.13 Over the
past few years, the introduction of various fluorine-containing
functional groups into coumarins has been extensively
investigated.14 In 2014, Zou group published Mn(OAc)3-
mediated direct Csp2−H radical trifluoromethylation of
coumarins with CF3SO2Na (Langlois reagent) (Scheme
1c).15 Although the CF3 group can be introduced to coumarin
moieties smoothly, this protocol suffers from using equivalent
transition metal as oxidant. In recent years, photocatalysis has
become a powerful tool in organic synthesis because of the
advantages such as mild reaction conditions, low energy
consumption, and operational simplicity.16 In 2018, Deng and
coworkers developed visible-light-promoted Csp2-H radical
difluoromethylation of coumarins with NaSO2CF2H (Scheme
1d).17 In this context, we found that few examples have been
reported about the visible-light-induced radical 2,2,2-trifluor-
oethylation of arenes,18 especially the 2,2,2-trifluoroethylation
of O-heteroarenes. To our knowledge, the 2,2,2-trifluoroethy-
lation of coumarins is still unexplored. Based on our continual
efforts in C−H functionalization and fluorine chemistry,2c,9,19
we herein report an efficient method for direct Csp2-H radical
2,2,2-trifluoroethylation of coumarins with readily available
CF3CH2I under visible-light irradiation (Scheme 1B).
iPr2NEt
5
6
7
8
KF
CsF
K2CO3
Cs2CO3
K3PO4
KOtBu
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
9
10
11
12
13
14
15
16
CH3CN
DMSO
DMSO
c
17
18
d
89
a
Reaction conditions: 1a (0.20 mmol, 1.0 equiv), 2 (0.60 mmol, 3.0
equiv), photocatalysts (2 mol %), base (0.40 mmol, 2.0 equiv) in the
indicated solvent (2.0 mL); irradiation by 3 W blue LEDs at room
temperature for 12 h under Ar atmosphere. NR = no reaction.
b
c
Isolated yield. The photocatalyst loading was decreased to 1 mol %.
d
CF3CH2I (2, 0.8 mmol, 4.0 equiv).
equiv), CF3CH2I (2, 4.0 equiv), Ir(ppy)3 (2 mol %), and
K2CO3 (2.0 equiv) in DMSO (2 mL) at room temperature
under a 3 W blue LED irradiation for 12 h (Table 1, entry 18).
With the optimized reaction conditions in hand (Table 1,
entry 18), the substrate scope of various coumarins was then
investigated. It was found that the 2,2,2-trifluoroethylation
reaction tolerates a wide range of substituents on the benzene
ring or oxygen-containing heterocycle of coumarin. As revealed
in Scheme 2, coumarins with methyl group at the different
position of benzene ring afforded the expected 2,2,2-
trifluoroethylated coumarins (3b−3e) in 81−86% yields.
Meanwhile, moderate to excellent reaction yields (56−94%)
were provided when coumarins were substituted by groups
such as −tBu, −iPr, −OMe, −OEt, and −OBn at the C-7
position (3f−3j). Then, we were pleased to find that
coumarins containing reactive functional groups (esters,
alkenes, alkynes) were all compatible under the standard
conditions, and the expected products 3k−3n were acquired in
41−54% yields. The expected product 3l or 3m was acquired
in a moderate yield, presumably due to the partial
decomposition of substrates 1l and 1m under the standard
conditions. Moreover, coumarins bearing a cycloalkoxy group,
including cyclopropylmethoxy, cyclopentoxyl, and cyclohex-
yloxy, underwent the desired radical 2,2,2-trifluoroethylation
with high efficiency (products 3o−3q, 80−89% yields). The
introduction of the 2,2,2-trifluoroethyl group on 3H-benzo-
[f ]chromen-3-one 1r and 7,8,9,10-tetrahydro-2H-benzo[h]-
chromen-2-one 1s afforded the target products 3r and 3s in 56
and 31% yields, respectively. Satisfyingly, coumarins bearing
halogen groups (chloro, bromo) were well-tolerated, and the
desired products 3t and 3u were obtained in 90 and 84%
yields, respectively. Then, it was found that a coumarin with a
RESULTS AND DISCUSSION
■
We started our investigation by the model reaction of
coumarin (1a) with 1,1,1-trifluoro-2-iodoethane (CF3CH2I)
(2) using Ir(ppy)3 as a photocatalyst in DMSO at room
temperature under a 3 W blue LED irradiation for 12 h. To our
disappointment, no detectable amount of the desired product
was found (Table 1, entry 1). After extensive experiments, we
found that the reaction could be conducted in the presence of
organic base Et3N, and the desired product 3a was obtained in
18% isolated yield (Table 1, entry 2). The structure of
compound 3a was confirmed by X-ray diffraction (XRD) (see
the Supporting Information for details). Thus, several bases
i
(DBU, Pr2NEt, KF, CsF, K2CO3, Cs2CO3, K3PO4, and
KOtBu) were tested in the reaction (Table 1, entries 3−10).
The results illustrated that K2CO3 was the optimal choice for
this reaction, providing 3a in 81% yield (Table 1, entry 7).
Among the applied photocatalysts, Ir(ppy)3 delivered the best
yield, while other photocatalysts such as Eosin Y, Eosin B, and
Rose bengal were inefficient (Table 1, entries 7, 11−13). Then,
we carried out the reactions in several different solvents and
found that no reaction occurred in dioxane, N,N-dimethylfor-
mamide (DMF), or acetonitrile (CH3CN) (Table 1, entries
14−16). The yield of the target product reduced obviously
when the photocatalyst loading was decreased to 1 mol %
(Table 1, entry 17). To our delight, when the amount of
CF3CH2I was increased to 4.0 equiv, the desired product 3a
was obtained in 89% yield. Finally, the optimal reaction
conditions were established as follows: coumarin (1a, 1.0
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a,b
Scheme 2. Substrate Scope of Coumarins
a
Reaction conditions: 1a (0.20 mmol, 1.0 equiv), 2 (0.80 mmol, 4.0 equiv), Ir(ppy)3 (2 mol %), and K2CO3 (0.40 mmol, 2.0 equiv) in DMSO (2
b
c
mL); irradiation by 3 W blue LEDs at room temperature for 12 h under Ar atmosphere. Isolated yields. NR = no reaction.
methoxyl group at the C-4 position gave a moderate yield of 3v
(51%), while coumarins with a phenyl group on the oxygen-
containing heterocycle provided the corresponding products
3w−3y in good yields (83−87%). To our disappointment,
when N-Boc-protected aminocoumarin 1z with methyl group
at the C-4 position was employed, only a trace amount of the
desired product 3z was found. When 7-ethoxy-4-methyl-2H-
chromen-2-one 1z′ was used as the substrate, the desired
products 3z′ could be obtained in 71% yield, indicating that
methyl group at the C-4 position has a minor effect on the
reactivity of the substrate. The low reactivity of 1z is possibly
due to the amide substituent. After that, the influence of
electronic effects on the reaction was explored. When
coumarin bearing an electron-withdrawing group (−NO2) at
the C-6 position (denoted as 1-NO2) was used as the
substrate, no detectable amount of the desired product was
found. Finally, to further demonstrate the practical utility of
the method, 3a was synthesized in a gram scale under the
standard reaction conditions to afford the desired product in
74% yield.
delight, the above three target products were prepared for the
first time.
To probe the plausible reaction mechanism, some
preliminary mechanistic experiments were conducted, as
shown in Scheme 3. It was found that the reaction was
completely shut down when 2.0 equiv of radical scavenger
Scheme 3. Mechanistic Experiments
To further explore the synthetic value of our method in the
late-stage synthetic modifications, several biologically active
molecules were subjected to the Csp2-H 2,2,2-trifluoroethyla-
tion protocol to prepare their CF3CH2 analogs. As shown in
Scheme 2, a fungicide (osthole) and a Chinese herbal medicine
(angelicin) were 2,2,2-trifluoroethylated at C3 of the coumarin
moiety to give 2,2,2-trifluoroethylated osthole (TF-osthole)
and 2,2,2-trifluoroethylated angelicin (TF-angelicin) in 43 and
34% yields, respectively. The moderate yields in these two
reactions were presumably due to the low substrate conversion
rate. Moreover, flavone afforded the desired product TF-
flavone in 61% yield under the standard conditions. To our
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atmosphere. The solvents and reagents were purchased from
commercial sources without further purification unless otherwise
mentioned. Products were purified by flash chromatography on 100−
200 mesh silica gels, SiO2. All NMR spectra were obtained on Bruker
AVANCE III systems using CDCl3 or (CD3)2SO as solvent with TMS
as internal standard substance at 400 MHz for 1H NMR, 100 MHz for
13C NMR, and 376 MHz for 19F NMR. The chemical shifts (δ) are
reported in ppm relative to tetramethylsilane. The multiplicities of
signals are designated by the following abbreviations: s (singlet), d
(doublet), t (triplet), q (quarter), m (multiplet), dd (doublet and
doublet), dt (doublet and triplet), and dq (doublet and quarter). The
mass spectra were indicated by GC−MS (Thermo Fisher Scientific
DSQ II). High-resolution mass spectrometry (HRMS) data were
obtained on an Agilent Technologies 1290-6540 UHPLC/Accurate-
Mass Quadrupole Time-of Flight (Q-TOF) LC/MS using ESI as the
ion source. Measured values are reported to four decimal places of the
calculated value. X-ray analysis was performed with a single-crystal X-
ray diffractometer. Melting points were measured with an XT4A
microscopic melting point apparatus and were uncorrected. IR data
were measured by Fourier transform infrared spectrometry (BRUKER
TENSOR 27). An oil bath was used as the heat source for reactions
that require heating. Coumarin derivatives 1a−1c, 1h−1i, 1v, 1z′, 1-
NO2, osthole, angelicin, flavone, and 1,1,1-trifluoro-2-iodoethane
(CF3CH2I) 2 were purchased from commercial sources.
TEMPO (2,2,6,6-tetramethyl-1-piperidinyloxyl) was added to
the standard reaction mixture of 1a and 2. Meanwhile, the
TEMPO−CH2CF3 adduct 4 was detected by GC−MS, and
the yield was estimated as 38% by 19F NMR (Scheme 3a).
When 1,1-diphenylethylene (2.0 equiv) as a radical trapping
reagent was added to the reaction mixture, the yield of 3a
dramatically decreased to 8%, and the adduct 5 could be
detected by GC−MS (Scheme 3b). These experimental results
illustrated that the CF3CH2 radical was produced under the
optimal reaction conditions. Then, control experiments
showed that a blue light source and photocatalyst were both
essential for the reaction efficiency (Scheme 3c). Moreover,
light ON−OFF experiments were conducted, which showed
that the desired product 3a was formed only under continuous
irradiation (Scheme 3d). This result ruled out the possibility of
the radical chain propagation (see Supporting Information for
details).
On the basis of our experimental observations and previous
literature reports,6,15,16b a plausible reaction mechanism for the
2,2,2-trifluoroethylation of coumarins is proposed, as shown in
Scheme 4. First, under the irradiation of a blue LED, the
Super energy saving LED lamps (3 W Blue LED, made in China)
were used for blue light irradiation. A magnetic hot plate stirrer was
placed in the dark cassette for stirring. The material of the reaction
vessel (Schlenk tubes) was borosilicate glass, and the reaction solution
was placed at a distance of ∼1.0 cm from the 3 W LED (460−470
nm). An air conditioner was used to maintain the reaction
temperature at room temperature.
Scheme 4. Proposed Reaction Mechanism
General Experimental Procedure for the Synthesis of Coumarins
1d−1g and 1r−1u.20 A mixture of phenol derivatives (10.0 mmol),
trifluoromethanesulfonic acid (10.0 mmol) and propiolic acid (5.0
mmol) in PhCl (25 mL) was stirred at 100 °C for 1 h. After
completion of reaction as indicated by TLC, the reaction mixture was
poured into H2O, neutralized with NaHCO3 solution and extracted
CH2Cl2. The organic layer was dried over anhydrous Na2SO4. The
solvent was removed in vacuum, and the products were purified by
silica gel column chromatography (EtOAc-petroleum ether) to give
the desired product.
General Experimental Procedure for the Synthesis of Coumarins
1j and 1l−1q.21 A mixture of 7-hydroxycoumarin (486.4 mg, 3.0
mmol), alkyl or aryl halide (6.0 mmol), and potassium carbonate
(1.24 g, 9.0 mmol) in DMF (20 mL) was stirred at various
temperatures (from 30 to 85 °C) for times ranging from 1 h to
overnight. The reaction mixture was extracted with ethyl acetate, and
the combined extracts were washed with water. The organic layer was
dried over anhydrous Na2SO4 and evaporated to dryness. The residue
then was purified by column chromatography on silica gel with
petroleum ether/ethyl acetate to yield the products.
General Experimental Procedure for the Synthesis of Coumarins
1k.22 To a solution of umbelliferone (1.0 g, 6.2 mmol) in DCM (10
mL) was added acetic anhydride (6.7 g, 6.8 mmol) and pyridine (0.02
mL). The reaction mass was stirred at r.t. under nitrogen atmosphere
for 16 h. All the volatiles were removed under reduced pressure.
Crude mass was diluted with water (50 mL), extracted with ethyl
acetate (3 × 50 mL). The combined organic layers were dried
(Na2SO4), filtered, and concentrated under reduced pressure. The
crude product was purified by column chromatography on silica gel
using petroleum ether/ethyl acetate (5/1) to afford 1k as a white
solid.
photocatalyst Ir(ppy)3 is excited into *Ir(ppy)3. Then, a single
electron transfer (SET) from excited-state *Ir(ppy)3 to
CF3CH2I 2 generates a strong oxidant IVIr(ppy)3 and the
CF3CH2 radical. After that, CF3CH2 radical adds to the C-3
position of coumarin 1a to form the radical intermediate A.
Subsequently, the carbocation intermediate B is formed by
SET with strong oxidant IVIr(ppy)3. Finally, deprotonation of
B affords the desired product 3a.
CONCLUSION
■
In conclusion, we have developed the first visible-light-induced
direct Csp2-H radical 2,2,2-trifluoroethylation of coumarins
with commercially available and cheap reagent CF3CH2I at
room temperature. The reaction can be carried out under mild
conditions and is compatible with a variety of functional
groups (esters, alkenes, alkynes, and cycloalkoxy group). In
addition, this benign protocol makes it particularly suitable for
late-stage functionalization of natural products and pharma-
ceuticals.
General Experimental Procedure for the Synthesis of Coumarins
1w−1y.23 A dried Schlenk test tube containing a magnetic stirring bar
was charged under air with coumarins (1.0 mmol), arylboronic acids
(3.0 mmol), Pd(OAc)2 (10 mol %), 5-nitro-1,10-phenanthroline (15
mol %), and dry DMF (5.0 mL). Then, the O2 was introduced to the
tube to form an O2 balloon. The tube was sealed, and the mixture was
treated at 80 °C for 12 h. The resulting mixture was allowed to room
temperature and extracted with ethyl acetate three times. The
EXPERIMENTAL SECTION
General Information. All manipulations were performed in dried
glass reaction tube equipped with a magnetic stir bar under argon
■
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combined organic layers were dried with anhydrous Na2SO4 and
concentrated under reduced pressure. The resulting residue was
purified by column chromatography on silica gel with petroleum/
EtOAc to afford the desired product.
(petroleum ether/EtOAc = 3:1). Mp = 66−67 °C. IR (cm−1) 3054,
2972, 2919, 2857, 1717, 1612, 1506, 1452, 1394, 1348, 1279, 1232,
1122, 1004, 887, 839, 762; 1H NMR (400 MHz, CDCl3, ppm): δ 7.62
(d, J = 9.5 Hz, 1 H), 7.35 (d, J = 8.5 Hz, 1 H), 6.84 (dd, J = 8.5 Hz,
2.4 Hz, 1 H), 6.81 (d, J = 2.4 Hz, 1 H), 6.23 (d, J = 9.4 Hz, 1 H),
5.48−5.44 (m, 1 H), 4.56 (d, J = 6.7 Hz, 2 H), 1.80 (s, 3 H), 1.76 (s,
3 H); 13C{1H} NMR (100 MHz, CDCl3, ppm): δ 162.1, 161.3, 155.9,
143.5, 139.3, 128.7, 118.6, 113.2, 112.9, 112.4, 101.6, 65.4, 25.8, 18.3;
HRMS (ESI-TOF) m/z: [M + H]+ Calcd for C14H15O3 231.1016;
Found 231.1013.
General Experimental Procedure for the Synthesis of Coumarins
1z.24 A 25 mL three-necked round-bottom flask was charged with 7-
amino-4-methyl-2H-chromen-2-one (700.7 mg, 4 mmol), CH2Cl2 (8
mL), and Et3N (566.7 mg, 5.6 mmol). Then, the reaction solution
was cooled to 0 °C. Pivaloyl chloride (578.8 mg, 4.8 mmol) was
added dropwise. After addition, the solution was stirred at room
temperature for 10 h. Then, the reaction mixture was quenched with
water and extracted with CH2Cl2. The organic layer was dried and
concentrated, and the resulting residue was purified by column
chromatography on silica gel (petroleumether/ethyl acetate = 2/1) to
provide N-(4-methyl-2-oxo-2H-chromen-7-yl)pivalamide 1z (828.8
mg, 80% yield).
7-(But-2-yn-1-yloxy)-2H-chromen-2-one (1m).21 White solid,
83% yield (533.4 mg). Column chromatography on silica gel
(petroleum ether/EtOAc = 3:1). Mp = 127−128 °C. 1H NMR
(400 MHz, CDCl3, ppm): δ 7.64 (d, J = 9.5 Hz, 1 H), 7.38 (d, J = 8.6
Hz, 1 H), 6.93 (d, J = 2.4 Hz, 1 H), 6.89 (dd, J = 8.6 Hz, 2.4 Hz, 1
H), 6.26 (d, J = 9.5 Hz, 1 H), 4.71 (q, J = 2.3 Hz, 2 H), 1.86 (t, J = 2.3
Hz, 3 H); 13C{1H} NMR (100 MHz, CDCl3, ppm): δ 161.2, 160.9,
155.7, 143.4, 128.7, 113.4, 113.2, 112.9, 102.0, 84.9, 72.9, 56.9, 3.7;
GC-MS (EI, m/z): [M]+ 214.1.
7-(Prop-2-yn-1-yloxy)-2H-chromen-2-one (1n). White solid, 55%
yield (330.6 mg). Column chromatography on silica gel (petroleum
ether/EtOAc = 3:1). Mp = 119−120 °C. IR (cm−1) 3273, 3124,
3080, 3053, 2951, 2946, 2851, 2119, 1714, 1614, 1504, 1467, 1401,
1343, 1277, 1231, 1128, 1016, 835, 714; 1H NMR (400 MHz, CDCl3,
ppm): δ 7.64 (d, J = 9.5 Hz, 1 H), 7.40 (d, J = 8.5 Hz, 1 H), 6.93 (d, J
= 2.4 Hz, 1 H), 6.91 (dd, J = 8.5 Hz, 2.4 Hz, 1 H), 6.27 (d, J = 9.5 Hz,
1 H), 4.76 (d, J = 2.4 Hz, 2 H), 2.57 (t, J = 2.4 Hz, 1 H); 13C{1H}
NMR (100 MHz, CDCl3, ppm): δ 161.0, 160.6, 155.7, 143.3, 128.8,
113.7, 113.2, 113.1, 102.2, 77.2, 76.6, 56.2; HRMS (ESI-TOF) m/z:
[M + H]+ Calcd for C12H9O3 201.0546; Found 201.0544.
8-Methyl-2H-chromen-2-one (1d).20 White solid, 53% yield
(424.6 mg). Column chromatography on silica gel (petroleum
ether/EtOAc = 35:1). Mp = 108−109 °C. 1H NMR (400 MHz,
CDCl3, ppm): δ 7.70 (d, J = 9.5 Hz, 1 H), 7.38 (d, J = 7.3 Hz, 1 H),
7.32 (d, J = 7.6 Hz, 1 H), 7.18 (t, J = 7.6 Hz, 1 H), 6.41 (d, J = 9.5 Hz,
1 H), 2.46 (s, 3 H); 13C{1H} NMR (100 MHz, CDCl3, ppm): δ
161.1, 152.4, 143.8, 133.2, 126.4, 125.6, 124.0, 118.6, 116.3, 15.4;
GC-MS (EI, m/z): [M]+ 160.1.
5,7-Dimethyl-2H-chromen-2-one (1e).20 White solid, 65% yield
(565.5 mg). Column chromatography on silica gel (petroleum ether/
1
EtOAc = 25:1). Mp = 135−136 °C. H NMR (400 MHz, CDCl3,
ppm): δ 7.87 (d, J = 9.8 Hz, 1 H), 6.98 (s, 1 H), 6.92 (s, 1 H), 6.35
(d, J = 9.7 Hz, 1 H), 2.48 (s, 3 H), 2.39 (s, 3 H); 13C{1H} NMR (100
MHz, CDCl3, ppm): δ 161.1, 154.8, 142.8, 140.4, 135.7, 127.0, 115.3,
115.1, 114.7, 21.7, 18.2; GC-MS (EI, m/z): [M]+ 174.2.
7-(Cyclopropylmethoxy)-2H-chromen-2-one (1o). White solid,
90% yield (583.8 mg). Column chromatography on silica gel
(petroleum ether/EtOAc = 3:1). Mp = 66−68 °C. IR (cm−1) 3084,
3016, 2930, 2874, 1725, 1614, 1505, 1466, 1399, 1348, 1280, 1231,
1195, 1122, 988, 897, 831, 753; 1H NMR (400 MHz, CDCl3, ppm): δ
7.63 (d, J = 9.5 Hz, 1 H), 7.36 (d, J = 8.6 Hz, 1 H), 6.85 (dd, J = 8.6
Hz, 2.4 Hz, 1 H), 6.80 (d, J = 2.4 Hz, 1 H), 6.24 (d, J = 9.5 Hz, 1 H),
3.86 (d, J = 7.0 Hz, 2 H), 1.35−1.25 (m, 1 H), 0.71−0.66 (m, 2 H),
0.41−0.37 (m, 2 H); 13C{1H} NMR (100 MHz, CDCl3, ppm): δ
162.3, 161.3, 155.9, 143.4, 128.7, 113.0, 112.9, 112.4, 101.4, 73.3,
10.0, 3.3; HRMS (ESI-TOF) m/z: [M + H]+ Calcd for C13H13O3
217.0859; Found 217.0856.
7-(tert-Butyl)-2H-chromen-2-one (1f). White solid, 32% yield
(323.6 mg). Column chromatography on silica gel (petroleum ether/
EtOAc = 30:1). Mp = 97−98 °C. IR (cm−1) 3066, 2960, 2870, 1726,
1
1615, 1545, 1467, 1402, 1367, 1230, 1149, 1107, 966, 856, 758; H
NMR (400 MHz, CDCl3, ppm): δ 7.69 (d, J = 9.5 Hz, 1 H), 7.42 (d, J
= 8.0 Hz, 1 H), 7.34−7.31 (m, 2 H), 6.37 (d, J = 9.5 Hz, 1 H), 1.35
(s, 9 H); 13C{1H} NMR (100 MHz, CDCl3, ppm): δ 161.2, 156.4,
154.1, 143.2, 127.3, 122.0, 116.4, 115.7, 113.7, 35.3, 31.1; HRMS
(ESI-TOF) m/z: [M + H]+ Calcd for C13H15O2 203.1067; Found
203.1064.
7-Isopropyl-2H-chromen-2-one (1g). White solid, 31% yield
(291.8 mg). Column chromatography on silica gel (petroleum
ether/EtOAc = 30:1). Mp = 61−63 °C. IR (cm−1) 3044, 2961,
2924, 2873, 1727, 1615, 1552, 1460, 1415, 1322, 1228, 1147, 1109,
970, 883, 838, 752; 1H NMR (400 MHz, CDCl3, ppm): δ 7.67 (d, J =
9.5 Hz, 1 H), 7.39 (d, J = 8.0 Hz, 1 H), 7.18 (s, 1 H), 7.15 (dd, J = 8.0
Hz, 1.4 Hz, 1 H), 6.35 (d, J = 9.5 Hz, 1 H), 3.04−2.94 (m, 1 H), 1.29
(s, 3 H), 1.27 (s, 3 H); 13C{1H} NMR (100 MHz, CDCl3, ppm): δ
161.2, 154.3, 154.1, 143.4, 127.7, 123.1, 116.8, 115.6, 114.5, 34.3,
23.7; HRMS (ESI-TOF) m/z: [M + H]+ Calcd for C12H13O2
189.0910; Found 189.0907.
7-(Cyclopentyloxy)-2H-chromen-2-one (1p). White solid, 81%
yield (559.5 mg). Column chromatography on silica gel (petroleum
ether/EtOAc = 3:1). Mp = 61−63 °C. IR (cm−1) 3059, 2952, 2869,
1723, 1612, 1503, 1436, 1400, 1353, 1276, 1231, 1195, 1157, 1122,
970, 882, 832, 752; 1H NMR (400 MHz, CDCl3, ppm): δ 7.63 (d, J =
9.5 Hz, 1 H), 7.34 (d, J = 9.3 Hz, 1 H), 6.80 (dd, J = 7.6 Hz, 2.4 Hz, 1
H), 6.79 (s, 1 H), 6.23 (d, J = 9.4 Hz, 1 H), 4.82−4.78 (m, 1 H),
2.00−1.76 (m, 6 H), 1.70−1.62 (m, 2 H); 13C{1H} NMR (100 MHz,
CDCl3, ppm): δ 161.5, 161.4, 155.9, 143.5, 128.7, 113.8, 112.7, 112.1,
102.3, 80.2, 32.8, 24.1; HRMS (ESI-TOF) m/z: [M + H]+ Calcd for
C14H15O3 231.1016; Found 231.1013.
7-(Benzyloxy)-2H-chromen-2-one (1j).21 White solid, 75% yield
(567.6 mg). Column chromatography on silica gel (petroleum ether/
7-(Cyclohexyloxy)-2H-chromen-2-one (1q).21 White solid, 45%
yield (329.4 mg). Column chromatography on silica gel (petroleum
1
EtOAc = 3:1). Mp = 153−156 °C. H NMR (400 MHz, CDCl3,
ppm): δ 7.63 (d, J = 9.5 Hz, 1 H), 7.44−7.35 (m, 6 H), 6.91 (dd, J =
8.6 Hz, 2.4 Hz, 1 H), 6.88 (d, J = 2.4 Hz, 1 H), 6.24 (d, J = 9.5 Hz, 1
H), 5.12 (s, 2 H); 13C{1H} NMR (100 MHz, CDCl3, ppm): δ 161.9,
161.2, 155.8, 143.4, 135.8, 128.8, 128.7, 128.4, 127.5, 113.3, 113.2,
112.7, 101.9, 70.5; GC-MS (EI, m/z): [M]+ 252.2.
1
ether/EtOAc = 3:1). Mp = 97−98 °C. H NMR (400 MHz, CDCl3,
ppm): δ 7.62 (d, J = 9.5 Hz, 1 H), 7.35 (d, J = 9.2 Hz, 1 H), 6.81 (dd,
J = 7.6 Hz, 2.4 Hz, 1 H), 6.81 (s, 1 H), 6.23 (d, J = 9.4 Hz, 1 H),
4.35−4.29 (m, 1 H), 2.01−1.99 (m, 2 H), 1.83−1.80 (m, 2 H), 1.61−
1.25 (m, 6 H); 13C{1H} NMR (100 MHz, CDCl3, ppm): δ 161.3,
161.2, 156.0, 143.4, 128.7, 113.9, 112.8, 112.2, 102.4, 76.1, 31.5, 25.4,
23.6; GC-MS (EI, m/z): [M]+ 244.1.
2-Oxo-2H-chromen-7-yl acetate (1k).22 White solid, 80% yield
(1.01 g). Column chromatography on silica gel (petroleum ether/
1
EtOAc = 3:1). Mp = 142−143 °C. H NMR (400 MHz, CDCl3,
3H-Benzo[f]chromen-3-one (1r).20 White solid, 42% yield (824.1
mg). Column chromatography on silica gel (petroleum ether/EtOAc
= 25:1). Mp = 97−99 °C. 1H NMR (400 MHz, CDCl3, ppm): δ 8.50
(d, J = 9.5 Hz, 1 H), 8.23 (d, J = 7.6 Hz, 1 H), 8.00 (d, J = 9.0 Hz, 1
H), 7.92 (d, J = 8.0 Hz, 1 H), 7.70 (dt, J = 7.0 Hz, 1.2 Hz, 1 H), 7.57
(dt, J = 8.1 Hz, 1.0 Hz, 1 H), 7.47 (d, J = 9.0 Hz, 1 H), 6.59 (d, J = 9.8
Hz, 1 H); 13C{1H} NMR (100 MHz, CDCl3, ppm): δ 160.9, 153.9,
ppm): δ 7.69 (d, J = 9.5 Hz, 1 H), 7.48 (d, J = 8.4 Hz, 1 H), 7.11 (d, J
= 2.1 Hz, 1 H), 7.05 (dd, J = 8.4 Hz, 2.2 Hz, 1 H), 6.39 (d, J = 9.5 Hz,
1 H), 2.34 (s, 3 H); 13C{1H} NMR (100 MHz, CDCl3, ppm): δ
168.7, 160.3, 154.7, 153.2, 142.9, 128.6, 118.4, 116.7, 116.1, 110.5,
21.1; GC-MS (EI, m/z): [M]+ 204.2.
7-((3-Methylbut-2-en-1-yl)oxy)-2H-chromen-2-one (1l). White
solid, 72% yield (498.1 mg). Column chromatography on silica gel
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139.1, 133.1, 130.3, 129.0, 128.3, 126.1, 121.4, 117.1, 115.7, 113.0;
GC-MS (EI, m/z): [M]+ 196.1.
extracted with ethyl acetate three times. The combined organic layer
was washed with saturated NaCl solution, dried with anhydrous
Na2SO4, and filtered. The filtrate was concentrated in vacuo. The
crude product was purified by flash column chromatography on silica
gel (petroleum ether/EtOAc) to afford desired products.
7,8,9,10-Tetrahydro-2H-benzo[h]chromen-2-one (1s).20 White
solid, 37% yield (370.3 mg). Column chromatography on silica gel
(petroleum ether/EtOAc = 25:1). Mp = 137−138 °C. 1H NMR (400
MHz, CDCl3, ppm): δ 7.66 (d, J = 9.4 Hz, 1 H), 7.21 (d, J = 7.9 Hz, 1
H), 7.01 (d, J = 7.9 Hz, 1 H), 6.34 (d, J = 9.5 Hz, 1 H), 2.91 (t, J = 5.7
Hz, 2 H), 2.85 (t, J = 5.9 Hz, 2 H), 1.86−1.81 (m, 4 H); 13C{1H}
NMR (100 MHz, CDCl3, ppm): δ 161.4, 152.2, 143.9, 142.5, 125.6,
125.3, 124.4, 116.1, 115.0, 30.0, 22.5, 22.4 22.1; GC-MS (EI, m/z):
[M]+ 200.2.
Gram-Scale Reaction for the Synthesis of 3a. A dried 100 mL
round-bottomed flask equipped with a magnetic stir bar was charged
with coumarin 1a (730.7 mg, 5.0 mmol, 1.0 equiv), Ir(ppy)3 (65.5
mg, 0.1 mmol, 2 mol %), K2CO3 (1.382 g, 10.0 mmol, 2.0 equiv),
1,1,1-trifluoro-2-iodoethane (CF3CH2I) (4.199 g, 20.0 mmol, 4.0
equiv) and DMSO (45.0 mL). The reaction mixture was then stirred
and put under irradiation with a 3 W blue LED at room temperature
for 12 h under Ar atmosphere. The reaction mixture was washed with
water and extracted with ethyl acetate three times. The combined
organic layer was washed with saturated NaCl solution, dried with
anhydrous Na2SO4, and filtered. The filtrate was concentrated in
vacuo. The crude product was purified by flash column chromatog-
raphy on silica gel (petroleum ether/EtOAc = 8:1) to afford the pure
product 3a (844.2 mg) in 74% yield.
7-Chloro-2H-chromen-2-one (1t).20 White solid, 36% yield (325.1
mg). Column chromatography on silica gel (petroleum ether/EtOAc
1
= 10:1). Mp = 133−134 °C. H NMR (400 MHz, CDCl3, ppm): δ
7.68 (d, J = 9.6 Hz, 1 H), 7.42 (d, J = 8.3 Hz, 1 H), 7.34 (d, J = 1.8
Hz, 1 H), 7.26 (dd, J = 8.3, 1.8 Hz, 1 H), 6.42 (d, J = 9.6 Hz, 1 H);
13C{1H} NMR (100 MHz, CDCl3, ppm): δ 160.0, 154.4, 142.7,
137.8, 128.7, 125.0, 117.4, 117.2, 116.6; GC-MS (EI, m/z): [M]+
180.1.
7-Bromo-2H-chromen-2-one (1u).25 White solid, 41% yield
(461.3 mg). Column chromatography on silica gel (petroleum
ether/EtOAc = 10:1). Mp = 122−123 °C. 1H NMR (400 MHz,
CDCl3, ppm): δ 7.66 (d, J = 9.6 Hz, 1 H), 7.51 (d, J = 1.6 Hz, 1 H),
7.41 (dd, J = 8.2 Hz, 1.8 Hz, 1 H), 7.34 (d, J = 8.3 Hz, 1 H), 6.43 (d, J
= 9.6 Hz, 1 H); 13C{1H} NMR (100 MHz, CDCl3, ppm): δ 159.9,
154.3, 142.7, 128.8, 127.9, 125.8, 120.2, 117.8, 116.9; GC-MS (EI, m/
z): [M]+ 224.0.
3-(2,2,2-Trifluoroethyl)-2H-chromen-2-one (3a). White solid, 89%
yield (40.6 mg). Column chromatography on silica gel (petroleum
ether/EtOAc = 5:1). Mp = 94−96 °C. IR (cm−1) 3055, 3010, 2922,
2854, 1719, 1612, 1508, 1451, 1365, 1262, 1140, 1103, 1069, 840,
759; 1H NMR (400 MHz, CDCl3, ppm): δ 7.77 (s, 1 H), 7.56 (dt, J =
7.8 Hz, 1.6 Hz, 1 H), 7.51 (dd, J = 7.8 Hz, 1.4 Hz, 1 H), 7.35 (d, J =
8.3 Hz, 1 H), 7.31 (dt, J = 7.4 Hz, 1.0 Hz, 1 H), 3.46 (dq, J = 10.5 Hz,
0.6 Hz, 2 H); 13C{1H} NMR (100 MHz, CDCl3, ppm): δ 160.94,
4-Phenyl-2H-chromen-2-one (1w).23 White solid, 60% yield
(134.7 mg). Column chromatography on silica gel (petroleum
ether/EtOAc = 10:1). Mp = 94−95 °C. 1H NMR (400 MHz,
CDCl3, ppm): δ 7.58−7.52 (m, 4 H), 7.50 (dd, J = 8.0 Hz, 1.4 Hz, 1
H), 7.47−7.45 (m, 2 H), 7.42 (dd, J = 8.3 Hz, 0.9 Hz, 1 H), 7.23 (dt,
J = 8.2 Hz, 1.1 Hz, 1 H), 6.39 (s, 1 H); 13C{1H} NMR (100 MHz,
CDCl3, ppm): δ 160.8, 155.7, 154.2, 135.2, 131.9, 129.7, 128.9, 128.5,
127.0, 124.2, 119.0, 117.3, 115.2; GC-MS (EI, m/z): [M]+ 222.1.
4-(p-Tolyl)-2H-chromen-2-one (1x).23 White solid, 55% yield
(130.0 mg). Column chromatography on silica gel (petroleum ether/
1
153.63, 143.17, 132.18, 129.50 (C−F, JC−F = 275.6 Hz), 127.98,
126.75 (C−F, 1JC−F = 275.6 Hz), 124.74, 124.00 (C−F, 1JC−F = 275.6
Hz), 121.24 (C−F, 1JC−F = 275.6 Hz), 118.70, 118.63 (C−F, 3JC−F
=
3
3
2.9 Hz), 118.60 (C−F, JC−F = 2.9 Hz), 118.58 (C−F, JC−F = 2.9
Hz), 118.55 (C−F, 3JC−F = 2.9 Hz), 116.74, 34.43 (C−F, 2JC−F = 31.0
2
2
Hz), 34.12 (C−F, JC−F = 31.0 Hz), 33.81 (C−F, JC−F = 31.0 Hz),
33.50 (C−F, 2JC−F = 31.0 Hz); 19F NMR (376 MHz, CDCl3, ppm): δ
−65.16 (s); HRMS (ESI-TOF) m/z: [M + H]+ Calcd for C11H8F3O2
229.0471; Found 229.0469.
6-Methyl-3-(2,2,2-trifluoroethyl)-2H-chromen-2-one (3b). White
solid, 83% yield (40.2 mg). Column chromatography on silica gel
(petroleum ether/EtOAc = 5:1). Mp = 115−117 °C. IR (cm−1) 3054,
3009, 2961, 2925, 2862, 1722, 1629, 1579, 1488, 1433, 1366, 1260,
1184, 1136, 925, 884, 814, 771; 1H NMR (400 MHz, CDCl3, ppm): δ
7.71 (s, 1 H), 7.35 (dd, J = 8.4 Hz, 1.8 Hz, 1 H), 7.29 (s, 1 H), 7.23
(d, J = 8.4 Hz, 1 H), 3.44 (q, J = 10.5 Hz, 2 H), 2.41 (s, 3 H);
13C{1H} NMR (100 MHz, CDCl3, ppm): δ 161.17, 151.76, 143.17,
134.51, 133.19, 129.54 (C−F, 1JC−F = 275.6 Hz), 127.76, 126.79 (C−
F, 1JC−F = 275.6 Hz), 124.03 (C−F, 1JC−F = 275.6 Hz), 121.28 (C−F,
1
EtOAc = 10:1). Mp = 108−110 °C. H NMR (400 MHz, CDCl3,
ppm): δ 7.53 (d, J = 7.4 Hz, 2 H), 7.40 (d, J = 7.9 Hz, 1 H), 7.37−
7.32 (m, 4 H), 7.22 (dt, J = 8.2 Hz, 1.1 Hz, 1 H), 6.37 (s, 1 H), 2.46
(s, 3 H); 13C{1H} NMR (100 MHz, CDCl3, ppm): δ 160.9, 155.8,
154.2, 139.9, 132.3, 131.8, 129.6, 128.4, 127.1, 124.1, 119.1, 117.3,
114.9, 21.4; GC-MS (EI, m/z): [M]+ 236.1.
6-Methoxy-4-phenyl-2H-chromen-2-one (1y).23 White solid, 62%
yield (156.4 mg). Column chromatography on silica gel (petroleum
ether/EtOAc = 10:1). Mp = 151−152 °C. 1H NMR (400 MHz,
CDCl3, ppm): δ 7.54−7.53 (m, 3 H), 7.47−7.45 (m, 2 H), 7.35 (d, J
= 9.0 Hz, 1 H), 7.13 (dd, J = 9.0, 2.9 Hz, 1 H), 6.93 (d, J = 2.9 Hz, 1
H), 6.38 (s, 1 H), 3.74 (s, 3 H); 13C{1H} NMR (100 MHz, CDCl3,
ppm): δ 161.0, 155.9, 155.4, 148.6, 135.3, 129.7, 128.9, 128.3, 119.4,
119.0, 118.2, 115.6, 110.0, 55.8; GC-MS (EI, m/z): [M]+ 252.1.
N-(4-Methyl-2-oxo-2H-chromen-7-yl)pivalamide (1z). White
solid, 80% yield (828.8 mg). Column chromatography on silica gel
(petroleum ether/EtOAc = 2:1). Mp = 206−207 °C. IR (cm−1) 3343,
3192, 3089, 2957, 2875, 1697, 1619, 1576, 1518, 1473, 1399, 1360,
1209, 1168, 1065, 886, 845, 748, 688; 1H NMR (400 MHz,
(CD3)2SO, ppm): δ 9.59 (s, 1 H), 7.84 (d, J = 1.7 Hz, 1 H), 7.70 (d, J
= 8.7 Hz, 1 H), 7.65 (dd, J = 8.7 Hz, 1.7 Hz, 1 H), 6.25 (s, 1 H), 2.40
(s, 3 H), 1.25 (s, 9 H); 13C{1H} NMR (100 MHz, (CD3)2SO, ppm):
δ 177.1, 160.1, 153.5, 153.1, 142.8, 125.5, 115.9, 114.8, 112.2, 106.2,
27.0, 17.9; HRMS (ESI-TOF) m/z: [M + H]+ Calcd for C15H18NO3
260.1281; Found 260.1280.
3
1JC−F = 275.6 Hz), 118.44, 118.42 (C−F, JC−F = 2.8 Hz), 118.39
(C−F, 3JC−F = 2.8 Hz), 118.36 (C−F, 3JC−F = 2.8 Hz), 118.33 (C−F,
3JC−F = 2.8 Hz), 116.42, 34.42 (C−F, 2JC−F = 30.9 Hz), 34.11 (C−F,
2JC−F = 30.9 Hz), 33.80 (C−F, 2JC−F = 30.9 Hz), 33.49 (C−F, 2JC−F
=
30.9 Hz), 20.72; 19F NMR (376 MHz, CDCl3, ppm): δ −65.19 (s);
HRMS (ESI-TOF) m/z: [M + H]+ Calcd for C12H10F3O2 243.0627;
Found 243.0626.
7-Methyl-3-(2,2,2-trifluoroethyl)-2H-chromen-2-one (3c). White
solid, 86% yield (41.7 mg). Column chromatography on silica gel
(petroleum ether/EtOAc = 5:1). Mp = 113−116 °C. IR (cm−1) 3053,
3004, 2952, 2924, 2854, 1717, 1622, 1425, 1371, 1260, 1193, 1145,
1101, 829, 777; 1H NMR (400 MHz, CDCl3, ppm): δ 7.73 (s, 1 H),
7.37 (d, J = 7.8 Hz, 1 H), 7.14 (s, 1 H), 7.12 (d, J = 7.9 Hz, 1 H), 3.43
(q, J = 10.5 Hz, 2 H), 2.46 (s, 3 H); 13C{1H} NMR (100 MHz,
1
CDCl3, ppm): δ 161.22, 153.75, 143.60, 143.19, 129.58 (C−F, JC−F
= 275.6 Hz), 127.64, 126.82 (C−F, 1JC−F = 275.6 Hz), 125.94, 124.07
General Experimental Procedure for the Synthesis of 3. A dried
25 mL Schlenk tube equipped with a magnetic stir bar was charged
with coumarins 1 (0.20 mmol, 1.0 equiv), 1,1,1-trifluoro-2-iodoethane
(CF3CH2I) (2, 0.80 mmol, 4.0 equiv), Ir(ppy)3 (2.62 mg, 0.004
mmol, 2 mol %), K2CO3 (0.40 mmol, 2.0 equiv), and DMSO (2.0
mL). The reaction mixture was then stirred and put under irradiation
with a 3 W blue LED at room temperature for 12 h under Ar
atmosphere. The reaction mixture was washed with water and
1
1
(C−F, JC−F = 275.6 Hz), 121.31 (C−F, JC−F = 275.6 Hz), 117.24
(C−F, 3JC−F = 2.9 Hz), 117.21 (C−F, 3JC−F = 2.9 Hz), 117.18 (C−F,
3JC−F = 2.9 Hz), 117.15 (C−F, 3JC−F = 2.9 Hz), 116.86, 116.33, 34.38
(C−F, 2JC−F = 30.9 Hz), 34.07 (C−F, 2JC−F = 30.9 Hz), 33.76 (C−F,
2
2JC−F = 30.9 Hz), 33.45 (C−F, JC−F = 30.9 Hz), 21.81; 19F NMR
(376 MHz, CDCl3, ppm): δ −65.26 (s); HRMS (ESI-TOF) m/z: [M
+ H]+ Calcd for C12H10F3O2 243.0627; Found 243.0627.
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1
8-Methyl-3-(2,2,2-trifluoroethyl)-2H-chromen-2-one (3d). White
solid, 84% yield (40.7 mg). Column chromatography on silica gel
(petroleum ether/EtOAc = 5:1). Mp = 130−132 °C. IR (cm−1) 3055,
3007, 2952, 2924, 2854, 1709, 1605, 1462, 1363, 1285, 1251, 1188,
1139, 1072, 836, 771; 1H NMR (400 MHz, CDCl3, ppm): δ 7.75 (s, 1
H), 7.40 (dd, J = 7.5 Hz, 0.4 Hz, 1 H), 7.33 (d, J = 7.6 Hz, 1 H), 7.20
(t, J = 7.6 Hz, 1 H), 3.46 (q, J = 10.5 Hz, 2 H), 2.46 (s, 3 H); 13C{1H}
NMR (100 MHz, CDCl3, ppm): δ 161.14, 151.99, 143.57, 133.48,
1251, 1140, 1094, 836, 779; H NMR (400 MHz, CDCl3, ppm): δ
7.69 (s, 1 H), 7.38 (d, J = 8.6 Hz, 1 H), 6.86 (dd, J = 8.6 Hz, 2.4 Hz, 1
H), 6.81 (d, J = 2.4 Hz, 1 H), 3.87 (s, 3.0 Hz, 1 H), 3.40 (q, J = 10.5
Hz, 2 H); 13C{1H} NMR (100 MHz, CDCl3, ppm): δ 163.14, 161.34,
155.50, 143.32, 129.64 (C−F, 1JC−F = 275.6 Hz), 128.93, 126.89 (C−
F, 1JC−F = 275.6 Hz), 124.13 (C−F, 1JC−F = 275.6 Hz), 121.38 (C−F,
1JC−F = 275.6 Hz), 114.72 (C−F, 3JC−F = 2.9 Hz), 114.69 (C−F, 3JC−F
3
3
= 2.9 Hz), 114.66 (C−F, JC−F = 2.9 Hz), 114.63 (C−F, JC−F = 2.9
1
1
2
129.56 (C−F, JC−F = 275.6 Hz), 126.81 (C−F, JC−F = 275.6 Hz),
Hz), 112.97, 112.37, 100.64, 55.83, 34.30 (C−F, JC−F = 31.0 Hz),
126.26, 125.68, 124.31, 124.05 (C−F, 1JC−F = 275.6 Hz), 121.29 (C−
2
2
33.99 (C−F, JC−F = 31.0 Hz), 33.68 (C−F, JC−F = 31.0 Hz), 33.37
1
3
(C−F, JC−F = 31.0 Hz); 19F NMR (376 MHz, CDCl3, ppm): δ
2
F, JC−F = 275.6 Hz), 118.44, 118.15 (C−F, JC−F = 2.9 Hz), 118.13
(C−F, 3JC−F = 2.9 Hz), 118.11 (C−F, 3JC−F = 2.9 Hz), 118.09 (C−F,
−65.41 (s); HRMS (ESI-TOF) m/z: [M + H]+ Calcd for C12H10F3O3
259.0577; Found 259.0575.
3JC−F = 2.9 Hz), 34.37 (C−F, 2JC−F = 30.9 Hz), 34.07 (C−F, 2JC−F
=
2
2
7-Ethoxy-3-(2,2,2-trifluoroethyl)-2H-chromen-2-one (3i). White
solid, 94% yield (51.2 mg). Column chromatography on silica gel
(petroleum ether/EtOAc = 5:1). Mp = 133−135 °C. IR (cm−1) 3100,
3051, 2991, 2925, 2851, 1718, 1616, 1511, 1475, 1357, 1250, 1141,
1094, 834, 779; 1H NMR (400 MHz, CDCl3, ppm): δ 7.68 (s, 1 H),
7.37 (d, J = 8.6 Hz, 1 H), 6.85 (dd, J = 8.6 Hz, 2.4 Hz, 1 H), 6.79 (d, J
= 2.3 Hz, 1 H), 4.09 (q, J = 7.0 Hz, 2 H), 3.40 (q, J = 10.5 Hz, 2 H),
1.45 (t, 7.0 Hz, 3 H); 13C{1H} NMR (100 MHz, CDCl3, ppm): δ
30.9 Hz), 33.75 (C−F, JC−F = 30.9 Hz), 33.45 (C−F, JC−F = 30.9
Hz), 15.34; 19F NMR (376 MHz, CDCl3, ppm): δ −65.20 (s);
HRMS (ESI-TOF) m/z: [M + H]+ calcd for C12H10F3O2, 243.0627;
Found 243.0627.
5,7-Dimethyl-3-(2,2,2-trifluoroethyl)-2H-chromen-2-one (3e).
White solid, 81% yield (41.5 mg). Column chromatography on silica
gel (petroleum ether/EtOAc = 5:1). Mp = 149−152 °C. IR (cm−1)
3110, 3055, 3005, 2951, 2924, 2852, 1718, 1618, 1455, 1365, 1276,
1252, 1194, 1145, 1101, 842, 775; 1H NMR (400 MHz, CDCl3,
ppm): δ 7.90 (s, 1 H), 6.98 (s, 1 H), 6.94 (s, 1 H), 3.44 (q, J = 10.5
Hz, 2 H); 13C{1H} NMR (100 MHz, CDCl3, ppm): δ 161.21, 154.36,
1
162.53, 161.41, 155.51, 143.34, 129.65 (C−F, JC−F = 275.6 Hz),
128.88, 126.90 (C−F, 1JC−F = 275.6 Hz), 124.14 (C−F, 1JC−F = 275.6
Hz), 121.39 (C−F, 1JC−F = 275.6 Hz), 114.55 (C−F, 3JC−F = 2.9 Hz),
114.52 (C−F, 3JC−F = 2.9 Hz), 114.49 (C−F, 3JC−F = 2.9 Hz), 114.46
1
143.26, 140.33, 135.77, 129.60 (C−F, JC−F = 275.6 Hz), 127.29,
3
1
1
(C−F, JC−F = 2.9 Hz), 113.35, 112.23, 101.08, 64.28, 34.30 (C−F,
126.85 (C−F, JC−F = 275.6 Hz), 124.09 (C−F, JC−F = 275.6 Hz),
2JC−F = 31.0 Hz), 33.99 (C−F, 2JC−F = 31.0 Hz), 33.68 (C−F, 2JC−F
=
1
3
121.33 (C−F, JC−F = 275.6 Hz), 116.40 (C−F, JC−F = 2.9 Hz),
116.37 (C−F, 3JC−F = 2.9 Hz), 116.35 (C−F, 3JC−F = 2.9 Hz), 116.32
31.0 Hz), 33.37 (C−F, 2JC−F = 31.0 Hz), 14.51; 19F NMR (376 MHz,
CDCl3, ppm): δ −65.41 (s); HRMS (ESI-TOF) m/z: [M + H]+
Calcd for C13H12F3O3 273.0733; Found 273.0732.
3
2
(C−F, JC−F = 2.9 Hz), 115.23, 114.85, 34.57 (C−F, JC−F = 30.8
2
2
Hz), 34.26 (C−F, JC−F = 30.8 Hz), 33.96 (C−F, JC−F = 30.8 Hz),
33.65 (C−F, JC−F = 30.8 Hz), 21.72, 18.17; 19F NMR (376 MHz,
2
7-(Benzyloxy)-3-(2,2,2-trifluoroethyl)-2H-chromen-2-one (3j).
White solid, 87% yield (58.2 mg). Column chromatography on silica
gel (petroleum ether/EtOAc = 5:1). Mp = 152−153 °C. IR (cm−1)
3110, 3049, 3016, 2955, 2922, 2860, 1700, 1614, 1508, 1463, 1357,
CDCl3, ppm): δ −65.35 (s); HRMS (ESI-TOF) m/z: [M + H]+
Calcd for C13H12F3O2 257.0784; Found 257.0781.
7-(tert-Butyl)-3-(2,2,2-trifluoroethyl)-2H-chromen-2 one (3f).
White solid, 76% yield (43.2 mg). Column chromatography on silica
gel (petroleum ether/EtOAc = 5:1). Mp = 88−89 °C. IR (cm−1)
3061, 2962, 2921, 2872, 1721, 1621, 1556, 1467, 1366, 1260, 1187,
1143, 877, 834, 781; 1H NMR (400 MHz, CDCl3, ppm): δ 7.74 (s, 1
H), 7.43 (d, J = 8.6 Hz, 1 H), 7.36−7.33 (m, 2 H), 3.44 (q, J = 10.5
Hz, 2 H), 1.35 (s, 9 H); 13C{1H} NMR (100 MHz, CDCl3, ppm): δ
1
1269, 1130, 1101, 918, 828, 777, 742; H NMR (400 MHz, CDCl3,
ppm): δ 7.69 (s, 1 H), 7.44−7.35 (m, 6 H), 6.94 (dd, J = 8.6 Hz, 2.4
Hz, 1 H), 6.89 (d, J = 2.3 Hz, 1 H), 5.14 (s, 2 H), 3.40 (q, J = 10.5
Hz, 2 H); 13C{1H} NMR (100 MHz, CDCl3, ppm): δ 162.16, 161.32,
1
155.41, 143.25, 135.66, 129.64 (C−F, JC−F = 275.6 Hz), 128.96,
128.80, 128.45, 127.51, 126.88 (C−F, 1JC−F = 275.6 Hz), 124.12 (C−
F, 1JC−F = 275.6 Hz), 121.36 (C−F, 1JC−F = 275.6 Hz), 114.89 (C−F,
1
161.31, 156.88, 153.71, 143.02, 129.58 (C−F, JC−F = 275.6 Hz),
127.44, 126.82 (C−F, 1JC−F = 275.6 Hz), 124.06 (C−F, 1JC−F = 275.6
3JC−F = 2.9 Hz), 114.86 (C−F, 3JC−F = 2.9 Hz), 114.83 (C−F, 3JC−F
=
Hz), 122.31, 121.31 (C−F, 1JC−F = 275.6 Hz), 117.50 (C−F, 3JC−F
=
2.9 Hz), 114.80 (C−F, 3JC−F = 2.9 Hz), 113.65, 112.57, 101.73, 70.60,
3
3
2
2
2.9 Hz), 117.47 (C−F, JC−F = 2.9 Hz), 117.44 (C−F, JC−F = 2.9
Hz), 116.41 (C−F, 3JC−F = 2.9 Hz), 116.25, 113.52, 35.36, 34.39 (C−
F, 2JC−F = 30.9 Hz), 34.08 (C−F, 2JC−F = 30.9 Hz), 33.77 (C−F, 2JC−F
34.31 (C−F, JC−F = 31.0 Hz), 34.00 (C−F, JC−F = 31.0 Hz), 33.70
(C−F, JC−F = 31.0 Hz), 33.39 (C−F, JC−F = 31.0 Hz); 19F NMR
(376 MHz, CDCl3, ppm): δ −65.37 (s); HRMS (ESI-TOF) m/z: [M
+ H]+ Calcd for C18H14F3O3 335.0890; Found 273.0887.
2
2
2
= 30.9 Hz), 33.46 (C−F, JC−F = 30.9 Hz), 31.02; 19F NMR (376
MHz, CDCl3, ppm): δ −65.28 (s); HRMS (ESI-TOF) m/z: [M +
2-Oxo-3-(2,2,2-trifluoroethyl)-2H-chromen-7-yl acetate (3k).
White solid, 42% yield (24.0 mg). Column chromatography on silica
gel (petroleum ether/EtOAc = 5:1). Mp = 145−147 °C. IR (cm−1)
2955, 2922, 2857, 1722, 1623, 1506, 1461, 1371, 1206, 1141, 1107,
H]+ Calcd for C15H16F3O2 285.1097; Found 285.1099.
7-Isopropyl-3-(2,2,2-trifluoroethyl)-2H-chromen-2-one (3g).
White solid, 56% yield (30.3 mg). Column chromatography on silica
gel (petroleum ether/EtOAc = 5:1). Mp = 118−120 °C. IR (cm−1)
3050, 2963, 2925, 2858, 1711, 1620, 1558, 1463, 1364, 1259, 1184,
1143, 1101, 875, 833, 781; 1H NMR (400 MHz, CDCl3, ppm): δ 7.74
(s, 1 H), 7.42 (d, J = 7.8 Hz, 1 H), 7.20 (d, J = 1.8 Hz, 1 H), 7.17 (d, J
= 1.4 Hz, 1 H), 3.44 (q, J = 10.5 Hz, 2 H), 3.06−2.95 (m, 1 H), 1.30
(s, 3 H), 1.28 (s, 3 H); 13C{1H} NMR (100 MHz, CDCl3, ppm): δ
1
831, 788; H NMR (400 MHz, CDCl3, ppm): δ 7.75 (s, 1 H), 7.51
(d, J = 8.4 Hz, 1 H), 7.14 (d, J = 2.1 Hz, 1 H), 7.09 (dd, J = 8.4 Hz,
2.3 Hz, 1 H), 3.45 (q, J = 10.5 Hz, 2 H), 2.35 (s, 3 H); 13C{1H} NMR
(100 MHz, CDCl3, ppm): δ 168.62, 160.57, 154.20, 153.41, 142.55,
129.44 (C−F, 1JC−F = 275.6 Hz), 128.70, 126.68 (C−F, 1JC−F = 275.6
1
1
Hz), 123.93 (C−F, JC−F = 275.6 Hz), 121.17 (C−F, JC−F = 275.6
1
Hz), 118.76, 118.04 (C−F, 3JC−F = 2.8 Hz), 118.02 (C−F, 3JC−F = 2.8
161.26, 154.53, 153.92, 143.13, 129.58 (C−F, JC−F = 275.6 Hz),
127.78, 126.82 (C−F, 1JC−F = 275.6 Hz), 124.06 (C−F, 1JC−F = 275.6
3
3
Hz), 118.00 (C−F, JC−F = 2.8 Hz), 117.98 (C−F, JC−F = 2.8 Hz),
Hz), 123.45, 121.30 (C−F, 1JC−F = 275.6 Hz), 117.33 (C−F, 3JC−F
=
2
2
116.49, 110.31, 34.42 (C−F, JC−F = 31.0 Hz), 34.11 (C−F, JC−F
=
3
3
2
2
2.8 Hz), 117.31 (C−F, JC−F = 2.8 Hz), 117.29 (C−F, JC−F = 2.8
Hz), 117.27 (C−F, 3JC−F = 2.8 Hz), 116.64, 114.34, 34.37, 34.36 (C−
F, 2JC−F = 31.0 Hz), 34.08 (C−F, 2JC−F = 31.0 Hz), 33.77 (C−F, 2JC−F
31.0 Hz), 33.80 (C−F, JC−F = 31.0 Hz), 33.49 (C−F, JC−F = 31.0
Hz), 21.11; 19F NMR (376 MHz, CDCl3, ppm): δ −65.19 (s);
HRMS (ESI-TOF) m/z: [M + H]+ Calcd for C13H10F3O4 287.0526;
Found 287.0525.
2
= 31.0 Hz), 33.46 (C−F, JC−F = 31.0 Hz), 23.62; 19F NMR (376
MHz, CDCl3, ppm): δ −65.27 (s); HRMS (ESI-TOF) m/z: [M +
7-((3-Methylbut-2-en-1-yl)oxy)-3-(2,2,2-trifluoroethyl)-2H-chro-
men-2-one (3l). White solid, 43% yield (26.9 mg). Column
chromatography on silica gel (petroleum ether/EtOAc = 5:1). Mp
= 113−115 °C. IR (cm−1) 3068, 2955, 2922, 2857, 1700, 1615, 1510,
1462, 1361, 1269, 1246, 1134, 1102, 831, 781; H NMR (400 MHz,
CDCl3, ppm): δ 7.69 (s, 1 H), 7.38 (d, J = 8.6 Hz, 1 H), 6.87 (dd, J =
H]+ Calcd for C14H14F3O2 271.0940; Found 271.0939.
7-Methoxy-3-(2,2,2-trifluoroethyl)-2H-chromen-2-one (3h).
White solid, 91% yield (47.0 mg). Column chromatography on silica
gel (petroleum ether/EtOAc = 5:1). Mp = 126−128 °C. IR (cm−1)
3101, 3057, 3008, 2952, 2922, 2852, 1716, 1617, 1510, 1458, 1359,
1
2778
https://dx.doi.org/10.1021/acs.joc.0c02739
J. Org. Chem. 2021, 86, 2772−2783

The Journal of Organic Chemistry
pubs.acs.org/joc
Article
8.6 Hz, 2.4 Hz, 1 H), 6.83 (d, J = 2.3 Hz, 1 H), 5.49−5.45 (m, 1 H),
4.59 (d, J = 6.7 Hz, 2 H), 3.41 (q, J = 10.5 Hz, 2 H), 1.81 (s, 3 H),
1.77 (s, 3 H); 13C{1H} NMR (100 MHz, CDCl3, ppm): δ 162.42,
(cm−1) 3057, 3010, 2960, 2869, 1702, 1614, 1508, 1435, 1359, 1269,
1247, 1150, 1136, 831, 776, 731; 1H NMR (400 MHz, CDCl3, ppm):
δ 7.68 (s, 1 H), 7.36 (d, J = 8.5 Hz, 1 H), 6.81 (dd, J = 8.6 Hz, 2.4 Hz,
1 H), 6.79 (d, J = 2.2 Hz, 1 H), 4.82−4.78 (m, 1 H), 3.40 (q, J = 10.5
Hz, 2 H), 2.00−1.64 (m, 8 H); 13C{1H} NMR (100 MHz, CDCl3,
ppm): δ 161.83, 161.48, 155.46, 143.39, 129.67 (C−F, 1JC−F = 275.6
1
161.43, 155.47, 143.30, 139.42, 129.65 (C−F, JC−F = 275.4 Hz),
128.84, 126.89 (C−F, 1JC−F = 275.4 Hz), 124.13 (C−F, 1JC−F = 275.4
Hz), 121.39 (C−F, 1JC−F = 275.4 Hz), 118.53, 114.55 (C−F, 3JC−F
=
3
3
Hz), 128.82, 126.91 (C−F, 1JC−F = 275.6 Hz), 124.15 (C−F, 1JC−F
=
=
2.9 Hz), 114.53 (C−F, JC−F = 2.9 Hz), 114.49 (C−F, JC−F = 2.9
3
1
3
Hz), 114.46 (C−F, JC−F = 2.9 Hz), 113.64, 112.27, 101.35, 65.52,
275.6 Hz), 121.40 (C−F, JC−F = 275.6 Hz), 114.29 (C−F, JC−F
2
2
3
3
34.31 (C−F, JC−F = 30.9 Hz), 34.00 (C−F, JC−F = 30.9 Hz), 33.69
(C−F, 2JC−F = 30.9 Hz), 33.39 (C−F, 2JC−F = 30.9 Hz), 25.82, 18.30;
19F NMR (376 MHz, CDCl3, ppm): δ −65.40 (s); HRMS (ESI-
3.0 Hz), 114.26 (C−F, JC−F = 3.0 Hz), 114.23 (C−F, JC−F = 3.0
3
Hz), 114.20 (C−F, JC−F = 3.0 Hz), 114.19, 111.96, 102.01, 80.34,
2
2
34.29 (C−F, JC−F = 30.8 Hz), 33.99 (C−F, JC−F = 30.8 Hz), 33.68
(C−F, 2JC−F = 30.8 Hz), 33.37 (C−F, 2JC−F = 30.8 Hz), 32.78, 24.06;
19F NMR (376 MHz, CDCl3, ppm): δ −65.44 (s); HRMS (ESI-
TOF) m/z: [M + H]+ Calcd for C16H16F3O3 313.1046; Found
313.1047.
TOF) m/z: [M + H]+ Calcd for C16H16F3O3 313.1046; Found
313.1045.
7-(But-2-yn-1-yloxy)-3-(2,2,2-trifluoroethyl)-2H-chromen-2-one
(3m). White solid, 54% yield (32.0 mg). Column chromatography on
silica gel (petroleum ether/EtOAc = 5:1). Mp = 145−146 °C. IR
(cm−1) 3100, 3055, 3007, 2925, 2856, 2227, 1713, 1617, 1508, 1352,
1264, 1142, 837, 781; 1H NMR (400 MHz, CDCl3, ppm): δ 7.70 (s, 1
H), 7.40 (d, J = 8.6 Hz, 1 H), 6.95 (d, J = 2.3 Hz, 1 H), 6.92 (dd, J =
8.6 Hz, 2.4 Hz, 1 H), 4.72 (q, J = 2.4 Hz, 2 H), 3.41 (q, J = 10.5 Hz, 2
H), 1.86 (t, J = 2.3 Hz, 1 H); 13C{1H} NMR (100 MHz, CDCl3,
7-(Cyclohexyloxy)-3-(2,2,2-trifluoroethyl)-2H-chromen-2-one
(3q). White solid, 89% yield (58.1 mg). Column chromatography on
silica gel (petroleum ether/EtOAc = 5:1). Mp = 135−137 °C. IR
(cm−1) 3055, 2944, 2861, 1703, 1612, 1505, 1435, 1356, 1243, 1144,
1
832, 779, 731; H NMR (400 MHz, CDCl3, ppm): δ 7.67 (s, 1 H),
7.36 (d, J = 8.6 Hz, 1 H), 6.84 (dd, J = 8.6 Hz, 2.3 Hz, 1 H), 6.81 (d, J
= 2.1 Hz, 1 H), 4.35−4.29 (m, 1 H), 3.39 (q, J = 10.5 Hz, 2 H),
2.01−1.79 (m, 4 H), 1.61−1.31 (m, 6 H); 13C{1H} NMR (100 MHz,
1
ppm): δ 161.32, 161.22, 155.28, 143.25, 129.61 (C−F, JC−F = 275.6
Hz), 128.87, 126.86 (C−F, 1JC−F = 275.6 Hz), 124.10 (C−F, 1JC−F
=
=
1
3
1
275.6 Hz), 121.35 (C−F, JC−F = 275.6 Hz), 115.04 (C−F, JC−F
CDCl3, ppm): δ 161.53, 161.46, 155.55, 143.36, 129.66 (C−F, JC−F
3
3
= 275.6 Hz), 128.90, 126.91 (C−F, 1JC−F = 275.6 Hz), 124.15 (C−F,
3.0 Hz), 115.02 (C−F, JC−F = 3.0 Hz), 115.00 (C−F, JC−F = 3.0
3
1
1JC−F = 275.6 Hz), 121.40 (C−F, JC−F = 275.6 Hz), 114.32 (C−F,
Hz), 114.98 (C−F, JC−F = 3.0 Hz), 113.65, 112.74, 101.84, 85.08,
72.80, 57.00, 34.32 (C−F, 2JC−F = 30.9 Hz), 34.01 (C−F, 2JC−F = 30.9
3JC−F = 3.0 Hz), 114.29 (C−F, 3JC−F = 3.0 Hz), 114.26 (C−F, 3JC−F
=
2
2
Hz), 33.70 (C−F, JC−F = 30.9 Hz), 33.39 (C−F, JC−F = 30.9 Hz),
3.67; 19F NMR (376 MHz, CDCl3, ppm): δ −65.39 (s); HRMS (ESI-
TOF) m/z: [M + H]+ Calcd for C15H12F3O3 297.0733; Found
297.0730.
3.0 Hz), 114.23 (C−F, 3JC−F = 3.0 Hz), 114.22, 112.05, 102.13, 76.17,
2
2
34.29 (C−F, JC−F = 30.8 Hz), 33.99 (C−F, JC−F = 30.8 Hz), 33.68
(C−F, 2JC−F = 30.8 Hz), 33.37 (C−F, 2JC−F = 30.8 Hz), 31.44, 25.42,
23.57; 19F NMR (376 MHz, CDCl3, ppm): δ −65.44 (s); HRMS
(ESI-TOF) m/z: [M + H]+ Calcd for C17H18F3O3 327.1203; Found
327.1201.
7-(Prop-2-yn-1-yloxy)-3-(2,2,2-trifluoroethyl)-2H-chromen-2-one
(3n). White solid, 41% yield (23.1 mg). Column chromatography on
silica gel (petroleum ether/EtOAc = 5:1). Mp = 93−94 °C. IR
(cm−1) 3243, 2923, 2858, 2128, 1714, 1612, 1504, 1440, 1360, 1271,
1246, 1152, 1105, 1016, 836, 772; 1H NMR (400 MHz, CDCl3,
ppm): δ 7.71 (s, 1 H), 7.42 (d, J = 8.3 Hz, 1 H), 6.95 (s, 1 H), 6.93
(d, J = 2.4 Hz, 1 H), 4.77 (d, J = 2.4 Hz, 2 H), 3.40 (q, J = 10.5 Hz, 2
H), 2.58 (t, J = 2.4 Hz, 1 H); 13C{1H} NMR (100 MHz, CDCl3,
2-(2,2,2-Trifluoroethyl)-3H-benzo[f]chromen-3-one (3r). White
solid, 56% yield (31.2 mg). Column chromatography on silica gel
(petroleum ether/EtOAc = 5:1). Mp = 146−149 °C. IR (cm−1) 3109,
3067, 3020, 2922, 2851, 1708, 1627, 1584, 1517, 1362, 1255, 1207,
1
1137, 1100, 1070, 820, 753; H NMR (400 MHz, CDCl3, ppm): δ
8.55 (s, 1 H), 8.25 (d, J = 8.4 Hz, 1 H), 8.02 (d, J = 9.0 Hz, 1 H), 7.93
(d, J = 8.1 Hz, 1 H), 7.72 (dt, J = 8.1 Hz, 0.9 Hz, 1 H), 7.60 (t, J = 7.9
Hz, 1 H), 7.48 (d, J = 9.0 Hz, 1 H), 3.57 (q, J = 10.4 Hz, 2 H);
13C{1H} NMR (100 MHz, CDCl3, ppm): δ 161.09, 153.53, 139.03,
1
ppm): δ 161.19, 160.83, 155.23, 143.11, 129.60 (C−F, JC−F = 275.5
Hz), 128.99, 126.84 (C−F, 1JC−F = 275.5 Hz), 124.09 (C−F, 1JC−F
=
=
1
3
275.5 Hz), 121.33 (C−F, JC−F = 275.5 Hz), 115.40 (C−F, JC−F
3
3
2.9 Hz), 115.37 (C−F, JC−F = 2.9 Hz), 115.34 (C−F, JC−F = 2.9
1
3
133.60, 130.39, 129.62 (C−F, JC−F = 275.6 Hz), 129.14, 128.86,
Hz), 115.31 (C−F, JC−F = 2.9 Hz), 113.49, 113.03, 101.96, 77.24,
128.52, 128.86 (C−F, 1JC−F = 275.6 Hz), 126.29, 124.10 (C−F, 1JC−F
= 275.6 Hz), 121.34 (C−F, 1JC−F = 275.6 Hz), 121.33, 117.59 (C−F,
76.68, 56.28, 34.34 (C−F, 2JC−F = 31.1 Hz), 34.03 (C−F, 2JC−F = 31.1
2
2
Hz), 33.72 (C−F, JC−F = 31.1 Hz), 33.41 (C−F, JC−F = 31.1 Hz);
19F NMR (376 MHz, CDCl3, ppm): δ −65.36 (s); HRMS (ESI-
3JC−F = 2.9 Hz), 117.56 (C−F, 3JC−F = 2.9 Hz), 117.53 (C−F, 3JC−F
=
2.9 Hz), 117.50 (C−F, 3JC−F = 2.9 Hz), 116.78, 112.89, 34.77 (C−F,
TOF) m/z: [M + H]+ Calcd for C14H10F3O3 283.0577; Found
283.0576.
2JC−F = 30.9 Hz), 34.46 (C−F, 2JC−F = 30.9 Hz), 34.15 (C−F, 2JC−F
=
2
30.9 Hz), 33.84 (C−F, JC−F = 30.9 Hz); 19F NMR (376 MHz,
CDCl3, ppm): δ −65.11 (s); HRMS (ESI-TOF) m/z: [M + H]+
Calcd for C15H10F3O2 279.0627; Found 279.0625.
7-(Cyclopropylmethoxy)-3-(2,2,2-trifluoroethyl)-2H-chromen-2-
one (3o). White solid, 85% yield (50.7 mg). Column chromatography
on silica gel (petroleum ether/EtOAc = 5:1). Mp = 140−142 °C. IR
(cm−1) 3086, 3010, 2924, 2858, 1719, 1616, 1508, 1468, 1357, 1272,
1248, 1135, 1093, 998, 835, 778; 1H NMR (400 MHz, CDCl3, ppm):
δ 7.69 (s, 1 H), 7.38 (d, J = 8.6 Hz, 1 H), 6.88 (dd, J = 8.6 Hz, 2.4 Hz,
1 H), 6.80 (d, J = 2.3 Hz, 1 H), 3.87 (d, J = 7.0 Hz, 2 H), 3.40 (q, J =
10.5 Hz, 2 H), 1.33−1.24 (m, 1 H), 0.71−0.67 (m, 2 H), 0.41−0.37
(m, 2 H); 13C{1H} NMR (100 MHz, CDCl3, ppm): δ 162.55, 161.39,
155.48, 143.31, 129.65 (C−F, 1JC−F = 275.6 Hz), 128.88, 126.89 (C−
F, 1JC−F = 275.6 Hz), 124.14 (C−F, 1JC−F = 275.6 Hz), 121.38 (C−F,
1JC−F = 275.6 Hz), 114.59 (C−F, 3JC−F = 2.9 Hz), 114.56 (C−F, 3JC−F
3-(2,2,2-Trifluoroethyl)-7,8,9,10-tetrahydro-2H-benzo[h]-
chromen-2-one (3s). White solid, 31% yield (17.5 mg). Column
chromatography on silica gel (petroleum ether/EtOAc = 5:1). Mp =
122−124 °C. IR (cm−1) 3110, 3063, 3009, 2936, 2862, 1719, 1622,
1
1433, 1360, 1255, 1190, 1136, 1102, 834, 778; H NMR (400 MHz,
CDCl3, ppm): δ 7.71 (s, 1 H), 7.22 (d, J = 8.0 Hz, 1 H), 7.03 (d, J =
8.0 Hz, 1 H), 3.43 (q, J = 10.4 Hz, 2 H), 2.91 (t, J = 5.7 Hz, 2 H),
2.85 (t, J = 5.8 Hz, 2 H), 1.86−1.81 (m, 4H); 13C{1H} NMR (100
MHz, CDCl3, ppm): δ 161.44, 151.83, 143.69, 142.94, 129.64 (C−F,
1
1JC−F = 275.5 Hz), 126.89 (C−F, JC−F = 275.5 Hz), 125.59, 125.47,
3
3
= 2.9 Hz), 114.53 (C−F, JC−F = 2.9 Hz), 114.50 (C−F, JC−F = 2.9
124.44, 124.13 (C−F, 1JC−F = 275.5 Hz), 121.37 (C−F, 1JC−F = 275.5
2
Hz), 113.39, 112.27, 101.21, 73.43, 34.30 (C−F, JC−F = 31.0 Hz),
3
3
2
2
Hz), 116.67 (C−F, JC−F = 2.9 Hz), 116.65 (C−F, JC−F = 2.9 Hz),
33.99 (C−F, JC−F = 31.0 Hz), 33.68 (C−F, JC−F = 31.0 Hz), 33.38
116.63 (C−F, 3JC−F = 2.9 Hz), 116.61 (C−F, 3JC−F = 2.9 Hz), 116.01,
(C−F, JC−F = 31.0 Hz), 9.56, 3.30; 19F NMR (376 MHz, CDCl3,
2
2
2
ppm): δ −65.41 (s); HRMS (ESI-TOF) m/z: [M + H]+ Calcd for
C15H14F3O3 299.0890; Found 299.0893.
34.33 (C−F, JC−F = 30.9 Hz), 34.02 (C−F, JC−F = 30.9 Hz), 33.71
(C−F, 2JC−F = 30.9 Hz), 33.40 (C−F, 2JC−F = 30.9 Hz), 22.50, 22.42,
22.01; 19F NMR (376 MHz, CDCl3, ppm): δ −65.29 (s); HRMS
(ESI-TOF) m/z: [M + H]+ Calcd for C15H14F3O2 283.0940; Found
283.0942.
7-(Cyclopentyloxy)-3-(2,2,2-trifluoroethyl)-2H-chromen-2-one
(3p). White solid, 80% yield (50.0 mg). Column chromatography on
silica gel (petroleum ether/EtOAc = 5:1). Mp = 129−131 °C. IR
2779
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The Journal of Organic Chemistry
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Article
3,7-Chloro-3-(2,2,2-trifluoroethyl)-2H-chromen-2-one (3t). White
solid, 90% yield (47.3 mg). Column chromatography on silica gel
(petroleum ether/EtOAc = 5:1). Mp = 107−109 °C. IR (cm−1) 3110,
3063, 3014, 2926, 2849, 1720, 1604, 1516, 1361, 1256, 1148, 1092,
1068, 831, 779, 708; 1H NMR (400 MHz, CDCl3, ppm): δ 7.73 (s, 1
H), 7.44 (d, J = 8.3 Hz, 1 H), 7.35 (d, J = 1.8 Hz, 1 H), 7.29 (dd, J =
8.3 Hz, 1.9 Hz, 1 H), 3.44 (dq, J = 10.4 Hz, 0.5 Hz, 2 H); 13C{1H}
NMR (100 MHz, CDCl3, ppm): δ 160.22, 153.84, 142.34, 138.20,
129.37 (C−F, 1JC−F = 275.6 Hz), 128.77, 126.62 (C−F, 1JC−F = 275.6
4-(p-Tolyl)-3-(2,2,2-trifluoroethyl)-2H-chromen-2-one (3x).
White solid, 83% yield (52.8 mg). Column chromatography on silica
gel (petroleum ether/EtOAc = 5:1). Mp = 107−110 °C. IR (cm−1)
3078, 3010, 2924, 2858, 1716, 1605, 1508, 1450, 1354, 1291, 1253,
1
1199, 1136, 1068, 948, 882, 827, 765, 712; H NMR (400 MHz,
CDCl3, ppm): δ 7.53 (dt, J = 7.7 Hz, 1.6 Hz, 1 H), 7.38 (dd, J = 8.3
Hz, 0.8 Hz, 1 H), 7.35 (d, J = 7.8 Hz, 2 H), 7.16 (dd, J = 7.6 Hz, 1.1
Hz, 1 H), 7.13 (d, J = 7.8 Hz, 2 H), 7.00 (dd, J = 8.0 Hz, 1.4 Hz, 1
H), 3.35 (q, J = 10.1 Hz, 2 H), 2.47 (s, 3 H); 13C{1H} NMR (100
MHz, CDCl3, ppm): δ 161.04, 156.34, 153.02, 139.19, 132.11,
130.49, 129.63, 129.44 (C−F, 1JC−F = 277.1 Hz), 128.08, 126.67 (C−
F, 1JC−F = 277.1 Hz), 124.31, 123.89 (C−F, 1JC−F = 277.1 Hz), 121.12
Hz), 125.39, 123.86 (C−F, 1JC−F = 275.6 Hz), 121.11 (C−F, 1JC−F
=
3
3
275.6 Hz), 118.68 (C−F, JC−F = 2.9 Hz), 118.65 (C−F, JC−F = 2.9
3
3
Hz), 118.62 (C−F, JC−F = 2.9 Hz), 118.59 (C−F, JC−F = 2.9 Hz),
117.24, 117.09, 34.45 (C−F, JC−F = 31.0 Hz), 34.14 (C−F, JC−F
31.0 Hz), 33.83 (C−F, JC−F = 31.0 Hz), 33.51 (C−F, JC−F = 31.0
Hz); 19F NMR (376 MHz, CDCl3, ppm): δ −65.11 (s); HRMS (ESI-
TOF) m/z: [M + H]+ Calcd for C11H7ClF3O2 263.0081; Found
263.0081.
1
3
2
2
(C−F, JC−F = 277.1 Hz), 120.56, 116.73, 116.25 (C−F, JC−F = 2.8
=
3
3
2
2
Hz), 116.22 (C−F, JC−F = 2.8 Hz), 116.19 (C−F, JC−F = 2.8 Hz),
3
2
116.16 (C−F, JC−F = 2.8 Hz), 33.15 (C−F, JC−F = 31.0 Hz), 32.84
(C−F, 2JC−F = 31.0 Hz), 32.53 (C−F, 2JC−F = 31.0 Hz), 32.22 (C−F,
2JC−F = 31.0 Hz), 21.36; 19F NMR (376 MHz, CDCl3, ppm): δ
−63.35 (s); HRMS (ESI-TOF) m/z: [M + H]+ Calcd for C18H14F3O2
319.0940; Found 319.0940.
7-Bromo-3-(2,2,2-trifluoroethyl)-2H-chromen-2-one (3u). White
solid, 84% yield (51.6 mg). Column chromatography on silica gel
(petroleum ether/EtOAc = 5:1). Mp = 104−106 °C. IR (cm−1) 3109,
3053, 3008, 2956, 2922, 2854, 1717, 1634, 1601, 1558, 1481, 1405,
6-Methoxy-4-phenyl-3-(2,2,2-trifluoroethyl)-2H-chromen-2-one
(3y). White solid, 84% yield (56.2 mg). Mp = 95−96 °C. IR (cm−1)
3090, 3067, 3022, 2952, 2922, 2852, 1715, 1626, 1570, 1492, 1437,
1350, 1287, 1253, 1200, 1136, 830, 710; 1H NMR (400 MHz, CDCl3,
ppm): δ 7.58−7.52 (m, 3 H), 7.33 (d, J = 9.0 Hz, 1 H), 7.27−7.24
(m, 2 H), 7.12 (dd, J = 9.0 Hz, 3.0 Hz, 1 H), 6.39 (d, J = 2.9 Hz, 1
H), 3.65 (s, 3 H), 3.34 (q, J = 10.1 Hz, 2 H); 13C{1H} NMR (100
MHz, CDCl3, ppm): δ 161.12, 155.95, 155.79, 147.46, 133.50, 129.38
(C−F, 1JC−F = 277.2 Hz), 129.26, 129.02, 128.12, 126.61 (C−F, 1JC−F
1
1362, 1256, 1151, 1101, 1063, 935, 830, 782, 717; H NMR (400
MHz, CDCl3, ppm): δ 7.72 (s, 1 H), 7.51 (d, J = 1.6 Hz, 1 H), 7.44
(dd, J = 8.3 Hz, 1.8 Hz, 1 H), 7.36 (d, J = 8.3 Hz, 1 H), 3.43 (q, J =
10.4 Hz, 2 H); 13C{1H} NMR (100 MHz, CDCl3, ppm): δ 160.15,
1
153.76, 142.43, 129.33 (C−F, JC−F = 275.6 Hz), 128.88, 128.23,
126.57 (C−F, 1JC−F = 275.6 Hz), 126.16, 123.82 (C−F, 1JC−F = 275.6
Hz), 121.06 (C−F, 1JC−F = 275.6 Hz), 120.03, 118.94 (C−F, 3JC−F
=
= 277.2 Hz), 123.84 (C−F, 1JC−F = 277.2 Hz), 121.07 (C−F, 1JC−F
=
3
3
2.9 Hz), 118.91 (C−F, JC−F = 2.9 Hz), 118.88 (C−F, JC−F = 2.9
3
Hz), 118.85 (C−F, 3JC−F = 2.9 Hz), 117.58, 34.48 (C−F, 2JC−F = 30.9
277.2 Hz), 120.87, 119.17, 117.70, 116.57 (C−F, JC−F = 2.8 Hz),
116.55 (C−F, 3JC−F = 2.8 Hz), 116.53 (C−F, 3JC−F = 2.8 Hz), 116.51
(C−F, 3JC−F = 2.8 Hz), 111.01, 55.68, 33.23 (C−F, 2JC−F = 31.0 Hz),
2
2
Hz), 34.17 (C−F, JC−F = 30.9 Hz), 33.86 (C−F, JC−F = 30.9 Hz),
33.55 (C−F, 2JC−F = 30.9 Hz); 19F NMR (376 MHz, CDCl3, ppm): δ
−65.10 (s); HRMS (ESI-TOF) m/z: [M + H]+ Calcd for
C11H7BrF3O2 306.9576; Found 306.9575.
2
2
32.92 (C−F, JC−F = 31.0 Hz), 32.61 (C−F, JC−F = 31.0 Hz), 32.30
(C−F, JC−F = 31.0 Hz); 19F NMR (376 MHz, CDCl3, ppm): δ
2
−63.32 (s); HRMS (ESI-TOF) m/z: [M + H]+ Calcd for C18H14F3O3
335.0890; Found 335.0888.
4-Methoxy-3-(2,2,2-trifluoroethyl)-2H-chromen-2-one (3v).
White solid, 51% yield (26.3 mg). Column chromatography on silica
gel (petroleum ether/EtOAc = 5:1). Mp = 80−83 °C. IR (cm−1)
3011, 2955, 2924, 2857, 1720, 1623, 1493, 1456, 1353, 1258, 1210,
1117, 954, 835, 766; 1H NMR (400 MHz, CDCl3, ppm): δ 7.72 (dd, J
= 8.0 Hz, 1.4 Hz, 1 H), 7.58 (dt, J = 7.8 Hz, 1.6 Hz, 1 H), 7.38 (d, J =
7.7 Hz, 1 H), 7.33 (dt, J = 7.6 Hz, 1.0 Hz, 1 H), 4.10 (s, 3 H), 3.53 (q,
J = 10.2 Hz, 2 H); 13C{1H} NMR (100 MHz, CDCl3, ppm): δ
7-Ethoxy-4-methyl-3-(2,2,2-trifluoroethyl)-2H-chromen-2-one
(3z′). White solid, 71% yield (40.6 mg). Column chromatography on
silica gel (petroleum ether/EtOAc = 5:1). Mp = 104−106 °C. IR
(cm−1) 3095, 2988, 2947, 2897, 1719, 1609, 1509, 1432, 1390, 1348,
1
1286, 1258, 1144, 1097, 1031, 902, 831, 782, 732; H NMR (400
MHz, CDCl3, ppm): δ 7.55 (d, J = 8.9 Hz, 1 H), 6.87 (dd, J = 8.9 Hz,
2.5 Hz, 1 H), 6.79 (d, J = 2.5 Hz, 1 H), 4.09 (q, J = 7.0 Hz, 2 H), 3.56
(q, J = 10.3 Hz, 2 H), 2.45 (s, 1 H), 1.45 (t, J = 7.0 Hz, 3 H); 13C{1H}
NMR (100 MHz, CDCl3, ppm): δ 162.23, 161.53, 154.29, 151.70,
1
167.09, 162.64, 153.38, 132.66, 129.59 (C−F, JC−F = 275.6 Hz),
126.83 (C−F, 1JC−F = 275.6 Hz), 124.30, 124.06 (C−F, 1JC−F = 275.6
Hz), 123.79, 121.30 (C−F, 1JC−F = 275.6 Hz), 117.32, 116.10, 106.73
(C−F, 3JC−F = 2.8 Hz), 106.70 (C−F, 3JC−F = 2.8 Hz), 106.67 (C−F,
1
1
130.17 (C−F, JC−F = 276.5 Hz), 127.41 (C−F, JC−F = 276.5 Hz),
126.10, 124.64 (C−F, 1JC−F = 276.5 Hz), 121.88 (C−F, 1JC−F = 276.5
3
3JC−F = 2.8 Hz), 106.64 (C−F, JC−F = 2.8 Hz), 62.34, 29.89 (C−F,
3
Hz), 113.32, 113.04, 112.30 (C−F, JC−F = 2.7 Hz), 112.27 (C−F,
2JC−F = 31.7 Hz), 29.57 (C−F, 2JC−F = 31.7 Hz), 29.25 (C−F, 2JC−F
=
3JC−F = 2.7 Hz), 112.24 (C−F, 3JC−F = 2.7 Hz), 112.21 (C−F, 3JC−F
=
2
31.7 Hz), 28.93 (C−F, JC−F = 31.7 Hz); 19F NMR (376 MHz,
CDCl3, ppm): δ −64.42 (s); HRMS (ESI-TOF) m/z: [M + H]+
Calcd for C12H10F3O3 259.0577; Found 259.0576.
2
2.7 Hz), 101.10, 64.22, 32.06 (C−F, JC−F = 30.9 Hz), 31.75 (C−F,
2JC−F = 30.9 Hz), 31.44 (C−F, 2JC−F = 30.9 Hz), 31.14 (C−F, 2JC−F
=
30.9 Hz), 15.86, 14.55; 19F NMR (376 MHz, CDCl3, ppm): δ −64.53
(s); HRMS (ESI-TOF) m/z: [M + H]+ Calcd for C14H14F3O3
287.0890; Found 287.0888.
4-Phenyl-3-(2,2,2-trifluoroethyl)-2H-chromen-2-one (3w). White
solid, 87% yield (52.9 mg). Column chromatography on silica gel
(petroleum ether/EtOAc = 5:1). Mp = 103−105 °C. IR (cm−1) 3071,
3007, 2924, 2855, 1722, 1607, 1562, 1489, 1450, 1353, 1293, 1253,
1133, 1108, 950, 840, 762, 703; 1H NMR (400 MHz, CDCl3, ppm): δ
7.58−7.52 (m, 4 H), 7.40 (dd, J = 8.3 Hz, 0.8 Hz, 1 H), 7.25 (d, J =
7.6 Hz, 1 H), 7.16 (dt, J = 7.6 Hz, 1.1 Hz, 1 H), 6.97 (dd, J = 8.0 Hz,
1.4 Hz, 1 H), 3.34 (q, J = 10.1 Hz, 2 H); 13C{1H} NMR (100 MHz,
CDCl3, ppm): δ 160.97, 156.07, 153.04, 133.49, 132.21, 129.39 (C−
7-Methoxy-8-(3-methylbut-2-en-1-yl)-3-(2,2,2-trifluoroethyl)-2H-
chromen-2-one (TF-Osthole). White solid, 43% yield (28.1 mg).
Column chromatography on silica gel (petroleum ether/EtOAc =
5:1). Mp = 148−149 °C. IR (cm−1) 3109, 3010, 2922, 2855, 1717,
1
1614, 1503, 1452, 1367, 1269, 1152, 1099, 846, 806, 767; H NMR
(400 MHz, CDCl3, ppm): δ 7.67 (s, 1 H), 7.31 (d, J = 8.6 Hz, 1 H),
6.86 (d, J = 8.6 Hz, 1 H), 5.23−5.19 (m, 1 H), 3.93 (s, 3 H), 3.53 (d,
J = 7.3 Hz, 2 H), 3.41 (q, J = 10.6 Hz, 2 H), 1.84 (s, 3 H), 1.67 (s, 3
H); 13C{1H} NMR (100 MHz, CDCl3, ppm): δ 161.43, 160.47,
152.47, 143.55, 132.82, 129.72 (C−F, 1JC−F = 275.6 Hz), 126.96 (C−
F, 1JC−F = 275.6 Hz), 126.38, 124.20 (C−F, 1JC−F = 275.6 Hz), 121.34
1
F, JC−F = 277.1 Hz), 129.22, 128.98, 128.19, 128.01, 126.61 (C−F,
1
1JC−F = 277.1 Hz), 121.39, 123.84 (C−F, JC−F = 277.1 Hz), 121.07
1
(C−F, JC−F = 277.1 Hz), 120.40, 116.77, 116.25 (C−F,3JC−F = 2.8
3
3
Hz), 116.22 (C−F, JC−F = 2.8 Hz), 116.19 (C−F, JC−F = 2.8 Hz),
3
2
1
3
116.16 (C−F, JC−F = 2.8 Hz), 33.16 (C−F, JC−F = 31.2 Hz), 32.84
(C−F, 2JC−F = 31.2 Hz), 32.53 (C−F, 2JC−F = 31.2 Hz), 32.22 (C−F,
2JC−F = 31.2 Hz); 19F NMR (376 MHz, CDCl3, ppm): δ −63.36 (s);
HRMS (ESI-TOF) m/z: [M + H]+ Calcd for C17H12F3O2 305.0784;
Found 305.0783.
(C−F, JC−F = 275.6 Hz), 120.93, 117.91, 114.53 (C−F, JC−F = 2.9
3
3
Hz), 114.51 (C−F, JC−F = 2.9 Hz), 114.49 (C−F, JC−F = 2.9 Hz),
3
114.47 (C−F, JC−F = 2.9 Hz), 112.85, 107.68, 56.09, 34.25 (C−F,
2JC−F = 30.8 Hz), 33.94 (C−F, 2JC−F = 30.8 Hz), 33.64 (C−F, 2JC−F
=
30.8 Hz), 33.33 (C−F, JC−F = 30.8 Hz), 25.78, 21.94, 17.92; 19F
2
2780
https://dx.doi.org/10.1021/acs.joc.0c02739
J. Org. Chem. 2021, 86, 2772−2783

The Journal of Organic Chemistry
pubs.acs.org/joc
Article
NMR (376 MHz, CDCl3, ppm): δ −65.34 (s); HRMS (ESI-TOF)
m/z: [M + H]+ Calcd for C17H18F3O3 327.1203; Found 327.1205.
3-(2,2,2-Trifluoroethyl)-2H-furo[2,3-h]chromen-2-one (TF-Angel-
icin). White solid, 34% yield (18.2 mg). Column chromatography on
silica gel (petroleum ether/EtOAc = 5:1). Mp = 153−155 °C. IR
(cm−1) 3105, 3064, 3005, 2951, 2922, 2856, 1708, 1616, 1442, 1364,
7326; Email: yusheng.wu@tetranovglobal.com; Fax: (+1)-
732-253-7327
Authors
Xiaoyu Chen − Green Catalysis Center and College of
Chemistry, Zhengzhou University, Zhengzhou, Henan
450001, People’s Republic of China
Linlin Li − Green Catalysis Center and College of Chemistry,
Zhengzhou University, Zhengzhou, Henan 450001, People’s
Republic of China
Congcong Pei − Green Catalysis Center and College of
Chemistry, Zhengzhou University, Zhengzhou, Henan
450001, People’s Republic of China
1
1260, 1141, 1073, 922, 823, 773, 743; H NMR (400 MHz, CDCl3,
ppm): δ 7.87 (s, 1 H), 7.71 (d, J = 2.2 Hz, 1 H), 7.47 (d, J = 8.5 Hz, 1
H), 7.40 (d, J = 8.6 Hz, 1 H), 7.14 (d, J = 1.6 Hz, 1 H), 3.47 (q, J =
10.5 Hz, 2 H); 13C{1H} NMR (100 MHz, CDCl3, ppm): δ 161.03,
1
157.52, 148.03, 146.10, 144.35, 129.60 (C−F, JC−F = 275.5 Hz),
1
1
126.85 (C−F, JC−F = 275.5 Hz), 124.10 (C−F, JC−F = 275.5 Hz),
123.89, 121.35 (C−F, 1JC−F = 275.5 Hz), 116.79, 115.95 (C−F, 3JC−F
3
3
= 2.9 Hz), 115.92 (C−F, JC−F = 2.9 Hz), 115.89 (C−F, JC−F = 2.9
3
Hz), 115.86 (C−F, JC−F = 2.9 Hz), 113.39, 109.21, 104.06, 34.48
Jingya Li − Tetranov Biopharm, LLC, Zhengzhou 450052,
People’s Republic of China
(C−F, 2JC−F = 30.9 Hz), 34.17 (C−F, 2JC−F = 30.9 Hz), 33.86 (C−F,
2JC−F = 30.9 Hz), 33.55 (C−F, JC−F = 30.9 Hz); 19F NMR (376
2
MHz, CDCl3, ppm): δ −65.32 (s); HRMS (ESI-TOF) m/z: [M +
Complete contact information is available at:
https://pubs.acs.org/10.1021/acs.joc.0c02739
H]+ Calcd for C13H8F3O3 269.0420; Found 269.0421.
2-Phenyl-3-(2,2,2-trifluoroethyl)-4H-chromen-4-one (TF-Fla-
vone). White solid, 61% yield (37.1 mg). Column chromatography
on silica gel (petroleum ether/EtOAc = 5:1). Mp = 90−92 °C. IR
(cm−1) 3072, 2955, 2922, 2857, 1641, 1572, 1468, 1398, 1355, 1260,
1132, 1079, 1028, 839, 762, 700; 1H NMR (400 MHz, CDCl3, ppm):
δ 8.28 (dd, J = 8.0 Hz, 1.3 Hz, 1 H), 7.70 (dt, J = 7.8 Hz, 1.6 Hz, 1
H), 7.60−7.53 (m, 5 H), 7.45 (dt, J = 8.0 Hz, 1.0 Hz, 2 H), 3.51 (q, J
= 10.2 Hz, 2 H); 13C{1H} NMR (100 MHz, CDCl3, ppm): δ 177.18,
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
We are grateful to the National Natural Science Foundation of
China (Grants 21172200 and 21702191) for financial support.
1
165.60, 156.07, 134.08, 132.61, 130.71, 129.96 (C−F, JC−F = 277.0
Hz), 128.88, 128.50, 127.19 (C−F, 1JC−F = 277.0 Hz), 126.20, 125.48,
124.42 (C−F, 1JC−F = 277.0 Hz), 122.68, 121.65 (C−F, 1JC−F = 277.0
Hz), 118.01, 112.28 (C−F, 3JC−F = 2.4 Hz), 112.26 (C−F, 3JC−F = 2.4
REFERENCES
■
3
3
Hz), 112.24 (C−F, JC−F = 2.4 Hz), 112.22 (C−F, JC−F = 2.4 Hz),
(1) (a) Jeschke, P. The Unique Role of Fluorine in the Design of
Active Ingredients for Modern Crop Protection. ChemBioChem 2004,
2
2
30.26 (C−F, JC−F = 31.2 Hz), 29.95 (C−F, JC−F = 31.2 Hz), 29.63
(C−F, JC−F = 31.2 Hz), 29.32 (C−F, JC−F = 31.2 Hz); 19F NMR
(376 MHz, CDCl3, ppm): δ −63.91 (s); HRMS (ESI-TOF) m/z: [M
+ H]+ Calcd for C17H12F3O2 305.0784; Found 305.0785.
2
2
5, 570−589. (b) Muller, K.; Faeh, C.; Diederich, F. Fluorine in
̈
Pharmaceuticals: Looking Beyond Intuition. Science 2007, 317, 1881−
1886. (c) Babudri, F.; Farinola, G. M.; Naso, F.; Ragni, R. Fluorinated
Organic Materials for Electronic and Optoelectronic Applications: the
Role of the Fluorine Atom. Chem. Commun. 2007, 1003−1022.
(d) Purser, S.; Moore, P. R.; Swallow, S.; Gouverneur, V. Fluorine in
Medicinal Chemistry. Chem. Soc. Rev. 2008, 37, 320−330. (e) Ji, Y.;
Brueckl, T.; Baxter, R. D.; Fujiwara, Y.; Seiple, I. B.; Su, S.;
Blackmond, D. G.; Baran, P. S. Innate C-H Trifluoromethylation of
Heterocycles. Proc. Natl. Acad. Sci. U. S. A. 2011, 108, 14411−14415.
(f) Furuya, T.; Kamlet, A. S.; Ritter, T. Catalysis for Fluorination and
Trifluoromethylation. Nature 2011, 473, 470−477.
ASSOCIATED CONTENT
* Supporting Information
The Supporting Information is available free of charge at
https://pubs.acs.org/doi/10.1021/acs.joc.0c02739.
■
sı
Mechanistic experiments and NMR spectra (PDF)
Accession Codes
CCDC 2030924 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-
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AUTHOR INFORMATION
Corresponding Authors
■
Dapeng Zou − Green Catalysis Center and College of
Chemistry, Zhengzhou University, Zhengzhou, Henan
450001, People’s Republic of China; Phone: (+86)-371-
6776-6865; Email: zdp@zzu.edu.cn; Fax: (+86)-371-
6776-3390
Yangjie Wu − Green Catalysis Center and College of
Chemistry, Zhengzhou University, Zhengzhou, Henan
450001, People’s Republic of China; orcid.org/0000-
0002-0134-0870; Phone: (+86)-371-6776-6865;
Email: wyj@zzu.edu.cn; Fax: (+86)-371-6776-3390
Yusheng Wu − Tetranov Biopharm, LLC, Zhengzhou
450052, People’s Republic of China; Tetranov International,
Inc., New Brunswick, New Jersey 08901, United States;
orcid.org/0000-0001-7023-9541; Phone: (+1)-732-253-
2781
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