Photoredox-Catalyzed Cascade Radical Cyclization of Ester Arylpropiolates with CF3SO2Cl to Construct 3-Trifluoromethyl Coumarin Derivatives

Article abstract of DOI:10.1021/acs.joc.8b00581

We report a highly efficient method to construct 3-trifluoromethyl coumarins using CF₃SO₂Cl as the trifluoromethyl radical source with ester 3-arylpropiolates. The reaction incorporated a cascade cyclization/dearomatization/ester mig

Full text of DOI:10.1021/acs.joc.8b00581

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Note
Photoredox-Catalyzed Cascade Radical Cyclization of Ester Arylpropiolates
with CF3SO2Cl to Construct 3-Trifluoromethyl-Coumarin Derivatives
Long Chen, Lianlian Wu, Weijie Duan, Tao Wang, Letian
Li, Keke Zhang, Jingmei Zhu, Zhi Peng, and Fei Xiong
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.8b00581 • Publication Date (Web): 07 Jun 2018
Downloaded from http://pubs.acs.org on June 7, 2018
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Page 1 of 9
The Journal of Organic Chemistry
PhotoredoxꢀCatalyzed Cascade Radical Cyclization of Ester
Arylpropiolates with CF3SO2Cl to Construct 3ꢀTrifluoromethylꢀ
Coumarin Derivatives
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Long Chen, †, ‡ Lianlian Wu, ‡ Weijie Duan, ‡ Tao Wang, *,†, ‡ Letian Li, ‡ Keke Zhang, ‡ Jingmei Zhu, ‡
Zhi Peng, ‡ Fei Xiong *,†, ‡
† National Research Center for Carbohydrate Synthesis and Key Laboratory of Chemical Biology, Jiangxi Normal
University, Nanchang, Jiangxi 330022, P. R. China
‡ College of Chemistry and Chemical Engineering, Jiangxi Normal University, Nanchang, Jiangxi 330022, P. R. China
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ABSTRACT: We reported a highly efficient method to construct 3ꢀtrifluoromethy coumarins using CF3SO2Cl as the
trifluoromethyl
radical source with ester 3ꢀarylpropiolates. The reaction incorporated a cascade cyclization/dearomatization/ester migration/
oxidization/ rearomatization process to afford various 3ꢀtrifluoromethyl coumarins under visible light irradiation in good to
excellent
yields.
KEYWORDS: Photoredoxꢀcatalyzed; Trifluoromethylation; Coumarin; Radical; Cascade reaction
Naturally occurring coumarins are found extensively in plants,
fungi and bacteria.1 This class of compounds is well known
for its significant biological and pharmacological properties.2
Some coumarin analogues are used as P450s inhibitor.2a Some
show antiꢀinflammatory,2b antitumor,2c antineurodegeneraꢀ
tive,2d anticoagulant,2e antimicrobial,2e antiꢀHIV,2e and
Much attention has focused on synthesis of organic fluorine
compounds due to their unique properties, such as improving
lighting fastness for dyes.7 Organic fluorine compounds also
provide better membrane permeability and bioavailability than
their nonꢀfluorinated analogues.8 Trifluoromethylation has
gained increasing interest in recent years. The trifluoromethyl
group(CF3ꢀ) is a versatile component and essential structural
motif in pharmaceuticals, agrochemicals, dyes, and organic
materials.9 Addition of the CF3 moiety is typically
accomplished by means of transition metals catalyzed crossꢀ
coupling technology. However, these strategies generally
required the stoichiometric metal reagents. Recently, the
introduction of CF3 was achieved in a catalytic fashion by
antioxidant activities.2e
Coumarins have also found
widespread applications in several fields, including cosmetics,
pesticides, fluorescent dyes, chemical and biological probes.3
Over the past several decades, various synthetic strategies
have been developed for preparing coumarins. In 2000,
Fujiwara’s group discovered Pdꢀcatalytic intramolecular
hydroarylation of CꢀC triple bond as an efficient methodology
to construct coumarin moieties.4 Other Lewis acids, such as
Au, Fe, etc., also smoothly promoted the transformation.5
Recently, direct functionalization of activated alkynoates has
been utilized to synthesize 3ꢀsubstitued coumarins,6 including,
copper, or palladiumꢀcatalyzed reaction using either
a
nucleophilic or electrophilic source of CF3 (TMSCF3,
CF3SO2Na or Togni’s reagent, Umemoto’s reagent, CF3SO2Cl,
etc.).10 Among these reagents, CF3SO2Cl is also an efficient
reagent for introducing CF3 moiety onto a wide range of
substrates by transition metal or photoredoxꢀcatalyzed
reaction.11 For example, Kamigata and coꢀworkers discovered
the RuCl2(PPh3)3ꢀcatalyzed trifluoromethylation of arenes and
heteroarenes in 1990.12 MacMillan’s group reported a similar
transformation in 2011 using a photocatalyst instead of
RuCl2(PPh3)3. This strategy could considerably extend the
scope of substrates (Scheme 1, a).9 Trifluoromethylation of
3ꢀtrifluoromethylation with Togni’s reagent,6b
phosphorylation with dialkyl H‑phosphonate,6c, 6d 3‑difluoroꢀ
acetylation with ethyl 3ꢀ
bromodifluoroacetate,6e
trifluoromethylthiolation and thiocyanation with AgSCF3 and
AgSCN, and 3ꢀsulfonation with
respectively,6f
3
‑
aryldiazonium,6g among many others. These transformations
proceeded in a similar reaction pathway. First, a radical is
generated by external oxidants, reductants or photocatalysts,
and is added to the αꢀposition of C=O in alkynoates to produce
the vinyl radical intermediate. Second, an intramolecular
radical cyclization forms a ringꢀclosed radical intermediate via
6ꢀendo or 5ꢀexo annulation with ester migration. Third, the
radical intermediate is oxidized to the corresponding cation
intermediate. Finally, deprotonation and aromatization afford
the corresponding 3ꢀsubsititued coumarin derivatives.
silyl enol ethers and olefins generally constructed CF3ꢀCsp3
13
bond in 2014 (Scheme 1, b).10c,
Gu’s group presented a
direct annulation approach for preparation of a variety of
indole derivatives using arylsulfonyl chlorides with oꢀ
azidoarylalkynes via visibleꢀlight induced cyclization process
in 2017 (Scheme 1, c).14 Furthermore, visible lightꢀpromoted
chlorotrifluoromethylation of alkynes was described by Han’s
group in 2017.15 In addition, photoredox catalysis, a powerful
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Page 2 of 9
synthetic strategy, has been widely applied in catalytic
obtained in 45% yield (Table 1, entry 1). Encouraged by this
result, we optimized the reaction conditions with respect to
photocatalysts, solvents, trifluoromethyl sources, etc... The
results are outlined in Table 1 and Table S4. A survey of
photocatalysts demonstrated that Ru(bpy)3Cl2 exhibited the
best catalytic effect. Other photocatalysts, such as Eosin Y,
Rose Bengal and facꢀIr(ppy)3, showed lower catalytic
efficiency (Table 1, entries 1ꢀ4). The screening of solvents
showed that use of single solvent, such as DCM, DMF,
DMSO, H2O, DCM, THF, MeOH, NMP, etc., did not favor
the reaction (isolated yield<30%, See Table S4, entries 5ꢀ8
and 21ꢀ24), while coꢀsolvents greatly improved the yields. The
existence of water in CH3CN solvent was evidently beneficial
to the transformation process (Table 1, entries 5ꢀ8).
Meanwhile, a mixture of MeCN/H2O (v/v=10:1) provided the
highest yield (68%, Table 1, entry 7). Further investigation
showed that trifluoromethyl reagents greatly affected the
reaction efficiency. For example, popular electrophilic
trifluoromethyl sources, such as Togni and Umemoto’s
reagents, did not provide the desired product in an acceptable
yield, as detected by GCMS (Table 1, entry 9, 10). No desired
products were detected by TLC and GCMS with other
trifluoromethyl reagents, such as TMSCF3, CF3SO2Na, etc.
(Table 1, entry 11, 12). The product was obtained in poor
yield when CF3I was used as trifluoromethyl source (Table 1,
entry 13). We also observed that products were not formed
without light radiation or photocatalyst (Table 1. entry 14, 15).
Inert gas was beneficial to the reaction while residual air
slowed down the reaction and/or decreased the conversion
ratio. The results of full screening of reaction conditions are
outlined in supporting information (Table S4).
trifluoromethylation over the past several years.16
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5
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7
8
Herein we report a highly efficient method to construct 3ꢀ
trifluoromethyl coumarins using CF3SO2Cl via visible lightꢀ
promoted cascade radical cyclization with ester 3ꢀ
arylpropiolates. Ding’s group reported
a
similar
transformation using Togni’s reagent in 2014.6b Their strategy
delivered a moderate yield but limited scope of substrates. Use
of electronꢀdeficient 3ꢀarylpropiolates gave low yields. In
addition, the characterization of structures seemed incorrect in
comparation 1HNMR data of 3a in their report (the structure of
9
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3a, see Scheme 1, e) and those of 3b in this work. HNMR
spectra of two compounds were identical, however, the
structure of 3b in this work was unambiguously confirmed by
Xꢀray crystal analysis (Figure 1, Figure S1).
Scheme 1: Trifluoromethylation of sp2 and sp3ꢀC using
CF3SO2Cl as trifluoromethyl source
Previous works:
H
CF3
Photocatalyst(1ꢀ2 mol%)
R
+
CF3SO2Cl
R
(a)
(b)
K2HPO4,MeCN, rt
26w lightsource
X
X
MacMillan,D.W.C Nature 2011, 224
R2
CF3
R2
CF3SO2Cl(2 equiv)
R
Ru(Phen)3Cl2(1 mol%)
R
+
CF3SO2Cl
N
R1
O
NaOAc(3.5 equvi)/AcOH
Visible Light,rt, 12h
O
N
R1
Yield: 50ꢀ95%
DolbierW. R., jr; Org. Lett. 2014, 4594
Eosin Y (3 mol%)
Na2HPO4(1 equiv)
Ph
CF3
Ph
CF3SO2Cl
+
(c)
1,4ꢀCHD/CH3CN
rt,14h,blue LEDs
N
Yield: 31%
N3
H
Table 1. Optimization of Reaction Conditions a
Gu, LꢀJ; Chem. Commun.2017, 4203
Ir(ppy)3 (2 mol%)
Li2CO3 (0.5 equiv)
CF3
R
Ar
R
CF3SO2Cl
+
Ar
(d)
(e)
acetone, 25 oC,
blue LEDs, 12h
H
Yield: 34ꢀ85%
Photocatalyst (1 mol%)
CF3
Cl
Han, S. B.; Org. Lett.
R2
solvent
CF3 reagent
blue LEDs (16W), N2
40°C, 48~72h
R=alkyl,amide, ester
R2
2017
, 1962
O
1a
O
O
3a
O
2
O
R1
CF3
O
R1
H
Cu(OAc)2 (10 mol %)
Yieldb (%)
O
Entry
Catalyst
CF3 source
Solvent
+
K2CO3 (2.0 equiv)
MeCN, 60°C
I
O
3a: R1=CH3
O
O
CF3
17 example
Yields: up to 66% R2=Ph
Ru(bpy)3Cl2
eosin Y
CF3SO2Cl
CF3SO2Cl
CF3SO2Cl
CF3SO2Cl
CF3SO2Cl
CF3SO2Cl
CF3SO2Cl
MeCN
MeCN
MeCN
MeCN
45
1
2
Togni's reagent
NR
NR
25
This work:
2014
, 16, 4240ꢀ4243
3
4
5
6
7
Rose bengal
f acꢀIr(ppy)3
Ru(bpy)3Cl2
Ru(bpy)3Cl2
Ru(bpy)3Cl2
Ding,QꢀP; Org. Lett.
R2
R2
MeCN:H2O(1:1)
MeCN:H2O(4:1)
MeCN:H2O(10:1)
MeCN:H2O(20:1)
50
R1
H
O
CF3
O
Ru(bpy)3Cl2
visibe light
CF3SO2Cl
52
R1
O
O
68
28 examples
Yields: up to 85%
8
Ru(bpy)3Cl2
CF3SO2Cl
60
NR
9
Ru(bpy)3Cl2
Ru(bpy)3Cl2
MeCN:H2O(10:1)
MeCN:H2O(10:1)
Togni's Reagent
trace
10
11
Umemoto's Reagent
Figure 1: Xꢀray Structure of Compound 3b
NR
NR
20
Ru(bpy)3Cl2
Ru(bpy)3Cl2
Ru(bpy)3Cl2
MeCN:H2O(10:1)
MeCN:H2O(10:1)
MeCN:H2O(10:1)
MeCN
TMSCF3
CF3SO2Na
CF3I
12
13
14c
15d
none
CF3SO2Cl
CF3SO2Cl
NR
NR
MeCN
Ru(bpy)3Cl2
a Reaction conditions: 1a (0.2 mmol), 2 (0.4 mmol, 2 equiv), catalyst (1
mol%), solvent (3 mL), irradiation with blue LEDs (16W), at 40°C under
N2 atmosphere for 48~72h. b Isolated yields. c Without photocatalyst ,
d Without visible light irradiation.
With the optimized reaction conditions in hand, the scopes
of the reaction were explored (Table 2 and Table 3). First,
various 3ꢀphenylpropiolates were evaluated under the
optimized reaction conditions (Table 2). In general, pꢀ
substituted phenyl 3ꢀphenylpropiolates containing electronꢀ
donating groups or electronꢀwithdrawing groups showed good
reactivity with CF3SO2Cl that afforded the corresponding 3ꢀ
Initially, the reaction between phenyl 3ꢀphenylpropiolate 1a
and CF3SO2Cl (2a) was carried out in acetonitrile at ambient
temperature for 48 hours under nitrogen atmosphere, upon
irradiation with a 16 W blue LEDs strip in the present of
Ru(bpy)3Cl2 (0.01 equiv) as photocatalyst. Compound 3a was
2
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compatibility of R2 group was also investigated under the
trifluoromethyl coumarins in good to excellent yields (Table 2,
3aꢀ3n)
Furthermore, the pꢀsubstituted R1 groups did not show
1
2
3
4
5
6
7
8
optimized conditions (Table 3). All substrates bearing
different functional groups located on phenyl ring, such as
alkyl, halogen, methoxyl, cyano, trifluoromethyl, etc.,
provided the desired products in good yields (Table 3, 5bꢀ5h).
To our satisfaction, ester methylpropiolate (4a) was also found
to be suitable for the reaction and converted into the desired
product 5a in 57% yield.
.
the electronic effect (Table 2, 3aꢀ3n). For example, substrates
bearing Bu or CF3 group located on pꢀposition gave 85% and
t
80% yields, respectively.
Table 2. Scopes of aryl Phenylpropiolate
Table 3. Scopes of pꢀtBuꢀphenyl arylpropiolates
9
Ru(bpy)3Cl2 (1 mol%)
CH3CN/H2O = 10 : 1
CF3
O
H
O
10
11
12
13
14
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R1
CF3SO2Cl
R1
blue LEDs(16W), N2
40°C, 48~72h
O
3
O
2a
1
CF3
O
CF3
CF3
CF3
O
iPr
O
O
O
O
Et
O
O
3a
3b
3c
3d
77%, 48h
68%, 48h
70%, 48h
72%, 48h
CF3
CF3
CF3
CF3
tBu
O
O
Br
O
O
F
F3C
S
O
O
Cl
O
O
3e 85%, 48h
3f 72%, 60h
3g 71%, 60h
3h 75%, 60h
CF3
CF3
CF3
CF3
F3CO
O
O
I
O
O
O
O
O
O
O
3i 74%, 60h
3j 80%, 66h
3k 79%, 66h
O
3l
61%, 72h
F
CF3
CF3
CF3
CF3
To investigate the mechanism of the reaction, the control
reaction and luminescent quenching of photocatalyst were
performed. Under standard reaction conditions, TEMPO
(2,2,6,6ꢀtetramethylꢀ1ꢀpiperidinyloxy), an effective and
popular radical scavenger, was added to the reaction. The
TEMPO adduct X was detected by GCMS analysis and 3a
was not observed. This result indicated that the reaction was
completely inhibited by the radical scavenger (Scheme 2, 1).
Furthermore, luminescent quenching of [Ru(bpy)3]2+Cl2 was
carried out (shown in Scheme 2, 2). The emission of
[Ru(bpy)3]2+Cl2 was observed at ~610 nm when it was excited
at 450 nm, while addition of triflyl chloride evidently
decreased the luminescent intensity of *[Ru(bpy)3]2+Cl2
(Scheme 2, 2ꢀb). On the other hand, 1a did not quench
luminescence of *[Ru(bpy)3]2+Cl2 (Scheme 2, 2ꢀa). These
results indicated the existence of single electron transfer
between [Ru(bpy)3]2+Cl2 and triflyl chloride. Based on the
redox potentials of triflyl chloride and *[Ru(bpy)3]2+Cl2,9
triflyl chloride can acquire an electron from [Ru(bpy)3]2+Cl2
under visible light irradiation to furnish Ru3+ and CF3
radical.11a In addition, the reaction required long reaction time
(48ꢀ72h). Photon flux density and photonic efficiency possibly
determined the reaction rate of the photoredoxꢀcatalyzed
process. Faster reaction rate was observed in microreactor or
continuousꢀflow than that in batch reactor.18
NC
O
O
O
O
F
O
O
O
O
3m 57%,72h
3n
60%, 72h
3o
3p
80%, 48h
76%, 72h
CF3
CF3
F3C
CF3
CF3
O
O
O
O
O
3q
O
O
O
CF3
3r'
3q'
3r
3q+3q'(p:o=1.5:1) 84%, 54h
3r+3r'(p:o=2:1) 72%, 50h
CN
Rs= CH3
CF3
Rs
CF3
CF3
i-Pr
O
O
O
O
3s
3t
52%, 72h
trace
3q
3r
Reaction Conditions: 1 (0.2 mmol), 2a (0.4 mmol, 2.0 equiv), Ru(bpy)3Cl2
(1 mol%), MeCN:H2O =10:1,The reaction is in N2 atmosphere at 40°C for 48 ꢀ
72 h. The structue of the isomer was determined by cultivation of single
crystal and 1HNMR. Isolated yields are shown.
Next, we investigated the steric effect of substrates bearing
a methyl in paraꢀ, metaꢀ, or orthoꢀposition. These results
indicated that 1b (paraꢀ) and 1r (metaꢀ) were easily converted
to the corresponding coumarins 3b and 3r, 3rʹ. The structures
of 3b and 3r were determined by NMR and Xꢀray crystal
structure analysis (see Table 2).
When metaꢀCH3 was
replaced by CF3 group, two regioisomers of 3q and 3qʹ were
also obtained in 84% yield. For substrates 1qꢀ1r with metaꢀ
substituted, the regioselectivity was obviously observed, that
could be attributed to the slight steric hindrance effect of
metaꢀmethyl group.6i,17 However, substrates 3s (R1=orthoꢀCH3,
Scheme 2 Mechanism Investigation
i
CF3, Pr) did not give desired products (detected by GCMS,
Table 2, 3s). To our surprise, 3t (R1=orthoꢀCN, a linear group)
was obtained in 52% yield under the optimized conditions.
The results strongly suggested the subtle steric effect of the
ortho group in the transformation process. Furthermore, the
3
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1
2
■ EXPERIMENTAL SECTION
3
4
5
6
7
8
9
General Information. All reagents and solvents were
commercially available and used without further purification.
Unless otherwise noted, all reactions run under nitrogen
atmosphere. Purification of all products was carried out by
4000
3000
2000
1000
0
PC
PC+1a
4000
3000
2000
1000
0
0 equvi
20 equvi
40 equvi
60 equvi
80 equvi
100 equvi
1
flash chromatography using 200ꢀ300 mesh silica gel. H, 13C
20 equvi
40 equvi
60 equvi
80 equvi
100 equvi
120 equvi
150 equvi
and 19F NMR spectra were recorded on a Bruker Ascend
instrument at 400 MHz, 100 MHz respectively. Chemical
shifts were reported in δ ppm referenced to an internal TMS
standard for 1H NMR(δ=0.00), CDCl3 (δ 77.00) for 13C NMR.
The following abbreviations were used to explain
multiplicities: s = singlet, d = doublet, t = triplet, q = quartet,
hept = heptaplet, m = multiplet, and br=broad. Highꢀresolution
mass spectra (HRMS) were obtained on an Agilent mass
spectrometer using ESIꢀTOF (electrospray ionizationꢀtime of
flight). GCꢀMS spectra were recorded on a ShimazuꢀGCꢀMS
2010QPꢀUltra.
Preparation of starting materials. To a solution of the
phenol (5.0 mmol, 1.0 equiv) in CH2Cl2 (20 mL) was added 3ꢀ
phenylpropiolic acid (5.5 mmol, 1.1 equiv) at 0 °C, then a
mixture of DCC (7.5 mmol, 1.5 equiv) and DMAP (0.5 mmol,
0.1 equiv) in CH2Cl2 (10 mL) was added dropwise. The
mixture was stirred at room temperature for 12 hours. Then
the crude mixture was filtered and washed with CH2Cl2 (20
mL). The combined organic phase was concentrated under
reduced pressure to give a residue which was purified by a
silica gel column chromatography (petroleum ether/EtOAc =
60:1) to give the alkynoate products 1.
1a
2a
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400
500
600
700
800
900
400
500
600
700
800
900
Wavelength/nm
Wavelength/nm
On the basis of our experimental results and previous
literatures,6g we propose that the reaction may involve a
cascade radical process triggered by visible light irradiation.
The proposed mechanism is depicted in Scheme 3. Initially,
singleꢀelectron transfer (SET) reduction of triflyl chloride
along with oxidation of *[Ru(bpy)3]2+ to [Ru(bpy)3]3+ produces
trifluoromethyl radical upon visible light irradiation.
Subsequently, an electrophilic addition of trifluoromethyl
radical to pꢀmethylphenyl 3ꢀphenylpropiolate(1b) generates
intermediate A, that is transformed into radical B by 5ꢀ
exocyclization process. Some similar bicyclic products were
reported in the related references.19 Sequentially radical
intermediate B is further transformed into radical C by 1,2ꢀ
ester migration, which is consistent with the structures of
3b,3q,3r (see Figure S1ꢀS3). The ester migration process was
also proposed in previous works.6a,6i,17 The intermediate C
undergoes a second SET process with strongly oxidizing Ru3+
photocatalyst and is transformed into cation intermediate D,
followed by proton releasing and reꢀaromatization to give the
desired product 3b. Further mechanism research is underway
in our laboratory.
General procedure for the synthesis of 3ꢀ
Trifluoromethyl Coumarin. A mixture of 1 (0.2 mmol),
CF3SO2Cl (2a) (0.4 mmol, 2.0 equiv), Photocatalyst (0.002
mmol, 1 mol%) in degassed MeCN/H2O (3.0 mL) (v/v=10:1)
were stirred at 40ºC under nitrogen atmosphere and irradiation
by a commercially available Blue LEDs (16W) for 48~72h.
After disappearance of 1 detected by TLC, the reaction
mixture was washed by ethyl acetate (5.0mL*3), the combined
organic phase was concentrated in vacuo and the residue was
purified by column chromatography on silica gel (eluted with
PE/EA=80:1~60:1) to provide the desired product 3.
Scheme 3. Possible Reaction mechanism
Crystal Sample Preparation and Crystal Structure
Determination: Single crystal (3b as example) was obtained
using AcOEt/cyclohexane (1:2) as solvent and the structure
was analyzed by singleꢀcrystal Xꢀray diffraction. A suitable
dimensions crystal was selected for data collection.
Diffraction intensities were collected on a Rigaku Xꢀray
diffractometer with Graphite monochromated MoKα (0.71073
Å) radiation and the ωꢀ2θ variableꢀscan mode. The crystal was
kept at 293(2) K during data collection. The structure was
solved using the program SHELXTL and refined with the
SHELXLꢀ2014/1 (Sheldrick, 2014). The position of the
hydrogen atoms was S2 calculated by assuming ideal
geometries but not refined. All nonꢀhydrogen atoms were
refined with anisotropic thermal parameters by fullꢀmatrix
leastꢀsquares procedures on F2.
In summary, we reported
a facile assembly of 3ꢀ
trifluoromethylation coumarins through visible lightꢀpromoted
cascade radical cyclization process using ester arylpropiolates
with commercial and inexpensive CF3SO2Cl. The reaction was
efficient with a wide variety of functional group tolerance. As
a result, the transformation offered a significant pathway to
introduce trifluoromethyl into the scaffold of versatile
coumarins under mild and environmentꢀfriendly conditions.
Further mechanism investigations of this type of
transformation process are ongoing in our laboratory.
4ꢀphenylꢀ3ꢀ(trifluoromethyl)ꢀ2Hꢀchromenꢀ2ꢀone
（3a）:
a pale white crystalline solid (68 %, 39.4 mg) mp: 124 – 126
1
°C. H NMR (400 MHz, CDCl3) δ 7.66 – 7.60 (m, 1H), 7.57 –
7.49 (m, 3H), 7.40 (d, J = 8.3 Hz, 1H), 7.29 – 7.18 (m, 3H),
7.02 (d, J = 8.0 Hz, 1H) ppm. 19F NMR (376 MHz, CDCl3) δ ꢀ
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57.44 ppm. 13C NMR (100 MHz, CDCl3) δ 156.9, 156.3, HRMS (ESIꢀTOF) calcd for C16H9F4O2. [M+H]+ 309.0539,
1
2
3
4
5
6
7
8
153.4, 134.2, 133.4, 132.9, 129.3 (d, J = 4.0 Hz), 128.5, 127.3
(d, J = 1.5 Hz), 124.8, 121.9 (q, J = 273.5 Hz), 119.5, 116.8,
115.0 (q, J = 30.0 Hz) ppm. HRMS (ESIꢀTOF) calcd for
C16H10F3O2. [M+H]+ 291.0633, found 291.0627.
found 309.0542.
7ꢀchloroꢀ4ꢀphenylꢀ3ꢀ(trifluoromethyl)ꢀ2Hꢀchromenꢀ2ꢀ
one (3g): a white oil liquid (71 %, 46.0 mg) mp: 112 – 114
1
°C. H NMR (400 MHz, CDCl3) δ 7.57 – 7.52 (m, 3H), 7.41
7ꢀmethylꢀ4ꢀphenylꢀ3ꢀ(trifluoromethyl)ꢀ2Hꢀchromenꢀ2ꢀ
(s, 1H), 7.29 – 7.22 (m, 2H), 7.17 (dd, J = 8.7 Hz, J = 2.0 Hz,
1H), 6.95 (d, J = 8.6 Hz, 1H) ppm. 19F NMR (376 MHz,
CDCl3) δ ꢀ 57.47 ppm. 13C NMR (100 MHz, CDCl3) δ 156.3,
155.7, 153.6, 140.4, 132.4, 130.2, 129.6, 128.7, 127.2 (d, J =
1.5 Hz), 125.5, 121.7 (q, J = 273.6 Hz), 118.2, 117.0, 114.9 (q,
one (3b): a pale white crystalline solid (70 %, 42.5 mg)
1
mp:129 – 130 °C. H NMR (400 MHz, CDCl3) δ 7.55 – 7.48
(m, 3H), 7.28 – 7 .22 (m, 2H), 7.20 (s, 1H), 7.00 (d, J = 8.2
Hz, 1H), 6.88 (d, J = 8.2 Hz, 1H), 2.46 (s, 3H) ppm. 19F NMR
(376 MHz, CDCl3) δ ꢀ 57.26 ppm. 13C NMR (100 MHz,
CDCl3) δ 157.0, 156.7, 153.6, 146.0, 133.1, 129.2, 129.0,
128.4, 127.3 (d, J = 1.6 Hz), 126.1, 122.1 (q, J = 273.3 Hz)
117.1, 117.0, 113.8 (q, J = 29.8 Hz), 21.8 ppm. HRMS (ESIꢀ
TOF) calcd for C17H12F3O2. [M+H]+ 305.0789, found
305.0788.
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12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
J
=
30.3 Hz) ppm. HRMS (ESIꢀTOF) calcd for
C16H8ClF3O2Na. [M+Na]+ 347.0063, found 347.0069.
7ꢀbromoꢀ4ꢀphenylꢀ3ꢀ(trifluoromethyl)ꢀ2Hꢀchromenꢀ2ꢀ
one (3h): a pale white crystalline solid (75 %, 55.2 mg) mp:
1
140 – 142 °C. H NMR (400 MHz, CDCl3) δ 7.58 (d, J = 1.7
Hz, 1H), 7.56 – 7.51 (m, 3H), 7.32 (dd, J = 8.6Hz, J = 1.8 Hz,
1H), 7.27 – 7.21 (m, 2H), 6.87 (d, J = 8.6 Hz, 1H) ppm. 19F
NMR (376 MHz, CDCl3) δ ꢀ 57.52 ppm. 13C NMR (100 MHz,
CDCl3) δ 156.4, 155.6, 153.5, 132.4, 130.2, 129.6, 129.0,
128.6 (d, J = 6.4 Hz), 128.3, 127.2 (d, J = 1.6 Hz), 121.7 (q, J
= 273.6 Hz), 120.1, 118.5, 115.2 (q, J = 30.5 Hz) ppm. HRMS
(ESIꢀTOF) calcd for C16H9BrF3O2. [M+H]+ 368.9738, found
368.9733.
7ꢀethylꢀ4ꢀphenylꢀ3ꢀ(trifluoromethyl)ꢀ2Hꢀchromenꢀ2ꢀone
(3c): a pale white crystalline solid (72 %, 45.8 mg) mp: 100 –
1
101 °C. H NMR (400 MHz, CDCl3) δ 7.56 – 7.48 (m, 3H),
7.27 – 7.22 (m, 3H), 7.04 (d, J = 8.3 Hz, 1H), 6.91 (d, J = 8.3
Hz, 1H), 2.75 (q, J = 7.6 Hz, 2H), 1.27 (t, J = 7.6 Hz, 3H)
ppm. 19F NMR (376 MHz, CDCl3) δ ꢀ 57.26 ppm. 13C NMR
(100 MHz, CDCl3) δ 157.0, 156.7, 153.7, 152.2, 133.1, 129.2,
129.1, 128.4, 127.3 (d, J = 1.6 Hz), 125.0, 122.1 (q, J =
273.3Hz), 115.7, 113.9 (q, J = 30.0 Hz), 29.0, 14.9 ppm.
HRMS (ESIꢀTOF) calcd for C18H14F3O2. [M+H]+ 319.0946,
7ꢀiodineꢀ4ꢀphenylꢀ3ꢀ(trifluoromethyl)ꢀ2Hꢀchromenꢀ2ꢀ
one (3i): a pale white crystalline solid (74 %, 61.6 mg) mp:
1
found 319.0940
.
155 – 157 °C. H NMR (400 MHz, CDCl3) δ 7.79 (d, J = 1.4
Hz, 1H), 7.57 – 7.49 (m, 4H), 7.25 – 7.20 (m, 2H), 6.68 (d, J =
8.5 Hz, 1H) ppm. 19F NMR (376 MHz, CDCl3) δ ꢀ 57.53 ppm.
13C NMR (100 MHz, CDCl3) δ 156.4, 155.5, 153.1, 134.2,
132.4, 130.0, 129.6, 128.6, 127.2 (d, J = 1.5 Hz), 126.0, 121.8
(q, J = 273.7 Hz), 119.0, 115.4 (q, J = 31.2 Hz), 100.6 ppm.
HRMS (ESIꢀTOF) calcd for C16H8IF3O2Na. [M+Na]+
438.9419, found 438.9424.
7ꢀisopropylꢀ4ꢀphenylꢀ3ꢀ(trifluoromethyl)ꢀ2Hꢀchromenꢀ
2ꢀone (3d): a pale white crystalline solid (72 %, 45.8 mg)
1
mp: 115 – 117 °C. H NMR (400 MHz, CDCl3) δ 7.55 – 7.49
(m, 3H), 7.28 – 7.22 (m, 3H), 7.09 – 7.05 (m, 1H), 6.92 (d, J =
8.3 Hz, 1H), 3.00 (dt, J = 13.7, J = 6.9 Hz, 1H), 1.27 (d, J =
6.9 Hz, 6H) ppm. 19F NMR (376 MHz, CDCl3) δ ꢀ 57.27 ppm.
13C NMR (100 MHz, CDCl3) δ 156.9, 156.7 (d, J = 7.2 Hz),
153.8, 133.2, 129.2 (d, J = 3.7 Hz), 128.4, 127.3 (d, J = 1.5
Hz), 126.7, 123.6, 122.1 (q, J = 273.4 Hz), 117.4, 114.4, 113.9
(q, J = 30.1 Hz), 34.3, 23.5 ppm. HRMS (ESIꢀTOF) calcd for
C19H16F3O2. [M+H]+ 333.1102, found 333.1102.
4ꢀphenylꢀ3,7ꢀdiꢀ(trifluoromethyl)ꢀ2Hꢀchromenꢀ2ꢀone
(3j): a pale white crystalline solid (80 %, 57.2 mg) mp：100
1
– 102 °C. H NMR (400 MHz, CDCl3) δ 7.66 (s, 1H), 7.59 –
7.53 (m, 3H), 7.44 (d, J = 8.4 Hz, 1H), 7.29 – 7.24(m, 2H),
7.18 (d, J = 8.4 Hz, 1H) ppm. 19F NMR (376 MHz, CDCl3) δ ꢀ
57.82, ꢀ 63.31 ppm. 13C NMR (100 MHz, CDCl3) δ 155.8,
155.3, 153.1, 135.4 (q, J = 33.6 Hz), 132.1, 130.3, 129.8,
128.8, 127.2 (d, J = 1.5 Hz),123.1 (q, J = 270.6 Hz), 122.1,
121.5 (q, J = 273.9 Hz), 121.2 (d, J = 3.4 Hz), 117.0 (q, J =
30.4 Hz), 114.3 (q, J = 3.9 Hz) ppm. HRMS (ESIꢀTOF) calcd
for C17H9F6O2. [M+H]+ 359.0507, found 359.0509.
7ꢀ(tertꢀbutyl)ꢀ4ꢀphenylꢀ3ꢀ(trifluoromethyl)ꢀ2Hꢀchromenꢀ
2ꢀone (3e): a pale white crystalline solid (85 %, 58.8 mg)
1
mp: 228 – 230 °C. H NMR (400 MHz, CDCl3) δ 7.55 – 7.49
(m, 3H), 7.40 (d, J = 1.8 Hz, 1H), 7.27 – 7.21 (m, 3H), 6.93
(d, J = 8.5 Hz, 1H), 1.34 (s, 9H) ppm. 19F NMR (376 MHz,
CDCl3) δ ꢀ 57.27 ppm. 13C NMR (100 MHz, CDCl3) δ 159.1,
156.8 (d, J = 4.8 Hz), 153.6, 133.1, 129.2, 128.8, 128.4, 127.3
(d, J = 1.0 Hz), 122.4, 122.1 (q, J = 273.4 Hz), 117.0, 114.0
(q, J = 28.6 Hz), 113.6, 35.4, 30.9 ppm. HRMS (ESIꢀTOF)
calcd for C20H18F3O2. [M+H]+ 347.1259, found 347.1253.
4ꢀphenylꢀ3ꢀ(trifluoromethyl)ꢀ7ꢀ(trifluoromethoxy)ꢀ2Hꢀ
chromenꢀ2ꢀone (3k): a pale white crystalline solid (79 %,
59.0 mg) mp: 64 – 66 °C. H NMR (400 MHz, CDCl3) δ 7.60
– 7.50 (m, 3H), 7.30 – 7.21 (m, 3H), 7.11 – 7.01 (m, 2H) ppm.
19F NMR (376 MHz, CDCl3) δ ꢀ 57.58, ꢀ 57.78 ppm. 13C NMR
(100 MHz, CDCl3) δ 156.1, 155.7, 154.2, 152.9, 132.4, 131.0,
129.6, 128.7, 127.2 (d, J = 1.5 Hz), 121.7 (q, J = 273.7 Hz),
120.2 (q, J = 258.9 Hz), 117.8, 116.8, 115.0 (q, J = 30.0 Hz),
108.5 ppm. HRMS (ESIꢀTOF) calcd for C17H8F6O3Na.
[M+Na]+ 397.0275, found 397.0270.
1
7ꢀfluoroꢀ4ꢀphenylꢀ3ꢀ(trifluoromethyl)ꢀ2Hꢀchromenꢀ2ꢀ
one (3f): a pale yellow crystalline solid (72 %, 44.3 mg) mp:
1
113 – 115 °C. H NMR (400 MHz, CDCl3) δ 7.58 – 7.50 (m,
3H), 7.28 – 7.21 (m, 2H), 7.12 (dd, J = 8.6 Hz, J = 2.4 Hz,
1H), 7.05 – 6.99 (m, 1H), 6.97 – 6.90 (m, 1H) ppm. 19F NMR
(376 MHz, CDCl3) δ ꢀ 57.41, ꢀ 101.20 ppm. 13C NMR (100
MHz, CDCl3) δ 165.8 (d, J = 256.8 Hz), 156.2 (d, J = 46.8
Hz), 154.8 (d, J = 13.3 Hz), 135.5, 132.7, 131.4 (d, J = 10.5
Hz), 129.5, 128.6, 127.2 (d, J = 1.5 Hz), 121.8 (q , J = 273.5
Hz), 116.3 (dd, J = 13.1 Hz, J = 10.5 Hz), 114.0 (q, J =
30.1Hz) 113.1 (d, J = 22.4 Hz), 104.3 (d, J = 25.5 Hz) ppm.
7ꢀcarboxylateꢀ4ꢀphenylꢀ3ꢀ(trifluoromethyl)ꢀ2Hꢀ
chromenꢀ2ꢀone (3l): a pale white crystalline solid (61 %,
42.5 mg) mp: 122 – 124 °C. H NMR (400 MHz, CDCl3) δ
8.01 (d, J = 1.4 Hz, 1H), 7.82 (dd, J = 8.4 Hz, J = 1.5 Hz, 1H),
1
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TOF) calcd for C17H9F6O2. [M+H]+, 359.0507, found
Page 6 of 9
7.60 – 7.53 (m, 3H), 7.29 – 7.23 (m, 2H), 7.10 (d, J = 8.4 Hz,
1H), 3.97 (s, 3H) ppm. 19F NMR (376 MHz, CDCl3) δ ꢀ 57.70
ppm. 13C NMR (100 MHz, CDCl3) δ 165.1, 156.0, 155.7,
153.0, 135.0, 132.4, 129.6, 129.4, 128.7, 127.3 (d, J = 1.6 Hz),
125.1, 122.7, 121.6 (q, J = 273.9 Hz), 118.0, 116.7 (q, J = 30.0
Hz), 52.9 ppm. HRMS (ESIꢀTOF) calcd for C18H11F3O4Na.
[M+Na]+ 371.0507, found 371.0510.
359.0510.
1
2
3
4
5
6
7
8
4ꢀphenylꢀ3,8ꢀdiꢀ(trifluoromethyl)ꢀ2Hꢀchromenꢀ2ꢀone
(3q'): a pale yellow crystalline solid (50 %, 36.0 mg) mp: 102
– 104 °C. 1H NMR (400 MHz, CDCl3) δ 7.89 – 7.84 (m, 1H),
7.61 – 7.56 (m, 3H), 7.53 (d, J = 8.8 Hz, 1H), 7.29 – 7.25 (m,
3H) ppm. 19F NMR (376 MHz, CDCl3) δ ꢀ 57.74, ꢀ 63.38 ppm.
13C NMR (100 MHz, CDCl3) δ 156.1, 155.3, 155.2, 131.7,
130.6 (d, J = 3.2 Hz), 129.9, 128.9, 127.2 (d, J = 1.6 Hz),
126.6 (q, J = 4.1 Hz), 123.1 (q, J = 270.7 Hz), 121.5 (q, J =
273.8 Hz), 119.7, 117.9, 116.4 (q, J = 30.7 Hz) ppm. HRMS
(ESIꢀTOF) calcd for C17H9F6O2. [M+H]+ 359.0507, found
359.0501.
7ꢀcyanoꢀ4ꢀphenylꢀ3ꢀ(trifluoromethyl)ꢀ2Hꢀchromenꢀ2ꢀ
one (3m): a pale white crystalline solid (57 %, 35.9 mg) mp:
158 – 160 °C. H NMR (400 MHz, CDCl3) δ 7.69 (d, J = 1.4
Hz, 1H), 7.60 – 7.54 (m, 3H), 7.48 – 7.42 (m, 1H), 7.28 – 7.23
(m, 2H), 7.15 (d, J = 8.3 Hz, 1H) ppm. 19F NMR (376 MHz,
CDCl3) δ ꢀ 57.86 ppm. 13C NMR (100 MHz, CDCl3) δ 155.5,
154.8, 152.9, 131.7, 130.3, 130.0, 128.9, 127.6, 127.2 (d, J =
1.5 Hz), 123.0, 121.3 (q, J = 274.0 Hz), 120.6, 117.5 (q, J =
27.2 Hz), 116.9, 116.8 ppm. HRMS (ESIꢀTOF) calcd for
C17H8F3NO2Na. [M+Na]+ 338.0405, found 338.0399.
9
1
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
6ꢀmethylꢀ4ꢀphenylꢀ3ꢀ(trifluoromethyl)ꢀ2Hꢀchromenꢀ2ꢀ
one (3r): a pale yellow crystalline solid (48 %, 29.2 mg) mp:
1
174 – 176 °C. H NMR (400 MHz, CDCl3) δ 7.57 – 7.50 (m,
3H), 7.43 (m, 1H), 7.30 (d, J = 8.4 Hz, 1H), 7.27 – 7.22 (m,
2H), 6.76 (s, 1H), 2.27 (s, 3H) ppm. 19F NMR (376 MHz,
CDCl3) δ ꢀ 57.34 ppm. 13C NMR (100 MHz, CDCl3) δ 156.9,
156.6, 151.6, 135.2, 134.7, 133.0, 129.3, 128.8, 128.5, 127.3
(d, J = 1.5 Hz), 122.0 (q, J = 273.5 Hz), 119.1, 116.6, 114.9
(q, J = 29.7 Hz), 20.90 ppm. HRMS (ESIꢀTOF) calcd for
C17H12F3O2. [M+H]+ 305.0789, found 305.0787.
7ꢀ(sꢀmethyl)ꢀ4ꢀphenylꢀ3ꢀ(trifluoromethyl)ꢀ2Hꢀchromenꢀ
2ꢀone (3n): a pale yellow crystalline solid (60 %, 40.3 mg) m
p: 78 – 80 °C. 1H NMR (400 MHz, CDCl3) δ 7.55 – 7.50 (m, 3
H), 7.26 – 7.22 (m, 2H), 7.20 (s, 1H), 7.01 (d, J = 8.3 Hz, 1H),
6.88 (d, J = 8.2 Hz, 1H), 2.46 (s, 3H) ppm. 19F NMR (376 M
Hz, CDCl3) δ ꢀ 57.14 ppm. 13C NMR (100 MHz, CDCl3) δ 157
.1, 156.4, 151.8, 135.3, 133.3, 129.2, 128.4, 127.3 (d, J = 1.6
Hz), 127.0, 126.4, 126.1, 122.0 (q, J = 273.4 Hz), 119.3, 114.7
(q, J = 30.0 Hz), 15.5 ppm. HRMS (ESIꢀTOF) calcd for C17H
12F3O2S. [M+H]+ 337.0510, found 337.0505.
8ꢀmethylꢀ4ꢀphenylꢀ3ꢀ(trifluoromethyl)ꢀ2Hꢀchromenꢀ2ꢀ
one (3r'): a yellow oil liquid (24 %, 14.6 mg) mp: 115 – 117
1
°C. H NMR (400 MHz, CDCl3) δ 7.54 – 7.49 (m, 3H), 7.47
(d, J = 7.4 Hz, 1H), 7.26 – 7.22 (m, 2H), 7.09 (t, J = 7.8 Hz,
1H), 6.83 (d, J = 8.0 Hz, 1H), 2.51 (s, 3H) ppm. 19F NMR
(376 MHz, CDCl3) δ ꢀ 57.41 ppm. 13C NMR (100 MHz,
CDCl3) δ 157.2, 156.5, 151.9, 135.3, 133.2, 129.2, 128.4,
127.3 (d, J = 1.6 Hz), 127.0, 126.4, 124.2, 122.0 (q, J = 273.4
Hz), 119.3, 114.7 (q, J = 30.2 Hz), 15.5 ppm. HRMS (ESIꢀ
TOF) calcd for C17H12F3O2. [M+H]+ 305.0789, found
305.0790.
5,7ꢀdifluoroꢀ4ꢀphenylꢀ3ꢀ(trifluoromethyl)ꢀ2Hꢀchromenꢀ
2ꢀone (3o): a pale white crystalline solid (76 %, 49.6 mg)
1
mp: 101 – 103 °C. H NMR (400 MHz, CDCl3) δ 7.59 –
7.51(m, 3H), 7.27 – 7.23 (m, 1H), 7.15 – 7.00 (m, 2H), 6.98 –
6.90 (m, 1H) ppm. 19F NMR (376 MHz, CDCl3) δ ꢀ 61.87, ꢀ
111.45 (d, J = 6.4 Hz), 122.53 (d, J = 6.3 Hz) ppm. 13C NMR
(100 MHz, CDCl3) δ 156.0, 154.2, 150.6 (d, J = 36.3 Hz),
133.1, 132.3, 131.1 (q, J = 4.5 Hz), 129.7, 128.8, 127.2 (d, J =
1.6 Hz), 124.0, 122.1 (q, J = 271.8 Hz) 121.5 (q, J = 274.0
5ꢀcyanoꢀ4ꢀphenylꢀ3ꢀ(trifluoromethyl)ꢀ2Hꢀchromenꢀ2ꢀ
one (3t): a pale white crystalline solid (51 %, 32.1 mg) mp:
Hz), 120.5, 118.8 (q, J = 31.6 Hz). HRMS (ESIꢀTOF)）calcd
for C16H8F5O2. [M+H]+ 327.0444, found 327.0439.
1
120 – 122 °C. H NMR (400 MHz, CDCl3) δ 7.66 – 7.60 (m,
1H), 7.56 – 7.51 (m, 3H), 7.42 (d, J = 8.3 Hz, 1H), 7.27 (s,
1H), 7.25 (s, 1H), 7.23 – 7.18 (m, 1H), 7.02 (dd, J = 8.1 Hz, J
= 1.3 Hz, 1H) ppm. 19F NMR (376 MHz, CDCl3) δ ꢀ 57.46
ppm. 13C NMR (100 MHz, CDCl3) δ 156.8, 156.3, 153.5,
143.3, 134.1, 132.9, 132.6, 129.3 (d, J = 5.1 Hz), 128.5, 127.3
(d, J = 1.5 Hz), 124.8, 121.9 (q, J = 273.7 Hz), 119.5, 116.9,
115.1 (q, J = 30.1 Hz) ppm. HRMS (ESIꢀTOF) calcd for
C17H8F3NO2Na. [M+Na]+ 338.0405, found 338.0399.
6,8ꢀdimethylꢀ4ꢀphenylꢀ3ꢀ(trifluoromethyl)ꢀ2Hꢀchromenꢀ
2ꢀone (3p): a pale white crystalline solid (80 %, 50.8 mg)
1
mp: 109 – 111 °C. H NMR (400 MHz, CDCl3) δ 7.57 – 7.47
(m, 3H), 7.29 (s, 1H), 7.25 – 7.19 (m, 2H), 6.58 (s, 1H), 2.46
(s, 3H), 2.22 (s, 3H) ppm. 19F NMR (376 MHz, CDCl3) δ ꢀ
57.30 ppm. 13C NMR (100 MHz, CDCl3) δ 157.1, 156.6,
150.0, 136.6, 133.9, 133.4, 129.1, 128.4, 127.3 (d, J = 1.6 Hz),
126.5, 126.0, 122.1 (q, J = 273.4 Hz), 119.0, 114.5 (q, J = 29.9
Hz), 20.8, 15.4 ppm. HRMS (ESIꢀTOF) calcd for C18H14F3O2.
[M+H]+ 319.0946, found 319.0940.
4ꢀmethylꢀ7ꢀ(tertꢀbutyl)ꢀ3ꢀ(trifluoromethyl)ꢀ2Hꢀchromenꢀ
2ꢀone (5a): a yellow crystalline solid (57 %, 32.4 mg) mp:
1
148 – 150 °C. H NMR (400 MHz, CDCl3) δ 7.73 (d, J = 8.5
Hz, 1H), 7.41 (dd, J = 8.6 Hz, J = 1.9 Hz, 1H), 7.36 – 7.33 (m,
1H), 2.66 (s, 3H), 1.36 (s, 9H) ppm. 19F NMR (376 MHz,
CDCl3) δ ꢀ 56.70 ppm. 13C NMR (100 MHz, CDCl3) δ 158.9,
156.2, 154.8, 153.2, 125.5, 123.0 (q, J = 273.3 Hz), 122.5,
116.6, 114.4 (q, J = 30.3 Hz),113.8, 35.4, 30.9, 15.6 ppm.
HRMS (ESIꢀTOF) calcd for C15H15F3O2Na. [M+Na]+
307.0922, found 307.0916.
4ꢀphenylꢀ3,6ꢀdiꢀ(trifluoromethyl)ꢀ2Hꢀchromenꢀ2ꢀone
(3q): a pale yellow crystalline solid (34 %, 24.1 mg) mp: 129
1
– 131 °C. H NMR (400 MHz, CDCl3) δ 7.91 (d, J = 7.5 Hz,
1H), 7.56 (dd, J = 4.9Hz, J = 1.7 Hz, 3H), 7.31 – 7.27 (m,
2H), 7.25 – 7.20 (m, 2H) ppm. 19F NMR (376 MHz, CDCl3) δ
ꢀ 57.74, ꢀ 63.72 ppm. 13C NMR (100 MHz, CDCl3) δ 156.1,
155.3, 155.2, 131.7, 130.6, 129.9, 128.9, 127.6, 127.2, 126.6
(d, J = 4.0 Hz), 123.1 (q, J = 270.6 Hz), 121.5 (q, J = 274.0
Hz), 119.7, 117.9, 116.4 (q, J = 31.3 Hz) ppm. HRMS (ESIꢀ
7ꢀ(tertꢀbutyl)ꢀ4ꢀ(2ꢀtolyl)ꢀ3ꢀ(trifluoromethyl)ꢀ2Hꢀ
chromenꢀ2ꢀone (5b): a pale yellow crystalline solid (72 %,
1
50.4 mg) mp: 202 – 204 °C. H NMR (400 MHz, CDCl3) δ
6
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The Journal of Organic Chemistry
7.47 – 7.37 (m, 2H), 7.36 – 7.28 (m, 2H), 7.22 (dd, J = 8.5, 1.8
128.1, 122.8, 121.8 (q, J = 273.3 Hz), 118.0, 116.0, 114.3 (q, J
= 30.7 Hz), 113.9, 113.5, 35.6, 30.8 ppm. HRMS (ESIꢀTOF)
calcd for C21H17NF3O2. [M+H]+ 372.1211, found 372.1210.
1
2
3
4
5
6
7
8
Hz, 1H), 7.07 (d, J = 7.3 Hz, 1H), 6.80 (d, J = 8.5 Hz, 1H),
2.11 (s, 3H), 1.34 (s, 9H) ppm. 19F NMR (376 MHz, CDCl3) δ
ꢀ 59.18 ppm. 13C NMR (100 MHz, CDCl3) δ 159.2, 156.8,
156.7, 153.6, 134.4, 132.9, 130.2, 129.2, 128.2, 127.0 (d, J =
1.4 Hz), 125.9, 122.6, 122.1 (q, J = 273.3 Hz), 116.3, 114.3 (q,
J = 29.8 Hz), 113.7, 35.5, 30.9, 19.4 ppm. HRMS (ESIꢀTOF)
calcd for C21H20F3O2. [M+H]+ 361.1415, found 361.1410.
7ꢀ(tertꢀbutyl)ꢀ4ꢀ(4ꢀtrifluoromethphenyl)ꢀ3ꢀ
(trifluoromethyl)ꢀ2Hꢀchromenꢀ2ꢀone (5h): a pale white
1
crystalline solid (82 %, 67.8 mg) mp: 157 – 159 °C. H NMR
(400 MHz, CDCl3) δ 7.82 (d, J = 8.1 Hz, 2H), 7.49 – 7.39 (m,
3H), 7.32 – 7.26 (m, 1H), 6.86 (d, J = 8.5 Hz, 1H), 1.36 (s,
9H) ppm. 19F NMR (376 MHz, CDCl3) δ ꢀ 57.26, ꢀ 62.84 ppm.
13C NMR (100 MHz, CDCl3) δ 159.7, 156.3, 155.1, 153.6,
136.9, 131.5 (q, J = 32.7 Hz), 128.4, 127.9 (d, J = 1.4 Hz),
125.5 (q, J = 3.6 Hz), 123.8 (q, J = 270.7 Hz), 122.7, 121.9 (q,
J = 273.4 Hz), 116.3, 114.3 (q, J = 30.5 Hz), 113.8, 35.5, 30.8
ppm. HRMS (ESIꢀTOF) calcd for C21H17F6O2. [M+H]+
415.1133, found 415.1129.
7ꢀ(tertꢀbutyl)ꢀ4ꢀ(4ꢀmethoxyphenyl)ꢀ3ꢀ(trifluoromethyl)ꢀ
9
2Hꢀchromenꢀ2ꢀone (5c): a yellow crystalline solid (78 %,
1
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
58.6 mg) mp: 95 – 97 °C. H NMR (400 MHz, CDCl3) δ 7.40
(d, J = 1.8 Hz, 1H), 7.25 (dd, J = 8.5 Hz, J = 1.8 Hz, 1H), 7.20
– 7.15 (m, 2H), 7.04 (d, J = 8.6 Hz, 3H), 3.90 (s, 3H), 1.34 (s,
9H) ppm. 19F NMR (376 MHz, CDCl3) δ ꢀ 57.14 ppm. 13C
NMR (100 MHz, CDCl3) δ 160.3, 159.0, 156.9 (d, J = 9.6
Hz), 153.5, 130.9, 130.1, 128.9 (d, J = 1.7 Hz), 125.1, 122.4,
122.2 (q, J = 273.3 Hz), 117.3, 114.2, 113.9, 113.6, 55.4, 35.4,
30.9 ppm. HRMS (ESIꢀTOF) calcd for C21H20F3O3. [M+H]+
377.1365, found 377.1359.
■
ASSOCIATED CONTENT
7ꢀ(tertꢀbutyl)ꢀ4ꢀ(4ꢀfluorophenyl)ꢀ3ꢀ(trifluoromethyl)ꢀ2Hꢀ
Supporting Information.
chromenꢀ2ꢀone (5d): a pale white crystalline solid (85 %,
1
61.8 mg) mp: 142 – 144 °C. H NMR (400 MHz, CDCl3) δ
The Supporting Information is available free of charge on the
ACS Publications website at DOI: 10.1021/acs.joc.xxxxxxx.
7.41 (d, J = 1.7 Hz, 1H), 7.31–7.19 (m, 5H), 6.94 (d, J = 8.5
Hz, 1H), 1.35 (s, 9H) ppm. 19F NMR (376 MHz, CDCl3) δ ꢀ
57.18, ꢀ 111.40 ppm. 13C NMR (100 MHz, CDCl3) δ 163.1 (d,
J = 248.0 Hz), 159.4, 156.2 (d, J = 62.4 Hz), 153.5, 129.3 (d, J
= 6.8 Hz), 129.0 (d, J = 3.5 Hz), 128.6, 122.6, 122.0 (q, J =
273.7 Hz), 116.9, 115.9, 115.7, 114.3 (q, J = 29.4 Hz), 113.7,
35.5, 30.8 ppm. HRMS (ESIꢀTOF) calcd for C20H16F4O2Na.
[M+Na]+ 387.0984, found 387.0979.
1
Xꢀray crystallographic data of 3b, 3q and 3r; copies of H, 13C
and 19F NMR spectra for all compounds (PDF)
Crystallographic data for 3b (CIF), CCDC 1573908
Crystallographic data for 3q (CIF), CCDC 1573909
Crystallographic data for 3r (CIF), CCDC 1573910
■
AUTHOR INFORMATION
Corresponding Author
7ꢀ(tertꢀbutyl)ꢀ4ꢀ(4ꢀchlorophenyl)ꢀ3ꢀ(trifluoromethyl)ꢀ
2Hꢀchromenꢀ2ꢀone (5e): a pale white crystalline solid (75
%, 57.0 mg) mp: 173 – 175 °C. 1H NMR (400 MHz, CDCl3) δ
7.67 (d, J = 8.2 Hz, 2H), 7.41 (d, J = 1.8 Hz, 1H), 7.28 – 7.23
(m, 1H), 7.14 (d, J = 8.3 Hz, 2H), 6.92 (d, J = 8.5 Hz, 1H),
1.34 (s, 9H). 19F NMR (376 MHz, CDCl3) δ ꢀ 57.15 ppm. 13C
NMR (100 MHz, CDCl3) δ 159.5, 156.4, 155.5, 153.6, 132.0,
131.8, 129.0 (d, J = 1.5 Hz), 128.5, 123.6, 122.6, 122.0 (q, J =
273.3 Hz), 116.5, 114.2 (q, J = 30.0 Hz), 113.7, 35.5, 30.9
ppm. HRMS (ESIꢀTOF) calcd for C20H17ClF3O2. [M+H]+
381.0869, found 381.0864.
*Email: wangtao@jxnu.edu.cn
*Email: xiongfei@jxnu.edu.cn
Notes
The authors declare no competing financial interest.
■
ACKNOWLEDGMENT
We gratefully acknowledge to the National Natural Science
Foundation of China (21562026, 21762025), the Natural Science
Foundation of Jiangxi Province (20161BAB203084), and Jiangxi
Educational Committee (GJJ150362) for financial support.
We also thank Prof. X. Peng (Dept. of Chem. and Biochem., Univ.
of Wisconsin Milwaukee).
7ꢀ(tertꢀbutyl)ꢀ4ꢀ(4ꢀbromophenyl)ꢀ3ꢀ(trifluoromethyl)ꢀ
2Hꢀchromenꢀ2ꢀone (5f): a pale white crystalline solid (81
%, 68.7 mg) mp: 178 – 179 °C. 1H NMR (400 MHz, CDCl3) δ
7.67 (d, J = 8.4 Hz, 2H), 7.42 (d, J = 1.7 Hz, 1H), 7.30 – 7.24
(m, 1H), 7.15 (d, J = 8.4 Hz, 2H), 6.94 (d, J = 8.5 Hz, 1H),
1.35 (s, 9H) ppm. 19F NMR (376 MHz, CDCl3) δ ꢀ 57.14 ppm.
13C NMR (100 MHz, CDCl3) δ 159.5, 156.4, 155.5, 153.6,
132.0, 131.8, 129.0 (d, J = 1.5 Hz), 128.5, 123.6, 122.6, 122.0
(q, J = 273.3 Hz), 116.5, 114.2 (q, J = 30.0 Hz), 113.7, 35.5,
30.9 ppm. HRMS (ESIꢀTOF) calcd for C20H16BrF3O2Na.
[M+Na]+ 447.0183, found 447.0184.
■
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The Journal of Organic Chemistry
gh sp(3) Fraction Using the Photoredox Coupling of Organotriflu
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