Recyclable alkylated Ru(bpy)32+ complex as a visible-light photoredox catalyst for perfluoroalkylation

Article abstract of DOI:10.1016/j.tet.2018.01.040

A recyclable Ruthenium tris [4,4′-bis (dinonylmethyl)-2,2′-bipyridine] (Ru[(DNM)₂bpy]₃²⁺) photocatalyst (PC) was synthesized. Hexane-phase-selective solubility allowed its simple and efficient separation from reaction products via solvent extraction. The excellent catalytic activity and recoverability were demonstrated in batch and flow perfluoroalkylation reactions of coumarin under visible-light irradiation. High reaction rates and easy reusability of the catalyst make this approach attractive for large-scale applications.

Full text of DOI:10.1016/j.tet.2018.01.040

Accepted Manuscript
2+
Recyclable alkylated Ru(bpy)
perfluoroalkylation
complex as a visible-light photoredox catalyst for
3
Xiaodan Zhang, Yaming Li, Xinyu Hao, Kun Jin, Rong Zhang, Chunying Duan
PII:
S0040-4020(18)30088-7
10.1016/j.tet.2018.01.040
TET 29255
DOI:
Reference:
To appear in: Tetrahedron
Received Date: 22 October 2017
Revised Date: 18 January 2018
Accepted Date: 22 January 2018
Please cite this article as: Zhang X, Li Y, Hao X, Jin K, Zhang R, Duan C, Recyclable alkylated
2+
Ru(bpy)
doi: 10.1016/j.tet.2018.01.040.
complex as a visible-light photoredox catalyst for perfluoroalkylation, Tetrahedron (2018),
3
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Recyclable alkylated Ru(bpy)32+ complex as a visible-
light photoredox catalyst for perfluoroalkylation
Xiaodan Zhang, Yaming Li*, Xinyu Hao, Kun Jin, Rong Zhang and Chunying Duan*
State Key Laboratory of Fine Chemicals, Dalian University of Technology
Dalian, 116024, China, Tel./fax: +86-411-84986295; E-mail: ymli@dlut.edu.cn (Y. Li)

1
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Tetrahedron
journal homepage: www.elsevier.com
2+
Recyclable alkylated Ru(bpy)3 complex as a visible-light photoredox catalyst for
perfluoroalkylation
Xiaodan Zhang, Yaming Li*, Xinyu Hao, Kun Jin, Rong Zhang and Chunying Duan*
State Key Laboratory of Fine Chemicals, Dalian University of Technology,
Dalian 116024, China. Tel./fax: +86-411-84986295; E-mail: ymli@dlut.edu.cn (Y. Li)
ARTICLE INFO
ABSTRACT
2+
A recyclable Ruthenium tris [4,4’-bis (dinonylmethyl)-2,2’-bipyridine] (Ru[(DNM)2bpy]3
)
Article history:
Received
Received in revised form
Accepted
photocatalyst (PC) was synthesized. Hexane-phase-selective solubility allowed its simple and
efficient separation from reaction products via solvent extraction. The excellent catalytic
activity and recoverability were demonstrated in batch and flow perfluoroalkylation reactions
of coumarin under visible-light irradiation. High reaction rates and easy reusability of the catalyst
make this approach attractive for large-scale applications.
Available online
Keywords:
coumarin
2009 Elsevier Ltd. All rights reserved
.
perfluoroalkylation
visible light
recoverable photocatalyst
1. Introduction
based heterogeneous complex immobilized by polyacrylate,
which was used to catalyze the aerobic phosphonylation of N-
aryl tetrahydroisoquinolines under visible light. Bergbreiter
separately carried out the polymeric reaction, oxidative C-C
bond cleavage of aldehydes and [2+2] cycloaddition of
bis(enone)s in 20139a and 20169b catalyzed by
polyisobutylene (PIB)-polymer-tagged Ru complexes, which
could be recycled by extraction with heptane.
Visible light can serve as an attractive, sustainable, non-
toxic, easy to use and universally available energy source.
Photocatalysis involving visible light to trigger reactions is
an alternative type of catalysis and a variety of photoredox
catalysts have been used for a broad range of synthetic
transformations including trifluoromethylation of arenes and
heteroarenes, which are the fundamental building blocks of
many top-selling pharmaceuticals and agrochemicals1.
MacMillan reported on
a
strategy for the direct
trifluoromethylation of unactivated arenes and heteroarenes
using a Ru complex photocatalyst (PC) and a household
light bulb2-4. Following this report, more intensive research
on visible light photocatalyzed trifluoromethylation has been
pursued in recent years. In 2015, Stephenson5 reported a
strategy for the use of trifluoroacetic anhydride in a scalable and
operationally simple trifluoromethylation reaction using pyridine
N-oxide, via photoredox catalysis, to realize facile
decarboxylation to the CF3 radical.
2+
Several transition-metal complexes such as [Ru(phen)]3
,
[Ru(bpy)3]2+, Ir(I) complexes, [Ir(ppy)2(dtbpy)]+, and neutral
fac-Ir(ppy)3 are the most versatile PC for a broad range of
reactions owing to their long excited state lifetime and good
chemical stability6. Unfortunately, large-scale applications
in industrial area with these Ru or Ir complexes PCs are
currently limited7. Issues including catalyst cost, catalyst
toxicity or contamination, make catalyst recycling desirable.
Hence, chemists have focused on the modification of PC
ligands (Scheme 1). In 2014, Kobayashi8 reported an Ir-
Scheme 1. Reported recoverable Ru and Ir complex PCs immobilized
by polymers
A common problem encountered with the mentioned
heterogeneous catalysts is poor mass transport. Moreover,
heterogeneous supported PCs were impenetrable by visible
light, which greatly reduces the quantum yield for a given
reaction. In 2016, Reiser7 developed a (PIB-polymer-tagged)

2
Tetrahedron
fac-Ir(ppy)3
PC,
which
catalyzed
deiodination,
anhydride/pyridine N-oxide under irradiation from a blue
ACCEPTED MANUSCRIPT
deiodination/cyclization, and E/Z isomerization, and showed high
activity due to its homogeneous nature in solution. However,
since the molecular weight distribution of (PIB-polymer-tagged)
fac-Ir(ppy)3, solubility limitations (activity) and catalyst leaching
problems occured. We aimed to develop a recyclable and
homogeneous Ru complex PC with an accurate structure. Our
initial strategy was to design a long alkyl-chain-bound bipyridine
Ru complex as a phase-selectively soluble homogeneous PC that
could be extracted by hexane and reused.
light emitting diode (LED) for 12 h. When using 1 mol%
traditional Ru(bpy)3Cl2 PC and CH3CN solvent, 3-
trifluoromethyl coumarin (7a) was obtained in 63% yield
(
entry
2+
1). Next Ru[(DNM)2bpy]3
(4) was used as PC. Considering
the poor solubility of Ru[(DNM)2bpy]32+ in CH3CN, we chose a
CH3CN/CH2Cl2 mixed solvent system. After 12 h irradiation,
7a was obtained in a slightly low yield of 55% (entry 2).
Increasing the reaction time to 24 h increased the yield of 7a
to 66% (entry 3), which was comparable to that obtained
when using the Ru(bpy)3Cl2 PC. Upon further extension of
the reaction time to 36 h, the product yield remained
unchanged. Finally, when reducing the amount of catalyst to
0.5 mol%, the yield of 7a decreased to 48% (entry 5).
With particular interest in photochemistry and fluorine
chemistry, we describe herein an alkyl-bound bipyridine Ru
complex, which serves as a recoverable, reusable and hexane-
soluble PC. This PC showed good catalytic activity for the
perfluoroalkylation of coumarin under visible light, in the
presence of trifluoroacetic and pentafluoropropionic anhydride as
the CF3 and C2F5 sources, respectively. The reaction proceeded
on a range of substrates and had been demonstrated on a
significant scale in both batch and flow reactor.
Table 1 Optimization of the trifluoromethylation reaction conditionsa
2. Results and discussion
Entry
Photocatalyst (PC)
Ru(bpy)3Cl2
Solvent
Time
12
Yield(%)
63
1
2
CH3CN
2+
Ru[(DNM)2bpy]3
CH2Cl2/CH3CN (5/5)
CH2Cl2/CH3CN (5/5)
CH2Cl2/CH3CN (5/5)
CH2Cl2/CH3CN (5/5)
12
55
2+
3
Ru[(DNM)2bpy]3
24
66
2+
4
Ru[(DNM)2bpy]3
36
64
5b
Ru[(DNM)2bpy]3
24
48
2+
aReaction conditions: coumarin (0.4 mmol), PC (1 mol %), pyridine N-oxide (0.82
mmol), trifluoroacetic anhydride (0.8 mmol), and solvent (1 mL), irradiation with
15 W blue LED at room temperature; isolated yields.
Scheme 2. Recoverable alkyl-bound Ru complex photocatalyst
and recovery process.
b PC (0.5mol %)
As shown in Scheme 2, the substrate for the photochemical
2+
reaction and the Ru[(DNM)2bpy]3 PC were dissolved in an
2+
A recyclability test on the Ru[(DNM)2bpy]3 PC in the
CH3CN/CH2Cl2 mixed solvent to form a homogeneous solution
(step 1). After the completion of reaction, the solvent was
removed by vacuum evaporation (step 2). Then, two immiscible
solvents, hexane and CH3CN, were added to dissolve the residue,
leading to organic biphasic formation. The less polar PC was
extracted by hexane based on the huge solubility gap between the
nonpolar and polar solvents (step 3). The recovered PC in hexane
could be separated and reused for use in the next reaction (step 4).
trifluoromethylation of coumarin was further investigated
(Table 2). After completion of the 1st run reaction, the
CH3CN/CH2Cl2 mixed solvent was evaporated under reduced
pressure, and the residue was redissolved in CH3CN. The
2+
recycled Ru[(DNM)2bpy]3 was extracted 5 times with hexane
and collected for the next run. The product 3-trifluoromethyl
coumarin (7a) remained in the CH3CN phase, which was
desolventized by rotary evaporation and purified by silica gel
column chromatography.
As shown in Table 2, a new trifluoromethyl reaction (2nd run)
was then performed using fresh reactants under the same
2+
conditions. The recycled Ru[(DNM)2bpy]3 was collected and
reused without significant loss of catalytic activity (yield 64%).
After the 6th run, only a slight decrease in the yield (51%) of 3-
trifluoromethyl coumarin (7a) was observed. The approximate
yield (0.3%) of the residual 7a in the hexane phase was
determined by 19F-NMR using trifluoromethyl phenyl sulfide as
an internal standard. In addition, leaching of the Ru species from
the initial catalyst into the polar phase during the recycling
process was investigated. After the 1st and 6th runs, the amount of
2+
Scheme 3. Synthesis of Ru[(DNM)2bpy]3
2+
The synthesis of the Ru[(DNM)2bpy]3 PC is shown in
Scheme 3. Commercially available 4,4’-dimethyl-2,2’-dipyridine
(1) first reacted with 1-bromononane and converted to the alkyl-
bound bipyridine ligand, 4,4’-bis (dinonylmethyl)-2,2’-bipyridine,
which was then allowed to react with RuCl3 to generate the alkyl-
bound bipyridine Ru complex (4) (for detailed synthetic
procedures, see experimental section and supplementary
information).
2+
the recovered Ru[(DNM)2bpy]3 PC were 93% and 53%
respectively, corresponding to the initial amount of Ru PC used
(measured by UV-vis spectroscopy). Inductively coupled plasma
mass spectroscopy (ICP-MS) analysis revealed that the amount
of the recovered Ru species was 57% after the 6th run. Thus,
2+
To demonstrate the feasibility of the phase-selectively
soluble homogeneous PC, trifluoromethylation of coumarin
catalyzed by Ru[(DNM)2bpy]3 (4) was applied as the model
Ru[(DNM)2bpy]3
(4) showed excellent catalytic activity in the
photocatalyzed trifluoromethylation of coumarin, and could be
successfully recovered and reused for 6 cycles with no significant
loss of activity.
2+
reaction (Table 1). The reaction conditions were optimized
for the trifluoromethylation of coumarin with trifluoroacetic

3
Table 2 Yields of 3-trifluoromethyl coumarin (7a) obtained using the
Ru[(DNM)2bpy]3
studies. The potentially valuable products 7k and 8k were
ACCEPTED MANUSCRIPT
2+ a
obtained in good yields of 64% and 71%, respectively. Finally,
we extended this method to a nitrogen-containing heterocycle, N-
methyl quinolinone. As expected, the trifluoromethyl and
pentafluoroethyl N-methyl quinolinones were obtained in 65%
and 61% yields, respectively (7l, 8l).
Run
1
2
3
4
5
6
Yield (%)
66
64
64
61
57
51
aReaction conditions: coumarin (0.4 mmol), pyridine N-oxidie (0.82 mmol),
trifluoroacetic anhydride (0.8 mmol), and CH3CN (0.5 mL), CH2Cl2 (0.5 mL),
irradiation with 15 W blue LED at room temperature; isolated yields.
On the basis of the experimental results and reported
literatures11, a plausible mechanism was proposed in
Scheme 4. Initially trifluoroacetic anhydride (TFAA, 6a
was coupled by the electron-poor auxiliary pyridine
oxidant to form TFAA adduct (
irradiated by a blue LED to the excited state [Ru(II)]*
which was oxidatively quenched by with the generation of
Ru(III). The
was reduced by the excited [Ru(II)]* and
)
Having encouraged by the efficiency and recyclability of the
N-
2+
Ru[(DNM)2bpy]3
photocatalyzed trifluoromethylation of
A
). The Ru(II) PC was
coumarin, we further investigated the substrates scope for both
trifluoromethylation and pentafluoroethylation, since the latter
has rarely been explored10. Pentafluoroethylation of coumarin
was implemented under the same photocatalytic conditions using
pentafluoropropionic anhydride, which is cheap and
commercially available, instead of trifluoroacetic anhydride. As
expected, the visible light-mediated trifluoromethylation and
pentafluoroethylation of coumarins bearing electron-donating and
electron-withdrawing groups proceeded smoothly to afford the
desired products in moderate to good yields (Table 3). Both
trifluoromethyl and pentafluoroethyl coumarins were obtained in
66% and 68% yields, respectively (7a, 8a). Coumarins bearing
alkyl groups gave the corresponding trifluoromethyl and
pentafluoroethyl products in moderate yields (7b-7d, 8b-8d), for
example, 6-t-butyl coumarin gave 7d and 8d in 56% and 60%
yields, respectively. Notably, coumarins with 7-methoxy or
acetoxy groups were transformed into the desired products in
satisfactory yields (7e-7f, 8e-8f). Coumarins with a halogen (Cl-
or Br-) group were also tolerated under the reaction conditions,
and products 7g, 7h, 8g, 8h were isolated in good yields.
Unfortunately, when a coumarin bearing a strong electron-
withdrawing group (-NO2) at the 6-position was used, poor yields
of the corresponding trifluoromethyl and pentafluoroethyl
products (7i and 8i) were obtained, i.e., 23% and 27%,
,
A
A
underwent decarboxylation to produce CF3 radical, CO2, and
pyridine. The CF3 radical attacked the 3-position of
coumarin (5a) to produce intermediate
B
. Afterwards the
was oxidized by Ru(III) to form carbocation
and Ru(II). Finally 3-trifluoromethyl
intermediate
intermediate
B
C
coumarin (7a) was produced in a process of deprotonation
assisted by pyridine.
Scheme 4. Proposed reaction mechanism
respectively.
Satisfactorily,
trifluoromethylation
and
To further demonstrate the generality and practicability of
pentafluoroethylation of 4-methyl-7-methoxy coumarin afforded
the products in high yields of 85% and 86%, respectively (7j, 8j).
As family members of coumarin derivatives, 4-phenyl-coumarins
are widely distributed in natural products and used in biological
trifluoromethylation
catalyzed
by
the
recyclable
2+
Ru[(DNM)2bpy]3
,
the electron-rich arene and xanthine
derivative were investigated under the given conditions (Scheme
5). The p-dimethoxybenzene and 7-(2-Chloroethyl)theophylline
afforded the corresponding trifluoromethylated products (9 and
10) in 40% and 32% yield, respectively.
Table 3 Substrate scope of coumarina
Ru
R2
R2
O
O
pyridine N-oxide
R
O
+
R1
R1
CH2Cl2/CH3CN (1:1)
blue LED, 24 h, RT
R
O
R
O
O
O
R = CF3, 6a
6b
7a-7l
R = CF3,
Coumarin
R = C2F5,
R = C2F5, 8a-8l
R
R
O
R
O
R
O
Scheme 5. Trifluoromethylation for p-dimethoxybenzene and 7-(2-
O
O
O
O
O
2+
Chloroethyl)theophylline by the Ru[(DNM)2bpy]3
.
7a, 66%
8a, 68%
7b, 56%
8b, 53%
7c, 52%
8c, 55%
7d, 56%
8d, 60%
Owing to the recyclable nature of PC and low cost of the
fluorine sources, up-scaled procedure of the
R
Br
R
O
R
O
Cl
R
O
a
O
O
O
O
O
O
O
O
trifluoromethylation reaction was carried out (Scheme 6). 3
mmol of the coumarin was used, and the concentration was
1.5-fold (0.6 M) of that under the optimized condition (0.4
M). The reaction afforded 3-trifluoromethyl coumarin in
60% yield (385mg).
7e, 81%
8e, 85%
7f, 67%
8f, 65%
7g, 61%
8g, 59%
7h, 55%
8h, 58%
R
O
R
O
O2N
R
O
N
O
O
O
R
O
7j, 85%
8j, 86%
7i, 23%
8i, 27%
7l, 65%
8l, 61%
O
7k, 62%
8k, 65%
aReaction conditions: coumarin (0.4 mmol), PC (1 mol %), pyridine N-oxidie
(0.82 mmol), anhydride (0.8 mmol), and CH3CN (0.5 mL), CH2Cl2 (0.5 mL),
irradiation with 15 W blue LED at room temperature; isolated yields.

4
Tetrahedron
frequencies of 500, 126 and 470 MHz, respectively. Chemical
ACCEPTED MANUSCRIPT
shifts for 1H NMR were reported in ppm relative to TMS. All 13
C
NMR spectra were reported in ppm relative to deuterated
chloroform (77.00 ppm). The following abbreviations are used to
set multiplicities: s = singlet, d = doublet, t = triplet, dd = doublet
of doublets, q = quartet, tq = triplet of quartets, qt = quartet of
triplets, and m = multiplet. Coupling constants (J) were reported
in Hertz (Hz). GC-MS data were also recorded. High-resolution
mass spectrometry data were recorded on
spectrometer in the ESI mode.
a
Tof mass
Scheme 6. Up-scaled trifluoromethylation reaction of coumarin.
Recently, the use of continuous flow micro-reactors for
photochemical applications has received much attention as it
helps to overcome the issues associated with batch
photochemistry. The narrow channel of a typical micro-reactor
facilitates a uniform irradiation of the entire reaction mixture.
Consequently, photochemical reactions can be accelerated
substantially, and lower PC loadings are often feasible.
Furthermore, scale-up of photochemical reactions is facilitated in
continuous flow reactors12. Herein, we present a general
protocol for visible light-induced trifluoromethylation of
4.2
Preparation
of
ruthenium,
tris
(4,4’-bis
(dinonylmethyl)-2,2’-bipyridine) (Ru[(DNM)2bpy]32+).
To a Schlenk flask was added 4,4’-bis (dinonylmethyl)-2,2’-
bipyridine (619 mg, 0.9 mmol), RuCl3·3H2O (78 mg, 0.3 mmol),
NaH2PO2 (10.6 mg, 0.1 mmol), and ethanol 30 mL to form a
deep brown solution. The reaction mixture was stirred and
refluxed at 90 °C under Ar for 12 h, whereupon the color
changed to red-brown or dark orange. After cooling to room
temperature, 100 mL of hexane and 100 mL of water were
poured into the reaction solution, leading to organic biphasic
formation. The upper hexane layer was separated and dried with
Na2SO4, and then concentrated under vacuum. After evaporation,
the residue was purified by column chromatography on silica
coumarin with trifluoroacetic anhydride/pyridine
N-oxide in
a continuous flow reactor (Scheme 7). The starting material
solution was pumped continuously into a fluorinated
ethylene propylene (FEP) tube reactor, which was irradiated
by a blue LED. The reaction afforded 3-trifluoromethyl
coumarin (7a) in 65 % yield for a residence time of 5 h, thus
demonstrating a much shorter reaction time than that under
the batch condition (24 h).
2+
with eluent EtOAc to give the orange-red Ru[(DNM)2bpy]3
(514 mg, 77 %). 1H NMR (500 MHz, CDCl3) δ 8.61 (s, 1H), 7.60
(d, J = 5.8 Hz, 1H), 7.27 (d, J = 6.0 Hz, 2H), 2.93 – 2.75 (m, 1H),
1.85 – 1.54 (m, 4H), 1.39 – 1.07 (m, 28H), 0.90 – 0.81 (m,6H);
13C NMR (126 MHz, CDCl3) δ 158.96 (s), 156.85 (s), 150.54 (s),
126.92 (s), 124.46 (s), 45.67 (s), 35.55 (d, J = 9.8 Hz), 31.88 (s),
29.69 (s), 29.61 (s), 29.54 (d, J = 2.6 Hz), 29.30 (s), 27.59 (d, J =
3.5 Hz), 22.64 (s), 14.07 (s). HRMS (ESI) m/z: [M-2Cl]2+ Calcd.
For C144H252N6Ru 1083.9474; found 1083.9459.
4.3 General procedure for visible light-catalyzed coumarin
trifluoromethylation, pentafluoroethylation and in
continuous reactor.
a
Scheme 7. Trifluoromethylation of coumarin in continuous system.
4.3.1 Procedure for the visible light-catalyzed reaction.
A flame-dried reaction vessel with a magnetic stirring bar was
sequentially charged with coumarin or p-dimethoxybenzene or 7-
(2-Chloroethyl)theophylline (0.4 mmol), PC (0.004 mmol),
pyridine N-oxide (0.82 mmol, 78 mg), CH2Cl2 (0.5 mL) and
CH3CN (0.5 mL). Trifluoroacetic anhydride (0.8 mmol, 168 mg)
was then added to the resulting homogeneous solution. The
mixture was stirred at room temperature under irradiation from a
blue LED. The solvent in the reaction mixture was removed
under reduced pressure. The residue was redissolved in 2 mL of
CH3CN, and extracted 5 times with hexane (5 mL each time).
The PC was extracted into the hexane layer and separated for use
in the next reaction. The CH3CN layer was dried with Na2SO4
and concentrated under vacuum. After separation and
evaporation, the residue was purified by column chromatography
on silica gel (200–300 mesh size) using petroleum ether/EtOAc
as the eluent to give the trifluoromethyl coumarin.
3. Conclusion
In summary, a recoverable alkyl-bound bipyridine Ru
complex was successfully synthesized as
a
PC.
2+
Ru[(DNM)2bpy]3 showed excellent catalytic performance
as well as recyclability for both batch and flow reactions in a
homogeneous solvent. Meanwhile the perfluoroalkyl
reactions proceeded well for a wide range of coumarin
substrates, and also gave good yields in a up-scale process.
Moreover, the use of a continuous flow system for this
reaction would significantly shorten the reaction time. The
use of an alkyl-bound Ru complex would mitigate
environment pollution as a recyclable environmentally
friendly PC and made it possible for large-scale reaction
catalyzed by visible light industrially beyond laboratory.
4. Experimental section
4.1 General information
4.3.2 Procedure for the visible light-catalyzed scale-up
reaction.
All reagents unless otherwise noted were obtained from
commercial sources and used without further purification.
pyridine N-oxide (98.0%) and Trifluoroacetic anhydride
(>99.0%) were used without any purification. All these reactions
were monitored by TLC with silica gel GF254 precoated plates.
The products were isolated by column chromatography on silica
gel (200–300 mesh size).1H NMR, 13C NMR and 19F NMR
spectra were recorded on INOVA 500 instruments with operating
A flame-dried flask with a magnetic stirring bar was
sequentially charged with coumarin (3 mmol, 438 mg), PC (0.03
mmol), pyridine N-oxide (6.15 mmol, 584 mg), CH2Cl2 (2.5 mL)
and CH3CN (2.5 mL). Trifluoroacetic anhydride (6 mmol, 1260
mg) was then added to the resulting homogeneous solution. The
mixture was stirred at room temperature under irradiation from a
blue LED. The solvent in the reaction mixture was removed
under reduced pressure. The residue was redissolved in 10 mL of

5
CH3CN, and extracted with 30 mL of hexane. The PC was
extracted into the hexane layer and separated. The CH3CN layer
was dried with Na2SO4 and then concentrated under vacuum.
After separation and evaporation, the residue was purified by
column chromatography on silica gel (200–300 mesh size) using
petroleum ether/EtOAc as the eluent to give the trifluoromethyl
coumarin.
7-Methoxyl-3-(trifluoromethyl)-2H-1-Benzopyran-2-one
ACCEPTED MANUSCRIPT
1
(7e, CAS:1562426-78-1). A white solid (77.5 mg, 81%); H
NMR (500 MHz, CDCl3) δ 8.09 (s, 1H), 7.52 (d, J = 8.7 Hz, 1H),
6.93 (dd, J = 8.7, 2.3 Hz, 1H), 6.84 (d, J = 2.3 Hz, 1H), 3.92 (s,
3H); 13C NMR (126 MHz, CDCl3) δ 165.01 (s), 156.84 (s),
156.38 (s), 143.26 (q, J = 4.8 Hz), 130.59 (s), 121.77 (q, J =
271.5 Hz), 113.77 (q, J = 33.3 Hz), 113.76 (s), 110.38 (s), 100.74
(s), 56.04 (s); 19F NMR (470 MHz, CDCl3) δ -65.68 (s). GC-MS
(EI, m/z): 244(M+, 78), 216(73), 201 (100), 69(40).
4.3.3 Procedure for the visible light-catalyzed reaction in a
continuous flow reactor.
7-Acetyloxy-3-(trifluoromethyl)-2H-1-Benzopyran-2-one (7f,
CAS:1562426-82-7). A white solid (71.8 mg, 67%); H NMR
A test tube was filled with a mixed solvent of CH2Cl2 (0.5
mL) and CH3CN (0.5 mL), in which coumarin (0.4 mmol, 58.4
mg), PC (0.004 mmol), pyridine N-oxide (0.82 mmol, 78 mg),
and trifluoroacetic anhydride (0.8 mmol, 168 mg) were
dissolved. The solution was pumped into PTFE-FEP tube (1/32
inner diameter) using a pump (Syrris Ltd) at a flow rate of 9 ꢀL
min−1. The solution stream flowed into a 2.7 mL convection flow
coil (CFC) reactor (1/32 inner diameter), which was irradiated by
two 15 W blue LEDs on both sides and maintained at room
temperature (residence time: 5 h). The product stream exiting the
reactor was collected in a test tube, and the solvent was removed
under reduced pressure. The residue was redissolved in 2 mL of
CH3CN, and extracted 5 times with hexane (5 mL each time).
The PC was extracted into the hexane layer. The CH3CN layer
was dried with Na2SO4 and then concentrated under vacuum.
After separation and evaporation, the residue was purified by
column chromatography on silica gel (200–300 mesh size) using
petroleum ether/EtOAc as the eluent to give the trifluoromethyl
coumarin.
1
(500 MHz, CDCl3) δ 8.14 (s, 1H), 7.63 (d, J = 8.5 Hz, 1H), 7.20
(d, J = 2.2 Hz, 1H), 7.16 (dd, J = 8.5, 2.2 Hz, 1H), 2.36 (s, 3H);
13C NMR (126 MHz, CDCl3) δ 168.30 (s), 155.51 (s), 155.39 (s),
155.22 (s), 142.72 (q, J = 4.9 Hz), 130.31 (s), 121.32 (q, J =
272.0 Hz), 119.36 (s), 117.04 (q, J = 33.4 Hz), 114.47 (s), 110.52
(s), 21.11 (s); 19F NMR (470 MHz, CDCl3) δ -66.14 (s). GC-MS
(EI, m/z): 230(M+, 26), 202(27), 43(100), 32(38).
6-Chloro-3-(trifluoromethyl)-2H-1-Benzopyran-2-one (7g).
1
A white solid (62.3 mg, 61%); mp 160-161 °C; H NMR (500
MHz, CDCl3) δ 8.09 (s, 1H), 7.63 (d, J = 11.8 Hz, 2H), 7.36 (d, J
= 8.7 Hz, 1H); 13C NMR (126 MHz, CDCl3) δ 155.18 (s), 153.04
(s), 142.07 (q, J = 4.9 Hz), 134.36 (s), 130.68 (s), 128.54 (s),
121.06 (q, J = 272.4 Hz), 118.98 (q, J = 33.5 Hz), 118.53 (s),
117.75 (s); 19F NMR (470 MHz, CDCl3) δ -66.35 (s). HRMS
(ESI) m/z: [M+Na]+ Calcd. For C10H4ClF3O2Na 270.9758; found
270.9750.
6-Bromo-3-(trifluoromethyl)-2H-1-Benzopyran-2-one (7h,
1
3-(trifluoromethyl)-2H-1-Benzopyran-2-one (7a, CAS:
497959-34-9). A white solid (56.4 mg, 66%); 1H NMR (500
MHz, CDCl3) δ 8.17 (s, 1H), 7.69 (t, J = 7.9 Hz, 1H), 7.64 (d, J =
6.7 Hz, 1H), 7.44 – 7.34 (m, 2H); 13C NMR (126 MHz, CDCl3) δ
155.85 (s), 154.62 (s), 143.32 (q, J = 4.8 Hz), 134.42 (s), 129.47
(s), 125.26 (s), 121.33 (q, J = 272.0 Hz), 117.68 (q, J = 33.4 Hz),
116.96 (s), 116.76 (s); 19F NMR (470 MHz, CDCl3) δ -66.18 (s).
GC-MS (EI, m/z): 214(M+, 100), 186(57), 136(52), 63(34).
CAS:1562426-73-6). A white solid (63.8 mg, 55%); H NMR
(500 MHz, CDCl3) δ 8.09 (s, 1H), 7.76 (dd, J = 7.0, 2.2 Hz, 2H),
7.30 (d, J = 9.5 Hz, 1H); 13C NMR (126 MHz, CDCl3) δ 155.11
(s), 153.49 (s), 142.01 (q, J = 4.9 Hz), 137.16 (s), 131.63 (s),
121.04 (q, J = 272.4 Hz), 118.90 (q, J = 33.4 Hz), 118.75 (s),
118.25 (s), 117.84 (s); 19F NMR (470 MHz, CDCl3) δ -66.34 (s).
GC-MS (EI, m/z): 292(M+, 71), 294(70), 157(89), 87(100).
6-Nitro-3-(trifluoromethyl)-2H-1-Benzopyran-2-one
(7i,
1
6-Methyl-3-(trifluoromethyl)-2H-1-Benzopyran-2-one (7b,
CAS: 500552-10-3). A yellow solid (24.2 mg, 23%); H NMR
(500 MHz, CDCl3) δ 8.58 (d, J = 2.0 Hz, 1H), 8.54 (dd, J = 9.1,
2.3 Hz, 1H), 8.25 (s, 1H), 7.56 (d, J = 9.1 Hz, 1H); 13C NMR
(126 MHz, CDCl3) δ 157.85 (s), 154.11 (s), 144.50 (s), 142.02 (q,
J = 5.0 Hz), 128.86 (s), 125.24 (s), δ 120.70 (q, J = 272.7 Hz),
120.14 (q, J = 34.1 Hz), 118.41 (s), 116.81 (s); 19F NMR (470
MHz, CDCl3) δ -66.51 (s). GC-MS (EI, m/z): 256(M+, 59),
157(100), 87(83), 62(55).
1
CAS: 1562426-71-4). A white solid (52.1 mg, 56%); H NMR
(500 MHz, CDCl3) δ 8.10 (s, 1H), 7.48 (dd, J = 8.5, 1.8 Hz, 1H),
7.40 (s, 1H), 7.29 (d, J = 8.5 Hz, 1H), 2.44 (s, 3H); 13C NMR
(126 MHz, CDCl3) δ 156.12 (s), 152.83 (s), 143.26 (q, J = 4.9
Hz), 135.53 (s), 135.19 (s), 129.11 (s), 121.44 (q, J = 272.0 Hz),
117.58 (q, J = 33.1 Hz), 116.73 (s), 116.55 (s), 20.70 (s); 19F
NMR (470 MHz, CDCl3) δ -66.14 (s). GC–MS (EI, m/z):
228(M+, 100), 200(48), 199(43), 131(43).
7-Methoxy-4-Methyl-3-(trifluoromethyl)-2H-1-Benzopyran-
2-one (7j, CAS: 1562426-86-1). A white solid (87.2 mg, 85%);
1H NMR (500 MHz, CDCl3) δ 7.70 (d, J = 9.1 Hz, 1H), 6.92 (dd,
J = 9.1, 2.5 Hz, 1H), 6.78 (d, J = 2.5 Hz, 1H), 3.91 (s, 3H), 2.63
(dd, J = 4.2, 2.0 Hz, 3H); 13C NMR (126 MHz, CDCl3) δ 164.40
(s), 156.32 (s), 155.13 (s), 155.10 (d, J = 1.2 Hz), 127.16 (s),
123.15 (q, J = 274.7 Hz), 113.37 (s), 112.47 (s), 112.00 (q, J =
30.3 Hz), 100.43 (s), 55.96 (s), 15.65 (q, J = 4.1 Hz); 19F NMR
(470 MHz, CDCl3) δ -56.33 (q, J = 1.9 Hz). GC-MS (EI, m/z):
258(M+, 68), 230(99), 215(100), 32(17).
6,8-Dimethyl-3-(trifluoromethyl)-2H-1-Benzopyran-2-one
(7c). A white solid (47.7 mg, 52%); mp 126-127 °C; H NMR
1
(500 MHz, CDCl3) δ 8.07 (s, 1H), 7.34 (s, 1H), 7.22 (s, 1H), 2.43
(s, 3H), 2.40 (s, 3H); 13C NMR (126 MHz, CDCl3) δ 156.30 (s),
151.22 (s), 143.60 (q, J = 4.8 Hz), 136.92 (s), 134.62 (s), 126.78
(s), 126.29 (s), 121.56 (q, J = 271.9 Hz), 117.14 (q, J = 33.0 Hz),
116.36 (s), 20.61 (s), 15.26 (s); 19F NMR (470 MHz, CDCl3) δ -
66.05 (s). HRMS (ESI) m/z: [M + Na] + Calcd For C12H9F3O2Na
265.0452; found 265.0446.
6-t-Butyl-3-(trifluoromethyl)-2H-1-Benzopyran-2-one (7d).
A white solid (60.6 mg, 56%); mp 162-163 °C; H NMR (500
4-Methlylphenyl-3-(trifluoromethyl)-2H-1-Benzopyran-2-
one (7k, CAS: 1621190-87-1). A white solid (74.6 mg, 62%); 1H
NMR (500 MHz, CDCl3) δ 7.61 (t, J = 7.7 Hz, 1H), 7.40 (d, J =
8.1 Hz, 1H), 7.33 (d, J = 7.7 Hz, 2H), 7.19 (t, J = 7.7 Hz, 1H),
7.14 (d, J = 7.7 Hz, 2H), 7.06 (d, J = 8.1 Hz, 1H), 2.47 (s, 3H);
13C NMR (126 MHz, CDCl3) δ 157.21 (d, J = 2.0 Hz), 156.41
(s),153.43 (s), 139.38 (s), 133.98 (s), 129.87 (s), 129.32 (s),
129.14 (s), 127.28 (d, J = 1.5 Hz), 124.68 (s), 121.93 (q, J=275.2
1
MHz, CDCl3) δ 8.17 (s, 1H), 7.73 (d, J = 8.8 Hz, 1H), 7.58 (s,
1H), 7.33 (d, J = 8.8 Hz, 1H), 1.37 (s, 9H); 13C NMR (126 MHz,
CDCl3) δ 156.24 (s), 152.72 (s), 148.61 (s), 143.81 (q, J = 4.9
Hz), 132.26 (s), 125.68 (s), 121.49 (q, J = 271.9 Hz), 117.38 (q, J
= 33.3 Hz), 116.27 (s), 113.80 (s), 34.65 (s), 31.22 (s); 19F NMR
(470 MHz, CDCl3) δ -66.11 (s). HRMS (ESI) m/z: [M+Na]+
Calcd. For C14H13F3O2Na 293.0765; found 293.0733.
Hz), 119.66 (s), 116.81 (s), 115.05 (q, J = 30.1 Hz), 21.39 (s); 19
F

6
Tetrahedron
ACCEPTED MANUSCRIPT
NMR (470 MHz, CDCl3) δ -57.39 (s). GC-MS (EI, m/z):
7-Acetyloxy-3-(pentafluoroethyl)-2H-1-Benzopyran-2-one
304(M+, 100), 289(99), 276(64), 199(74).
(8f). A white solid (85.3 mg, 65%); mp 175-176 °C;. H NMR
(500 MHz, CDCl3) δ 8.14 (s, 1H), 7.64 (d, J = 8.5 Hz, 1H), 7.20
(d, J = 2.2 Hz, 1H), 7.16 (dd, J = 8.5, 2.2 Hz, 1H), 2.36 (s, 3H);
13C NMR (126 MHz, CDCl3) δ 168.27 (s), 155.62 (s), 155.43 (s),
155.07 (t, J = 2.0 Hz), 145.47 (t, J = 7.7 Hz), 130.34 (s), 119.33
(s), 118.95 (qt, J = 287.2, J = 38.1 Hz), 115.55 (t, J = 24.4 Hz),
114.70 (s), 111.58 (tq, J = 256.4, J = 40.1 Hz), 110.42 (s), 21.09
(s); 19F NMR (470 MHz, CDCl3) δ -83.04 (s, 3F), -114.98 (s, 2F).
HRMS (ESI) m/z: [M+Na]+ Calcd. For C13H7F5O4Na 345.0162;
found 345.0156.
1
1-Methyl-3-(trifluoromethyl)-2(1H)-Quinolinone (7l, CAS:
1
1890080-20-2). A white solid (60.5mg, 65%); H NMR (500
MHz, CDCl3) δ 8.12 (s, 1H), 7.77 – 7.60 (m, 2H), 7.41 (d, J = 8.6
Hz, 1H), 7.32 (t, J = 7.8 Hz, 1H), 3.75 (s, 3H); 13C NMR (126
MHz, CDCl3) δ 158.00 (s), 141.00 (s), 138.86 (q, J = 5.2 Hz),
133.15 (s), 130.44 (s), 122.92 (s), 122.40 (q, J = 271.7 Hz),
121.13 (q, J = 30.3 Hz), 118.06 (s), 114.40 (s), 29.52 (s); 19F
NMR (470 MHz, CDCl3) δ -66.16 (s). GC-MS (EI, m/z): 227(M+,
69), 179(78), 176(100), 121(68).
6-Chloro-3-(pentafluoroethyl)-2H-1-Benzopyran-2-one (8g).
A white solid (69.3 mg, 59%); mp 162-163 °C; H NMR (500
3-(pentafluoroethyl)-2H-1-Benzopyran-2-one (8a). A white
solid (69.0 mg, 68%); mp 151-152 °C; H NMR (500 MHz,
1
1
MHz, CDCl3) δ 8.09 (s, 1H), 7.64 (d, J = 10.0 Hz, 2H), 7.36 (d, J
= 8.5 Hz, 1H); 13C NMR (126 MHz, CDCl3) δ 154.76 (t, J = 2.0
Hz), 153.22 (s), 144.89 (t, J = 7.9 Hz), 134.60 (s), 130.64 (s),
128.56 (s), 118.68 (qt, J = 287.3, J = 38.5 Hz), 118.45 (s), 117.90
(s), 117.62 (t, J = 24.1 Hz), 111.43 (tq, J = 256.4, J = 40.1 Hz);
19F NMR (470 MHz, CDCl3) δ -82.96 (s, 3F), -115.10 (s, 2F).
HRMS (ESI) m/z: [M+Na]+ Calcd. For C11H4ClF5O2Na
320.9718; found 320.9708.
CDCl3) δ 8.17 (s, 1H), 7.70 (t, J = 7.9 Hz, 1H), 7.64 (d, J = 7.5
Hz, 1H), 7.39 (t, J = 7.5 Hz, 2H); 13C NMR (126 MHz, CDCl3) δ
155.45 (t, J = 2.1 Hz), 154.86 (s), 146.13 (t, J = 7.8 Hz), 134.70
(s), 129.50 (s), 125.23 (s), 117.00 (s), 116.94 (s), 118.80 (qt, J =
287.2, J = 38.1 Hz), 116.29 (t, J = 24.0 Hz), 111.62 (tq, J =
256.7, J = 40.5 Hz); 19F NMR (470 MHz, CDCl3) δ -83.04 (s,
3F), -114.98 (s, 2F). HRMS (ESI) m/z: [M+Na]+ Calcd. For
C11H5F5O2Na 287.0107; found 287.0102.
6-Bromo-3-(pentafluoroethyl)-2H-1-Benzopyran-2-one (8h).
A white solid (78.4 mg, 58%) mp 166-167 °C; H NMR (500
6-Methyl-3-(pentafluoroethyl)-2H-1-Benzopyran-2-one (8b).
A white solid (60.0 mg, 53%); mp 153-154 °C; H NMR (500
1
1
MHz, CDCl3) δ 8.09 (s, 1H), 7.83 – 7.67 (m, 2H), 7.29 (d, J = 8.6
Hz, 1H); 13C NMR (126 MHz, CDCl3) δ 154.69 (t, J = 2.0 Hz),
153.69 (s), 144.81 (t, J = 7.8 Hz), 137.39 (s), 131.65 (s), 118.68
(qt, J = 287.2, J = 38.2 Hz), 118.67 (s), 118.41 (s), 117.79 (s),
117.56 (t, J = 24.3 Hz), 111.41 (tq, J = 256.4, J = 40.6 Hz); 19F
NMR (470 MHz, CDCl3) δ -82.97 (s, 3F), -115.09 (s, 2F). HRMS
(ESI) m/z: [M+Na]+ Calcd. For C11H4BrF5O2Na 364.9205; found
364.9213.
MHz, CDCl3) δ 8.11 (s, 1H), 7.49 (d, J = 8.4 Hz, 1H), 7.42 (s,
1H), 7.28 (d, J = 8.4 Hz, 1H), 2.45 (s, 3H); 13C NMR (126 MHz,
CDCl3) δ 155.70 (s), 153.01 (s), 146.13 (t, J = 7.7 Hz), 135.80
(s), 135.19 (s), 129.16 (s), 118.80 (qt, J = 287.2, J = 38.1 Hz),
116.74 (s), 116.58 (s), 115.99 (t, J = 24.9 Hz), 111.69 (tq, J =
256.6, J = 40.4 Hz), 20.63 (s); 19F NMR (470 MHz, CDCl3) δ -
83.11 (s, 3F), -114.95 (s, 2F). HRMS (ESI) m/z: [M+Na]+ Calcd.
For C12H7F5O2Na 301.0264; found 301.0253.
6-Nitro-3-(pentafluoroethyl)-2H-1-Benzopyran-2-one (8i). A
yellow solid (32.4 mg, 27%); mp 222-223 °C; H NMR (500
6,8-Dimethyl-3-(pentafluoroethyl)-2H-1-Benzopyran-2-one
(8c). A white solid (62.3 mg, 55%); mp 156-157 °C; H NMR
1
1
MHz, CDCl3) δ 8.60 (d, J = 2.2 Hz, 1H), 8.55 (dd, J = 9.1, 2.2
Hz, 1H), 8.26 (s, 1H), 7.56 (d, J = 9.1 Hz, 1H); 13C NMR (126
MHz, CDCl3) δ 158.03 (s), 153.70 (s), 144.89 (t, J = 7.9 Hz),
144.46 (s), 129.05 (s), 125.29 (s), 118.90 (t, J = 24.5 Hz), 118.56
(qt, J = 287.3, J = 38.2 Hz), 118.33 (s), 116.92 (s), 111.18 (tq, J
= 256.3, J = 40.2 Hz); 19F NMR (470 MHz, CDCl3) δ -82.86 (s,
3F), -115.26 (s, 2F). HRMS (ESI) m/z: [M+Na]+ Calcd. For
C11H4F5NO4Na 331.9958; found 331.9942.
(500 MHz, CDCl3) δ 8.08 (s, 1H), 7.35 (s, 1H), 7.23 (s, 1H), 2.43
(s, 3H), 2.40 (s, 3H); 13C NMR (126 MHz, CDCl3) δ 155.87 (t, J
= 2.0 Hz), 151.43 (s), 146.39 (t, J = 7.8 Hz), 137.14 (s), 134.59
(s), 126.79 (s), 126.21 (s), 118.87 (qt, J = 287.2, J = 38.0 Hz),
116.57 (s), 115.60 (t, J = 24.0 Hz), 111.77 (tq, J = 256.5, J = 40.4
Hz), 20.58 (s), 15.18 (s); 19F NMR (470 MHz, CDCl3) δ -83.13
(s, 3F), -114.90 (s, 2F). HRMS (ESI) m/z: [M+Na]+ Calcd. For
C13H9F5O2Na 315.0425; found 315.0420.
7-Methoxy-4-Methyl-3-(pentafluoroethyl)-2H-1-
6-t-Butyl-3-(pentafluoroethyl)-2H-1-Benzopyran-2-one (8d).
A white solid (74.3 mg, 60%); mp 185-186 °C; H NMR (500
Benzopyran-2-one (8j). A white solid (109.0 mg, 86%); mp 209-
1
1
210 °C; H NMR (500 MHz, CDCl3) δ 7.71 (d, J = 9.1 Hz, 1H),
MHz, CDCl3) δ 8.16 (s, 1H), 7.74 (dd, J = 8.8, 2.2 Hz, 1H), 7.58
(d, J = 2.2 Hz, 1H), 7.34 (d, J = 8.8 Hz, 1H), 1.37 (s, 9H); 13C
NMR (126 MHz, CDCl3) δ 155.80 (t, J = 2.0 Hz), 152.95 (s),
148.58 (s), 146.58 (s), 132.55 (s), 125.66 (s), 118.86 (qt, J =
287.1 Hz, J = 38.2 Hz), 116.54 (s), 116.49 (s), 115.92 (t, J = 23.9
Hz), 111.73 (td, J = 256.7 Hz, J = 40.4 Hz), 34.68 (s), 31.24 (s);
19F NMR (470 MHz, CDCl3) δ -83.09 (s, 3F), -114.91 (s, 2F).
HRMS (ESI) m/z: [M+Na]+ Calcd. For C15H13F5O2Na 343.0733;
found 343.0724.
6.92 (dd, J = 9.1, 2.5 Hz, 1H), 6.79 (d, J = 2.5 Hz, 1H), 3.91 (s,
3H), 2.62 (t, J = 2.5 Hz, 3H); 13C NMR (126 MHz, CDCl3) δ
164.48 (s), 157.35 (s), 156.25 (t, J = 1.9 Hz), 155.25 (s), 127.13
(s), 119.43 (qt, J = 287.6, J = 38.6 Hz), 119.42 (tq, J = 257.1, J =
40.8Hz), 113.38 (s), 112.78 (s), 110.40 (t, J = 22.1 Hz), 100.29
(s), 55.97 (s), 16.24 (td, J = 7.3, 1.4 Hz); 19F NMR (470 MHz,
CDCl3) δ -83.43 (s), -106.67 (s). HRMS (ESI) m/z: [M+Na]+
Calcd. For C13H9F5O3Na 331.0370; found 331.0376.
4-Methlylphenyl-3-(pentafluoroethyl)-2H-1-Benzopyran-2-
one (8k). A white solid (89.2 mg, 65%); mp 159-160 °C;. H
7-Methoxyl-3-(pentafluoroethyl)-2H-1-Benzopyran-2-one
(8e). A white solid (103mg, 85%); mp 160-161 °C; H NMR
1
1
NMR (500 MHz, CDCl3) δ 7.61 (t, J = 7.7 Hz, 1H), 7.38 (d, J =
8.1 Hz, 1H), 7.30 (d, J = 7.8 Hz, 2H), 7.16 (t, J = 7.7 Hz, 1H),
7.09 (d, J = 7.8 Hz, 2H), 6.89 (d, J = 8.1 Hz, 1H), 2.46 (s, 3H);
13C NMR (126 MHz, CDCl3) δ 160.21 (t, J = 2.2 Hz), 156.11 (t, J
= 2.1 Hz), 153.45 (s), 138.88 (s), 134.21 (s), 130.04 (s), 129.44
(s), 128.73 (s), 127.16 (s), 124.63 (s), 120.35 (s), 118.89 (qt, J =
275.2 Hz, J = 37.5 Hz ), 116.60 (s), 113.57 (t, J = 20.9 Hz),
112.71 (tq, J = 260.4 Hz, J = 40.7 Hz ), 21.35 (s); 19F NMR (470
(500 MHz, CDCl3) δ 8.08 (s, 1H), 7.52 (d, J = 8.7 Hz, 1H), 6.93
(dd, J = 8.7, 2.4 Hz, 1H), 6.84 (d, J = 2.4 Hz, 1H), 3.92 (s, 3H);
13C NMR (126 MHz, CDCl3) δ 165.24 (s), 157.13 (s), 155.92 (s),
145.86 (t, J = 7.6 Hz), 130.60 (s), 118.93 (qt, J = 287.1, J = 38.5
Hz), 113.80 (s), 112.03 (t, J = 24.2 Hz), 111.87 (tq, J = 256.3, J =
40.4 Hz), 110.72 (s), 100.57 (s), 56.05 (s); 19F NMR (470 MHz,
CDCl3) δ -83.29 (s, 3F), -114.73 (s, 2F). HRMS (ESI) m/z:
[M+Na]+ Calcd. For C12H7F5O3Na 317.0219; found 317.0213.

7
MHz, CDCl3) δ -81.80 (s, 3F), -106.22 (s, 2F). HRMS (ESI) m/z:
(d) Barata-Vallejo S, Bonesi SM, Postigo A. Org Biomol
Chem. 2015; 13: 11153-11183;
ACCEPTED MANUSCRIPT
[M+Na]+ Calcd. For C18H11F5O2Na 377.0577; found 377.0586.
(e) Pan X, Xia H, Wu J. Org Chem Front. 2016; 3: 1163-1185;
(f) Chatterjee T, Iqbal N, Y You, Cho EJ. Acc Chem Res. 2016;
49: 2284-2294.
1-Methyl-3-(pentafluoroethyl)-2(1H)-Quinolinone (8l).
A
1
white solid (66.6 mg, 61%); mp 153-154 °C;. H NMR (500
MHz, CDCl3) δ 8.12 (s, 1H), 7.75 – 7.66 (m, 2H), 7.41 (d, J = 8.6
Hz, 1H), 7.32 (t, J = 7.5 Hz, 1H), 3.75 (s, 3H); 13C NMR (126
MHz, CDCl3) δ 157.90 (t, J = 1.9 Hz), 141.47 (t, J = 8.5 Hz),
141.20 (s), 133.36 (s), 130.48 (s), 122.85 (s), 119.82 (t, J = 22.4
Hz), 119.18 (qt, J = 282.2, J = 38.4 Hz), 118.23 (s), 114.35 (s),
112.69 (qt, J = 255.6, J = 40.2Hz), 29.63 (s); 19F NMR (470
MHz, CDCl3) δ -82.43 (s), -114.19 (s). HRMS (ESI) m/z:
[M+Na]+ Calcd. For C11H8F5NONa 300.0418; found 300.0424.
3. (a) Nagib DA, Scott ME, MacMillan, DW. J Am Chem Soc.
2009; 131: 10875-10877;
(b) Pham PV, Nagib DA, MacMillan DW. Angew Chem, Int Ed,
2011, 50, 6119-6122;
(c) Sahoo B, Li JL, Glorius F. Angew Chem, Int Ed. 2015; 54:
11577-11580;
(d) Tomita R, Koike T, M Akita. Angew Chem, Int Ed. 2015; 54:
12923-12927;
(e) Iqbal N, Jung J, Park S, Cho EJ. Angew Chem, Int Ed. 2014;
53: 539-542;
1,4-Dimethoxy-2-(trifluoromethyl)-Benzene (9, CAS: 84355-
10-2). A colourless oil (33.4 mg, 40%); H NMR (500 MHz,
1
(f) Xie J, Yuan X, Abdukader A, Zhu C, Ma J. Org Lett. 2014;
16: 1768-1771;
(g) Xu P, Abdukader A, Hu K, Cheng Y, Zhu C. Chem Commun.
2014; 50: 2308-2310;
(h) Ye Y, Sanford MS. J Am Chem Soc. 2012; 134: 9034-9037;
(i) Wei Q, Chen JR, Hu XQ, Yang XC, Lu B, Xiao WJ. Org
Lett. 2015; 17: 4464-4467;
CDCl3) δ 7.11 (d, J = 3.0 Hz, 1H), 7.01 (dd, J = 9.0, 3.0 Hz, 1H),
6.94 (d, J = 9.0 Hz, 1H), 3.85 (s, 3H), 3.79 (s, 3H); 13C NMR
(126 MHz, CDCl3) δ 153.00 (s), 151.55 (s), 123.43 (q, J = 272.5
Hz), 119.44 (q, J = 31.0 Hz), 118.09 (s), 113.63 (s), 112.86 (q, J
= 5.4 Hz), 56.55 (s), 55.86 (s); 19F NMR (470 MHz, CDCl3) δ -
62.41 (s). GC-MS (EI, m/z): 191(M+, 100), 206(82), 129(33),
163(28).
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3478-3481;
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1,3-Dimethyl-8-(trifluoromethyl)-7-(2-chloroethyl)-3,7-
dihydro-1H-purine-2,6-dione (10). A white solid (39.1 mg,
1
32%); mp 96-97 °C; H NMR (500 MHz, CDCl3) δ 4.78 (t, J =
6.4 Hz, 2H), 3.94 (t, J = 6.4 Hz, 2H), 3.61 (s, 3H), 3.43 (s, 3H);
13C NMR (126 MHz, CDCl3) δ 155.13 (s), 151.19 (s), 147.10 (s),
139.26 (q, J = 40.1 Hz), 118.07 (q, J = 271.8 Hz), 108.95 (s),
47.91 (s), 41.66 (s), 29.96 (s), 28.30 (s); 19F NMR (470 MHz,
CDCl3) δ -60.56 (s). HRMS (ESI) m/z: [M+Na]+ Calcd. For
C10H10ClF3N4O2Na 333.0342; found 333.0351.
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Acknowledgement
This work was supported by the National Natural Science
Foundation of China (NSFC) (Project Nos. 21176039 and
20923006).
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