Visible-Light Mediated ortho-Trifluoromethylation of Aniline Derivatives

Article abstract of DOI:10.1021/acs.joc.9b01987

A general visible-light mediated ortho-C-H trifluoromethylation of aniline derivatives by using a low-cost and stable Langlois reagent (CF₃SO₂Na) as the "CF₃" source has been developed. In contrast to previous reports, this strategy allowed access to elusive trifluoromethyl lactams. Furthermore, mechanism experiments revealed that a copper/photoredox dual catalytic mechanism enabled general trifluoromethylation of aniline derivatives.

Full text of DOI:10.1021/acs.joc.9b01987

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Note
Visible-Light Mediated ortho-Trifluoromethylation of Aniline Derivatives
Chao Tian, Qiyue Wang, Xueqi Wang, Guanghui An, and Guangming Li
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.9b01987 • Publication Date (Web): 19 Sep 2019
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Visible-Light Mediated ortho-Trifluoromethylation of Aniline
Derivatives
Chao Tian,† Qiyue Wang,† Xueqi Wang,† Guanghui An*, †, ‡ and Guangming Li*, †
†Key Laboratory of Functional Inorganic Material Chemistry (MOE), School of Chemistry and Materials Science, Heilongjiang University, No. 74, Xuefu
Road, Nangang District, Harbin 150080, People’s Republic of China;
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‡College of Materials Science and Chemical Engineering, Harbin Engineering University, Harbin, Heilongjiang 150001, China.
Eosin Y
Cu
R1
R1
N
N
O
O
H
H
Regioselectivity Dual catalysis
Functionalization of lactams
CF3
H
O
O
N
O
O
N
H
O
N
Cl
O
N
H
H
H
CF3
CF3
CF3
CF3
ABSTRACT: A general visible-light mediated ortho-C-H trifluoromethylation of aniline derivatives by using the low-
costing and stable Langlois reagent (CF3SO2Na) as the “CF3” source has been developed. In contrary to previous reports,
this strategy allowed access to elusive trifluoromethyl lactams. Furthermore, the mechanism experiments revealed that a
copper/photoredox dual catalytic mechanism enabled general trifluoromethylation of aniline derivatives.
The introduction of trifluoromethyl group into organic
compounds frequently renders remarkable changes in their
electronic properties, special size, and metabolic stability.1
In particular, trifluoromethyl anilines have played an
trifluoromethyl anilines remains highly desirable.
Scheme 1. Representative Compounds of ortho
Trifluoromethyl Anilines
important
role
in
numerous
pharmaceuticals,
Cl
O
N
Cl
NH2
CF3
agrochemicals, dyes and materials (Scheme 1).1a,2 Given
the harsh conditions of traditional synthetic methods,
tedious efforts have been devoted to developing
complementary protocols for efficient introduction of
trifluoromethyl moieties in regioselective manner.3
Among these impressive protocols, the most effective
route to trifluoromethyl anilines would be direct
trifluoromethylation of CH bonds of arenes, thanks to its
step economy and atom economy. Since seminal
publications by Shi,4 transition metal catalyzed C-H
trifluoromethylation of aniline substrates has been
developed continuously, which typically employed
appropriate directing groups (Scheme 2).5 Despite these
impressive advances, they typically require special
directing groups which coordinate with metal catalytic
center via carbonyl group in amides or via pyridine moiety
in picolinamides, leading to limitation of scope. Thus,
development of a distinct trifluoromethylation strategy
which would enable the synthesis of inaccessible
N
N
N
CF3
H
OH
Triflumizole
Mabuterol
SO3Na
F3C
O
H
OH
N
O
N
CF3
H
N
HN
H
NH2
H H
F3C
Cl
Dutasteride
Acid Red 266
Recently, visible light photoredox catalysis has become
a powerful tool in organic synthesis.6 It features with lower
energy consumption and higher atom economy, which are
cheaper and easier in contrast to UV reactors. Thus,
numerous visible light catalytic trifluoromethylation of
arenes have been developed.1d,7 However, visible-light
mediated ortho trifluoromethylation of aniline derivatives
have been scarcely documented.8 Herein, along our efforts
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in photoredox catalysis,9 we demonstrate a general
copper/photoredox dual catalytic system for ortho-
trifluoromethylation of aniline derivatives. It allows the
facile access to inaccessible pharmaceutically important
trifluoromethyl lactams.
Table 1. Optimization of ortho Trifluoromethylation
Conditionsa
photocatalyst (5 mol%)
cocatalyst (10 mol%)
oxidant (2 equiv.)
O
O
+
CF3SO2Na
N
H
N
Blue LED
MeCN, air, 20 h
H
N
H
N
CF3
10
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1a
2
3a
Scheme 2. C-H Trifluoromethylation of Aniline
Entry
1
Photocatalyst
Ru(bpy)3Cl2
4CzIPN
Eosin Y
-
Oxidant
Metal salt
Cu(OAc)2
Cu(OAc)2
Cu(OAc)2
Cu(OAc)2
Cu(OAc)2
Cu(OAc)2
Cu(OAc)2
Cu(OAc)2
Cu(OAc)2
CuCl2
Yield (%)b
15
Derivatives
Na2S2O8
Previous work:
CF3
Ln
O
2
Na2S2O8
13
H
O
R1
M
O
R1
R1
R
N
(a)
(b)
R
N
H
H
3
Na2S2O8
40
R
N
H
CF3
M=Pd, Cu
4
Na2S2O8
n.r.
n.r.
44
O
N
R1
O
5c
6
Eosin Y
Eosin Y
Eosin Y
Eosin Y
Eosin Y
Eosin Y
Eosin Y
Eosin Y
Eosin Y
Eosin Y
Eosin Y
Na2S2O8
O
R1
R1
N
R
N
R
N
H
R
H
H
M
H
CF3
N
N
K2S2O8
Ln
M=Cu, Fe
7
(NH4)2S2O8
PhI(OAc)2
PhI(TFA)2
(NH4)2S2O8
(NH4)2S2O8
(NH4)2S2O8
(NH4)2S2O8
(NH4)2S2O8
(NH4)2S2O8
60
This work:
8
33
R
R
R
(c)
O
N
O
N
N
O
9
20
Ln CuII
X
H
H
CF3
H
CF3
10
11
12
13
14
15
65
Regioselectivity
Dual catalysis
Functionalization of lactams
CuBr2
21
CuCl
30
Owing to its stability and safety, low toxicity and low
expense, we employed CF3SO2Na as CF3 source for our
optimization study on ortho-trifluoromethylation of N-
phenylpicolinamide (Table 1; for details see SI, Table S1).
Among diverse photocatalysts, Eosin Y showed the
highest reactivity, providing desired product 3a in 40%
yield (Table 1, entry 3). No expected product was detected
in the absence of photocatalyst or light, indicating that
trifluoromethylation process underwent a photocatalytic
routine (Table 1, entries 4-5). Further survey of different
oxidants, such as persulfate, hypervalent iodium reagents
revealed that (NH4)2S2O8 afforded the best reactivity
(Table 1, entries 6-9 vs entry 7). A thorough examination
of other cocatalysts was also performed (Table 1, entries
10-14; for details see SI, Table S1, entries 13-18): the yield
of 3a was improved to 65% when CuCl2 was employed
(Table 1, entry 10). The reaction vanished in the absence
of CuCl2, which could be attributed to the ability of copper
salts to trap and transfer trifluoromethyl radicals during the
reaction (Table 1, entry 15).
CuI
23
FeCl3
11
-
n.r.
aReaction conditions: 1a (0.2 mmol), 2 (3 equiv.), photocatalyst (5 mol%),
cocatalyst (10 mol%), oxidant (2 equiv.) and solvent (2 mL) under blue
LED irradiation in air for 20 h. bIsolated yield. cIn the dark.
Under the optimal conditions, the scope of this
trifluoromethylation method toward aniline derivatives
were explored (Scheme 3). Aniline derivatives with
electron donating and electron withdrawing groups can be
converted into products in 40%-65% yields (3a-3e).
Trifluoromethylation occurred at less hindered site of
meta-substituted aniline (3d). Besides picolinamides, other
aromatic amides bearing halides, methyl and methoxy
group also afforded corresponding products smoothly (3f-
3m). Ortho-substituted amides gave slightly better yields
than meta- and para- substituted ones (3g vs 3i and 3l). The
linear and branched alkyl anilides can provide the
corresponding ortho-trifluoromethyl anilides as well (3n–
3q). Notably, amides with dicarbonyl structure such as 3-
oxo-N-phenylbutanamide
and
2-oxo-N,2-
diphenylacetamide can successfully furnished elusive 3r
and 3s in 50% and 52% yields, respectively. Furthermore,
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amides other than carboxylic anilides e. g., N-
sulfonylaniline also gave elusive ortho
in pharmaceutical uses (Scheme 4). The carbonyl group of
these substrates cannot assist C-H activation via
coordination of metal catalysts under previous ortho
trifluoromethylation product 3t. The robustness of the
protocol was confirmed by the gram-scale reactions.
Trifluoromethylation of 1a gave amide 3a in 54% yield
trifluoromethylation paradigm4,5a,8b
. Gratifyingly, the
important building blocks in pharmaceutical compounds,
such as dihydroquinolinone and oxindole, underwent this
reaction smoothly, delivering the corresponding ortho-
products (5a-5c) in moderate yields. Notably, the medicine
chlorzoxazone (a muscle relaxant) also afforded
corresponding trifluoromethyl lactams 5d. Several
experiments on comparison of the protocol with previous
ortho trifluoromethylation paradigm4,5a,8b were carried out.
When using Umemoto’s reagent4 and Togni’s reagent5a,
lactam 4a were recovered with starting materials partially
decomposed. When subjecting to ref 8b’s conditions,
lactams 4a was recovered with quantitive yields.
(1.08
g,
Scheme
3).
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Scheme 3. Substrate Scope with Respect to
Trifluoromethylationa
Eosin Y (5 mol%)
CuCl2 (10 mol%)
(NH4)2S2O8 (2 equiv.)
O
R1
O
R1
+
CF3SO2Na
R
N
R
N
Blue LED
MeCN, air, 20 h
H
H
CF3
O
H
1
2
3
O
O
O
N
H
N
H
N
H
N
CF3
N
CF3
N
CF3
45%
b
3b,
3c,
40%
3a,
65% (54%)
Cl
CF3
O
O
O
N
H
N
Scheme 4. Substrate Scope with Respect to
Trifluoromethylation of Lactamsa
N
H
H
CF3
N
I
CF3
N
CF3
3d,
O
3e,
O
3f,
60%
60%
56%
Eosin Y (5 mol%)
CuCl2 (10 mol%)
Cl
O
(NH4)2S2O8 (2 equiv.)
Cl
R1
R1
N
H
N
H
N
+
CF3SO2Na
H
O
N
O
N
CF3
CF3
CF3
Blue LED
MeCN, air, 20 h
H
H
CF3
H
3g,
3h,
3k,
3i,
50%
58%
59%
4
2
5
O
O
O
O
O
N
N
N
H
O
H
H
O
CF3
CF3
CF3
N
N
H
O
Cl
O
N
Cl
O
N
H
H
H
CF3
CF3
CF3
46%
CF3
38%
3j,
3l,
O
61%
52%
47%
5b,
5c,
5d,
40%
5a,
43%,
O
O
n.r.b, n.r.c, n.r.d
N
N
H
N
H
H
CF3
aReaction conditions: 4 (0.2 mmol), 2 (3 equiv.), Eosin Y (5 mol%),
(NH4)2S2O8 (2 equiv.), CuCl2 (10 mol%), and MeCN (2 mL) under blue
LED irradiation in air for 20 h; isolated yield of the product. bSubjecting
to ref 4’s conditions. cSubjecting to ref 5a’s conditions. dSubjecting to ref
8b’s conditions using A360WE as blue LED.
CF3
44%
CF3
Br
3m,
O
3n,
O
3o,
45%
62%
O
O
N
H
N
N
H
H
CF3
CF3
CF3
3p,
3q,
3r,
50%
65%
54%
O
O
S
N
N
O
H
H
CF3
O
CF3
To gain insights into the mechanism of the reaction, a
series of control experiments were carried out (Scheme 5).
When TEMPO was added as a radical inhibitor, this
reaction was completely suppressed, implying a single
electron transfer (SET) process (Scheme 5a). The
trifluoromethyl radical was trapped using 1,1-
diphenylethylene in the presence of CF3SO2Na, and the
coupling product (7) was obtained in 40 % yield (Scheme
5b), which suggests the generation of trifluoromethyl
radical. Moreover, we found that the reaction vanished
without oxidant (Table S1 entry 12),
3s,
3t,
50%
52%
aReaction conditions: 1 (0.2 mmol), 2 (3 equiv.), Eosin Y (5 mol%),
(NH4)2S2O8 (2 equiv.), CuCl2 (10 mol%), and MeCN (2 mL) under blue
LED irradiation in air for 20 h; isolated yield of the product. bGram scale;
7.5 mmol 1a was added.
Intriguing by the successful trifluoromethylation of
dicarbonyl amides and sulfonamides, we investigate the
synthesis of previous inaccessible medicinal related
trifluoromethyl lactams to show the potential applications
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rate-determining step.11
Given literature reports10,12 and our control experiments,
we proposed dual copper/photoredox
Scheme 5. Control Experiments
Eosin Y (5 mol%)
a
CuCl2 (10 mol%)
Na2S2O8 (2 equiv.)
O
O
+
CF3SO2Na
(a)
N
N
trifluoromethylation mechanism (Scheme 6). Upon photo
irradiation of Eosin Y, excited state Eosin Y* is formed,
which reacts with (NH4)2S2O8 to give Eosin Y·+ and
TEMPO
(3 equiv.)
Blue LED
MeCN, air, 20 h
H
H
CF3
1f
2
3f
, trace
10
11
12
13
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Eosin Y (5 mol%)
CuCl2 (10 mol%)
Na2S2O8 (2 equiv.)
·− 10
SO4
.
The latter radical anion oxidizes CF3SO2Na to
CF3
(b)
(c)
(d)
1f
+
+
+
+
+
CF3SO2Na
3f
+
Ph
Ph
Blue LED
MeCN, air, 20 h
Ph
Ph
generate trifluoromethyl radical. Similar to the report by
MacMillan’s group,13 the trifluoromethyl radical would be
rapid captured by Cu species and a Cu-CF3 species was
formed. Furthermore, Eosin Y·+ and aniline A would
generate radical intermediate B and the photocatalyst
through a SET process. By releasing a proton, radical
cation B is converted to C, which would be oxidized by
Cu(III) species and coordinate with Cu-CF3 species to
6
2
25%
7
, 40%
Eosin Y (5 mol%)
CuCl2 (10 mol%)
Na2S2O8 (2 equiv.)
CF3
O
O
CF3SO2Na
N
H
N
Blue LED
MeCN, air, 20 h
H
8
2
9
, no reaction
Eosin Y (5 mol%)
CuCl2 (10 mol%)
Na2S2O8 (2 equiv.)
O
O
CF3SO2Na
N
N
Blue LED
MeCN, air, 20 h
CF3
10
2
11
, no reaction
O
form D. Complex
D
undergoes intramolecular
and
Eosin Y (5 mol%)
CuCl2 (10 mol%)
Na2S2O8 (2 equiv.)
O
trifluoromethylation, affording intermediate
E
CF3SO2Na
without
(e)
N
H
N
H
with D2O
Blue LED
H
H/D
regenerating the Cu catalyst. Finally, intermediate E
tautomerises to afford product F.
MeCN, air, 20 h
1f
2
No deuterium incorporation
1f
Eosin Y (5 mol%)
CuCl2 (10 mol%)
Na2S2O8 (2 equiv.)
In summary, we have developed a general visible light
irradiation strategy to access various ortho-trifluoromethyl
aniline derivatives. The protocol can be performed by
using a combination of readily available reagents. This
photochemical protocol allows the rapid access to previous
elusive ortho-trifluoromethyl lactams. Mechanism
investigation suggests that the reactions undergo a dual
catalytic process via coordination of N atom at amide
moiety.
H/D
H/D
H/D
H/D
H/D
H/D
H/D
H/D
H/D
O
O
(f)
+
CF3SO2Na
Blue LED
MeCN, air, 5 h
N
N
H
H
CF3
kH:kD=1.04:1
1n/1n-D5
2
Intermolecular competition
Eosin Y (5 mol%)
CuCl2 (10 mol%)
Na2S2O8 (2 equiv.)
H/D
H/D
H/D
H/D
H/D
H/D
H/D
H/D
O
O
(g)
+
CF3SO2Na
Blue LED
MeCN, air, 5 h
N
N
H
H
CF3
H/D
1n 1n-D5
kH:kD=1.11:1
2
Parallel competition
or
indicating that the Eosin Y can not directly oxidized
Langlois reagent to generate trifluoromethyl radical in the
reaction.10 The reaction of ortho disubstituted amides 8
was rather sluggish, and no para product 9 was observed
with the recovery of 8 in 95% (Scheme 5c). No desired
product was detected by reacting N-methyl-N-
phenylacetamide (10) under the standard conditions,
indicating that the N-H group was indispensable (Scheme
5d). Besides, no deuterium was incorporated into the
recovered starting material when D2O was added in the
reaction. This suggests that an irreversible C–H cleavage
event occurred during the reaction (Scheme 5e). To
explore the role of the C−H activation step, the experiment
of kinetic isotope effects (KIE) was performed through the
intermolecular competition (Scheme 5f) and parallel
competition (Scheme 5g). The kinetic isotope effect factor
of 1.04 and 1.11 suggests that the C-H activation is not the
EXPERIMENTAL SECTION
General Information. Unless otherwise noted, all reagents
were obtained from commercial suppliers and used without
further purification. The reaction product was isolated by column
chromatography on a silica gel (236–400 mesh) column using
petroleum ether (PE) with a boiling range from 60 to 90 °C and
EtOAc. 1H, 13C and 19F NMR spectra were recorded on 400, 101,
376 MHz NMR spectrometers using DMSO or CDCl3 as solvent.
1
Data for H NMR, 13C NMR and 19F NMR were recorded as
follows: chemical shift (δ, ppm), multiplicity (s=singlet,
d=doublet, t=triplet, m=multiplet, q=quartet, coupling constant (s)
in Hz). In addition, 1H and 13C NMR spectra used
tetramethylsilane as the internal standard and 19F NMR spectra
are reported relative to trifluoroacetic acid (δ −76.55 ppm) as an
external reference. HRMS were conducted
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Scheme 6. Proposed Mechanism
5
6
CF3SO2Na
CF3
7
8
2-
2-
S2O8
SO42- + SO4
SO4
9
O
10
11
12
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Ln CuII
X
R
N
CF3
H
Eosin Y
O
Eosin Y
E
Ln
N
X
CuII
R
CF3
Ln CuIII
CF3
X
Blue Light
D
Eosin Y
O
R
NH
O
O
O
N
e
CF3
H
H
R
N
R
N
R
-H
F
C
B
A
on an Agilent 6540Q-TOF LC/MS equipped with electrospray
ionization (ESI) probe operating in positive ion mode.
Borosilicate glass tube was used as a reaction tube. The reaction
mixture is irradiated with two Kessil® LEDs (Saltwater Aquarium
residue was purified by column chromatography on silica gel to
give the pure product.
Gram-Scale Reaction. To a flask equipped with a magnetic
stir bar, 1a (1.49 g, 7.5 mmol, 1 equiv.), CF3SO2Na (3.51 g, 22.5
mmol, 3 equiv.), CuCl2 (100.8 mg, 0.75 mmol, 0.1 equiv.), Eosin
Y (259.5 mg, 0.38 mmol, 0.05 equiv.), Na2S2O8 (3.42 g, 15 mmol,
2 equiv.) and solvent (75 mL) was added sequentially and the
flask was sealed and irradiated with Blue LED lamps for 20 hours.
After completion, the solvent was evaporated under reduced
pressure and the residue was diluted with EtOAc, and washed
with brine. The water phase was extracted with EtOAc and the
combined organic phase was dried over Na2SO4. The solvent was
evaporated in vacuo and the residue was purified by column
chromatography on silica gel to give the pure product 3a in 54%
yield (1.08 g).
Light
A360WE
Series
Tuna
Blue;
http://www.kessil.com/products/saltwater_A360.php) from 5 cm
away and the vial temperature remained 60 °C. The lights,
reaction vessel, and stir plate are all placed behind 5 mm thick
hardboard with silver paper for the duration of the reaction. We
have not used any filters. Unless otherwise noted, all reagents
were weighed and handled in air, and all reactions were carried
out in air.
General experimental procedure for the synthesis of
corresponding products. To a vial equipped with a magnetic stir
bar, aniline derivatives 1 or 4 (0.2 mmol, 1 equiv.), CF3SO2Na
(93.6 mg, 0.6 mmol, 3 equiv.), CuCl2 (2.7 mg, 0.02 mmol, 0.1
equiv.), Eosin Y (6.92 mg, 0.01 mmol, 0.05 equiv.), Na2S2O8
(91.3 mg, 0.4 mmol, 2 equiv.) and solvent (2 mL) was added
sequentially and the vial was sealed and irradiated with Blue LED
lamps for 20 hours. After completion, the solvent was evaporated
under reduced pressure and the residue was diluted with EtOAc,
and washed with brine. The water phase was extracted with
EtOAc (2 × 30 mL) and the combined organic phase was dried
over Na2SO4. The solvent was evaporated in vacuo and the
KIE measured by intermolecular competition. To a vial
equipped with a magnetic stir bar, 1n (13.5 mg, 0.1 mmol, 0.5
equiv.), 1n-D5 (14.0 mg, 0.1 mmol, 0.5 equiv.), CF3SO2Na (93.6
mg, 0.6 mmol, 3 equiv.), CuCl2 (2.7 mg, 0.02 mmol, 0.1 equiv.),
Eosin Y (6.92 mg, 0.01 mmol, 0.05 equiv.), Na2S2O8 (91.3 mg,
0.4 mmol, 2 equiv.) and solvent (2 mL) was added sequentially
and the vial was irradiated with Blue LED lamps for 5 hours. 1H
NMR analysis of the isolated product demonstrated the KIE of
1.04.
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KIE measured by parallel competition. To a vial equipped
PE/EtOAc (9:1); 1H NMR (400 MHz, DMSO-d6) δ 10.64 (s, 1H),
with a magnetic stir bar, 1n (27.0 mg, 0.2 mmol, 1 equiv.) or 1n-
D5 (28.0 mg, 0.2 mmol, 1 equiv.), CF3SO2Na (93.6 mg, 0.6 mmol,
3 equiv.), CuCl2 (2.7 mg, 0.02 mmol, 0.1 equiv.), Eosin Y (6.92
mg, 0.01 mmol, 0.05 equiv.), Na2S2O8 (91.3 mg, 0.4 mmol, 2
equiv.) and solvent (2 mL) was added sequentially and the vial
was irradiated with Blue LED lamps for 5 hours. 1H NMR
analysis of the isolated product demonstrated the KIE of 1.11.
N-(2-(trifluoromethyl)phenyl)picolinamide (3a): white solid,
34.4 mg, 65% yield, known compound.5c Eluent: PE/EtOAc (9:1);
1H NMR (400 MHz, DMSO-d6) δ 10.54 (s, 1H), 8.74 (d, J = 4.7
Hz, 1H), 8.21 (dd, J = 19.3, 8.0 Hz, 2H), 8.09 (td, J = 7.7, 1.6 Hz,
1H), 7.84 – 7.62 (m, 3H), 7.41 (t, J = 7.7 Hz, 1H). 13C{1H} NMR
(101 MHz, DMSO-d6) δ 162.7, 149.2, 149.0, 139.0, 135.6 (q, J =
1.8 Hz), 134.0, 128.0, 126.9 (q, J = 5.2 Hz), 125.8, 124.1 (q, J =
252.4 Hz), 123.1, 120.9 (q, J = 29.5 Hz). 19F NMR (376 MHz,
DMSO-d6) δ -60.1. HRMS (ESI) m/z calcd for C13H10F3N2O+
[M+H]+: 267.0740; found: 267.0738.
8.74 (d, J = 4.7 Hz, 1H), 8.40 (s, 1H), 8.19 (d, J = 7.8 Hz, 1H),
8.11 (td, J = 7.7, 1.6 Hz, 1H), 7.81 (d, J = 8.5 Hz, 1H), 7.75 –
7.69 (m, 1H), 7.49 (d, J = 8.5 Hz, 1H). 13C{1H} NMR (101 MHz,
DMSO-d6) δ 162.8, 149.3, 148.6, 139.1, 138.4, 137.0 (q, J = 1.5
Hz), 128.8 (q, J = 5.4 Hz), 128.3, 126.9 (q, J = 272.9 Hz), 125.6,
124.3, 123.0, 119.3 (q, J = 30.4 Hz). 19F NMR (376 MHz,
DMSO-d6) δ -60.1. HRMS (ESI) m/z calcd for C13H9ClF3N2O+
[M+H]+: 301.0350; found: 301.0349.
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N-(2,4-bis(trifluoromethyl)phenyl)picolinamide (3e): white
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solid, 37.7 mg, 56% yield. Eluent: PE/EtOAc (9:1); H NMR
(400 MHz, DMSO-d6) δ 10.80 (s, 1H), 8.76 (d, J = 4.5 Hz, 1H),
8.62 (d, J = 8.7 Hz, 1H), 8.22 (d, J = 7.8 Hz, 1H), 8.19 – 8.09 (m,
2H), 8.07 (s, 1H), 7.77 – 7.71 (m, 1H). 13C{1H} NMR (101 MHz,
DMSO-d6) δ 162.8, 149.3, 148.4, 140.3 (q, J = 30.6 Hz), 139.2,
131.3 (q, J = 3.3 Hz), 129.8 (q, J = 282.7 Hz), 125.7, 125.0, 124.9,
124.3 (q, J = 1.7 Hz), 121.6 (q, J = 281.3 Hz), 120.6, 120.4 (q, J
= 30.7 Hz). 19F NMR (376 MHz, DMSO-d6) δ -60.6, -61.4.
HRMS (ESI) m/z calcd for C14H9F6N2O+ [M+H]+: 335.0614;
found: 335.0615.
N-(2-methyl-6-(trifluoromethyl)phenyl)picolinamide
(3b):
white solid, 22.6 mg, 40% yield, known compound.5c Eluent:
PE/EtOAc (9:1); 1H NMR (400 MHz, DMSO-d6) δ 10.61 (s, 1H),
8.72 (d, J = 4.7 Hz, 1H), 8.14 (d, J = 7.8 Hz, 1H), 8.06 (td, J =
7.7, 1.6 Hz, 1H), 7.75 (d, J = 8.1 Hz, 1H), 7.68 (ddd, J = 7.5, 4.8,
1.2 Hz, 1H), 7.55 (t, J = 7.9 Hz, 1H), 7.28 (d, J = 7.6 Hz, 1H),
2.48 (s, 3H). 13C{1H} NMR (101 MHz, DMSO-d6) δ 163.05,
149.35 (q, J = 30.3 Hz), 149.12, 145.64, 138.78, 138.11 (q, J =
5.0 Hz), 136.32 (q, J = 2.0 Hz), 132.63, 130.21, 127.75, 126.78,
124.16 (q, J = 270.3 Hz), 124.03, 21.14. 19F NMR (376 MHz,
DMSO-d6) δ -54.0. HRMS (ESI) m/z calcd for C14H12F3N2O+
[M+H]+: 281.0896; found: 281.0898.
N-(2-(trifluoromethyl)phenyl)benzamide (3f): white solid,
31.7 mg, 60% yield, known compound.4 Eluent: PE/EtOAc (9:1);
1H NMR (400 MHz, DMSO-d6) δ 10.13 (s, 1H), 7.94 (d, J = 7.2
Hz, 2H), 7.79 (d, J = 7.6 Hz, 1H), 7.73 (t, J = 7.7 Hz, 1H), 7.60
(t, J = 7.3 Hz, 1H), 7.53 (td, J = 7.0, 6.5, 3.6 Hz, 4H). 13C{1H}
NMR (101 MHz, DMSO-d6) δ 166.8, 136.3 (q, J = 1.6 Hz), 136.1,
134.4, 133.6, 132.3, 130.4 (q, J = 283.5 Hz), 128.1, 128.0, 127.2
(q, J = 30.2 Hz), 127.0 (q, J = 4.8 Hz). 19F NMR (376 MHz,
DMSO-d6) δ -59.8. HRMS (ESI) m/z calcd for C14H11F3NO+
[M+H]+: 266.0787; found: 266.0788.
N-(4-methoxy-2-(trifluoromethyl)phenyl)picolinamide (3c):
2-chloro-N-(2-(trifluoromethyl)phenyl)benzamide (3g): white
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yellow solid, 26.8 mg, 45% yield. Eluent: PE/EtOAc (9:1); H
solid, 34.6 mg, 58% yield. Eluent: PE/EtOAc (9:1); H NMR
NMR (400 MHz, DMSO-d6) δ 10.32 (s, 1H), 8.72 (d, J = 4.5 Hz,
1H), 8.15 (d, J = 7.8 Hz, 1H), 8.07 (td, J = 7.7, 1.6 Hz, 1H), 7.94
(d, J = 8.9 Hz, 1H), 7.68 (ddd, J = 7.4, 4.8, 1.1 Hz, 1H), 7.30 (dd,
J = 8.9, 2.7 Hz, 1H), 7.25 (d, J = 2.8 Hz, 1H), 3.83 (s, 3H). 13C{1H}
NMR (101 MHz, DMSO-d6) δ 162.96, 157.10, 149.31, 149.16,
138.84, 128.66, 128.20 (q, J = 1.8 Hz), 127.79, 124.05 (q, J =
269.4 Hz), 123.59 (q, J = 29.7 Hz), 122.71, 118.95, 112.01 (q, J
= 5.3 Hz), 56.27. 19F NMR (376 MHz, DMSO-d6) δ -60.37.
(400 MHz, DMSO-d6) δ 10.29 (s, 1H), 7.79 (d, J = 7.9 Hz, 1H),
7.74 (t, J = 7.6 Hz, 1H), 7.52 (tt, J = 16.1, 6.6 Hz, 6H). 13C{1H}
NMR (101 MHz, DMSO-d6) δ 166.6, 136.8, 135.4 (q, J = 1.7
Hz), 133.7, 131.6, 131.3, 130.4 (q, J = 30.9 Hz), 129.2, 128.0,
127.7, 127.0 (q, J = 5.0 Hz), 126.6, 126.3, 124.0 (q, J = 273.4
Hz). 19F NMR (376 MHz, DMSO-d6) δ -59.6. HRMS (ESI) m/z
calcd for C14H10ClF3NO+ [M+H]+: 300.0398; found: 300.0395.
2-iodo-N-(2-(trifluoromethyl)phenyl)benzamide (3h) white
+
1
HRMS (ESI) m/z calcd for C14H12F3N2O2 [M+H]+: 297.0845;
solid, 46.1 mg, 59% yield. Eluent: PE/EtOAc (9:1); H NMR
found: 297.0844.
(400 MHz, DMSO-d6) δ 10.24 (s, 1H), 7.93 (d, J = 7.7 Hz, 1H),
7.81 – 7.71 (m, 2H), 7.59 (d, J = 7.8 Hz, 1H), 7.52 (q, J = 7.4 Hz,
2H), 7.42 (d, J = 7.1 Hz, 1H), 7.22 (td, J = 8.9, 7.8, 1.4 Hz, 1H).
N-(5-chloro-2-(trifluoromethyl)phenyl)picolinamide
(3d):
white solid, 35.8 mg, 60% yield, known compound.5c Eluent:
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13C{1H} NMR (101 MHz, DMSO-d6) δ 169.1, 142.6, 139.7,
59.8. HRMS (ESI) m/z calcd for C14H10ClF3NO+ [M+H]+:
300.0398; found: 300.0399.
135.5 (q, J = 1.9 Hz), 133.6, 131.6, 131.1, 129.7 (q, J = 279.1
Hz), 128.5 (q, J = 27.1 Hz), 127.0 (q, J = 5.0 Hz), 125.4, 122.7,
118.6, 93.9. 19F NMR (376 MHz, DMSO-d6) δ -59.5. HRMS (ESI)
m/z calcd for C14H10F3INO+ [M+H]+: 391.9754; found: 391.9756.
3-chloro-N-(2-(trifluoromethyl)phenyl)benzamide (3i): white
4-bromo-N-(2-(trifluoromethyl)phenyl)benzamide (3m): white
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solid, 31.2 mg, 45% yield. Eluent: PE/EtOAc (9:1); H NMR
(400 MHz, DMSO-d6) δ 10.22 (s, 1H), 7.86 (dd, J = 11.3, 8.6 Hz,
2H), 7.81 – 7.72 (m, 3H), 7.69 (d, J = 8.6 Hz, 1H), 7.53 (t, J = 8.8
Hz, 2H). 13C{1H} NMR (101 MHz, DMSO-d6) δ 166.0, 136.0 (q,
J = 1.9 Hz), 133.6, 133.5, 132.2, 131.9 (q, J = 27.6 Hz), 130.2,
128.4 (q, J = 274.9 Hz), 128.1, 127.4, 127.0 (q, J = 5.3 Hz), 126.1.
19F NMR (376 MHz, DMSO-d6) δ -59.8. HRMS (ESI) m/z calcd
for C14H10BrF3NO+ [M+H]+: 343.9892; found: 343.9893.
N-(2-(trifluoromethyl)phenyl)acetamide (3n): white solid,
18.0 mg, 44% yield, known compound.4 Eluent: PE/EtOAc (2:1);
1H NMR (400 MHz, DMSO-d6) δ 9.53 (s, 1H), 7.70 (d, J = 7.9
Hz, 1H), 7.65 (t, J = 7.7 Hz, 1H), 7.44 (dd, J = 19.2, 7.9 Hz, 2H),
2.03 (s, 3H). 13C{1H} NMR (101 MHz, DMSO-d6) δ 169.7, 136.1,
133.4, 130.8, 126.9 (q, J = 30.2 Hz), 126.7 (q, J = 5.3 Hz), 124.1
(q, J = 273.3 Hz), 23.3. 19F NMR (376 MHz, DMSO-d6) δ -59.8.
HRMS (ESI) m/z calcd for C10H9F3NO+ [M+H]+: 204.0631;
found: 204.0633.
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solid, 29.8 mg, 50% yield. Eluent: PE/EtOAc (9:1); H NMR
(400 MHz, DMSO-d6) δ 10.28 (s, 1H), 7.96 (s, 1H), 7.89 (d, J =
7.5 Hz, 1H), 7.79 (d, J = 7.9 Hz, 1H), 7.73 (t, J = 7.5 Hz, 1H),
7.67 (dd, J = 7.8, 2.1 Hz, 1H), 7.58 (d, J = 7.9 Hz, 1H), 7.55 –
7.50 (m, 2H). 13C{1H} NMR (101 MHz, DMSO-d6) δ 165.5,
136.4, 135.9 (q, J = 2.0 Hz), 133.8, 133.7, 133.2, 132.1, 131.8,
129.6 (q, J = 287.2 Hz), 129.3, 128.4, 128.0 (q, J = 31.2 Hz),
127.0 (q, J = 5.1 Hz), 126.9. 19F NMR (376 MHz, DMSO-d6) δ -
59.8. HRMS (ESI) m/z calcd for C14H10ClF3NO+ [M+H]+:
300.0398; found: 300.0395.
4-methyl-N-(2-(trifluoromethyl)phenyl)benzamide (3g): white
1
solid, 33.8 mg, 61% yield. Eluent: PE/EtOAc (9:1); H NMR
(400 MHz, DMSO-d6) δ 10.00 (s, 1H), 7.84 (d, J = 8.1 Hz, 2H),
7.77 (d, J = 7.9 Hz, 1H), 7.71 (t, J = 7.7 Hz, 1H), 7.52 (dd, J =
7.3, 4.6 Hz, 2H), 7.32 (d, J = 7.9 Hz, 2H), 2.37 (s, 3H). 13C{1H}
NMR (101 MHz, DMSO-d6) δ 166.6, 142.3, 136.4 (q, J = 5.1
Hz), 135.0 (q, J = 286.2 Hz), 131.7, 131.6, 129.5, 128.1, 127.8,
127.1 (q, J = 36.3 Hz), 127.0 (q, J = 2.0 Hz), 126.7, 21.5. 19F
NMR (376 MHz, DMSO-d6) δ -59.8. HRMS (ESI) m/z calcd for
C15H13F3NO+ [M+H]+: 280.0944; found: 280.0940.
N-(2-(trifluoromethyl)phenyl)isobutyramide (3o): white solid,
28.5 mg, 62% yield. Eluent: PE/EtOAc (4:1); 1H NMR (400 MHz,
DMSO-d6) δ 9.42 (s, 1H), 7.71 (dd, J = 7.8, 1.5 Hz, 1H), 7.65 (t,
J = 7.6 Hz, 1H), 7.43 (t, J = 9.0 Hz, 2H), 2.65 (hept, J = 6.6 Hz,
1H), 1.08 (d, J = 6.8 Hz, 6H). 13C{1H} NMR (101 MHz, DMSO-
d6) δ 176.4, 136.2 (q, J = 5.1 Hz), 133.4, 131.0, 127.2, 126.7 (q,
J = 5.1 Hz), 125.7 (q, J = 29.1 Hz), 124.1 (q, J = 273.1 Hz), 34.5,
19.7. 19F NMR (376 MHz, DMSO-d6) δ -59.8. HRMS (ESI) m/z
calcd for C11H13F3NO+ [M+H]+: 232.0944; found: 232.0946.
N-(2-(trifluoromethyl)phenyl)pivalamide (3p): white solid,
31.7 mg, 65% yield, known compound.8b Eluent: PE/EtOAc (9:1);
1H NMR (400 MHz, DMSO-d6) δ 9.04 (s, 1H), 7.72 (d, J = 7.8
Hz, 1H), 7.66 (t, J = 7.8 Hz, 1H), 7.46 (t, J = 7.8 Hz, 1H), 7.36
(d, J = 7.9 Hz, 1H), 1.20 (s, 9H). 13C{1H} NMR (101 MHz,
DMSO-d6) δ 177.7, 136.8 (q, J = 1.8 Hz), 133.4, 131.5, 127.4,
126.7 (q, J = 5.2 Hz), 126.5 (q, J = 30.5 Hz), 124.1 (q, J = 273.3
Hz), 39.0, 27.6. 19F NMR (376 MHz, DMSO-d6) δ -59.8. HRMS
(ESI) m/z calcd for C12H15F3NO+ [M+H]+: 246.1100; found:
246.1103.
4-methoxy-N-(2-(trifluoromethyl)phenyl)benzamide
(3k):
white solid, 30.2 mg, 52% yield, known compound.8b Eluent:
PE/EtOAc (9:1); 1H NMR (400 MHz, DMSO-d6) δ 9.92 (s, 1H),
7.92 (d, J = 8.8 Hz, 2H), 7.77 (d, J = 7.9 Hz, 1H), 7.71 (t, J = 7.6
Hz, 1H), 7.55 – 7.46 (m, 2H), 7.05 (d, J = 8.8 Hz, 2H), 3.82 (s,
3H). 13C{1H} NMR (101 MHz, DMSO-d6) δ 166.1, 162.5, 136.5
(q, J = 1.9 Hz), 133.6 (q, J = 274.7 Hz) 133.5, 131.7, 130.0, 127.7,
127.0 (q, J = 5.5 Hz), 126.8 (q, J = 27.3 Hz), 126.5, 114.2, 55.9.
19F NMR (376 MHz, DMSO-d6) δ -59.7. HRMS (ESI) m/z calcd
for C15H13F3NO2+ [M+H]+: 296.0893; found: 296.0895.
4-chloro-N-(2-(trifluoromethyl)phenyl)benzamide (3l): white
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solid, 28.2 mg, 47% yield. Eluent: PE/EtOAc (9:1); H NMR
(400 MHz, DMSO-d6) δ 10.22 (s, 1H), 7.97 – 7.89 (m, 2H), 7.79
(d, J = 7.8 Hz, 1H), 7.73 (t, J = 7.6 Hz, 1H), 7.61 (d, J = 8.4 Hz,
2H), 7.53 (t, J = 9.3 Hz, 2H). 13C{1H} NMR (101 MHz, DMSO-
d6) δ 165.8, 137.1, 136.0 (q, J = 1.8 Hz), 133.6, 133.1, 131.6,
130.4 (q, J = 270.4 Hz), 130.0, 129.2, 128.1, 127.0 (q, J = 5.0
Hz), 126.9 (d, J = 29.2 Hz). 19F NMR (376 MHz, DMSO-d6) δ -
N-(2-(trifluoromethyl)phenyl)cyclohexanecarboxamide (3q):
white solid, 29.1 mg, 54% yield, known compound.8b Eluent:
PE/EtOAc (9:1); 1H NMR (400 MHz, DMSO-d6) δ 9.37 (s, 1H),
7.70 (d, J = 7.9 Hz, 1H), 7.64 (t, J = 7.6 Hz, 1H), 7.42 (t, J = 8.5
Hz, 2H), 2.39 (t, J = 11.3 Hz, 1H), 1.81 – 1.71 (m, 4H), 1.62 (d,
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J = 11.5 Hz, 1H), 1.44 – 1.31 (m, 2H), 1.22 (dq, J = 24.6, 12.3
Hz, 3H). 13C{1H} NMR (101 MHz, DMSO-d6) δ 175.4, 136.2 (q,
J = 1.9 Hz), 133.3, 130.9, 127.0, 126.7 (q, J = 5.2 Hz), 125.6 (q,
5-(trifluoromethyl)-2H-benzo[b][1,4]oxazin-3(4H)-one (5b):
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white solid, 16.7 mg, 38% yield. Eluent: PE/EtOAc (4:1); H
NMR (400 MHz, DMSO-d6) δ 10.90 (s, 1H), 7.29 – 7.24 (m, 1H),
7.15 (d, J = 1.9 Hz, 1H), 7.11 (d, J = 8.4 Hz, 1H), 4.67 (s, 2H).
13C{1H} NMR (101 MHz, DMSO-d6) δ 164.8, 146.6, 128.3,
124.6 (q, J = 270.8 Hz), 123.2 (q, J = 32.3 Hz), 120.6 (q, J = 4.0
Hz), 117.3, 112.8 (q, J = 3.8 Hz), 67.2. 19F NMR (376 MHz,
J = 27.8 Hz), 124.1 (q, J = 273.1 Hz), 44.3, 29.4, 25.9, 25.7. 19
F
NMR (376 MHz, DMSO-d6) δ -59.8. HRMS (ESI) m/z calcd for
C14H17F3NO+ [M+H]+: 272.1257; found: 272.1256.
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3-oxo-N-(2-(trifluoromethyl)phenyl)butanamide (3r): white
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solid, 24.5 mg, 50% yield; Eluent: PE/EtOAc (4:1). H NMR
DMSO-d6) δ -60.8. HRMS (ESI) m/z calcd for C9H7F3NO2
(400 MHz, DMSO-d6) δ 9.79 (s, 1H), 7.72 (d, J = 7.8 Hz, 1H),
7.67 (t, J = 7.7 Hz, 1H), 7.57 (d, J = 8.0 Hz, 1H), 7.43 (t, J = 7.6
Hz, 1H), 3.59 (s, 2H), 2.19 (s, 3H). 13C{1H} NMR (101 MHz,
DMSO-d6) δ 203.3, 166.5, 135.5, 133.5, 129.9, 126.9 (q, J = 34.4
[M+H]+: 218.0423; found: 218.0426.
7-(trifluoromethyl)indolin-2-one (5c): white solid, 16.2 mg, 40%
1
yield. Eluent: PE/EtOAc (9:1); H NMR (400 MHz, DMSO-d6)
δ 10.80 (s, 1H), 7.44 (dd, J = 14.7, 7.7 Hz, 2H), 7.08 (t, J = 7.7
Hz, 1H), 3.56 (s, 2H). 13C{1H} NMR (101 MHz, DMSO-d6) δ
177.2, 141.3 (q, J = 2.1 Hz), 128.7, 128.4, 124.2 (q, J = 4.7 Hz),
Hz), 126.7 (q, J = 4.9 Hz), 124.0 (q, J = 273.5 Hz), 51.6, 30.5. 19
F
NMR (376 MHz, DMSO-d6) δ -59.8. HRMS (ESI) m/z calcd for
C11H11F3NO2+ [M+H]+: 246.0736; found: 246.0734.
124.2 (q, J = 271.7 Hz), 121.7, 110.7 (q, J = 32.5 Hz), 35.4. 19
F
2-oxo-2-phenyl-N-(2-(trifluoromethyl)phenyl)acetamide (3s):
NMR (376 MHz, DMSO-d6) δ -60.6. HRMS (ESI) m/z calcd for
C9H7F3NO+ [M+H]+: 202.0474; found: 202.0473.
1
yellow solid, 30.6 mg, 52% yield. Eluent: PE/EtOAc (9:1); H
NMR (400 MHz, DMSO-d6) δ 10.72 (s, 1H), 8.05 (d, J = 7.3 Hz,
2H), 7.82 (d, J = 7.8 Hz, 1H), 7.78 – 7.73 (m, 2H), 7.71 (d, J =
7.8 Hz, 1H), 7.62 (t, J = 7.7 Hz, 2H), 7.55 (t, J = 7.4 Hz, 1H).
13C{1H} NMR (101 MHz, DMSO-d6) δ 189.9, 165.0, 135.3,
134.2 (q, J = 2.0 Hz), 133.9, 133.1, 131.7 (d, J = 281.7 Hz), 131.2,
130.0, 129.6, 128.2, 127.1 (q, J = 5.2 Hz), 125.6 (q, J = 29.7 Hz).
19F NMR (376 MHz, DMSO-d6) δ -59.8. HRMS (ESI) m/z calcd
for C15H11F3NO2+ [M+H]+: 294.0736; found: 294.0738.
5-chloro-4-(trifluoromethyl)benzo[d]oxazol-2(3H)-one (5d):
1
white solid, 22.0 mg, 46% yield. Eluent: PE/EtOAc (9:1); H
NMR (400 MHz, DMSO-d6) δ 12.12 (s, 1H), 7.57 (d, J = 8.5 Hz,
1H), 7.37 (d, J = 8.5 Hz, 1H). 13C{1H} NMR (101 MHz, DMSO-
d6) δ 154.6, 143.2, 130.8 (q, J = 2.0 Hz), 125.6 (q, J = 2.2 Hz),
124.5, 122.8 (q, J = 272.7 Hz), 114.4, 109.7 (q, J = 33.5 Hz). 19
F
NMR (376 MHz, DMSO-d6) δ -57.1. HRMS (ESI) m/z calcd for
C8H4ClF3NO2+ [M+H]+: 237.9877; found: 237.9875.
4-methyl-N-(2-(trifluoromethyl)phenyl)benzenesulfonamide
(3t): white solid, 31.8 mg, 50% yield, known compound.16 Eluent:
PE/EtOAc (4:1); 1H NMR (400 MHz, DMSO-d6) δ 9.87 (s, 1H),
7.67 (dd, J = 14.8, 8.0 Hz, 3H), 7.55 (t, J = 7.4 Hz, 1H), 7.41 (dd,
J = 15.1, 7.9 Hz, 3H), 7.00 (d, J = 8.0 Hz, 1H), 2.38 (s, 3H).
13C{1H} NMR (101 MHz, DMSO-d6) δ 143.7, 138.7, 134.7,
133.7, 130.2, 128.7, 127.8, 127.6 (q, J = 5.3 Hz), 127.3 (q, J =
35.9 Hz), 123.7 (q, J = 273.6 Hz), 21.5. 19F NMR (376 MHz,
DMSO-d6) δ -58.4. HRMS (ESI) m/z calcd for C14H13F3NO2S+
[M+H]+: 316.0614; found: 316.0613.
(3,3,3-trifluoroprop-1-ene-1,1-diyl)dibenzene (7): colorless
oil, 20.1 mg, 40% yield. Eluent: PE; 1H NMR (400 MHz, CDCl3)
δ 7.41 – 7.36 (m, 3H), 7.34 (d, J = 7.8 Hz, 3H), 7.29 – 7.21 (m,
4H), 6.13 (q, J = 8.3 Hz, 1H). 13C{1H} NMR (101 MHz, CDCl3)
δ 152.5 (q, J = 5.9 Hz), 140.1, 137.3, 129.4, 129.1 (q, J = 1.7 Hz),
128.5, 128.0, 128.0, 123.1 (q, J = 270.7 Hz), 115.5 (q, J = 33.7
Hz), 113.6. 19F NMR (376 MHz, CDCl3) δ -55.7. HRMS (ESI)
m/z calcd for C15H12F3+ [M+H]+: 249.0886; found: 249.0889.
ASSOCIATED CONTENT
Supporting Information
8-(trifluoromethyl)-3,4-dihydroquinolin-2(1H)-one
(5a):
The Supporting Information is available free of charge on the
ACS Publications website.
1
white solid, 18.4 mg, 43% yield. Eluent: PE/EtOAc (4:1); H
NMR (400 MHz, DMSO-d6) δ 9.03 (s, 1H), 7.50 (t, J = 6.5 Hz,
2H), 7.12 (t, J = 7.7 Hz, 2H), 3.04 – 2.84 (m, 2H), 2.55 – 2.50 (m,
2H). 13C{1H} NMR (101 MHz, DMSO-d6) δ 171.0, 136.0 (q, J =
2.1 Hz), 132.8, 127.7, 126.3 (q, J = 269.6 Hz), 125.0 (q, J = 5.2
Hz), 122.8, 115.0 (q, J = 30.1 Hz), 30.5, 25.5. 19F NMR (376
1H NMR of mechanistic studies and copies of 1H NMR, 13
NMR and 19F NMR spectra (PDF)
C
AUTHOR INFORMATION
Corresponding Author
MHz, DMSO-d6)
δ
-59.4. HRMS (ESI) m/z calcd for
*E-mail for G.A.: chemagh@163.com.
*E-mail for G.L.: gmli@hlju.edu.cn.
C10H9F3NO+ [M+H]+: 216.0631; found: 216.0632.
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Notes
(3) (a) Xiao, P.; Rong, J.; Ni, C.; Guo, J.; Li, X.; Chen, D.;
The authors declare no competing financial interest.
Hu, J. Radical (Phenylsulfonyl)difluoromethylation of
Isocyanides with PhSO2CF2H under Transition-Metal-
Free Conditions. Org. Lett. 2016, 18, 5912-5915; (b) Wang,
J.; Zhang, X.; Wan, Z.; Ren, F. TCDA: Practical Synthesis
and Application in the Trifluoromethylation of Arenes and
Heteroarenes. Org. Process Res. Dev. 2016, 20, 836-839;
(c) Liang, Z.; Wang, F.; Chen, P.; Liu, G. Copper-
Catalyzed Intermolecular Trifluoromethylthiocyanation of
Alkenes: Convenient Access to CF3-Containing Alkyl
Thiocyanates. Org. Lett. 2015, 17, 2438-2441; (d) Li, X.;
Zhao, J.; Zhang, L.; Hu, M.; Wang, L.; Hu, J. Copper-
ACKNOWLEDGMENTS
The authors gratefully acknowledge support from National
Natural Science Foundation of China (21502046), Natural
Science Foundation of Heilongjiang Province (B2016008) and
the University Nursing Program for Young Scholars with
Creative Talents in Heilongjiang Province (UNPYSCT-2017124).
The Fundamental Research Funds for the Central Universities
from Harbin Engineering University (HEUCFD1412,
HEUCFJ161002, HEUCFJ171006, and HEUCFJ181008) were
also acknowledged. Dr. Guijie Mao was acknowledged for her
help in the NMR spectrum.
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Trifluoromethylation
Using
Phenyl
Trifluoromethyl Sulfoxide. Org. Lett. 2015, 17, 298-301.
(4) Zhang, L. S.; Chen, K.; Chen, G. H.; Li, B. J.; Luo, S.;
Guo, Q. Y.; Wei, J. B.; Shi, Z. J. Palladium-Catalyzed
Trifluoromethylation of Aromatic C–H Bond Directed by
an Acetamino Group. Org. Lett. 2013, 15, 10-13.
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