Trifluoromethylations of Alkenes Using PhICF3Cl as Bifunctional Reagent

Article abstract of DOI:10.1021/acs.joc.9b01901

We described a trifluoromethylation of alkenes using PhICF₃Cl as bifunctional reagent. Chlorotrifluoromethylated products were obtained when nonconjugated alkenes were treated with PhICF₃Cl in 1,4-dioxane at 60 °C, while vinyl C-H tr

Full text of DOI:10.1021/acs.joc.9b01901

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Trifluoromethylations of Alkenes Using PhICFCl as Bifunctional Reagent
Cong Xu, Wanqiao Huang, Ruzhong Zhang, Chi Gao, Yuxin Li, and Mang Wang
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.9b01901 • Publication Date (Web): 04 Oct 2019
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The Journal of Organic Chemistry
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Trifluoromethylations of Alkenes Using PhICF3Cl as Bifunctional
Reagent
Cong Xu,‡ Wanqiao Huang,† Ruzhong Zhang,† Chi Gao,† Yuxin Li,‡ and Mang Wang*,†,#
†Jilin Province Key Laboratory of Organic Functional Molecular Design & Synthesis, College of
Chemistry, Northeast Normal University, Changchun 130024, China
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‡National Engineering Laboratory for Druggable Gene and Protein Screening, School of Life Sciences,
Northeast Normal University, Changchun 130117, China
#State Key Laboratory of Elemento-organic Chemistry, Nankai University, Tianjin 300071, China
Cl
CF3
CF3
CF Cl
+ PhI
3
CF
Cl
3 and
easy-handled bifunctional reagent with
uncatalyzed condition
broad scope of unactivated alkenes
Abstract: We described a trifluoromethylation of alkenes using PhICF3Cl as bifunctional reagent.
Chlorotrifluoromethylated products were obtained when non-conjugated alkenes were treated with
PhICF3Cl in 1,4-dioxane at 60 oC, while vinyl C-H trifluoromethylated products were yielded by further
elimination of hydrochloride in the case of those conjugated alkene substrates in DMF. Broad substrate
scope, especially including complex alkenes bearing biological active motifs, suggests that this mild
reaction is feasible for late-stage modification in drug discovery.
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The development of trifluoromethylation reactions is of great significance in organic synthesis because
the incorporation of CF3 into target molecules often enhances their physical, chemical or biological
properties, which include lipophilicity, metabolic stability, hydrophobicity or binding selectivity.1,2 As
powerful transformation to increase molecular complexity,3 trifluoromethylation-based
difunctionalization reaction of alkenes can incorporate two functional groups including CF3 across a
double bond. In this field, the chlorotrifluoromethylation is relatively scarce though Cl is a convertible
functional group for product diversity. Previous work usually used a CF3 agent, such as Togni, Umemoto
or Langlois reagent, along with an external Cl source, for chlorotrifluoromethylations of alkenes via a
metal-catalytic, photo-catalytic, or electro-catalytic strategy (Scheme 1A).4 The reaction was difficult to
achieve using CF3Cl as bifunctional reagent via the Kharasch reaction as a result of the relatively high
dissociation energy of the C-Cl bond.5 CF3SO2Cl was reported to be used as both CF3 and Cl source in
chlorotrifluoromethylations of alkenes under catalytic conditions (Scheme 1B),6 but simple and mild
method is still desired.
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Scheme 1. Chlorotrifluoromethylations of Alkenes.
Previous works:
Cl
CF
Cl
source
3 source and
A
B
CF3
CF3
metal-/photo-/electro-catalysis
Cl
CF
2Cl
3SO
metal-/photo-catalysis
This work:
Cl
CF Cl 1
( )
PhI
3
CF3
alkenes = styrenes
CF3
C
uncatalyzed
Recently, we successfully synthesized an externally coordinated CF3-containing λ3-iodane,
PhICF3Cl (1).7 Compared with internally coordinated and neutral Togni’s reagents, compound 1 has an
iodonium-like character, which results in an enhanced CF3-transfer ability in a wide range of electrophilic
trifluoromethylation reactions without catalyst.7a-c Considering the unique feature of PhICF3Cl, and of the
important applications of trifluoromethylation of alkenes, we envisioned a chlorotrifluoromethylation of
alkenes. Herein, we reported this trifluoromethylation, in which all tested alkenes, including non-
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conjugated alkenes and conjugated alkenes, are compatible with the uncatalyzed conditions to furnish
chlorotrifluoromethylated products and olefin C-H trifluoromethylated products, respectively.
1
2
3
4
5
6
Table 1. Optimization of Reaction Conditions.a,b
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8
9
O
O
CF Cl 1
( )
PhI
3
CF3
N
N
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1,4-dioxane
Cl
O
O
2a
3a
entry
1
temp
(℃)
time
(h)
yield of 3a
(equiv)
(%)
1
2
1.1
1.1
1.1
1.1
1.1
1.5
1.7
2.0
2.0
1.7
2.0
2.0
2.0
25
40
50
60
70
60
60
60
60
60
60
60
60
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12
12
0
0
3
38
57
55
77
82
88
>99
95
92
90
0
4
5
6
7
8
9c
10c
11d
12c
13e
aReaction conditions: 2a (0.2 mmol), 1,4-dioxane (2 mL),
N2. b19F NMR yield using benzotrifluoride as an internal
c
d
standard. 1,4-dioxane (1 mL). 1,4-dioxane (0.5 mL).
eUnder air condition.
We initially examined the trifluoromethylation of non-conjugated alkene 2a using PhICF3Cl as the
CF3 source in 1,4-dioxane. As shown in Table 1, the temperature has significant influence on the reaction.
Lower temperature resulted in lower yield or even no reaction occured with almost all the substrate 2a
recovered. Higher temperature could increase the yield of 3a up to 57%, along with trace amount of
byproducts, including vinyl-CF3 product, allyl-CF3 product and hydrotrifluoromethylated product (entries
1-5). Increasing the amount of 1 could slightly improve the yield of 3a (entry 6-8). Further brief survey
revealed that other solvents, such as DMF, DCM, THF, EtOAc were less effective for this reaction (see
the SI). Gratifyingly, optimal result was obtained by increasing the concentration of the reaction
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furnishing 3a in excellent yield (entry 9). However, further increasing the concentration and less amount
of 1 decreased the yields marginally (entry 10 and 11). Shorter reaction time also led to inefficient results
(entry 12). Nitrogen atmosphere proved to be crucial for achieving the transformation from 2a to 3a (entry
13).
1
2
3
4
5
6
Scheme 2. Substrate Scope of Chlorotrifluoromethylation of Alkenes.a
7
8
9
CF Cl 1
( )
PhI
3
R
R
CF3
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60
1,4-Dioxane, N2,
16 h, 60 oC
Cl
2
3
non-conjugated alkenes
O
3c
R = Me, : 93% (88%)
3d
R = OMe, : 86% (79%)
3e
R = tBu, : 81%(74%)
3f
R = Ph, : 87%(81%)
3g
R = CN, : 98%(92%)
3h
R = CF3, : 88%(82%)
3i
R = F, : 94%(87%)
3j
R = Br, : 84%(79%)
R
CF3
N
Cl
O
S
Cl
CF3
O
O
O
3a
: >99%(91%)
Cl
O
Me
Cl
CF3
Me
O
3l
Me
: 58%
CF3
Me
3k
R = OCF3, : 90%(82%)
3b
: 92%(84%)
drug-molecule-derived alkenes
Cl
Cl
CF3
O
CF3
O
4
Cl
O
CF3
N
O
O
O
O
O
Ph
2
O
4-methylumbelliferone derivative
(S)-(+)-ibuprofen derivative
oxaprozin derivative
Ph
3n
3o
3m
: 79%(75%)
dr ~ 1:1
: 57%(50%)
: 96%(88%)
O
O
4
O
O
CF3
H
Cl
N
O
H
H
F3C
4
O
Cl
Cl
estrone derivative
3q
indomethacin derivative
: 92%(85%)
3p
: 64%(58%)
conjugated alkenes
Cl
Cl
Cl
O
CF3
CF3
CF3
CF3
O
R
R
Cl
: trace
3u
R = NO2, : trace
3r
R = OMe, : 87%
3x
b
3v
R = NH2, : complex
R = OH,
3t
: 91%(83%)
3s
R = Ph,
: 72%(63%)
3w
: complex
All yields are 19F NMR yields using benzotrifluoride as an internal standard. Isolated yields are in
o
1
parentheses. Reaction conditions: alkenes (0.2 mmol), (0.4 mmol), 1,4-dioxane (1.0 mL), 60 C.
a16h; b40h.
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The above reaction presented a simple and efficient process for olefin chlorotrifluoromethylation.
Thus, we investigated the substrate scope of the reaction under optimized conditions. As described in
Scheme 2, terminal alkenes, including phthalimide (2a), ester (2b), sulfonic esters (2c-2k), proved
suitable substrates and provided the desired products 3a-k in 81−99% 19F NMR yields. For internal olefin,
we examined 2,3-Dimethyl-2-butene (2l) under identically condition. Desired 3l was obtained in 58% 19F
NMR. However, it was inseparable due to its volatility.4f When drug-containing compounds, 4-
methylumbelliferone (2m), ibuprofen (2n), oxaprozin (2o), indomethacin (2p), and estrone (2q)
derivatives, were treated with PhICF3Cl, reactions also proceeded smoothly under identically conditions
to deliver chlorotrifluoromethylated products 3m-q in moderate to excellent 19F NMR yields (57−96%).
Intriguingly, in the case of (S)-(+)-ibuprofen derivative 2n, the stereochemistry at the α-position of its
carbonyl group was almost retained under the mild reaction condition (see the SI). Encouraged by the
results of non-conjugated alkenes, we further explored the reaction of conjugated alkenes with 1. As we
expected, chlorotrifluoromethylation of styrene derivatives 2r-t occurred smoothly and afforded the
desired products 3r-t in good yields. In the case of substrate 2r possessing electron-donating substituent
on the phenyl ring, product 3r was too unstable to be isolated.6e However, reactions of styrenes bearing
electron-withdrawing substituents (2u, 2x) were sluggish. In the cases of styrenes with OH or NH2 group
on the phenyl ring (2v, 2w), the experimental results were complex likely because of the sensitivity of
these substrates to the oxidative reaction system.
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Interestingly, when 1,1-diphenylethene (4a) was subjected to the above reaction conditions, vinyl-
CF3 product (5a) was obtained along with chlorotrifluoromethylated product (6a) at 60 ℃ (Scheme 3,
entry 1). Although 6a was detected as main product at lower temperature (entry 2), it could not be isolated
due to its sensitivity to the column chromatography. It was found that the ratio of 5a to 6a was increased
at higher temperature, but the conversion of 4a was incomplete in this case due to the decomposition of
PhICF3Cl. Thus, we rescreened the reaction conditions. Delightfully, by switching the solvent from 1,4-
dioxane to DMF, the vinyl-CF3 product 5a could be isolated in excellent yield at 60 ℃ (entry 3). The
conversion of 6a into 5a could be clearly detected during the reaction (entries 4 and 5).
Scheme 3. Trifluoromethylation of 1,1-Diphenylethene (4a).
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Cl
Ph
Ph
Ph
CF Cl
PhI
1
2
3
4
3
CF3
CF3
+
12 h
Ph
6a
Ph
Ph
4a
5a
5
6
7
8
entry solvent
temp (oC) yield of
yield of
5a
6a
1
2
3
4
5
1,4-dioxane 60 oC
1,4-dioxane 50 oC
DMF
DMF
DMF
22%
6%
74%
65%
-
60 oC
40 oC
> 99%
42%
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60
39%
-
40 then 60oC 95%
All yields are 19F NMR yields using benzotrifluoride as an
internal standard.
Scheme 4. Substrate Scope of Csp2-H Trifluoromethylation of Conjugated Alkenes.a
CF3
R3
H
CF Cl
PhI
R1
R1
3
R3
DMF, N2, 12 h
60~100 oC
R2
R2
4
5
1
2
a
5a
5b
5c
5d
5e
, R = R = Ph, >99% (98%)
1
2
a
, R = R = 4-FPh, >99% (96%)
1
2
b
, R = R = 4-ClPh, 94% (89%)
1
2
b
, R = R = 4-BrPh, 96% (92%)
R1
R1
1
2
c
, R = R = 4-OMePh, 87% (81%)
CF3
1
2
c
5f
, R = R = 4-MePh, 80% (75%)
R2
R2
1
2
a
5g
5h
, R = 4-FPh, R = Ph, 86% (76%, 1.1/1)
1
2
b
, R = 4-ClPh, R = Ph, 93% (88%, 1.1/1)
1
2
a
5i
5j
, R = 2-naphthyl, R = Ph, 86% (79%, 1.6/1)
1
2
b
, R = 2-MePh, R = Ph, 98% (92%, 1/1.2)
CF3
CF3
MeO
MeO
MeO
MeO
N
N
H
H
2r
5k
64%d (61%)
4l
5l
67%a (62%)
Ph
Ph
CF3
Ph
CF3
Ph
4m
5m
51%d (46%)
4n
5n
86%e (79%)
Reaction conditions: alkenes (0.2 mmol), DMF (2.0 mL), 60 oC.
(0.34 mmol);
(0.34 mmol),
a1
b1
o
o
o
70 oC; (0.22 mmol);
c1
(0.4 mmol), 70 C, 24 h;
(0.5 mmol), 60 C, 12 h, then 100 C, 12 h.
d1
e1
All yields are 19F NMR yields using benzotrifluoride as an internal standard. Isolated yields are in
parentheses. The ratio of isomers Z to E are in parentheses.
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Trifluoromethylated alkenes are vital structural unit, which have been widely applicated in medicinal
chemistry8 and material science.9 Taking both step and atom economy into consideration, C-H
trifluoromethylation of alkenes provides a direct route to CF3-containing alkenes.10 It is clear that the
reaction of 4a and 1 presents a new and efficient vinyl C-H trifluoromethylation of alkenes. Thus, we set
out to investigate the scope of the reaction. To our delight, most tested trifluoromethylations of gem-diaryl
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substituted alkenes 4a-j using 1 as CF3 reagent were efficient leading to 5a-j in high F NMR yields
(Scheme 4), in which electronic effect was clearly observed. For example, the reactions of 4c and 4d
bearing electron-deficient substituent on the phenyl ring often provided 5c and 5d in moderate yields
along with the formation of chlorotrifluoromethylated products 6c and 6d. Fortunately, 5c, d could be
achieved in 94% and 96% 19F NMR yield respectively, at higher temperature. By comparison,
trifluoromethylations of 4 with electron-rich substituents were highly efficient. Bistrifluoromethylated
products 7 usually accompanied to decrease the yields of 5.10i,11 By the use of 1 equivalence of 1, 5e and
5f were obtained in good yields. For alkenes 4g-j having two different aryl substituents, a mixture of E-
and Z-isomers 5g-j were resulted. Styrenes seemed to be inefficient substrates under identical reaction
conditions. The reaction of 1 with vinylbenzene either in dioxane or in DMF was complex and no
corresponding trifluoromethylated products were identified in two cases. Furthermore, polymerization
product wasn’t detected in the reaction system by HRMS. Only electron-rich styrene 2r gave 5k in 64%
19F NMR yield. Although increasing reaction temperature proved to benefit the generation of 5k but
usually made the reaction complex, especially in dioxane. By comparison, the reaction of 2r in DMF
furnished 5k at lower temperature. When internal alkenes 4l and 4m were tested, trifluoromethylations
19
occurred. 5l and 5m were obtained in 67% and 51% F NMR yield respectively. We also tested the
reaction of trisubstituted alkene substrates, in which 4n gave 5n in 86% 19F NMR yield. Unfortunately,
non-conjugated alkenes used in scheme 2 could not furnish vinyl CH trifluoromethylated products under
the identical conditions. Chlorotrifluoromethylated products were still main products, while the reactions
turned to be complex at higher temperature or after longer time. Nevertheless, chlorotrifluoromethylated
products 3 could lead to the vinyl-CF3 products in the presence of DBU.4a,10m Based on our experimental
results, we speculated that the type of substrates (conjugated or non-conjugated) determined the products,
the solvent should not be a deciding factor.
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Scheme 5. Radical-Clock Experiment.a,b
1
2
3
Cl
4
5
6
7
CF Cl 1)
PhI
(
3
60oC, N2
CF3
Ph
Ph
8
9
DMF
1,4-dioxane
42%
15%
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59
60
a
1
Reaction conditions: alkene (0.2 mmol), (0.34
mmol), Solvent (2 mL),12h, N2. bBased on 19
F
NMR using PhCF3 as the internal standard.
To gain mechanistic insight into this reaction, a radical-clock experiment was conducted (Scheme
5). When (1-cyclopropylvinyl)benzene was treated with 1 in either DMF or 1,4-dioxane, ring-opening
product (see SI) was obtained in 42% and 15% 19F NMR yield, respectively. Such results suggested that
a radical process was likely involved for the chlorotrifloromethylation of alkenes with PhICF3Cl under
catalyst-free conditions. We conducted an electrochemical study (see the SI for details). Analysis of the
resulting cyclic voltammogram of 1 mM DMF solution of 1 and 4a under 60 ℃ respectively, 1 showed
one reduction process with a peak potential of -0.641 V (this reduction wave could be unambiguously
identified as the reduction of the hypervalent bond15), 4a showed one oxidation process with a peak
potential of -0.694 V. According to the data, an initial SET process from olefin to reagent 1 might be
feasible.
Although the exact mechanism requires further investigation and ionic pathway can’t be ruled out at
this time, based on current experimental results, a plausible reaction mechanism was proposed as
described in Scheme 6. Initially, the reaction of alkene with PhICF3Cl undergoes a SET process to
generate radical cation I and hypervalent iodine radical II along with the release of Cl to the reaction
mixture. The coupling of radical cation I with CF3 radical, generated from II with the concomitant release
of PhI, affords carbocation III. Chlorotrifluoromethylated product 3 or 6 is formed by the nucleophilic
attack of Cl to III. In the case of electron-rich conjugated alkenes 4 as the substrates,
chlorotrifluoromethylated product 6 tends to convert into thermodynamically stable conjugated alkenes 5
likely via further elimination of HCl, while -H elimination reaction of III for direct formation of 5 can
not be excluded.
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Scheme 6. Plausible Mechanism.
1
2
radical cation pathway
ionic pathway
3
4
5
CF Cl
PhI
CF Cl
3
PhI
3
CF3
CF
[PhI
]
+
3
H
H
I
6
7
II
Ph
I
IV
2
4
or
8
9
Cl
Cl
PhI
PhI
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11
12
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60
Cl
CF3
CF3
CF3
H
H
Cl
Cl
III
3
6
or
III
Cl
H
H
CF3
5
In conclusion, we have demonstrated a catalyst-free chlorotrifluoromethylation of alkenes using
PhICF3Cl as bifunctional reagent. Radical-clock experiment showed that a CF3 radical process was
involved. Vinyl C-H trifluoromethylated products were yielded by further elimination of hydrochloride
in the case of those conjugated alkene substrates. This protocol is tolerant of a range of functional groups,
especially some complex molecules bearing biological active motifs or drug fragments, displaying
potential for further applications in medicinal and biological chemistry research.
EXPERIMENTAL SECTION
General Method. Unless otherwise stated, all starting materials and solvents were obtained from
commercial suppliers and used without further purification. All new compounds were fully characterized.
Column chromatography was performed using silica gel (particle size 300-400 mesh ASTM, purchased
from Taizhou, China). The heat source is oil bath. 1H NMR, 13C NMR and NOESY spectra were recorded
at 25 ℃ on a Bruker 600 MHz or Varian 500 MHz, 400 MHz, and 151 MHz or 125 MHz spectrometer,
respectively by using TMS as internal standard. 19F NMR were recorded at 25 ℃ on a Bruker 565 MHz
or Varian 470 MHz spectrometer by using (trifluoromethyl)benzene (δ -62.8 ppm) as external standard.
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Data for H, C, F were recorded as follows: chemical shift (δ, ppm), multiplicity (s = singlet, d =
doublet, t = triplet, q = quartet, m = multiplet, dd = doublet of doublets, ddd = doublet of doublet of
doublets, dt = doublet of triplets, dq = doublet of quartets, td = triplet of doublets). High-resolution mass
spectra (HRMS) were obtained using a Bruker micro TOF II focus spectrometer (ESI). Substrates 2, 4, 6
were prepared following the known procedure.10i,12,13 Products 3b,4a 3c,4a 3m,6e 3s,4d,6e,6f 3t,6f 5a-c10o,
5d10i, 5e-f10o, 5h-i10o, 5k10o, 5n14 are known compounds.
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Procedures for the Synthesis of Substrates 2o. The solution of hex-5-en-1-ol (1.5 mmol, 180 μL), 3-
(4,5-diphenyloxazol-2-yl)propanoic acid (1 mmol, 294 mg), dicyclohexylmethanediimine (DCC) (2
mmol, 516 mg) and N,N-dimethylpyridin-4-amine (DMAP) (0.1 mmol, 13 mg) in DCM (2 mL) was
stirred at room temperature for overnight. The reaction mixture was diluted with dichloromethane, and
then washed with water. The organic layer was dried over anhydrous magnesium sulfate, and concentrated
in vacuo. The residue was purified by column chromatograph (PE: EA= 10:1) to afford the product as a
colorless oil (323 mg, 86 %).
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hex-5-en-1-yl 3-(4,5-diphenyloxazol-2-yl)propanoate (2o). Yield 86%; 323 mg; colorless oil; H
NMR (600 MHz, CDCl3, δ): 7.64 – 7.62 (m, 2H), 7.58 – 7.56 (m, 2H), 7.37 – 7.29 (m, 6H), 5.76 (ddt, J
= 16.9, 10.2, 6.7 Hz, 1H), 5.01 – 4.93 (m, 2H), 4.13 (t, J = 6.6 Hz, 2H), 3.18 (t, J = 7.6 Hz, 2H), 2.91 (t,
J = 7.5 Hz, 2H), 2.05 (q, J = 7.2 Hz, 2H), 1.67 – 1.62 (m, 2H), 1.47 – 1.42 (m, 2H). 13C{1H} NMR (151
MHz, CDCl3, δ): 172.1, 161.8, 145.4, 138.3, 135.1, 132.5, 129.0, 128.6 (2C), 128.5 (2C), 128.4, 128.1,
127.9 (2C), 126.5 (2C), 114.9, 64.8, 33.3, 31.2, 28.0, 25.2, 23.6. HRMS (ESI-TOF) m/z: [M + H]+ Calcd
for C24H26NO3 376.1907; Found 376.1915.
Procedures for the Synthesis of Substrates 2p. The solution of hex-5-en-1-ol (1.5 mmol, 180 μL), 2-
(1-(4-chlorobenzoyl)-5-methoxy-2-methyl-1H-indol-3-yl)acetic
acid
(1
mmol,
358
mg),
dicyclohexylmethanediimine (DCC) (1.2 mmol, 247 mg) and N,N-dimethylpyridin-4-amine (DMAP) (1.2
mmol, 146 mg) in DCM (10 mL) was stirred at room temperature for overnight. The reaction mixture was
diluted with dichloromethane, and then washed with water. The organic layer was dried over anhydrous
magnesium sulfate, and concentrated in vacuo. The residue was purified by column chromatograph (PE:
EA= 10:1) to afford the product as a yellow oil (251 mg, 57 %).
hex-5-en-1-yl 2-(1-(4-chlorobenzoyl)-5-methoxy-2-methyl-1H-indol-3-yl)acetate (2p). Yield 57%;
251 mg; yellow oil; 1H NMR (600 MHz, CDCl3, δ): 7.67 – 7.65 (m, 2H), 7.48 – 7.46 (m, 2H), 6.97 (d, J
= 2.5 Hz, 1H), 6.87 (d, J = 9.0 Hz, 1H), 6.67 (dd, J = 9.0, 2.5 Hz, 1H), 5.74 (ddt, J = 16.9, 10.2, 6.7 Hz,
1H), 4.99 – 4.93 (m, 2H), 4.10 (t, J = 6.6 Hz, 2H), 3.83 (s, 3H), 3.66 (s, 2H), 2.39 (s, 3H), 2.03 (q, J = 7.1
Hz, 2H), 1.66 – 1.61 (m, 2H), 1.43 – 1.38 (m, 2H). 13C{1H} NMR (151 MHz, CDCl3, δ): 170.9, 168.3,
156.0, 139.2, 138.2, 135.9, 133.9, 131.2 (2C), 130.8, 130.7, 129.1 (2C), 115.0, 114.9, 112.7, 111.7, 101.3,
65.0, 55.7, 33.2, 30.4, 28.1, 25.2, 13.4. HRMS (ESI-TOF) m/z: [M + H]+ Calcd for C25H27ClNO4
440.1623; Found 440.1611.
General Procedures for the Synthesis of Products 3 (3a as an Example). To a dried
polytetrafluoroethene (PTFE) sealed pressure tube was added alkene 2a (43 mg, 0.2 mmol), 1 (124 mg,
0.4 mmol) and anhydrous 1,4-dioxane (1.0 mL) in sequence under N2. After the reaction mixture was
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stirred at 60 ℃ (oil bath) for 16 h, PhCF3 as an internal standard (0.0812 mmol, 10 μL) was added and the
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yield was calculated to be >99% from F NMR integrals. The reaction mixture was purified by silica
column chromatography (eluent: petroleum ether/EtOAc = 5/1) to give 58 mg (91%) of 3a as white solid
(the yield was calculated based on 2a).
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2-(4-chloro-6,6,6-trifluorohexyl)isoindoline-1,3-dione (3a). Prepared according to the description in
the general experimental procedure: yield 91%; 58 mg; white solid; mp 70−71 ℃; 1H NMR (600 MHz,
CDCl3, δ): 7.86 – 7.84 (m, 2H), 7.74 – 7.72 (m, 2H), 4.19 – 4.15 (m, 1H), 3.74 (t, J = 6.6 Hz, 2H), 2.65 –
2.50 (m, 2H), 2.03 – 1.97 (m, 1H), 1.92 – 1.76 (m, 3H). 13C{1H} NMR (151 MHz, CDCl3, δ): 168.4 (2C),
134.1 (2C), 132.0 (2C), 125.1 (q, J = 277.6 Hz), 123.3 (2C), 53.4 (d, J = 3.3 Hz), 42.4 (q, J = 28.6 Hz),
37.0, 35.2, 25.3. 19F NMR (565 MHz, CDCl3, δ): -63.8 (t, J = 10.4 Hz, 3F). HRMS (ESI-TOF) m/z: [M +
H]+ Calcd for C14H14ClF3NO2 320.0660; Found 320.0648.
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5-chloro-7,7,7-trifluoroheptyl benzoate (3b). 3b was obtained as a colorless oil (51.7 mg, 84%).
5-chloro-7,7,7-trifluoroheptyl 4-methylbenzenesulfonate (3c). 3c was obtained as a colorless oil (63
mg, 88%).
5-chloro-7,7,7-trifluoroheptyl 4-methoxybenzenesulfonate (3d). Prepared according to the
description in the general experimental procedure: yield 79%; 59.1 mg; colorless oil; 1H NMR (600 MHz,
CDCl3, δ): 7.83 (d, J = 8.4 Hz, 2H), 7.01 (d, J = 9.0 Hz, 2H), 4.05 – 4.01 (m, 3H), 3.88 (s, 3H), 2.63 –
2.54 (m, 1H), 2.53 – 2.44 (m, 1H), 1.81 – 1.76 (m, 1H), 1.73 – 1.56 (m, 4H), 1.50 – 1.41 (m, 1H). 13C{1H}
NMR (151 MHz, CDCl3, δ): 163.8, 130.1 (2C), 127.4, 125.2 (q, J = 277.5 Hz), 114.5 (2C), 69.8, 55.7,
53.7 (q, J = 3.3 Hz), 42.3 (q, J = 28.5 Hz), 37.2, 28.1, 22.1. 19F NMR (565 MHz, CDCl3, δ): -63.8 (t, J =
10.4 Hz, 3F). HRMS (ESI-TOF) m/z: [M + Na]+ Calcd for C14H18ClF3O4SNa 397.0459; Found 397.0467.
5-chloro-7,7,7-trifluoroheptyl 4-(tert-butyl)benzenesulfonate (3e). Prepared according to the
description in the general experimental procedure: yield 74%; 59.2 mg; colorless oil; 1H NMR (600 MHz,
CDCl3, δ): 7.83 (d, J = 8.4 Hz, 2H), 7.57 (d, J = 8.4 Hz, 2H), 4.08 – 4.03 (m, 3H), 2.64 – 2.56 (m, 1H),
2.54 – 2.45 (m, 1H), 1.83 – 1.78 (m, 1H), 1.75 – 1.66 (m, 3H), 1.65 – 1.58 (m, 1H), 1.52 – 1.45 (m, 1H),
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1.36 (s, 9H). C{1H} NMR (151 MHz, CDCl3, δ): 157.8, 133.0, 127.7 (2C), 126.3 (2C), 125.2 (q, J =
277.6 Hz), 70.0, 53.7 (q, J = 2.9 Hz), 42.4 (q, J = 28.5 Hz), 37.2, 35.3, 31.0 (3C), 28.2, 22.1. 19F NMR
(565 MHz, CDCl3, δ): -63.8 (t, J = 10.1 Hz, 3F). HRMS (ESI-TOF) m/z: [M + Na]+ Calcd for
C17H24ClF3O3SNa 423.0979; Found 423.0971.
5-chloro-7,7,7-trifluoroheptyl [1,1'-biphenyl]-4-sulfonate (3f). Prepared according to the description
in the general experimental procedure: yield 81%; 68 mg; colorless oil; 1H NMR (600 MHz, CDCl3, δ):
7.97 (d, J = 8.4 Hz, 2H), 7.76 (d, J = 8.4 Hz, 2H), 7.61 (d, J = 7.2 Hz, 2H), 7.49 (t, J = 7.5 Hz, 2H), 7.44
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(t, J = 7.3 Hz, 1H), 4.11 (t, J = 6.3 Hz, 2H), 4.08 – 4.04 (m, 1H), 2.64 – 2.55 (m, 1H), 2.54 – 2.45 (m,
1H), 1.84 – 1.61 (m, 5H), 1.53 – 1.49 (m, 1H). 13C{1H} NMR (151 MHz, CDCl3, δ): 146.8, 140.0, 134.5,
129.1 (2C), 128.8, 128.4 (2C), 127.9 (2C), 127.4 (2C), 125.2 (q, J = 277.5 Hz), 70.2, 53.7 (q, J = 3.2 Hz),
42.4 (q, J = 28.4 Hz), 37.2, 28.2, 22.1. 19F NMR (565 MHz, CDCl3, δ): -63.8 (t, J = 10.6 Hz, 3F). HRMS
(ESI-TOF) m/z: [M + Na]+ Calcd for C19H20ClF3O3SNa 443.0666; Found 443.0673.
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5-chloro-7,7,7-trifluoroheptyl 4-cyanobenzenesulfonate (3g). Prepared according to the description
in the general experimental procedure: yield 91%; 67.2 mg; colorless oil; 1H NMR (600 MHz, CDCl3, δ):
8.04 (d, J = 9.0 Hz, 2H), 7.88 (d, J = 9.0 Hz, 2H), 4.14 (t, J = 6.3 Hz, 2H), 4.09 – 4.05 (m, 1H), 2.68 –
2.59 (m, 1H), 2.56 – 2.47 (m, 1H), 1.87 – 1.60 (m, 5H), 1.54 – 1.47 (m, 1H). 13C{1H} NMR (151 MHz,
CDCl3, δ): 140.3, 133.1 (2C), 128.5 (2C), 125.1 (q, J = 277.8 Hz), 117.6, 117.0, 71.1, 53.7 (q, J = 3.3
Hz), 42.4 (q, J = 28.5 Hz), 37.1, 28.2, 22.0. 19F NMR (565 MHz, CDCl3, δ): -63.8 (t, J = 10.6 Hz, 3F).
HRMS (ESI-TOF) m/z: [M + Na]+ Calcd for C14H15ClF3NO3SNa 392.0305; Found 392.0311.
5-chloro-7,7,7-trifluoroheptyl 4-(trifluoromethyl)benzenesulfonate (3h). Prepared according to the
description in the general experimental procedure: yield 82%; 67.6 mg; colorless oil; 1H NMR (600 MHz,
CDCl3, δ): 8.04 (d, J = 8.4 Hz, 2H), 7.85 (d, J = 8.4 Hz, 2H), 4.13 (t, J = 6.3 Hz, 2H), 4.08 – 4.04 (m,
1H), 2.66 – 2.57 (m, 1H), 2.55 – 2.46 (m, 1H), 1.85 – 1.60 (m, 5H), 1.54 – 1.46 (m, 1H). 13C{1H} NMR
(151 MHz, CDCl3, δ): 139.7, 135.5 (q, J = 33.2 Hz), 128.4 (2C), 126.5 (q, J = 3.8 Hz, 2C), 125.1 (q, J =
277.6 Hz), 123.0 (q, J = 273.1 Hz), 70.9, 53.7 (q, J = 3.3 Hz), 42.4 (q, J = 28.4 Hz), 37.1, 28.2, 22.0. 19F
NMR (565 MHz, CDCl3, δ): -63.3 (s, 3F), -63.8 (t, J = 10.3 Hz, 3F). HRMS (ESI-TOF) m/z: [M + Na]+
Calcd for C14H15ClF6O3SNa 435.0227; Found 435.0215
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5-chloro-7,7,7-trifluoroheptyl 4-fluorobenzenesulfonate (3i). Prepared according to the description
in the general experimental procedure: yield 87%; 63 mg; colorless oil; 1H NMR (600 MHz, CDCl3, δ):
7.96 – 7.92 (m, 2H), 7.27 – 7.24 (m, 2H), 4.09 – 4.04 (m, 3H), 2.66 – 2.57 (m, 1H), 2.55 – 2.47 (m, 1H),
1.85 – 1.60 (m, 5H), 1.53 – 1.45 (m, 1H). 13C{1H} NMR (151 MHz, CDCl3, δ): 165.8 (d, J = 256.7 Hz),
132.1 (d, J = 3.3 Hz), 130.7 (d, J = 9.7 Hz, 2C), 125.1 (q, J = 277.7 Hz), 116.7 (d, J = 22.8 Hz, 2C), 70.3,
53.7 (d, J = 3.3 Hz), 42.4 (q, J = 28.4 Hz), 37.2, 28.1, 22.1. 19F NMR (565 MHz, CDCl3, δ): -63.8 (t, J =
10.4 Hz, 3F), -103.0 (m, 1F). HRMS (ESI-TOF) m/z: [M + Na]+ Calcd for C13H15ClF4O3SNa 385.0259;
Found 385.0265
5-chloro-7,7,7-trifluoroheptyl 4-bromobenzenesulfonate (3j). Prepared according to the description
in the general experimental procedure: yield 79%; 66.5 mg; colorless oil; 1H NMR (600 MHz, CDCl3, δ):
7.78 (d, J = 8.4 Hz, 2H), 7.71 (d, J = 8.4 Hz, 2H), 4.09 – 4.04 (m, 3H), 2.66 – 2.58 (m, 1H), 2.55 – 2.46
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(m, 1H), 1.85 – 1.59 (m, 5H), 1.53 – 1.45 (m, 1H). C{1H} NMR (151 MHz, CDCl3, δ): 135.1, 132.7
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(2C), 129.3 (2C), 129.1, 125.1 (q, J = 277.6 Hz), 70.5, 53.7 (q, J = 3.2 Hz), 42.4 (q, J = 28.5 Hz), 37.2,
28.2, 22.1. 19F NMR (565 MHz, CDCl3, δ): -63.8 (t, J = 10.2 Hz, 3F). HRMS (ESI-TOF) m/z: [M + Na]+
Calcd for C13H15BrClF3O3SNa 444.9458; Found 444.9450.
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5-chloro-7,7,7-trifluoroheptyl 4-(trifluoromethoxy)benzenesulfonate (3k). Prepared according to the
description in the general experimental procedure: yield 82%; 70.2 mg; colorless oil; 1H NMR (600 MHz,
CDCl3, δ): 7.98 (d, J = 9.0 Hz, 2H), 7.39 (d, J = 8.4 Hz, 2H), 4.11 (t, J = 6.3 Hz, 2H), 4.08 – 4.04 (m,
1H), 2.66 – 2.58 (m, 1H), 2.55 – 2.46 (m, 1H), 1.85 – 1.60 (m, 5H), 1.54 – 1.46 (m, 1H). 13C{1H} NMR
(151 MHz, CDCl3, δ): 153.0, 134.4, 130.1 (2C), 125.1 (q, J = 277.6 Hz), 121.0 (2C), 120.2 (q, J = 260
Hz), 70.5, 53.7 (q, J = 3.0 Hz), 42.4 (q, J = 28.6 Hz), 37.2, 28.2, 22.0. 19F NMR (565 MHz, CDCl3, δ): -
57.7 (s, 3F), -63.8 (t, J = 10.2 Hz, 3F). HRMS (ESI-TOF) m/z: [M + Na]+ Calcd for C14H15ClF6O4SNa
451.0176; Found 451.0159.
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4-methyl-2-oxo-2H-chromen-7-yl 4-chloro-6,6,6-trifluorohexanoate (3m). 3m was obtained as a
white solid (63.7 mg, 88%).
5-chloro-7,7,7-trifluoroheptyl (2S)-2-(4-isobutylphenyl)propanoate (3n). Prepared according to the
description in the general experimental procedure: yield 75%; 58.8 mg; colorless oil; 1H NMR (600 MHz,
CDCl3, δ): 7.19 (d, J = 7.8 Hz, 2H), 7.09 (d, J = 7.8 Hz, 2H), 4.12 – 4.01 (m, 3H), 3.68 (q, J = 7.2 Hz,
1H), 2.63 – 2.52 (m, 1H), 2.51 – 2.41 (m, 3H), 1.87 – 1.74 (m, 2H), 1.72 – 1.48 (m, 7H), 1.42 – 1.35 (m,
1H), 0.89 (d, J = 6.6 Hz, 6H). 13C{1H} NMR (151 MHz, CDCl3, δ): 174.7, 140.5, 137.8 (d, J = 3.4 Hz),
129.3 (2C), 127.1 (2C), 125.2 (q, J = 277.6 Hz), 64.0, 53.8 (d, J = 3.0 Hz), 45.2, 45.0, 42.3 (q, J = 28.5
Hz), 37.4 (d, J = 2.9 Hz), 30.1, 27.80 (d, J = 2.7 Hz), 22.4, 22.3, 22.0, 18.4 (d, J = 2.9 Hz). 19F NMR (565
MHz, CDCl3, δ): -63.8 (t, J = 10.2 Hz, 3F). HRMS (ESI-TOF) m/z: [M + H]+ Calcd for C20H29ClF3O2
393.1803; Found 393.1799.
5-chloro-7,7,7-trifluoroheptyl 3-(4,5-diphenyloxazol-2-yl)propanoate (3o). Prepared according to
the description in the general experimental procedure: yield 50%; 47.9 mg; colorless oil; 1H NMR (600
MHz, CDCl3, δ): 7.63 (d, J = 7.1 Hz, 2H), 7.57 (d, J = 7.1 Hz, 2H), 7.38 – 7.30 (m, 6H), 4.15 (t, J = 6.2
Hz, 2H), 4.09 – 4.04 (m, 1H), 3.19 (t, J = 7.5 Hz, 2H), 2.92 (t, J = 7.5 Hz, 2H), 2.64 – 2.55 (m, 1H), 2.53
– 2.45 (m, 1H), 1.85 – 1.79 (m, 1H), 1.76 – 1.60 (m, 4H) , 1.53 – 1.46 (m, 1H). 13C{1H} NMR (151 MHz,
CDCl3, δ): 172.0, 161.7, 145.4, 135.1, 132.5, 129.0, 128.7 (2C), 128.6 (2C), 128.5, 128.1, 127.9 (2C),
126.5 (2C), 125.2 (q, J = 277.5 Hz), 64.3, 53.9 (q, J = 3.0 Hz), 42.4 (q, J = 28.5 Hz), 37.5, 31.2, 27.9,
23.6, 22.5. 19F NMR (565 MHz, CDCl3, δ): -63.8 (t, J = 10.2 Hz, 3F). HRMS (ESI-TOF) m/z: [M + Na]+
Calcd for C25H25ClF3NO3Na 502.1367; Found 502.1362.
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5-chloro-7,7,7-trifluoroheptyl 2-(1-(4-chlorobenzoyl)-5-methoxy-2-methyl-1H-indol-3-yl)acetate
(3p). Prepared according to the description in the general experimental procedure: yield 58%; 63 mg;
yellow oil; 1H NMR (400 MHz, CDCl3, δ): 7.66 (d, J = 8.8 Hz, 2H), 7.47 (d, J = 8.8 Hz, 2H), 6.85 (d, J
= 9.0 Hz, 1H), 6.96 (d, J = 2.5 Hz, 1H), 6.67 (dd, J = 9.0, 2.5 Hz, 1H), 4.12 (t, J = 6.3 Hz, 2H), 4.05 –
3.99 (m, 1H), 3.83 (s, 3H), 3.67 (s, 2H), 2.62 – 2.42 (m, 2H), 2.40 (s, 3H), 1.83 – 1.51 (m, 5H), 1.48 –
1.37 (m, 1H). 13C{1H} NMR (151 MHz, CDCl3, δ): 170.9, 168.3, 156.0, 139.3, 136.0, 133.9, 131.2 (2C),
130.8, 130.6, 129.1 (2C), 125.2 (q, J = 277.5 Hz), 115.0, 112.6, 111.5, 101.4, 64.5, 55.7, 53.9 (q, J = 3.1
Hz), 42.3 (q, J = 28.4 Hz), 37.5, 30.4, 28.0, 22.5, 13.4. 19F NMR (565 MHz, CDCl3, δ): -63.7 (t, J = 10.2
Hz, 3F). HRMS (ESI-TOF) m/z: [M + Na]+ Calcd for C26H26Cl2F3NO4Na 566.1083; Found 566.1096.
(8R,9S,13S,14S)-3-((5-chloro-7,7,7-trifluoroheptyl)oxy)-13-methyl-6,7,8,9,11,12,13,14,15,16-
decahydro-17H-cyclopenta[a]phenanthren-17-one (3q). Prepared according to the description in the
general experimental procedure: yield 85%; 77.5 mg; colorless oil; 1H NMR (600 MHz, CDCl3, δ): 7.19
(d, J = 9.0 Hz, 1H), 6.70 (dd, J = 8.4, 2.4 Hz, 1H), 6.64 (d, J = 2.4 Hz, 1H), 4.16 – 4.12 (m, 1H), 3.95 (t,
J = 6.0 Hz, 2H), 2.94 – 2.85 (m, 2H), 2.68 – 2.48 (m, 3H), 2.41 – 2.37 (m, 1H), 2.27 – 2.23 (m, 1H), 2.17
– 2.11 (m, 1H), 2.07 – 1.98 (m, 2H), 1.96 – 1.89 (m, 2H), 1.85 – 1.40 (m, 11H), 0.91 (s, 3H). 13C{1H}
NMR (151 MHz, CDCl3, δ): 220.9, 157.0, 137.8, 132.1, 126.4, 125.3 (q, J = 277.6 Hz), 114.6, 112.1,
67.4, 54.0 (q, J = 3.4 Hz), 50.4, 48.0, 44.0, 42.5 (q, J = 28.4 Hz), 38.4, 37.8, 35.9, 31.6, 29.7, 28.6, 26.6,
26.0, 22.8, 21.6, 13.9. 19F NMR (565 MHz, CDCl3, δ): -63.8 (t, J = 10.4 Hz, 3F). HRMS (ESI-TOF) m/z:
[M + Na]+ Calcd for C25H32ClF3O2Na 479.1935; Found 479.1932.
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4-(1-chloro-3,3,3-trifluoropropyl)-1,1'-biphenyl (3s). 3r was obtained as a white solid (35.8 mg,
63%).
2-(1-chloro-3,3,3-trifluoropropyl)naphthalene (3t). 3s was obtained as a colorless oil (42.8 mg, 83%).
General Procedures for the Synthesis of Products 5 (5a as an Example). To a dried
polytetrafluoroethene (PTFE) sealed pressure tube (10 mL) was added alkene 4a (35.2 μL, 0.2 mmol), 1
(105 mg, 0.34 mmol) and anhydrous DMF (2.0 mL) in sequence under N2. After the reaction mixture was
stirred at 60 ℃ (oil bath) for 12 h, PhCF3 as an internal standard (0.0812 mmol, 10 μL) was added and the
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yield was calculated to be >99 % from F NMR integrals. The reaction mixture was purified by silica
column chromatography (eluent: petroleum ether) to give 48.6 mg (98 %) of 5a as colorless oil (the yield
was calculated based on 4a). Procedure for the synthesis of product 5a (1 mmol scale): To a dried
polytetrafluoroethene (PTFE) sealed pressure tube (50 mL) was added alkene 4a (176 μL, 1.0 mmol), 1
(524 mg, 1.7 mmol) and anhydrous DMF (10 mL) in sequence under N2. After the reaction mixture was
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stirred at 60 °C (oil bath) for 12 h. The reaction mixture was purified by silica column chromatography
(eluent: petroleum ether) to give 228 mg (92 %) of 5a (the yield was calculated based on 4a).
4,4'-(3,3,3-trifluoroprop-1-ene-1,1-diyl)bis(fluorobenzene) (5b). 5b was obtained as a colorless oil
(54.5 mg, 96%).
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4,4'-(3,3,3-trifluoroprop-1-ene-1,1-diyl)bis(chlorobenzene) (5c). 5c was obtained as a colorless oil
(56.3 mg, 89%).
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4,4'-(3,3,3-trifluoroprop-1-ene-1,1-diyl)bis(bromobenzene) (5d). 5d was obtained as a colorless oil
(78.4 mg, 92%).
4,4'-(3,3,3-trifluoroprop-1-ene-1,1-diyl)bis(methoxybenzene) (5e). 5e was obtained as a yellow oil
(49.9 mg, 81%).
4,4'-(3,3,3-trifluoroprop-1-ene-1,1-diyl)bis(methylbenzene) (5f). 5f was obtained as a colorless oil
(41.4 mg, 75%).
(E/Z)-1-fluoro-4-(3,3,3-trifluoro-1-phenylprop-1-en-1-yl)benzene (5g). Prepared according to the
description in the general experimental procedure: yield 76%; 40.4 mg; colorless oil. 1H NMR of the
minor-isomer (600 MHz, CDCl3, δ): 7.40 – 7.32 (m, 3H), 7.24 – 7.21 (m, 4H), 7.01 (t, J = 8.7 Hz, 2H),
6.07 (q, J = 8.2 Hz, 1H). 1H NMR of the major-isomer (600 MHz, CDCl3, δ): 7.40 – 7.32 (m, 3H), 7.24
– 7.21 (m, 4H), 7.07 (t, J = 9.3 Hz, 2H), 6.11 (t, J = 8.3 Hz, 1H). 13C{1H} NMR of the E/Z mixture (151
MHz, CDCl3, δ): 164.3, 163.7, 162.6, 162.0, 151.5 (q, J = 5.5 Hz), 151.4 (q, J = 5.6 Hz), 140.0, 137.0,
136.2 (d, J = 3.4 Hz), 133.1 (d, J = 3.5 Hz), 131.0 (d, J = 1.7 Hz), 130.9 (d, J = 1.7 Hz), 129.8, 129.8,
129.5, 129.0 (d, J = 3.5 Hz), 128.6, 128.5, 128.1, 127.9, 122.99 (q, J = 270.6 Hz), 122.97 (q, J = 270.7
Hz), 115.8 (q, J = 33.9 Hz), 115.6, 115.4, 115.3 (q, J = 33.5 Hz), 115.2, 115.1. 19F NMR of the minor-
isomer (565 MHz, CDCl3, δ): -55.62 (d, J = 9.0 Hz, 3F), -111.75 (m, 1F). 19F NMR of the major-isomer
(565 MHz, CDCl3, δ): -55.61 (d, J = 9.0 Hz, 3F), -112.9 (m, 1F). HRMS (ESI-TOF) m/z: [M + H]+ Calcd
for C15H11F4 267.0791; Found 267.0795.
1-chloro-4-(3,3,3-trifluoro-1-phenylprop-1-en-1-yl)benzene (5h). 5h was obtained as a yellow oil
(49.6 mg, 88%).
2-(3,3,3-trifluoro-1-phenylprop-1-en-1-yl)naphthalene (5i). 5i was obtained as a white solid (47.1
mg, 79%).
(E/Z)-1-methyl-2-(3,3,3-trifluoro-1-phenylprop-1-en-1-yl)benzene (5j). Prepared according to the
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description in the general experimental procedure: yield 92%; 48.2 mg; colorless oil. H NMR of the
minor-isomer (600 MHz, CDCl3, δ): 7.26 – 7.21 (m, 8H), 7.14 (d, J = 7.2 Hz, 1H), 5.79 (q, J = 8.6 Hz,
1H), 2.07 (s, 3H). 13C{1H} NMR of the minor-isomer (151 MHz, CDCl3, δ): 153.3 (q, J = 5.8 Hz), 141.2,
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137.5, 135.7, 130.7, 129.4, 129.1 (d, J = 1.5 Hz), 128.63, 128.58, 128.4, 127.9 (2C), 125.8, 122.8 (q, J =
271.0 Hz), 117.9 (q, J = 34.0 Hz), 20.1. 19F NMR of the minor-isomer (565 MHz, CDCl3, δ): -55.7 (d, J
= 8.6 Hz, Z-isomer). 1H NMR of the major-isomer (600 MHz, CDCl3, δ): 7.35 – 7.28 (m, 8H), 7.17 (d, J
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= 7.2 Hz, 1H), 6.27 (q, J = 8.0 Hz, 1H), 2.05 (s, 3H). C{1H} NMR of the major-isomer (151 MHz,
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CDCl3, δ): 151.7 (q, J = 5.6 Hz), 138.4, 136.3, 135.8, 130.1, 129.4, 128.8 (d, J = 2.0 Hz), 128.6 (2C),
127.0 (2C), 125.3, 123.1 (q, J = 270.6 Hz), 115.6 (q, J = 33.5 Hz), 19.5. 19F NMR of the major-isomer
(565 MHz, CDCl3, δ): -57.2 (d, J = 8.3 Hz). HRMS (ESI-TOF) m/z: [M + H]+ Calcd for C16H14F3
263.1042; Found 263.1047.
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(E)-1-methoxy-4-(3,3,3-trifluoroprop-1-en-1-yl)benzene (5k). 5k was obtained as a colorless oil
(24.6 mg, 61%).
10-(trifluoromethyl)-5H-dibenzo[b,f]azepine (5l). Prepared according to the description in the
general experimental procedure: yield 62%; 32.4 mg; yellow solid; mp 126−127 °C. 1H NMR (600 MHz,
CDCl3, δ): 7.35 (d, J = 7.8 Hz, 1H), 7.28 (s, 1H), 7.20 (q, J = 7.8 Hz, 2H), 7.08 (d, J = 7.2 Hz, 1H), 7.02
(t, J = 7.5 Hz, 1H), 6.97 (t, J = 7.5 Hz, 1H), 6.73 (d, J = 7.8 Hz, 1H), 6.69 (d, J = 7.8 Hz, 1H), 5.11 (s,
1H). 13C{1H} NMR (151 MHz, CDCl3, δ): 150.4, 150.1, 135.8 (q, J = 6.5 Hz), 131.4, 131.0, 131.0 (q, J
= 28.4 Hz), 130.3, 128.0 (q, J = 2.6 Hz), 126.9, 125.1, 123.92, 123.91 (q, J = 274.7 Hz), 123.6, 121.1,
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119.7. F NMR (565 MHz, CDCl3, δ): -61.6 (s, 3F). HRMS (ESI-TOF) m/z: [M + H]+ Calcd for
C15H11F3N 262.0838; Found 262.0845.
(E)-1-methoxy-4-(3,3,3-trifluoro-2-methylprop-1-en-1-yl)benzene (5m). Prepared according to the
description in the general experimental procedure: yield 46%; 19.9 mg; colorless oil. 1H NMR (600 MHz,
CDCl3, δ): 7.28 (d, J = 8.3 Hz, 2H), 6.97 (s, 1H), 6.92 (d, J = 8.4 Hz, 2H), 3.83 (s, 3H), 2.01 (s, 3H).
13C{1H} NMR (151 MHz, CDCl3, δ): 159.5, 130.8, 130.7 (2C), 127.5, 124.8 (q, J = 272.6 Hz), 124.2 (q,
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J = 28.8 Hz), 113.9 (2C), 55.3, 12.2. F NMR (565 MHz, CDCl3, δ): -69.1 (s, 3F). HRMS (ESI-TOF)
m/z: [M + H]+ Calcd for C11H12F3O 217.0835; Found 217.0829.
4,4'-(3,3,3-trifluoro-2-(trifluoromethyl)prop-1-ene-1,1-diyl)bis(methoxybenzene) (7e). The structure
F3C
CF3
MeO
OMe
of 7e:
4,4'-(3,3,3-trifluoro-2-(trifluoromethyl)prop-1-ene-1,1-diyl)bis(methylbenzene) (7f). The structure
F3C
CF3
Me
Me
of 7f:
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Supporting Information
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The Supporting Information is available free of charge on the ACS Publications website at DOI:.
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Table S1(Screen of solvent); Chiral HPLC spectra; CV spectrum of reagent 1 and 4a; H, C{1H}, F
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NMR and NOESY spectra.
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Author Information
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Corresponding Author
*E-mail: wangm452@nenu.edu.cn
Author Contributions
The manuscript was written through contributions of all authors. All authors have given approval to the
final version of the manuscript.
Notes
The authors declare no competing financial interest.
Acknowledgements
We thank the National Natural Science Foundation of China (21672032 and 21802016) and the
Department of Science and Technology of Jilin Province (20190103127JH) for funding support of this
work.
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‑ , and Stereoselective Trifluoromethylation of Styrenes via Visible Light-Driven Single-Electron
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(11) When 4e was treated with 1 (2 equiv.), a mixture of 5e (NMR yield: 49%) and
1
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bistrifluoromethylated
product
7e
(4,4'-(3,3,3-trifluoro-2-(trifluoromethyl)prop-1-ene-1,1-
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diyl)bis(methoxybenzene)), 19F NMR yield: 44 %) was obtained, which could not be separated from each
other.
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of Unactivated Alkenes Using Readily Available Ag(O2CCF2SO2F) and N-Fluorobenzenesulfonimide.
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1–6.
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