Free-Radical Bromotrifluoromethylation of Olefin via Single-Electron Oxidation of NaSO2CF3 by NaBrO3

Article abstract of DOI:10.1021/acs.joc.6b02812

A free-radical bromotrifluoromethylation of olefin by using NaSO₂CF₃ and NaBrO₃ has been achieved. Sodium bromate acts not only as a single-electron oxidant but also as a bromine source. A radical-clock experiment and electron-spin-resonance detection support a radical process.

Full text of DOI:10.1021/acs.joc.6b02812

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Article
A Free-Radical Bromotrifluoromethylation of Olefin via
Single-Electron Oxidation of NaSO2CF3 by NaBrO3
Zhong-Quan Liu, and Dong Liu
J. Org. Chem., Just Accepted Manuscript • Publication Date (Web): 05 Jan 2017
Downloaded from http://pubs.acs.org on January 5, 2017
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A
FreeꢀRadical Bromotrifluoromethylation of Olefin via
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SingleꢀElectron Oxidation of NaSO2CF3 by NaBrO3
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ZhongꢀQuan Liu,*†,‡ and Dong Liu‡
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† School of Petrochemical Engineering, Institute for Natural and Synthetic Organic Chemistry, Jiangsu
Key Laboratory of Advanced Catalytic Materials and Technology, Changzhou University,
Changzhou 213164, P. R. China;
‡ State Key Laboratory of Applied Organic Chemistry, Lanzhou University, Lanzhou, Gansu, 730000,
P. R. China.
Abstract: A free radical bromotrifluoromethylation of olefin by using NaSO2CF3 and
NaBrO3 has been achieved. Sodium bromate acts not only as a singleꢀelectron oxidant,
but also as a bromine source. Radical clock experiment and electron spin resonance
detection support a radical process.
INTRODUCTION
The importance of organofluorine compounds provides an increasing driving force
for development of efficient strategy for direct installation of fluorine atom into
organic molecules.1 Among these synthetic methods, halotrifluoromethylation of
alkenes represents one of the most effective accesses to fluorinated compounds.2
Along with trifluoromethyl (CF3) group,3ꢀ5 introduction of halogen atom allows
versatile transformations for further manipulations. Therefore, various strategies for
halotrifluoromethylation have been explored in the past decades.6 However, most of
these studies focus on iodotrifluoromethylation.7 Only a few protocols have been
successfully achieved to introduce halogen atoms such as Cl and Br. Traditional
halotrifluoromethylation suffers from complex operations with gaseous BrCF3 and/or
CF3SO2Br8 and ICF3.9 Hence, more convenient and practical strategies for
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halotrifluoromethylation are highly desirable.
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Recently, we developed an efficient iodotrifluoromethylation by using sodium
trifluoromethanesulfinate (NaSO2CF3, Langlois reagent) and iodine pentoxide
(I2O5).10 The radical CF3 is generated through singleꢀelectron oxidation of NaSO2CF3
by a safe and cheap I(V) reagent (I2O5), which also acts as a donor of iodine atom. A
wide range of molecules such as alkenes, alkynes, and enynes have been successfully
iodotrifluoromethylated via this strategy. As a continuous idea, we began to envision
whether a proper hypervalent bromide could not only oxidize CF3ꢀderivatived anion
to CF3 radical, but also supply a bromine atom, and subsequently an efficient radical
bromotrifluoromethylation of alkenes would be achieved (Scheme 1). Fortunately, we
found this hypervalent bromide reagent and explored an efficient approach for
bromotrifluoromethylation of alkenes.
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Scheme 1. A hypotheses of radical bromotrifluoromethylation.
RESULTS AND DISCUSSION
In order to test the hypotheses, a series of optimizing experiments were carried out
(Table 1). Several bromides were screened and sodium bromate (NaBrO3) was found
to be the most effective reagent (entries 1ꢀ3). Then the amount of NaSO2CF3 and the
oxidant, the temperature, as well as the solvent were examined (entries 4ꢀ8). Finally,
the corresponding product was isolated in 85% yield through careful modification
(entry 7).
Table 1. Modification of the Typical Reaction Conditionsa
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sol. (mL)
DCM/H2O
T
entry a (equiv)
ox. (equiv)
yield (%)b
(0C)
7
8
9
1
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3
4
5
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7
8
3
3
3
3
3
3
5
5
NaBrO3(1.5)
KBrO3 (1.5)
NaBrO(1.5)
NaBrO3 (3)
NaBrO3(1.5)
NaBrO3(2.5)
NaBrO3(2.5)
NaBrO3(2.5)
90
90
2.5/1(3.5)
2.5/1(3.5)
2.5/1(3.5)
2.5/1(3.5)
4/1(3.5)
4/1(3.5)
4/1(10)
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NR
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60
69
85
70
90
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90
110
110
110
100
4/1(10)
a
b
Reaction conditions: pentꢀ4ꢀenꢀ1ꢀyl 4ꢀchlorobenzoate (1 equiv, 0.2 mmol), 24 h, sealed tube.
Isolated yields.
As depicted in Table 2, a wide range of unactivated alkenes can give βꢀCF3 alkyl
bromate as the major products in moderate to high yields under the typical reaction
conditions. Various functional groups such as halogens (Cl, Br), NO2, sulfonate,
sulfamide, carboxylate, aldehyde, ether, carbonyl, hydroxyl, and epoxides can be
wellꢀtolerated in this system (1−19). It is noteworthy that the
bromotrifluoromethylation occurs selectively at the less hindered and relatively
electronꢀrich position (16 and 17). Additionally, nonterminal alkenes are also
compatible with this approach (20 and 21). In case of a trisubstituted olefin, the
desired product was isolated in excellent regioꢀselectivity (21), which should be due
to the stability of the radical intermediate and steric effect.
Table 2. NaBrO3ꢀPromoted Bromotrifluoromethylation of Unactivated Alkenesa
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O
O
O
4
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O
O
CF3
O
CF3
MeO
O
CF3
Br
Br
Br
Br
O
Cl
1, 85 %b
3, 76 %
2, 72 %
O
O
O
O
O
O
CF3
CF3
N
CF3
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O
Pr2N
Br
Pr2N
Br
S
S
O O
6, 71 %
4, 67 %
5, 67 %
O O
O
O
O
S
O
CF3
O
CF3
O
CF3
Br
Br
Br
N
Br
9, 61 %
7, 61 %
8, 60 %
Br
O
O
Br
Br
CF3
O
CF3
N
N
CF3
10, 79 %
3
O
Br
O
11, 80 %
12, 86 %
Br
Br
Br
O
O
CF3
CF3
CF3
O
HO
OHC
15, 60 %
14, 55 %
13, 63 %
O
Br
O
O
O
O
H
CF3
O
O
O
CF3
Br
O
Br
H
H
F3C
O
16, 67 %
17, 62 %
18, 56 %
O
O
S
O
O
H
Br
O
Br
O
H
H
O2N
CF3
F3C
O
CF3
O
20, 68 % (dl: 2.4/1)c
Br
21, 60 % (19/1)d
19, 55 %
a Reaction conditions: alkene (1 equiv, 0.2 mmol), NaSO2CF3 (5 equiv, 1.0 mmol), NaBrO3 (2.5 equiv,
0.5 mmol), CH2Cl2/H2O (4/1, 10 mL), 110 oC, sealed tube. b Isolated yields. c Obtained as a mixture of
diastereoisomers. The ratio of the major two isomers was determined by 19F NMR spectroscopy.
regioꢀselective isomer was obtained and the ratio was determined by 19F NMR spectroscopy.
A
d
Furthermore, we found that styrenes and its derivatives are also amenable to this
system (Table 3). Substrates with both electronꢀdonating and electronꢀwithdrawing
groups in the aromatic core gave moderate to good yield of the corresponding
products (22ꢀ28). An addition/elimination product was obtained with indene (29).
Finally, the large scale experiment was carried out. And we found that this reaction
can be easily scaled up to gram level (eq. 1). It is interesting that the scaledꢀup
reaction (5 mmol, 1.1 g, 7.5 h, 80% isolated yield) is even more efficient than that in
0.2 mmol scale (44 mg, 24 h, 72% isolated yield, Table 2, 2), which indicates that this
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method could be potentially applied in chemical industry.
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Table 3. NaBrO3ꢀPromoted Bromotrifluoromethylation of Styrenesa
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Br
Br
Br
Br
CF3
Br
CF3
CF3 Cl
CF3
Cl
Cl
22, 64 %b
23, 60 %
24, 57 %
25
, 65 %
Br
Br
Br
CF3
CF3
CF3
CF3
Ph
O2N
29, 60 %
26, 47 %
28, 61 %
27, 64 %
a Reaction conditions: styrene (1 equiv, 0.2 mmol), NaSO2CF3 (5 equiv, 1.0 mmol), NaBrO3 (2.5 equiv,
0.5 mmol), CH2Cl2/H2O (4/1, 10 mL), 110 oC, sealed tube. b Isolated yields.
As demonstrated in Figure 1, the products βꢀCF3 alkyl bromates are useful synthons
in synthetic organic chemistry. It can be easily converted into various different
compounds such as azide, alkene, borate, and alkane etc.
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O
O
O
CF3
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H
MeO
Zn, AgOAc
HOAc, rt
60 % (rsm: 30 %)
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O
CF3
CF3
O
CF3
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CuI, Ph3P
NaN3
O
3
O
3
O
3
DMF, rt
MeOLi
DMF, rt
B
Br
N3
MeO
O
O
MeO
MeO
80 %
50 % (rsm: 30 %)
K2CO3
DMF, 75 0
C
O
O
CF3
MeO
90 %, (E/Z = 9/1)
Figure 1. Functional group transformation of the products.
In order to investigate the mechanism, a set of mechanistic studies involving radical
clock experiments and electron spin resonance (ESR) detection combining with spin
trapping technology were carried out (Scheme 2 and Figure 2). It can be seen from
Scheme 2 that (2ꢀvinylcyclopropyl)methyl 4ꢀchlorobenzoate gave the corresponding
ring opening product (30) in 72% yield. The CF3 radical would be formed through one
electron oxidation of NaSO2CF3 by NaBrO3. It adds to the double bond followed by
ring opening of cyclopropane generating a βꢀallylic Cꢀcentered radical. As expected,
the ESR signal of radical adduct of radical CF3 to 2ꢀmethylꢀ2ꢀnitrosopropane (MNP)
was clearly recorded, which should belong to trifluoromethyl tꢀbutyl nitroxide (Figure
2a, g = 2.0074, aN = aF = 12.25 G).10a Furthermore, the secondary βꢀCF3
carbonꢀcentered radical was also trapped by MNP and the corresponding adduct was
detected by ESR (Figure 2b, g = 2.0073, aN = 14.65 G, aH = 4.92 G).10a In fact, the last
bromination step is not very clear by now. One possible pathway is bromine atom
abstraction by βꢀCF3ꢀCꢀcentered radical from Br2, which is observed in the system.
However, another process involving oneꢀelectron oxidation of βꢀCF3ꢀCꢀcentered
radical to give a carbocation followed by Br anion addition cannot be ruled out
especially in case of styrenes.
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Cl
Cl
typical
conditions
Br
O
O
NaSO2CF3
SET[O]
+
F3C
O
O
NaBrO3
CF3
Cl
30, 72 %
E/Z = 6/1
O
F3C
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O
Scheme 2. Radical clock experiment.
Figure 2a. ESR signal of radical trifluoromethyl tꢀbutyl nitroxide radical (g = 2.0074, aN = aF = 12.25
G).
Figure 2b. ESR signal of radical Nꢀ(tertꢀbutyl)ꢀNꢀ(3,3,3ꢀtrifluoroꢀ1ꢀ(naphthalenꢀ2ꢀyl)propyl) nitroxide
(g = 2.0073, aN = 14.65 G, aH = 4.92 G).
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CONCLUSIONS
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In summary, a radical bromotrifluoromethylation of alkenes by using two simple
salts (NaSO2CF3 and NaBrO3) was developed. Sodium bromate plays dual roles in
this process. It not only acts as one electron oxidant which converts the SO2CF3 anion
to radical CF3, but also provides the bromine atom. Through this strategy, two useful
functional groups (CF3 and Br) can be simultaneously installed into a wide range of
organic molecules.
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EXPERIMENTAL SECTION
General Information: All chemicals were commercially available and used as
received without further purification. Reactions were monitored by thinꢀlayer
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chromatography (TLC). H NMR, C NMR, and F NMR spectra were recorded at
400, 100, and 375 MHz, respectively. Chemical shifts (δ) are given relative to internal
TMS. The NMR data are presented as follows: chemical shift (ppm), multiplicity (s =
singlet, d = doublet, t = triplet, m = multiplet, br = broad), coupling constant J (Hz),
and integration. HRMS spectra (ESIꢀTOF) were recorded in CH2Cl2 or acetonitrile.
Electron spin resonance (ESR) data were measured on an Xꢀband EPR spectrometer
and the calculated hyperfine splittings g values are obtained by using
2,2ꢀdiphenylꢀ1ꢀpicrylhydrazyl (DPPH) as a standard.
1. General procedure for the synthesis of (2ꢀVinylcyclopropyl)methyl
4ꢀchlorobenzoate
1.1 General procedure for the synthesis of (Z)ꢀ4ꢀHydroxybutꢀ2ꢀenꢀ1ꢀyl
4ꢀchlorobenzoate. To a solution of 2ꢀButeneꢀ1,4ꢀdiol (1.76 g, 20.0 mmol, 2.0 equiv)
in dry CH2Cl2 was added Et3N (2.09 mL, 15.0 mmol, 1.5 equiv) and DMAP (122.2
mg, 1.0 mmol, 0.1 equiv) at 0 oC. After subsequent addition of commercially available
4ꢀChlorobenzoyl chloride (1.75 g, 10.0 mmol, 1.0 equiv), the solution was stirred for
o
3 h at 0 C. The reaction was quenched with sat. NaHCO3, brine, dried over
anhydrous Na2SO4, and concentrated under reduced pressure. The crude product was
purified by silica gel chromatography (hexane/EtOAc = 5/1) to afford
(Z)ꢀ4ꢀhydroxybutꢀ2ꢀenꢀ1ꢀyl 4ꢀchlorobenzoate (A) (70%, 3.16 g) as a white solid.
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(Z)ꢀ4ꢀHydroxybutꢀ2ꢀenꢀ1ꢀyl 4ꢀchlorobenzoate. H NMR (400 MHz, CDCl3): δ 7.96
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(d, J = 8.4 Hz, 2H), 7.40 (d, J = 8.4 Hz, 2H), 5.94 – 5.88 (m, 1H), 5.77 – 5.70 (m, 1H),
4.92 (d, J = 7.2 Hz, 1H), 4.32 (d, J = 4.8 Hz, 2H), 2.24 – 2.14 (m, 1H); 13C NMR (101
MHz, CDCl3): δ 165.8, 139.6, 133.7, 131, 128.7, 128.4, 125.3, 60.8, 58.5. MS(EI):
m/z(%): 111(19.27), 139(100), 141(31.34), 223(16.35), 225(5.18) , 240(0.69).
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1.2
General
procedure
for
the
synthesis
of
(2ꢀ(Hydroxymethyl)cyclopropyl)methyl 4ꢀchlorobenzoate. To a solution of A (2.26
g, 10.0 mmol) in dry DCM was stirred for 10 min before added a solution of
diethylzinc (1 M in hexanes, 100.0 mL) and Diiodomethane (8.04 mL, 100.0 mmol)
o
was added dropwise at ꢀ10 °C under N2, and the solution was stirred at ꢀ10 C for 60
min. then the mixture was stirred at 0 oC for 4 h. Saturated aqueous NH4Cl was added,
and the mixture was extracted with brine, DCM. The organic phase was dried over
MgSO4, filtered. The crude product (2ꢀ(hydroxymethyl)cyclopropyl)methyl
4ꢀchlorobenzoate (B) was obtained. (50%, 1.20 g) as a light yellow oil.
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(2ꢀ(Hydroxymethyl)cyclopropyl)methyl 4ꢀchlorobenzoate. H NMR (400 MHz,
CDCl3): δ 7.95 (d, J = 8.6 Hz, 2H), 7.38 (d, J = 8.6 Hz, 2H), 4.59 (dd, J = 11.9, 5.8 Hz,
1H), 4.13 (dd, J = 11.9, 8.9 Hz, 1H), 3.84 (dd, J = 11.9, 5.7 Hz, 1H), 3.51 (dd, J = 11.8,
8.5 Hz, 1H), 2.33 (s, 1H), 1.41 – 1.31 (m, 2H), 0.90 – 0.85 (m, 1H), 0.29 (q, J = 5.6
Hz, 1H); 13C NMR (101 MHz, CDCl3): δ 165.7, 139.4, 130.9, 128.7, 128.5, 65.4, 62.3,
18.6, 14.4, 7.8. MS(EI): m/z(%): 111(19.27), 139(100), 141(31.34), 223(16.35),
225(5.18) , 240(0.69)
1.3 General procedure for the synthesis of (2ꢀFormylcyclopropyl)methyl
4ꢀchlorobenzoate. To a solution of B (1.20 g, 5.0 mmol) in dry DCM was added
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Sodium bicarbonate (840 mg, 10.0 mmol) at 0 C. After addition of DessꢀMartin
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periodinane (4.24 g, 10.0 mmol), the solution was stirred for 4h at 0 C. The mixture
was purified by silica gel chromatography (hexane/ EtOAc = 5/1) to afford
(2ꢀformylcyclopropyl)methyl 4ꢀchlorobenzoate (C, 70%, 1.0 g) as a light yellow oil.
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(2ꢀFormylcyclopropyl)methyl 4ꢀchlorobenzoate. H NMR (400 MHz, CDCl3): δ
9.63 (d, J = 4.0 Hz, 1H), 7.93 (d, J = 8.4 Hz, 2H), 7.39 (d, J = 8.4 Hz, 2H), 4.77 (dd, J
= 12.0, 6.1 Hz, 1H), 4.18 (dd, J = 12.0, 9.2 Hz, 1H), 2.17 – 2.11 (m, 1H), 2.05 – 1.95
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(m, 1H), 1.43 (dd, J = 11.8, 5.6 Hz, 1H), 1.37 – 1.33 (m, 1H); C NMR (101 MHz,
CDCl3): δ 199.8, 165.4, 139.5, 131.0, 128.7, 128.3, 63.2, 26.6, 22.5, 12.9. MS(EI):
m/z(%): 111(21.75), 139(100), 141(33.32), 236(7.36), 238(2.32)
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1.4 General procedure for the synthesis of (2ꢀVinylcyclopropyl)methyl
4ꢀchlorobenzoate. A solution of methyltriphenylphosphonium bromide (1.50 g, 4.4
mmol) in anhydrous THF was placed in a flask flushed with nitrogen at ꢀ78 oC. To the
flask was slowly added 1.75 mL (4.4 mmol) of 2.5 M nꢀbutyllithium with stirring.
After addition, the reaction mixture was stirred for an additional 30 min and then
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added C (1.00 g, 3.5 mmol), the solution was stiired for seveal hours at 0 C. The
mixture was quenched slowly with saturated aqueous NH4Cl. The organic and
aqueous layers were separated, and the aqueous layer was washed ether. The ether
solutions were combined and dried over anhydrous magnesium sulfate. The crude
product (2ꢀvinylcyclopropyl)methyl 4ꢀchlorobenzoate (D, 50%, 413 mg) as a
colorless oil.
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(2ꢀVinylcyclopropyl)methyl 4ꢀchlorobenzoate. H NMR (400 MHz, CDCl3): δ 8.01
(d, J = 8.4 Hz, 2H), 7.43 (d, J = 8.4 Hz, 2H), 5.75 – 5.66 (m, 1H), 5.22 – 5.18 (m, 1H),
5.08 (dd, J = 10.4, 1.2 Hz, 1H), 4.48 (dd, J = 11.7, 6.9 Hz, 1H), 4.16 (dd, J = 11.7, 8.5
Hz, 1H), 1.78 – 1.71 (m, 1H), 1.58 – 1.48 (m, 1H), 1.08 – 1.03 (m, 1H), 0.63 (q, J =
5.6 Hz, 1H); 13C NMR (101 MHz, CDCl3): δ 165.8, 139.2, 136.2, 131.0), 128.9, 128.6,
115.7, 65.7, 19.7, 16.8, 10.6. MS(EI): m/z(%): 111(21.00), 139(100), 141(33.78),
196(1.91), 236(7.32).
2. Transformation of the products.
2.1 To a solution of the alkyl bromide (1 equiv, 0.20 mmol) in dry DMF was added
NaN3 (8 equiv, 4 times), then was stirring for 4 h. The reaction mixture was then
diluted with DMF, filtered through silica gel with copious washings, concentrated,
and purified by column chromatography (hexane/AcOEt = 20/1) gave the
corresponding product ( 50% yield ).
4ꢀAzidoꢀ6,6,6ꢀtrifluorohexyl 4ꢀmethoxybenzoate(E).
A
colorless oil after
purification by flash column chromatography (petroleum ether/ethyl acetate = 20/1,
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Yield: 50%, 35.4 mg). H NMR (400 MHz, CDCl3): δ 7.98 (d, J = 8.8 Hz, 2H), 6.92
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(d, J = 8.8 Hz, 2H), 4.35 – 4.32 (m, 2H), 3.86 (s, 3H), 3.75 – 3.69 (m, 1H), 2.41 –
2.26 (m, 2H), 2.01 – 1.87 (m, 2H), 1.85 – 1.68 (m, 2H); 19F NMR (376 MHz, CDCl3):
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δ ꢀ64.05 (t, J = 10.5 Hz, 3F); C NMR (101 MHz, CDCl3): δ 166.2, 163.5, 131.6,
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125.6 (q, J = 277.1 Hz), 122.4, 113.6, 63.7, 56.5 (q, J = 2.7 Hz), 55.4, 38.6 (q, J =
28.3 Hz), 31.4, 25.1. HRMS (ESI, m/z): Calculated for C14H16N3F3O3Na1 (M+Na)+
354.1036, found 354.1032.
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2.2. To a solution of the alkyl bromide (1 equiv, 0.25 mmol) in dry DMF was added
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potassium carbonate (2 equiv, 0.5 mmol), then was stirring in 75 C for 4h. The
reaction was washed with DCM, brine, dried over anhydrous Na2SO4, and
concentrated under reduced pressure. Purification by silicaꢀgel chromatography
(hexane/AcOEt = 20/1) gave the corresponding product (90% yield).
(E)ꢀ6,6,6ꢀTrifluorohexꢀ4ꢀenꢀ1ꢀyl 4ꢀmethoxybenzoate(F). A colorless oil after
purification by flash column chromatography (petroleum ether/ethyl acetate = 20/1,
1
Yield: 90%, 51.8 mg). H NMR (400 MHz, CDCl3): δ 7.99 (d, J = 8.8 Hz, 2H), 6.92
(d, J = 8.8 Hz, 2H), 6.46 – 6.41 (m, 1H), 5.72 – 5.64 (m, 1H), 4.32 (t, J = 6.3 Hz, 2H),
3.86 (s, 3H), 2.34 – 2.32 (m, 2H), 1.96 – 1.88 (m, 2H); 19F NMR (376 MHz, CDCl3):
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δ ꢀ58.20 (d, J = 8.6 Hz, 1F), ꢀ64.05 (dd, J = 6.3, 2.3 Hz, 9F); C NMR (101 MHz,
CDCl3): δ 166.2, 163.4, 139.5 (q, J = 6.5 Hz), 131.5, 122.9 (q, J = 269.2 Hz), 122.5,
119.1 (q, J = 33.4 Hz), 113.6, 63.5, 55.3, 28.1, 27.2. HRMS (ESI, m/z): Calculated for
C14H15F3O3H1 (M+H)+ 289.1046, found 289.1050.
2.3. The alkyl bromide (1 equiv, 0.25 mmol), Zn (4 equiv, 65 mg), and AgOAc (0.03
mmol, 5 mg) were mixed together in HOAc (0.5 mL), under vigorous stirring. 0.05mL
of concentrated HCl (37%) was added dropise over a 1 min period. The mixture was
further stirred for 5 min. and then filtered. The reaction mixture was then diluted with
DCM, filtered through silica gel with copious washings (DCM), concentrated, and
purified by column chromatography (hexane/AcOEt = 20/1) gave the corresponding
product (60% yield).
6,6,6ꢀTrifluorohexyl 4ꢀmethoxybenzoate(G). A colorless oil after purification by
flash column chromatography (petroleum ether/ethyl acetate = 20/1, Yield: 60%, 34.8
mg). 1H NMR (400 MHz, CDCl3): δ 7.99 (d, J = 8.8 Hz, 2H), 6.92 (d, J = 8.8 Hz, 2H),
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4.29 (t, J = 6.4 Hz, 2H), 3.86 (s, 3H), 2.16 – 2.04 (m, 2H), 1.82 – 1.75 (m, 2H), 1.68 –
1.60 (m, 2H), 1.56 – 1.48 (m, 1H); 19F NMR (376 MHz, CDCl3): δ ꢀ66.36 (s, 3F); 13C
NMR (101 MHz, CDCl3): δ 166.3, 163.3, 131.5, 127.1 (q, J = 277.3 Hz), 122.6, 113.6,
64.2, 55.4, 33.6 (q, J = 28.4 Hz), 28.4, 25.3, 21.7 (q, J = 2.9 Hz). HRMS (ESI, m/z):
Calculated for C14H18F3O3 (M+H)+ 291.1203, found 291.1199.
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2.4. In air, CuI (4.8 mg, 0. 025 mmol), PPh3 (8.6 mg, 0.033 mmol), LiOMe (20 mg,
0.5 mmol), and bis(pinacolato)diboron (96.5mg, 0.38 mmol) were added to a Schlenk
tube equipped with a stir bar. The vessel was evacuated and filled with argon (three
cycles). DMF (0.5 mL), the alkyl bromide (0.25 mmol) were added in turn by syringe
under an argon atmosphere. The resulting reaction mixture was stirred vigorously at
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25 C for 18 h. The reaction mixture was then diluted with EtOAc, filtered through
silica gel with copious washings (Et2O or EtOAc), concentrated, and purified by
column chromatography (hexane/AcOEt = 20/1) gave the corresponding product
(80% yield).
6,6,6ꢀTrifluoroꢀ4ꢀ(4,4,5,5ꢀtetramethylꢀ1,3,2ꢀdioxaborolanꢀ2ꢀyl)hexyl
4ꢀmethoxybenzoate(H). A colorless oil after purification by flash column
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chromatography (petroleum ether/ethyl acetate = 20/1, Yield: 80%, 66.5 mg). H
NMR (400 MHz, CDCl3): δ 7.98 (d, J = 8.9 Hz, 2H), 6.90 (d, J = 8.9 Hz, 2H), 4.27 (t,
J = 6.4 Hz, 2H), 3.84 (s, 3H), 2.39 – 2.25 (m, 1H), 2.17 – 2.04 (m, 1H), 1.82 – 1.74
(m, 2H), 1.69 – 1.53 (m, 2H), 1.38 – 1.23 (m, 1H), 1.23 (s, 12H); 19F NMR (376 MHz,
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CDCl3): δ ꢀ64.94 (t, J = 11.2 Hz, 3F); C NMR (101 MHz, CDCl3): δ 166.3, 163.3,
131.5, 127.4 (q, J = 277.0 Hz), 122.8, 113.5, 83.6, 64.5, 55.3, 35.0 (q, J = 28.0 Hz),
27.8, 27.3, 24.7, 24.6. HRMS (ESI, m/z): Calculated for C20H29B1F3O5 (M+H)+
417.2055, found 417.2060.
Typical Experimental Procedure for the Synthesis of 1ꢀ30. A mixture of alkene (1
equiv, 0.2 mmol), NaSO2CF3 (5 equiv, 1.0 mmol), NaBrO3 (2.5 equiv, 0.5 mmol) and
CH2Cl2/H2O (4/1, 10 mL) was heated in a sealed tube at 110 oC for the 24 h. After the
reaction finished, it was abstracted by CH2Cl2 (3 × 5 mL). The organic layer was dried
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with anhydrous Na2SO4, the filtrate was evaporated under vacuum and purified by
column chromatography to afford the desired product.
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4ꢀBromoꢀ6,6,6ꢀtrifluorohexyl 4ꢀchlorobenzoate(1). A colorless oil after purification
by flash column chromatography (petroleum ether/ethyl acetate = 20/1, Yield: 85%,
63.4 mg). 1H NMR (400 MHz, CDCl3): δ 7.96 (d, J = 8.6 Hz, 2H), 7.41 (d, J = 8.6 Hz,
2H), 4.36 (t, J = 5.6 Hz, 2H), 4.25 – 4.19 (m, 1H), 2.90 – 2.64 (m, 2H), 2.14 – 2.04 (m,
2H), 2.01 – 1.91 (m, 2H); 19F NMR (376 MHz, CDCl3): δ ꢀ63.79 (t, J = 10.2 Hz, 3F);
13C NMR (101 MHz, CDCl3): δ 165.6, 139.5, 130.9, 128.7, 128.5, 125.2 (q, J = 278.1
Hz), 64.0, 44.2 (q, J = 3.1 Hz), 43.1 (q, J = 28.5 Hz), 35.0, 26.5. HRMS (ESI, m/z):
Calculated for C13H13Br1Cl1F3O2Na1 (M+Na)+ 394.9632, found 394.9631.
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4ꢀBromoꢀ6,6,6ꢀtrifluorohexyl 4ꢀmethoxybenzoate(2).
A
colorless oil after
purification by flash column chromatography (petroleum ether/ethyl acetate = 20/1,
1
Yield: 72%, 53.1 mg). H NMR (400 MHz, CDCl3): δ 7.98 (d, J = 8.8 Hz, 2H), 6.92
(d, J = 8.8 Hz, 2H), 4.32 (t, J = 5.5 Hz, 2H), 4.24 – 4.19 (m, 1H), 3.85 (s, 3H),
2.87ꢀ2.67(m, 2H), 2.13 – 2.03 (m, 2H), 2.01 – 1.90 (m, 2H); 19F NMR (376 MHz,
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CDCl3): δ ꢀ63.79 (t, J = 10.2 Hz, 3F); C NMR (101 MHz, CDCl3): δ 166.2, 163.4,
131.5, 125.2 (q, J = 278.0 Hz), 122.5, 113.6, 67.9, 63.4, 55.4, 44.3 (q, J = 3.1 Hz),
43.1 (q, J = 28.5 Hz), 35.1, 26.6. HRMS (ESI, m/z): Calculated for C14H16Br1F3O3Na1
(M+Na)+ 391.0127, found 391.0135.
4ꢀBromoꢀ6,6,6ꢀtrifluorohexyl benzo[d][1,3]dioxoleꢀ5ꢀcarboxylate(3). A colorless
oil after purification by flash column chromatography (petroleum ether/ethyl acetate =
20/1, Yield: 76%, 58.2 mg). 1H NMR (400 MHz, CDCl3): δ 7.63 (d, J = 8.2 Hz, 1H),
7.44 (s, 1H), 6.83 (d, J = 8.2 Hz, 1H), 6.03 (s, 2H), 4.32 (t, J = 5.4 Hz, 2H), 4.24 –
4.18 (m, 1H), 2.89 – 2.64 (m, 2H), 2.12 – 2.02 (m, 2H), 1.98 – 1.89 (m, 2H); 19F
NMR (376 MHz, CDCl3): δ ꢀ63.79 (t, J = 10.2 Hz, 3F); 13C NMR (101 MHz, CDCl3):
δ 165.8, 151.7, 147.7, 125.3, 125.2 (q, J = 278.1 Hz), 124.0, 109.4, 108.0, 101.8, 63.7,
44.3 (q, J = 3.1 Hz), 43.1 (q, J = 28.5 Hz), 35.0, 26.6. HRMS (ESI, m/z): Calculated
for C14H14Br1F3O4Na1 (M+ Na)+ 404.9920, found 404.9930.
4ꢀBromoꢀ6,6,6ꢀtrifluorohexyl 4ꢀ(N,Nꢀdipropylsulfamoyl)benzoate(4). A colorless oil
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after purification by flash column chromatography (petroleum ether/ethyl acetate =
20/1, Yield: 67%, 67.2 mg). 1H NMR (400 MHz, CDCl3): δ 8.14 (d, J = 8.4 Hz, 2H),
7.87 (d, J = 8.4 Hz, 2H), 4.40 – 4.39 (m, 2H), 4.23 – 4.21 (m, 1H), 3.11 – 3.07 (m,
4H), 2.86 – 2.69 (m, 2H), 2.13 – 2.08 (m, 2H), 1.99 – 1.93 (m, 2H), 1.57 – 1.49 (m,
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4H), 0.86 (t, J = 7.4 Hz, 6H); F NMR (376 MHz, CDCl3): δ ꢀ63.76 (t, J = 10.2 Hz,
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3F); C NMR (151 MHz, CDCl3): δ 165.1, 144.4, 133.3, 130.2, 127.0, 125.1 (q, J =
278.7 Hz), 64.4, 49.9, 44.1, 43.0 (q, J = 28.1 Hz), 34.9, 26.5, 21.9, 11.1. HRMS (ESI,
m/z): Calculated for C19H28Br1F3O4N1S1 (M+ H)+ 502.0869, found 502.0862.
2ꢀBromoꢀ4,4,4ꢀtrifluorobutyl 4ꢀ(N,Nꢀdipropylsulfamoyl)benzoate(5). A colorless oil
after purification by flash column chromatography (petroleum ether/ethyl acetate =
20/1, Yield: 67%, 63.3 mg). 1H NMR (400 MHz, CDCl3): δ 8.17 (d, J = 8.5 Hz, 2H),
7.90 (d, J = 8.5 Hz, 2H), 4.64 – 4.62 (m, 2H), 4.46 – 4.40 (m, 1H), 3.12 – 3.08 (m,
4H), 2.96 – 2.79 (m, 2H), 1.60 – 1.52 (m, 4H), 0.87 (t, J = 7.4 Hz, 6H); 19F NMR (376
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MHz, CDCl3): δ ꢀ63.94 (t, J = 10.0 Hz, 3F); C NMR (101 MHz, CDCl3): δ 164.4,
144.9, 132.4, 130.4, 127.2, 125.0 (q, J = 277.8 Hz), 67.4, 49.9, 39.9 (q, J = 29.6 Hz),
38.9 (q, J = 3.1 Hz), 21.9, 11.1. HRMS (ESI, m/z): Calculated for C17H24Br1F3O4N1S1
(M+H)+ 474.0556, found 474.0562.
5ꢀBromoꢀ7,7,7ꢀtrifluoroheptyl picolinate(6). A colorless oil after purification by
flash column chromatography (petroleum ether/ethyl acetate = 20/1, Yield: 71%, 50.2
mg). 1H NMR (400 MHz, CDCl3): δ 8.75 (d, J = 4.1 Hz, 1H), 8.11 (d, J = 7.8 Hz, 1H),
7.83 (td, J = 7.8, 1.6 Hz, 1H), 7.48 – 7.45 (m, 1H), 4.42 (t, J = 6.7 Hz, 2H), 4.17 –
4.10 (m, 1H), 2.82 – 2.63 (m, 2H), 2.01 – 1.80 (m, 4H), 1.79 – 1.53 (m, 2H); 19F
NMR (376 MHz, CDCl3): δ ꢀ63.81 (t, J = 10.2 Hz, 3F); 13C NMR (101 MHz, CDCl3):
δ 165.1, 150.0, 148.0, 137.0, 125.2 (q, J = 278.0 Hz), 127.0, 125.1, 65.4, 44.5 (q, J =
3.1 Hz), 43.0 (q, J = 28.5 Hz), 37.9, 28.0, 23.7. HRMS (ESI, m/z): Calculated for
C13H16Br1F3N1O2 (M+H)+ 354.0311, found 354.0314.
4ꢀBromoꢀ6,6,6ꢀtrifluorohexyl 1ꢀmethylꢀ1Hꢀindoleꢀ3ꢀcarboxylate(7). A colorless oil
after purification by flash column chromatography (petroleum ether/ethyl acetate =
1
20/1, Yield: 61%, 47.0 mg). H NMR (400 MHz, CDCl3): δ 8.14 (dd, J = 6.4, 2.6 Hz,
1H), 7.79 (s, 1H), 7.38 – 7.35 (m, 1H), 7.32 – 7.29 (m, 2H), 4.40 – 4.36 (m, 2H), 4.28
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–4.22 (m, 1H), 3.84 (s, 3H), 2.88 – 2.68 (m, 2H), 2.19 – 2.07 (m, 2H), 2.05 –1.93 (m,
2H); 19F NMR (376 MHz, CDCl3): δ ꢀ63.73 (t, J = 10.2 Hz, 3F); 13C NMR (101 MHz,
CDCl3): δ 164.9, 137.2, 135.3, 126.5, 125.2 (q, J = 278.1 Hz), 122.8, 121.9, 121.5,
109.8, 106.7, 62.4, 44.5 (q, J = 3.1 Hz), 43.1 (q, J = 28.5 Hz), 35.2, 33.5, 26.8. HRMS
(ESI, m/z): Calculated for C16H17Br1F3N1O2 Na1 (M+Na)+ 414.0287, found 414.0283.
2ꢀBromoꢀ4,4,4ꢀtrifluorobutyl 3ꢀphenylpropanoate(8). A colorless oil after
purification by flash column chromatography (petroleum ether/ethyl acetate = 40/1,
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Yield: 60%, 40.6 mg). H NMR (400 MHz, CDCl3): δ 7.33 – 7.29 (m, 2H), 7.24
–7.21(m, 3H), 4.40 – 4.26 (m, 2H), 4.25 – 4.18 (m, 1H), 2.99 (t, J = 7.6 Hz, 2H), 2.74
– 2.57 (m, 4H); 19F NMR (376 MHz, CDCl3): δ ꢀ64.00 (t, J = 10.1 Hz, 3F); 13C NMR
(101 MHz, CDCl3): δ 172.0 , 139.9, 128.6, 128.2, 126.4, 125.0 (q, J = 278.7 Hz), 66.4,
39.4 (q, J = 29.5 Hz), 38.9 (q, J = 3.2 Hz), 35.5, 30.7. HRMS (ESI, m/z): Calculated
for C13H14Br1F3O2Na1 (M+Na)+ 361.0021, found 361.0018.
4ꢀBromoꢀ6,6,6ꢀtrifluorohexyl 4ꢀbromobenzenesulfonate(9). A colorless oil after
purification by flash column chromatography (petroleum ether/ethyl acetate = 20/1,
1
Yield: 61%, 55.4 mg). H NMR (400 MHz, CDCl3): δ 7.77 (d, J = 8.6 Hz, 2H), 7.71
(d, J = 8.6 Hz, 2H), 4.11ꢀ4.09 (m, 3H), 2.83 – 2.58(m, 2H), 2.01 – 1.98 (m, 2H),
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1.84ꢀ1.81 (m, 2H); 19F NMR (376 MHz, CDCl3): δ ꢀ63.76 (d, J = 4.1 Hz, 3F); C
NMR (101 MHz, CDCl3): δ 134.9, 132.6, 129.3, 129.1, 125.0 (q, J = 278.2 Hz), 69.7,
43.7, 43.0 (q, J = 28.6 Hz), 34.3, 26.8. HRMS (ESI, m/z): Calculated for
C12H13Br2F3O3Na1 (M+Na)+ 474.8796, found 474.8802.
2ꢀ(4ꢀBromoꢀ6,6,6ꢀtrifluorohexyl)isoindolineꢀ1,3ꢀdione(10). A colorless oil after
purification by flash column chromatography (petroleum ether/ethyl acetate = 20/1,
Yield: 79%, 57.5 mg). 1H NMR (400 MHz, CDCl3): δ 7.84 (dd, J = 5.4, 3.1 Hz, 2H),
7.71 (dd, J = 5.4, 3.1 Hz, 2H), 4.21ꢀ4.18( m, J = 7.5 Hz, 1H), 3.74ꢀ3.71 (t, J = 6.4 Hz,
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2H), 2.83 – 2.56 (m, 2H), 2.02 – 1.90 (m, 2H), 1.89 – 1.82 (m, 2H); F NMR (376
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MHz, CDCl3): δ ꢀ63.82 (t, J = 10.1 Hz, 3F); C NMR (101 MHz, CDCl3): δ 168.3,
134.0, 132.0, 125.1 (q, J = 278.1 Hz), 123.26 (s), 43.9 (q, J = 3.1 Hz), 43.0 (q, J =
28.6 Hz), 36.8, 35.5, 26.4. HRMS (ESI, m/z): Calculated for C14H13Br1N1F3O2Na1
(M+Na)+ 385.9974, found 385.9980.
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2ꢀ(3ꢀBromoꢀ5,5,5ꢀtrifluoropentyl)isoindolineꢀ1,3ꢀdione(11). A colorless oil after
purification by flash column chromatography (petroleum ether/ethyl acetate = 20/1,
Yield: 80%, 56.0 mg). 1H NMR (400 MHz, CDCl3): δ 7.85 (dd, J = 5.4, 3.0 Hz, 2H),
7.73 (dd, J = 5.4, 3.1 Hz, 2H), 4.19 – 4.12 (m, 1H), 3.98 – 3.83 (m, 2H), 2.89 – 2.71
(m, 2H), 2.40 –2.31 (m, 1H), 2.26 – 2.16 (m, 1H); 19F NMR (376 MHz, CDCl3): δ
ꢀ63.60 (t, J = 10.1 Hz, 3F); 13C NMR (101 MHz, CDCl3): δ 168.1, 134.1, 131.9, 125.1
(q, J = 278.2 Hz), 123.4, 42.9 (q, J = 28.7 Hz), 41.0 (q, J = 3.2 Hz), 36.8, 36.1. HRMS
(ESI, m/z): Calculated for C13H11Br1F3N1O2Na1 (M+Na)+ 371.9817, found 371.9822.
1ꢀBromoꢀ4ꢀ((4ꢀbromoꢀ6,6,6ꢀtrifluorohexyl)oxy)benzene(12). A colorless oil after
purification by flash column chromatography (petroleum ether/ethyl acetate = 20/1,
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Yield: 86%, 66.5 mg). H NMR (400 MHz, CDCl3): δ 7.23 (d, J = 9.2 Hz, 2H), 6.81
(d, J = 9.2 Hz, 2H), 4.26 – 4.19 (m, 1H), 3.99 – 3.96 (m, 2H), 2.88 – 2.66 (m, 2H),
2.19 – 2.03 (m, 2H), 1.98 – 1.91 (m, 2H); 19F NMR (376 MHz, CDCl3): δ ꢀ63.77 (t, J
= 10.2 Hz, 3F); 13C NMR (101 MHz, CDCl3): δ 157.3, 129.3, 125.7, 125.2 (q, J =
279.0 Hz), 115.7, 67.0, 44.5, 43.2 (q, J = 28.5 Hz), 35.2, 27.0. HRMS (ESI, m/z):
Calculated for C12H14Br2F3O (M+H)+ 388.9363, found 388.9365.
4ꢀ((4ꢀBromoꢀ6,6,6ꢀtrifluorohexyl)oxy)ꢀ3ꢀmethoxybenzaldehyde(13). A colorless oil
after purification by flash column chromatography (petroleum ether/ethyl acetate =
1
20/1, Yield: 63%, 46.5 mg). H NMR (400 MHz, CDCl3): δ 9.85 (s, 1H), 7.45 – 7.41
(m, 2H), 6.96 (d, J = 8.4 Hz, 1H), 4.31 – 4.25 (m, 1H), 4.20 – 4.10 (m, 2H), 3.92 (s,
19
3H), 2.88 – 2.65 (m, 2H), 2.20 – 2.11 (m, 2H), 2.07 – 1.97 (m, 2H); F NMR (376
13
MHz, CDCl3): δ ꢀ63.76 (t, J = 10.2 Hz, 3F); C NMR (101 MHz, CDCl3): δ 190.9,
153.7, 149.9, 130.3, 126.6, 125.2 (q, J = 278.1 Hz), 111.6, 109.4, 68.0, 56.0, 44.5 (q, J
= 3.2 Hz), 43.1 (q, J = 28.6 Hz), 35.2, 26.8. HRMS (ESI, m/z): Calculated for
C14H16Br1F3O3Na1 (M+Na)+ 391.0127, found 391.0133.
5ꢀBromoꢀ7,7,7ꢀtrifluoroheptanꢀ1ꢀol(14). A colorless oil after purification by flash
column chromatography (petroleum ether/ethyl acetate = 5/1, Yield: 55%, 27.3 mg).
1H NMR (400 MHz, CDCl3): δ 4.17 – 4.11 (m, 1H), 3.64 (t, J = 5.9 Hz, 2H), 2.85 –
2.61 (m, 2H), 1.93 – 1.80 (m, 3H), 1.69 – 1.47 (m, 4H); 19F NMR (376 MHz, CDCl3):
13
δ ꢀ63.85 (t, J = 9.9 Hz, 3F); C NMR (151 MHz, CDCl3): δ 125.3 (q, J = 278.7 Hz),
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62.3, 44.9, 43.0 (q, J = 27.6 Hz), 38.2, 31.6, 29.6, 23.5, 22.5. MS(EI): m/z(%):
77(11.77), 81(14.43), 87(12.22), 111(15.44), 131(24.19), 151(100.00), 152(7.60),
247(0.04), 249(0.05). Characterization data matched that reported in the literature. 10a
2ꢀ(5ꢀBromoꢀ7,7,7ꢀtrifluoroheptyl)oxirane(15). A colorless oil after purification by
flash column chromatography (petroleum ether/ethyl acetate = 5/1, Yield: 60%, 33.0
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mg). H NMR (400 MHz, CDCl3): δ 4.19 – 4.12 (m, 1H), 2.94 –2.91 (m, 1H), 2.87 –
2.59 (m, 3H), 2.48 (dd, J = 4.8, 2.8 Hz, 1H), 1.95 – 1.80 (m, 2H), 1.64 – 1.46 (m, 6H);
19F NMR (376 MHz, CDCl3): δ ꢀ63.82 (t, J = 10.0 Hz, 3F); 13C NMR (151 MHz,
CDCl3): δ 125.2 (q, J = 279.0 Hz), 52.1, 47.0, 44.8, 43.0 (q, J = 28.8 Hz), 38.3, 32.19,
26.9, 25.2. HRMS (ESI, m/z): Calculated for C9H14Br1F3O1Na1 (M+Na)+ 297.0072,
found 297.0069.
7ꢀ((4ꢀBromoꢀ6,6,6ꢀtrifluorohexyl)oxy)ꢀ2Hꢀchromenꢀ2ꢀone(16). A colorless oil after
purification by flash column chromatography (petroleum ether/ethyl acetate = 10/1,
1
Yield: 67%, 49.0 mg). H NMR (400 MHz, CDCl3): δ 7.62 (d, J = 9.4 Hz, 1H), 7.36
(d, J = 8.5 Hz, 1H), 6.83 – 6.78 (m, 2H), 6.23 (d, J = 9.4 Hz, 1H), 4.27 – 4.22 (m, 1H),
4.07 – 4.06 (m, 2H), 2.88 – 2.66 (m, 2H), 2.19 – 2.13 (m, 2H), 2.05 – 1.96 (m, 2H);
19F NMR (376 MHz, CDCl3): δ ꢀ63.75 (t, J = 10.2 Hz, 3F); 13C NMR (101 MHz,
CDCl3): δ 161.9, 161.1, 155.8, 143.4, 128.8, 125.2 (q, J = 278.0 Hz), 113.2 , 112.8,
112.6, 101.3, 67.3, 44.4 (q, J = 3.1 Hz), 43.1 (q, J = 28.5 Hz), 35.1, 26.9. HRMS (ESI,
m/z): Calculated for C15H15Br1F3O3 (M+H)+ 379.0151, found 379.0154.
2ꢀOxoꢀ2Hꢀchromenꢀ7ꢀyl 3ꢀbromoꢀ5,5,5ꢀtrifluoropentanoate(17). A colorless oil
after purification by flash column chromatography (petroleum ether/ethyl acetate =
20/1, Yield: 62%, 46.7 mg). 1H NMR (400 MHz, CDCl3): δ 7.70 (d, J = 9.6 Hz, 1H),
7.51 (d, J = 8.4 Hz, 1H), 7.16 – 7.14 (m, 1H), 7.09 – 7.07 (m, 1H), 6.41 (d, J = 9.6 Hz,
1H), 4.62 – 4.55 (m, 1H), 3.37 (dd, J = 16.7, 4.8 Hz, 1H), 3.21 (dd, J = 16.7, 8.8 Hz,
1H), 2.97 – 2.87 (m, 2H); 19F NMR (376 MHz, CDCl3): δ ꢀ63.77 (t, J = 10.2 Hz, 3F);
13C NMR (101 MHz, CDCl3): δ 167.2, 160.1, 154.6, 152.5, 142.7, 128.7, 124.9 (q, J =
278.2 Hz), 118.2, 117.0, 116.4, 110.3, 43.1, 42.1 (q, J = 29.1 Hz), 36.69 – 36.63(m).
HRMS (ESI, m/z): Calculated for C14H11Br1F3O4 (M+H)+ 378.9787, found 378.9790.
(8R,9S,13S,14S)ꢀ13ꢀMethylꢀ17ꢀoxoꢀ7,8,9,11,12,13,14,15,16,17ꢀdecahydroꢀ6Hꢀcyclo
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penta[a]phenanthrenꢀ3ꢀyl 3ꢀBromoꢀ5,5,5ꢀtrifluoropentanoate(18). A colorless oil
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after purification by flash column chromatography (petroleum ether/ethyl acetate =
1
5/1, Yield: 56%, 53.5 mg). H NMR (400 MHz, CDCl3): δ 7.30 (d, J = 8.4 Hz, 1H),
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6.89 – 6.84 (m, 2H), 4.60 – 4.56 (m, 1H), 3.29 (dd, J = 16.5, 5.1 Hz, 1H), 3.17 (dd, J
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= 16.5, 8.4 Hz, 1H), 2.96 – 2.87 (m, 4H), 2.54 – 1.95 (m, 8H), 1.68 – 1.43 (m, 5H),
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0.91 (s, 3H); F NMR (376 MHz, CDCl3): δ ꢀ63.79 (t, J = 10.0 Hz, 3F); C NMR
(151 MHz, CDCl3): δ 220.6, 168.1, 148.1, 138.2, 137.8, 126.5, 125.0 (q, J = 278.2
Hz), 121.3, 118.5, 50.4, 47.9, 44.1, 43.3, 42.1 (q, J = 29.1 Hz), 37.9, 37.0 (q, J = 3.2
Hz), 35.8, 31.5, 29.4, 26.3, 25.7, 21.6, 13.8. HRMS (ESI, m/z): Calculated for
C23H30Br1F3 N1O3 (M+NH4)+ 504.1358, found 504.1362.
(8R,9S,13S,14S)ꢀ3ꢀ((4ꢀBromoꢀ6,6,6ꢀtrifluorohexyl)oxy)ꢀ13ꢀmethylꢀ6,7,8,9,11,12,13,
14,15,16ꢀdecahydroꢀ17Hꢀcyclopenta[a]phenanthrenꢀ17ꢀone(19). A colorless oil after
purification by flash column chromatography (petroleum ether/ethyl acetate = 5/1,
1
Yield: 55%, 53.3 mg). H NMR (400 MHz, CDCl3): δ 7.20 (d, J = 8.8 Hz, 1H), 6.71
(dd, J = 8.5, 2.2 Hz, 1H), 6.65 (s, 1H), 4.26 – 4.20 (m, 1H), 3.98 (t, J = 5.4 Hz, 2H),
2.92 – 2.87 (m, 2H), 2.84 – 2.68 (m, 2H), 2.54 – 2.47 (m, 1H), 2.42 – 2.38 (m, 1H),
2.28 – 2.23 (m, 1H), 2.19 – 1.89 (m, 9H), 1.71 – 1.39 (m, 5H), 0.91 (s, 3H); 19F NMR
(376 MHz, CDCl3): δ ꢀ63.70 (t, J = 10.2 Hz, 3F); 13C NMR (151 MHz, CDCl3): δ
220.1, 156.7, 137.7, 132.2, 126.3, 125.2 (q, J = 278.7 Hz), 114.5, 120.0 , 66.6, 50.3,
47.9, 44.7, 43.9, 43.1 (q, J = 28.8 Hz), 38.9, 35.8, 35.3, 31.5, 29.6, 27.1, 26.5, 25.9,
21.5, 13.8. HRMS (ESI, m/z): Calculated for C24H31Br1F3O2 (M+H)+ 487.1454, found
487.1449.
(3ꢀBromoꢀ4ꢀ(trifluoromethyl)cyclopentyl)methyl 4ꢀnitrobenzenesulfonate(20): A
yellow solid after purification by flash column chromatography (petroleum ether/ethyl
acetate = 20/1, Yield: 68%, 58.7 mg). 1H NMR (400 MHz, CDCl3): δ 8.43 (d, J = 8.8
Hz, 6.8H), 8.12 (dd, J = 8.9, 2.5 Hz, 6.8H), 4.43ꢀ4.40 (m, 1H), 4.24ꢀ4.18 (m, 2.4H),
4.14ꢀ4.10 (m, 6.8H), 3.17 – 3.11 (m, 1H), 3.05 – 2.98 (m, 2.4H), 2.84ꢀ2.80 (m, 1.2H),
2.59ꢀ2.42 (m, 5H), 2.31ꢀ2.21 (m, 2H), 2.07 – 1.97 (m, 3.49H), 1.93ꢀ1.84 (m, 5H); 19F
13
NMR (376 MHz, CDCl3): δ ꢀ71.06 (d, J = 9.2 Hz), ꢀ71.23 (d, J = 9.4 Hz); C NMR
(101 MHz, CDCl3): δ 150.9, 141.5, 129.2, 126.7 (d, J = 278.9 Hz), 124.6, 72.8, 52.5
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(q, J = 27.6 Hz), 42.8 (q, J = 2.6 Hz), 40.8, 37.3, 28.2. HRMS (ESI, m/z): Calculated
for C13H13Br1N1F3O5S1Na1 (M+Na)+ 453.9542, found 453.9545.
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3ꢀBromoꢀ3ꢀmethylꢀ2ꢀ(trifluoromethyl)butyl 4ꢀmethoxybenzoate(21): A colorless oil
after purification by flash column chromatography (petroleum ether/ethyl acetate =
40/1, Yield: 60%, 44.1 mg). 1H NMR (400 MHz, CDCl3): δ 7.99 (d, J = 9.0 Hz, 2H),
6.93 (d, J = 9.0 Hz, 2H), 4.83 (dd, J = 12.4, 2.4 Hz, 1H), 4.71 (dd, J = 12.2, 5.8 Hz,
1H), 3.86 (s, 3H), 3.04 – 2.95 (m, 1H), 2.06 (s, 3H), 1.94 (s, 3H); 19F NMR (376 MHz,
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CDCl3): δ ꢀ62.78 (d, J = 9.2 Hz), ꢀ72.88 (s); C NMR (151 MHz, CDCl3): δ 165.6,
163.7, 131.7, 125.6 (q, J = 284.0 Hz), 121.9, 113.7, 62.1, 61.2, 55.4, 54.6 (q, J = 24.4
Hz), 34.8, 32.08. HRMS (ESI, m/z): Calculated for C14H17Br1F3O3 (M+H)+ 369.0310,
found 369.0308.
1ꢀ(1ꢀBromoꢀ3,3,3ꢀtrifluoropropyl)ꢀ4ꢀchlorobenzene(22): A colorless oil after
purification by flash column chromatography (petroleum ether, Yield: 64%, 36.8 mg).
1H NMR (400 MHz, CDCl3): δ 7.35 (d, J = 8.5 Hz, 2H), 7.35 (d, J = 8.5 Hz, 2H), 5.14
– 5.10 (m, 1H), 3.17 – 3.03 (m, 2H); 19F NMR (376 MHz, CDCl3): δ ꢀ64.09 (t, J = 9.6
Hz, 3F); 13C NMR (101 MHz, CDCl3): δ 138.6, 134.9, 129.2, 128.5, 124.6 (q, J =
278.3 Hz), 43.9 (q, J = 28.6 Hz), 42.4 (q, J = 3.2 Hz). MS(EI): m/z(%): 103(12.67),
138(12.07), 143(69.37), 145(22.64), 151(12.13), 207(100.00), 209(32.91), 286(1.73),
288(2.41). Characterization data matched that reported in the literature. 10a, 11
1ꢀ(1ꢀBromoꢀ3,3,3ꢀtrifluoropropyl)ꢀ3ꢀchlorobenzene(23): A colorless oil after
purification by flash column chromatography (petroleum ether, Yield: 60%, 25.1 mg).
1H NMR (400 MHz, CDCl3): δ 7.41 (s, 1H), 7.32 – 7.28 (m, 3H), 5.10 – 5.05 (m, 1H),
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3.15 – 3.02 (m, 2H); F NMR (376 MHz, CDCl3): δ ꢀ64.13 (t, J = 9.7 Hz, 3F); C
NMR (151 MHz, CDCl3): δ 142.0, 134.7, 130.2, 127.3, 126.5 (q, J = 278.7 Hz), 125.3,
123.7, 43.8 (q, J = 28.8 Hz), 42.1. MS(EI): m/z(%): 103(15.25), 142(37.70),
143(83.83), 145(29.90), 174(100), 207(88.04), 209(28.95). Characterization data
matched that reported in the literature. 10a
1ꢀ(1ꢀBromoꢀ3,3,3ꢀtrifluoropropyl)ꢀ2ꢀchlorobenzene(24): A colorless oil after
purification by flash column chromatography (petroleum ether, Yield: 57%, 23.8 mg).
1H NMR (400 MHz, CDCl3): δ 7.55 (dd, J = 7.8, 1.4 Hz, 1H), 7.38 (dd, J = 7.8, 1.4
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Hz, 1H), 7.32 (td, J = 7.6, 1.2 Hz, 1H), 7.28 – 7.23 (m, 1H), 5.70 (t, J = 7.2 Hz, 1H),
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3.18 – 3.09 (m, 2H); F NMR (376 MHz, CDCl3): δ ꢀ64.28 (t, J = 9.7 Hz, 3F); C
NMR (101 MHz, CDCl3): δ 137.4, 132.5, 130.1, 130.1, 128.8, 127.6, 124.7 (q, J =
278.5 Hz), 42.8 (q, J = 28.8 Hz), 38.7 (q, J = 3.1 Hz). MS(EI): m/z(%): 125(17.48),
143(54.81), 161(16.06), 187(22.90), 207(100), 209(31.60). Characterization data
matched that reported in the literature. 10a
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1ꢀBromoꢀ4ꢀ(1ꢀbromoꢀ3,3,3ꢀtrifluoropropyl)benzene(25): A colorless oil after
purification by flash column chromatography (petroleum ether, Yield: 65%, 43.0 mg).
1H NMR (400 MHz, CDCl3): δ 7.50 (d, J = 8.5 Hz, 2H), 7.28 (d, J = 8.5 Hz, 2H), 5.12
– 5.08 (m, 1H), 3.17 – 3.00 (m, 2H); 19F NMR (376 MHz, CDCl3): δ ꢀ64.09 (t, J = 9.8
Hz, 3F); 13C NMR (101 MHz, CDCl3): δ 139.1, 132.2, 128.7, 124.6 (d, J = 278.5 Hz),
123.0, 43.9 (q, J = 28.6 Hz), 42.4 (q, J = 3.3 Hz). MS(EI): m/z(%): 77(17.53),
102(11.14), 103(15.64), 151(20.87), 152(14.86), 172(15.41), 187(61.03), 189(57.46),
251(100), 253(87.76), 332(3.94). Characterization data matched that reported in the
literature. 10a, 12
1ꢀ(1ꢀBromoꢀ3,3,3ꢀtrifluoropropyl)ꢀ4ꢀnitrobenzene(26): A slight yellow solid after
purification by flash column chromatography (petroleum ether, Yield: 47%, 27.8 mg).
1H NMR (400 MHz, CDCl3): δ 8.24 (d, J = 8.8 Hz, 2H), 7.59 (d, J = 8.7 Hz, 2H), 5.19
19
–5.16 (m, 1H), 3.21 – 3.07 (m, 2H); F NMR (376 MHz, CDCl3): δ ꢀ64.05 – ꢀ63.98
(m, 3F); 13C NMR (101 MHz, CDCl3): δ 148.0, 146.7, 128.2, 124.4 (q, J = 278.5 Hz),
124.2, 43.7 (q, J = 28.8 Hz), 41.0 (q, J = 3.4 Hz). HRMS (ESI, m/z): Calculated for
C9H7Br1F3O2N1Na1 (M+Na)+ 319.9504, found 319.9512.
4ꢀ(1ꢀBromoꢀ3,3,3ꢀtrifluoropropyl)ꢀ1,1'ꢀbiphenyl(27):
A
white solid after
purification by flash column chromatography (petroleum ether, Yield: 64%, 42.2 mg).
1H NMR (400 MHz, CDCl3): δ 7.61 – 7.58 (m, 4H), 7.49 – 7.44 (m, 4H), 7.39 – 7.36
(m, 1H), 5.24 –5.22 (m, 1H), 3.23 – 3.11 (m, 2H); 19F NMR (376 MHz, CDCl3): δ
ꢀ64.08 (t, J = 9.8 Hz, 3F); 13C NMR (101 MHz, CDCl3): δ 142.0, 140.1, 139.0, 128.8,
127.7, 127.6, 127.5, 127.1, 124.7 (q, J = 278.3 Hz), 43.8 (q, J = 28.4 Hz), 43.3 (q, J =
3.3 Hz). MS(EI): m/z(%): 92(10.79), 165(19.85), 178(18.57), 180(16.30), 185(9.86),
248(19.87), 249(100.00), 328(2.67), 330(2.41). Characterization data matched that
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2ꢀ(1ꢀBromoꢀ3,3,3ꢀtrifluoropropyl)naphthalene(28): A white solid after purification
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by flash column chromatography (petroleum ether, Yield: 61%, 37.0 mg). H NMR
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(400 MHz, CDCl3): δ 7.90 – 7.83 (m, 4H), 7.56 – 7.51 (m, 3H), 5.36 (t, J = 7.2 Hz,
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1H), 3.28 – 3.19 (m, 2H); F NMR (376 MHz, CDCl3): δ ꢀ64.09 (t, J = 9.7 Hz, 3F);
13C NMR (101 MHz, CDCl3): δ 137.2, 133.4, 132.9, 129.2, 128.1, 127.8, 126.9, 126.8,
126.1, 124.8 (q, J = 277.9 Hz), 124.3, 44.0 (q, J = 3.3 Hz), 43.8 (q, J = 28.4 Hz).
MS(EI): m/z(%): 152(19.71), 153(21.20), 154(22.28), 159(28.29), 183(24.60),
223(100.00), 302(8.43), 304(7.87). Characterization data matched that reported in the
literature. 10a, 11
2ꢀ(Trifluoromethyl)ꢀ1Hꢀindene(29): A colorless oil after purification by flash
column chromatography (petroleum ether, Yield: 60%, 22.0 mg). 1H NMR (400 MHz,
CDCl3): δ 7.53 – 7.49 (m, 2H), 7.36 – 7.33 (m, 2H), 7.32 – 7.30 (m, 1H), 3.63 (s, 2H);
19F NMR (376 MHz, CDCl3): δ ꢀ62.08 (d, J = 1.0 Hz, 3F); 13C NMR (101 MHz,
CDCl3): δ 143.0, 141.7, 134.9, 134.6 (q, J = 5.2 Hz), 127.1, 127.0, 124.2, 123.2 (q, J
= 268.1 Hz), 122.9, 36.8.MS(EI): m/z(%): 57(100), 81(47.52), 125(29.99), 151(16.10),
168(18.57), 184(72.17). Characterization data matched that reported in the literature.
10a, 13
2ꢀBromoꢀ7,7,7ꢀtrifluoroheptꢀ4ꢀenꢀ1ꢀyl 4ꢀchlorobenzoate(30): A colorless oil after
purification by flash column chromatography (petroleum ether/ethyl acetate = 20/1,
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Yield: 72%, 55.1 mg). H NMR (400 MHz, CDCl3): δ 8.00 (d, J = 8.5 Hz, 2H), 7.44
(d, J = 8.5 Hz, 2H), 5.83 – 5.54 (m, 2H), 4.58 – 4.49 (m, 2H), 4.29 – 4.23 (m, 2H),
2.91 – 2.75 (m, 3H), 2.71 – 2.64 (m, 1H); 19F NMR (376 MHz, CDCl3): δ ꢀ65.97 (t, J
= 10.7 Hz), ꢀ66.44 (t, J = 10.6 Hz); 13C NMR (151 MHz, CDCl3): δ 165.0, 139.9,
132.9, 131.1, 128.9, 125.7(q, J = 277.1 Hz), 122.3, 67.5, 49.0, 38.2, 37.3(q, J = 29.9
Hz), 33.1. HRMS (ESI, m/z): Calculated for C14H14Br1Cl1F3O2 (M+H)+ 384.9815,
found 384.9812.
AUTHOR INFORMATION
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Corresponding Author:
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Eꢀmail: liuzhq@lzu.edu.cn
Notes
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The authors declare no competing financial interest.
ACKNOWLEDGMENT
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This project is supported by the National Natural Science Foundation of China (Nos.
21272096, 21472080, 21672089), the Program for Changjiang Scholars and
Innovative Research Team in University (PCSIRT: IRT15R28), and the Fundamental
Research Funds for the Central Universities (lzujbkyꢀ2016ꢀ50, lzujbkyꢀ2016ꢀct02).
Supporting Information
1
Copies of H, 19F, 13C NMR spectral for all reaction products. This material is
available free of charge via the Internet at http://pubs.acs.org.
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