Synthesis of α-trifluoromethyl ketones via the Cu-catalyzed trifluoromethylation of silyl enol ethers using an electrophilic trifluoromethylating agent

Article abstract of DOI:10.1021/jo500713f

A method has been developed for the synthesis of α-trifluoromethyl ketones via the Cu-catalyzed trifluoromethylation of silyl enol ethers with an electrophilic trifluoromethylating agent, which produces a trifluoromethyl radical.

Full text of DOI:10.1021/jo500713f

Article
pubs.acs.org/joc
Synthesis of α‑Trifluoromethyl Ketones via the Cu-Catalyzed
Trifluoromethylation of Silyl Enol Ethers Using an Electrophilic
Trifluoromethylating Agent
Lun Li,† Qing-Yun Chen,*,† and Yong Guo*,†
†Key Laboratory of Organofluorine Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, 345 Lingling
Road, Shanghai 200032, P. R. of China
S
* Supporting Information
ABSTRACT: A method has been developed for the synthesis of α-
trifluoromethyl ketones via the Cu-catalyzed trifluoromethylation of
silyl enol ethers with an electrophilic trifluoromethylating agent, which
produces a trifluoromethyl radical.
Scheme 1. Comparison with Highly Related Reference
Methods
INTRODUCTION
■
Organofluorine compounds are widely used in agrochemicals,
pharmaceuticals and functional materials because of the unique
properties associated with the introduction of fluorine atoms,
such as enhanced lipophilicity, binding selectivity, and
metabolic stability.1,2 In recent years, a large number of
methods have been developed for the incorporation of CF3
groups into suitably activated parent molecules.3 Among them,
the synthesis of α-CF3-substituted carbonyl compounds
represents an important transformation.4 The α-CF3-substi-
tuted ketones can be synthesized from enolates or their
equivalents, alkenes, and other substrates by the reactions with
electrophilic and radical trifluoromethylating reagents.4−7 In
1994, Umemoto et al.5b reported the development of procedure
for the trifluoromethylation of reactive enolate anions, which is
a reaction mediated by an organoboronic ester. In 2012,
Grushin et al.4 developed a method for the nucleophilic
trifluoromethylation of α-halogenated ketones, and Xiao6i and
Maiti6k recently reported the synthesis of α-CF3-substituted
carbonyl compounds from olefins. In 2011, MacMillan et al.6h
successfully generated α-CF3-substituted carbonyl compounds
by visible-light photocatalyst. In this particular report, gaseous
trifluoromethyl iodide was used as the trifluoromethylating
agent, which limited the practical appeal of this procedure.
From a practical perspective, the development of a solid
trifluoromethylating source would be desirable, although more
expensive.8 Compared to the synthesis of α-CF3-substituted β-
ketoesters by electrophilic trifluoromethylation,9 the synthesis
of α-CF3-substituted ketones by electrophilic trifluoromethylat-
ing agents is more challenging (Scheme 1). In Xiao’s work,6i an
electrophilic trifluoromethylation reagent was used to generate
a trifluoromethyl radical. Inspired by this work, we envisaged
that the reaction of a suitably substituted silyl enol ether with
an electrophilic trifluoromethylating agent under redox
conditions would provide access to α-CF3 ketones in good
yield. The reaction will be beneficial and practical because it has
a wide scope of substrates with no requirement for gaseous
starting materials, strong bases (such as lithium diisopropyla-
mide, LDA), or conditions of a very low temperature.
RESULTS AND DISCUSSION
■
The reaction of 1a′ with Umemoto’s electrophilic reagent 2a in
the presence of a copper catalyst in DMF at room temperature
was initially selected as a model reaction to identify the
optimum conditions for the transformation. Among the copper
salts screened for this reaction, CuI provided the best results in
terms of the yield (55%) of desired ketone product (Table 1,
entries 1−4). The yield of the product was increased
significantly to 81% when Togni’s reagent 2b was used as the
trifluoromethylating agent (Table 1, entry 5). Various different
copper salts were then screened in conjunction with Togni’s
reagent, and the results revealed that CuSCN gave the best
yield of α-CF3 ketone (Table 1, entries 5−13). These
conditions were then applied to ethyl-substituted 1a instead
of 1a′, and the yield was improved to 95% (Table 1, entry 14).
Received: March 27, 2014
© XXXX American Chemical Society
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a
a
Table 1. Screening of Reaction Conditions
Table 2. Reactions with Nonsubstituted Silyl Enol Ethers
b
entry
1
2
cat.
yield (%)
1
1a′
1a′
1a′
1a′
1a′
1a′
1a′
1a′
1a′
1a′
1a′
1a′
1a′
1a
2a
2a
2a
2a
2b
2b
2b
2b
2b
2b
2b
2b
2b
2b
2b
2b
2c
CuI
55
31
14
10
81
83
18
45
73
32
89
15
27
95
0
2
CuCl
CuOAc
3
4
Cu(PF4)(MeCN)4
CuI
5
6
CuCl
7
CuOAc
8
Cu(PF4)(MeCN)4
CuBr
9
c
10
11
12
13
14
CuTc
CuSCN
Cu(OAc)2
Cu(OTf)2
CuSCN
CuSCN
CuSCN
−
d
15
1a
e
16
1a
42
35
f
17
1a
a
General conditions: silyl enol ether 1a′ or 1a (0.2 mmol), CF3 source
(0.3 mmol), copper salt (0.02 mmol), DMF (2 mL), under nitrogen
b
c
atomosphere, rt, 12 h. Yield based on 19F NMR. CuTc is copper(I)
a
Reaction conditions: 1 (0.5 mmol), 2b (0.75 mmol), CuSCN (0.05
d
e
thiophene-2-carboxylate. With MeCN as solvent. With MeOH as
solvent; Reaction conditions: 1a (0.2 mmol), 2c (0.8 mmol),
mmol), DMF (5 mL), under nitrogen atmosphere, rt, 12 h. Isolated
yield is show, and yields based on 19F NMR spectroscopy are in
parentheses.
f
PhI(OAc)2 (0.4 mmol), DMF (2 mL), under nitrogen atomosphere,
rt, 12 h.
The use of other solvents, such as MeCN or MeOH, led to no
reaction or a low yield of the desired product (Table 1, entries
15 and 16). It is noteworthy that when the reaction was
conducted in the presence of the nucleophilic trifluoromethyl
reagent 2c (i.e., Ruppert−Prakash reagent) using PhI(OAc)2 as
an oxidant, the desired product was formed in a low yield of
only 35% (Table 1, entry 17).
With the optimal conditions in hand, we proceeded to
evaluate the scope of the reaction using a wide variety of
different nonsubstituted silyl enol ethers (Table 2). The
presence of an electron-donating (3b, 3f, 3i) or electron-
withdrawing (3c−e, 3h, 3j, 3k) substituent on the aromatic ring
was well tolerated under the optimized conditions, especially
ortho-substituents (3h, 3i, 3j). Heterocyclic compounds also
reacted smoothly under the optimized conditions to give the
corresponding α-trifluoromethylated products in good yields
(e.g., 3g, 89% and 3l, 84%). The presence of a naphthyl moiety
was also well tolerated (3n), and the conjugated diene 1m gave
the terminal addition product 3m exclusively in 71% yield.
These conditions were applicable for synthesis of aliphatic
ketones 3q and 3r.
at room temperature, most likely because of negative steric and
electronic effects. To overcome these issues, the reaction
temperature was increased to 50 °C, which led to an increase in
the yield of the desired product 4a to 84%. With these new
conditions in hand, we proceeded to investigate the α-
trifluoromethylation of a range of other silyl enol ether
substrates at 50 °C (Scheme 2). A variety of different
substituted aromatic compounds reacted smoothly under the
optimized conditions, including those bearing electron-
donating (4g,h) and electron-withdrawing (4b−f,k) substitu-
ents on the aromatic moiety, which gave the corresponding
products in high yields (85−99%). The presence of an ethyl
(4i) or propyl (4j) substituent on double bond was also well
tolerated. Notably, several cyclic (4m,l) and aliphatic (4n,o)
compounds also underwent the trifluoromethylation reaction to
give the corresponding products in good yield (78−89%).
Interestingly, the application of the optimized conditions to a
silyl enol ether bearing a fluorine atom on the double bond
provided access to the corresponding α-F-α-CF3-substituted
carbonyl compound in good yield (4p, 74%). Although the 19
F
NMR yield for compound 4q was 67%, the isolated yield was
much lower at 25%. This low yield was attributed to the higher
volatility of 4q, which would have led to significant losses
during its purification. With respect to its general application as
a synthetic method for the α-trifluoromethylation of ketones
To extend the scope of the substrates, we also examined the
application of the optimized conditions to substituted silyl enol
ethers (Table 3). Unfortunately, our initial efforts in this regard
resulted in a poor conversion when the reaction was conducted
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a
Table 3. Reactions with Substituted Silyl Enol Ethers
a
Reaction conditions: 1 (0.5 mmol), 2b (0.75 mmol), CuSCN (0.05 mmol), DMF (5 mL), at a nitrogen atmosphere, 50 °C, 12 h; Isolated yields are
showed and yields based on 19F NMR spectroscopy are in parentheses.
moderate to high yields (64−88%). The presence of bulky
substituents on the double bond of the silyl enol ether led to
large steric effects, which made it difficult for the addition of
CF3 to take place and resulted in the incomplete conversion of
the silyl enol ethers and lower than expected isolated yields of
4v (71%) and 4w (88%) based on recovered staring material.
Furthermore, the trifluoromethylation of methylated estrone
using this method gave the product 4r in 76% yield, which was
higher than the yield reported using Umemoto’s method
(44%).5b
Scheme 2. Mechanistic Experiments
A preliminary investigation of the reaction mechanism
suggested that the reaction most likely involved a CF3 radical.
The 19F NMR yield of the α-CF3-substituted ketone (3a) was
reduced from 95 to 25% when the reaction was conducted
under the optimized conditions in the presence of TEMPO
(Scheme 2). Furthermore, TEMPO-CF3 was detected in the
reaction mixture by 19F NMR spectroscopy and GC−MS. A
radical-clock experiment was also conducted and confirmed the
existence of a CF3 radical in the reaction mixture which was
captured by both of the double bonds. In this experiment, the
CF3 product was formed in a total yield of 80% by 19F NMR
spectroscopy (3o:3p = 1:1). It was not possible to separate
compounds 3o and 3p by flash column chromatography, and
the compounds were therefore isolated by preparative HPLC.
The reactivity of the substituted enol form of the alkene toward
the addition of the CF3 radical was close to that of a terminal
alkene. A reduction in the reaction temperature from 25 to 0
°C, however, resulted in a decrease in the total yield to 40%,
although the ratio of 3o:3p was still 1:1 (Scheme 2).
and silyl enol ethers, it is important to note that this method
also allows for the synthesis of compounds containing a CF3-
substituted quaternary carbon center, which can be difficult to
access using the previously published procedures.10 In this
study, we have successfully prepared several compounds (4s−
w) containing a CF3-substituted quaternary carbon center in
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3,3,3-Trifluoro-1-phenylpropan-1-one (3a).4 Triethyl((1-
phenylvinyl)oxy)silane (46.8 mg, 0.2 mmol), Togni’s reagent (95.6
mg, 0.3 mmol), CuSCN (2.42 mg, 0.02 mmol), and DMF (2 mL)
were used. The mixture was stirred at room temperature for 12 h. The
compound was purified by column chromatography and isolated as a
solid in 88% yield (33 mg). 1H NMR (CDCl3, 400 MHz): δ = 3.78 (q,
J = 10.2 Hz, 2H), 7.48−7.51 (m, 2H), 7.60−7.64 (m, 1H), 7.91−7.93
(m, 2H). 19F NMR (CDCl3, 376 MHz): δ = −62.1 (t, J = 10.2 Hz).
3,3,3-Trifluoro-1-(3-methoxyphenyl)propan-1-one (3b).4
Triethyl((1-(3-methoxyphenyl)vinyl)oxy)silane (52.8 mg, 0.2 mmol),
Togni’s reagent (95.6 mg, 0.3 mmol), CuSCN (2.42 mg, 0.02 mmol),
and DMF (2 mL) were used. The mixture was stirred at room
temperature for 12 h. The compound was purified by column
Based on these experimental results, we propose that the
copper(I)-mediated trifluoromethylation of silyl enol ethers
might proceed via the mechanism shown in Scheme 3. Briefly,
Scheme 3. Proposed Mechanism
1
chromatography and isolated as an oil in 94% yield (40.8 mg). H
NMR (CDCl3, 400 MHz): δ = 3.76 (q, J = 10.2 Hz, 2H), 3.83 (s, 3H),
7.13−7.16 (m, 1H), 7.36−7.40 (m, 1H), 7.44−7.46 (m, 2H). 19F
NMR (CDCl3, 376 MHz): δ = −62.2 (t, J = 10.2 Hz).
3,3,3-Trifluoro-2-methyl-1-(3-nitrophenyl)propan-1-one
(3c).6i Triethyl((1-(3-nitrophenyl)vinyl)oxy)silane (55.8 mg, 0.2
mmol), Togni’s reagent (95.6 mg, 0.3 mmol), CuSCN (2.42 mg,
0.02 mmol), and DMF (2 mL) were used. The mixture was stirred at
room temperature for 12 h. The compound was purified by column
the reaction of copper(I) with Togni’s reagent would produce
the CF3 radical with concomitant oxidation of copper(I) to
copper(II). The CF3 radical would then add to silyl enol ether 1
to give radical intermediate 5, which would be oxidized by
copper(II) to give cationic intermediate 6 together with the
regeneration of copper(I). It is known that Cu(II) is effective in
the oxidation of such radicals.6b Finally, the loss of the silyl
group of 6 would produce the α-CF3-substituted ketone.
In conclusion, we have developed an efficient and general
method for the synthesis of α-CF3-substituted ketones under
mild conditions via the reaction of silyl enol ethers with an
electrophilic trifluoromethylating reagent (i.e., Togni’s reagent
II) in the presence of CuSCN. This newly developed method
exhibited good functional group tolerance and substrate
applicability and could also be used to construct CF3-
substituted quaternary carbon centers. Given the mild
conditions and broad substrate scope of this protocol, we
envisage that it will be widely used by synthetic chemists
working in the fields of medicinal and agrochemical research.
1
chromatography and isolated as a solid in 78% yield (36.4 mg). H
NMR (CDCl3, 400 MHz): δ = 3.86 (q, J = 10.2 Hz, 2H), 7.74 (t, J =
7.9, 8.3 Hz, 1H), 8.27 (d, J = 7.9 Hz, 1H), 8.48 (d, J = 8.3 Hz, 1H),
8.73 (s, 1H). 19F NMR (CDCl3, 376 MHz): δ = −62.0 (t, J = 10.2
Hz).
3,3,3-Trifluoro-1-(4-(trifluoromethyl)phenyl)propan-1-one
(3d).7c triethyl((1-(4-(trifluoromethyl)phenyl)vinyl)oxy)silane (151.1
mg, 0.5 mmol), Togni’s reagent (239 mg, 0.75 mmol), CuSCN (6.05
mg, 0.05 mmol), DMF (5 mL) were used. The mixture was stirred at
room temperature for 12 h. The compound was purified by column
1
chromatography and isolated as a solid in 94% yield (121 mg); H
NMR (CDCl3, 400 MHz): δ = 3.81 (q, J = 10.0 Hz, 2H), 7.76 (d, J =
8.2 Hz, 2H), 8.03 (d, J = 8.2 Hz, 2H); 13C NMR (CDCl3, 100 MHz):
δ = 42.6 (q, J = 29.1 Hz), 123.6 (q, J = 273 Hz), 123.9 (q, J = 277.2
Hz), 126.3 (q, J = 3.3 Hz), 128.3, 135.7 (q, J = 32.8 Hz), 138.6, 189.1;
19F NMR (CDCl3, 376 MHz): δ = −62.1 (t, J = 10.0 Hz, 3F), −63.4
(s, 3F); IR (neat) ν/cm−1: 2954, 1705, 1328, 1137, 1064; EI-MS m/z:
256 (6.45), 173 (100). HRMS (EI): calcd for C10H6OF6 (M+)
256.0323, found 256.0321.
1-(4-chlorophenyl)-3,3,3-trifluoropropan-1-one (3e).4 ((1-(4-
Chlorophenyl)vinyl)oxy)triethylsilane (53.6 mg, 0.2 mmol), Togni’s
reagent (95.6 mg, 0.3 mmol), CuSCN (2.42 mg, 0.02 mmol), and
DMF (2 mL) were used. The mixture was stirred at room temperature
for 12 h. The compound was purified by column chromatography and
isolated as a solid in 95% yield (42 mg). 1H NMR (CDCl3, 400 MHz):
δ = 3.75 (q, J = 9.5 Hz, 2H), 7.46 (d, J = 7.1 Hz, 2H), 7.85 (d, J = 7.1
Hz, 2H). 19F NMR (CDCl3, 376 MHz): δ = −62.1 (t, J = 9.5 Hz).
1-([1,1′-Biphenyl]-4-yl)-3,3,3-trifluoropropan-1-one (3f).4
((1-([1,1′-Biphenyl]-4-yl)vinyl)oxy)triethylsilane (62 mg, 0.2 mmol),
Togni’s reagent (95.6 mg, 0.3 mmol), CuSCN (2.42 mg, 0.02 mmol),
and DMF (2 mL) were used. The mixture was stirred at room
temperature for 12 h. The compound was purified by column
EXPERIMENTAL SECTION
General Experimental Details. DMF were purified by distillation
over CaH2. Silyl enol ethers was synthesized according to the method
reported by Shreeve.11 NMR spectra were obtained on 300 or 400
■
1
MHz spectrometers and recorded at 25 °C. Chemical shifts for H
NMR spectra are reported in ppm downfield from TMS, chemical
shifts for 13C NMR spectra are recorded in ppm relative to internal
chloroform (δ 77.0 ppm for 13C), and chemical shifts for 19F NMR are
reported in ppm downfield from fluorotrichloromethane (CFCl3).
Coupling constants (J) are reported in hertz. The terms m, s, d, t, and
q refer to multiplet, singlet, doublet, triplet, and quartet, respectively.
13C NMR was broad-band decoupled from hydrogen nuclei. Infrared
spectra (IR) were recorded with an infrared spectrometer; absorbance
frequencies are given at maximum intensity in cm−1. The mass
analyzer type uesd for the HRMS is time-of-flight mass spectrometry
(TOF-MS) or Fourier transform ion cyclotron resonance mass
spectrometry (FTICR-MS). Column chromatography was performed
using silica gel (mesh 300−400).
General Procedure of Trifluoromethylation of Silyl Enol
Ethers. A 10 mL Schlenk tube was charged with a stir bar, Togni’s
reagent 2b (0.3 or 0.75 mmol), and CuSCN (0.02 or 0.05 mmol)
under N2 atmosphere. To the mixture were added silyl enol ethers (0.2
or 0.5 mmol) and DMF (2 or 5 mL). The mixture was stirred at room
temperature or 50 °C for 12 h. Then, 4 or 10 mL water was added, the
resulting mixture was extracted with DCM (2 or 5 mL × 3), and the
organic extracts were washed with brine, dried over anhydrous
Na2SO4, and concentrated in vacuo. The residue was purified by
column chromatography on silica gel using a hexane/DCM mixture as
eluent.
1
chromatography and isolated as a solid in 89% yield (47.2 mg). H
NMR (CDCl3, 400 MHz): δ = 3.81 (q, J = 10.2 Hz, 2H), 7.41−7.49
(m, 3H), 7.61−7.63 (m, 2H), 7.71 (d, J = 8.6 Hz, 2H), 7.99 (d, J = 8.6
Hz, 2H). 19F NMR (CDCl3, 376 MHz): δ = −62.0 (t, J = 10.2 Hz).
3,3,3-Trifluoro-1-(thiophen-2-yl)propan-1-one (3g).4
Triethyl((1-(thiophene-2-yl)vinyl)oxy)silane (48 mg, 0.2 mmol),
Togni’s reagent (95.6 mg, 0.3 mmol), CuSCN (2.42 mg, 0.02
mmol), NS DMF (2 mL) were used. The mixture was stirred at room
temperature for 12 h. The compound was purified by column
1
chromatography and isolated as a solid in 89% yield (29.6 mg). H
NMR (CDCl3, 400 MHz): δ = 3.69 (q, J = 10.0 Hz, 2H), 7.15−7.17
(m, 1H), 7.70−7.74 (m, 2H). 19F NMR (CDCl3, 376 MHz): δ =
−62.0 (t, J = 10.0 Hz).
3,3,3-trifluoro-1-(4-fluoro-2-(trifluoromethyl)phenyl)-
propan-1-one (3h). Triethyl((1-(4-fluoro-2-(trifluoromethyl)-
phenyl)vinyl)oxy)silane (160.1 mg, 0.5 mmol), Togni’s reagent (239
D
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1
mg, 0.75 mmol), CuSCN (6.05 mg, 0.05 mmol), and DMF (5 mL)
were used. The mixture was stirred at room temperature for 12 h. The
compound was purified by column chromatography and isolated as an
oil in 68% yield (93 mg). 1H NMR (CDCl3, 400 MHz): δ = 3.66 (q, J
= 9.8 Hz, 2H), 7.31−7.36 (m, 1H), 7.43−7.46 (m, 1H), 7.49−7.53 (m,
1H). 13C NMR (CDCl3, 100 MHz): δ = 46.1 (q, J = 29.0 Hz), 115.1
(dq, J = 25.2, 5.3 Hz), 119.1 (d, J = 21.3 Hz), 122.4 (q, J = 273.9 Hz),
123.2 (q, J = 277 Hz), 130.2, 130.3, 134.2, 163.5 (d, J = 254.9 Hz),
191.9. 19F NMR (CDCl3, 376 MHz): δ = −58.5 (s, 3F), −62.4 (t, J =
9.8 Hz, 3F), −105.29 to −105.21 (m, 1F); IR (neat) ν/cm-1:2950,
1724, 1316, 1143, 1054. EI-MS m/z: 274 (4.96), 191 (100). HRMS
(EI): calcd for C10H5OF7 (M+) 274.0229, found 274.0228.
chromatography and isolated as an solid in 71% yield (76 mg). H
NMR (CDCl3, 400 MHz): δ = 3.06−3.16 (m, 2H), 6.84−6.92 (m,
1H), 7.09 (d, J = 15.1 Hz, 1H), 7.46−7.51 (m, 2H), 7.57−7.61 (m,
1H), 7.94 (d, J = 7.4 Hz, 2H). 13C NMR (CDCl3, 100 MHz): δ = 37.1
(q, J = 30.5 Hz), 125.2 (q, J = 277.5 Hz), 128.6, 128.7, 131.4, 133.3,
134.6 (q, J = 3.8 Hz), 137.1, 189.5. 19F NMR (CDCl3, 376 MHz): δ =
−65.3 (t, J = 10.2 Hz). IR (neat) ν/cm−1: 2946, 1676, 1621, 1578,
1057. EI-MS m/z: 214 (22.99), 105 (100). HRMS (EI): calcd for
C11H9OF3 (M+) 214.0605, found 214.0610.
3,3,3-Trifluoro-1-(naphthalen-1-yl)propan-1-one (3n).6i
Triethyl((1-(naphthalen-2-yl)vinyl)oxy)silane (56.8 mg, 0.2 mmol),
Togni’s reagent (95.6 mg, 0.3 mmol), CuSCN (2.42 mg, 0.02 mmol),
and DMF (2 mL) were used. The mixture was stirred at room
temperature for 12 h. The compound was purified by column
1-(2,4-Dimethylphenyl)-3,3,3-trifluoropropan-1-one (3i).4
((1-(2,4-Dimethylphenyl)vinyl)oxy)triethylsilane (52.4 mg, 0.2
mmol), Togni’s reagent (95.6 mg, 0.3 mmol), CuSCN (2.42 mg,
0.02 mmol), and DMF (2 mL) were used. The mixture was stirred at
room temperature for 12 h. The compound was purified by column
1
chromatography and isolated as an oil in 92% yield (43.8 mg). H
NMR (CDCl3, 400 MHz): δ = 3.88 (q, J = 10.1 Hz, 2H), 7.46−7.50
(m, 1H), 7.53−7.57 (m, 1H), 7.59−7.64 (m, 1H), 7.81−7.88 (m, 2H),
8.03 (d, J = 8.2 Hz, 1H), 8.71 (d, J = 8.6 Hz, 1H). 19F NMR (CDCl3,
376 MHz): δ = −61.9 (t, J = 10.1 Hz).
1
chromatography and isolated as an oil in 93% yield (40.2 mg); H
NMR (CDCl3, 400 MHz): δ = 2.36 (s, 3H), 2.52 (s, 3H), 3.73 (q, J =
10.1 Hz, 2H), 7.09−7.10(m, 2H), 7.52−7.56(m, 1H); 19F NMR
(CDCl3, 376 MHz): δ = −62.5 (t, J = 10.1 Hz).
1-Phenyl-2-(trifluoromethyl)hept-6-en-1-one (3o). Triethyl-
((1-phenylhepta-1,6-dien-1-yl)oxy)silane (151.1 mg, 0.5 mmol),
Togni’s reagent (239 mg, 0.75 mmol), CuSCN (6.05 mg, 0.05
mmol), and DMF (5 mL) were used. The mixture was stirred at room
temperature for 24 h. The compound was separated by HPLC. Oil. 1H
NMR (CDCl3, 400 MHz): δ = 1.35−1.43 (m, 2H), 1.86−1.92 (m,
1H), 2.02−2.15 (m, 3H), 4.16−4.22 (m, 1H), 4.93−4.99 (m, 2H),
5.67−5.74 (m, 1H), 7.49−7.53 (m, 2H), 7.61−7.65 (m, 1H), 7.95−
7.97 (m, 2H). 13C NMR (CDCl3, 100 MHz): δ = 26.2, 26.3, 33.4, 49.2
(q, J = 26.1 Hz), 115.4, 124.9 (q, J = 281 Hz), 128.5, 128.9, 134.0,
136.8, 137.4, 194.4. 19F NMR (CDCl3, 376 MHz): δ = −66.2 (d, J =
8.2 Hz). IR (neat) ν/cm−1: 3077, 2926, 1693, 1597, 1459, 1262. EI-
MS m/z: 256 (14.95), 105 (100). HRMS (EI): calcd for C14H15OF3
(M+) 256.1075, found 256.1079.
Phenyl(2-(2,2,2-trifluoroethyl)cyclopentyl)methanone (3p).
Triethyl((1-phenylhepta-1,6-dien-1-yl)oxy)silane (151.1 mg, 0.5
mmol), Togni’s reagent (239 mg, 0.75 mmol), CuSCN (6.05 mg,
0.05 mmol), and DMF (5 mL) were used. The mixture was stirred at
room temperature for 24 h. The compound was separated by HPLC.
Oil. 1H NMR (CDCl3, 400 MHz): δ = 1.65−1.76 (m, 1H), 1.80−1.90
(m, 2H), 1.93−2.08 (m, 3H), 2.17−2.29 (m, 1H), 2.28−2.39 (m, 1H),
2.40−2.49 (m, 1H), 3.92−3.99 (m, 1H), 7.43−7.49 (m, 2H), 7.54−
7.59 (m, 1H), 7.91−7.97 (m, 2H). 13C NMR (CDCl3, 100 MHz): δ =
23.5, 30.1, 31.6, 34.3 (q, J = 27.9 Hz), 37.4, 47.7, 127.2 (q, J = 277.3
Hz), 128.2, 128.7, 133.0, 137.1, 202.2. 19F NMR (CDCl3, 376 MHz):
δ = −64.8 (t, J = 10.9 Hz). IR (neat) ν/cm−1: 3062, 2961, 1679, 1597,
1448, 1256. EI-MS m/z: 256 (14.95), 105 (100). HRMS (EI): calcd
for C14H15OF3 (M+) 256.1075, found 256.1079.
1-(2-Chloro-6-fluorophenyl)-3,3,3-trifluoropropan-1-one
(3j). ((1-(2-Chloro-6-fluorophenyl)vinyl)oxy)triethylsilane (143.1 mg,
0.5 mmol), Togni’s reagent (239 mg, 0.75 mmol), CuSCN (6.05 mg,
0.05 mmol), and DMF (5 mL) were used. The mixture was stirred at
room temperature for 12 h. The compound was purified by column
chromatography and isolated as an oil in 82% yield (98 mg). 1H NMR
(CDCl3, 400 MHz): δ = 3.68 (q, J = 10.1 Hz, 2H), 7.04−7.09 (m,
1H), 7.23−7.25 (m, 1H), 7.34−7.40 (m, 1H). 13C NMR (CDCl3, 100
MHz): δ = 47.6 (q, J = 28.9 Hz), 114.7 (d, J = 21.4 Hz), 123.2 (q, J =
277 Hz), 126.2, 127.1, 131.4, 132.4, 159.3 (d, J = 251.8 Hz), 189.3. 19F
NMR (CDCl3, 376 MHz): δ = −62.5 (t, J = 10.1 Hz, 3F), −113.42 to
−113.48 (m, 1F). IR (neat) ν/cm−1: 2942, 1725, 1372, 1138, 1102. EI-
MS m/z: 240 (25.85), 157 (100). HRMS (EI): calcd for C9H5OF4Cl
(M+) 239.9965, found 239.9969.
1-(3-Chloro-5-fluorophenyl)-3,3,3-trifluoropropan-1-one
(3k). ((1-(3-Chloro-5-fluorophenyl)vinyl)oxy)triethylsilane (143.1
mg, 0.5 mmol), Togni’s reagent (239 mg, 0.75 mmol), CuSCN
(6.05 mg, 0.05 mmol), and DMF (5 mL) were used. The mixture was
stirred at room temperature for 12 h. The compound was purified by
column chromatography and isolated as an oil in 85% yield (101 mg).
1H NMR (CDCl3, 400 MHz): δ = 3.78 (q, J = 9.8 Hz, 2H), 7.35−7.38
(m, 1H), 7.51−7.54 (m, 1H), 7.69 (s, 1H). 13C NMR (CDCl3, 100
MHz): δ = 42.3 (q, J = 29.0 Hz), 113.7 (d, J = 22.9 Hz), 121.7 (d, J =
24.4 Hz), 123.5 (q, J = 277.7 Hz), 124.5 (d, J = 3.0 Hz), 136.1 (d, J =
10.0 Hz), 138.3, 162.7 (d, J = 253.3 Hz), 187.4. 19F NMR (CDCl3, 376
MHz): δ = −62.6 (t, J = 9.8 Hz, 3F), −108.8 (t, J = 8.0 Hz, 1F). IR
(neat) ν/cm−1: 2948, 1709, 1372, 1130, 1108. EI-MS m/z: 240 (45.9),
157 (100). HRMS (EI): calcd for C9H5OF4Cl (M+) 239.9965, found
239.9966.
1-((3r,5r,7r)-Adamantan-1-yl)-3,3,3-trifluoropropan-1-one
(3r).6h ((1-((3r,5r,7r)-Adamantan-1-yl)vinyl)oxy)triethylsilane (58.4
mg, 0.2 mmol), Togni’s reagent (95.6 mg, 0.3 mmol), CuSCN (2.42
mg, 0.02 mmol), and DMF (2 mL) were used. The mixture was stirred
at room temperature for 12 h. The compound was purified by column
3,3,3-Trifluoro-1-(1-tosyl-1H-indol-3-yl)propan-1-one (3l). 1-
Tosyl-3-(1-((triethylsilyl)oxy)vinyl)-1H-indole (213.8 mg, 0.5 mmol),
Togni’s reagent (239 mg, 0.75 mmol), CuSCN (6.05 mg, 0.05 mmol),
and DMF (5 mL) were used. The mixture was stirred at room
temperature for 12 h. The compound was purified by column
1
chromatography and isolated as a solid in 80% yield (39 mg). H
NMR (CDCl3, 400 MHz): δ = 1.64−1.82 (m, 12H), 2.07 (s, 3H), 3.27
(q, J = 10.8 Hz, 2H). 19F NMR (CDCl3, 376 M): δ = −62.2 (d, J =
10.8 Hz).
1
chromatography and isolated as an solid in 84% yield (159 mg). H
3,3,3-Trifluoro-2-methyl-1-phenylpropan-1-one (4a).5c
Triethyl((1-phenylprop-1-en-1-yl)oxy)silane (49.6 mg, 0.2 mmol),
Togni’s reagent (95.6 mg, 0.3 mmol), CuSCN (2.42 mg, 0.02 mmol),
and DMF (2 mL) were used. The mixture was stirred at 50 °C for 12
h. The compound was purified by column chromatography and
isolated as an oil in 84% yield (34 mg). 1H NMR (CDCl3, 400 MHz):
δ = 1.46 (d, J = 7.1 Hz, 3H), 4.19−4.27 (m, 1H), 7.47−7.51 (m, 2H),
7.59−7.61 (m, 1H), 7.92−7.95 (m, 2H). 19F NMR (CDCl3, 376
MHz): δ = −68.3 (d, J = 8.1 Hz).
3,3,3-Trifluoro-2-methyl-1-(3-(trifluoromethyl)phenyl)-
propan-1-one (4b). Triethyl((1-(3-(trifluoromethyl)phenyl)prop-1-
en-1-yl)oxy)silane (158.1 mg, 0.5 mmol), Togni’s reagent (239 mg,
0.75 mmol), CuSCN (6.05 mg, 0.05 mmol), and DMF (5 mL) were
used. The mixture was stirred at 50 °C for 12 h. The compound was
NMR (CDCl3, 400 MHz): δ = 2.37 (s, 3H), 3.74 (q, J = 9.5 Hz, 2H),
7.29 (d, J = 8.3 Hz, 2H), 7.36−7.41 (m, 2H), 7.85 (d, J = 8.3 Hz, 2H),
7.93−7.95 (m, 1H), 8.27 (s, 1H), 8.32−8.34 (m, 1H). 13C NMR
(CDCl3, 100 MHz): δ = 21.6, 43.8 (q, J = 27.7 Hz), 113.1, 120.7,
123.1, 123.9 (q, J = 277.5 Hz), 125.2, 126.3, 127.1, 127.2, 130.4, 132.9,
134.1, 134.8, 146.3, 184.7. 19F NMR (CDCl3, 376 MHz): δ = −61.8 (t,
J = 9.5 Hz). IR (neat) ν/cm−1: 2985, 1667, 1539, 1389, 1146. EI-MS
m/z: 381 (5.08), 105 (100). HRMS (EI): calcd for C18H14NO3F3S
(M+) 381.0647, found 381.0651.
(E)-5,5,5-Trifluoro-1-phenylpent-2-en-1-one (3m). Triethyl-
((1-phenylbuta-1,3-dien-1-yl)oxy)silane (130.2 mg, 0.5 mmol),
Togni’s reagent (239 mg, 0.75 mmol), CuSCN (6.05 mg, 0.05
mmol), and DMF (5 mL) were used. The mixture was stirred at room
temperature for 12 h. The compound was purified by column
E
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Article
purified by column chromatography and isolated as an oil in 92% yield
(124 mg). 1H NMR (CDCl3, 400 MHz): δ = 1.47 (d, J = 7.0 Hz, 3H),
4.18−4.29 (m, 1H), 7.65 (t, J = 7.8, 7.9 Hz, 1H), 7.86 (d, J = 7.9 Hz,
1H), 8.11 (d, J = 7.8 Hz, 1H), 8.17 (s, 1H). 13C NMR (CDCl3, 100
MHz): δ = 11.6, 44.7 (q, J = 26.8 Hz), 123.6 (q, J = 272.4 Hz), 125.1
(q, J = 280.5 Hz), 125.5 (q, J = 3.7 Hz), 129.8, 130.5 (q, J = 3.7 Hz),
131.8, 131.9 (q, J = 33.3 Hz), 136.4, 193.3. 19F NMR (CDCl3, 376
MHz): δ = −63.0 (s, 3F), −68.2 (d, J = 6.8 Hz). IR (neat) ν/cm−1:
2958, 1702, 1332, 1135, 1075. EI-MS m/z: 270 (0.43), 173 (100).
HRMS (EI): calcd for C11H8OF6 (M+) 270.0479, found 270.0475.
1-(3-Bromophenyl)-3,3,3-trifluoro-2-methylpropan-1-one
(4c). ((1-(3-Bromophenyl)prop-1-en-1-yl)oxy)triethylsilane (163.1
mg, 0.5 mmol), Togni’s reagent (239 mg, 0.75 mmol), CuSCN
(6.05 mg, 0.05 mmol), and DMF (5 mL) were used. The mixture was
stirred at 50 °C for 12 h. The compound was purified by column
δ = −68.7 (d, J = 9.9 Hz). IR (neat) ν/cm−1: 2953, 1690, 1411, 1229,
1134. EI-MS m/z: 216 (11.53), 119 (100). HRMS (EI): calcd for
C11H11OF3 (M+) 216.0762, found 216.0767.
3,3,3-Trifluoro-1-(4-methoxyphenyl)-2-methylpropan-1-one
(4h). Triethyl((1-(4-methoxyphenyl)prop-1-en-1-yl)oxy)silane (55.6
mg, 0.2 mmol), Togni’s reagent (95.6 mg, 0.3 mmol), CuSCN (2.42
mg, 0.02 mmol), and DMF (2 mL) were used. The mixture was stirred
at 50 °C for 12 h. The compound was purified by column
1
chromatography and isolated as an oil in 96% yield (44.4 mg). H
NMR (CDCl3, 400 MHz): δ = 1.46 (d, J = 7.0 Hz, 3H), 3.89 (s, 3H),
4.15−4.23 (m, 1H), 6.97 (d, J = 8.8 Hz, 2H), 7.95 (d, J = 8.8 Hz, 2H).
13C NMR (CDCl3, 100 MHz): δ = 11.7, 43.9 (q, J = 27 Hz), 55.6,
114.1, 125.4 (q, J = 283 Hz), 128.7, 130.9, 164.2, 192.8. 19F NMR
(CDCl3, 376 MHz): δ = −68.7 (d, J = 7.9 Hz). IR (neat) ν/cm−1:
2953, 1682, 1463, 1132, 846. EI-MS m/z: 232 (13.95), 135 (100).
HRMS (EI): calcd for C11H11O2F3 (M+) 232.0711, found 232.0712.
1-Phenyl-2-(trifluoromethyl)butan-1-one (4i). Triethyl((1-
phenylbut-1-en-1-yl)oxy)silane (131.1 mg, 0.5 mmol), Togni’s reagent
(239 mg, 0.75 mmol), CuSCN (6.05 mg, 0.05 mmol), and DMF (5
mL) were used. The mixture was stirred at 50 °C for 12 h. The
compound was purified by column chromatography and isolated as an
oil in 81% yield (88 mg). 1H NMR (CDCl3, 400 MHz): δ = 0.94 (t, J
= 7.4 Hz, 3H), 1.93−1.97 (m, 1H), 2.06−2.11 (m, 1H), 4.06−4.16 (m,
1H), 7.47−7.51 (m, 2H), 7.59−7.63 (m, 1H), 7.93−7.96 (m, 2H). 13C
NMR (CDCl3, 100 MHz): δ = 11.5, 20.4, 50.7 (q, J = 24.9 Hz), 125.0
(q, J = 280.3 Hz), 128.5, 128.8, 133.9, 136.9, 194.5. 19F NMR (CDCl3,
376 MHz): δ = −66.2 (d, J = 8.2 Hz). IR (neat) ν/cm−1: 2977, 1690,
1449, 1254, 1168. EI-MS m/z: 216 (18.83), 105 (100). HRMS (EI):
calcd for C11H11OF3 (M+) 216.0762, found 216.0764.
1
chromatography and isolated as an oil in 86% yield (121 mg). H
NMR (CDCl3, 400 MHz): δ = 1.46 (d, J = 7.2 Hz, 3H), 4.13−4.21
(m, 1H), 7.38 (t, J = 7.9 Hz, 1H), 7.74 (d, J = 7.9 Hz, 1H), 7.85 (d, J =
7.9 Hz, 1H), 8.06 (s, 1H). 13C NMR (CDCl3, 100 MHz): δ = 11.7,
44.7 (q, J = 26.8 Hz), 123.5, 125.2 (q, J = 280.5 Hz), 127.2, 130.6,
131.8, 137.0, 137.6, 193.3. 19F NMR (CDCl3, 376 MHz): δ = −68.6
(d, J = 7.9 Hz). IR (neat) ν/cm−1: 2953, 1698, 1422, 1266, 1135. EI-
MS m/z: 280 (6.05), 183 (100). HRMS (EI): calcd for C10H8OF3Br
(M+) 279.9711, found 279.9714.
3,3,3-Trifluoro-1-(4-fluorophenyl)-2-methylpropan-1-one
(4d). Triethyl((1-(4-fluorophenyl)prop-1-en-1-yl)oxy)silane (133.1
mg, 0.5 mmol), Togni’s reagent (239 mg, 0.75 mmol), CuSCN
(6.05 mg, 0.05 mmol), DMF (5 mL) were used. The mixture was
stirred at 50 °C for 12 h. The compound was purified by column
chromatography and isolated as an oil in 88% yield (97 mg). 1H NMR
(CDCl3, 400 MHz): δ = 1.45 (d, J = 7.1 Hz, 3H), 4.14−4.22 (m, 1H),
7.13−7.18 (m, 2H), 7.95−7.99 (m, 2H). 13C NMR (CDCl3, 100
MHz): δ = 11.5, 44.3 (q, J = 26.4 Hz), 116.1 (d, J = 21.8 Hz), 125.2
(q, J = 280.3 Hz), 131.4 (d, J = 9.3 Hz), 132.1, 166.2 (d, J = 257 Hz),
192.8. 19F NMR (CDCl3, 376 MHz): δ = −68.3 (d, J = 8.2 Hz, 3F),
−103.3 to −103.4(m, 1F). IR (neat) ν/cm−1: 2955, 1664, 1463, 1135,
852. EI-MS m/z: 220 (6.34), 123 (100). HRMS (EI): calcd for
C10H8OF4 (M+) 220.0511, found 220.0512.
1-Phenyl-2-(trifluoromethyl)pentan-1-one (4j).13 Triethyl((1-
phenylpent-1-en-1-yl)oxy)silane (55.3 mg, 0.2 mmol), Togni’s reagent
(95.6 mg, 0.3 mmol), CuSCN (2.42 mg, 0.02 mmol), and DMF (2
mL) were used. The mixture was stirred at 50 °C for 12 h. The
compound was purified by column chromatography and isolated as an
oil in 74% yield (34 mg). 1H NMR (CDCl3, 400 MHz): δ = 0.89 (t, J
= 7.5 Hz, 3H), 1.26−1.36 (m, 2H), 1.78−1.88 (m, 1H), 2.02−2.12 (m,
1H), 4.13−4.24 (m, 1H), 7.47−7.51 (m, 2H), 7.59−7.63 (m, 1H),
7.93−7.95 (m, 2H). 19F NMR (CDCl3, 376 MHz): δ = −66.3 (d, J =
8.2 Hz).
1-(2,4-Difluorophenyl)-3,3,3-trifluoro-2-methylpropan-1-
one (4k). ((1-(2,4-Difluorophenyl)prop-1-en-1-yl)oxy)triethylsilane
(142.1 mg, 0.5 mmol), Togni’s reagent (239 mg, 0.75 mmol),
CuSCN (6.05 mg, 0.05 mmol), and DMF (5 mL) were used. The
mixture was stirred at 50 °C for 12 h. The compound was purified by
column chromatography and isolated as an oil in 85% yield (101 mg).
1H NMR (CDCl3, 400 MHz): δ = 1.44 (d, J = 7.2 Hz, 3H), 4.10−4.18
1-(4-Chlorophenyl)-3,3,3-trifluoro-2-methylpropan-1-one
(4e).12 ((1-(4-Chlorophenyl)prop-1-en-1-yl)oxy)triethylsilane (56.4
mg, 0.2 mmol), Togni’s reagent (95.6 mg, 0.3 mmol), CuSCN (2.42
mg, 0.02 mmol), and DMF (2 mL) were used. The mixture was stirred
at 50 °C for 12 h. The compound was purified by column
1
chromatography and isolated as a solid in 87% yield (41 mg). H
NMR (CDCl3, 400 MHz): δ = 1.45 (d, J = 7.0 Hz, 3H), 4.13−4.21
(m, 1H), 7.47 (d, J = 8.6 Hz, 2H), 7.88 (d, J = 8.6 Hz, 2H). 19F NMR
(CDCl3, 376 MHz): δ = −68.2 (d, J = 8.2 Hz).
(m, 1H), 6.86−6.92 (m, 1H), 6.97−7.01 (m, 1H), 7.87−7.92 (m, 1H).
13C NMR (CDCl3, 100 MHz): δ = 11.1, 49.1 (dq, J = 26.3, 8.6 Hz),
105.1 (dd, J = 26.8, 25.8 Hz), 113.0 (dd, J = 21.5, 3.2 Hz), 121.5, 125.3
(q, J = 279.9 Hz), 133.5 (dd, J = 10.8, 3.8 Hz), 162.4 (dd, J = 256.6,
12.4 Hz), 166.5 (dd, J = 259, 12.4 Hz), 191.5. 19F NMR (CDCl3, 376
MHz): δ = −69.0 (d, J = 7.9 Hz, 3F), −100.20 to −100.25 (m, 1F),
−100.56 to −100.59 (m, 1F). IR (neat) ν/cm−1: 2956, 1698, 1464,
1173, 978. EI-MS m/z: 238 (3.45), 141 (100). HRMS (EI): calcd for
C10H7OF5 (M+) 238.0417, found 238.0412.
1-(4-Bromophenyl)-3,3,3-trifluoro-2-methylpropan-1-one
(4f). ((1-(4-Bromophenyl)prop-1-en-1-yl)oxy)triethylsilane (163 mg,
0.5 mmol), Togni’s reagent (239 mg, 0.75 mmol), CuSCN (6.05 mg,
0.05 mmol), and DMF (5 mL) were used. The mixture was stirred at
50 °C for 12 h. The compound was purified by column
1
chromatography and isolated as an oil in 95% yield (132.4 mg). H
NMR (CDCl3, 400 MHz): δ = 1.44 (d, J = 7.0 Hz, 3H), 4.13−4.21
(m, 1H), 7.62 (d, J = 8.4 Hz, 2H), 7.79 (d, J = 8.4 Hz, 2H). 13C NMR
(CDCl3, 100 MHz): δ = 11.7, 44.5 (q, J = 26.4 Hz), 125.3 (q, J =
280.5 Hz), 129.6, 130.2, 132.4, 134.6, 193.6. 19F NMR (CDCl3, 376
MHz): δ = −68.3 (d, J = 8.1 Hz). IR (neat) ν/cm−1: 2963, 1690, 1404,
1272, 1111. EI-MS m/z: 280 (6.05), 183 (100). HRMS (EI): calcd for
C10H8OF3Br (M+) 279.9711, found 279.9708.
3,3,3-Trifluoro-2-methyl-1-(p-tolyl)propan-1-one (4g).
Triethyl((1-(p-tolyl)prop-1-en-1-yl)oxy)silane (131.1 mg, 0.5 mmol),
Togni’s reagent (239 mg, 0.75 mmol), CuSCN (6.05 mg, 0.05 mmol),
and DMF (5 mL) were used. The mixture was stirred at 50 °C for 12
h. The compound was purified by column chromatography and
isolated as an oil in 99% yield (107 mg). 1H NMR (CDCl3, 400
MHz): δ = 1.46 (d, J = 7.0 Hz, 3H), 2.42 (s, 3H), 4.18−4.28 (m, 1H),
7.30 (d, J = 8.2 Hz, 2H), 7.85 (d, J = 8.2 Hz, 2H). 13C NMR (CDCl3,
100 MHz): δ = 11.7, 21.6, 44.1 (q, J = 26.4 Hz), 125.4 (q, J = 279.5
Hz), 128.7, 129.6, 133.2, 145.0, 194.0. 19F NMR (CDCl3, 376 MHz):
2-(Trifluoromethyl)-2,3-dihydro-1H-inden-1-one (4l).5c ((1H-
Inden-3-yl)oxy)triethylsilane (49.2 mg, 0.2 mmol), Togni’s reagent
(95.6 mg, 0.3 mmol), CuSCN (2.42 mg, 0.02 mmol), and DMF (2
mL) were used. The mixture was stirred at 50 °C for 12 h. The
compound was purified by column chromatography and isolated as a
1
solid in 78% yield (31 mg). H NMR (CDCl3, 400 MHz): δ = 3.28−
3.35 (m, 1H), 3.37−3.47 (m, 2H), 7.39−7.43 (m, 1H), 7.49−7.51 (d, J
= 7.8 Hz, 1H), 7.62−7.66 (m, 1H), 7.78−7.81 (d, J = 7.9 Hz, 1H). 19F
NMR (CDCl3, 376 MHz): δ = −67.8 (d, J = 9.5 Hz).
2-(Trifluoromethyl)-3,4-dihydronaphthalen-1(2H)-one
(4m).5c ((3,4-Dihydronaphthalen-1-yl)oxy)triethylsilane (52.1 mg, 0.2
mmol), Togni’s reagent (95.6 mg, 0.3 mmol), CuSCN (2.42 mg, 0.02
mmol), and DMF (2 mL) were used. The mixture was stirred at 50 °C
for 12 h. The compound was purified by column chromatography and
isolated as a solid in 89% yield (38 mg). 1H NMR (CDCl3, 400 MHz):
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δ = 2.23−2.31 (m, 1H), 2.45−2.51 (m, 1H), 3.04−3.10 (m, 2H),
3.22−3.28 (m, 1H), 7.25 (d, J = 7.8 Hz, 1H), 7.30−7.34 (m, 1H),
7.48−7.52 (m, 1H), 8.04 (d, J = 8.3 Hz, 1H). 19F NMR (CDCl3, 376
MHz): δ = −67.6 (d, J = 9.5 Hz).
cm−1: 2954, 1689, 1474, 1263, 1127. EI-MS m/z: 216 (0.26), 105
(100). HRMS (EI): calcd for C11H11OF3 (M+) 216.0762, found
216.0765.
2-Methyl-2-(trifluoromethyl)-3,4-dihydronaphthalen-1(2H)-
one (4t).5c Triethyl((2-methyl-3,4-dihydronaphthalen-1-yl)oxy)silane
(54.9 mg, 0.2 mmol), Togni’s reagent (95.6 mg, 0.3 mmol), CuSCN
(2.42 mg, 0.02 mmol), and DMF (2 mL) were used. The mixture was
stirred at 50 °C for 12 h. The compound was purified by column
chromatography and isolated as an oil in 77% yield (35 mg). 1H NMR
(CDCl3, 400 MHz): δ = 1.43 (s, 3H), 2.11−2.18 (m, 1H), 2.39−2.47
(m, 1H), 3.04−3.06 (m, 2H), 7.22−7.25 (m, 1H), 7.30−7.34 (m, 1H),
7.47−7.51 (m, 1H), 8.05 (d, J = 7.4 Hz, 1H). 19F NMR (CDCl3, 376
MHz): δ = −73.1 (s).
2-Methyl-2-(trifluoromethyl)-2,3-dihydro-1H-inden-1-one
(4u).5c Triethyl((2-methyl-1H-inden-3-yl)oxy)silane (52.1 mg, 0.2
mmol), Togni’s reagent (95.6 mg, 0.3 mmol), CuSCN (2.42 mg, 0.02
mmol), and DMF (2 mL) were used. The mixture was stirred at 50 °C
for 12 h. The compound was purified by column chromatography and
isolated as an oil in 86% yield (37 mg). 1H NMR (CDCl3, 400 MHz):
δ = 1.49 (s, 3H), 3.02 (d, J = 17.6 Hz, 1H), 3.56 (d, J = 17.6 Hz, 1H),
7.40−7.45 (m, 1H), 7.47−7.49 (m, 1H), 7.63−7.68 (m, 1H), 7.79−
7.81 (m, 1H). 19F NMR (CDCl3, 376 MHz): δ = −73.8 (s).
Phenyl(1-(trifluoromethyl)cyclopentyl)methanone (4v).
(Cyclopentylidene(phenyl)methoxy)triethylsilane (144.2 mg, 0.5
mmol), Togni’s reagent (239 mg, 0.75 mmol), CuSCN (6.05 mg,
0.05 mmol), and DMF (5 mL) were used. The mixture was stirred at
50 °C for 12 h. The compound was purified by column
chromatography and isolated as an oil in 71% yield (69 mg, brsm).
1H NMR (CDCl3, 400 MHz): δ = 1.62−1.67 (m, 2H), 1.72−1.78 (m,
2H), 2.24−2.31 (m, 2H), 2.46−2.53 (m, 2H), 7.40−7.44 (m, 2H),
7.50−7.54 (m, 1H), 7.82 (d, J = 7.9 Hz, 2H). 13C NMR (CDCl3, 100
MHz): δ = 26.2, 32.8 (q, J = 1.5 Hz), 64.1 (q, J = 24.2 Hz), 127.1 (q, J
= 281.8 Hz), 129.2 (q, J = 2.3 Hz), 128.1, 132.3, 136.7, 198.5. 19F
NMR (CDCl3, 376 MHz): δ = −68.5 (s). IR (neat) ν/cm−1: 2966,
1682, 1447, 1240, 1159. EI-MS m/z: 242 (0.71), 105 (100). HRMS
(EI): calcd for C13H13OF3 (M+) 242.0918, found 242.0922.
Phenyl(1-(trifluoromethyl)cyclohexyl)methanone (4w).
(Cyclohexylidene(phenyl)methoxy)triethylsilane (151.1 mg, 0.5
mmol), Togni’s reagent (239 mg, 0.75 mmol), CuSCN (6.05 mg,
0.05 mmol), and DMF (5 mL) were used. The mixture was stirred at
50 °C for 12 h. The compound was purified by column
chromatography and isolated as an oil in 88% yield (85 mg, brsm).
1H NMR (CDCl3, 400 MHz): δ = 1.04−1.12 (m, 2H), 1.15−1.23 (m,
1H), 1.57−1.70 (m, 5H), 2.59−2.63 (m, 2H), 7.40−7.44 (m, 2H),
7.48−7.52 (m, 1H), 7.67−7.69 (m, 2H). 13C NMR (CDCl3, 100
MHz): δ = 21.9, 24.9, 28.7 (q, J = 1.9 Hz), 57.2 (q, J = 22.9 Hz), 126.1
(q, J = 283.2 Hz), 127.6, 128.2, 131.5, 139.4, 200.9. 19F NMR (CDCl3,
376 MHz): δ = −71.2 (s). IR (neat) ν/cm−1: 2943, 1687, 1457, 1246,
1002. EI-MS m/z: 256 (1.82), 105 (100). HRMS (EI): calcd for
C14H15OF3 (M+) 256.1075, found 256.1073.
4-Phenyl-2-(trifluoromethyl)cyclohexanone (4o). Triethyl((3-
(trifluoromethyl)-1,2,3,6-tetrahydro-[1,1′-biphenyl]-4-yl)oxy)silane
(144.1 mg, 0.5 mmol), Togni’s reagent (239 mg, 0.75 mmol), CuSCN
(6.05 mg, 0.05 mmol), and DMF (5 mL) were used. The mixture was
stirred at 50 °C for 12 h. The compound was purified by column
1
chromatography and isolated as a solid in 84% yield (102 mg). H
NMR (CDCl3, 400 MHz): δ = 1.94−2.09 (m, 2H), 2.24−2.29 (m,
1H), 2.47−2.61 (m, 3H), 3.10−3.14 (m, 1H), 3.27−3.31 (m, 1H),
7.22−7.27 (m, 3H), 7.31−7.35 (m, 2H). 13C NMR (CDCl3, 100
MHz): δ = 34.4, 34.5, 42.1, 42.4, 53.3 (q, J = 25.7 Hz), 124.6 (q, J =
278.8 Hz), 126.8, 127.3, 129.0, 143.2, 200.2. 19F NMR (CDCl3, 376
MHz): δ = −69.2 (d, J = 8.2 Hz). IR (neat) ν/cm−1: 2960, 1720, 1496,
1391, 1061. EI-MS m/z: 242 (50.93), 104 (100). HRMS (EI): calcd
for C13H13OF3 (M+) 242.0918, found 242.0920.
2-Fluoro-2-(trifluoromethyl)-3,4-dihydronaphthalen-1(2H)-
one (4p). Triethyl((2-fluoro-3,4-dihydronaphthalen-1-yl)oxy)silane
(139.1 mg, 0.5 mmol), Togni’s reagent (239 mg, 0.75 mmol),
CuSCN (6.05 mg, 0.05 mmol), and DMF (5 mL) were used. The
mixture was stirred at 50 °C for 12 h. The compound was purified by
column chromatography and isolated as a solid in 74% yield (86 mg).
1H NMR (CDCl3, 400 MHz): δ = 2.60−2.70 (m, 2H), 3.18−3.22 (m,
2H), 7.31 (d, J = 7.8 Hz, 1H), 7.37−7.41 (m, 1H), 7.56−7.61 (m,
1H), 8.09 (d, J = 7.9 Hz, 1H). 13C NMR (CDCl3, 100 MHz): δ = 24.2
(d, J = 7 Hz), 28.5 (d, J = 22.6 Hz), 90.5 (dq, J = 194.6, 31.2 Hz),
122.1 (qd, J = 285, 28.8 Hz), 127.5, 128.6, 128.8, 130.6, 134.9, 142.6,
186.3 (d, J = 20.3 Hz). 19F NMR (CDCl3, 376 MHz): δ = −77.5 (d, J
= 9.5 Hz, 3F), −172.79 to −172.92 (m, 1F). IR (neat) ν/cm−1: 2950,
1708, 1326, 1175, 953. EI-MS m/z: 232 (33.38), 118 (100). HRMS
(EI): calcd for C11H8OF4 (M+) 232.0511, found 232.0514.
2,3,3,3-Tetrafluoro-2-methyl-1-phenylpropan-1-one (4q).
Triethyl((2-fluoro-1-phenylprop-1-en-1-yl)oxy)silane (133.1 mg, 0.5
mmol), Togni’s reagent (239 mg, 0.75 mmol), CuSCN (6.05 mg, 0.05
mmol), and DMF (5 mL) were used. The mixture was stirred at 50 °C
for 12 h. The compound was purified by column chromatography and
isolated as an oil in 25% yield (27 mg). 1H NMR (CDCl3, 400 MHz):
δ = 1.87 (d, J = 22.6 Hz, 3H), 7.46−7.51 (m, 2H), 7.60−7.65 (m, 1H),
8.02−8.06 (m, 2H). 13C NMR (CDCl3, 100 MHz): δ = 18.9 (dq, J =
22.1, 1.5 Hz), 97.4 (dq, J = 202.2, 30.5 Hz), 122.0 (qd, J = 285.4, 29.0
Hz), 128.5, 130.0, 133.8, 134.1, 193.4 (d, J = 25.2 Hz). 19F NMR
(CDCl3, 376 MHz): δ = −78.6 (d, J = 7.9 Hz, 3F), −165.48 to
−165.59 (m, 1F). IR (neat) ν/cm−1: 2958, 1697, 1301, 1200, 1108. EI-
MS m/z: 220 (0.93), 105 (100). HRMS (EI): calcd for C10H8OF4
(M+) 220.0511, found 220.0509.
(13S)-3-Methoxy-13-methyl-16-(trifluoromethyl)-7,8,9,-
11,12,13,15,16-octahydro-6H-cyclopenta[a]phenanthren-17-
(14H)-one (4r).5b Triethyl((3-methoxy-13-methyl-7,8,9,11,12,13,-
14,15-octahydro-6H-cyclopenta[a]phenanthren-17-yl)oxy)silane
(199.3 mg, 0.5 mmol), Togni’s reagent (239 mg, 0.75 mmol), CuSCN
(6.05 mg, 0.05 mmol), and DMF (5 mL) were used. The mixture was
stirred at 50 °C for 12 h. The compound was purified by column
ASSOCIATED CONTENT
■
S
* Supporting Information
Copies of 1H, 13C, and 19F NMR spectra for all new
compounds. This material is available free of charge via the
Internet at http://pubs.acs.org.
1
chromatography and isolated as a solid in 76% yield (134 mg). H
NMR (CDCl3, 400 MHz): δ = 0.96 (s, 3H), 1.42−1.70 (m, 5H),
1.92−2.02 (m, 3H), 2.24−2.29 (m, 2H), 2.38−2.41 (m, 1H), 2.88−
2.91 (m, 2H), 3.18−3.29 (m, 1H), 3.77 (s, 3H), 6.63−6.64 (m, 1H),
6.69−6.73 (m, 1H), 7.16−7.19 (m, 1H). 19F NMR (CDCl3, 376
MHz): δ = −66.2 (d, J = 10.9 Hz).
3,3,3-Trifluoro-2,2-dimethyl-1-phenylpropan-1-one (4s).
Triethyl((2-methyl-1-phenylprop-1-en-1-yl)oxy)silane (131.1 mg, 0.5
mmol), Togni’s reagent (239 mg, 0.75 mmol), CuSCN (6.05 mg, 0.05
mmol), and DMF (5 mL) were used. The mixture was stirred at 50 °C
for 12 h. The compound was purified by column chromatography and
isolated as an oil in 64% yield (69 mg). 1H NMR (CDCl3, 400 MHz):
δ = 1.54 (s, 6H), 7.38−7.42 (m, 2H), 7.46−7.50 (m, 1H), 7.60−7.63
(m, 2H). 13C NMR (CDCl3, 100 MHz): δ = 20.7 (q, J = 2.9 Hz), 53.3
(q, J = 26.7 Hz), 126.8 (q, J = 282.3 Hz), 127.7, 128.2, 131.5, 138.1,
200.7. 19F NMR (CDCl3, 376 MHz): δ = −72.7 (s). IR (neat) ν/
AUTHOR INFORMATION
■
Corresponding Authors
*E-mail: chenqy@sioc.ac.cn.
*E-mail: yguo@sioc.ac.cn.
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
This work was supported by National Basic Research Program
of China (973 Program) (No. 2012CB821600), National
G
dx.doi.org/10.1021/jo500713f | J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
Article
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dx.doi.org/10.1021/jo500713f | J. Org. Chem. XXXX, XXX, XXX−XXX