Synthesis of novel 2-trifluoromethyl-1-methylene-3-phenylindene derivatives via carbocyclization reaction of 2-trifluoromethyl-1,1-diphenyl-1,3-enynes

Article abstract of DOI:10.1016/j.jfluchem.2011.06.031

Trifluoromethylated enynyl sulfones 3 were reacted with PhLi at -78 °C for 2-4 h to give 2-trifluoromethyl-1,1-diphenyl-1,3-enynes 6 in good yields. Carbocyclization reaction of 6 with 10 mol% of Pd(OAc)₂ in cosolvent of CF₃COOH and

Full text of DOI:10.1016/j.jfluchem.2011.06.031

Journal of Fluorine Chemistry 132 (2011) 1227–1231
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Journal of Fluorine Chemistry
journal homepage: www.elsevier.com/locate/fluor
Synthesis of novel 2-trifluoromethyl-1-methylene-3-phenylindene derivatives
via carbocyclization reaction of 2-trifluoromethyl-1,1-diphenyl-1,3-enynes
*
Ji Hye Hwang, Yeon Hui Jung, Youn Young Hong, Sung Lan Jeon, In Howa Jeong
Department of Chemistry, Yonsei University, Wonju 220-710, South Korea
A R T I C L E I N F O
A B S T R A C T
Article history:
Trifluoromethylated enynyl sulfones 3 were reacted with PhLi at ꢀ78 8C for 2–4 h to give 2-
trifluoromethyl-1,1-diphenyl-1,3-enynes 6 in good yields. Carbocyclization reaction of 6 with 10 mol%
of Pd(OAc)2 in cosolvent of CF3COOH and MC (4:1) at room temperature for 1 h afforded 2-
trifluoromethyl-1-methylene-3-phenylindene derivatives 7 in good yields.
Received 31 March 2011
Received in revised form 20 June 2011
Accepted 21 June 2011
Available online 2 July 2011
ß 2011 Published by Elsevier B.V.
Keywords:
Trifluoromethylated enynyl sulfones
2-Trifluoromethyl-1,1-diphenyl-1,3-
enynes
Carbocyclization reaction
2-Trifluoromethyl-1-methylene-3-
phenylindene derivatives
1. Introduction
[15]. 1,3-Disubstituted 2-trifluoromethylated indenes were
synthesized by reduction of
a-trifluoromethyl-b-phenylated
The indene ring system has been found as an important
framework in many drug candidates possessing interesting
biological activities [1–5]. Numerous methods for the synthesis
of this family of compounds have been well documented in the
previous literatures [6–11], but methods are mostly related to the
synthesis of nonfluorinated indene derivatives. However, there
have been quite limited methodologies for the preparation of
trifluoromethylated indenes. Since the introduction of a trifluor-
omethyl group into the organic molecules has often increased the
biological properties [12,13], many efforts have been devoted to
the development of synthetic methodologies for the preparation of
trifluoromethylated indenes. 1-Trifluoromethylindene was pre-
pared from the reaction of 2,2,3-trifluoro-3-(trifluoromethyl)in-
danone with zinc in the presence of HCl, in which 2,2,3-trifluoro-3-
(trifluoromethyl)indanone was synthesized by the radical-addi-
tion reaction of benzaldehyde to hexafluoropropene [14]. Gassman
also prepared a series of trifluoromethylated indenes through the
photoinduced addition of trifluoromethyl iodide to indene
followed by dehydroiodination, the addition of (trifluoromethyl)-
trimethylsilane to 1-indanone followed by dehydration or the
sigmatropic cyclization of the appropriate phenylvinyl carbocation
enones, followed by cyclization reaction in the presence of AlCl3
[16,17]. One-pot synthesis of 2-trifluoromethyl indene was
established by the reaction of the di-Grignard reagent of
a, -
a0
dichloro-o-xylene with trifluoroacetate, followed by dehydration
[18]. Recently, 1,1-disubstituted 3-trifluoromethylated indenes
were synthesized through the cyclization of 1-trifluoromethyl-1-
phenylallyl amine derivatives by TMSOTf [19]. However, the most
of these methods focused on the preparation of trifluoromethy-
lated indenes. In spite of importance of 1-methylene indene
derivatives such as Sulindac in recent years [3,4], to our
knowledge, the methods for the preparation of trifluoromethylated
1-methylene indenes have not been reported in the previous
literatures. Herein, we wish to report a novel and general approach
to 2-trifluoromethyl-1-methylene-3-phenylindenes via the carbo-
cyclization reaction of 2-trifluoromethyl-1,1-diphenyl-1,3-enynes.
2. Results and discussion
Trifluoromethylated enynyl sulfones 3a–h (E/Z = 9/91) as
precursors to 2-trifluoromethyl-1,1-diphenyl-1,3-enynes were
prepared in 84–99% yields from the oxidation of trifluoromethy-
lated enynyl sulfides 2a–h (E/Z = 9/91) which were synthesized in
78–98% yields from the reaction of pentafluoroethyl phenyl
dithioketal 1 with aryl or alkyl substituted ethynyllithium reagents
(2.5 equiv.) (Scheme 1) [20]. The assignment of E and Z isomers of
* Corresponding author. Tel.: +82 33 760 2240; fax: +82 33 763 4323.
E-mail address: jeongih@yonsei.ac.kr (I.H. Jeong).
0022-1139/$ – see front matter ß 2011 Published by Elsevier B.V.
doi:10.1016/j.jfluchem.2011.06.031

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J.H. Hwang et al. / Journal of Fluorine Chemistry 132 (2011) 1227–1231
CF3
CF3
SPh
R1C CLi (2.5 equiv)
THF, 0 oC 15 oC, 16 h
MCPBA (2.2 equiv)
CH2Cl2, rt, 3 h
SPh
SO2Ph
C C6H5
SPh
F3CF2C
C
C
C
C
R1
R1
C6H5
C6H5
2a (R1 = C6H5, 98%)
3a (R1 = C6H5, 98%)
1
2b (R1 = p-CH3C6H4, 86%)
2c (R1 = m-CH3C6H4, 78%)
2d (R1 = m-FC6H4, 93%)
2e (R1 = p-CH3OC6H4, 97%)
2f (R1 = n-C5H11, 89%)
3b (R1 = p-CH3C6H4, 90%)
3c (R1 = m-CH3C6H4, 84%)
3d (R1 = m-FC6H4, 92%)
3e (R1 = p-CH3OC6H4, 84%)
3f (R1 = n-C5H11, 99%)
3g (R1 = n-C7H15, 97%)
3h (R1 = n-C8H17, 95%)
2g (R1 = n-C7H15, 87%)
2h (R1 = n-C8H17, 81%)
Scheme 1.
3a–h was made by the comparison of chemical shift of authentic
sample in 19F NMR spectroscopy [21] and the anisotropic effect of
the sulfonyl group. Therefore, the chemical shift of the CF3 group
(Z-isomer) arranged to the same side of the sulfonyl group could be
deshielded. It has been established that 19F NMR signal
(ꢁꢀ55.70 ppm) in the Z-isomer is less shielded than that
(ꢁꢀ59.00 ppm) in the E-isomer.
underwent 5-exo-dig carbocyclization to give 9-benzylidene-
9H-fluorene derivatives [24]. Therefore, we examined the
possibility of carbocyclization of 7 under palladium catalyzed
condition. After screening the palladium catalyzed condition, it
was found that the use of 10 mol% Pd(OAc) in the presence of
CF3CO2H and CH2Cl2 (4:1) provided 2-trifluoromethy-1-methy-
lene-3-phenylindenes 7 via 5-exo-dig carbocyclization exclusive-
ly. In this carbocyclization, aryl-substituted 1,3-enynes 6a–e
afforded 1-methylene indenes 7a–e as one isomer predominately,
whereas alkyl-substituted 1,3-enynes 6f–h provided 1-methy-
lene indenes 7f–h in the same stereoisomer ratios of 5/4. The
results of these reactions were summarized in Table 2. In the case
of carbocyclization of trimethylsilyl- or triisopropylsilyl-substi-
tuted 1,3-enynes 6i–j, protodesilylation product 7i was obtained
(Scheme 3). We did not observe the 6-endo-dig carbocyclization.
Other palladium-catalyzed system did not provide the better
results. Assignment of 5-exo-dig hydroarylation product 7 was
based on 1H NMR chemical shift. The 1H NMR of 7f showed that
the peak of vinyl protons of E and Z isomer appeared as a triplet at
Since 1 was not reacted with trimethylsilyl or triisopropylsilyl
substituted ethynyllithium reagents, enynyl sulfones 3i–j (E/
Z = 35/65) were prepared in 64–72% yields as a mixture of E and Z
isomers from the reaction of
b
-fluoro- -trifluoromethylvinyl
b
sulfone 5, formed by oxidation of
b
-fluoro-b-trifluoromethylvinyl
sulfide 4 [22], with trimethylsilyl or triisopropylsilyl substituted
ethynyllithium reagents in CH2Cl2 at 0 8C for 3 h (Scheme 2).
Vinyl sulfones 3 are very reactive species to react with
organolithium reagents. Thus, further reactions of 3a–j with
phenyllithium reagents (2.2 equiv.) in THF at ꢀ78 8C for 2–4 h
afforded the corresponding 2-trifluoromethyl-1,1-diphenyl-1,3-
enynes 6a–j in 63–77% yields. The use of other solvents such as
hexane or ether in this reaction caused not only to retard the
reaction, but also to decrease the yield of 6. Reaction temperature
in this reaction was also important to maximize the yield of 6. The
results of these reactions were summarized in Table 1. A recent
study has established that this type of addition-elimination
reaction of 3 with aryl, alkyl or trialkylsilyl ethynyllithium reagent
provided the corresponding trifluoromethylated endiynes in good
yields [23]. Advantage for the exchange of sulfonyl group in enynyl
sulfones 3 to phenyl group is to utilize two phenyl rings for the Pd-
catalyzed cyclization of arene-alkyne substrates via intramolecular
electrophilic hydroarylation.
d
= 6.93 and 6.78 ppm, respectively. The chemical shifts of
two vinyl protons of 7i in the 1H NMR are 6.36 and 6.15 ppm,
respectively. It was postulated that this reaction proceeds
via ortho-palladation of 6 to give intermediate [I], which under-
goes the insertion to a triple bond to give vinylpalladium species
[II]. Protiodepalladation of [II] affords 1-methylene indenes 7
(Scheme 4).
3. Conclusion
In conclusion, we synthesized 2-trifluoromethy-1-methylene-
3-phenylindene derivatives 7 via 5-exo-dig carbocyclization of 2-
trifluoromethyl-1,1-diphenyl-1,3-enynes 6 by the use of 10 mol%
Pd(OAc) in the presence of CF3CO2H and CH2Cl2 (4:1). Aryl-
substituted 1,3-enynes 6a–e afforded 1-methylene indenes 7a–e
as one isomer predominately, whereas alkyl-substituted ones 6f–h
Recently, intramolecular palladium-catalyzed hydroarylation
of alkynes became a powerful tool for the construction of carbo-
and heterocycles. Especially, hydroarylation of o-alkynyl biaryls
has been studied, in which it was found that a variety of o-alkynyl
biaryls having electron-neutral or electron-deficient group
SPh
CF3
CF3
R1C CLi (1.5 equiv)
CH2Cl2, 0 oC, 3 h
TiCl4/LiAlH4
THF, reflux, 3 h
92%
MCPBA (2.2 equiv)
SPh
SO2Ph
F3CF2C C C6H5
F
F
CH2Cl2, reflux, 24 h
97%
SPh
C6H5
4
C6H5
5
1
CF3
SO2Ph
C
C
R1
C6H5
3i (R1 = TMS, 72%)
3j (R1 = TIPS, 64%)
Scheme 2.

J.H. Hwang et al. / Journal of Fluorine Chemistry 132 (2011) 1227–1231
1229
Table 1
Preparation of 2-trifluoromethyl-1,1-diphenyl-1,3-enynes 6.
CF3
CF3
C6H5Li (2.2 equiv)
THF, -78 oC, t (h)
SO2Ph
C
C
C
C
R1
R1
6
3
.
Compound no
R1
t (h)
Yield (%)a
6a
6b
6c
6d
6e
6f
C6H5
3
3
3
3
3
2
2
2
4
4
63
75
72
77
71
71
70
73
74
74
p-CH3C6H4
m-CH3C6H4
p-CH3OC6H4
m-FC6H4
n-C5H11
6g
6h
6i
n-C7H15
n-C8H17
(CH3)3Si
6j
[(CH3)2CH]3Si
a
Isolated yield.
Table 2
Preparation of 2-trifluoromethyl-1-methylene-3-phenylindenes 7. ‘
CF3
Pd(OAC)2 (10 mol%)
C
F3C
R1
C
R1
CF3COOH : MC = 4 : 1, rt, 1 h
H
6
7
.
Compound no
R1
Yield (%)a
7a
7b
7c
7d
7e
7f
C6H5
81
70
71
60
58
83
78
80
p-CH3C6H4
m-CH3C6H4
p-CH3OC6H4
m-FC6H4
n-C5H11
7g
7h
n-C7H15
n-C8H17
a
Isolated yield.
provided 7f–h as a mixture of E and Z isomers (5:4). In the case of
carbocyclization of trimethylsilyl- or triisopropylsilyl-substituted
1,3-enynes 6i–j, reduced product 7i was obtained.
were dried by general purification method. Flash chromatography
was performed on 40–60 m silica gel (230–400 mesh).
m
4.1. General procedure for the preparation of 2-trifluoromethyl-1-
phenyl-1-phenylthio-1,3-enynes (2)
4. Experimental
A 25 mL two-neck round bottom flask equipped with a
magnetic stirrer bar, a septum and nitrogen tee connected to an
argon source was charged with 1-alkyne (5.0 mmol) and 10 mL of
THF. The reaction mixture was cooled to 0 8C and n-BuLi (2.5 M
1H and 13C NMR spectra were recorded on a 400 MHz Bruker
AVANCEII++ NMR spectrometer with tetramethylsilane (TMS) as an
internal standard and 19F NMR spectra were also recorded on a
400 MHz Bruker AVANCEII++ NMR spectrometer with CFCl3 as an
internal standard and the upfield as negative. All chemical shifts (d)
CF3
are expressed in parts per million and coupling constant (J) are
given in Hertz. Mass spectra were obtained by using Agilent
Technologies 6890N GC/5973 Network MSD (EI, 70 eV). Elemental
analysis data were obtained by using EA1110 elemental analyzer.
Melting points were determined in open capillary tubes and are
uncorrected.
Pd(OAC)2 (10 mol%)
C
F3C
C
R1
CF3COOH : MC = 4 : 1, rt, 1 h
H
6i, R = (CH3)3Si (69%)
6j, R = [(CH3)2CH]3Si (65%)
H
7i
6i-j
Commercially available reagents were purchased from
Aldrich, Lancaster, Tokyo Kasei and Fluorochem. All solvents
Scheme 3.

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J.H. Hwang et al. / Journal of Fluorine Chemistry 132 (2011) 1227–1231
CF3
CF3
Pd(OAc)2
-AcOH
C
AcOH
-Pd(OAc)2
C
Pd
AcO
C
F3C
R1
F3C
R1
C
R1
R1
PdOAc
[II]
H
7
6
[I]
Scheme 4.
solution in hexane) 2.0 mL (5.0 mmol) was added dropwise. After
the reaction mixture was stirred at 0 8C for 1 h, 1,1-bis(phe-
nylthio)-2,2,3,3,3-pentafluoropropyl benzene (1) (2.0 mmol) dis-
solved in THF (4 mL) was added at 0 8C. The reaction mixture was
warmed to 15 8C and then stirred for 16 h. The reaction mixture
was extracted with ether twice, dried over anhydrous MgSO4 and
chromatographed on SiO2 column. Elution with hexane provided
1,3-enynyl sulfides 2.
(18), 217 (25), 208 (100), 189 (34), 77 (15). Anal. calcd for
24H17F3SO3: C, 65.15; H, 3.87. Found: C, 64.93; H, 3.83.
C
4.2.2. 2-Trifluoromethyl-1-phenyl-1-phenylsulfonyl-1-nonen-3-yne
(3f)
3f (E/Z = 91/9) was prepared in 99% yield (0.603 g) according to
the general procedure. 3f: yellow oil; 1H NMR (CDCl3)
d 7.75–7.02
(m, 20H), 2.53 (t, J = 6.8 Hz, 2H, E-isomer), 2.09 (t, J = 6.8 Hz, 2H, Z-
isomer), 1.70–1.31 (m, 6H, E-isomer), 1.31–0.87 (m, 6H, Z-isomer),
0.87 (m, 3H, E-isomer), 0.78 (t, J = 7.2 Hz, 3H, Z-isomer); 19F NMR
4.1.1. 2-Trifluoromethyl-4-methoxyphenyl-1-phenyl-1-phenylthio-
1-buten-3-yne (2e)
(CDCl3, internal standard CFCl3)
d
ꢀ55.96 (s, 3F, Z-isomer), 59.39 (s,
2e (E/Z = 91/9) was prepared in 97% yield (0.796 g) according to
3F, E-isomer); MS, m/z (relative intensity) 406 (M+, 1), 285 (15),
265 (10), 225 (26), 209 (92), 183 (46), 165 (20), 152 (18), 139 (41),
125 (31), 111 (89), 83 (100), 77 (50), 55 (21). Anal. calcd for
the general procedure. 2e: colorless oil; 1H NMR (CDCl3)
d 7.55–
6.82 (m, 14H, E-isomer), 7.40–6.73 (m, 14H, Z-isomer), 3.84 (s, 3H,
E-isomer), 3.76 (s, 3H, Z-isomer); 19F NMR (CDCl3, internal
C22H21F3SO2: C, 65.01; H, 5.21. Found: C, 64.87; H, 5.15.
standard CFCl3)
d
ꢀ56.34 (s, 3F, E-isomer), 58.72 (s, 3F, Z-isomer);
MS, m/z (relative intensity) 410 (M+, 100), 395 (18), 326 (11), 298
4.2.3. 2-Trifluoromethyl-1-phenyl-1-phenylsulfonyl-4-
(19), 289 (11), 217 (13), 189 (19), 121 (8), 77 (7). Anal. calcd for
trimethylsilyl-1-buten-3-yne (3i)
C
24H17F3SO: C, 70.23; H, 4.17. Found: C, 70.12; H, 4.15.
A 25 mL two-neck round bottom flask equipped with a
magnetic stirrer bar, a septum and nitrogen tee connected to an
argon source was charged with trimethylsilylacetylene (0.294 g,
3.0 mmol) and 8 mL of ether. The reaction mixture was cooled to
0 8C and MeLi (1.6 M solution in ether) 1.87 mL (3.0 mmol) was
added dropwise. Another 25 mL two-neck round bottom flask
equipped with a magnetic stirrer bar, a septum and nitrogen tee
connected to an argon source was charged with 517 (0.660 g,
2.0 mmol) and 15 mL of CH2Cl2. After the reaction mixture was
stirred at 0 8C, trimethylsilylethynyllithium prepared from above
was added dropwise at 0 8C, followed by strring for 3 h. The
reaction mixture was extracted with CH2Cl2 twice, dried over
anhydrous Na2CO3 and chromatographed on SiO2 column. Elution
with a mixture of hexane and ethyl acetate (20:1) provided 3i (E/
Z = 36/64) in 72% yield (0.588 g). 3i: mp 72–73 8C; 1H NMR (CDCl3)
4.1.2. 2-Trifluoromethyl-1-phenyl-1-phenylthio-1-nonen-3-yne (2f)
2f (E/Z = 91/9) was prepared in 89% yield (0.666 g) according to
the general procedure. 2f: yellow oil; 1H NMR (CDCl3)
(m, 20H), 2.50 (t, J = 6.8 Hz, 2H, E-isomer), 2.13 (t, J = 6.8 Hz, 2H, Z-
isomer), 1.68–1.31 (m, 6H, E-isomer), 1.31–1.06 (m, 6H, Z-isomer),
0.92 (t, J = 7.2 Hz, 3H, E-isomer), 0.80 (t, J = 7.2 Hz, 3H, Z-isomer);
19F NMR (CDCl3, internal standard CFCl3)
58.82 (s, 3F, Z-isomer); MS, m/z (relative intensity) 374 (M+, 10),
318 (26), 297 (20), 265 (15), 241 (100), 209 (28), 183 (13), 165 (10),
139 (14), 121 (12), 91 (7), 77 (9). Anal. calcd for C22H21F3S: C, 70.56;
H, 5.65. Found: C, 70.42; H, 5.59.
d 7.36–6.96
d
ꢀ56.69 (s, 3F, E-isomer),
4.2. General procedure for the preparation of 2-trifluoromethyl-1-
phenyl-1-phenylsulfonyl-1,3-enynes (3)
d
7.79–6.99 (m, 20H), 0.33 (s, 9H, E-isomer), ꢀ0.11 (s, 9H, Z-
isomer); 19F NMR (CDCl3, internal standard CFCl3)
d
ꢀ55.75 (s, 3F,
A
25 mL two-neck round bottom flask equipped with a
Z-isomer), 59.09 (s, 3F, E-isomer); MS, m/z (relative intensity) 408
(M+, 5), 344 (13), 233 (10), 183 (10), 171 (31), 170 (35), 151 (59),
135 (17), 127 (27), 125 (39), 105 (28), 97 (13), 77 (100), 51 (33).
Anal. calcd for C20H19F3SO2Si: C,58.80; H, 4.69. Found: C, 58.65; H,
4.66.
magnetic stirrer bar, a septum and nitrogen tee connected to an
argon source was charged with 1,3-enynylsulfides 2 (1.5 mmol)
and 15 mL of CH2Cl2. The reaction mixture was cooled to 0 8C and
MCPBA (3.2 mmol) dissolved in 5 mL of CH2Cl2 was added at 0 8C,
followed by stirring at room temperature for 3 h. A mixture of
NaHCO3 and 10% NaHSO3 solution was added into the reaction
mixture which was extracted with CH2Cl2 twice, dried over
anhydrous K2CO3 and chromatographed on SiO2 column. Elution
with a mixture of hexane and ethyl acetate (4:1) provided 1,3-
enynyl sulfones 3.
4.3. General procedure for the preparation of 2-trifluoromethyl-1,1-
diphenyl-1,3-enynes (6)
A 25 mL two-neck round bottom flask equipped with a
magnetic stirrer bar, a septum and nitrogen tee connected to
an argon source was charged with 1,3-enynyl sulfone
3
4.2.1. 2-Trifluoromethyl-4-methoxyphenyl-1-phenyl-1-
phenylsulfonyl-1-buten-3-yne (3e)
3e (E/Z = 91/9) was prepared in 84% yield (0.557 g) according to
the general procedure. 3e: mp = 84–86 8C; 1H NMR (CDCl3)
d 7.74–
6.91 (m, 14H, E-isomer), 7.62–6.69 (m, 14H, Z-isomer), 3.83 (s, 3H,
E-isomer), 3.72 (s, 3H, Z-isomer); 19F NMR (CDCl3, internal
(1.0 mmol) and 5 mL of THF. The reaction mixture was cooled
to ꢀ78 8C and phenyllithium (2.0 M solution in di-n-butyl ether)
1.1 mL (2.2 mmol) was added dropwise. After the reaction
mixture was stirred at 0 8C for 2–4 h, the reaction mixture was
quenched with NaCl solution. The reaction mixture was extracted
with ether twice, dried over anhydrous MgSO4 and chromato-
graphed on SiO2 column. Elution with hexane provided 1,1-
diphenyl-1,3-enynes 6.
standard CFCl3)
d
ꢀ55.66 (s, 3F, Z-isomer), 58.93 (s, 3F, E-isomer);
MS, m/z (relative intensity) 442 (M+, 3), 378 (48), 289 (10), 232

J.H. Hwang et al. / Journal of Fluorine Chemistry 132 (2011) 1227–1231
1231
4.3.1. 2-Trifluoromethyl-4-methoxyphenyl-1,1-diphenyl-1-buten-3-
yne (6d)
NMR (CDCl3) d 7.84–7.09 (m, 18H), 6.93 (t, J = 7.6 Hz, 1H, one
isomer), 6.78 (t, J = 7.6 Hz, 1H, other isomer), 2.88 (dt, J = 7.6,
7.2 Hz, 2H, one isomer), 2.70 (dt, J = 7.6, 7.2 Hz, 2H, other isomer),
1.74–1.59 (m, 6H, one isomer), 1.43–1.26 (m, 6H, other isomer),
0.95 (t, J = 7.2 Hz, 6H); 19F NMR (CDCl3, internal standard CFCl3)
d
6d was prepared in 77% yield (0.291 g) according to the general
procedure. 6d: yellow oil; 1H NMR (CDCl3)
d
7.48–6.79 (m, 14H),
3.79 (s, 3H); 13C NMR (CDCl3)
d
160.2, 155.0, 140.9, 139.4, 133.2,
130.2, 129.3, 129.2, 128.7, 128.2, 128.0, 122.5 (q, J = 274.7 Hz),
114.9, 114.2, 112.8 (q, J = 33.2 Hz), 95.4, 83.9, 55.5; 19F NMR
ꢀ52.78 (s, 3F, one isomer), ꢀ53.07 (s, 3F, other isomer); MS, m/z
(relative intensity) 342 (M+, 25), 285 (8), 272 (100), 265 (8), 251
(12), 239 (10), 215 (12), 202 (8). Anal. calcd for C22H21F3: C, 77.17;
H, 6.18. Found: C, 76.93; H, 6.15.
(CDCl3, internal standard CFCl3)
d
ꢀ57.08 (s, 3F); MS, m/z (relative
intensity) 378 (M+, 100), 357 (13), 309 (18), 294 (23), 265 (30), 239
(8), 208 (8), 165 (11), 147 (8), 132 (8), 77 (7). Anal. calcd for
C
24H17F3O: C, 76.18; H, 4.53. Found: C, 75.92; H, 4.48.
4.4.3. 2-Trifluoromethyl-1-methylene-3-phenyl-1H-indene (7i)
7i was prepared in 69% yield (0.188 g) according to the general
4.3.2. 2-Trifluoromethyl-1,1-diphenyl-1-nonen-3-yne (6f)
procedure. 7i: yellow oil; 1H NMR (CDCl3)
d 7.73–7.15 (m, 9H), 6.37
6f was prepared in 71% yield (0.243 g) according to the general
(s, 1H), 6.15 (s, 1H); 13C NMR (CDCl3) 149.1, 142.4, 141.2, 135.8,
132.7, 128.7, 128.6, 128.5, 127.9, 127.2, 124.5, 123.5 (q,
J = 32.2 Hz), 122.1, 119.8, 115.6; 19F NMR (CDCl3, internal standard
procedure. 6f: colorless oil; 1H NMR (CDCl3)
d
7.60–7.16 (m, 10H),
2.25 (t, J = 6.8 Hz, 2H), 1.44–1.21 (m, 6H), 0.86 (t, J = 6.8 Hz, 3H); 19
NMR (CDCl3, internal standard CFCl3)
F
d
ꢀ57.50 (s, 3F); MS, m/z
CFCl3)
d
ꢀ54.13 (s, 3F); MS, m/z (relative intensity) 272 (M+, 100),
(relative intensity) 342 (M+, 39), 285 (80), 260 (30), 244 (23), 233
(25), 215 (100), 202 (43), 189 (20), 165 (20), 115 (12), 91 (16), 83
(21), 77 (7), 55 (15). Anal. calcd for C22H21F3: C, 77.17; H, 6.18.
Found: C, 76.88; H, 6.19.
251 (29), 239 (31), 220 (8), 203 (13), 202 (26). Anal. calcd for
C17H11F3: C, 74.99; H, 4.07. Found: C, 74.80; H, 4.04.
Acknowledgment
4.3.3. 2-Trifluoromethyl-4-trimethylsilyl-1,1-diphenyl-1-buten-3-
yne (6i)
1This work was supported by a grant from the Korea Sanhak
Foundation (2010-68).
6i was prepared in 74% yield (0.255 g) according to the general
procedure. 6i: colorless oil; 1H NMR (CDCl3)
d
7.38–7.34 (m, 10H),
156.5, 141.3, 140.5, 139.0, 129.8,
128.9, 127.9, 127.2, 122.1 (q, J = 274.7 Hz), 112.3 (q, J = 33.2 Hz),
100.8, 98.9, 11.0; 19F NMR (CDCl3, internal standard CFCl3)
0.33 (s, 9H); 13C NMR (CDCl3)
d
References
d
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247 (19), 226 (10), 213 (10), 77 (16). Anal. calcd for C20H19F3Si: C,
69.74; H, 5.56. Found: C, 69.55; H, 5.60.
4.4. General procedure for the preparation of 2-trifluoromethyl-1-
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A 25 mL two-neck round bottom flask equipped with a magnetic
stirrer bar, a septum and nitrogen tee connected to an argon source
waschargedwith6(1.0 mmol), 1 mLofCH2Cl2 and 4 mLofCF3CO2H.
Pd(OAc)2 was added into the reaction mixture and the reaction
mixture was stirred at room temperature for 1 h. The reaction
mixture was extracted with ether twice, dried over anhydrous
MgSO4 and chromatographed on SiO2 column. Elution with hexane
provided 2-trifluoromethyl-1-methylene-3-phenylindenes 7.
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4.4.1. 2-Trifluoromethyl-1-(4-methoxyphenyl)methylene-3-phenyl-
1H-indene (7d)
7d was prepared in 60% yield (0.227 g) according to the general
procedure. 7d: mp 157–159 8C; 1H NMR (CDCl3)
d
8.01–7.07 (m,
14H), 3.92 (s, 3H); 19F NMR (CDCl3, internal standard CFCl3)
d
ꢀ56.74 (s, 3F); MS, m/z (relative intensity) 378 (M+, 100), 363 (11),
309 (9), 294 (12), 265 (15), 239 (7), 189 (8), 147 (5), 132 (5). Anal.
calcd for C24H17F3O: C, 76.18; H, 4.53. Found: C, 75.94; H, 4.48.
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4.4.2. 2-Trifluoromethyl-1,1-diphenyl-1-nonen-3-yne (7f)
7f (E and Z isomer ratio = 5:4) was prepared in 83% yield
(0.284 g) according to the general procedure. 7f: yellow oil; 1H