New approaches to β-trifluoromethylated enone derivatives

Article abstract of DOI:10.1016/j.jfluchem.2004.09.021

β-Trifluoromethylated enaminones 1 were prepared stereospecifically or high stercoselectively in 31-92% yields from the reaction of Weinreb amides with trifluoropropynyl lithium, followed by quenching with H₂O in the presence of amine derivativ

Full text of DOI:10.1016/j.jfluchem.2004.09.021

Journal of Fluorine Chemistry 125 (2004) 1629–1638
www.elsevier.com/locate/fluor
New approaches to b-trifluoromethylated enone derivatives
a,
In Howa Jeong , Sung Lan Jeon , Myong Sang Kim , Bum Tae Kim
a
a
b
*
aDepartment of Chemistry, Yonset University, Wonju 220-710, South Korea
bKorea Research Institute of Chemical Technology, Daejeon 305-606, South Korea
Available online 22 October 2004
Abstract
b-Trifluoromethylated enaminones 1 were prepared stereospecifically or high stercoselectively in 31–92% yields from the reaction of
Weinreb amides with trifluoropropynyl lithium, followed by quenching with H2O in the presence of amine derivatives. b-Trifluoromethylated
enaminone 1a was reacted with aryl or alkynyl Grignard reagents to give Michael addition products 5 at 0 8C, whereas addition–elimination
adducts, b-aryl (or alkynyl)-b-trifluoromethylated enones 6, were obtained stereospecifically in 50–92% yields after stirring at room
temperature for several hours.
# 2004 Elsevier B.V. All rights reserved.
Keywords: Trifluoropropynyl lithium; Weinreb amides; b-Trifluoromethylated enaminones; b-Trifluoromethylated enones
1. Introduction
the presence of sodium dithionite and sodium bicarbonate,
followed by quenching with H2O also provided b-
trifluoromethylated enones having no substituent at a- or
b-position [8].
Trifluoromethylated building blocks have been receiving
increasing attention because of their potential to give
new synthetic routes to a variety of trifluoromethylated
compounds, some of which exhibit unique biological or
physical properties in the areas of agrochemicals, pharma-
ceuticals and material science [1,2]. In the course of our
synthetic studies on trifluoromethylated building blocks,
we needed a facile and convenient synthetic route to b-
trifluoromethylated enones, which are quite useful synthetic
intermediates for the preparation of trifluoromethylated
heterocyclic compounds [3–5]. However, the only several
methods for the preparation of b-trifluoromethylated enones
have been reported in the previous literatures. b-Trifluor-
omethylated enones having no substituent at a- or b-position
were prepared from the reaction of methyl ketones with
a-trifluoromethyl iminium trifluoroacetates [6]. Dolbier
carried out the reactions of 1,1-bis(dimethylamino)-2,2,2-
trifluoroethane with silyl enol ethers or ketones having
a-hydrogen to afford b-trifluoromethylated enones having
no substituent at a- or b-position [7]. The reactions of enol
vinyl ethers with 1-bromo-1-chloro-2,2,2-trifluoroethane in
b-Trifluoromethyl-b-methylated enones were also
synthesized via Wittig reaction. Triphenylphosphoranyli-
den-2-propanone was reacted with trifluoromethylated
ketones to give b-trifluoromethyl-b-methylated enones
[9]. A couple of methods for the preparation of b-chloro-
b-trifluoromethylated enones has been reported in the
previous literatures. Eguchi prepared b-chloro-b-trifluor-
omethylated enones from the reaction of silyl enol ethers
with CF3CCl3 in the presence of CuCl, followed by
dehydrochlorination with Et3N or DBN [10]. b-Chloro-b-
trifluoromethylated enones were also prepared from the
reaction of trifluoromethylated 1,3-diketone with Vilsmier
reagent formed from DMF and oxalyl chloride [4,11].
Recently, several researchers showed b-trifluoromethyl
enaminones were quite useful synthetic intermediate to
give a variety of heterocyclic compounds via amine
exchange reaction with nucleophiles [12–15]. b-Trifluor-
omethyl enaminones were prepared from the reaction of
methyl ketones with trifluoroacetonitrile in the presence of
N-ethylanilino magnesium bromide [16]. The treatment of
trifluoromethylated b-diketones with ammonium acetate
and ammonium bicarbonate also resulted in the formation of
* Corresponding author. Tel.: +82 33 760 2240; fax: +82 33 763 4323.
E-mail address: jeongih@dragon.yonsei.ac.kr (I.H. Jeong).
0022-1139/$ – see front matter # 2004 Elsevier B.V. All rights reserved.
doi:10.1016/j.jfluchem.2004.09.021

1630
I.H. Jeong et al. / Journal of Fluorine Chemistry 125 (2004) 1629–1638
b-trifluoromethyl enaminones in a mixture of isomeric
aminoenones [17]. Huang also synthesized b-trifluoro-
methyl enaminones from the reaction of N-aryl trifluoro-
methyl imidoyl iodides with methyl ketones in the presence
of sodium hydride [12]. All of the previous methods for the
preparation of b-trifluoromethylated enones had several
drawbacks such as a lack of generality, low yield preparation
and tedious procedure. In the present paper, we would like to
describe a novel and efficient method for the preparation
of several types of b-trifluoromethylated enones, such as
b-trifluoromethyl enaminones [18], b-aryl-b-trifluoro-
methylated enones and b-alkynyl-b-trifluoromethylated
enones from the same starting material.
The reaction temperature in this reaction is quite important
to control the reaction. These experimental results indicate
that low reaction temperature is not effective for the addition
of trifluoropropynyl lithium toward amide functionality
and also high reaction temperature cause backward process
of addition intermediate [I]. To consume N-methoxy-N-
methylbenzamide completely, an excess of trifluoropropy-
nyl lithium (2.0 equiv.) was used under the optimized
reaction temperature. The treatment of trifluoropropynyl
lithium (2.0 equiv.) with N-methoxy-N-methylbenzamide
(1.0 equiv.) at ꢀ78 8C followed by warming to 0 8C and
quenching with H2O resulted in the formation of desired
product 1a in 84% yield based on 98% conversion of
N-methoxy-N-methylbenzamide. The results of these reac-
tions are summarized in Scheme 1 and Table 1. The same
reaction was performed between trifluoropropynyl lithium
(2.0 equiv.) and N,N-dimethylbenzamide (1.0 equiv.)
instead of N-methoxy-N-methylbenzamide under the same
reaction condition, but no desired product 1a was obtained
and N,N-dimethylbenzamide was recovered quantitatively
(Scheme 2). This result implies that N-methoxy group in
Weinreb benzamide plays an important role to give lithium
complex in intermediate [I]. N-Methoxy-N-methylaceta-
mide was also reacted with trifluoropropynyl lithium under
the same reaction condition to give the corresponding
b-trifluoromethyl enaminone 1b (E/Z = 14/86) in 60% yield.
A plausible mechanism for the formation of 1a seems
likely that the reaction of trifluoropropynyl lithium with
Weinreb benzamide afforded intermediate [I] which was
reacted with H2O to give ynone intermediate [II]. Then,
intermediate [II] was rapidly reacted with N-methoxy-N-
methylamine formed from the reaction to give 1a
(Scheme 3). To prove the formation of intermediate [I], a
trapping reaction with trimethylsilyl chloride was carried
and silyl ether derivative 2 was obtained in 80% yield. The
assignment of E and Z isomers of 1a was made by the
comparison of chemical shift in 19F NMR spectroscopy.
It has been well established that 19F NMR signal in the
Z-isomer of CF3-trisubstituted vinylic compounds is more
shielded than that in the E-isomer [23]. Therefore, two
singlet peaks at ꢀ65.97 and 61.84 ppm in the 19F NMR
spectrum are due to a CF3 group in the Z and E isomers of 1a,
respectively. Determination of the configuration of 1a
was also supported by NOE observation (1.2%) between
N-methyl group and the vinyl proton of (E)-1a, whereas no
NOE observation was detected in (Z)-1a.
2. Results and discussion
2.1. Preparation of b-trifluoromethylated enaminones 1
It is well known that Weinreb amides are quite useful
reagents to control nucleophilic addition–elimination reac-
tion of amine functionality by organometallic reagents
[19–22]. Therefore, the reaction of trifluoropropynyl lithium
with Weinreb amide may provide a nice method for the
preparation of b-trifluoromethylated ynone, which cannot
be easily prepared via previous methods. We first examine
the influence of reaction temperature on the reaction to
optimize reaction condition. The reaction of trifluoropro-
pynyl lithium (1.0 equiv.) formed from the reaction of
trifluoropropyne (1.1 equiv.) with n-BuLi (1.1 equiv.) was
reacted with N-methoxy-N-methylbenzamide (1.0 equiv.) at
ꢀ78 8C followed by warming to ꢀ30 8C and quenching
with H2O afforded an E- and Z-isomeric mixture of
b-trifluoromethyl enaminone 1a (E/Z = 13/87) in 62% yield
based on 27% conversion of N-methoxy-N-methylbenza-
mide instead of b-trifluoromethylated ynone. When
trifluoropropynyl lithium was reacted with N-methoxy-N-
methylbenzamide at ꢀ78 8C followed by warming to 0 8C
and quenching with H2O, an E- and Z-isomeric mixture of 1a
was obtained in 64% yield based on 60% conversion of
N-methoxy-N-methylbenzamide. It seems likely that the
high reaction temperature condition makes high conversion
of N-methoxy-N-methylbenzamide. Thus, the same reaction
was carried out at ꢀ78 8C followed by warming to room
temperature and quenching with H2O to make a high
conversion of N-methoxy-N-methylbenzamide. Unexpec-
tively, only N-methoxy-N-methylbenzamide was recovered
in 98% yield and the desired product 1a was not obtained.
Since arylamino group of enaminone was exchanged with
hydrazine or amidine to give the corresponding pyrazole or
Scheme 1.

I.H. Jeong et al. / Journal of Fluorine Chemistry 125 (2004) 1629–1638
1631
Table 1
Reaction of trifluoropropynyl lithium with N-methoxy-N-methylbenzamide
Entry
X (equiv.)
Condition
Recovered
amide (%)
Yield (%)a,b
1
2
3
4
5
6
a
1
ꢀ78 8C ! ꢀ30 8C
ꢀ78 8C ! ꢀ10 8C
ꢀ78 8C ! 0 8C
ꢀ78 8C ! 10 8C
ꢀ78 8C ! rt
73
64
40
63
98
<2
62
63
64
63
0
1
1
Scheme 4.
1
1
0.5
ꢀ78 8C ! 0 8C
84
presence of a variety of amines. Therefore, treatment of
intermediate [I] with H2O in the presence of the same
equivalence of piperidine at 0 8C and then stirring at room
temperature for 1 h resulted in the formation of 1c (Z-isomer
only) in 92% yield. The similar reactions of intermediate [I]
with N,N-dimethylamine, N-benzyl-N-methylamine, mor-
pholine and benzylamine afforded the only Z-isomer of
corresponding enaminones 1d, 1e, 1f and 1g in 77–89%
yields (Scheme 4 and Table 2). The reaction of intermediate
[I] with H2O in the presence of aniline provided the
corresponding enaminone 1h (Z-isomer only) in 31% yield
along with 1a (E/Z = 13/97, 50% yield). It is postulated
that the formation of 1a could be due to the low reactivity
of aniline toward intermediate [II] as compare with
N-methoxy-N-methylamine. The stereospecificity for the
formation of 1c–h can be rationalized by hydrogen bond
interaction between hydrogen of amine group and oxygen of
carbonyl group after addition of amine group to ynone
intermediate [II].
Isolated yields based on the conversion of amide.
b
An isomeric mixture of product (E/Z = 13/87) was obtained.
pyrimidine [12], 1a was examined to figure out whether N-
methoxy-N-methyl group of 1a can be exchanged with other
amines or not. The treatment of 1a with piperidine at room
temperature for 3 h in THF resulted in the formation of
piperidine-substituted enaminone 1c (only Z-isomer) in 97%
yield stereospecifically. The similar reactions of 1a with
dimethylamine, benzylamine, n-butylamine, also afforded
the corresponding enaminones 1d, 1g and 1k in 70–99%
yields. However, when 1a was treated with bulky amines
such as diisopropylamine or 2,6-dimethylpiperidine, the
reaction did not proceed at all and 1a was recovered in
quantitative yield. The reaction of 1a with aniline under the
same reaction condition provided a trace amount of desire
product 1h. These results indicate that steric effect is quite
important in this exchange reaction. The formation of
intermediate [II] and successful exchange reaction of N-
methoxy-N-methyl group of 1a with amines stimulated us to
carry out the reaction of intermediate [I] with H2O in the
Similarly, an isomeric mixture of enaminones 1i (E/
Z = 25/75) and 1j (E/Z = 17/83) were obtained in 55% and
74% yields from the reaction of intermediate [I] with H2O in
Scheme 2.
Scheme 3.

1632
I.H. Jeong et al. / Journal of Fluorine Chemistry 125 (2004) 1629–1638
Table 2
Preparation of a variety of b-trifluoromethyl enaminones
Compound no.
R
R1R2NH
Yield (%)a
E/Zb
1c
1d
1e
1f
1g
1h
1i
C6H5
C6H5
C6H5
C6H5
C6H5
C6H5
C6H5
C6H5
–(CH2)5NH–
92
0/100
0/100
0/100
0/100
0/100
0/100
25/75
17/83
(CH3)2NH
77
Bn(CH3)NH
89
–(CH2)2O(CH2)2NH–
BnNH2
82
83
C6H5NH2
31 (50c)
55 (20d)
74 (5e)
[(CH3)2CH]2NH
–CH(CH3)(CH2)3CH(CH3)NH–
1j
a
Isolated yield.
The ratio was determined by analysis of the 1H NMR and 19F NMR spectra and NOE of the 1H NMR.
b
c
d
e
1a was obtained in 50% yield.
1a was obtained in 20% yield.
1a was obtained in 5% yield.
the presence of sterically hindered amines such as
diisopropyl amine and 2,6-dimethylpiperidine. Especially,
the reactions of intermediate [I] with 2,2,6,6-tetramethylpi-
peridine and hexamethyldisilazane did not provide enam-
inones, but only 1a was obtained in 60% and 61% yields
from each reaction.
reactions of b-trifluoromethylated enaminones [12–15] or
b-chloro (or fluoro)-b-trifluoromethylated enones [4–5,24]
with heteroatom nucleophiles (N, O, S) have been well
established in the previous literatures, there was no report on
the addition–elimination reactions of b-trifluoromethylated
enaminones or b-chloro-b-trifluoromethylated enones with
carbon nucleophiles such as Grignard reagents or organo-
lithium reagents. Therefore, we first examined on the
reaction of 1a with phenyllithium. When 1a (1 equiv.) was
reacted with phenyllithium (1 equiv.) at ꢀ78 8C in THF, a
messy reaction mixture was obtained. The reaction of 1a
(1 equiv.) with phenylmagnesium bromide (1 equiv.) in
ether at ꢀ78 8C followed by warming to 0 8C did not
undergo at all and thus 1a was recovered quantitatively.
When 1a was reacted with 2 equiv. of phenylmagnesium
bromide under the same reaction condition, however, 1,4-
addition product 5a was obtained in 45% yield. The use of
3 equiv. of phenylmagnesium bromide in this reaction
caused to increase the formation of 5a to 76% yield. Then,
we examined this reaction on the influence of reaction
temperature. Treatment of 1a with 3 equiv. of phenylmag-
nesium bromide in ether at ꢀ78 8C followed by warming to
room temperature and then stirring at room temperature for
Treatment of intermediate [I] with H2O in the presence of
bidendate amines such as hydrazine or benzamidine resulted
in the formation of heterocyclic compounds, pyrazole 3
or pyrimidine 4, in 72% and 71% yields, respectively
(Scheme 5). No other regioisomer was observed in the
formation of 3.
2.2. Preparation of b-aryl (or alkynyl)-b-
trifluoromethylated enones 6
The synthetic methods for the preparation of b-aryl-b-
trifluoromethylated enones and b-alkynyl-b trifluoromethy-
lated enones have been quite limited and only one paper
described the preparation of b-methyl-b-trifluoromethy-
lated enones and b-phenyl-b-trifluoromethylated enones
[9]. There was no report on the synthesis of b-alkynyl-b-
trifluoromethylated enones. Although addition–elimination
Scheme 5.

I.H. Jeong et al. / Journal of Fluorine Chemistry 125 (2004) 1629–1638
1633
Scheme 6.
Table 3
Preparation of b-aryl (or alkynyl)-b-trifluoromethylated enones 6
Compound no.
R
X
Condition
Yield (%)a
6a
6b
6c
6d
6e
6f
6g
6h
6i
C6H5
3
3
3
3
3
3
3
3
3
3
ꢀ78 8C ! rt, 4 h
ꢀ78 8C ! rt, 3 h
ꢀ78 8C ! rt, 12 h
ꢀ78 8C ! rt, 12 h
ꢀ78 8C ! rt, 4 h
ꢀ78 8C ! rt, 7 h
ꢀ78 8C ! rt, 9 h
ꢀ78 8C ! rt, 15 h
ꢀ78 8C ! rt, 1 h
ꢀ78 8C ! rt, 13 h
72
71
76
74
67
84
90
92
50
80
4-CH3O–C6H4
4-CF3–C6H4
3-CF3–C6H4
3,4-OCH2O–C6H3
C4H3S
CH3CBC
C6H5CBC
CH3(CH2)3CBC
(CH3)3SiCBC
6j
a
Isolated yield.
bromide under the similar reaction condition afforded the
corresponding enones 6b–f (only E-isomer) in 67–84%
yields. We also carried out the reaction of 1a with
alkynylmagnesium bromides such as propynylmagnesium
bromide, phenylethynylmagnesium bromide, hexynylmag-
nesium bromide and trimethylethynylmagnesium bromide
to afford the corresponding b-alkynyl-b-trifluoromethy-
lated enones 6g–j in 50–92% yields. The results of these
reactions are summarized in Scheme 6 and Table 3.
The stereospecific formation of 6 can be rationalized by
hydrogen bond interaction between oxygen of N-methoxy
group or fluorine of trifluoromethyl group and hydrogen in
addition intermediate [III] which provides E-isomer of
enone by anti-elimination of N-methoxy-N-methyl group
(Scheme 7).
Scheme 7.
4 h resulted in the formation of b-phenyl-b-trifluoromethy-
lated enones 6a (only E-isomer) in 72% yield. The
reaction of 1a with p-methoxyphenylmagnesium bromide,
p-trifluoromethylphenylmagnesium bromide, m-trifluoro-
methylphenylmagnesium bromide, 3,4-(methylenedioxy)-
phenylmagnesium bromide and thiophen-2-ylmagnesium
Scheme 8.

1634
I.H. Jeong et al. / Journal of Fluorine Chemistry 125 (2004) 1629–1638
The reaction of 1a with methylmagnesium bromide at
condenser was filled with slush of dry ice and isopropyl
alcohol, 3,3,3-trifluoropropyne (0.564 g, 6.0 mmol) was
slowly added into flask by condensation via dry ice
condenser. To a THF solution of 3,3,3-trifluoropropyne
was added n-BuLi (6.0 mmol) at ꢀ78 8C and the reaction
mixture was stirred at ꢀ78 8C for 0.5 h under argon
atmosphere. N-Methoxy-N-methylbenzamide (0.495 g,
3.0 mmol) or N-methoxy-N-methylacetamide (0.309 g,
3.0 mmol) was added into a mixture at ꢀ78 8C and then
warmed to 0 8C. H2O (5 mL) or a mixture of H2O (5 mL)
and amine (3.0 mmol) was added into a mixture and then
allowed to stir for 1 h at 0 8C. The reaction mixture was
extracted with ether twice. The ether solution was dried and
chromatographed on SiO2 column. Elution with a mixture of
hexane and ethyl acetate (9:1) provided enaminones 1.
ꢀ78 8C followed by warming to 0 8C afforded a desired
product 6k in only 33% yield along with 1,4-addition
product 5b (40%)and reducing product 7 (5%) (Scheme 8).
When 1a was treated with Grignard reagent having longer
alkyl chain such as ethylmagnesium bromide or cyclohex-
ylmagnesium bromide, however, only reducing product 7
was obtained in 63% and 70% yields, respectively.
3. Conclusions
The reaction of N-methoxy-N-methylbenzamide
(1 equiv.) with trifluoropropynyl lithium (2 equiv.) at
ꢀ78 8C and then 0 8C, followed by quenching with H2O
afforded stereoselectively b-trifiuoromethylated enaminone
1a in 84% yield. Enaminone 1a was treated with sterically
less hindered amine derivatives to give amine exchange
products in high yields stereospecifically. When the reaction
mixture formed from the reaction of N-methoxy-N-
methylbenzamide (1 equiv.) with trifluoropropynyl lithium
(2 equiv.) at ꢀ78 8C and then 0 8C was quenched with H2O
in the presence of amine derivatives, b-trifiuoromethylated
enaminones 1 were obtained in good yields stereospecifi-
cally. b-Trifluoromethylated enaminone 1a was reacted with
aryl or alkynyl Grignard reagents (3 equiv.) at room
temperature for several hours to give b-aryl (or alkynyl)-
b-trifluoromethylated enones 6. However, the reaction of 1a
with alkylmagnesium bromide yielded reducing products as
a major product.
4.1.1. 4,4,4-Trifluoro-3-(N-methoxy-N-methyl)amino-1-
phenyl-2-buten-1-one 1a
1a (E/Z = 13/87) was prepared in 84% yield according to
the general procedure (addition of N-methoxy-N-methyl-
1
benzamide followed by quenching with H2O). 1a: oil; H
NMR (CDCl3) Z-isomer d 7.95–7.90 (m, 2H), 7.57–7.47 (m,
3H), 6.19 (s, 1H), 3.32 (s, 3H), 3.04 (s, 3H), E-isomer d 7.95–
7.90 (m, 2H), 7.57–7.47 (m, 3H), 6.44 (s, 1H), 3.64 (s, 3H),
2.99 (s, 3H); 19F NMR (CDCl3) d ꢀ65.97 (s, 3F, Z-isomer),
ꢀ61.84 (s, 3F, E-isomer); MS, m/z (relative intensity) 259
(M+, 7), 228 (81), 130 (21), 105 (67), 91 (100), 77 (58),
69 (6), 51 (13); IR (neat) 3062, 2938, 1673, 1599, 1580,
1561, 1450, 1281, 1180, 752, 690 cmꢀ1. Anal. Calcd. for
C12H12F3NO2: C, 55.60; H, 4.67. Found: C, 55.38; H, 4.62.
4.1.2. 5,5,5-Trifluoro-4-(N-methoxy-N-methyl)amino-3-
penten-2-one 1b
4. Experimental
1b (E/Z = 14/86) was prepared in 60% yield according to
the general procedure (addition of N-methoxy-N-methyla-
1H NMR were recorded on a 200 MHz Gemini-200 NMR
spectrometer and 19F NMR spectra were recorded on a
100 MHz Bruker AC-100F NMR spectrometer with tetra-
methylsilane (TMS) and CFCl3 as an internal standard,
respectively and the upfield as negative. All chemical shifts
(d) are expressed in parts per million and coupling constant
(J) are given in Hertz. Infrared spectra were determined on a
Mattson Genesis series FT High Resolution Spectro-
photometer. Mass spectra were obtained by using GC/
MS-Qp1000-Shimadzu (El, 70 eV). Melting points were
determined in open capillary tubes and are unconnected.
Commercially available reagents were purchased from
Aldrich, Lancaster, Tokyo Kasei and Fluorochem. All
solvents were dried by general purification method.
1
cetamide followed by quenching with H2O). 1b: oil; H
NMR (CDCl3) Z-isomer d 5.79 (s, 1H), 3.56 (s, 3H), 3.11 (s,
3H), 2.29 (s, 3H), E-isomer d 6.05 (s, 1H), 3.58 (s, 3H), 2.92
(s, 3H), 2.30 (s, 3H); 19F NMR (CDCl3) d ꢀ65.59 (s, 3F, Z-
isomer), ꢀ61.30 (s, 3F, E-isomer); MS, m/z (relative
intensity) 197 (M+, 2), 166 (21), 157 (16), 155 (17), 148
(7), 110 (5), 82 (9), 69 (7), 43 (100); IR (neat) 3048, 2979,
1721, 1574, 1558, 1372, 1281, 1188 cmꢀ1. Anal. Calcd. for
C7H10F3NO2: C, 42.65; H, 5.11. Found: C, 42.51; H, 5.06.
4.1.3. (Z)-4,4,4-Trifluoro-1-phenyl-3-(1-piperidinyl)-2-
buten-1-one 1c
1c was prepared in 92% yield according to the general
procedure (addition of N-methoxy-N-methylbenzamide
followed by quenching with a mixture of H2O and
piperidine). 1c: oil; 1H NMR (CDCl3) d 7.91–7.87 (m,
2H), 7.51–7.39 (m, 3H), 6.22 (s, 1H), 3.24 (s, 4H), 1.68 (s,
6H); 19F NMR (CDCl3) d ꢀ64.46 (s, 3F); MS, m/z (relative
intensity) 283 (M+, 37), 266 (52), 131 (21), 105 (33), 103
(17), 91 (11), 83 (100), 77 (25), 69 (11); IR (neat) 3062,
2941, 1645, 1599, 1581, 1564, 1470, 1279, 1180, 1126, 771,
4.1. General procedure for the preparation of
enaminones 1
A 25 mL two-neck round-bottomed flask equipped with a
magnetic stirrer bar, septum and dry ice condenser
connected to an argon source was charged with THF
(10 mL) and then cooled to ꢀ78 8C. After a dry ice

I.H. Jeong et al. / Journal of Fluorine Chemistry 125 (2004) 1629–1638
1635
632 cmꢀ1. Anal. Calcd. for C15H16F3NO: C, 63.60; H, 5.69.
Found: C, 63.45; H, 5.63.
4.1.8. (Z)-4,4,4-Trifluoro-1-phenyl-3-(phenylamino)-2-
buten-1-one 1h
1h was prepared in 31% yield according to the general
procedure (addition of N-methoxy-N-methylbenzamide
followed by quenching with a mixture of H2O and aniline),
4.1.4. (Z)-4,4,4-Trifluoro-3-(dimethylamino)-1-phenyl-2-
buten-1-one 1d
1
1d was prepared in 77% yield according to the general
procedure (addition of N-methoxy-N-methylbenzamide fol-
lowed by quenching with a mixture of H2O and dimethy-
lamine). 1d: oil; 1H NMR (CDCl3) d 7.93–7.88(m, 2H), 7.51–
7.44 (m, 3H), 6.23 (s, 1H), 3.05 (s, 6H); 19F NMR (CDCl3) d
ꢀ65.10 (s, 3F); MS, m/z (relative intensity) 243 (M+, 19), 226
(100), 166 (30), 138 (16), 105 (46), 91 (32), 77 (54), 69 (12);
IR (neat) 3064, 2973, 1678, 1575, 1550, 1470, 1290, 1174,
1100, 748, 690 cmꢀ1 Anal. Calcd. for C12H12F3NO: C, 59.26;
H, 4.97. Found: C, 59.13; H, 4.93.
1h: oil; H NMR (CDCl3) d 12.52 (s, 1H), 7.98–7.93 (m,
2H), 7.55–7.24 (m, 8H), 6.44 (s, 1H); 19F NMR (CDCl3) d
ꢀ63.59 (s, 3F); MS, m/z (relative intensity) 291 (M+, 61),
222 (36), 186 (18), 144 (14), 105 (76), 77 (100), 69 (2), 51
(44); IR (neat) 3064, 2960, 1630, 1599, 1570, 1530, 1292,
1189, 1143, 754, 687 cmꢀ1. Anal. Calcd. for C16H12F3NO:
C, 65.98; H, 4.15. Found: C, 65.71; H, 4.13.
4.1.9. 3-(Diisopropylamino)-4,4,4-trifluoro-1-phenyl-2-
buten-1-one 1i
1i (E/Z = 25/75) was prepared in 55% yield according to
the general procedure (addition of N-methoxy-N-methyl-
benzamide followed by quenching with a mixture of H2O
and diisopropylamine). 1i: oil; 1H NMR (CDCl3) Z-isomer d
7.94–7.88 (m, 2H), 7.57–7.24 (m, 3H), 6.80 (s, 1H), 3.70–
3.64 (m, 2H), 1.25 (d, J = 6.7 Hz, 6H), E-isomer d 7.95–7.90
(m, 2H), 7.57–7.47 (m, 3H), 6.13 (s, 1H), 3.80–3.69 (m, 2H),
1.31 (d, J = 6.7 Hz, 6H); 19F NMR (CDCl3) d ꢀ64.63 (s, 3F,
Z-isomer), ꢀ60.52 (s, 3F, E-isomer); MS, m/z (relative
intensity) 299 (M+, 12), 256 (19), 105 (21), 88 (14), 86 (72),
84 (100), 77 (10), 74 (17), 59 (17); IR (neat) 3061, 2978,
4.1.5. (Z)-4,4,4-Trifluoro-3-(N-benzyl-N-methylamino)-1-
phenyl-2-buten-1-one 1e
1e was prepared in 89% yield according to the general
procedure (addition of N-methoxy-N-methylbenzamide fol-
lowed by quenching with a mixture of H2O and N-benzyl-N-
methylamine). 1e: oil; 1H NMR (CDCl3) d 7.91–7.86(m, 2H),
7.51–7.23 (m, 8H), 6.37 (s, 1H), 4.47 (s, 2H), 2.88 (s, 3H); 19
F
NMR (CDCl3) d ꢀ64.35 (s, 3F); MS, m/z (relative intensity)
319 (M+, 18), 302 (22), 214 (25), 120 (17), 110 (22), 105 (37),
91 (100), 77 (28), 62 (25); IR (neat) 3062, 2926, 1643, 1572,
1540, 1468, 1282, 1178, 748, 688 cmꢀ1. Anal. Calcd. for
C18H16F3NO: C, 67.70; H, 5.05. Found: C, 67.85; H, 5.10.
1668, 1634, 1596, 1581, 1480, 1273, 1176, 755, 697 cmꢀ1
.
Anal. Calcd. for C16H20F3NO: C, 64.20; H, 6.74. Found: C,
64.38; H, 6.80.
4.1.6. (Z)-4,4,4-Trifluoro-3-morpholino-1-phenyl-2-buten-
1-one 1f
4.1.10. 4,4,4-Trifluoro-3-(2,6-dimethyl-1-piperidinyl)-1-
phenyl-2-buten-1-one 1j
1f was prepared in 82% yield according to the general
procedure (addition of N-methoxy-N-methylbenzamide
followed by quenching with a mixture of H2O and
1j (E/Z = 17/83) was prepared in 74% yield according to
the general procedure (addition of N-methoxy-N-methyl-
benzamide followed by quenching with a mixture of H2O
1
morpholine). 1f: mp 62–63 8C; H NMR (CDCl3) d 7.92–
1
7.87 (m, 2H), 7.57–7.41 (m, 3H), 6.30 (s, 1H), 3.82–3.77 (m,
4H), 3.34–3.29 (m, 4H); 19F NMR (CDCl3) d ꢀ64.30 (s, 3F);
MS, m/z (relative intensity) 285 (M+, 40), 268 (50), 180 (28),
131 (23), 105 (96), 91 (100), 86 (27), 77 (50); IR (KBr) 3063,
2931, 1648, 1575, 1535, 1472, 1279, 1180, 1126, 751,
692 cmꢀ1. Anal. Calcd. for C14H14F3NO2: C, 58.95; H, 4.95.
Found: C, 58.76; H, 4.88.
and 2,6-dimethylpiperidine). 1j: mp 43–44 8C; H NMR
(CDCl3) Z-isomer d 7.92–7.87 (m, 2H), 7.58–7.43 (m, 3H),
7.02 (s, 1H), 3.11–3.07 (m, 2H), 1.69–1.19 (m, 6H), 1.07 (d,
J = 6.5 Hz, 6H), E-isomer d 7.92–7.87 (m, 2H), 7.58–7.43
(m, 3H), 6.45 (s, 1H), 3.11–3.07 (m, 2H), 1.69–1.19 (m, 6H),
1.07 (d, J = 6.5 Hz, 6H); 19F NMR (CDCl3) d ꢀ64.28 (s, 3F,
Z-isomer), ꢀ62.14 (s, 3F, E-isomer); MS, m/z (relative
intensity) 311 (M+, 35), 206 (28), 131 (28), 111 (23), 105
(100), 96 (33), 77 (55), 55 (43); IR (KBr) 3060, 2935, 1681,
4.1.7. (Z)-3-(Benzylamino)-4,4,4-trifluoro-1-phenyl-2-
buten-1-one 1g
1596, 1581, 1480, 1315, 1263, 1184, 1119, 759, 701 cmꢀ1
.
1g was prepared in 83% yield according to the general
procedure (addition of N-methoxy-N-methylbenzamide
followed by quenching with a mixture of H2O and
Anal. Calcd. for C17H20F3NO: C, 65.58; H, 6.48. Found: C,
65.51; H, 6.46.
1
benzylamine). 1g: oil; H NMR (CDCl3) d 11.01 (s, 1H),
4.2. Preparation of 4,4,4-trifluoro-1-(N-methoxy-N-
methylamino)-1-phenyl-1-trimethylsiloxyl-2-butyne 2
7.91–7.87 (m, 2H), 7.51–7.25 (m, 8H), 6.29 (s, 1H), 4.61 (d,
J = 6.3 Hz, 2H); 19F NMR (CDCl3) d ꢀ66.80 (s, 3F); MS,
m/z (relative intensity) 305 (M+, 49), 236 (6), 200 (10), 131
(9), 105 (27), 91 (100), 77 (20), 65 (17); IR (neat) 3033,
2885, 1630, 1599, 1572, 1520, 1325, 1190, 1138, 755,
685 cmꢀ1. Anal. Calcd. for C17H14F3NO: C, 66.88; H, 4.62.
Found: C, 66.71; H, 4.58.
A 25 mL two-neck round-bottomed flask equipped with
a magnetic stirrer bar, septum and dry ice condenser
connected to an argon source was charged with THF
(10 mL) and then cooled to ꢀ78 8C. After a dry ice
condenser was filled with slush of dry ice and isopropyl

1636
I.H. Jeong et al. / Journal of Fluorine Chemistry 125 (2004) 1629–1638
alcohol, 3,3,3-trifluoropropyne (0.564 g, 6.0 mmol) was
slowly added into flask by condensation via dry ice
condenser. To a THF solution of 3,3,3-trifluoropropyne
was added n-BuLi (6.0 mmol) at ꢀ78 8C and the reaction
mixture was stirred at ꢀ78 8 C for 0.5 h under argon
atmosphere. N-Methoxy-N-methylbenzamide (0.495 g,
3.0 mmol) was added into a mixture at ꢀ78 8C and then
warmed to 0 8C. Trimethylsilyl chloride (0.347 g, 3.2 mmol)
was added into a mixture and then allowed to stir for 1 h at
room temperature followed by quenching with H2O. The
reaction mixture was extracted with ether twice. The ether
solution was dried and chromatographed on SiO2 column.
Elution with a mixture of hexane and ethyl acetate (19:1)
connected to an argon source was charged with THF
(10 mL) and then cooled to ꢀ78 8C. After a dry ice
condenser was filled with slush of dry ice and isopropyl
alcohol, 3,3,3-trifluoropropyne (0.564 g, 6.0 mmol) was
slowly added into flask by condensation via dry ice
condenser. To a THF solution of 3,3,3-trifluoropropyne
was added n-BuLi (6.0 mmol) at ꢀ78 8C and the reaction
mixture was stirred at ꢀ78 8C for 0.5 h under argon
atmosphere. N-Methoxy-N-methylbenzamide (0.495 g,
3.0 mmol) was added into a mixture at ꢀ78 8C and then
warmed to 0 8C. A mixture of H2O (10 mL) and
benzamidine hydrochloride hydrate (1.027 g, 6.5 mmol)
was added into a mixture and then allowed to stir for 1 h at
0 8C. The reaction mixture was extracted with ether twice.
The ether solution was dried and chromatographed on SiO2
column. Elution with a mixture of hexane and ethyl acetate
1
provided 2 in 80% yield. 2: oil; H NMR (CDCl3) d 7.65–
7.60 (m, 2H), 7.38–7.35 (m, 3H), 3.46 (s, 3H), 2.40 (s, 3H),
0.20 (s, 9H); 19F NMR (CDCl3) d ꢀ51.20 (s, 3F); MS, m/z
(relative intensity) 271 (M+ ꢀ60, 100), 242 (36), 208 (12),
179 (11), 151 (23), 105 (27), 77 (10), 73 (47); IR (neat) 3067,
2960, 2262, 1450, 1273, 1214, 1147, 1087, 1024, 892,
844 cmꢀ1. Anal. Calcd. for C15H20F3NO2Si: C, 54.36; H,
6.08. Found: C, 54.49; H, 5.99.
1
(1:2) provided 4 in 71% yield. 4: mp 74–75 8C; H NMR
(CDCl3) d 8.66–8.61 (m, 2H), 8.30–8.25 (m, 2H), 7.90 (s,
1H), 7.60–7.52 (m, 6H); 19F NMR (CDCl3) d ꢀ70.53 (s,
3F); MS, m/z (relative intensity) 300 (M+, 68), 231 (8),
197 (13), 128 (100), 103 (92), 77 (88), 51 (53); IR (KBr)
3066, 2945, 1591, 1377, 1184, 1140 cmꢀ1. Anal. Calcd.
for C17H11F3N2: C, 68.00; H, 3.69. Found: C, 67.88;
H, 3.65.
4.3. Preparation of 3-trifluoromethyl-5-phenyl-1H-
pyrazole 3
A 25 mL two-neck round-bottomed flask equipped with
a magnetic stirrer bar, septum and dry ice condenser
connected to an argon source was charged with THF
(10 mL) and then cooled to ꢀ78 8C. After a dry ice
condenser was filled with slush of dry ice and isopropyl
alcohol, 3,3,3-trifluoropropyne (0.564 g, 6.0 mmol) was
slowly added into flask by condensation via dry ice
condenser. To a THF solution of 3,3,3-trifluoropropyne
was added n-BuLi (6.0 mmol) at ꢀ78 8C and the reaction
mixture was stirred at ꢀ78 8C for 0.5 h under argon
atmosphere. N-Methoxy-N-methylbenzamide (0.495 g,
3.0 mmol) was added into a mixture at ꢀ78 8C and then
warmed to 0 8C. A mixture of H2O (10 mL) and hydrazine
hydrate (0.368 g, 6.5 mmol) was added into a mixture and
then allowed to stir for 1 h at 0 8C. The reaction mixture was
extracted with ether twice. The ether solution was dried and
chromatographed on SiO2 column. Elution with a mixture of
hexane and ethyl acetate (1:2) provided 3 in 72% yield. 3:
4.5. Preparation of 4,4,4-trifluoro-3-(N-methoxy-N-
methyl)amino-1,3-diphenyl-1-butanone 5a
To a dry ether (5 mL) solution of phenylmagnesium
bromide (3.0 mmol) was added 1a (0.259 g, 1.0 mmol) at
ꢀ78 8C and the reaction mixture was slowly warmed at 0 8C.
The reaction mixture was quenched with saturated NH4Cl
solution and then extracted with ether twice. The solution
was dried and chromatographed on SiO2 column. Elution
with a mixture of hexane and ethyl acetate (1:19) provided
5a in 76% yield. 5a: oil; 1H NMR (CDCl3) d 7.99–7.94 (m,
2H), 7.60–7.20 (m, 8H), 3.99 (s, 2H), 3.58 (s, 3H), 2.58 (s,
3H); 19F NMR (CDCl3) d ꢀ67.37 (s, 3F); MS, m/z (relative
intensity) 337 (M+, 9), 306 (5), 268 (22), 218 (47), 118 (9),
105 (100), 77 (22); IR (neat) 3062, 2963, 1743, 1560, 1541,
1507, 1248, 1177, 1036, 742, 699 cmꢀ1. Anal. Calcd.
for C18H18F3NO2: C, 64.09; H, 5.38. Found: C, 64.02;
H, 5.37.
1
mp 105–106 8C; H NMR (CDCl3) d 12.58 (s, 1H), 7.60–
7.40 (m, 5H), 6.75 (s, 1H); 19F NMR (CDCl3) d ꢀ62.78 (s,
3F); MS, m/z (relative intensity) 212 (M+, 100), 164 (26),
142 (21), 115 (41), 105 (17), 86 (25), 77 (16), 69 (20), 62
4.6. General procedure for the preparation of b-aryl
(or alkynyl)-b-trifluoromethylated enones 6
(25); IR (KBr) 3420, 3118, 3024, 1279, 1167, 1153 cmꢀ1
.
To a dry ether (5 mL) solution of aryl (or alkynyl)mag-
nesium bromide (3.0 mmol) was added 1a (0.259 g,
1.0 mmol) at ꢀ78 8C and the reaction mixture was warmed
at room temperature. The reaction mixture was stirred at
room temperature for several hours and then quenched with
saturated NH4Cl solution. The reaction mixture was
extracted with ether twice. The solution was dried and
chromatographed on SiO2 column. Elution with a mixture of
hexane and ethyl acetate (1:19) provided 6.
Anal. Calcd. for C10H7F3N2: C, 56.61; H, 3.33. Found: C,
56.50; H, 3.35.
4.4. Preparation of 4-trifluoromethyl-2,6-
diphenylpyrimidine 4
A 25 mL two-neck round-bottomed flask equipped with a
magnetic stirrer bar, septum and dry ice condenser

I.H. Jeong et al. / Journal of Fluorine Chemistry 125 (2004) 1629–1638
1637
4.6.1. (E)-4,4,4-Trifluoro-1,3-diphenyl-2-buten-1-one 6a
4.6.6. (E)-4,4,4-Trifluoro-1-phenyl-3-(thiophen-2-yl)-2-
buten-1-one 6f
6a was prepared in 72% yield according to the general
procedure (stirring at room temperature for 4 h). 6a: oil; 1H
NMR (CDCl3) d 7.85–7.80 (m, 2H), 7.57–7.35 (m, 3H), 7.27
(s, 6H); 19F NMR (CDCl3) d ꢀ66.78 (s, 3F); MS, m/z
(relative intensity) 276 (M+, 68), 275 (100), 257 (4), 207 (9),
178 (8), 151 (18), 128 (4), 105 (35), 95 (7), 77 (55), 51 (12);
IR (neat) 3062, 2934, 1677, 1598, 1581, 1470, 1316, 1281,
1129, 743, 691 cmꢀ1. Anal. Calcd. for C16H11F3O: C, 69.56;
H, 4.01. Found: C, 69.65; H, 3.97.
6f was prepared in 84% yield according to the general
procedure (stirring at room temperature for 7 h). 6f: oil; 1H
NMR (CDCl3) d 7.90–7.84 (m, 2H), 7.59–7.42 (m, 3H),
7.39–7.29 (m, 1H), 7.17–7.12 (m, 2H), 6.98–6.87 (m, 1H);
19F NMR (CDCl3) d ꢀ66.86 (s, 3F); MS, m/z (relative
intensity) 282 (M+, 13), 213 (100), 185 (15), 105 (28), 77
(62), 63 (10), 51 (31); IR (neat) 3066, 2931, 1672, 1598,
1324, 1279, 1180, 1035 cmꢀ1. Anal. Calcd. for C14H9F3 OS:
C, 59.57; H, 3.21. Found: C, 59.38; H, 3.26.
4.6.2. (E)-4,4,4-Trifluoro-3-(4-methoxyphenyl)-1-phenyl-2-
buten-1-one 6b
4.6.7. (E)-3-Trifluoromethyl-1-phenyl-2-hexen-4-yn-1-one
6g
6b was prepared in 71% yield according to the general
procedure (stirring at room temperature for 3 h). 6b: oil; 1H
NMR (CDCl3) d 7.85–7.80 (m, 2H), 7.57–7.35 (m, 3H),
7.26–7.19 (m, 3H), 6.80–6.75 (m, 2H), 3.74 (s, 3H); 19F
NMR (CDCl3) d ꢀ66.67 (s, 3F); MS, m/z (relative intensity)
306 (M+, 100), 291 (19), 275 (85), 237 (18), 228 (23), 165
(13), 131 (13), 105 (56), 77 (68); IR (neat) 3060, 2960, 1674,
1609, 1480, 1279, 1174, 1033 cmꢀ1. Anal. Calcd. for
C17H13F3O2: C, 66.67; H, 4.28. Found: C, 66.55; H, 4.24.
6g was prepared in 90% yield according to the general
procedure (stirring at room temperature for 9 h). 6g: oil; 1H
NMR (CDCl3) d 7.97–7.92 (m, 2H), 7.66–7.46 (m, 3H), 7.45
(s, 1H), 2.04 (s, 3H); 19F NMR (CDCl3) d ꢀ68.13 (s, 3F);
MS, m/z (relative intensity) 238 (M+, 50), 210 (13), 169 (18),
141 (18), 115 (18), 105 (100), 77 (82), 51 (32); IR (neat)
3064, 2922, 2223, 1675, 1600, 1325, 1288, 1187,
1015 cmꢀ1. Anal. Calcd. for C13H9F3O: C, 65.55; H,
3.81. Found: C, 65.48; H, 3.80.
4.6.3. (E)-4,4,4-Trifluoro-3-(4-trifluoromethylphenyl)-1-
phenyl-2-buten-1-one 6c
4.6.8. (E)-3-Trifluoromethyl-1,5-diphenyl-2-penten-4-yn-1-
one 6h
6c was prepared in 76% yield according to the general
procedure (stirring at room temperature for 12 h). 6c: oil; 1H
6h was prepared in 92% yield according to the general
procedure (stirring at room temperature for 15 h). 6h: oil; 1H
NMR (CDCl3) d 7.86–7.81 (m, 2H), 7.71–7.39 (m, 8H); 19
F
NMR (CDCl3) d ꢀ63.54 (s, 3F), ꢀ66.92 (s, 3F); MS, m/z
(relative intensity) 344 (M+, 49), 325 (10), 275 (100), 219
(11), 169(9), 138(13), 105(54), 77(49);IR(neat)3063, 2934,
1679, 1598, 1480, 1327, 1280, 1171, 1069 cmꢀ1. Anal. Calcd.
for C17H10F6O: C, 59.31; H, 2.93. Found: C, 59.17; H, 2.95.
NMR (CDCl3) d 8.02–7.97 (m, 2H), 7.68–7.28 (m, 9H); 19
F
NMR (CDCl3) d ꢀ67.56 (s, 3F); MS, m/z (relative intensity)
300 (M+, 58), 251 (21), 231 (47), 202 (44), 126 (42), 102
(61), 77 (100), 51 (36); IR (neat) 3064, 2929, 2205, 1673,
1599, 1317, 1230, 1145, 1047 cmꢀ1. Anal. Calcd. for
C18H11F3O: C, 72.00; H, 3.69. Found: C, 71.83; H, 3.73.
4.6.4. (E)-4,4,4-Trifluoro-3-(3-trifluoromethylphenyl)-1-
phenyl-2-buten-1-one 6d
4.6.9. (E)-3-Trifluoromethyl-1-phenyl-2-nonen-4-yn-1-one
6i
6d was prepared in 76% yield according to the general
procedure (stirring at room temperature for 12 h). 6d: oil; 1H
NMR (CDCl3) d 8.00–7.38 (m, 10H); 19F NMR (CDCl3) d
ꢀ63.43 (s, 3F), ꢀ66.94 (s, 3F); MS, m/z (relative intensity)
344 (M+, 4), 275 (5), 251 (5), 167 (38), 149 (100), 119 (24),
105 (61), 91 (13); IR (neat) 3078, 2930, 1667, 1598, 1482,
1337, 1269, 1170, 1075 cmꢀ1. Anal. Calcd. for C17H10F6O:
C, 59.31; H, 2.93. Found: C, 59.21; H, 2.94.
6i was prepared in 50% yield according to the general
procedure (stirring at room temperature for 1 h). 6i: oil; 1H
NMR(CDCl3) d 7.97–7.92 (m, 2H), 7.62–7.46 (m, 3H), 7.37
(s, 1H), 2.35 (t, J = 6.7 Hz, 2H), 1.54–1.21 (m, 4H), 0.86 (t,
J = 7.1 Hz, 3H); 19F NMR (CDCl3) d ꢀ68.15 (s, 3F); MS, m/
z (relative intensity) 280 (M+, 9), 251 (61), 238 (82), 183
(30), 144 (26), 115 (27), 105 (91), 77 (100); IR (neat) 3066,
2961, 2215, 1675, 1598, 1287, 1186, 1014 cmꢀ1. Anal.
Calcd. for C16H15F3O: C, 68.56; H, 5.39. Found: C, 68.67;
H, 5.34.
4.6.5. (E)-3-(Benzo[d][1,3]dioxol-5-yl)-4,4,4-trifluoro-1-
phenyl-2-buten-1-one 6e
6e was prepared in 67% yield according to the general
procedure (stirring at room temperature for 4 h). 6e: oil; 1H
NMR (CDCl3) d 7.92–7.78 (m, 2H), 7.71 (s, 1H), 7.56–7.35
(m, 3H), 6.74–6.61 (m, 3H), 5.89 (s, 2H); 19F NMR (CDCl3)
d ꢀ66.77 (s, 3F); MS, m/z (relative intensity) 320 (M+, 76),
290 (19), 262 (25), 251 (52), 213 (14), 165 (17), 143 (13),
118 (13), 105 (100), 77 (82); IR (neat) 3065, 2912, 1673,
1598, 1282, 1178, 1039 cmꢀ1. Anal. Calcd. for C17H11F3O3:
C, 63.76; H, 3.46. Found: C, 63.61; H, 3.42.
4.6.10. (E)-3-Trifluoromethyl-5-trimethylsilyl-1-phenyl-2-
penten-4-yn-1-one 6j
6j was prepared in 80% yield according to the general
procedure (stirring at room temperature for 13 h). 6j: oil; 1H
NMR (CDCl3) d 7.96–7.91 (m, 2H), 7.67–7.46 (m, 3H), 7.36
(s, 1H), 0.10 (m, 9H); 19F NMR (CDCl3) d ꢀ67.73 (s, 3F);
MS, m/z (relative intensity) 296 (M+, 6), 222 (9), 187 (35),
152 (34), 105 (59), 77 (100); IR (neat) 3064, 2936, 2154,

1638
I.H. Jeong et al. / Journal of Fluorine Chemistry 125 (2004) 1629–1638
1648, 1600, 1285, 1186, 1063 cmꢀ1. Anal. Calcd. for
C15H15F3OSi: C, 60.79; H, 5.10. Found: C, 60.72; H, 5.08.
References
[1] J.T. Welch, S. Eswarakrishnan, Fluorine in Bioorganic Chemistry,
Wiley, New York, 1991.
4.6.11. (E)-4,4,4-Trifluoro-3-methyl-1-phenyl-2-buten-1-
one 6k
[2] R.E. Bank, B.E. Smart, J.C. Tatlow, Organofluorine Chemistry
Principle and Commercial Applications, Plenum Press, New York,
1994.
To a dry ether (5 mL) solution of methylmagnesium
bromide (3.0 mmol) was added 1a (0.259 g, 1.0 mmol) at
ꢀ78 8C and the reaction mixture was warmed at 0 8C
followed by quenching with saturated NH4Cl solution. The
reaction mixture was extracted with ether twice. The
solution was dried and chromatographed on SiO2 column.
Elution with a mixture of hexane and ethyl acetate (1:19)
provided 6k in 33% yield along with 5b (40%) and 7 (5%).
[3] K.I. Pashkevich, A.Ya. Aizikovich, I.Ya. Postovskii, Izv. Akad. Nauk
SSSR, Ser. Khim. (1981) 455.
[4] R. Amaud, A. Bensadat, A. Ghobsi, A. Laurent, I.L. Drean, S. Lesniak,
A. Sehni, Bull. Soc. Chim. Fr. 131 (1994) 844–853.
[5] J. Diab, A. Laurent, I.L. Drean, J. Fluorine Chem. 84 (1997) 145–147.
[6] C. Ates, Z. Janousek, H.G. Viehe, Tetrahedron Lett. 34 (1993) 5711–
5714.
[7] Y. Xu, W.R. Dolbier Jr., Tetrahedron Lett. 39 (1998) 9151–9154.
[8] H. Plenkiewicz, W. Dmowski, M. Lipinski, J. Fluorine Chem. 111
(2001) 227–232.
1
6k: oil; H NMR (CDCl3) d 7.98–7.92 (m, 2H), 7.67–7.44
(m, 3H), 7.23 (q, J = 1.4 Hz, 1H), 2.16 (d, J = 1.4 Hz, 3H);
19F NMR (CDCl3) d ꢀ71.36 (s, 3F); MS, m/z (relative
intensity) 214 (M+, 4), 145 (7), 118 (6), 105 (100), 77 (70);
IR (neat) 3064, 2933, 1679, 1598, 1369, 1295, 1179,
1100 cmꢀ1. Anal. Calcd. for C11H9F3O: C, 61.69; H, 4.24.
Found: C, 61.57; H, 4.20. 5b: oil; 1H NMR (CDCl3) d 8.01–
7.90 (m, 2H), 7.62–7.42 (m, 3H), 3.48 (d, J = 15.1 Hz, 1H),
3.42 (s, 3H), 3.27 (d, J = 15.1 Hz, 1H), 2.70 (s, 3H), 1.55 (s,
3H); 19F NMR (CDCl3) d ꢀ74.65 (s, 3F); MS, m/z (relative
intensity) 275 (M+, 6), 244 (24), 206 (35), 156 (35), 124 (16),
105 (100), 91 (18), 77 (79), 56 (46); IR (neat) 3063, 2958,
1682, 1599, 1323, 1295, 1147, 1097 cmꢀ1. Anal. Calcd. for
C13H16F3NO2: C, 56.72; H, 5.86. Found: C, 56.81; H, 5.88.
[9] D.L. Dull, I. Baxter, H.S. Mosher, J. Org. Chem. 32 (1967)
1622–1623.
[10] T. Okano, T. Uekawa, S. Eguchi, Bull. Chem. Soc. Jpn. 62 (1989)
2575–2579.
[11] G. Alvemhe, A. Bensadat, A. Ghobsi, A. Laurent, E. Laurent, J.
Fluorine Chem. 81 (1997) 169–172.
[12] H.-B. Yu, W.-Y. Stewart, J. Fluorine Chem. 84 (1997) 65–67.
[13] V.Ya. Sosnovskikh, V.A. Kutsenko, Russ. Chem. Bull. 48 (1999) 540–
551.
[14] V.Ya. Sosnovskikh, V.A. Kutsenko, Y.G. Yatluk, Russ. Chem. Bull. 48
(1999) 1395–1396.
[15] V.Ya. Sosnovskikh, V.A. Kutsenko, A.Ya. Aizikovich, V.Yu. Korotnev,
Russ. Chem. Bull. 48 (1999) 2112–2116.
[16] V.Ya. Sosnovskikh, I.S. Ovsyannikov, Zh. Org. Khim. (1990) 26.
[17] N.S. Karpenko, V.I. Filyakova, K.I. Pashkevich, Zh. Org. Khim. 33
(1997) 1807–1809.
1
7: mp 77–78 8C; H NMR (CDCl3) d 10.74 (s, 1H), 7.99–
[18] I.H. Jeong, S.L. Jeon, Y.K. Min, B.T. Kim, Tetrahedron Lett. 43 (2002)
7171–7174.
7.86 (m, 2H), 7.59–7.39 (m, 3H), 6.22 (s, 1H), 3.12 (d,
J = 5.7 Hz, 3H); 19F NMR (CDCl3) d ꢀ67.73 (s, 3F); MS, m/
z (relative intensity) 229 (M+, 77), 212 (24), 152 (20), 118
(12), 105 (100), 84 (16), 77 (70); IR (KBr) 3067, 2953, 1743,
1600, 1324, 1295, 1183, 1140 cmꢀ1. Anal. Calcd. for
C11H10F3NO: C, 57.64; H, 4.40. Found: C, 57.58; H, 4.41.
[19] R. Bergman, B. Nilsson, B. Wickberg, Tetrahedron Lett. 31 (1990)
2783–2786.
[20] B.H. Lipshutz, S.S. Pfeiffer, W. Chrisman, Tetrahedron Lett. 40 (1999)
7889–7892.
[21] A. Gomtsyan, Org. Lett. 2 (2000) 11–13.
[22] A. Gomtsyan, R.J. Koenig, C.H. Lee, J. Org. Chem. 66 (2001) 3613–
3616.
[23] J.P. Begue, D. Bonnet-Delpon, D. Mesureur, M. Ourevitch, Magn.
Reson. Chem. 29 (1991) 675–678.
Acknowledgment
[24] M. Ohkoshi, M. Yoshida, H. Matsuyama, M. Iyoda, Tetrahedron Lett.
42 (2001) 33–36.
This work was supported by Korea Research Foundation
Grant (KRF-2003-041-C00199).