Reaction of 1,2-unsaturated trifluoromethyl ketones and their conversion to 1-(trifluoromethyl)furan derivatives

Article abstract of DOI:10.1002/ejoc.200700280

A novel synthetic approach leading to 1-(trifluoromethyl)furan derivatives is reported. 4-Aryl-1,1,1-trifluorobut-3-en-2-one was iodinated and subsequently reduced to give the corresponding alcohol. The resultant iodo compound was then subjected to coupli

Full text of DOI:10.1002/ejoc.200700280

FULL PAPER
DOI: 10.1002/ejoc.200700280
Reaction of 1,2-Unsaturated Trifluoromethyl Ketones and Their Conversion to
1-(Trifluoromethyl)furan Derivatives
Dehui Zhang[a] and Chengye Yuan*[a]
Keywords: Fluorinated substituents / Furans / Intramolecular cyclization / Ag catalysis / Synthetic methods
A novel synthetic approach leading to 1-(trifluoromethyl)fu-
ran derivatives is reported. 4-Aryl-1,1,1-trifluorobut-3-en-2-
one was iodinated and subsequently reduced to give the cor-
responding alcohol. The resultant iodo compound was then
subjected to coupling with phenylacetylene to furnish an (E)-
3-aryl-2-(2-phenylethynyl)-1-(trifluoromethyl)allyl alcohol,
which could be cyclized by means of AgOTf to furnish a 2-
(trifluoromethyl)furan in fair yield.
(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim,
Germany, 2007)
Introduction
Results and Discussion
First of all, the preparation of 1,2-unsaturated trifluoro-
methyl ketones reported by us[4] was re-examined in order
to optimize the reaction conditions and to investigate the
scope of this procedure (Scheme 1).
As reported by Uneyama, N-substituted trifluoroacetimid-
oyl chloride is a trifluoromethyl building block for fluori-
nated nitrogen heterocycles.[1] We demonstrated that in ad-
dition to (trifluoromethyl)imidazole and -triazole deriva-
tives,[2] this precursor was applied successfully for the asym-
metric synthesis of trifluoromethylated 1- or 2-aminophos-
phonic acids by a 1,3-proton shift reaction, which repre-
sents a reducing agent free, biomimetic, reductive amin-
ation.[3] Moreover, a facile synthetic protocol for the forma-
tion of 1,2-unsaturated trifluoromethyl ketones was
introduced by us.[4] This new and convenient one-pot pro-
cedure is based on the reaction of the anion derived from
alkylphosphonates with N-phenyltrifluoroacetimidoyl chlo-
ride followed by a reaction with an aldehyde and acid hy-
drolysis. Since it is well documented that 1,2-unsaturated
ketones are a class of reactive intermediates that give
Michael addition and/or aldol condensation products
through 1,4- or 1,2-addition, respectively, with various nu-
cleophiles, the chemical behaviour of this trifluoromethyl-
ated 1,2-unsaturated ketone attracted our interest. As a re-
sult of this investigation, we have found a synthetic method
leading to a 2-(trifluoromethyl)furan derivative with poten-
tial biological significance. The synthetic strategy used in
this method is helpful for the preparation of biologically
active small molecules and for their structural modifications
as well.
Scheme 1. Reagents and reaction conditions: [a] LDA (2 equiv.),
–70 °C; then CH3P(O)(OEt)2/ArCHO; then 2  HCl, 4 h.
As shown in Table 1, substrates bearing either electron-
withdrawing or electron-donating aryl substituents are ac-
commodated well in this reaction, giving good to excellent
yields. This method turns out to be practical and efficient
for the preparation of various 1,2-unsaturated trifluorome-
thyl ketones. Compounds 1c and 1f were previously re-
ported to be prepared by the reaction of 1,1,1-trifluoroacet-
aldehyde with p-substituted benzaldehydes.[5] Compound 1d
was prepared by the reaction of 1,2-unsaturated-3-methoxy-
ethyl trifluoromethyl ketone with N,N-dimethylaniline in
the presence of ZnCl2 in CH2Cl2.[6] Compound 1g was pre-
pared in a similar manner.[7] Our method is much better
than these since, in our case, the starting materials are easily
available and the reaction conditions are milder, offering
good yields. The spectroscopic data are reported in the elec-
tronic supporting information.
[a] State Key Laboratory of Bio-organic and Natural Products
Chemistry, Shanghai Institute of Organic Chemistry, Chinese
Academy of Sciences,
354 Fenglin Road, Shanghai 200032, China
Fax: +86-21-5492-5379
For the study of the chemical behaviour of 1, our prelimi-
nary attention was paid to the reaction of 1 with various
nucleophiles including nitroacetonitrile, ethoxyethene, 1-
E-mail: yuancy@mial.sioc.ac.cn
Supporting information for this article is available on the
WWW under http://www.eurjoc.org or from the author.
3916
© 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2007, 3916–3924

Preparation of 1,2-Unsaturated Trifluoromethyl Ketones
FULL PAPER
Table 1. Preparation of 1,2-unsaturated trifluoromethyl ketones.
In order to eliminate the influence of the trifluoromethyl
group through the conjugated system on the coupling reac-
tion, 2 was reduced by the Luche method. It was quite suc-
cessful, since all the sensitive groups in the substrates re-
mained unchanged (Table 3).
Entry
Compound
X
% Yield[a]
1
2
3
4
5
6
7
8
9
1a
1b
1c
1d
1e
1f
1g
1h
1i
H
85 (59)
80 (63)
84
72
79 (72)
79
67
81 (59)
94
CH3
OCH3
N(CH3)2
F
Cl
CN
Table 3. Reduction of compound 2.[a]
Entry
Compound
X
% Yield[b]
p-NO2
m-NO2
1
2
3
4
5
6
7
8
9
3a
H
77
93
85
3b
CH3
OCH3
N(CH3)2
F
Cl
CN
3c
[a] Yields of the products indicated in brackets were reported by us
previously.[4] The reported yields were significantly increased by
more carefully following the procedure.
3d+3dЈ
3e
48.5 and 22.1[c]
92
90
85
Ͼ99
62
3f
3g
3h
p-NO2
m-NO2
(trimethylsiloxy)cyclohexene, 1-cyclohex-1-enyl piperidine,
cyclohexanone, diethyl phosphite, trifluoroacetoacetate and
trifluoro-2,4-dioxopentylphosphonate under Michael ad-
dition reaction conditions. Unfortunately, all of these trials
failed as shown by the formation of inseparable mixtures
instead of the desired 1,4-addition products. These results
could be rationalized by the presence of the trifluoromethyl
group in this conjugated 1,2-unsaturated ketone system. Af-
ter we having finished this experimental work, a similar
phenomenon was reported by Nenejdenko et al. who
showed that trifluoromethyl enones gave 1,4-conjugated-ad-
dition products with ethyl nitroacetate only under special
reaction conditions, that is in the presences of calcinated
potassium fluoride as the base.[8] On the other hand, as
found by us, compound 1 underwent smoothly an aldol
condensation with acetone. This 1,2-addition was shown to
be an enantioselective process, when -proline was used as
the catalyst. This result will be reported by us elsewhere in
due course.[9]
3i
[a] Reduction occurred smoothly with NaBH4. [b] Isolated yields
based on compounds 2. [c] Ref.[10]
.
Compounds 3 are useful synthetic precursors in which
the strong electronic influence of the trifluoromethyl car-
bonyl group on the double bond is eliminated. Coupling of
3 with phenylacetylene catalyzed by transition metals
turned out to be successful (Scheme 2), providing good to
excellent yields (Table 4). During the period of the study on
this reaction, we also found that Pd(PPh3)4 and CuI to-
gether with triethylamine were more effective than
[PdCl2(PPh3)2], the classical catalyst in Sonogashira coup-
ling reactions.[11]
Here we wish to describe a novel synthetic protocol for
the preparation of 2-(trifluoromethyl)furans through the
following sequences of the reactions, starting from 1,2-un-
saturated trifluoromethyl ketones.
Compound 1 was transformed into the corresponding 1-
iodinated intermediate 2 by I2 in pyridine. Iodination pro-
ceeded smoothly at room temperature, and 48 h was usually
required for the completion of the reaction. The yield of
the iodination was quite satisfactory (Table 2).
Scheme 2. Reagents and reaction conditions: [a] I2, pyridine, CCl4;
[b] NaBH4, CeCl3·7H2O, CH3OH; [c] YC6H4CϵCH, Pd(PPh3)4,
CuI and NEt3, 50 °C under Ar; [d] 5 mol-% AgOTf, CH2ClCH2Cl,
80 °C.
Table 2. α-Iodination of 1,2-unsaturated trifluromethyl ketones.[a]
The unique structure of 4 makes it a very promising
building block for the synthesis of polysubstituted furans.
Previously, a variety of synthetic methods leading to poly-
substituted furans was reported including the cyclization of
3-alkynyl allylic alcohols under basic conditions[12] or cata-
lyzed by Ru[13] or Pd.[14] Recently, Qing’s group reported
the synthesis of trifluoroethylfurans by a Pd-catalyzed cycli-
zation.[11] However, they failed to obtain trifluoromethyl-
substituted furan derivatives by this strategy.[15] Since poly-
substituted furans have potential biological activities and
could be used as building blocks in natural-product synthe-
sis, our attention was paid to realizing the formation of
them starting from 4.
Entry
Compound
X
% Yield[b]
1
2
3
4
5
6
7
8
9
2a
2b
2c
2d
2e
2f
2g
2h
2i
H
72
83
80
CH3
OCH3
N(CH3)2
F
Cl
CN
[c]
–
92
72
68
55
65
p-NO2
m-NO2
[a] Compounds 1 were stirred under a N2 atmosphere in CCl4/
pyridine, treated with I2/CCl4/pyridine and stirred for 48 h at room
temperature. [b] Isolated yields based on compound 1. [c] Ref.[10]
,
the product is unstable.
Eur. J. Org. Chem. 2007, 3916–3924
© 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
3917

D. H. Zhang, C. Y. Yuan
FULL PAPER
Table 4. Pd-catalyzed reaction of 3 with terminal alkynes.[a]
After a series of efforts, we found that a AgOTf-catalyzed
intramolecular reaction[16] was fully satisfactory for our
purpose. It is well known that AgI-catalyzed cyclization re-
actions have been widely applied for a number of years.[17]
However, we found that the commonly used AgNO3 on sil-
ica gel had no effect on this reaction, as mentioned above.
At room temperature, AgOTf did not catalyze the reaction
either. However, when we tried the conditions given in the
literature, to our delight, this catalytic system showed high
activity under conditions. Most substrates were converted
smoothly to the expected 1-trifluoromethylfurans in good
to excellent yields (Table 5). We ascribed this mainly to the
use of ClCH2CH2Cl as solvent, which has a relatively high
boiling point.
Entry
Compound
X
Y
% Yield[b]
1
2
3
4
5
6
7
8
4a
4b
4c
4d
4e
4f
4g
4h
4i
4j
4k
4l
4m
4n
4o
4p
H
H
H
H
H
H
H
H
H
Cl
Cl
Cl
Cl
Cl
Cl
Cl
Cl
82
84
Ͼ99
97
88
88
94
89
88
87
80
83
82
84
85
83
CH3
OCH3
F
Cl
CN
p-NO2
m-NO2
H
CH3
N(CH3)3
F
9
10
11
12
13
14
15
16
Cl
CN
p-NO2
m-NO2
Table 5. Cyclization of 4 to α-(trifluoromethyl)furans catalyzed by
AgOTf.[a]
[a] The Sonogashira coupling process was modified: under Ar, a
mixture of 3, Pd(PPh3)4 and CuI was stirred and then followed by
the addition of Et3N and phenylacetylene. [b] Isolated yields based
on compounds 3.
Entry
Compound
X
Y
% Yield[b]
68
1
2
3
4
5
6
7
8
5a
5b
5c
5d
5e
5f
5g
5h
5i
5j
5k
5l
5m
5n
5o
5p
H
H
H
H
H
H
H
H
H
Cl
Cl
Cl
Cl
Cl
Cl
Cl
Cl
CH3
OCH3
F
Cl
CN
p-NO2
m-NO2
H
CH3
N(CH3)2
F
71
[c]
81
49
84
Our initial attempts at the conversion of 4 to 5 were fo-
cused on catalytic cyclization. It was not easy to select an
effective catalyst system. As found by us, even when
[PdCl2(PPh3)2] was used, only a 25% yield was obtained in
a low-polarity solvent such as cyclohexane. We assumed
that the low reaction yield may be associated with the re-
duction of Pd as shown by the formation Pd0 as black pre-
cipitates during the reaction. The reductive process could
not be reversed simply by the addition of an equiv. of an
oxidant such as Cu(OAc)2. It is interesting to note that
when the aprotic solvent THF or diisopropyl ether was ap-
plied as solvent, a small amount of dihydrofuran could be
obtained. However, in most cases, furans were obtained as
the main products. When other metal salts, such as
NaAuCl4·4H2O and Cu(OAc)2, were used, only an insepa-
rable mixture was obtained. We also examined the reactivity
of AgNO3 loaded on silica gel, but the result was also not
encouraging.
91
79[a]
65
9
10
11
12
13
14
15
16
66
[c]
71
78
Cl
CN
p-NO2
m-NO2
89[a]
76[a]
Ͼ99[a]
[a] The reaction took 48 h and 10 mol-% AgOTf was used, while
in other reaction system 5 mol-% AgOTf was used, and 24 h were
required for the reaction. [b] Isolated yield based on compound 4.
[c] As indicated by TLC, the reaction products are very compli-
cated; this is rationalized in the text.
The data in Table 5 demonstrate that substrates bearing
an electron-donating group (5c and 5k) were inactive in this
Scheme 3. A tentatively proposed catalytic cycle for the formation of 5.
3918
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© 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2007, 3916–3924

Preparation of 1,2-Unsaturated Trifluoromethyl Ketones
FULL PAPER
from CaH2 under N2. THF was freshly distilled from sodium under
N2 prior to use. Other reagents were purified by standard meth-
ods.[18] Column chromatography was performed with silica gel
(300–400 mesh). 1H NMR (300 MHz) and 19F NMR (282 MHz)
were recorded on a 300-MHz spectrometer with CDCl3 as the sol-
vent and tetramethylsilane (TMS) as the internal standard. Chemi-
cal shifts (δ) are reported in ppm relative to TMS. 19F NMR was
performed with CF3COOH as the external standard, downfield
shifts being designated as negative. IR spectra were obtained with
a Shimadzu IR-440 spectrometer. Mass spectra were obtained
reaction system. We supposed that the high electron density
of the substrates deactivated the catalytic capacity of Ag-
OTf by decomposition. Actually we indeed found some
black residue of silver in the reaction flask. It should also
be noted that substrates with electron-withdrawing groups
reacted more slowly than those bearing electron-donating
groups, though they provided pretty high yields. To clarify
this dilemma, we should first have a look at the plausible
mechanism of this cyclization (Scheme 3). In this mecha-
nism, AgOTf, acting as a Lewis acid, coordinates to the using EI ionization at 70 eV. All reactions were routinely monitored
by TLC.
triple bond, which greatly enhances the electrophilicity of
the latter moiety. However, the process is relatively difficult
for substrates bearing electron-withdrawing groups because
of their electron-deficiency. As a result, these substrates
usually react more slowly compared to others. But once this
process is complete, the more electron-deficient property
would make the hydroxyl group attack on the triple bond
easier, leading to the irreversibility of this reaction. There-
fore, it could be observed that yields are still high, although
the reaction rate seems slow.
General Procedure for Preparation of α,β-Unsaturated Trifluoro-
methyl Ketones 1: To a stirred solution of iPr2NH (20 mmol,
3.2 mL) in dry THF (40 mL) was added dropwise nBuLi (1.6  in
hexane; 20 mmol, 12.5 mL) at –78 °C. After 20 min, CH3P(O)-
(OEt)2 (10 mmol, 1.5 mL) was added. After the mixture was stirred
for 30 min at the same temperature, N-phenyltrifluoroacetimidyl
chloride (10 mmol, 1.60 mL) was gradually added with stirring,
and then the reaction mixture was kept at –70 °C for 1 h. A solu-
tion of substituted benzaldehyde (10 mmol, 1.51 g) in dry THF
(10 mL) was then added dropwise, and the temperature was main-
tained below –60 °C. The resulting mixture was then warmed to
room temperature over 2 h and stirred overnight. After the addition
of 2  HCl (20 mL) to the mixture, it was stirred at room tempera-
ture for another 4 h and then extracted with diethyl ether
(3ϫ20 mL). The combined extracts were washed successively with
5% aq NaHCO3 and brine until pH 6 was reached, and the organic
solution obtained was dried with anhydrous Na2SO4 and concen-
trated under reduced pressure. The crude product was subjected to
flash chromatography on silica gel (hexane/EtOAc = 5:1 to 20:1)
to afford pure 1.
To further confirm the configuration of the resulting α-
(trifluoromethyl)furans, compound 5h was examined by a
single-crystal X-ray analysis (see Figure 1).
1,1,1-Trifluoro-4-phenylbut-3-en-2-one (1a): Yellow oil, 1.71 g, 85%
3
yield. 1H NMR (300 MHz, CDCl3, 25 °C): δ = 7.97 (d, JH,H
=
3
16.2 Hz, 1 H, CH=CH), 7.66–7.42 (m, 5 H, Ar-H), 7.02 (d, JH,H
= 16.2 Hz, 1 H, CH=CH) ppm. 19F NMR (282 MHz, CDCl3,
25 °C): δ = –77.6 (s, 3 F, CF ) ppm. IR (KBr): ν = 1721, 1612,
˜
3
1600, 1578, 1452, 1266, 1147, 1059 cm–1. EI-MS: m/z (%) = 200 (6)
[M]+, 57 (100).
1,1,1-Trifluoro-4-(4-methylphenyl)but-3-en-2-one (1b): Light yellow
1
oil, 1.72 g, 80.2% yield. H NMR (300 MHz, CDCl3, 25 °C): δ =
3
3
7.88 (d, JH,H = 15.9 Hz, 1 H, CH=CH), 7.47 (d, JH,H = 8.4 Hz,
2 H, Ar-H), 7.18 (d, 3J = 8.4 Hz, 2 H, Ar-H), 6.90 (d, JH,H
=
3
15.9 Hz, 1 H, CH=CH), 2.34 (s, 3 H, CH3) ppm. 19F NMR
Figure 1. Crystal structure of compound 5h.
(282 MHz, CDCl3, 25 °C): δ = –77.5 (s, 3 F, CF3) ppm. IR (KBr):
ν = 1712, 1688, 1602, 1599, 1515, 1268, 1199, 1146, 1059 cm–1. EI-
˜
MS: m/z (%) = 214 (31) [M]+, 145 (100).
Conclusions
1,1,1-Trifluoro-4-(4-fluorophenyl)but-3-en-2-one (1e): Light yellow
solid, 1.72 g, 79% yield. M.p. 48–50 °C. 1H NMR (300 MHz,
An efficient synthesis leading to α-(trifluoromethyl)fu-
rans has been developed starting from the readily available
1,2-unsaturated trifluoromethyl ketones. Additionally, sev-
eral reactive intermediates with potential applications in or-
ganic synthesis, such as 1-iodinated 1,2-unsaturated trifluo-
roalkyl ketones and halogenated allylic alcohols, are de-
scribed.
3
CDCl3, 25 °C): δ = 7.93 (d, JH,H = 15.9 Hz, 1 H, CH=CH), 7.68–
3
7.63 (m, 2 H, Ar-H), 7.15 (t, JH,H = 8.1 Hz, 2 H, Ar-H), 6.94 (d,
3JH,H = 15.9 Hz, 1 H, CH=CH) ppm. 19F NMR (282 MHz,
CDCl3, 25 °C): δ = –77.6 (s, 3 F, CF3), –105.6 (m, 1 F) ppm. IR
(KBr): ν = 1712, 1612, 1590, 1510, 1420, 1323, 1266, 1160, 1141,
˜
1056 cm–1. EI-MS: m/z (%) = 218 (36) [M]+, 149 (100).
1,1,1-Trifluoro-4-(4-nitrophenyl)-but-3-en-2-one (1h): Yellow solid,
2.00 g, 81% yield. M.p. 98–99 °C. 1H NMR (300 MHz, CDCl3,
3
3
25 °C): δ = 8.32 (d, JH,H = 8.4 Hz, 2 H, Ar-H), 7.99 (d, JH,H
=
Experimental Section
3
15.9 Hz, 1 H, CH=CH), 7.83 (d, JH,H = 8.4 Hz, 2 H, Ar-H), 7.14
3
General Remarks: All reactions were performed under a N2 or Ar
atmosphere. Dichloromethane, iPr2NH, and Et3N were distilled
(d, JH,H = 15.9 Hz, 1 H, CH=CH) ppm. 19F NMR (282 MHz,
CDCl , 25 °C): δ = –77.7 (s, 3 F, CF ) ppm. IR (KBr): ν = 3082,
˜
3
3
Eur. J. Org. Chem. 2007, 3916–3924
© 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
3919

D. H. Zhang, C. Y. Yuan
FULL PAPER
1722, 1616, 1593, 1346, 1266, 1056 cm–1. EI-MS: m/z (%) = 245 (6)
(282 MHz, CDCl3, 25 °C): δ = –68.2 (s, 3 F, CF3) ppm. IR (KBr):
[M]+, 102 (100).
ν = 2227, 1707, 1581, 1415, 1300, 1199, 1158, 1094 cm–1. EI-MS:
˜
m/z (%) = 351 (24) [M]+, 127 (100). C11H5F3INO (351.07): calcd.
General Procedure for Preparation of α-Iodo α,β-Unsaturated Tri-
fluoromethyl Ketones 2: To a stirred solution of 1 (10 mmol) in
CCl4/pyridine (1:1, 40 mL) was added dropwise a solution of I2
(7.62 g, 30 mmol) in CCl4/pyridine (1:1, 40 mL) under an atmo-
sphere of N2 at 0 °C. The resulting mixture was then warmed to
room temperature and stirred for 48 h. Then 1  HCl (100 mL) was
added, and the mixture was extracted with diethyl ether
(3ϫ50 mL). The combined organic layers were washed with 1 
HCl until the pH turned acidic (approximately 4), and the layers
were treated with saturated aq NaHCO3 until neutral (this was es-
pecially essential since it facilitated layer separation). The organic
layers were again washed successively with saturated aqueous
Na2S2O3 and H2O, after which they were dried with anhydrous
Na2SO4 overnight and concentrated under reduced pressure. The
crude product was purified by flash chromatography on silica gel
(hexane/EtOAc = 5:1 to 20:1) to afford pure 2.
C 37.63, H 1.44, N 3.99; found C 37.79, H 1.54, N 4.00.
1,1,1-Trifluoro-3-iodo-4-(4-nitrophenyl)but-3-en-2-one (2h): Yellow
solid, 2.04 g, 55% yield. M.p. 73–74 °C. 1H NMR (300 MHz,
3
CDCl3, 25 °C): δ = 8.35 (d, JH,H = 9.0 Hz, 2 H, Ar-H), 8.24 (s, 1
3
H, =CH) 7.93 (d, JH,H = 9.0 Hz, 2 H, Ar-H) ppm. 19F NMR
(282 MHz, CDCl3, 25 °C): δ = –68.3 (s, 3 F, CF3) ppm. IR (KBr):
ν = 3108, 1709, 1603, 1573, 1523, 1414, 1342, 1202, 1158, 1093
˜
cm–1. EI-MS: m/z (%) = 371 (3) [M]+, 57 (100). C10H5ClF3IO
(371.06): calcd. C 32.37, H 1.36, N 3.77; found C 32.58, H 1.39, N
3.87.
1,1,1-Trifluoro-3-iodo-4-(3-nitrophenyl)but-3-en-2-one (2i): Yellow
solid, 2.41 g, 65% yield. M.p. 70–71 °C. 1H NMR (300 MHz,
3
CDCl3, 25 °C): δ = 8.73 (s, 1 H, Ar-H), 8.37 (d, JH,H = 8.7 Hz, 1
3
H, Ar-H), 8.24 (s, 1 H, =CH), 8.11 (d, JH,H = 7.8 Hz, 1 H, Ar-
3
H), 7.71 (t, JH,H = 7.5 Hz, 1 H) ppm. 19F NMR (282 MHz,
CDCl , 25 °C): δ = –68.1 (s, 3 F, CF ) ppm. IR (KBr): ν = 1702,
˜
3
3
1,1,1-Trifluoro-3-iodo-4-phenylbut-3-en-2-one (2a): Dark red oil
2.35 g, 72% yield. 1H NMR (300 MHz, CDCl3, 25 °C): δ = 8.23 (s,
1 H, =CH), 7.91–7.47 (m, 5 H, Ar-H) ppm. 19F NMR (282 MHz,
1589, 1532, 1444, 1352, 1277, 1164, 1101 cm–1. EI-MS: m/z (%) =
371 (32) [M]+, 302 (100). C10H5F3INO3 (371.06): calcd. C 32.37, H
1.36, N 3.77; found C 32.45, H 1.46, N 3.78.
CDCl , 25 °C): δ = –67.9 (s, 3 F, CF ) ppm. IR (KBr): ν = 1711,
˜
3
3
1588, 1570, 1448, 1305, 1204, 1149, 1112 cm–1. EI-MS: m/z (%) =
326 (8) [M]+, 102 (100). HRMS: calcd. for C10H6F3IO 325.9416;
found 325.9424.
General Procedure for Preparation of Halogenated Allylic Alcohols
3: To a solution of 2 (1 mmol) in CH3OH (7.5 mL) was added
CeCl3·7H2O (0.39 g, 1.05 mmol), and the solution was stirred for
10 min. NaBH4 (38 mg, 1 mmol) was then added. After the gas
release was over, the solution was stirred for another 30 min. Satu-
rated aqueous NH4Cl was added, and the solvent was removed
under reduced pressure, after which H2O was again added, and the
mixture was extracted with diethyl ether (3ϫ10 mL). The com-
bined organic layers were washed with brine and dried with anhy-
drous Na2SO4 overnight. The solvent was removed under reduced
pressure, and the residue was purified by flash chromatography on
silica gel (chloroform/hexane = 5:1 to 15:1) to afford pure 3.
1,1,1-Trifluoro-3-iodo-4-(4-methylphenyl)but-3-en-2-one (2b): Dark
1
red oil, 2.82 g, 83% yield. H NMR (300 MHz, CDCl3, 25 °C): δ
= 8.22 (s, 1 H, =CH), 7.87 (d, J = 8.4 Hz, 2 H, Ar-H), 7.31 (d,
3JH,H = 8.4 Hz, 2 H, Ar-H), 2.43 (s, 3 H, CH3) ppm. 19F NMR
(282 MHz, CDCl3, 25 °C): δ = –67.7 (s, 3 F, CF3) ppm. IR (KBr):
ν = 3030, 1706, 1608, 1583, 1562, 1303, 1203, 1149, 1105 cm–1. EI-
˜
MS: m/z (%) = 340 (45) [M]+, 116 (100). HRMS: calcd. for
C11H8F3IO 339.9572; found 339.9572.
1,1,1-Trifluoro-3-iodo-4-(4-methoxyphenyl)but-3-en-2-one (2c): Dark
(Z)-1,1,1-Trifluoro-3-iodo-4-phenylbut-3-en-2-ol (3a): White solid
253 mg, 77% yield. M.p. 52–53 °C. 1H NMR (300 MHz, CDCl3,
25 °C): δ = 7.56–7.38 (m, 5 H, Ar-H), 7.35 (s, 1 H, =CH), 4.50 (m,
1
red oil, 2.85 g, 80% yield. H NMR (300 MHz, CDCl3, 25 °C): δ
= 8.21 (s, 1 H, =CH), 8.05 (d, 3JH,H = 8.7 Hz, 2 H, Ar-H), 7.02 (d,
3JH,H = 8.7 Hz, 2 H, Ar-H), 3.90 (s, 3 H, OCH3) ppm. 19F NMR
(282 MHz, CDCl3, 25 °C): δ = –67.5 (s, 3 F, CF3) ppm. IR (KBr):
3
1 H, CHOH), 2.79 (d, JH,H = 8.4 Hz, 1 H, OH) ppm. 19F NMR
3
(282 MHz, CDCl3, 25 °C): δ = –75.9 (d, JH,F = 6.8 Hz, 3 F, CF3)
ν = 3075, 2904, 2844, 1700, 1605, 1581, 1560, 1427, 1373, 1263,
˜
ppm. IR (KBr): ν = 3323, 3026, 2725, 1624, 1496, 1446, 1254, 1174,
˜
1179, 1029 cm–1. EI-MS: m/z (%) = 356 (8) [M]+, 132 (100).
1079 cm–1. EI-MS: m/z (%) = 328 (8) [M]+, 132 (100). C10H8F3IO
HRMS: calcd. for C11H8F3IO2 355.9521; found 325.9525.
(328.07): calcd. C 36.61, H 2.46; found C 36.74, H 2.50.
1,1,1-Trifluoro-3-iodo-4-(4-fluorophenyl)but-3-en-2-one (2e): Dark
(Z)-1,1,1-Trifluoro-3-iodo-4-(4-methylphenyl)but-3-en-2-ol
(3b):
1
red oil, 3.16 g, 92% yield. H NMR (300 MHz, CDCl3, 25 °C): δ
White solid, 318 mg, yield: 93%. M.p.: 30–31 °C. 1H NMR
= 8.20 (s, 1 H, =CH), 7.96 (d, 3JH,H = 5.4 Hz, 1 H, Ar-H), 7.48 (d,
3
(300 MHz, CDCl3, 25 °C): δ = 7.46 (d, JH,H = 7.8 Hz, 2 H, Ar-
3
3JH,H = 5.4 Hz, 1 H, Ar-H), 7.21 (t, JH,H = 13 Hz, 2 H, Ar-H)
3
H), 7.29 (s, 1 H, =CH), 7.20 (d, JH,H = 7.8 Hz, 2 H, Ar-H), 4.46
ppm. 19F NMR (282 MHz, CDCl3, 25 °C): δ = –67.9 (s, 3 F, CF3),
3
(m, 1 H, CHOH), 2.84 (d, JH,H = 8.6 Hz, 1 H, OH), 2.36 (s, 3 H,
–105.6 (m, 1 F) ppm. IR (KBr): ν = 3079, 2928, 1711, 1597, 1509,
˜
CH3) ppm. 19F NMR (282 MHz, CDCl3, 25 °C): δ = –75.8 (d, 3JH,F
1303, 1242, 1162, 1097 cm–1. EI-MS: m/z (%) = 344 (29) [M]+, 40
= 6.5 Hz, 3 F, CF ) ppm. IR (KBr): ν = 3425, 3027, 2924, 1611,
˜
3
(100). HRMS: calcd. for C10H5F4IO 343.9321; found 343.9319.
1512, 1448, 1268, 1176, 1113, 1044 cm–1. EI-MS: m/z (%) = 342
(11) [M]+, 341 (100). C11H10F3IO (342.10): calcd. C 38.62, H 2.95;
found C 38.80, H 3.01.
4-(4-Chlorophenyl)-1,1,1-trifluoro-3-iodobut-3-en-2-one (2f): Yellow
solid, 2.60 g, 72% yield. M.p. 73–75 °C. 1H NMR (300 MHz,
3
CDCl3, 25 °C): δ = 8.18 (s, 1 H, =CH), 7.85 (d, JH,H = 8.4 Hz, 2
(Z)-1,1,1-Trifluoro-3-iodo-4-(4-methoxyphenyl)but-3-en-2-ol
(3c):
3
H, Ar-H), 7.48 (d, JH,H = 8.4 Hz, 2 H, Ar-H) ppm. 19F NMR
Orange oil, 304 mg, 85% yield. 1H NMR (300 MHz, CDCl3,
(282 MHz, CDCl3, 25 °C): δ = –67.9 (s, 3 F, CF3) ppm. IR (KBr):
3
25 °C): δ = 7.57 (d, JH,H = 12.0 Hz, 2 H, Ar-H), 7.27 (s, 1 H,
ν = 3095, 1698, 1582, 1491, 1411, 1201, 1155, 1091, 1010 cm–1. EI-
˜
=CH), 6.93 (d, 3JH,H = 12.0 Hz, 2 H, Ar-H), 4.46 (m, 1 H, CHOH),
MS: m/z (%) = 360 (3.9) [M]+ 136 (100). C10H5ClF3IO (360.50):
3.84 (s, 3 H, OCH3), 2.82 (s, 1 H, OH) ppm. 19F NMR (282 MHz,
calcd. C 33.32, H 1.40; found C 33.47, H 1.36.
3
CDCl3, 25 °C): δ = –75.9 (d, JH,F = 6.2 Hz, 3 F, CF3) ppm. IR
4-(4-Cyanophenyl)-1,1,1-trifluoro-3-iodobut-3-en-2-one (2g): Yellow
(KBr): ν = 3441, 3007, 2912, 2841, 1607, 1511, 1464, 1255, 1179,
˜
solid, 2.39 g, 68% yield. M.p. 80–81 °C. 1H NMR (300 MHz,
1031 cm–1. EI-MS: m/z (%) 358 (14) [M]+, 357 (100).
=
3
CDCl3, 25 °C): δ = 8.20 (s, 1 H, =CH), 7.89 (d, JH,H = 8.7 Hz, 2 C11H10F3IO2 (358.10): calcd. C 36.90, H 2.81; found C 37.01, H
3
H, Ar-H), 7.78 (d, JH,H = 8.7 Hz, 2 H, Ar-H) ppm. 19F NMR 2.99.
3920
www.eurjoc.org
© 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2007, 3916–3924

Preparation of 1,2-Unsaturated Trifluoromethyl Ketones
FULL PAPER
3JH,H = 7.5 Hz, 1 H, Ar-H), 7.60 (t, JH,H = 7.8 Hz, 1 H, Ar-H),
3
(Z)-4-[4-(Dimethylamino)phenyl]-1,1,1-trifluoro-3-iodobut-3-en-2-ol
(3d): Dark red solid, 180 mg, 48.5% yield. M.p. 53–56 °C. 1H NMR
7.43 (s, 1 H, =CH), 4.62 (m, 1 H, CHOH), 3.00 (d, J = 7.5 Hz, 1
3
(300 MHz, CDCl3, 25 °C): δ = 7.53 (d, JH,H = 9.0 Hz, 2 H, Ar- H, OH) ppm. 19F NMR (282 MHz, CDCl3, 25 °C): δ = –75.8 (d,
3
H), 7.11 (s, 1 H, =CH), 6.62 (d, JH,H = 9.0 Hz, 2 H, Ar-H), 4.33 3JH,F = 6.5 Hz, 3 F, CF ) ppm. IR (KBr): ν = 3469, 3088, 2926,
˜
3
3
(m, 1 H, CHOH), 2.91 [s, 6 H, N(CH3)2], 2.82 (d, JH,H = 4.2 Hz, 1616, 1529, 1354, 1267, 1177, 1130 cm–1. EI-MS: m/z (%) = 373 (49)
1 H, OH) ppm. 19F NMR (282 MHz, CDCl3, 25 °C): δ = –75.8 (d,
[M]+, 102 (100). C10H7F3INO3 (373.07): calcd. C 32.20, H 1.89, N
3.75; found C 32.28, H 2.09, N 3.70.
3JH,F = 5.6 Hz, 3 F, CF ) ppm. IR (KBr): ν = 3376, 2443, 1705,
˜
3
1609, 1523, 1366, 1271, 1169, 1128, 1062 cm–1. ESI-MS: m/z =
371.9 [M + H]+, 390.0 [M + CH3OH + H]+. HRMS: calcd. for
C12H13F3INO 370.9994; found 371.0003.
General Procedure for Preparation of Allylic Alcohols 4: To a 25-mL
flask purged with Ar was added 3 (1 mmol), Pd(PPh3)4 (57.5 mg,
0.05 mmol, 5 mol-%) and CuI (19.1 mg, 0.1 mmol, 10 mol-%). Dis-
tilled Et3N (6 mL) was then added dropwise to the solution. After
stirring for 30 min, phenylacetylene (0.17 mL, 153 mg, 1.5 mmol)
was added slowly into the mixture. The reaction system was then
warmed to 40–50 °C and kept at that temperature for 12 h. The
mixture was filtered, and the filtrate was extracted with diethyl
ether (3ϫ10 mL) and dried with anhydrous Na2SO4 overnight. The
solvent was removed under reduced pressure, and the residue was
purified by flash chromatography on silica gel (chloroform/hexane
= 5:1 to 15:1) to afford pure 4.
(Z)-1,1,1-Trifluoro-3-iodo-4-[4-(methylamino)phenyl]but-3-en-2-ol
1
(3dЈ): Brown oil, 82 mg, 22.1% yield. H NMR (300 MHz, CDCl3,
25 °C): δ = 7.56 (d, 3JH,H = 8.7 Hz, 2 H, Ar-H), 7.18 (s, 1 H, =CH),
6.60 (d, 3JH,H = 8.7 Hz, 2 H), 4.41 (q, 3JH,H = 6 Hz, 1 H, CHOH),
2.92 (s, 3 H, NHCH3), 3.29 (br., 2 H, OH, NHCH3) ppm. 19F
3
NMR (282 MHz, CDCl3, 25 °C): δ = –75.8 (d, JH,F = 5.6 Hz, 3
F, CF ) ppm. IR (KBr): ν = 3396, 1705, 1614, 1523, 1274, 1171,
˜
3
1129 cm–1. ESI-MS: m/z = 357.9 [M + H]+, 404 [M + CH3OH +
H]+.
(E)-1,1,1-Trifluoro-4-phenyl-3-(2-phenylethynyl)but-3-en-2-ol (4a):
White solid, 248 mg, 82 % yield. M.p. 77–78 °C. 1H NMR
(300 MHz, CDCl3, 25 °C): δ = 7.93 (d, JH,H = 8.4 Hz, 2 H, Ar-
(Z)-1,1,1-Trifluoro-4-(4-fluorophenyl)-3-iodobut-3-en-2-ol (3e): Light
yellow oil, 318 mg, 92% yield. 1H NMR (300 MHz, CDCl3, 25 °C):
δ = 7.46 (dd, J1 = 5.7 Hz, JH,H = 8.4 Hz, 2 H, Ar-H), 7.23 (s, 1
3
3
H), 7.53–7.34 (m, 8 H, Ar-H), 6.96 (s, 1 H, =CH), 4.64 (m, 1 H,
H, =CH), 7.02 (m, 2 H, Ar-H), 4.42 (m, 1 H, CHOH), 2.84 (s, 1
3
CF3CH), 2.84 (d, JH,H = 9.0 Hz, 1 H, OH) ppm. 19F NMR: δ =
H, OH) ppm. 19F NMR (282 MHz, CDCl3, 25 °C): δ = –75.8 (d,
–77.5 (d, 3JH,F = 6.6 Hz, 3 F, CF ) ppm. IR (KBr): ν = 3479, 3088,
˜
3JH,F = 5.9 Hz, 3 F, CF ), –111.3 (m, 1 F) ppm. IR (KBr): ν =
3
˜
3
3067, 2195, 1607, 1491, 1251, 1190, 1116, 1074 cm–1. EI-MS: m/z
(%) = 302 (4) [M]+, 105 (100). C18H13F3O (302.30): calcd. C 71.52,
H 4.33; found C 71.28, H 4.41.
3440, 2923, 1897, 1624, 1603, 1509, 1413, 1268, 1180, 1098 cm–1.
EI-MS: m/z (%) = 346 (12) [M]+, 345 (100). C10H7F4IO (346.06):
calcd. C 34.71, H 2.04; found C 34.63, H 2.01.
(E)-1,1,1-Trifluoro-4-(4-methylphenyl)-3-(2-phenylethynyl)but-3-en-
2-ol (4b): Light yellow oil, 265 mg, 84% yield. 1H NMR (300 MHz,
(Z)-4-(4-Chlorophenyl)-1,1,1-trifluoro-3-iodobut-3-en-2-ol (3f): White
solid, 326 mg, 90 % yield. M.p. 92–95 °C. 1H NMR (300 MHz,
3
CDCl3, 25 °C): δ = 7.74 (d, JH,H = 7.8 Hz, 2 H, Ar-H), 7.43–7.27
3
CDCl3, 25 °C): δ = 7.48 (d, JH,H = 8.6 Hz, 2 H, Ar-H), 7.20 (d,
3
(m, 5 H, Ar-H), 7.13 (d, JH,H = 7.8 Hz, 2 H, Ar-H), 6.62 (s, 1 H,
3JH,H = 8.6 Hz, 2 H, Ar-H), 7.30 (s, 1 H, =CH), 4.51 (m, 1 H,
CHOH), 2.89 (d, J = 7.5 Hz, 1 H, OH) ppm. 19F NMR (282 MHz,
=CH), 4.53 (q, 3JH,H = 5.1 Hz, 1 H, CF3CH), 2.83 (br., 1 H, OH),
2.29 (s, 3 H, CH3) ppm. 19F NMR (282 MHz, CDCl3, 25 °C): δ =
3
CDCl3, 25 °C): δ = –75.8 (d, JH,F = 6.5 Hz, 3 F, CF3) ppm. IR
–77.5 (d, 3JH,F = 5.1 Hz, 3 F, CF ) ppm. IR (KBr): ν = 3451, 3032,
˜
3
(KBr): ν = 3434, 2927, 1905, 1625, 1593, 1490, 1403, 1267, 1175,
˜
2925, 2199, 1608, 1512, 1491, 1443, 1270, 1171, 1069 cm–1. EI-MS:
m/z (%) = 316 (26) [M]+, 204 (26), 105 (100), 91 (16), 77 (19), 63
(9), 51 (18). C19H15F3O (316.33): calcd. C 72.14, H 4.78; found C
72.56, H 4.98.
1092 cm–1. EI-MS: m/z (%) = 364 (2) [M + 2]+, 363 (18), 262 (6)
[M]+, 261 (53), 294 (16), 292 (55), 174 (10), 131 (100), 101 (41), 75
(43), 69 (28), 63 (18), 51 (42), 41 (2). C10H7ClF3IO (362.52): calcd.
C 33.13, H 1.95; found C 33.45, H 1.92.
(E)-1,1,1-Trifluoro-4-(4-methoxyphenyl)-3-(2-phenylethynyl)but-3-
(Z)-4-(4-Cyanophenyl)-1,1,1-trifluoro-3-iodobut-3-en-2-ol (3g): Yel-
low solid, 300 mg, 85 % yield. M.p. 118–119 °C. 1H NMR
1
en-2-ol (4c): Yellow solid, 332 mg, Ͼ99% yield. M.p. 80–83 °C. H
3
NMR (300 MHz, CDCl3, 25 °C): δ = 7.91 (d, JH,H = 8.4 Hz, 2 H,
3
(300 MHz, CDCl3, 25 °C): δ = 7.70 (d, JH,H = 8.1 Hz, 2 H, Ar-
Ar-H), 7.54–7.34 (m, 5 H, Ar-H), 6.93 (d, 3JH,H = 8.4 Hz, 2 H, Ar-
H), 6.86 (s, 1 H, =CH), 4.60 (m, 1 H, CF3CH), 3.85 (s, 3 H, OCH3),
3
H), 7.62 (d, JH,H = 8.1 Hz, 2 H, Ar-H), 7.40 (s, 1 H, =CH), 4.59
3
(m, 1 H, CHOH), 2.98 (d, JH,H = 7.5 Hz, 1 H, OH) ppm. 19F
3
2.83 (d, JH,H = 8.7 Hz, 1 H, OH) ppm. 19F NMR (282 MHz,
3
NMR (282 MHz, CDCl3, 25 °C): δ = –75.8 (d, JH,F = 6.2 Hz, 3
3
CDCl3, 25 °C): δ = –77.6 (d, JH,F = 7.2 Hz, 3 F, CF3) ppm. IR
F, CF ) ppm. IR (KBr): ν = 3414, 2920, 2233, 1926, 1605, 1503,
˜
3
(KBr): ν = 3449, 3082, 2841, 2198, 1604, 1512, 1491, 1443, 1259,
˜
1411, 1348, 1267, 1175, 1132, 1019 cm–1. EI-MS: m/z (%) = 353
(77) [M]+, 284 (100). C11H7F3INO (353.08): calcd. C 37.42, H 2.00,
N 3.97; found C 36.99, H 2.21, N 3.79.
1178, 1070 cm–1. EI-MS: m/z (%) = 332 (18) [M]+, 105 (100).
C19H15F3O2 (332.33): calcd. C 68.67, H 4.55; found C 68.44, H
4.32.
(Z)-1,1,1-Trifluoro-3-iodo-4-(4-nitrophenyl)but-3-en-2-ol (3h):
(E)-1,1,1-Trifluoro-4-(4-fluorophenyl)-3-(2-phenylethynyl)but-3-en-
2-ol (4d): White solid, 310 mg, 97% yield. M.p. 79–80 °C. 1H NMR
(300 MHz, CDCl3, 25 °C): δ = 7.93 (t, 3JH,H = 7.5 Hz, 2 H, Ar-H),
7.52–7.38 (m, 5 H, Ar-H), 7.10 (t, 3JH,H = 8.7 Hz, 2 H, Ar-H), 6.93
Brown oil, 373 mg, Ͼ99 % yield. 1H NMR (300 MHz, CDCl3,
3
3
25 °C): δ = 8.27 (d, JH,H = 8.4 Hz, 2 H, Ar-H), 7.68 (d, JH,H
=
8.4 Hz, 2 H, Ar-H), 7.45 (s, 1 H, =CH), 4.61 (m, 1 H, CHOH), 2.92
(d, 3JH,H = 6.6 Hz, 1 H, OH) ppm. 19F NMR (282 MHz, CDCl3): δ
3
(s, 1 H, =CH), 4.64 (m, 1 H, CF3CH), 2.83 (d, JH,H = 8.4 Hz, 1
3
H, OH) ppm. 19F NMR (282 MHz, CDCl3, 25 °C): δ = –77.5 (d,
= –75.8 (d, JH,F = 6.2 Hz, 3 F, CF ) ppm. IR (KBr): ν = 3464,
˜
3
2983, 2854, 1596, 1519, 1347, 1267, 1177, 1130, 1014 cm–1. EI-MS:
m/z (%) = 373 (14) [M]+ , 131 (100). HRMS: calcd. for
C10H7F3INO3 372.9423; found 372.9424.
3JH,F = 6.3 Hz, 3 F, CF ), –110.3 (m, 1 F) ppm. IR (KBr): ν =
˜
3
3474, 3039, 2195, 1602, 1509, 1490, 1442, 1251, 1192, 1116, 1074
cm–1. EI-MS: m/z (%) = 320 (52) [M]+, 105 (100). C18H12F4O
(320.29): calcd. C 67.50, H 3.78; found C 67.55, H 3.80.
(Z)-1,1,1-Trifluoro-3-iodo-4-(3-nitrophenyl)but-3-en-2-ol (3i): Brown
oil, 231 mg, 62% yield. 1H NMR (300 MHz, CDCl3, 25 °C): δ =
(E)-4-(4-Chlorophenyl)-1,1,1-trifluoro-3-(2-phenylethynyl)but-3-en-
2-ol (4e): White solid, 296 mg, 88% yield. M.p. 94–96 °C. 1H NMR
3
8.42 (s, 1 H, Ar-H), 8.24 (d, JH,H = 8.4 Hz, 1 H, Ar-H), 7.84 (d,
Eur. J. Org. Chem. 2007, 3916–3924
© 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
3921

D. H. Zhang, C. Y. Yuan
FULL PAPER
(300 MHz, CDCl3, 25 °C): δ = 7.87 (d, JH,H = 7.4 Hz, 2 H, Ar- M.p. 124–126 °C. 1H NMR (300 MHz, CDCl3, 25 °C): δ = 7.84 (d,
3
H), 7.52–7.37 (m, 7 H, Ar-H), 6.92 (s, 1 H, =CH), 4.64 (m, 1 H, 3JH,H = 8.7 Hz, 2 H, Ar-H), 7.44 (d, JH,H = 8.7 Hz, 2 H, Ar-H),
3
3
3
3
CF3CH), 2.82 (d, JH,H = 8.4 Hz, 1 H, OH) ppm. 19F NMR
7.34 (d, JH,H = 8.7 Hz, 2 H, Ar-H), 6.82 (d, JH,H = 8.7 Hz, 2 H,
3
(282 MHz, CDCl3, 25 °C): δ = –77.5 (d, JH,F = 6.6 Hz, 3 F, CF3) Ar-H), 7.03 (s, 1 H, =CH), 4.57 (m, 1 H, CF3CH), 3.03 [s, 6 H,
3
ppm. IR (KBr): ν = 3468, 3086, 2194, 1589, 1490, 1442, 1252, 1194,
N(CH3)2], 2.71 (d, JH,H = 7.8 Hz, 1 H, OH) ppm. 19F NMR
˜
3
1096, 1012 cm–1. EI-MS: m/z (%) = 336 (15) [M]+, 105 (100).
(282 MHz, CDCl3, 25 °C): δ = –77.4 (d, JH,F = 6.0 Hz, 3 F, CF3)
C18H12ClF3O (336.74): calcd. C 64.20, H 3.59; found C 64.30, H ppm. IR (KBr): ν = 3524, 2904, 2819, 2185, 1612, 1599, 1525, 1491,
˜
3.52.
1368, 1195, 1126, 1087 cm–1. EI-MS: m/z (%) = 380 (5) [M]+, 379
(20), 282 (8), 267 (8), 202 (5), 122 (8), 101 (6), 50 (7), 44 (100).
C20H17ClF3NO (379.81): calcd. C 63.25, H 4.51, N 3.69; found C
63.73, H 4.55, N 3.47.
(E)-4-(4-Cyanophenyl)-1,1,1-trifluoro-3-(2-phenylethynyl)but-3-en-2-
ol (4f): Yellow solid, 289 mg, 88 % yield. M.p. 119–120 °C. 1H
3
NMR (300 MHz, CDCl3, 25 °C): δ = 8.01 (d, JH,H = 8.4 Hz, 2 H,
Ar-H), 7.69 (d, 3JH,H = 8.4 Hz, 2 H, Ar-H), 7.51–7.36 (m, 5 H, Ar-
(E)-3-[2-(4-Chlorophenyl)ethynyl]-1,1,1-trifluoro-4-(4-fluorophenyl)-
but-3-en-2-ol (4l): White solid, 294 mg, 83% yield. M.p. 83–84 °C.
3
H), 7.01 (s, 1 H, =CH), 4.70 (m, 1 H, CF3CH), 2.91 (d, JH,H
=
3
1H NMR (300 MHz, CDCl3, 25 °C): δ = 7.91 (d, JH,H = 5.4 Hz,
8.1 Hz, 1 H, OH) ppm. 19F NMR (282 MHz, CDCl3, 25 °C): δ =
3
3
–77.3 (d, 3JH,F = 6.9 Hz, 3 F, CF ) ppm. IR (KBr): ν = 3385, 2237,
1 H, Ar-H), 7.88 (d, JH,H = 5.4 Hz, 1 H, Ar-H), 7.42 (d, JH,H
=
˜
3
3
2198, 1601, 1489, 1338, 1261, 1168, 1139, 1124 cm–1. EI-MS: m/z
(%) = 327 (39) [M]+, 105 (100). C19H12F3NO (327.31): calcd. C
69.72, H 3.70, N 4.28; found C 69.67, H 3.69, N 4.17.
8.4 Hz, 2 H, Ar-H), 7.35 (d, JH,H = 8.4 Hz, 2 H, Ar-H), 7.09 (t,
3JH,H = 4.8 Hz, 2 H, Ar-H), 6.95 (s, 1 H, =CH), 4.64 (m, 1 H,
CF3CH), 2.77 (d, JH,H = 7.8 Hz, 1 H, OH) ppm. 19F NMR
3
3
(282 MHz, CDCl3, 25 °C): δ = –77.5 (d, JH,F = 6.9 Hz, 3 F, CF3),
(E)-1,1,1-Trifluoro-4-(4-nitrophenyl)-3-(2-phenylethynyl)but-3-en-2-
ol (4g): Yellow solid, 326 mg, 94 % yield. M.p. 147–149 °C. 1H
NMR (300 MHz, CDCl3, 25 °C): δ = 7.93 (d, JH,H = 7.5 Hz, 2 H,
–110.1 (m, 1 F) ppm. IR (KBr): ν = 3340, 2202, 1600, 1509, 1490,
˜
1346, 1257, 1196, 1125, 1014 cm–1. EI-MS: m/z (%) = 355 (13)
[M]+, 139 (100). C18H11ClF4O (354.73): calcd. C 60.95, H 3.13;
found C 60.94, H 3.14.
3
Ar-H), 7.55–7.34 (m, 7 H, Ar-H), 6.96 (s, 1 H, =CH), 4.64 (m, 1
H, CF3CH), 2.85 (d, JH,H = 8.7 Hz, 1 H, OH) ppm. 19F NMR
3
3
(E)-3-[2-(4-Chlorophenyl)ethynyl]-4-(4-chlorophenyl)-1,1,1-trifluoro-
but-3-en-2-ol (4m): White solid, 304 mg, 82% yield. M.p. 86–88 °C.
(282 MHz, CDCl3, 25 °C): δ = –77.5 (d, JH,F = 6.9 Hz, 3 F, CF3)
ppm. IR (KBr): ν = 3469, 2199, 1593, 1503, 1336, 1259, 1182, 1120
˜
3
1H NMR (300 MHz, CDCl3, 25 °C): δ = 8.26 (d, JH,H = 8.7 Hz,
cm–1. EI-MS: m/z (%) = 347 (17) [M]+, 105 (100). C18H12F3NO3
(347.30): calcd. C 62.25, H 3.48, N 4.03; found C 62.13, H 3.63, N
3.81.
3
3
2 H, Ar-H), 8.04 (d, JH,H = 8.7 Hz, 2 H, Ar-H), 7.42 (d, JH,H
=
3
8.7 Hz, 2 H), 7.37 (d, JH,H = 8.7 Hz, 2 H), 7.10 (s, 1 H, =CH),
3
4.75 (m, 1 H, CF3CH), 3.06 (d, JH,H = 7.5 Hz, 1 H, OH) ppm.
(E)-1,1,1-Trifluoro-4-(3-nitrophenyl)-3-(2-phenylethynyl)but-3-en-2-
ol (4h): Yellow solid, 309 mg, 89 % yield. M.p. 119–120 °C. 1H
NMR (300 MHz, CDCl3, 25 °C): δ = 9.19 (t, JH,H = 2.1 Hz, 1 H,
Ar-H), 8.21 (d, JH,H = 11.4 Hz, 1 H, Ar-H), 7.99 (d, JH,H
11.4 Hz, 1 H, Ar-H), 7.62–7.38 (m, 6 H, Ar-H), 7.04 (s, 1 H, =CH),
19F NMR (282 MHz, CDCl3, 25 °C): δ = –77.2 (d, JH,F = 5.1 Hz,
3
3 F, CF ) ppm. IR (KBr): ν = 3358, 1901, 1490, 1344, 1256, 1198,
˜
3
3
1125, 1093, 1013 cm–1. EI-MS: m/z (%) = 371 (56) [M]+, 231 (100).
C18H11Cl2F3O (371.19): calcd. C 58.25, H 2.99; found C 58.05, H
3.17.
3
3
=
3
4.71 (m, 1 H, CF3CH), 2.85 (d, JH,H = 7.8 Hz, 1 H, OH) ppm.
(E)-3-[2-(4-Chlorophenyl)ethynyl]-4-(4-cyanophenyl)-1,1,1-trifluoro-
but-3-en-2-ol (4n): Yellow solid, 304 mg, 84% yield. M.p. 127–
19F NMR (282 MHz, CDCl3, 25 °C): δ = –77.3 (d, 3JH,F = 7.5 Hz,
3 F, CF ) ppm. IR (KBr): ν = 3547, 2193, 1525, 1491, 1348, 1271,
˜
3
1
3
128 °C. H NMR (300 MHz, CDCl3, 25 °C): δ = 7.97 (d, JH,H
=
1157, 1130, 1072 cm–1. EI-MS: m/z (%) = 347 (1) [M]+, 105 (100).
C18H12F3NO3 (347.30): calcd. C 62.25, H 3.48, N 4.03; found C
62.31, H 3.62, N 3.91.
3
8.1 Hz, 2 H, Ar-H), 7.69 (d, JH,H = 8.1 Hz, 2 H, Ar-H), 7.41 (d,
3JH,H = 8.7 Hz, 2 H, Ar-H), 7.37 (d, JH,H = 8.7 Hz, 2 H, Ar-H),
3
7.03 (s, 1 H, =CH), 4.71 (m, 1 H, CF3CH), 2.90 (d, J = 7.8 Hz, 1
H, OH) ppm. 19F NMR (282 MHz, CDCl3, 25 °C): δ = –77.3 (d,
(E)-3-[2-(4-Chlorophenyl)ethynyl]-1,1,1-trifluoro-4-phenylbut-3-en-
2-ol (4i): White solid, 296 mg, 88% yield. M.p. 71–73 °C. 1H NMR
(300 MHz, CDCl3, 25 °C): δ = 7.88 (d, JH,H = 7.2 Hz, 2 H, Ar-
3JH,H = 6.6 Hz, 3 F, CF ) ppm. IR (KBr): ν = 3364, 2241, 2199,
˜
3
3
1601, 1589, 1490, 1344, 1259, 1182, 1124, 1013 cm–1. EI-MS: m/z
(%) = 362 (8) [M]+, 44 (100). C19H11ClF3NO (361.75): calcd. C
63.08, H 3.06, N 3.87; found C 63.41, H 3.23, N 3.68.
H), 7.42–7.31 (m, 7 H, Ar-H), 6.97 (s, 1 H, =CH), 4.68 (m, 1 H,
CF3CH), 2.91 (d, JH,H = 8.1 Hz, 1 H, OH) ppm. 19F NMR
3
3
(282 MHz, CDCl3, 25 °C): δ = –77.4 (d, JH,F = 6.9 Hz, 3 F, CF3)
(E)-3-[2-(4-Chlorophenyl)ethynyl]-1,1,1-trifluoro-4-(4-nitrophenyl)-
but-3-en-2-ol (4o): Yellow solid, 324 mg, 85% yield. M.p. 128–
ppm. IR (KBr): ν = 3449, 1490, 1334, 1255, 1176, 1128, 1089, 1014
˜
cm–1. EI-MS: m/z (%) = 336 (16) [M]+, 139 (100). HRMS: calcd.
1
3
129 °C. H NMR (300 MHz, CDCl3, 25 °C): δ = 8.27 (d, JH,H
=
for C18H12ClF3O 336.0529; found 336.0525.
3
8.4 Hz, 2 H, Ar-H), 8.04 (d, JH,H = 8.4 Hz, 2 H, Ar-H), 7.43 (d,
3JH,H = 8.1 Hz, 2 H), 7.38 (d, JH,H = 8.1 Hz, 2 H, Ar-H), 7.10 (s,
3
(E)-3-[2-(4-Chlorophenyl)ethynyl]-1,1,1-trifluoro-4-(4-methylphenyl)-
but-3-en-2-ol (4j): White solid, 305 mg, 87% yield. M.p. 81–83 °C.
1 H, =CH), 4.73 (m, 1 H, CF3CH), 2.82 (d, J = 7.5 Hz, 1 H, OH)
1H NMR (300 MHz, CDCl3, 25 °C): δ = 7.80 (d, JH,H = 8.1 Hz,
3
3
ppm. 19F NMR (282 MHz, CDCl3, 25 °C): δ = –77.2 (d, JH,F
=
3
3
2 H, Ar-H), 7.42 (d, JH,H = 6.3 Hz, 2 H, Ar-H), 7.34 (d, JH,H
=
6.9 Hz, 3 F, CF ) ppm. IR (KBr): ν = 3481, 2197, 1594, 1515, 1490,
˜
3
3
1343, 1261, 1179, 1139, 1013 cm–1. EI-MS: m/z (%) = 381 (21)
[M]+, 202 (100). C18H11ClF3NO3 (381.74): calcd. C 56.64, H 2.90,
N 3.67; found C 56.83, H 3.09, N 3.50.
6.3 Hz, 2 H, Ar-H), 7.22 (d, JH,H = 8.1 Hz, 2 H, Ar-H), 6.94 (s, 1
H, =CH), 4.53 (m, 1 H, CF3CH), 2.84 (d, 3JH,H = 6 Hz, 1 H, OH),
2.38 (s, 3 H, CH3) ppm. 19F NMR (282 MHz, CDCl3, 25 °C): δ =
–77.5 (d, 3JH,F = 5.1 Hz, 3 F, CF ) ppm. IR (KBr): ν = 3467, 2924,
˜
3
(E)-3-[2-(4-Chlorophenyl)ethynyl]-1,1,1-trifluoro-4-(3-nitrophenyl)-
but-3-en-2-ol (4p): Yellow solid, 317 mg, 83% yield. M.p. 101–
1603, 1580, 1490, 1254, 1173, 1125, 1013 cm–1. EI-MS: m/z (%) =
350 (6) [M]+, 139 (100). C19H14ClF3O (350.77): calcd. C 65.06, H
4.02; found C 65.03, H 4.03.
1
3
103 °C. H NMR (300 MHz, CDCl3, 25 °C): δ = 9.21 (t, JH,H
=
3
2.1 Hz, 1 H, Ar-H), 8.22 (d, JH,H = 11.7 Hz, 1 H, Ar-H), 7.93 (d,
(E)-3-[2-(4-Chlorophenyl)ethynyl]-4-[4-(dimethylamino)phenyl]- 3JH,H = 8.1 Hz, 1 H, Ar-H), 7.61–7.36 (m, 5 H, Ar-H), 7.07 (s, 1
1,1,1-trifluorobut-3-en-2-ol (4k): Orange solid, 304 mg, 80% yield.
3
H, =CH), 4.71 (m, 1 H, CF3CH), 2.85 (d, JH,H = 7.2 Hz, 1 H,
3922
www.eurjoc.org
© 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2007, 3916–3924

Preparation of 1,2-Unsaturated Trifluoromethyl Ketones
FULL PAPER
OH) ppm. 19F NMR (282 MHz, CDCl3, 25 °C): δ = –77.3 (d, 3JH,F
3JH,H = 8.4 Hz, 2 H, Ar-H), 7.40–7.26 (m, 5 H, Ar-H), 6.44 (s, 1 H,
= 7.5 Hz, 3 F, CF ) ppm. IR (KBr): ν = 3529, 3114, 2196, 1651,
furan-H), 4.06 (s, 2 H, ArCH2) ppm. 19F NMR (282 MHz, CDCl3,
˜
3
1590, 1527, 1492, 1351, 1270, 1160, 1074, 1012 cm–1. EI-MS: m/z
25 °C): δ = –61.0 (s, 3 F, CF ) ppm. IR (KBr): ν = 3076, 2927,
˜
3
(%) = 381 (2) [M]+, 139 (100). C18H11ClF3NO3 (381.74): calcd. C 2852, 1606, 1556, 1519, 1487, 1400, 1344, 1328, 1179, 1036 cm–1.
56.64, H 2.90, N 3.67; found C 56.77, H 3.03, N 3.59.
EI-MS: m/z (%) = 347 (100) [M]+. C18H12F3NO3 (347.30): calcd.
C 62.25, H 3.48, N 4.03; found C 62.13, H 3.38, N 3.91.
General Procedure for Preparation of Substituted 2-(Trifluoro-
methyl)furans 5: A mixture of 4 (69.4 mg, 0.2 mmol), AgOTf (3 mg,
0.01 mmol, 5 mol-%) and 1,2-dichloroethane (2 mL) was stirred,
protected from light, at 80 °C for the corresponding time men-
tioned in the text. The solution was evaporated under reduced pres-
sure, and the residue was purified by flash chromatography on neu-
tral aluminum oxide (hexane/EtOAc = 50:1 to 5:1) to afford pure
5.
3-(3-Nitrobenzyl)-5-phenyl-2-(trifluoromethyl)furan (5h): Light yel-
1
low solid, 55 mg, 79% yield. M.p. 85–87 °C. H NMR (300 MHz,
3
CDCl3, 25 °C): δ = 8.14–8.12 (m, 2 H, Ar-H), 7.66 (d, JH,H
=
8.7 Hz, 2 H, Ar-H), 7.57–7.48 (m, 5 H, Ar-H), 6.46 (s, 1 H, furan-
H), 4.06 (s, 2 H, ArCH2) ppm. 19F NMR (282 MHz, CDCl3): δ =
–61.0 (s, 3 F, CF ) ppm. IR (KBr): ν = 3126, 3088, 1630, 1555,
˜
3
1520, 1489, 1403, 1355, 1180, 1038 cm–1. EI-MS: m/z (%) = 347
(100) [M]+. C18H12F3NO3 (347.30): calcd. C 62.25, H 3.48, N 4.03;
found C 62.34, H 3.58, N 3.96.
3-Benzyl-5-phenyl-2-(trifluoromethyl)furan (5a): Light yellow oil,
41 mg, 68% yield. 1H NMR (300 MHz, CDCl3, 25 °C): δ = 7.64
3
(d, JH,H = 8.4 Hz, 2 H, Ar-H), 7.37–7.24 (m, 8 H, Ar-H), 6.43 (s,
3-Benzyl-5-(4-chlorophenyl)-2-(trifluoromethyl)furan (5i): Light yel-
1 H, furan-H), 3.94 (s, 2 H, ArCH2) ppm. 19F NMR (282 MHz,
1
low oil, 44 mg, 65% yield. H NMR (300 MHz, CDCl3, 25 °C): δ
3
CDCl , 25 °C): δ = –60.9 (s, 3 F, CF ) ppm. IR (KBr): ν = 3033,
˜
= 7.55 (d, JH,H = 9.0 Hz, 2 H, Ar-H), 7.35–7.23 (m, 7 H, Ar-H),
3
3
2927, 2855, 1628, 1555, 1487, 1402, 1324, 1179, 1125, 1033 cm–1.
EI-MS: m/z (%) = 302 (100) [M]+. C18H13F3O (302.30): calcd. C
71.52, H 4.33; found C 71.58, H 4.31.
6.41 (s, 1 H, furan-H), 3.93 (s, 2 H, ArCH2) ppm. 19F NMR
(282 MHz, CDCl3, 25 °C): δ = –60.9 (s, 3 F, CF3) ppm. IR (KBr):
ν = 3032, 2927, 2855, 1604, 1483, 1418, 1323, 1180, 1032 cm–1. EI-
˜
MS: m/z (%) = 336 (24) [M]+, 335 (100). C18H12ClF3O (336.74):
3-(4-Methylbenzyl)-5-phenyl-2-(trifluoromethyl)furan (5b): Light
1
calcd. C 64.20, H 3.59; found C 64.07, H 3.61.
yellow oil, 45 mg, 71% yield. H NMR (300 MHz, CDCl3, 25 °C):
3
δ = 7.55 (d, JH,H = 6.9 Hz, 2 H, Ar-H), 7.32–7.17 (m, 3 H, Ar-
5-(4-Chlorophenyl)-3-(4-methylbenzyl)-2-(trifluoromethyl)furan (5j):
Light yellow oil, 46 mg, 66% yield. 1H NMR (300 MHz, CDCl3,
H), 7.05 (s, 4 H, Ar-H), 6.35 (s, 1 H, furan-H), 3.82 (s, 2 H,
ArCH2), 2.25 (s, 3 H, ArCH3) ppm. 19F NMR (282 MHz, CDCl3,
3
3
25 °C): δ = 7.56 (d, JH,H = 8.7 Hz, 2 H, Ar-H), 7.34 (d, JH,H
=
25 °C): δ = –60.9 (s, 3 F, CF ) ppm. IR (KBr): ν = 2926, 2859,
˜
3
8.7 Hz, 2 H, Ar-H), 7.12 (s, 4 H, Ar-H), 6.42 (s, 1 H, furan-H),
3.89 (s, 2 H, ArCH2), 2.33 (s, 3 H, ArCH3) ppm. 19F NMR
(282 MHz, CDCl3, 25 °C): δ = –61.0 (s, 3 F, CF3) ppm. IR (KBr):
1629, 1516, 1487, 1401, 1325, 1178, 1056 cm–1. EI-MS: m/z (%) =
316 (100) [M]+. C19H15F3O (316.33): calcd. C 72.14, H 4.78; found
C 72.07, H 4.98.
ν = 3047, 2927, 1627, 1514, 1483, 1418, 1392, 1324, 1179, 1033
˜
cm–1. EI-MS: m/z (%) = 350 (21) [M]+, 349 (100). C19H14ClF3O
3-(4-Fluorobenzyl)-5-phenyl-2-(trifluoromethyl)furan (5d): Light yel-
1
(350.77): calcd. C 65.06, H 4.02; found C 65.13, H 4.05.
low oil, 52 mg, 81% yield. H NMR (300 MHz, CDCl3, 25 °C): δ
3
= 7.57 (d, JH,H = 9.3 Hz, 2 H, Ar-H), 7.33–7.08 (m, 5 H, Ar-H),
5-(4-Chlorophenyl)-3-(4-fluorobenzyl)-2-(trifluoromethyl)furan (5l):
6.93 (t, 3JH,H = 6.6 Hz, 2 H, Ar-H), 6.34 (s, 1 H, furan-H), 3.83 (s,
2 H, ArCH2) ppm. 19F NMR (282 MHz, CDCl3, 25 °C): δ = –60.9
Light yellow oil, 50 mg, 71% yield. 1H NMR (300 MHz, CDCl3,
3
3
25 °C): δ = 7.56 (d, JH,H = 8.7 Hz, 2 H, Ar-H), 7.34 (d, JH,H
=
3
(s, 3 F, CF ), –116.4 (m, 1 F) ppm. IR (KBr): ν = 3042, 1919, 1629,
˜
3
8.7 Hz, 2 H, Ar-H), 7.19 (d, JH,H = 5.7 Hz, 1 H, Ar-H), 7.16 (d,
3JH,H = 5.7 Hz, 1 H, Ar-H), 7.00 (t, J = 8.7 Hz, 2 H, Ar-H), 6.40
(s, 1 H, furan-H), 3.90 (s, 2 H, ArCH2) ppm. 19F NMR (282 MHz,
CDCl3, 25 °C): δ = –61.0 (s, 3 F, CF3), –116.2 (m, 1 F) ppm. IR
1606, 1511, 1487, 1402, 1326, 1226, 1180, 1033 cm–1. EI-MS: m/z
(%) = 320 (20) [M]+, 319 (100). C18H12F4O (320.29): calcd. C 67.50,
H 3.78; found C 67.59, H 3.77.
(KBr): ν = 2929, 2857, 1604, 1510, 1483, 1419, 1393, 1324, 1226,
˜
3-(4-Chlorobenzyl)-5-phenyl-2-(trifluoromethyl)furan (5e): Light yel-
1181, 1094, 1033 cm–1. EI-MS: m/z (%) = 355 (19) [M]+, 354 (100).
C18H11ClF4O (354.73): calcd. C 60.95, H 3.13; found C 61.40, H
3.36.
1
low oil, 33 mg, 49% yield. H NMR (300 MHz, CDCl3, 25 °C): δ
3
= 7.64 (d, JH,H = 8.4 Hz, 2 H, Ar-H), 7.38–7.27 (m, 5 H, Ar-H),
3
7.15 (d, JH,H = 8.4 Hz, 2 H, Ar-H), 6.41 (s, 1 H, furan-H), 3.91
(s, 2 H, ArCH2) ppm. 19F NMR (282 MHz, CDCl3, 25 °C): δ =
3-(4-Chlorobenzyl)-5-(4-chlorophenyl)-2-(trifluoromethyl)furan (5m):
–61.0 (s, 3 F, CF ) ppm. IR (KBr): ν = 2926, 2854, 1630, 1492,
˜
Light yellow oil, 58 mg, 78% yield. 1H NMR (300 MHz, CDCl3,
3
1401, 1324, 1179, 1127, 1034 cm–1. EI-MS: m/z (%) = 336 (18)
[M]+, 335 (100). C18H12ClF3O (336.74): calcd. C 64.20, H 3.59;
found C 64.32, H 3.68.
3
3
25 °C): δ = 7.56 (d, JH,H = 7.8 Hz, 2 H, Ar-H), 7.35 (d, JH,H
=
3
7.5 Hz, 2 H, Ar-H), 7.29 (d, JH,H = 7.5 Hz, 2 H, Ar-H), 7.15 (d,
3JH,H = 7.8 Hz, 2 H, Ar-H), 6.39 (s, 1 H, furan-H), 3.90 (s, 2 H,
ArCH2) ppm. 19F NMR (282 MHz, CDCl3, 25 °C): δ = –61.1 (s, 3
3-(4-Cyanobenzyl)-5-phenyl-2-(trifluoromethyl)furan (5f): Light yel-
low solid, 58 mg, 84 % yield. M.p. 116–118 °C. 1H NMR
F, CF ) ppm. IR (KBr): ν = 2928, 2856, 1725, 1629, 1604, 1483,
˜
3
1324, 1182, 1054, 1016 cm–1. EI-MS: m/z (%) = 371 (24) [M]+, 57
(100). C18H11Cl2F3O (371.19): calcd. C 58.25, H 2.99; found C
57.81, H 3.06.
3
(300 MHz, CDCl3, 25 °C): δ = 7.65 (d, JH,H = 8.4 Hz, 2 H, Ar-
3
H), 7.62 (d, JH,H = 8.4 Hz, 2 H, Ar-H), 7.43–7.31 (m, 5 H, Ar-
H), 6.42 (s, 1 H, furan-H), 4.01 (s, 2 H, ArCH2) ppm. 19F NMR
(282 MHz, CDCl3, 25 °C): δ = –61.0 (s, 3 F, CF3) ppm. IR (KBr):
5-(4-Chlorophenyl)-3-(4-cyanobenzyl)-2-(trifluoromethyl)furan (5n):
ν = 2995, 2224, 1608, 1553, 1488, 1401, 1331, 1307, 1177, 1148,
˜
1
Light yellow solid, 64 mg, 89% yield. M.p. 107–109 °C. H NMR
1106, 1035 cm–1. EI-MS: m/z (%) = 327 (73) [M]+, 44 (100).
C19H12F3NO (327.31): calcd. C 69.72, H 3.70, N 4.28; found C
69.41, H 3.85, N 4.24.
3
(300 MHz, CDCl3, 25 °C): δ = 7.62 (d, JH,H = 8.7 Hz, 2 H, Ar-
3
3
H), 7.58 (d, JH,H = 8.7 Hz, 2 H, Ar-H), 7.37 (d, JH,H = 8.7 Hz,
3
2 H, Ar-H), 7.33 (d, JH,H = 8.7 Hz, 2 H, Ar-H), 6.41 (s, 1 H,
3-(4-Nitrobenzyl)-5-phenyl-2-(trifluoromethyl)furan (5g): Light yel-
furan-H), 4.00 (s, 2 H, ArCH2) ppm. 19F NMR (282 MHz, CDCl3,
1
low solid, 63 mg, 91% yield. M.p. 76–78 °C. H NMR (300 MHz,
25 °C): δ = –61.1 (s, 3 F, CF ) ppm. IR (KBr): ν = 2225, 1627,
˜
3
3
CDCl3, 25 °C): δ = 8.19 (d, JH,H = 8.4 Hz, 2 H, Ar-H), 7.66 (d,
1608, 1484, 1420, 1394, 1306, 1187, 1120, 1032 cm–1. EI-MS: m/z
Eur. J. Org. Chem. 2007, 3916–3924
© 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
3923

D. H. Zhang, C. Y. Yuan
FULL PAPER
(%) = 362 (22) [M]+, 361 (100). C19H11ClF3NO (361.75): calcd. C
63.08, H 3.06, N 3.87; found C 63.49, H 2.96, N 3.63.
[4]
[5]
[6]
[7]
[8]
W. S. Huang, C. Y. Yuan, J. Chem. Soc. Perkin Trans. 1 1995,
741–742.
I. Katsuyama, S. Ogawa, H. Nakamura, Y. Yamaguchi, K. Fu-
nabiki, Heterocycles 1998, 779–786.
M. G. Gorbunova, I. I. Gerus, V. P. Kukhar, J. Fluorine Chem.
1993, 65, 25–28.
C. Yamagami, N. Motohashi, Eur. J. Med. Chem. Chim. Ther.
2002, 37, 127–134.
V. G. Nenajdenko, S. V. Druzhinin, E. S. Balenkova, Tetrahe-
dron Lett. 2005, 46, 8853–8855.
D. H. Zhang, C. Y. Yuan, unpublished results.
The instability of 2d is probably due to the proton exchange
between pyridine iodide and 2d followed by the elimination of
MeI. Such characteristic behavior is presumably associated
with the conjugated system of the trifluoromethyl enone. This
postulation was further supported by the following experiment.
When 2d was reduced by NaBH4 in the presence of
CeCl3·7H2O, as shown by 1H NMR, the major component
(48.5% yield) was the one that we expected while the minor
one (22.1% yield) was its analogue, which loses a methyl group
on the nitrogen (Table 3).
5-(4-Chlorophenyl)-3-(4-nitrobenzyl)-2-(trifluoromethyl)furan (5o):
Light yellow solid, 58 mg, 76% yield, M.p. 95–96 °C. 1H NMR
3
(300 MHz, CDCl3, 25 °C): δ = 8.19 (d, JH,H = 8.7 Hz, 2 H, Ar-
3
3
H), 7.59 (d, JH,H = 8.7 Hz, 2 H, Ar-H), 7.40 (d, JH,H = 4.5 Hz,
3
2 H, Ar-H), 7.37 (d, JH,H = 4.5 Hz, 2 H, Ar-H), 6.43 (s, 1 H,
furan-H), 4.05 (s, 2 H, ArCH2) ppm. 19F NMR (282 MHz, CDCl3,
25 °C): δ = –61.1 (s, 3 F, CF ) ppm. IR (KBr): ν = 2961, 2859,
˜
3
1729, 1605, 1521, 1483, 1423, 1340, 1286, 1180, 1037 cm–1. EI-MS:
m/z (%) = 382 (13) [M]+, 149 (100). C18H11ClF3NO3 (381.74):
calcd. C 56.64, H 2.90, N 3.67; found C 56.18, H 2.87, N 3.79.
[9]
[10]
5-(4-Chlorophenyl)-3-(3-nitrobenzyl)-2-(trifluoromethyl)furan (5p):
Light yellow solid, 76 mg, Ͼ99% yield. M.p. 107–109 °C. 1H NMR
(300 MHz, CDCl3, 25 °C): δ = 8.14 (s, 1 H, Ar-H), 8.11 (s, 1 H,
3
Ar-H), 7.59 (d, JH,H = 8.7 Hz, 2 H, Ar-H), 7.54 (s, 1 H, Ar-H),
3
7.53 (s, 1 H, Ar-H), 7.38 (d, JH,H = 8.7 Hz, 2 H, Ar-H), 6.44 (s, 1
H, furan-H), 4.06 (s, 2 H, ArCH2) ppm. 19F NMR (282 MHz,
CDCl , 25 °C): δ = –61.0 (s, 3 F, CF ) ppm. IR (KBr): ν = 3118,
˜
3
3
[11]
2936, 2867, 1629, 1520, 1482, 1356, 1331, 1186, 1058, 1035 cm–1.
EI-MS: m/z (%) = 382 (26) [M]+, 381 (100). C18H11ClF3NO3
(381.74): calcd. C 56.64, H 2.90, N 3.67; found C 56.63, H 2.94, N
3.56.
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Supporting Information (see also the footnote on the first page of
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1c, 1d, 1f, 1g and 1i.
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Acknowledgments
This Project was supported by the National Nature Science Foun-
dation of China (Grant No. 20372076 and 20672132).
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Published Online: June 18, 2007
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