Enantioselective reduction of α,β-unsaturated ketones bearing the trifluoromethyl group

Article abstract of DOI:10.1016/S0957-4166(01)00209-9

α,β-Unsaturated ketones bearing the trifluoromethyl group were enantioselectively reduced by a variety of reagents to the corresponding secondary allylic alcohols with e.e. in the range 87-99%. The influence of the trifluoromethyl group on the enantioselectivity is discussed.

Full text of DOI:10.1016/S0957-4166(01)00209-9

TETRAHEDRON:
ASYMMETRY
Pergamon
Tetrahedron: Asymmetry 12 (2001) 1259–1266
Enantioselective reduction of a,b-unsaturated ketones bearing
the trifluoromethyl group
Valentine G. Nenajdenko,* Konstantin I. Smolko and Elizabeth S. Balenkova
Department of Chemistry, Moscow State University, Moscow 119899, Russia
Received 15 March 2001; accepted 4 May 2001
Abstract—a,b-Unsaturated ketones bearing the trifluoromethyl group were enantioselectively reduced by a variety of reagents to
the corresponding secondary allylic alcohols with e.e. in the range 87–99%. The influence of the trifluoromethyl group on the
enantioselectivity is discussed. © 2001 Published by Elsevier Science Ltd.
1. Introduction
and the influence of the fluoroalkyl group on stereose-
lectivity was found to be unpredictable. Reduction of
a,b-unsaturated ketones which possess a CF3 group has
not been studied thoroughly. Kitazume et al. have
shown that the reduction of 1,1,1-trifluoro-4-phenyl-
buten-2-one by BINAL-H leads to the formation of
racemic allylic alcohol 1a (Scheme 1).5
Organofluorine compounds are promising biologically
active materials, and include insecticides and pharma-
ceuticals. To further understand the mechanism of their
action on receptors, individual isomers and enantiomers
of such compounds are required for testing.
The enantioselective reduction of ketones is one of the
most convenient and useful methods for the prepara-
tion of homochiral secondary alcohols.1–3 The reduc-
tion of several types of ketones bearing fluoroalkyl
groups has been investigated using various reagents4
Some microbiological methods for the reduction of
such ketones have also been studied. In the case of
baker’s yeast, reduction of the double bond takes place
and the reaction leads to mixtures of the saturated
ketone and saturated alcohol.5 However, using
OH
O
BINAL-H
CF3
CF3
racemic
1
1a
Scheme 1.
R
O
.
1. (CF3CO)2O, BF3 Me2S
CF3
2. KHCO3
1, R = H; 2, R = Me
Scheme 2.
* Corresponding author. E-mail: nen@acylium.chem.msu.ru
0957-4166/01/$ - see front matter © 2001 Published by Elsevier Science Ltd.
PII: S0957-4166(01)00209-9

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Geotrichum candidum, 1a was obtained in good yield
This method is useful for many types of alkenes; how-
ever, b-methylstyrenes do not react under these condi-
tions. Therefore, the corresponding ketone 3 was
prepared by reaction of N,N-dimethyltrifluoroacet-
amide with the appropriate alkenyllithium derivative
(Method B) (Scheme 3).
and excellent enantioselectivity.6
The aim of the work reported herein is the investigation
of the enantioselective reduction of a,b-unsaturated
ketones bearing the trifluoromethyl group by means of
various chemical reagents.
Other ketones were prepared by the reaction of 4-
dimethylamino-1,1,1-trifluorobut-3-en-2-one with
a
variety of aryllithium derivatives (Method C) (Scheme
4).8
2. Results and discussion
The yields and methods of preparation of ketones are
summarized in Table 1.
2.1. Synthesis of starting ketones
a,b-Unsaturated ketones bearing the trifluoromethyl
group were prepared by three different methods.
Ketones 1 and 2 were prepared by direct trifluoro-
acylation of the corresponding styrenes (Method A)
(Scheme 2).7
2.2. Reduction of ketone 1 by chiral reducing agents
Readily available ketone 1 was chosen as a model
substrate in the screening experiments searching for the
O
Br
t-BuLi
CF3CONMe2
Li
CF3
Et2O, -90°C
-80°C
3
Scheme 3.
1. RLi, THF. -78°C
O
O
Me2N
CF3 2. HCl, H2O
R
CF3
4
7
8
10
R =
S
Br
5
6
11
S
MeO
9
MeS
Scheme 4.
Table 1. Preparation of the starting ketones
Ketone
Method
Yield (%)
Ketone
Method
Yield (%)
1
2
3
4
5
6
A
A
B
C
C
C
34
27
85
78
84
76
7
8
9
10
11
C
C
C
C
C
76
68
77
51
95

V. G. Nenajdenko et al. / Tetrahedron: Asymmetry 12 (2001) 1259–1266
1261
best chiral reducing agent. Alpine-borane 12,9 DIP-
Chloride 13,3 DIP-Bromide 14,10 and reduction using
CBS catalysts2 15–18 by borane–dimethylsulfide com-
plex or catecholborane were tested (Scheme 5).
exothermically within several minutes, accompanied by
the formation of small amounts of the corresponding
saturated alcohol. The main product was racemic alco-
hol 1a.
Reduction of several types of trifluoromethyl-contain-
ing ketones by these reagents was reported recently.4
Ramachandran and Brown made a systematic study on
the reduction of aryl,11 alkyl11,12 and alkynyl13 ketones
by 13. CBS reduction of some trifluoromethyl ketones
has also been developed.14,15
We established that application of CBS catalyst 17 with
catecholborane reducing agent allowed the preparation
of alcohol 1a in 76% e.e. A better result (87% e.e.) was
obtained in the case of oxazaborolidine 18.17 We
assume that the improvement in the enantioselectivity is
due to the bulky CH2TMS group; some SiꢀF interac-
tions in the transition state are also possible.
Usually, reduction of most types of ketones by Alpine-
borane 12 proceeds very slowly, but a,b-acetylenic
ketones are known to react rapidly,16 furnishing the
corresponding propargylic alcohols. Moreover, a,b-
acetylenic ketones bearing the trifluoromethyl group
react even faster than the non-fluorinated analogues.
However, when we tried to use this reagent for the
reduction of ketone 1, we found that the reaction
proceeded too slowly and that only traces of the desired
product were detected after reacting for one month.
Reaction of ketone 1 with DIP-Chloride proceeded in
THF at room temperature over 5 days to give 1a in
92% isolated yield and 90% e.e. We found that the rate
of the reaction was dependent on the polarity of the
solvent. For example, the reaction was extremely slow
in hexane, but the rate was faster in THF,
dichloromethane and ether (reactions in these solvents
had approximately the same rate). However, the enan-
tioselectivity of the reaction was not dependent on the
nature of solvent.
Reduction of ketone 1 by borane–dimethylsulfide com-
plex in the presence of 20 mol% of the catalysts 15–17
led to formation of the racemic alcohol 1a. It was
reported that reduction of aryl trifluoromethyl ketones
with such reagents also proceeds with low enantioselec-
tivity.14 We believe that the absence of stereoselectivity
is due to fast reduction of the ketone by borane itself,
without participation of a catalyst. To confirm this we
investigated the reaction of ketone 1 with borane–
dimethylsulfide complex in the absence of the CBS
catalyst. It was found that the reaction proceeded
Reduction with DIP-Bromide proceeded at a higher
rate and with excellent enantioselectivity, but the yield
of the target product was lower. Being a stronger Lewis
acid than 13 it is possible that reagent 14 causes degra-
dation of the product and/or the starting ketone.
To summarize the first part of our investigation, we
found DIP-Chloride to be the best reagent for the
reduction of a,b-unsaturated ketones bearing a tri-
fluoromethyl group (Table 2).
Ph
Ph
BCl
BBr
O
B
B
N
2
2
R
12
13
14
R = H
Me
15
16
17
18
Bu
CH2TMS
Scheme 5.
Table 2. Reduction of ketone 1 by reagents 12–18
Reagent
Reaction conditions
Yield (%)
Configuration
E.e. (%)
12
13
14
rt, without solvent
rt, THF
rt, CH2Cl2
30°C, THF
0°C, THF
−30°C, THF
−30°C, THF
−87°C, toluene
−87°C, CH2Cl2
−87°C, toluene
0
92
56
65
75
90
65
85
87
81
–
S
S
–
90
\99
0
BH3·Me2S, 20 mol% of 15
Racemate
Racemate
Racemate
Racemate
R
0
0
0
78
76
87
BH3·Me2S, 20 mol% of 16
Catecholborane, 20 mol% of 17
Catecholborane, 20 mol% of 17
Catecholborane, 20 mol% of 18
R
R

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2.3. Stereochemistry of reduction
ever, the signals of the main diastereomer in the spec-
trum of the (S)-MPTA ester of 1a obtained by CBS
reduction with catecholborane was shifted upfield.
Therefore, we conclude that the configuration of 1a pre-
pared by means of reagents 13 and 14 by (S) and CBS
reduction leads to the (R)-product (Fig. 2).
We also investigated the stereochemistry of the reduc-
tion reactions. The absolute configuration of alcohol 4a,
prepared by reduction of ketone 4 by (−)-DIP-Chloride,
was determined by X-ray analysis.18 The product was
found to have (S)-configuration (Fig. 1).
The stereochemical outcome of the reductions of tri-
fluoromethyl ketones is in agreement with literature
models for the reduction of ketones with both
oxazaborolidines20 and DIP-Chloride.11 In the postu-
lated transition states for CBS reduction and reduc-
tion by DIP-Chloride (Scheme 6) the CF3 group
having greater conformational energy occupies the less
sterically hindered position rather than the other ketone
substituent. Therefore, CBS reduction should lead to
the (R)-product and reduction by (−)-DIP-Chloride
should result in formation of the (S)-product.
To determine the absolute configuration of alcohol 1a
we analyzed some (S)-MPTA19 derivatives by 19F NMR
spectroscopy. Comparison of the spectra then allowed
assignment of the configuration of 1a obtained from
reaction with the different reducing agents. The signals
for the CF3 groups of the (S)-MPTA ester of (S)-4a
shifted downfield compared to the signals of the minor
diastereomeric ester. The same effect was observed in
the spectrum of the (S)-MPTA esters of 1a, which were
obtained from the reduction of 1 with 13 and 14. How-
Figure 1. X-Ray structure of 4a.
Figure 2. 19F spectra of (S)-MPTA esters of racemic and scalemic 1a.

V. G. Nenajdenko et al. / Tetrahedron: Asymmetry 12 (2001) 1259–1266
1263
Ph
Ph
N
O
O
HO
B
B
O
Ph
CF3
O
H
H
(R)-1a
CF3
Cl
Ipc
B
O
HO
H
CF3
H
CF3
(S)-1a
Ph
Scheme 6.
2.4. Reduction of other a,b-unsaturated trifluoromethyl
ketones
air-sensitive compounds were conducted under argon
by means of usual Schlenk-type techniques.
Having found that DIP-Chloride was the optimal
reagent for the asymmetric reduction of ketone 1, we
investigated the preparation of other CF3-substituted
allylic alcohols (Table 3). The absolute configurations
were determined by comparison of chemical shifts of
the major diastereomer in 19F NMR spectra of (S)-
MPTA esters of obtained non-racemic alcohols and
their racemates, relying on the data for alcohol 4a. It
should be noted that in all cases studied the reduction
led to the corresponding (S)-alcohols.
Diphenylprolinol,22 catecholborane,23 butylboronic
acid,24 trimethylsilylmethaneboronic acid,17 borox-
ines,22,25 9-BBN26 and Alpine-borane27 were prepared
by literature procedures. Oxazaborolidines were pre-
pared by reaction of corresponding boroxines with
diphenylprolinol,22 except 17, which was prepared from
trimethylsilylmethaneboronic acid,17 and 15, which was
obtained by reaction of BH3·Me2S and diphenylproli-
nol.28 DIP-Bromide was prepared by hydroboration of
(+)-a-pinene by BH2Br–dimethylsulfide complex in
dichloromethane at room temperature, followed by
recrystallization in hexane.29
3. Conclusion
4.2. Preparation of ketones
DIP-Chloride was found to be the best reagent for the
reduction of a,b-unsaturated trifluoromethyl ketones
into the corresponding allylic alcohols. Good enantiose-
lectivities were achieved using a very straightforward
experimental procedure.
4.2.1. Preparation of (E)-1,1,1-trifluoro-3-methyl-4-
phenyl-3-buten-2-one 3. [(E)-2-Bromo-1-propenyl]ben-
zene was prepared from (E)-2-methyl-3-phenyl-2-
propenoic acid by a literature procedure.30
4. Experimental
4.1. General
Table 3. Reduction of a,b-unsaturated CF3 ketones
Ketones
Alcohol obtained
Configuration Yield (%)
1H and 13C NMR and 19F spectra were recorded on
Varian VXR-400 spectrometers with TMS or CFCl3 as
an internal standard. The IR spectra were obtained on
a UR-20 spectrometer in films. HPLC analysis was
performed using a Chiracel OD-H column. The e.e.s of
the prepared compounds were determined by HPLC or
19F NMR spectroscopy using (S)-MPTA derivatives.19
Acylation was performed with the (S)-MPTA-chloride
in dichloromethane solution in the presence of pyridine
and DMAP.19
Alcohols
E.e. (%)
2
3
4
5
6
7
8
9
2a
3a
4a
5a
6a
7a
8a
9a
10a
11a
S
S
S
S
S
S
S
S
S
S
85
92
85
90
88
81
91
89
78
75
90
92
\99
88
\99
\99
92
\99
91
10
11
THF, toluene and diethyl ether were dried and distilled
according to standard procedures.21 All operations with
87

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To a solution of [(E)-2-bromo-1-propenyl]benzene (10
mmol) in ether at −95°C was slowly added a solution of
tert-BuLi in pentane (22 mmol). After stirring at this
temperature for 15 min, the temperature was allowed to
rise to −78°C and the reaction mixture was stirred for
an additional 15 min. During this time a suspension of
organolithium derivatives was seen to form. A solution
of 2,2,2-trifluoro-N,N-dimethylacetamide (22 mmol)
was added over 20 min at −78°C. The cooling bath was
removed and the temperature of the mixture was
allowed to rise to 0°C with stirring. The mixture was
cooled to −30°C and quenched by the addition of a
saturated NH4Cl solution (10 mL). The organic layer
was removed, the aqueous was extracted three times
with ether and the combined organic layers were dried
over Na2SO4 and evaporated. The residue was dis-
solved in a mixture of hexanes and benzene (1:1) and
was passed through a short column of SiO2. The sol-
vent was removed in vacuo and the crude product was
purified by distillation (bp 89–92°C/2 mmHg). 85%
yield. IR (w, cm−1): 1605, 1720. lH (CDCl3) 2.12 (3H, s),
6.62 (1H, s), 7.15–7.54 (5H, m); lC (CDCl3) 17.05,
116.43 (q, J=293.12 Hz), 126.47, 128.56, 129.77,
130.46, 142.52, 164.12, 179.34 (q, J=34.32 Hz). Anal.
calcd for C11H9F3O: C, 61.68; H, 4.24. Found: C, 61.72;
H, 4.27%.
7.49–7.63 (4H, m), 7.88–7.91 (2H, m), 7.98 (1H, d,
J=8.21 Hz), 8.17 (1H, d, J=15, 73 Hz); lC (CDCl3)
116.45 (q, J=292.42 Hz), 118.41, 122.73, 125.32,
126.05, 126.59, 127.59, 128.96, 130.23, 131.72, 132.76,
133.71, 146.583, 180.85 (q, J=35.18 Hz). Anal. calcd
for C14H9F3O: C, 67.20; H, 3.63. Found: C, 67.23; H,
3.75%.
4.2.2.5. (E)-1,1,1-Trifluoro-4-(9-phenanthryl)-3-buten-
2-one 9. Yellow solid, mp 130–132°C; IR (w, cm−1):
1610, 1720; lH (CDCl3) 7.21 (1H, d, J=15.65 Hz),
7.63–7.76 (4H, m), 7.95 (1H, d, J=7.99 Hz), 8.12 (1H,
s), 8.18–8.21 (1H, m), 8.67 (1H, d, J=8.21 Hz), 8.72–
8.74 (1H, m), 8.83 (1H, d, J=15.65 Hz); lC (CDCl3)
116.45 (q, J=288.22 Hz), 118.88, 122.62, 123.25,
123.67, 127.22, 127.31, 128.00, 128.65, 129.32, 129.58,
129.65, 130.38, 130.54, 131.81, 180.32 (q, J=35.09 Hz).
Anal. calcd for C18H11F3O: C, 72.00; H, 3.69. Found:
C, 72.05; H, 3.71%.
4.3. Reduction of ketones
4.3.1. Reduction with boranes in the presence of
oxazaborolidines
4.3.1.1. General procedure for reductions with
BH3·Me2S. To a stirred solution of oxazaborolidine (1
mmol) and BH3·Me2S (0.5 mmol) in THF at −30°C,
ketone 1 (0.5 mmol) was added. The reaction was
monitored by TLC. After a few minutes the reaction
mixture was quenched with methanol and evaporated.
The residue was suspended in diethyl ether, washed
twice with 10% NaOH and dried over Na2SO4. The
solvent was removed in vacuo and the crude product
was purified by column chromatography (hexane/ethyl
acetate, 9:1). The yields of product are given in Table 2.
4.2.2. Ketones 4–11. Ketones 4–11 were prepared by
procedures reported in the literature.8
4.2.2.1. (E)-4-(4-Bromophenyl)-1,1,1-trifluoro-3-buten-
2-one 4. Light yellow solid, mp 55–57°C; IR (w, cm−1):
1620, 1720; lH (CDCl3) 6.91 (1H, dd, J=15.86, 0.82
Hz), 7.40 (2H, d, J=8.43 Hz), 7.49 (2H, d, J=8.43 Hz),
7.80 (2H, d, J=15.86 Hz); lC (CDCl3) 114.09 (q,
J=291.46 Hz), 117.05, 126.92, 130.41, 132.14, 132.51,
148.55, 179.80 (q, J=36.8 Hz). Anal. calcd for
C10H6BrF3O: C, 43.04; H, 2.17. Found: C, 43.24; H,
2.20%.
4.3.1.2. General procedure for reductions with cate-
cholborane. To a stirred solution of oxazaborolidine (1
mmol) in toluene was added ketone 1 (5 mmol). The
reaction mixture was immersed in an ethyl acetate–liq-
uid nitrogen bath and stirred for 30 min. A solution of
catecholborane (10 mmol) in toluene was added drop-
wise within 30 min. The reaction was monitored by
TLC and was complete within 2 h. The reaction mix-
ture was quenched with methanol and evaporated. The
residue was suspended in diethyl ether, washed with
10% NaOH until aqueous layer did not change color,
and dried with Na2SO4. The solvent was removed in
vacuo and the crude product was purified by column
chromatography (hexane/ethyl acetate, 9:1). The yields
and enantiomeric purities of product are given in Table
2.
4.2.2.2.
(E)-1,1,1-Trifluoro-4-(4-methoxyphenyl)-3-
buten-2-one 5. Light yellow solid, mp 50–52°C; IR (w,
cm−1): 1560, 1790; lH (CDCl3) 3.84 (3H, s), 6.86 (1H, d,
J=15.86 Hz), 6.93 (2H, d, J=8.68 Hz), 7.57 (2H, d,
J=8.68), 7.90 (1H, d, J=15.86 Hz); lC (CDCl3) 55.39,
113.88, 114.67, 119.41 (q, J=291.32 Hz), 126.07,
131.32, 149.89, 163.16, 179.59 (q, J=35.10 Hz). Anal.
calcd for C11H9F3O2: C, 57.40; H, 3.94. Found: C,
57.55; H, 3.96%.
4.2.2.3. (E)-1,1,1-Trifluoro-4-[4-(methylsulfanyl)phen-
yl]-3-buten-2-one 6. Yellow solid, mp 68–69°C; IR (w,
cm−1): 1590, 1690; lH (CDCl3) 2.52 (1H, s), 6.97 (1H, d,
J=15.88 Hz), 7.26 (2H, d, J=8.43 Hz), 7.50 (2H, d,
J=8.43 Hz), 7.91 (1H, d, J=15.88 Hz); lC (CDCl3)
14.68, 114.5 (q, J=290.83 Hz), 115.15, 118.36, 125.63,
129.52, 145.35, 149.52, 179.82 (q, J=35.19 Hz). Anal.
calcd for C11H9F3OS: C, 53.65; H, 3.68. Found: C,
53.61, H, 3.69%.
4.3.1.3. General procedure for reductions with DIP-
Chloride. The ketone (1 mmol) was placed in a flame
dried Schlenk bottom flask fitted with a rubber septum.
A solution of DIP-Cl in THF (1.1 mmol) was added
and the reaction mixture was allowed to stand at room
temperature with TLC analysis. After 5 days the reac-
tion was quenched by the addition of acetaldehyde (1.2
mmol) and the mixture was allowed to stand for an
additional 12 h. The reaction mixture was evaporated
in vacuo and the residue was dissolved in ether and
4.2.2.4. (E)-1,1,1-Trifluoro-4-(2-naphthyl)-3-buten-2-
one 7. Light yellow solid, mp 62–64°C; IR (w, cm−1):
1620, 1730; lH (CDCl3) 7.13 (1H, d, J=15, 73 Hz),

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1265
washed three times with 1 M NaOH. The organic layer
was dried over Na2SO4 and the solvent was removed.
The product was purified by column chromatography
(100 g of silica gel, hexanes/ethyl acetate, 10:1, as
eluent). The crude compounds were recrystallized from
hexanes or a mixture of hexanes and benzene. Com-
pounds 7, 8, 9 and 11 were purified by recrystallization
instead of chromatographic purification.
Hz), 124.39, 125.549, 126.03, 126.4, 128.64, 129.02,
131.06, 133.12, 133.59, 133.73. Anal. calcd for
C14H11F3O: C, 66.67; H, 4.40. Found: C, 66.73; H,
4.43%.
4.3.1.10. (S)-(E)-4-(9-Anthryl)-1,1,1-trifluoro-3-buten-
2-ol 8a. Light yellow solid, mp 114–117°C; [h]D=−8.7
(c=1.6, acetone); lH ((CD)3CO) 4.96–5.03 (m, 1H),
6.45 (1H, dd J=6.52 Hz, 15.58 Hz), 7.59–7.74 (4H, m),
7.98–8.02 (2H, m), 7.78 (1H, d, J=15.58 Hz); lC
((CD)3CO) 71.51 (q, J=32.1 Hz), 122.17, 123.40,
124.05, 125.22, 125.81, 126.06 (q, J=282.3 Hz), 126.83,
127.63, 127.71, 127.78, 127.81, 129.65, 131.14, 131.18,
132.50, 133.43, 133.56. Anal. calcd for C18H13F3O: C,
71.52; H, 4.33. Found: C, 71.49; H, 4.37%.
4.3.1.4. (S)-(E)-1,1,1-Trifluoro-4-phenyl-3-penten-2-ol
2a. Colorless oil, [h]D=−12 (c=1.6, CHCl3); lH
(CDCl3) 1.88 (3H, s), 2.44 (1H, bs), 4.45 (1H, q,
J=6.92 Hz), 6.60 (1H, s), 7.15–7.29 (5H, m); lC
(CDCl3) 13.63, 75.8 (q, J=32.05 Hz), 124.5 (q, J=
283.82 Hz), 127.3, 128.22, 129.07, 131.01, 131.83,
136.17. Anal. calcd for C11H11F3O: C, 61.11; H, 5.13.
Found: C, 61.42; H, 5.01%.
4.3.1.11. (S)-(E)-1,1,1-Trifluoro-4-(9-phenanthryl)-3-
buten-2-ol 9a. Light yellow solid, mp 165–167°C; [h]D=
−9.5 (c=1.6, acetone); lH ((CD)3CO) 4.99 (1H, m),
6.46 (1H, dd, J=15.48 Hz, 6.30 Hz), 7.37–7.83 (5H, m),
8.00–8.08 (2H, m), 8.23 (1H, dd, J=8.31 Hz, J=2.22
Hz), 8.81 (1H, d, J=7.62 Hz), 8.89 (1H, dd, J=7.65
Hz, J=1.86 Hz); lC ((CD)3CO) 71.92 (q, J=32.1 Hz),
123.7 (q, J=280.36 Hz), 123.81, 124.54, 125.69, 126.26,
127.31, 128.12, 128.20, 128.26, 128.29, 130.13, 131.61,
131.67, 132.99, 133.91, 134.01. Anal. calcd for
C18H13F3O: C, 71.52; H, 4.33. Found: C, 71.18; H,
4.52%.
4.3.1.5. (S)-(E)-1,1,1-Trifluoro-3-methyl-4-phenyl-3-
buten-2-ol 3a. Colorless oil, [h]D=−8 (c=1.6, CHCl3);
lH (CDCl3) 2.17 (3H, s), 2.95 (1H, bs), 4.81 (1H, dq,
J=2.2 Hz, 8.65 Hz), 5.76 (1H, d, J=8.65 Hz), 7.35–
7.42 (5H, m); lC (CDCl3) 16.70, 67.90 (q, J=31.4 Hz),
119.18, 123.33, 124.72 (q, J=282.22 Hz), 126.13,
128.21, 141.75, 144.46. Anal. calcd for C11H11F3O: C,
61.11; H, 5.13. Found: C, 61.77; H, 5.81%.
4.3.1.6. (S)-(E)-4-(4-Bromophenyl)-1,1,1-trifluoro-3-
buten-2-ol 4a. Colorless solid, mp 87–89°C; [h]D=−9.1
(c=1.6, CHCl3); lH (CDCl3) 2.87 (1H, s), 4.63 (1H, m),
6.57 (1H, dd, J=6.82 Hz, 15.11 Hz), 6.78. (1H, d,
J=15.11 Hz), 7.09 (2H, d, J=8.18 Hz), 7.19 (2H, d, J
8.57 Hz); lC (CDCl3) 72.57 (q, J=32.00 Hz), 119.05,
123.42, 124.55 (q, J=282.78 Hz), 130.00, 132.73,
134.44, 142.47. Anal. calcd for C10H8BrF3O: C, 42.73;
H, 2.87. Found: C, 42.75; H, 2.88%.
4.3.1.12. (S)-(E)-1,1,1-Trifluoro-4-(2-thienyl)-3-buten-
2-ol 10a. Colorless solid, mp 55–57°C; [h]D=−11 (c=
1.6, CHCl3); lH (CDCl3) 2.65 (1H, s), 4.5 (1H, m), 5.93
(1H, dd, J=15.87 Hz, 6.61 Hz), 6.88 (1H, d, JH3 -H
=
15.87 Hz), 6.91 (1H, dd, J=3.66 Hz, 4.88 Hz), 6.97
(1H, d, J=3.66 Hz), 7.16 (1H, d, J=4.88 Hz); lC
(CDCl3) 71.22 (q, J=32.04 Hz), 119.71, 122.65 (q,
J1C-F=282.31 Hz), 125.78, 127.52 (2C), 129.16, 140.22.
Anal. calcd for C8H7F3OS: C, 46.15; H, 3.39. Found:
C, 47.02; H, 3.27%.
4.3.1.7. (S)-(3E)-1,1,1-Trifluoro-4-(4-methoxyphenyl)-
3-buten-2-ol 5a. Colorless solid, [h]D=−12 (c=1.6,
CHCl3); lH (CDCl3) 2.85 (1H, s), 4.58 (1H, m), 6.05
(1H, dd, J=6.98 Hz, 15.87 Hz), 6.76 (1H, d, J=15.87
Hz), 6.87 (2H, d, J=8.57 Hz), 7.33 (2H, d, J=8.57 Hz);
lC (CDCl3) 55.17, 71.75 (q, J=32.05 Hz), 114.10,
118.28, 124.35 (q, J=280.78 Hz), 128.10, 128.18,
135.94. Anal. calcd for C11H11F3O2: C, 56.90; H, 4.77.
Found: C, 56.93; H, 4.79%.
4.3.1.13. (S)-(E)-4-(1-Benzothien-2-yl)-1,1,1-trifluoro-
3-buten-2-ol 11a. Colorless solid, mp 122–123°C; [h]D=
−21 (c=1.6, CHCl3); lH ((CD3)2CO) 4.83 (1H, m), 6.17
(1H, dd, J=15.57 Hz, 5.94 Hz), 7.23 (1H, d, J=15.57
Hz), 7.32–7.37 (2H, m), 7.42 (1H, s), 7.75–7.79 (1H, m),
7.83–7.88 (1H, m); lC ((CD3)2CO) 71.52 (q, J=32.2
Hz), 122.92, 123.04, 124.8 (q, J=280.56 Hz), 125.57,
125.35, 125.73, 130.44, 140.01, 140.56, 141.03. Anal.
calcd for C12H9F3OS: C, 55.81; H, 3.51. Found: C,
55.87; H, 3.52%.
4.3.1.8. (S)-(E)-1,1,1-Trifluoro-4-[4-(methylsulfanyl)-
phenyl]-3-buten-2-ol 6a. Colorless solid, mp 72–74°C;
[h]D=−7.5 (c=1.6, CHCl3); lH (CDCl3) 2.40 (3H, s),
4.52 (1H, m), 6.06 (1H, dd, J=16.1 Hz, 6.69 Hz), 6.70
(1H, d, J=16.1 Hz), 7.2 (2H, d, J=7.93 Hz), 7.23 (2H,
d, J=7.93 Hz); lC (CDCl3) 15.45, 71.55 (q, J=32.05
Hz), 119.85, 124.25 (q, J=279.25 Hz), 126.32, 127.2,
132.08, 135.61, 139.36. Anal. calcd for C11H11F3OS: C,
53.22; H, 4.47. Found: C, 53.31; H, 4.51%.
Acknowledgements
4.3.1.9. (S)-(E)-1,1,1-Trifluoro-4-(2-naphthyl)-3-buten-
2-ol 7a. Colorless solid, mp 67–69°C; [h]D=−9 (c=1.6,
CHCl3); lH (CDCl3) 2.77 (1H, s), 4.77 (1H, m), 6.26
(1H, dd, J=15.75 Hz, 6.47 Hz), 7.44–7.65 (5H, m),
7.83–7.89 (2H, m), 8.07–8.10 (1H, m); lC (CDCl3) 71.64
(q, J=32.04 Hz), 123.48, 123.78, 124.37 (q, J=282.3
The research described in this publication was sup-
ported by the Russian Fundamental Investigation
Foundation (Grant N 00-03-32760a). Dr. David Lind-
say (LMU, Mu¨nchen) is gratefully acknowledged for
his help with correction of the text.

1266
V. G. Nenajdenko et al. / Tetrahedron: Asymmetry 12 (2001) 1259–1266
13. Ramachandran, P. V.; Gong, B. Q.; Teodorovic, A. V.;
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