Synthesis of trifluoromethyl alcohols from tert-butoxy-β-(trifluoromethyl)styrenes and trifluoromethylbenzyl ketones under the conditions of the Leuckart-Wallach reaction

Article abstract of DOI:10.1016/j.jfluchem.2008.06.014

A novel pathway towards trifluoromethylalcohols by an unexpected reaction of tert-butoxy-β-(trifluoromethyl)styrenes or corresponding trifluoromethylbenzyl ketones under the conditions of the Leuckart-Wallach reaction was elaborated.

Full text of DOI:10.1016/j.jfluchem.2008.06.014

Journal of Fluorine Chemistry 129 (2008) 1052–1055
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Journal of Fluorine Chemistry
journal homepage: www.elsevier.com/locate/fluor
Synthesis of trifluoromethyl alcohols from tert-butoxy-b-
(trifluoromethyl)styrenes and trifluoromethylbenzyl ketones under
the conditions of the Leuckart–Wallach reaction
b
Vasiliy M. Muzalevskiy a, Valentine G. Nenajdenko a, , Aleksey V. Shastin ,
*
c,**
Elizabeth S. Balenkova a, Gu¨nter Haufe
a Moscow State University, Department of Chemistry, Leninskie Gory, Moscow 119992, Russia
b Institute of Problems of Chemical Physics, Chernogolovka, Moscow Region 142432, Russia
c Organisch-Chemisches Institut, Westfa¨lische Wilhelms-Universita¨t Mu¨nster, D-48149 Mu¨nster, Germany
A R T I C L E I N F O
A B S T R A C T
novel pathway towards trifluoromethylalcohols by an unexpected reaction of tert-butoxy-b-
Article history:
A
Received 25 April 2008
Received in revised form 13 June 2008
Accepted 15 June 2008
Available online 22 June 2008
(trifluoromethyl)styrenes or corresponding trifluoromethylbenzyl ketones under the conditions of the
Leuckart–Wallach reaction was elaborated.
ß 2008 Elsevier B.V. All rights reserved.
Dedicated to Professor Dr. Dennis P. Curran
in honor of his outstanding contributions to
the field of fluorine Chemistry.
Keywords:
tert-Butoxy-b-(trifluoromethyl)styrenes
Trifluoromethylbenzyl ketones
Leuckart–Wallach reaction
Trifluoromethylalcohols
1. Introduction
vinylic halogen atom of such alkenes can be easily substituted
by different nucleophiles [16,17]. With different alcoholates
The reductive amination of carbonyl compounds is attractive
for organic synthesis because ketones or aldehydes can be directly
transformed to the corresponding primary or secondary alkyla-
mines in one-pot reactions without isolation of the intermediate
imines or semi-aminals [1,2]. One of the oldest and widely used
pathways is the Leuckart–Wallach reaction, which includes a
number of methods, using formic acid or formates as reducing
agents [3–7]. On the other hand, a new catalytic olefination
reaction of aldehydes or ketones was discovered by our research
group, recently [8]. Based on this reaction, we elaborated new
methods for the synthesis of various fluorinated alkenes such as
corresponding alkoxy-
pared [18]. Here we describe our results of the reaction of
new tert-butoxy- -(trifluoromethyl)styrenes and derived from
it trifluoromethylbenzyl ketones under the conditions of the
Leuckart–Wallach reaction.
b-(trifluoromethyl)styrenes were pre-
b
2. Results and discussion
According to our recent protocol [18] seven new tert-butoxy-b-
(trifluoromethyl)styrenes 3, contaminated with small amounts of
its regioisomers 4, were prepared in good to excellent yields
(Scheme 1, Table 1).
b
-chloro-
b
-(trifluoromethyl)styrenes 1,
b-bromo-b-(trifluoro-
methyl)styrenes 2 or
b
-bromo- -fluorostyrenes [9–15]. The
b
Obviously the core of the tert-butoxy-b-(trifluoromethyl)styr-
enes 3 or 4 includes an enolether moiety. In combination with the
tert-butyl group, which is known to be a good leaving group, one
could expect that these compounds can be used as close relatives of
the corresponding ketones in various reactions. Having both these
* Corresponding author. Tel.: +7 495 9392276; fax: +7 495 9328846.
** Corresponding author. Tel.: +49 251 83 33281; fax: +49 251 83 9772.
E-mail addresses: nen@acylium.chem.msu.ru (V.G. Nenajdenko),
haufe@uni-muenster.de (G. Haufe).
facts in mind the prepared mixtures of tert-butoxy-b-(trifluor-
0022-1139/$ – see front matter ß 2008 Elsevier B.V. All rights reserved.
doi:10.1016/j.jfluchem.2008.06.014

V.M. Muzalevskiy et al. / Journal of Fluorine Chemistry 129 (2008) 1052–1055
1053
Scheme 3. Preparation of trifluoromethylalcohols 5 via trifluoromethyl ketones 6.
Scheme 1. Synthesis of tert-butoxy-b-(trifluoromethyl)styrenes 3 and 4.
Table 1
Table 2
Results of syntheses of tert-butoxy-b-(trifluoromethyl)styrenes 3 and trifluor-
Results of synthesis and reduction of trifluoromethylketones 6
omethyl alcohols 5
Entry
Compounds (3:4 ratio)
R
Yield 6 (%)
Yield 5 (%)
Entry
Compounds
R
Yield 3 + 4 (%)
Ratio 3:4
Yield 5 (%)
8
9
a (86:14)
b (100:0)
c (92:8)
4-ClC6H4
59
56
47
67
65
56
1
2
3
4
5
6
7
2a
1b
2c
2d
2e
2f
4-ClC6H4
4-NO2C6H4
3-MeOC6H4
2-MeOC6H4
2-BrC6H4
4-BrC6H4
Ph
84
68
88
97
70
72
74
86:14
100:0
92:8
67
64
54
47
49
71
58
4-NO2C6H4
3-MeOC6H4
10
100:0
100:0
92:8
observed when benzophenones were heated with formamide
giving diarylcarbinols as major products. Deuteration experi-
ments revealed the reduction occurring by hydride transfer
from the formate to the ketone [6]. Generally trifluoromethyl
ketones were reduced with borohydrides to give the correspond-
ing alcohols [30].
2g
90:10
3. Conclusion
We discovered
a
new pathway towards trifluoromethyl
-(trifluoromethyl)styrenes or
Scheme 2. Synthesis of trifluoromethyl alcohols 5.
alcohols from tert-butoxy-
5
b
3
corresponding trifluoromethylbenzyl ketones 6 under the condi-
tions of the Leuckart–Wallach reaction. Since the expected
trifluoromethyl amines were not found in the product mixture,
we continue our efforts to prepare these products.
omethyl)styrenes 3 and 4 were treated with formic acid and
formamide at 170 8C. Surprisingly, we found trifluoromethyl
alcohols 5 as the only products instead of the expected amines
(Scheme 2, Table 1).
The structure of the obtained compounds was confirmed
mainly by NMR spectroscopy and ESI-MS analysis. Moreover, the
1H NMR and 19F NMR spectroscopic data of compound 5g agree
with previously published values [19].
4. Experimental
4.1. General
The reactions proceeded in good to high yields for all substituted
aryl compounds. It should be noted, that in all cases the alcohols
were obtained as single regioisomers 5. No analogous products
derived from the minor regioisomeric styrenes 4 were found.
The synthesized trifluoromethyl alcohols 5 are quite interesting
compounds. For example enantiopure trifluoromethyl alcohols are
versatile intermediates for the synthesis of antiferroelectric liquid
crystalline molecules [20,21] and recently trifluoromethylated
GABA [22] and mevalonate analogues [23] were prepared. Similar
trifluoromethyl alcohols were previously prepared by nucleophilic
trifluoromethylation of the corresponding aldehydes using
Rupert’s reagent [24–26] or analogues [27,28]. However, most
variations of the Rupert–Prakash reaction have a common draw-
back: frequently low yields were obtained with enolizable
carbonyl compounds [29]. Thus, our pathway efficiently supple-
ments the existing methods.
We also tried to synthesize trifluoromethyl substituted amines
from trifluoromethyl-benzyl ketones 6, which were prepared
from the tert-butoxy-b-(trifluoromethyl)styrenes 3 by solvolysis
with HBr/HOAc. Heating of thus prepared trifluoromethyl ketones
6 with excess formic acid and formamide (Leuckart–Wallach
reaction) also lead to trifluoromethylalcohols 5 instead of the
expected amines. However, the overall yield of 5 based on 1 or 2 is
lower in the latter three-step reactions. The ketones 6 might be
intermediates of the reactions of the enol ethers 3 with formic acid
and formamide (Scheme 3, Table 2). A similar reduction was
NMR spectra were recorded on Bruker ARX 300 MHz and Bruker
AMX Avance 400 spectrometers in CDCl3 with TMS and CCl3F as
internal standards. Mass spectra (ESI-MS) were measured on a
MicroTof Bruker Daltonics. Column chromatography and TLC were
performed on silica gel Merck 60 and Merck 60F254 plates,
respectively. The
b-chloro- 1 and b-bromo-b-trifluoromethyl-
styrenes 2 were synthesized according to our previously reported
procedures [10,14].
4.2. Synthesis of tert-butoxy-b-(trifluoromethyl)styrenes (general
procedure)
A 50 mL one neck round bottomed flask was charged with dry
DMF (10 mL) and the corresponding styrene (1 or 2) (5 mmol) and
cooled down to 0 8C. Then a cooled to 0 8C solution of t-BuOK
(670 mg, 6 mmol) in dry DMF (10 mL) was added dropwise with
stirring. The reaction mixture was stirred for 24 h at room
temperature and poured into water (200 mL). The products were
extracted with CH2Cl2 (3 Â 20 mL). The combined extract was
washed with water (2Â 50 mL) and brine (50 mL) and dried over
Na2SO4. CH2Cl2 was evaporated in vacuum, and the residue was
passed through a short filter with silica gel using hexane or
appropriate mixtures of hexane and CH2Cl2. The regioisomers 3
and 4 could not be separated by column chromatography.1H NMR
data of compounds 3a–d, f, g are in agreement with literature
values.

1054
V.M. Muzalevskiy et al. / Journal of Fluorine Chemistry 129 (2008) 1052–1055
4.2.1. 1-[(1Z)-2-tert-Butoxy-3,3,3-trifluoroprop-1-enyl]-4-
chlorobenzene (3a)
5 mmol). Yield (3 + 4): 903 mg, 74%, colorless oil; Regioisomer
3g: 1H NMR (CDCl3):
1.36 (s, 9H, OC(CH3)3), 6.68 (s, 1H,
CH CCF3), 7.34 (d, J = 7.3 Hz, 1H, Ar), 7.40 (t, J = 7.3 Hz, 2H, Ar),
7.69 (d, J = 7.3 Hz, 2H, Ar). Regioisomer 4g: 1H NMR (CDCl3):
1.30 (s, 9H, OC(CH3)3), 5.84 (q, J = 7.8 Hz, 1H, CHCF3), 7.49–
7.54 (m, 2H, Ar), the other signals are identical to those of the
regioisomer 3g.
d
Obtained as a 86:14 mixture with 1-[(1Z)-1-tert-butoxy-3,3,3-
trifluoroprop-1-enyl]-4-chlorobenzene (4a) from styrene 2a
(1425 mg, 5 mmol). Yield (3 + 4): 1168 mg, 84%, colorless oil.
d
Regioisomer 3a: 1H NMR (CDCl3):
d
1.36 (s, 9H, OC(CH3)3), 6.62 (s,
1H, CH CCF3), 7.36 (d, J = 8.6 Hz, 2H, Ar), 7.63 (d, J = 8.6 Hz, 2H,
Ar); Regioisomer 4a: 1H NMR (CDCl3):
1.29 (s, 9H, OC(CH3)3), 5.33
d
(q, J = 7.6 Hz, 1H, CHCF3), 7.38 (d, J = 8.6 Hz, 2H, Ar), 7.45 (d,
J = 8.6 Hz, 2H, Ar).
4.3. General procedure for the synthesis of the
3-aryl-1,1,1-trifluoropropan-2-ols 5
4.2.2. 1-[(1Z)-2-tert-Butoxy-3,3,3-trifluoroprop-1-enyl]-4-
nitrobenzene (3b)
A mixture of corresponding tert-butoxy-b-(trifluoromethyl)-
styrenes 3, 4 (1 mmol) or ketone 6 (1 mmol), formic acid (184 mg,
4 mmol) and formamide (1.5 mL) were heated at 170 8C with reflux
condenser for 1 h. The reaction mixture was allowed to cool to
room temperature, diluted with CH2Cl2 (10 mL) and poured into
water (100 mL). The reaction products were extracted with CH2Cl2
(3Â 30 mL) and combined extract was dried over MgSO4. CH2Cl2
was evaporated in vacuo and the residue was purified by column
chromatography (silica gel, gradient cyclohexane/ethyl acetate).
Obtained from styrene 1b (1250 mg, 5 mmol). Yield: 1200 mg,
83%, yellow oil; 1H NMR (CDCl3):
d 1.32 (s, 9H, OC(CH3)3), 6.69 (s,
1H, CH CCF3), 7.83 (d, J = 8.8 Hz, 2H, Ar), 8.22 (d, J = 8.8 Hz, 2H, Ar).
4.2.3. 1-[(1Z)-2-tert-Butoxy-3,3,3-trifluoroprop-1-enyl]-3-
methoxybenzene (3c)
Obtained as a 92:8 mixture with 1-[(1Z)-1-tert-butoxy-3,3,3-
trifluoroprop-1-enyl]-3-methoxybenzene (4c) from styrene 2c
(1405 mg, 5 mmol). Yield (3 + 4): 1205 mg, 88%, colorless oil;
4.3.1. 3-(4-Chlorophenyl)-1,1,1-trifluoropropan-2-ol (5a)
Regioisomer 3c: 1H NMR (CDCl3):
d
1.36 (s, 9H, OC(CH3)3), 3.84 (s,
Yield: 150 mg, 67%, colorless crystals, mp 66–67 8C. 1H NMR
3H, OCH3), 6.65 (s, 1H, CH CCF3), 6.85–6.90 (m, 1H, Ar), 7.21 (d,
(300 MHz, CDCl3): d 2.46 (br s, 1H, OH), 2.78 (dd, J = 14.3 and
J = 7.3 Hz, 1H, Ar), 7.26–7.32 (m, 2H, Ar); Regioisomer 4c 1H
10.0 Hz, 1H, CH2), 2.98 (dd, J = 14.3 and 2.9 Hz, 1H, CH2), 3.98–4.11
(m, 1H, CHOH), 7.16 (d, J = 8.4 Hz, 2H, 4-ClC6H4–), 7.28 (d,
NMR (CDCl3):
d 1.30 (s, 9H, OC(CH3)3), 3.83 (s, 3H, OCH3),
5.84 (q, J = 7.8 Hz, 1H, CHCF3), 6.93–6.98 (m, 1H, Ar), 7.03–7.11
(m, 1H, Ar).
J = 8.4 Hz, 2H, 4-ClC6H4–); 19F NMR (282 MHz, CDCl3):
d
À79.59
(d, J = 6.5 Hz, CF3); 13C NMR (75 MHz, CDCl3):
d 35.4, 71.3 (q,
J = 31.0 Hz, C–CF3), 124.8 (q, J = 282.1 Hz, CF3), 128.9, 130.8, 133.1,
134.3. Anal. calcd. for C9H8ClF3O: C, 48.13; H, 3.59. Found: C, 48.13;
H 3.49.
4.2.4. 1-[(1Z)-2-tert-Butoxy-3,3,3-trifluoroprop-1-enyl]-2-
methoxybenzene (3d)
Obtained from styrene 2d (1405 mg, 5 mmol). Yield: 1363 mg,
97%, colorless oil; 1H NMR (CDCl3):
3H, OCH3), 6.89 (d, J = 8.0 Hz, 1H, Ar), 6.94 (t, J = 7.6 Hz, 1H, Ar),
6.95 (s, 1H, CH CCF3), 7.28 (td, J = 8.0 and 1.4 Hz, 1H, Ar), 7.96 (dd,
J = 7.6 and 1.4 Hz, 1H, Ar).
d
1.28 (s, 9H, OC(CH3)3), 3.85 (s,
4.3.2. 3-(4-Nitrophenyl)-1,1,1-trifluoropropan-2-ol (5b)
Yield: 150 mg, 64%, viscous oil. 1H NMR (300 MHz, CDCl3):
d
2.98 (dd, J = 14.2 and 10.0 Hz, 1H, CH2), 3.08–3.17 (m, 2H), 4.16–
4.30 (m, 1H, CHOH), 7.46 (d, J = 8.7 Hz, 2H, 4-NO2C6H4–), 8.12 (d,
J = 8.7 Hz, 2H, 4-NO2C6H4–); 19F NMR (282 MHz, CDCl3):
d
À79.68
4.2.5. 4.2.5 1-[(1Z)-2-tert-Butoxy-3,3,3-trifluoroprop-1-enyl]-2-
bromobenzene (3e)
Obtained from styrene 2e (1650 mg, 5 mmol). Yield: 1131 mg,
70%, colorless oil; 1H NMR (CDCl3):
d 1.24 (s, 9H, OC(CH3)3), 6.86 (s,
1H, CH CCF3), 7.19 (t, J = 7.8 Hz, 1H, Ar), 7.33 (t, J = 7.8 Hz, 1H, Ar),
7.62 (d, J = 7.8 Hz, 1H, Ar), 7.86 (d, J = 7.8 Hz, 1H, Ar).
(d, J = 6.4 Hz, CF3); 13C NMR (75 MHz, CDCl3):
d 35.8, 70.8 (q,
J = 31.4 Hz, C–CF3), 124.7 (q, J = 282.4 Hz, CF3), 123.7, 130.5, 144.1,
146.9. Anal. calcd. for C9H8F3NO3: C, 45.97; H, 3.43; N, 5.96; Found:
C, 45.83; H, 3.31; N, 5.73. ESI-MS (m/z): calcd. for C9H8F3NO3 [M]+
235.0456, found 235.0450.
4.3.3. 3-(3-Methoxyphenyl)-1,1,1-trifluoropropan-2-ol (5c)
4.2.6. 1-[(1Z)-2-tert-Butoxy-3,3,3-trifluoroprop-1-enyl]-4-
bromobenzene (3f)
Yield: 120 mg, 54%, pale yellow solid, mp 58–59 8C. 1H NMR
(300 MHz, CDCl3):
d 2.50 (br s, 1H, OH), 2.78 (dd, J = 14.2 and
Obtained as a 92:8 mixture with 1-[(1Z)-1-tert-butoxy-3,3,3-
trifluoroprop-1-enyl]-4-bromobenzene (4f) from styrene 2f
(1425 mg, 5 mmol). Yield (3 + 4): 1153 mg, 71%, colorless oil.
10.2 Hz, 1H, CH2), 3.01 (dd, J = 14.2 and 2.7 Hz, 1H, CH2), 3.78 (s,
3H, MeO), 4.03–4.16 (m, 1H, CHOH), 6.76–6.85 (m, 3H, 3-
MeOC6H4–), 7.24 (t, J = 7.7 Hz, 1H, 3-MeOC6H4–); 19F NMR
Regioisomer 3f: 1H NMR (CDCl3):
d
1.30 (s, 9H, OC(CH3)3), 6.55 (s,
(282 MHz, CDCl3):
d
À79.59 (d, J = 6.7 Hz, CF3); 13C NMR
1H, CH CCF3), 7.47 (d, J = 8.7 Hz, 2H, Ar), 7.52 (d, J = 8.7 Hz, 2H,
(75 MHz, CDCl3): d 36.2, 55.2, 71.3 (q, J = 30.8 Hz, C–CF3), 112.5,
115.2, 121.7, 124.9 (q, J = 282.1 Hz, CF3), 129.8, 137.3, 159.8. Anal.
calcd. for C10H11F3O2: C, 54.55; H, 5.04. Found: C, 54.88; H 5.33.
Ar); 19F NMR (282 MHz, CDCl3):
(CDCl3):
d
À67.23 (s, CF3); 13C NMR
d
28.8 (OC(CH3)3), 84.6 (OC(CH3)3), 120.8 (q, J = 4.5 Hz,
CH CCF3), 121.2 (q, J = 276.7 Hz, CF3), 140.7 (q, J = 32.7 Hz, C–
CF3); 129.4, 131.2, 131.5, 132.3 (Ar). Regioisomer 4f: 1H NMR
ESI-MS (m/z): calcd. for C10H11F3O2 [M]+ 220.0711, found
220.0705.
(CDCl3):
7.33 (d, J = 8.5 Hz, 2H, Ar); 19F NMR (282 MHz, CDCl3):
J = 7.7 Hz, CF3);13
NMR (CDCl3): 29.4 (OC(CH3)3), 82.6
d
1.23 (s, 9H, OC(CH3)3), 5.28 (q, J = 7.7 Hz, 1H, CHCF3),
d
À56.91 (d,
4.3.4. 3-(2-Methoxyphenyl)-1,1,1-trifluoropropan-2-ol (5d)
C
d
Yield: 101 mg, 47%, colorless oil. 1H NMR (300 MHz, CDCl3):
d
(OC(CH3)3), 106.6 (q, J = 34.9 Hz, C CHCF3); 129.0, 129.8, 132.2,
137.2 (Ar). Anal. Calcd. for C13H14BrF3O: C, C 48.32; H, 4.37. Found:
C, 48.42; H, 4.33.
2.95 (dd, J = 14.0 and 10.0 Hz, 1H, CH2), 3.07 (dd, J = 14.0 and
3.0 Hz, 1H, CH2), 3.87 (s, 3H, MeO), 4.11–4.23 (m, 1H, CHOH), 6.91
(d, J = 7.8 Hz, 1H, 2-MeOC6H4–), 6.97 (d, J = 7.8 Hz, 1H, 2-
MeOC6H4–), 7.19 (dd, J = 7.8 and 1.3 Hz, 1H, 2-MeOC6H4–), 7.28
(td, J = 7.8 and 1.3 Hz, 1H, 2-MeOC6H4–); 19F NMR (282 MHz,
4.2.7. [(1Z)-2-tert-Butoxy-3,3,3-trifluoroprop-1-enyl]benzene (3g)
Obtained as a 90:10 mixture with [(1Z)-1-tert-butoxy-3,3,3-
trifluoroprop-1-enyl]benzene (4g) from styrene 2g (1255 mg,
CDCl3):
31.6, 55.5, 70.8 (q, J = 30.6 Hz, C–CF3), 125.1 (q, J = 282.0 Hz, CF3),
d d
-79.90 (d, J = 6.8 Hz, CF3); 13C NMR (75 MHz, CDCl3):

V.M. Muzalevskiy et al. / Journal of Fluorine Chemistry 129 (2008) 1052–1055
1055
110.5, 121.2, 124.1, 128.8, 131.6, 157.3. Anal. calcd. for C10H11F3O2:
C, 54.55; H, 5.04. Found: C, 54.43; H 4.63.
4.4.3. 3-(3-Methoxyphenyl)-1,1,1-trifluoroacetone (6c)
Pale yellow viscous oil (206 mg, 47%). 1H NMR (300 MHz,
CDCl3): 3.79 (s, 3H, MeO), 3.97 (s, 2H, CH2), 6.72–6.81 (m, 2H, 3-
MeOC6H4–), 6.87 (dt, J = 7.9 and 2.0 Hz, 1H, 3-MeOC6H4–), 7.27 (t,
J = 7.9 Hz, 1H, 3-MeOC6H4–); 19F NMR (282 MHz, CDCl3):
-78.31
(s, CF3); 13C NMR (75 MHz, CDCl3):
43.0 (CH2), 55.2 (OCH3), 113.4,
d
4.3.5. 3-(2-Bromophenyl)-1,1,1-trifluoropropan-2-ol (5e)
Yield: 132 mg, 49%, yellowish solid, mp 56–57 8C. 1H NMR
d
(300 MHz, CDCl3):
d
2.33 (br s, 1H, OH), 2.90 (dd, J = 14.2 and
d
10.4 Hz, 1H, CH2), 3.28 (dd, J = 14.3 and 2.8 Hz, 1H, CH2), 4.20–4.34
(m, 1H, CHOH), 7.15 (td, J = 7.0 and 2.7 Hz, 1H, 2-BrC6H4–), 7.23–
7.33 (m, 2H, 2-BrC6H4–), 7.57 (d, J = 7.9 Hz, 1H, 2-BrC6H4–); 19F
115.37, 115.42 (q, J = 292.4 Hz, CF3), 121.9, 129.9, 131.7, 159.9,
188.7 (q, J = 35.3 Hz, C–CF3). 1H NMR spectra are in agreement with
published data [32].
NMR (282 MHz, CDCl3):
(75 MHz, CDCl3):
d
À79.77 (d, J = 6.6 Hz, CF3); 13C NMR
d
36.5, 69.8 (q, J = 31.1 Hz, C–CF3), 124.6, 124.8 (q,
Acknowledgements
J = 282.1 Hz, CF3), 127.6, 129.0, 132.3, 133.0, 135.2. Anal. calcd. for
C9H8BrF3O: C, 40.18; H, 3.00. Found: C, 40.64; H 2.97.
This project was supported by the Deutsche Forschungsge-
meinschaft (DFG) through grant Gz: 436 RUS 113/858/0-1 and
RFBR-DFG 07-03-91562-NNIO_a, and 08-03-00736_a.
4.3.6. 3-(4-Bromophenyl)-1,1,1-trifluoropropan-2-ol (5f)
Yield: 190 mg, 71%, white crystals, mp 75–76 8C. 1H NMR
(300 MHz, CDCl3):
d 2.25 (br s, 1H, OH), 2.80 (dd, J = 14.2 and
References
9.9 Hz, 1H, CH2), 2.98 (dd, J = 14.2 and 2.8 Hz, 1H, CH2), 4.03–4.13
(m, 1H, CHOH), 7.13 (d, J = 8.4 Hz, 2H, 4-BrC6H4–), 7.45 (d,
[1] M.B. Smith, J. March, March’s Advanced Organic Chemistry, Wiley–Interscience,
New York, 2007, pp. 1288–1292.
J = 8.4 Hz, 2H, 4-BrC6H4–); 19F NMR (282 MHz, CDCl3):
d
-79.61
(d, J = 6.6 Hz, CF3); 13C NMR (75 MHz, CDCl3):
d 35.5, 71.3 (q,
[2] B.M. Trost, T.R. Verhoeven, in: G. Wilkinson, F.G. Stone, E.W. Abel (Eds.),
Comprehensive Organometallic Chemistry, vol. 8, Pergamon, Oxford, 1982, p. 84.
[3] R. Leuckart, Ber. Dtsch. Chem. Ges. 18 (1885) 2341–2344.
[4] O. Wallach, Ber. Dtsch. Chem. Ges. 24 (1891) 3992–3993.
[5] For a review, see M.L. Moore, Org. React. 5 (1949) 301–330.
[6] For discussions of the mechanism, see P.I. Awachie, V.C. Agwada, Tetrahedron, 46
(1990) 1899–1910, and references cited therein.
J = 31.1 Hz, C–CF3), 121.2, 124.8 (q, J = 282.1 Hz, CF3), 131.2, 131.8,
134.8. Anal. calcd. for C9H8BrF3O: C, 40.18; H, 3.00. Found: C, 40.64;
H 3.06.
4.3.7. 3-Phenyl-1,1,1-trifluoropropan-2-ol (5g)
[7] For the effect of added formamide, see I. Helland, T. Lejon, Acta Chem. Scand. 53
(1999) 76–78.
Yield: 120 mg, 58%, colorless oil. 1H NMR (300 MHz, CDCl3):
d
[8] A.V. Shastin, V.N. Korotchenko, V.G. Nenajdenko, E.S. Balenkova, Tetrahedron 56
(2000) 6557–6563.
[9] V.G. Nenajdenko, A.V. Shastin, V.N. Korotchenko, G.N. Varseev, E.S. Balenkova, Eur.
J. Org. Chem. (2003) 302–308.
[10] V.N. Korotchenko, A.V. Shastin, V.G. Nenajdenko, E.S. Balenkova, Tetrahedron 57
(2001) 7519–7527.
[11] V.G. Nenajdenko, G.N. Varseev, V.N. Korotchenko, A.V. Shastin, E.S. Balenkova, J.
Fluorine Chem. 124 (2003) 115–118.
2.61 (br s, 1H, OH), 2.82 (dd, J = 14.2 and 10.2 Hz, 1H, CH2), 3.03 (dd,
J = 14.2 and 2.9 Hz, 1H, CH2), 4.03–4.17 (m, 1H, CHOH), 7.22–7.37
(m, 5H, C6H5–); 19F NMR (282 MHz, CDCl3):
d
-79.59 (d, J = 6.5 Hz,
CF3); 13C NMR (75 MHz, CDCl3):
d
36.1, 71.4 (q, J = 30.8 Hz, C–CF3),
124.9 (q, J = 282.1 Hz, CF3), 127.2, 128.7, 129.4, 135.9. 1H NMR and
19F NMR spectra are in agreement with published data [19]. Anal.
calcd. for C9H9F3O: C, 56.84; H, 4.77. Found: C, 56.47; H 4.86.
[13] V.G. Nenajdenko, G.N. Varseev, V.N. Korotchenko, A.V. Shastin, E.S. Balenkova, J.
Fluorine Chem. 124 (2004) 1339–1345.
[14] V.G. Nenajdenko, G.N. Varseev, A.V. Shastin, E.S. Balenkova, J. Fluorine Chem. 126
(2005) 907–913.
4.4. General procedure for the synthesis of the 3-aryl-1,1,1-
trifluoroacetones 6
[15] A.V. Shastin, V.M. Muzalevsky, E.S. Balenkova, V.G. Nenajdenko, Mendeleev
Commun. 16 (2006) 179–180.
[16] V.G. Nenajdenko, V.M. Muzalevskiy, A.V. Shastin, E.S. Balenkova, G. Haufe, J.
Fluorine Chem. 128 (2007) 818–826.
[17] V.M. Muzalevskiy, A.V. Shastin, E.S. Balenkova, V.G. Nenajdenko, Russ. Chem. Bull.
56 (2007) 1526–1533.
[18] V.M. Muzalevskiy, A.V. Shastin, E.S. Balenkova, V.G. Nenajdenko, G. Haufe, sub-
mitted for publication.
[19] Y. Kuroki, Y. Sakamaki, K. Iseki, I. Tsukuba, Org. Lett. 3 (2001) 457–459.
[20] Y. Suzuki, T. Hagiwara, I. Kawamura, N. Okamura, T. Kitazume, M. Kakimoto, Y.
Imai, Y. Ouchi, H. Takezoe, A. Fukuda, Liq. Cryst. 6 (1989) 167–174.
[21] K. Mikami, in: P.V. Ramachandran (Ed.), Asymmetric Fluoroorganic Chemistry:
Synthesis, Application and Future Directions, American Chemical Society,
Washington, DC, 2000, pp. 255–269.
A
mixture of the corresponding tert-butoxy-b-(trifluoro-
methyl)styrenes 3 and 4 (2 mmol), 48% HBr (670 mg, 4 mmol)
and glacial acetic acid (4 mL) were stirred at room temperature for
48 h. The reaction mixture was diluted with CH2Cl2 (20 mL) and
poured into water (100 mL). The reaction products were extracted
with CH2Cl2 (3 Â 30 mL) and the combined extract was dried over
MgSO4. CH2Cl2 was evaporated in vacuo and the residue was
purified by column chromatography (silica gel, CH2Cl2).
[22] E.N. Shaitanova, I.I. Gerus, M.Y. Belik, V.P. Kukhar, Tetrahedron: Asymmetry. 18
(2007) 192–198.
[23] I.S. Kondratov, I.I. Gerus, V.P. Kukhar, O.V. Manoilenko, Tetrahedron: Asymmetry.
18 (2007) 1918–1925.
[24] G.K.S. Prakash, A.K. Yudin, Chem. Rev. 97 (1997) 757–786.
[25] R.P. Singh, J.M. Shreeve, Tetrahedron 56 (2000) 7613–7632.
[26] G.K.S. Prakash, M. Mandal, J. Fluorine Chem. 112 (2001) 123–131.
[27] B.R. Langlois, T. Billard, in: V.A. Soloshonok (Ed.), Fluorine-Containing Synthons,
ACS Symposium Series, vol. 911, American Chemical Society, Washington, 2005,
pp. 57–86.
4.4.1. 3-(4-Chlorophenyl)-1,1,1-trifluoroacetone (6a)
White powder (264 mg, 59%), mp 88–89 8C. 1H NMR (300 MHz,
CDCl3):
(d, J = 8.4 Hz, 2H, 4-ClC6H4–); 19F NMR (282 MHz, CDCl3):
(s, CF3); 13C NMR (75 MHz, CDCl3):
42.2 (CH2), 115.7 (q,
d
3.98 (s, 2H, CH2), 7.14 (d, J = 8.4 Hz, 2H, 4-ClC6H4–), 7.33
d
-78.42
d
J = 292.4 Hz, CF3), 129.1, 131.0, 132.6, 134.1, 188.5 (q, J = 35.3 Hz,
C–CF3). 1H NMR spectra are in agreement with published data [31].
[28] T. Billard, B.R. Langlois, Eur. J. Org. Chem. (2007) 891–897, and references cited
therein.
[29] G.K.S. Prakash, J. Hu, in: V.A. Soloshonok (Ed.), Fluorine-Containing Synthons, ACS
Symposium Series, vol. 911, American Chemical Society, Washington, 2005, pp.
16–56.
[30] D.G. Kuhn, V.M. Kamhi, J.A. Furch, R.E. Diehl, G.T. Lowen, V. Kameswaran, Pestic.
Sci. 41 (1994) 279–286.
[31] P.V. Ramachandran, H.C. Brown, in: V.A. Soloshonok (Ed.), Enantiocontrolled
Synthesis of Fluoro-Organic Compounds, John Wiley & Sons, Chichester, 1999,
pp. 179–228.
4.4.2. 3-(4-Nitrophenyl)-1,1,1-trifluoroacetone (6b)
Yellow solid (260 mg, 56%), mp 81–82 8C. 1H NMR (300 MHz,
CDCl3):
8.23 (d, J = 8.7 Hz, 2H, 4-NO2C6H4–); 19F NMR (282 MHz, CDCl3):
78.56 (s, CF3); 13C NMR (75 MHz, CDCl3):
42.4 (CH2), 115.2 (q,
d 4.18 (s, 2H, CH2), 7.41 (d, J = 8.7 Hz, 2H, 4-NO2C6H4–),
d
-
d
J = 292.0 Hz, CF3), 124.0, 130.8, 137.6, 147.7, 187.6 (q, J = 36.2 Hz,
C–CF3). ESI-MS (m/z): calcd. for C9H6F3NO3 [M]+ 233.0300, found
233.0294.
[32] R.G. Pinder, R.W. Brimblecombe, D.M. Green, J. Med. Chem. 12 (1969) 322–324.