Nucleophilic difluoromethylation and difluoromethylenation using bromodifluoromethyl phenyl sulfone

Article abstract of DOI:10.1016/j.jfluchem.2005.07.011

Tetrakis(dimethylamino)ethylene (TDAE) was found to be an effective electron-transfer agent that promoted the reactions of bromodifluoromethyl phenyl sulfone with aldehydes to give structurally diverse (benzenesulfonyl) difluoromethylated alcohols in good yield, which can be further transformed into difluoromethyl alcohols and 1,1-difluoro-1-alkenes via reductive desulfonylation and Julia olefination, respectively.

Full text of DOI:10.1016/j.jfluchem.2005.07.011

Journal of Fluorine Chemistry 126 (2005) 1361–1367
www.elsevier.com/locate/fluor
Nucleophilic difluoromethylation and difluoromethylenation using
bromodifluoromethyl phenyl sulfone
a
a,b
a
G.K. Surya Prakash a, , Ying Wang , Jinbo Hu , George A. Olah
*
a Loker Hydrocarbon Research Institute and Department of Chemistry, University of Southern California,
Los Angeles, CA 90089-1661, USA
b Key Laboratory of Organofluorine Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences,
354 Feng-Lin Road, Shanghai 200032, China
Received 22 July 2005; accepted 25 July 2005
Available online 12 September 2005
Abstract
Tetrakis(dimethylamino)ethylene (TDAE) was found to be an effective electron-transfer agent that promoted the reactions of bromodi-
fluoromethyl phenyl sulfone with aldehydes to give structurally diverse (benzenesulfonyl)difluoromethylated alcohols in good yield, which
can be further transformed into difluoromethyl alcohols and 1,1-difluoro-1-alkenes via reductive desulfonylation and Julia olefination,
respectively.
# 2005 Elsevier B.V. All rights reserved.
Keywords: Fluorine; Bromodifluoromethyl phenyl sulfone; Difluoromethyl alcohol; 1,1-Difluoro-1-alkene
1. Introduction
introduce difluoromethyl and difluoromethylene function-
alities using a difluoromethyl phenyl sulfone as a synthon
under highly basic conditions.
gem-Difluorinated compounds, such as difluoromethyl
alcohols and 1,1-difluoro-1-alkenes, are highly useful for
pharmaceutical or agrochemical applications, since the
difluoromethylene functionality (CF2) is known to be an
isostere and isopolar to an oxygen atom [1]. Difluoromethyl
group (CF2H) can act as both a liphophilic isostere of
hydroxyl group (OH) and a hydrogen donor through
hydrogen bonding [2], while gem-difluorovinyl functionality
can act as a bioisostere for aldehydes and ketones [3] with a
different reactivity pattern. Many functionalized difluor-
omethyl compounds and 1,1-difluoro-1-alkenes are used as
enzyme inhibitors [4], pesticides [5], among others. More-
over, 1,1-difluoro-1-alkenes can be further converted into
different fluorinated compounds and polymers [6]. Thus, the
development of effective ways for the preparation of these
two classes of gem-difluorinated compounds is of great
significance. Recently, we have reported methods [7] to
Bromodifluoromethyl phenyl sulfone (PhSO2CF2Br) was
first synthesized by Burton and coworkers in 1981 [8],
however, its synthetic application has rarely been explored.
Recently, we have reported the use of bromodifluromethyl
phenyl sulfone for the preparation of fluroalkylsilanes [9].
Tetrakis(dimethylamino)ethylene (TDAE), as an efficient
reductant to generate substituted difluoromethylated carba-
nions from halo-difluoromethyl precursors, has been
reported by Dolbier and coworkers [10]. However, the
reaction between TDAE and bromodifluoromethyl phenyl
sulfone to generate (benzenesulfonyl)difluoromethyl anion
(PhSO2CF2À), has not been reported. In this paper, we
describe the efficient TDAE-mediated nucleophilic reac-
tions between bromodifluoromethyl phenyl sulfone (1) and
aldehydes (2). The resulting (benzensulfonyl)difluoro-
methyl alcohols (3) can be further transformed into
difluoromethyl alcohols (4) and 1,1-difluoro-1-alkenes (6)
via reductive desulfonylation and Julia olefination, respec-
tively (Scheme 1) [11].
* Corresponding author. Fax: +1 213 740 6270.
E-mail address: gprakash@usc.edu (G.K. Surya Prakash).
0022-1139/$ – see front matter # 2005 Elsevier B.V. All rights reserved.
doi:10.1016/j.jfluchem.2005.07.011

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G.K.S. Prakash et al. / Journal of Fluorine Chemistry 126 (2005) 1361–1367
Scheme 1. Difluoromethylation of aldehydes using 1.
2. Results and discussion
Na2HPO4 in methanol at À20 to À10 8C over 1 h. The
results of desulfonylations are shown in Table 2.
Nucleophilic addition reactions between 1 and 2 were
carried out according to the following procedure: under an
argon atmosphere, the TDAE was added dropwise to the
mixture of 1 and 2 in DMF solution under 60 W sun lamp
irradiation. The reaction conditions were carefully opti-
mized by using different reactant ratios, reaction tempera-
tures and light intensities, and we found the best product
yields can be obtained with the following reaction
conditions: 2.2 equivalents of TDAE, 2.2 equivalents of
sulfone (1) and 1.0 equivalents of aldehyde (2) in DMF were
stirred under the sun lamp at À30 8C for 1 h and then at room
temperature for 6 h. A variety of (benzenesulfonyl)difluoro-
methylated alcohols (3) were prepared in moderate to
good yields as shown in Table 1. However, the reactions of
1/TDAE system with ketones gave very poor yields of
products (10–30%) because of steric constrains.
Julia-type olefination of 3 were also successfully
achieved to give 1,1-difluoro-1-alkenes 6 in good yields.
First, the alcohols were converted into the mesylates by
using 2 equivalents of MsCl, 4 equivalents of Et3N, and
catalytic amount of 4-dimethylaminopyridine (DMAP) in
CH2Cl2 at 0 8C over 2 h. Then the mesylates underwent the
reductive elimination to give 1,1-difluoro-1-alkenes 5 by
treatment with 6 equivalents of 10% Na(Hg), 4 equivalents
of Na2HPO4 in CH3OH at À40 to 0 8C for 1 h. The Julia
olefinations of (benzenesufonyl)difluoromethyl alcohols (3)
are more difficult than that of the alcohols without fluorine
atoms because the high electronegativity of fluorine atoms in
the carbanion intermediate make it easier to undergo the
protonation to form difluoromethyl compounds 4. From the
19F NMR spectrum of the reaction mixture, we can see that
both the 1,1-difluoro-1-alkenes and the difluoromethyl
alcohols are formed. Thus, the choice of the right leaving
group becomes very important for the elimination of these
(benzenesulfonyl)difluoromethyl alcohol derivatives. We
explored acetate (Ac), tosylate (Ts), triflate, and mesylate
groups as the protecting groups for the alcohol, and found
that the mesylates were the best for the further reductive
elimination to give 1,1-difluoro-1-alkenes 6. This suggests
that neither the good leaving groups such as the triflate
(-OSO2CF3) and tosylate (-OSO2C6H4CH3) nor the rela-
tively stable leaving group such as acetate (OAc) were
suitable for this olefination protocol. This can be surmised
by considering that reactive leaving groups can be easily
displaced before the desulfonylation step and making further
reductive elimination difficult, while the stable leaving
group is difficult to be removed in the reductive elimination
of the carbanion intermediate, resulting in the formation of
difluoromethyl compounds. Considering the protonation
side-reaction, we also tried SmI2 as the reducing agent [11]
in the reductive elimination step to avoid using the protic
solvent MeOH, which is necessary in Na(Hg) reduction.
However, the result was not ideal and other products were
The mechanism of this reaction is proposed in Scheme 2,
which is similar to the early reports [10]. Initially, an
orange–red charge-transfer complex is formed between 1
and TDAE. Then two electrons from TDAE is transferred to
bromodifluoromethyl phenyl sulfone to generate (benzene-
sulfonyl)difluoromethyl anion (PhSO2CF2À) and BrÀ.
(Benzenesulfonyl)difluoromethyl anion undergoes further
addition into aldehydes to give (benzenesulfonyl)difluoro-
methyl alcohols 3. Here, the sun lamp irradiation is necessary
for inducing the electron transfer from TDAE to 1.
The resulting (benzenesulfonyl)difluoromethyl alcohols
are very useful intermediates, which can be further
converted into various fluorinated materials [12]. Two types
of reactions of the difluoromethyl alcohols were carried out
to demonstrate the utility of alcohols: the reductive
desulfonylation to give difluoromethyl compounds 4 and
the Julia olefination to give 1,1-difluoro-1-alkenes 6. The
results are outlined in Scheme 3.
Reductive desulfonylations of 3 were completed to give
difluoromethyl alcohols 4 in good yields by using 5
equivalents 10% Na(Hg) amalgam and 5 equivalents of

G.K.S. Prakash et al. / Journal of Fluorine Chemistry 126 (2005) 1361–1367
1363
Table 1
Nucleophilic (benzenesulfonyl)difluoromethylation of aldehydes using
PhSO2CF2Br/TDAE in DMF at À30 8C ꢀ RT under sun-lamp irradiation
Entry Aldehyde 2
Product 3
Yielda (%)
74
a
b
c
d
e
40
53
65
55
Scheme 3. Reductive desulfonylation and Julia olefination of 3.
3. Conclusions
Thenucleophilicreactionsofbromodifluoromethylphenyl
sulfone with aldehydes in the presence of TDAE were
completed successfully. The resulting difluoromethyl alco-
hols are very useful intermediates, which can undergo both
reductive desulfonylation to give difluoromethyl alcohols
and via Julia olefination to give 1,1-difluoro-1-alkenes in
good yields. The methodology provides convenient and
efficient ways to introduce the difluoromethyl group and
1,1-difluorovinyl functionality into the organic compounds.
f
70
82
g
h
57
4. Experimental
4.1. General
Materials and Instrumentation. Unless otherwise men-
tioned, all chemicals were purchased from commercial
sources. Bromodifluoromethyl phenyl sulfone 1 was
prepared using known procedures [8]. CH2Cl2 was distilled
over calcium hydride. Silica gel column chromatography
was used to isolate the products using 60–200 mesh silica
gel. 1H, 13C, and 19F NMR spectra were recorded on either a
400 MHz or 360 MHz NMR spectrometer. 1H NMR
chemical shifts were determined relative to the signal of
residual proton in CDCl3 d 7.26 or Acetone-d6 d 2.04. 13C
NMR chemical shifts were determined relative to the 13C
signal of sovent: CDCl3 d 77.0 or Acetone-d6 d 29.8. 19F
NMR chemical shifts were determined relative to internal
CFCl3 at d 0.0. High-resolution mass data of low boiling
compounds were recorded on a GC chromatograph with
micromass GCT (time of flight) mass spectrometer. Other
high-resolution mass data were recorded on a high-
resolution mass spectrometer in the EI mode.
i
80
a
Isolated yields.
formed rather than the expected alkenes. Finally, we
optimized the Julia olefination reaction of (benzenesulfo-
nyl)difluoromethyl alcohols with the OMs group as the
leaving group and the Na(Hg) as the reducing reagent for the
elimination step. The results are listed in Table 3.
4.2. Typical procedure for nucleophilic reactions of 1
with aldehydes
Under an argon atmosphere, bromodifluoromethyl
phenyl sulfone 1 (600 mg, 2.2 mmol), 5 mL DMF, and
benzaldehyde (106.1 mg, 1 mmol) were added into a dry
Schlenk flask and contents were cooled to À30 8C. After
Scheme 2. Mechanism of nucleophilic reaction of aldehydes with
PhSO2CF2Br/TDAE reagent.

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G.K.S. Prakash et al. / Journal of Fluorine Chemistry 126 (2005) 1361–1367
Table 2
Desulfonylation of (benzenesulfonyl)difluoromethyl alcohols 3 using Na(Hg) amalgam
Entry
a
Carbinol 3
Product 4
Yielda (%)
79
b
84
86
c
a
Isolated yields.
stirring the mixture for 15 min, TDAE (440 mg, 2.2 mmol)
was added in dropwise. Under the irradiation of sun lamp,
the reaction mixture was stirred at À30 8C for 1 h and then at
room temperature for 6 h. The completion of the reaction
was monitored by 19F NMR. The resulting orange–red
solution was filtered and the solid was washed with 100 mL
ether. After the ether layer was separated from the DMF
layer, the DMF layer was hydrolyzed with 50 mL brine and
extracted by ether (20 mL Â 3). Then the combined ether
layer was washed by brine five times and dried over
magnesium sulfate. After removing the solvent by a rotary
evaporator, the crude product was further purified by silica
gel column chromatography (first hexane: ethyl acet-
ate = 7:1, then hexane:ethyl acetate = 1:1) to give pure 2-
benzenesulfonyl-2,2-difluoro-1-phenylethanol (3a) (221 mg,
74% yield) as a colorless crystal. 1H NMR (CDCl3): d 3.92
(d, J = 4.4 Hz, 1H); 5.60 (dd, J = 21 Hz, 3 Hz, 1H); 7.36 (m,
3H); 7.48 (m, 2H); 7.56 (t, J = 8 Hz, 2H); 7.70 (t, J = 8 Hz,
1H); 7.98 (d, J = 8 Hz, 2H). 19F NMR (CDCl3): d À104.4
(dd, J = 238 Hz, 3 Hz, 1F); À119.9 (dd, J = 238 Hz, 21 Hz,
1F). MS (EI, m/z): 298 (M+), 156, 140, 127, 107, 77. The
data are consistent with the previous report [12].
(E)-1-Benzenesulfonyl-1,1-difluoro-4-phenyl-3-buten-2-
ol (3b): 40% yield, white solid. 1H NMR (CDCl3): d 3.07 (d,
J = 5.5 Hz, 1H); 5.15 (m, 1H); 6.25 (dd, J = 15.8 Hz, 6.7 Hz,
1H); 6.89 (d, J = 15.8 Hz, 1H); 7.29–7.43 (m, 5H); 7.63(t,
J = 8 Hz, 2H); 7.77 (t, J = 8 Hz, 1H); 8.00 (d, J = 8 Hz, 2H).
13C NMR (CDCl3): d 70.8 (dd, J = 23 Hz, 21 Hz); 120.3 (dd,
J = 293 Hz, 290 Hz); 120.3 (t, J = 2.3 Hz); 126.9; 128.5;
128.6; 129.3; 130.6; 132.8; 135.5; 135.6; 136.4. 19F NMR
(CDCl3): d À107.0 (dd, J = 237 Hz, 6 Hz, 1F); À116.6 (dd,
J = 237 Hz, 17 Hz, 1F). MS (EI, m/z): 324 (M+), 207, 133,
115, 105, 77. HRMS (EI): m/z calcd for C16H14F2O3S (M+)
324.0632, found 324.0642.
1-(Benzenesulfonyl)difluoromethyl-3-phenylpropanol
(3c): 53% yield, colorless liquid. 1H NMR (CDCl3): d 2.09
(m, 2H); 2.77 (m, 1H); 2.97 (m, 1H); 3.05 (b, 1H); 4.45 (m,
1H); 7.22–7.34 (m, 5H); 7.62 (t, J = 8 Hz, 2H); 7.77 (t,
J = 8 Hz, 1H); 8.00 (d, J = 8 Hz, 2H). 13C NMR (CDCl3): d
30.9 (b, 2C); 68.6 (dd, J = 24 Hz, 20 Hz); 121.2 (dd,
J = 294 Hz, 292 Hz); 126.2; 128.4; 128.5; 129.3; 130.5;
132.7; 135.5; 140.5. 19F NMR (CDCl3): d À109.2 (dd,
J = 238 Hz, 6 Hz, 1F); À116.9 (dd, J = 238 Hz, 19 Hz, 1F).
MS (EI, m/z): 326 (M+), 308, 167, 143, 104, 91, 77. HRMS
Table 3
Julia olefination reactions of (benzenesulfonyl)difluoromethyl alcohols 3
Entry
a
Carbinol 3
RCH CF2
6
Yielda (%)
60
PhCH CF2
c
Ph(CH2)2CH CF2
p-BrC6H4CH CF2
84
70
e
a
Isolated yields.

G.K.S. Prakash et al. / Journal of Fluorine Chemistry 126 (2005) 1361–1367
1365
(EI): m/z calcd for C16H16F2O3S (M+) 326.0788, found
326.0795.
126.5; 127.5; 129.4; 130.8; 132.0; 132.7; 135.8. 19F NMR
(CDCl3): d À101.8 (d, J = 237.8 Hz, 1F); À113.3 (ddd,
J = 237.3 Hz, 27.1 Hz, 3.6 Hz, 1F). MS (EI, m/z): 432 (M+),
243, 241, 240, 212, 178, 176, 77.
4-Chloro-[difluoro(phenylsulfonyl)methyl]-benzene-
methanol (3d): 65% yield, white solid. 1H NMR (CDCl3): d
3.46 (s, 1H); 5.57 (dd, J = 20.9 Hz, 2.3 Hz, 1H); 7.35 (d,
J = 8.5 Hz, 2H); 7.42 (d, J = 8.4 Hz, 2H); 7.62 (t, J = 8.1 Hz,
2H); 7.78 (t, J = 8.1 Hz, 1H); 7.99 (d, J = 8.1 Hz, 2H). 13C
NMR (CDCl3): d 70.6 (dd, J = 26.4 Hz, 20.2 Hz); 119.8 (dd,
J = 298.7 Hz, 289.6 Hz); 128.6; 129.38; 129.41; 130.6;
131.9; 132.3; 135.5; 135.7. 19F NMR (CDCl3): d À104.6 (d,
J = 241.5 Hz, 1F); À119.8 (dd, J = 241.5 Hz, 20.1 Hz, 1F).
MS (EI, m/z): 332 (M+), 143, 141, 77.
a-[(Benzenesulfonyl)difluoromethyl]-1-Pyrenemethanol
(3i): 80% yield, yellow solid. 1H NMR (CD3COCD3): d 6.18
(d, J = 6.2 Hz 1H); 6.80 (ddd, J = 21.7 Hz, 5.9 Hz, 3.4 Hz,
1H); 7.71 (t, J = 8.0 Hz, 2H); 7.84 (t, J = 7.6 Hz, 1H); 8.01–
8.33 (m, 9H); 8.40 (t, J = 8.8 Hz, 2H). 13C NMR
(CD3COCD3): d 67.9 (dd, J = 27.9 Hz, 19.6 Hz); 122.8
(dd, J = 299.2 Hz, 286.6 Hz); 123.5; 125.1; 125.2; 125.6;
126.3; 126.6; 127.1; 127.3; 128.2; 128.9; 129.0; 130.00;
4-Bromo-[difluoro(phenylsulfonyl)methyl]-benzene-
1
methanol (3e): 55% yield, light yellow solid. H NMR
130.05; 130.2; 131.3; 131.4; 132.1; 132.6; 135.4; 136.2. 19
F
NMR (CD3COCD3): d À102.7 (d, J = 239.1 Hz, 1F) À116.6
(dd, J = 239.7 Hz, 21.3 Hz, 1F). MS (EI, m/z): 422 (M+),
231, 203, 202, 77.
(CDCl3): d 3.57 (s, 1H); 5.55 (d, J = 21.0 Hz, 1H); 7.35
(d, J = 8.4 Hz, 2H); 7.51 (d, J = 8.6 Hz, 2H); 7.62 (t,
J = 8.2 Hz, 2H); 7.77 (t, J = 7.4 Hz, 1H); 7.99 (d,
J = 8.1 Hz, 2H). 13C NMR (CDCl3): d 70.6 (dd,
J = 25.5 Hz, 19.5 Hz); 119.8 (dd, J = 300.4 Hz,
289.8 Hz); 123.7; 129.4; 129.7; 130.6; 131.6; 135.7.
19F NMR (CDCl3): d À104.6 (d, J = 235.8 Hz, 1F);
À119.7 (dd, J = 239.8 Hz, 21.0 Hz, 1F). MS (EI, m/z):
376 (M+), 306, 235, 218, 185, 157, 136, 125, 106, 94.
HRMS (EI): m/z calcd for C14H11O3SF2Br (M+)
375.9580, found 375.9577.
4.3. Typical procedure for reductive desulfonylation
In a 50-mL Schlenk flask with Argon protection, 2-
(3a)
benzenesulfonyl-2,
2-difluoro-1-phenylethanol
(150 mg, 0.5 mmol) and Na2HPO4 (497 mg, 3.5 mmol) in
10 mL anhydrous methanol were added in. After the
solution was cooled to À20 8C, Na/Hg amalgam (10 wt.%
Na in Hg, 805 mg, 3.5 mmol) was added. The reaction
mixture was stirred at À20 to 0 8C for 1.5 h. Then the
solution was diluted with Et2O and the liquid was decanted
from the solid. After removing the solvent of the liquid
phase by rotate evaporator, 30 mL saturated NaCl solution
was added, which was then extracted by Et2O three times.
The combined ether solution was dried with MgSO4 and the
solvent was removed to give pure product 2,2-difluoro-1-
phenylethanol (4a) (62 mg, 79% yield) as a white solid. 1H
NMR (CDCl3): d 2.44 (b, 1H); 4.82 (td, J = 10.5 Hz, 4.8 Hz,
1H); 5.77 (td, J = 56.4 Hz, 4.8 Hz, 1H); 7.41 (m, 5H). 13C
a-[(Benzenesulfonyl)difluoromethyl]-1-naphthalene-
methanol (3f): 70% yield, white solid. 1H NMR (CDCl3): d
3.72 (d, J = 4.2 Hz, 1H); 5.77 (ddd, J = 21.6 Hz, 4.2 Hz,
2.9 Hz, 1H); 7.48–7.60 (m, 5H); 7.71 (t, J = 7.4 Hz, 1H);
7.81–7.87 (m, 3H); 7.95–8.03 (m, 3H). 13C NMR (CDCl3): d
71.3 (dd, J = 26.4 Hz, 19.7 Hz); 120.3 (dd, J = 298.9 Hz,
289.1 Hz); 124.9; 126.3; 126.7; 127.6; 128.0; 128.18;
128.21; 129.3; 130.6; 131.0; 132.6; 132.8; 133.7; 135.5. 19
F
NMR (CDCl3): d À104.0 (d, J = 238.6 Hz, 1F); À119.2 (dd,
J = 241.8 Hz, 21.6 Hz, 1F). MS (EI, m/z): 348 (M+), 157,
129, 77.
NMR (CDCl3):
d 73.6 (t, J = 20.0 Hz); 115.8 (t,
a-[(Benzenesulfonyl)difluoromethyl]-9-anthracene-
methanol (3g): 82% yield, yellow solid. 1H NMR (CDCl3): d
3.63 (d, J = 4.2 Hz, 1H); 7.33 (dd, J = 26.9 Hz, 4.2 Hz, 1H);
7.42-7.66 (m, 6H); 7.76 (t, J = 7.5 Hz, 1H); 8.01 (dd,
J = 14.2 Hz, 8.5 Hz, 2H); 8.10 (d, J = 7.8 Hz, 2H); 8.21 (d,
J = 8.9 Hz, 1H); 8.52 (s, 1H); 9.02 (d, J = 9 Hz, 1H). 13C
NMR (CDCl3): d 67.8 (dd, J = 28.4 Hz, 20.0 Hz); 121.5 (dd,
J = 305.3 Hz, 289.3 Hz); 122.6; 123.8; 124.8; 125.0; 126.0;
127.3; 128.9; 129.4; 130.67; 130.75; 132.3; 135.7. 19F NMR
(CDCl3): d À101.9 (d, J = 237.3 Hz, 1F); À113.6 (ddd,
J = 236.8 Hz, 26.8 Hz, 3.9 Hz, 1F). MS (EI, m/z): 398 (M+),
207, 179, 178, 77.
J = 245.9 Hz); 127.1; 128.6; 129.0; 135.8 (t, J = 3.7 Hz).
19F NMR (CDCl3): d À127.8 (ddd, 284.8 Hz, 56.5 Hz,
9.9 Hz, 1F); À128.3 (ddd, 284.8 Hz, 56.5 Hz, 11 Hz, 1F).
MS (EI, m/z): 158 (M+), 107, 79, 77. The data are consistent
with the previous report [13].
1-Benzenesulfonyl-1,1-difluoro-3-buten-2-ol (4b): 84%
1
yield, colorless liquid. H NMR (CDCl3): d 2.71 (b, 1H);
4.42 (m, 1H); 5.69 (td, J = 56 Hz, 4.6 Hz, 1H); 6.18 (dd,
J = 16 Hz, 6.4 Hz, 1H); 6.76 (d, J = 16 Hz, 1H); 7.24-7.41
(m, 5H). 13C NMR (CDCl3): d 72.1 (t, J = 24.5 Hz); 115.4 (t,
J = 245 Hz); 122.4 (t, J = 4 Hz); 126.7; 128.4; 128.6; 134.8;
135.7. 19F NMR (CDCl3): d À128.7 (ddd, J = 285 Hz,
56 Hz, 11 Hz, 1F); À129.6 (ddd, J = 285 Hz, 56 Hz, 10 Hz,
1F). MS (EI, m/z): 184 (M+), 133, 115, 77. The data are
consistent with the previous report [14].
a-[(Benzenesulfonyl)difluoromethyl]-10-chloro-9-
anthracenemethanol (3h): 57% yield, yellow solid. 1H NMR
(CDCl3): d 3.69 (d, J = 4.4 Hz, 1H); 7.35 (dd, J = 26.6 Hz,
4.3 Hz, 1H); 7.49-7.71 (m, 6H); 7.77 (t, J = 7.5 Hz, 1H);
8.09 (d, J = 7.9 Hz, 2H); 8.24 (d, J = 8.2 Hz, 1H); 8.61 (dd,
J = 18.1 Hz, 8.6 Hz, 2H); 9.07 (d, 8.2 Hz, 1H). 13C NMR
(CDCl3): d 67.7 (dd, J = 27.9 Hz, 19.6 Hz); 121.3 (dd,
J = 305.2 Hz, 289.7 Hz); 122.9; 123.7; 125.2; 126.0; 126.2;
1,1-Difluoro-4-phenyl-2-butanol (4c): 86% yield, color-
less liquid. 1H NMR (CDCl3): d 1.85 (m, 1H); 1.92 (m, 1H);
2.13 (b, 1H); 2.75 (m, 1H); 2.91 (m, 1H); 3.74 (m, 1H); 5.63
(td, J = 56 Hz, 4.2 Hz, 1H); 7.20–7.35 (m, 5H). 13C NMR
(CDCl3): d 30.9; 31.5 (t, J = 3.3 Hz); 70.2 (t, J = 23.5 Hz);

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G.K.S. Prakash et al. / Journal of Fluorine Chemistry 126 (2005) 1361–1367
116.3 (t, J = 244 Hz); 126.2; 128.4; 128.5; 140.9. 19F NMR
(CDCl3): d À130.0 (dd, J = 56 Hz, 11 Hz). MS (EI, m/z):
186 (M+), 168, 117, 91, 77. The data are consistent with the
previous report [13].
1-Bromo-4-(2,2-difluoroethenyl)-benzene (6e): 70%
yield, colorless liquid. 19F NMR (CDCl3): d À81.7 (dd,
J = 30.1 Hz, 26.2 Hz, 1F); À83.6 (d, J = 30.1 Hz, 1F). The
characterization data is consistent with an early report [17].
4.4. Typical procedure for Julia olefination of 3
Acknowledgment
A solution of 3a (150 mg, 0.5 mmol) and 4-N,N-
dimethylaminopyridine (DMAP) (catalytic amount) in
5 mL CH2Cl2 under Ar was cooled to 0 8C and treated with
Et3N (0.28 mL, 2 mmol). After stirring for 20 min, metha-
nesulfonyl chloride (0.08 mL, 1 mmol) was added dropwise
and the reaction mixture was stirred at 0 8C for 2 h. The
reaction mixture was quenched by buffer solution and
extracted with EtOAc (3 Â 25 mL). The combined organic
solution was washed by brine (2 Â 25 mL) and dried over
MgSO4. After removing the solvent, the crude product was
purified by column chromatography (9:1 hexane: EtOAc) to
Support of our work by Loker Hydrocarbon Research
Institute is gratefully acknowledged.
References
[1] R. Filler, Y. Kobayashi, Biomedical Aspects of Organofluorine
Chemistry, Kodansha and Elsevier Biomedical, Amsterdam, 1983.
[2] (a) J.A. Erickson, J.I. McKoughlin, J. Org. Chem. 60 (1995) 1626–
1631;
(b) R. Sasson, A. Hagooly, S. Rozen, Org. Lett. 5 (2003) 769–771;
(c) P. Kirsch, Modern Fluororganic Chemistry, Wiley-VCH, Wein-
hein, 2004.
1
give mesylate 5a 169 mg, 90% yield. H NMR (CDCl3): d
3.06 (s, 3H); 6.26 (dd, J = 16.5 Hz, 6.7 Hz, 1H); 7.44 (m, 3H),
7.53 (d, J = 7.8 Hz, 2H); 7.61 (t, J = 7.2 Hz, 2H); 7.76 (t,
J = 7.7 Hz, 1H); 7.97 (d, J = 8.2 Hz, 2H). 19F NMR (CDCl3):
d À105.5 (dd, J = 243.0 Hz, 6.7 Hz, 1F); À113.2 (dd,
J = 243.9 Hz, 16.5 Hz, 1F). MS (EI, m/z): 376.1 (M+), 185,
140, 107, 77. The mesylate 5a (100 mg, 0.27 mmol) in
anhydrous MeOH (5 mL) was cooled to À40 8C and treated
with Na2HPO4 (151 mg, 1.06 mmol) and 10% Na(Hg)
(368 mg, 1.60 mmol). After stiring for 1 h at À20 8C, the
reaction mixturewas diluted with 30 mL EtOAc and decanted
from the solid Hg residue. The organic solution was washed
by brine 30 mL and the brine was extracted with EtOAc
(3 Â 25 mL). The combined organic solution was dried over
MgSO4, condensed by reduced pressure and purified by
column chromatography (20:1 hexane: EtOAc) to give 2,2-
difluoroethenylbenzene (6a) 22 mg, 60% yield as colorless
liquid. 19F NMR (CDCl3): d À82.9 (dd, J = 33.6 Hz, 27.4 Hz,
1F), À84.8 (d, J = 31.7 Hz, 1F). The characterization data is
consistent with that early reported [15].
[3] W.B. Motherwell Jr., M.J. Tozer, B.C. Ross, J. Chem. Soc., Chem.
Commun. 19 (1989) 1437–1439.
[4] (a) Y. Chen, J.N. Freskos, A.F. Gasiecki, M.L. Grapperhaus, D.W. Jr.
Hansen, R.M. Heintz, I.K. Khanna, S.A. Kolodziej, S. Mantegani,
M.A. Massa, J.J. McDonald, D.A. Mischke, M.A. Nagy, E. Perrone,
M.A. Schmidt, D.P. Spangler, J.J. Talley, M. Trivedi, T.A. Wynn, D.P.
Becker, J.G. Rico, WO 2004000811, 2004 [Chem. Abstr. 140 (2004)
59663];
(b) M.F. Parker, K.E. McElhone, R.A. Mate, J.J. Bronson, Y. Gai, C.P.
Bergstrom, L.R. Marcin, J.E. Macor, WO 2003053912, 2003 [Chem.
Abstr. 139 (2003) 85645]
(c) W.R. Moor, G.L. Schatzman, E.T. Jarvi, R.S. Gross, J.R.
McCarthy, J. Am. Chem. Soc. 114 (1992) 360–361;
(d) K. Ando, J. Org. Chem. 69 (2004) 4203–4209;
(e) J.R. McCarthy, ACS Fluorine Division Tutorial, 219 National
ACS Meeting, San Francisco, March 26, 2000;
(f) J. Ichikawa, H. Fukui, Y. Ishibashi, J. Org. Chem. 68 (2003) 7800–
7805;
(g) J.T. Welch, Selective fluorination in organic and bioorganic
chemistry, ACS symposium series 456, American Chemical Society,
Washington, DC, 1991.
[5] (a) K. Otaka, D. Oohira, D. Takaoka, WO 2004006677, 2004;
(b) M. Markl, W. Schaper, O. Ort, H. Jakobi, R. Braun, G. Kraut-
strunk, U. Sanft, W. Bonin, H. Stark, S. Pasenok, I. Cabrera, WO
2000007998, 2000 [Chem. Abstr. 132 (2000) 166248];
(c) T. Abe, R. Tamai, M. Tamaru, H. Yano, S. Takahashi, N. Mur-
amatsu, WO 2003042153, 2003 [Chem. Abstr. 138 (2003) 401741];
(d) T. Abe, R. Tamai, M. Ito, M. Tamaru, H. Yano, S. Takahashi, N.
Muramatsu, WO 2003029211, 2003 [Chem. Abstr. 138 (2003)
304304];
Mesylate (5c): 87% yield, white solid. 1H NMR (CDCl3):
d 3.20 (s, 3H); 5.46 (m, 1H); 7.29 (m, 3H); 7.37 (t,
J = 6.9 Hz, 2H); 7.68 (t, J = 7.4 Hz, 2H); 7.85 (t, J = 7.9 Hz,
1H); 8.01 (d, J = 8.4 Hz, 2H). 13C NMR (CDCl3): d 30.7;
31.1; 39.1; 76.2 (dd, J = 26.0 Hz, 20.4 Hz); 119.5 (dd,
J = 286.0 Hz, 283.2 Hz); 126.4; 128.5; 128.6; 129.5; 130.7;
132.2; 135.9; 139.6. 19F NMR (CDCl3): d À107.2 (d,
J = 242.9 Hz, 1F); À110.0 (d, J = 245.0 Hz, 1F).
(e) K. Fuji, Y. Hatano, K. Tsutsumiuchi, Y. Nakahon, JP 2000086636,
2000 [Chem. Abstr. 132 (2000) 222532].
1
Mesylate (5e): 86% yield, light yellow solid. H NMR
[6] J.F. Liebman, A. Greenberg, W.R. Dolbier Jr., Fluorine-containing
Molecules: Structure, Reactivity, Synthesis and Applications, VCH,
New York, 1988.
(CDCl3): d 3.14 (s, 3H); 6.22 (dd, J = .7 Hz, 6.8 Hz, 1H);
7.41 (d, J = 8.3 Hz, 2H); 7.57 (dd, J = 8.7 Hz, 2H); 7.62 (t,
J = 7.9 Hz, 2H); 7.78 (t, J = 7.5 Hz, 1H); 7.96 (d, J = 7.4 Hz,
2H). 19F NMR (CDCl3): d À105.6 (d, J = 243.1 Hz, 1F);
À113.3 (d, J = 249.9 Hz, 1F).
[7] (a) G.K.S. Prakash, J. Hu, Y. Wang, G.A. Olah, Org. Lett. 6 (2004)
4315–4317 (and the references therein);
(b) G.K.S. Prakash, J. Hu, Y. Wang, G.A. Olah, Angew, Chem. Int.
Ed. 43 (2004) 5203–5206 (and the references therein);
(c) G.K.S. Prakash, J. Hu, Y. Wang, G.A. Olah, Eur. J. Org. Chem.
(2005) 2218–2223 (and the references therein).
(4,4-Difluoro-3-butenyl)-benzene (6c): 84% yield, color-
less liquid. 19F NMR (CDCl3): d À89.6 (d, J = 49 Hz, 1F);
À91.6 (dd, J = 49 Hz, 28 Hz, 1F). The characterization data
is consistent with an early report [16].
[8] D.J. Burton, D.M. Wiemers, J. Fluorine Chem. 18 (1981) 573–582.
[9] G.K.S. Prakash, J. Hu, G.A. Olah, J. Org. Chem. 68 (2003) 4457–4463.

G.K.S. Prakash et al. / Journal of Fluorine Chemistry 126 (2005) 1361–1367
1367
´
¨
[10] (a) S. Aıt-Mohand, N. Tekechi, M. Medebielle, W.R. Dolbier Jr., Org.
strunk, U. Sanft, W. Bonin, H. Stark, S. Pasenok, I. Cabrera, WO
2000007998, 2000 [Chem. Abstr. 132 (2000) 166248].
[12] G.P. Stahly, J. Fluorine Chem. 43 (1989) 53–66.
[13] S. Kaneko, T. Yamazaki, T. Tomoya, T. J. Org. Chem. 58 (1993) 2302–
2312.
Lett. 3 (2001) 4271–4273;
´
(b) M. Medebielle, K. Kato, W.R. Dolbier Jr., Tetrahedron Lett. 44
(2003) 7871–7873;
(c) C. Burkholder, W.R. Dolbier Jr., Tetrahedron Lett. 38 (1997) 821–
824;
´
(d) C. Burkholder, W.R. Dolbier Jr., M. Medebielle, J. Org. Chem. 63
[14] (a) T. Hagiwara, T. Fuchigami, Synlett (1995) 717–718;
(b) G.K.S. Prakash, M. Mandal, S. Schweizer, N.A. Petasis, G.A.
Olah, J. Org. Chem. 67 (2002) 3718–3723.
(1998) 5385–5397;
´
(e) C. Burkholder, W.R. Dolbier Jr., M. Medebielle, J. Fluorine Chem.
[15] B.V. Nguyen, D.J. Burton, J. Org. Chem. 62 (1997) 7758–7764.
[16] K. Kim, J.R. McCarthy, Tetrahedron Lett. 37 (1996) 3223–3226.
[17] V.G. Nenajdenko, G.N. Varseev, V.N. Korotchenko, A.V. Shastin, E.S.
Balenkova, J. Fluorine Chem. 124 (2003) 115–118.
109 (2001) 39–48.
[11] (a) K. Otaka, D. Oohira, D. Takaoka, WO 2004006677, 2004;
(b) M. Markl, W. Schaper, O. Ort, H. Jakobi, R. Braun, G. Kraut-