Preparation of 1-aryl-2,2-difluoro enol esters via dehydrosulfonylation of α-(phenylsulfonyl)difluoromethylated benzoates

Article abstract of DOI:10.1016/j.jfluchem.2007.03.004

1-Aryl-2,2-difluoro enol benzoates 4 has been prepared from α-(phenylsulfonyl)-difluoromethylated benzoates 3, which can be readily obtained from the reactions between simple aldehydes and PhSO₂CF₂H (or TMSCF₂SO₂

Full text of DOI:10.1016/j.jfluchem.2007.03.004

Journal of Fluorine Chemistry 128 (2007) 755–761
www.elsevier.com/locate/fluor
Preparation of 1-aryl-2,2-difluoro enol esters via dehydrosulfonylation
of a-(phenylsulfonyl)difluoromethylated benzoates
*
Laijun Zhang, Ya Li, Jinbo Hu
Key Laboratory of Organofluorine Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences,
354 Feng-Lin Road, Shanghai 200032, China
Received 30 January 2007; received in revised form 5 March 2007; accepted 5 March 2007
Available online 12 March 2007
Abstract
1-Aryl-2,2-difluoro enol benzoates 4 has been prepared from a-(phenylsulfonyl)-difluoromethylated benzoates 3, which can be readily
obtained from the reactions between simple aldehydes and PhSO2CF2H (or TMSCF2SO2Ph). 2,2-Difluoro enol esters 4 are relatively more stable
compounds than 2,2-difluoro enol sily ethers, and they promise to act as interesting fluorinated building blocks for further elaborations.
# 2007 Elsevier B.V. All rights reserved.
Keywords: 2,2-Difluoro enol benzoate; (Phenylsulfonyl)difluoromethyl; Dehydrosulfonylation
1. Introduction
become a highly useful way to synthesize structurally diverse
difluoromethylated and difluoromethylenated compounds [11–
13]. a-(Phenysulfonyl)difluoromethylated alcohols 2 can be
readily prepared via the reactions between corresponding
aldehydes and PhSO2CF2H (or TMSCF2SO2Ph) [11b,11e,13b].
In this article, we wish to report a facile preparation of 2,2-
difluoro enol esters from compounds 3 via a base-mediated
dehydrosulfonylation (Scheme 1). Since compounds 3 are
derived from 2 via simple benzoylation, this synthetic
methodology provides a new practical approach to prepare
2,2-difluoro enol esters 4.
2,2-Difluoro enol derivatives (such as 2,2-difluoro enol
silyl ethers) are important fluorine-containing building
blocks for the synthesis of many gem-difluorinated organic
compounds [1–5]. Initially, 2,2-difluoro enol silyl ethers
were prepared from chlorodifluoromethyl ketones [6] or from
acyltrifluoromethylsilane through Brook rearrangement
[7,8]. Trifluoroethanol has been widely used as an
inexpensive starting material for prepation of 2,2-difluoro
enol derivatives [4]. More recently, a novel C–F bond
cleavage chemistry with trifluoromethyl compounds has been
developed by Uneyama and co-workers, which significantly
expanded both the preparation and the synthetic applications
of 2,2-difluoro enol building blocks [5,9]. However,
compared to the 2,2-difluoro enol silyl ethers, 2,2-difluoro
enol carboxylic esters are less explored [6,8]. We envision
that 2,2-difluoro enol esters can be relatively more stable
than 2,2-difluoro enol silyl ethers [10], and such class of
compounds can be used as interesting fluorinated building
blocks for many applications.
Nucleophilic (phenylsulfonyl)difluoromethylation with
PhSO2CF2H or TMSCF2SO2Ph reagent has increasingly
* Corresponding author. Tel.: +86 21 54925174; fax: +86 21 64166128.
Scheme 1.
E-mail address: jinbohu@mail.sioc.ac.cn (J. Hu).
0022-1139/$ – see front matter # 2007 Elsevier B.V. All rights reserved.
doi:10.1016/j.jfluchem.2007.03.004

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L. Zhang et al. / Journal of Fluorine Chemistry 128 (2007) 755–761
Scheme 2.
2. Results and discussion
benzoates 4 in moderate to good yields. The remarkable
difference between para- and ortho-methoxy-substituted
substrates in the reaction (entries c and e) indicates that the
dehydrosulfonylation reaction is sensitive to the steric
hinderance. In the case of alkyl-substituted substrate 3h (entry
h), the reaction was not successful, probably due to the
difficulty in deprotonation of 3h to generate the anionic species
(Scheme 4, Eq. (2)).
a-(Phenylsulfonyl)difluoromethylated alcohols were pre-
pared in high yields from aldehydes 1 and PhSO2CF2H in the
presence of lithium hexamethyldisilazide (LHMDS) according
to the previous report (Scheme 2) [12e].
Initially, we observed that under the treatment of n-BuLi or
LHMDS in THF at room temperature, compounds 2 could not
undergo dehydrosulfonylation to give 2,2-difluoro enolates.
However, the corresponding benzoate form (3a) of alcohol 2a
readily underwent dehydrosulfonylation, and the correspond-
ing 2,2-difluoro enol benzoate 4a could be obtained (Table 1).
After a quick survey of reaction conditions, we found that
adding 1.2 equiv. of LHMDS in THF at room temperature was
the best conditions for the dehydrosulfonylation (Table 1, entry
3).
a-(Phenylsulfonyl)difluoromethylated alcohol 2a was
chlorinated by phosphorus pentachloride in CHCl3 at reflux
temperature to give chlorinated product 5 in 81% isolated yield
(Table 3, entry 3). Thionyl chloride could not chlorinate
compound 2a under similar reaction conditions, which is
different from the similar chlorination of a-trifluoromethylated
alcohols [14]. Mediated by LHMDS as a base in THF,
compound 5 was readily dehydrosulfonylated to give 2-(1-
chloro-2,2-difluorovinyl)naphthalene 6 in 54% yield (Scheme
5).
A variety of a-(phenylsulfonyl)difluoromethylated benzo-
ates 3 were prepared from corresponding alcohols 2 in good to
excellent isolated yields, following a deprotonation and
benzoylation (with benzoyl chloride) sequence (Scheme 3).
By using the optimized reaction conditions (Table 1, entry
3), we then investigated the scope of the LHMDS-mediated
dehydrosulfonylation reaction. The results are summarized in
Table 2. For most 1-(phenylsulfonyl)difluoromethylated
benzoates 3, the dehydrosulfonylation reactions occurred
smoothly to give the corresponding 1-aryl-2,2-difluoro enol
2,2-Difluoro enol benzoates 4 are stable compound at
ambient temperature, which can be stored in a refrigerator for
several months without any decomposition. Under KOH
aqueous solution, compounds 4c readily undergo hydrolysis
to give difluoromethyl ketones 7 in 72% isolated yields
(Scheme 6).
Table 1
Survey of reaction conditions for dehydrosulfonylation
Entry
LHMDS (equiv.)
Temperature (8C)
Time (min)
Yeild (%)a
1
2
3
1.2
2
À78
0
70
30
60
Trace
54
1.2
rt
65
a
Isolated yeild.
Scheme 3.

L. Zhang et al. / Journal of Fluorine Chemistry 128 (2007) 755–761
757
Table 2
Dehydrosulfonylation of (phenylsulfonyl)difluoromethylated benzoates 3
Entry
a
Substrate 3
Product 4
Yield (%)a
65
b
c
54
74
d
68
e
f
25
73
g
57
0
h
a
Isolated yield.
Scheme 4.

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L. Zhang et al. / Journal of Fluorine Chemistry 128 (2007) 755–761
Table 3
meter. High-resolution mass data were recorded on a high-
resolution mass spectrometer in the EI or MALDI mode.
Compounds 2 were prepared from aldehydes and PhSO2CF2H
according to previous report [12e].
Chlorination of a-(phenylsulfonyl)difluoromethylated alcohol 2a
3.1. Typical procedure for preparation of compounds 3
Under N2 atmosphere, into a 25-mL Schlenk flask
containing 2b (3.0 mmol, 0.894 g), HMPA (1.5 mL) in THF
(15 mL) at À78 8C, was added dropwise a THF solution
(3.40 mL) of (TMS)2NLi (LHMDS, 1.06 M, 3.60 mmol). The
reaction mixture was stirred at this temperature for 30 min,
followed by adding BzCl (4.5 mol, 0.632 g) and stirred for
another 2 h at this temperature. The reaction mixture was
quenched with saturated NH4Cl aqueous solution, and
extracted with ether (3Â 25 mL). The combined organic
phase was dried over MgSO4. After the removal of solvents
under vacuum, the crude product was purified by silica gel
column chromatography to give product 3b as a white solid
(1.110 g), yield: 92%.
aIsolated yield.
In conclusion, 1-aryl-2,2,-difluoro enol benzoates 4 has been
prepared from a-(phenylsulfonyl)difluoromethylated benzo-
ates 3, which can be readily obtained from the reactions
3.1.1. 2,2-Difluoro-1-(naphthalen-2-yl)-2-
(phenylsulfonyl)ethyl benzoate (3a)
between
simple aldehydes
and
PhSO2CF2H
(or
TMSCF2SO2Ph). 2,2-Difluoro enol esters 4 are relatively more
stable compounds than 2,2-difluoro enol sily ethers, and they
promise to act as interesting fluorinated building blocks for
further elaborations.
White solid; mp: 73–75 8C. IR (film): 3059, 1747, 1598,
1585, 1491, 1452, 1247, 1119 cmÀ1 1H NMR: d 8.13 (d,
.
J = 7.6 Hz, 2H), 8.00 (t, J = 7.6 Hz, 3H), 7.83 (t, J = 8.8 Hz,
3H), 7.70–7.59 (m, 3H), 7.57–7.45 (m, 6H), 6.90 (dd, J = 19.6,
5.3 Hz, 1H). 19F NMR: d À104.14 (d, J = 243.1 Hz, 1F),
À113.40 (dd, J = 242.2, 19.7 Hz, 1F). 13C NMR: d 164.085,
135.304, 133.900, 133.731, 133.450, 132.845, 130.566,
130.231, 129.280, 128.808, 128.602, 128.561, 128.530,
128.328, 127.707, 127.056, 126.563, 124.985, 120.136 (dd,
J = 297.1, 284.2 Hz), 71.841 (dd, J = 30.5, 19.6 Hz), 60.347.
MS (MALDI, m/z, %): 475.1 (M+ + Na), 358.3 (100.00).
HRMS (MALDI): calcd. for C25H18F2O4SNa (M+ + Na):
475.0786; Found: 475.0792.
3. Experimental
Unless otherwise mentioned, solvents and reagents were
purchased from commercial sources and used as received. THF
was freshly distilled over sodium. Difluoromethyl phenyl
1
sulfone was prepared using known procedures [11–13]. H
NMR spectra were recorded on Bruker 300 or Mercury 300
spectrometers with Me4Si as internal standard. 19F NMR
spectra were recorded on Bruker 300 or Mercury 300
spectrometers with CFCl3 as external standard. 13C NMR
spectra were recorded on Avance 500 or DPX-400 spectro-
meters. Mass spectra were obtained on a HP5989A spectro-
3.1.2. 2,2-Difluoro-1-phenyl-2-(phenylsulfonyl)ethyl
benzoate (3b)
White solid; mp: 106–108 8C. IR (film): 3068, 2965, 1736,
1601, 1584, 1497, 1267, 1120 cmÀ1 1H NMR: d 8.10 (d,
.
J = 7.2 Hz, 2H), 7.98 (d, J = 8.1 Hz, 2H), 7.70 (t, J = 8.0 Hz,
1H), 7.61–7.53 (m, J = 8.1 Hz, 5H), 7.47 (t, J = 7.5 Hz, 2H),
7.40–7.38 (q, 3H), 6.74 (dd, J = 19.8, 5.1 Hz, 1H), 19F NMR: d
À103.95 (dd, J = 243.1, 3.95 Hz, 1F), À113.27 (dd, J = 243.1,
20.6 Hz, 1F). 13C NMR: d 164.024, 135.323, 133.715, 133.477,
131.265, 130.584, 130.213, 129.931, 129.309, 128.795,
128.641, 128.520, 128.489, 119.970 (dd, J = 296.9,
283.6 Hz), 71.593 (dd, J = 30.3, 19.4 Hz). MS (EI, m/z, %):
261 (M+ À SO2Ph, 3.63), 105 (100.00). EA: calcd. for
C21H16F2O4S: C, 62.68; H, 4.01; Found: C, 62.67; H, 4.20.
Scheme 5.
3.1.3. 2,2-Difluoro-1-(4-methoxyphenyl)-2-
(phenylsulfonyl)ethyl benzoate (3c)
White solid; mp: 81–83 8C. IR (film): 3068, 2841, 1732,
1614, 1585, 1517, 1260, 1136 cmÀ1 1H NMR: d 8.08 (d,
.
J = 7.2 Hz, 2H), 7.97 (d, J = 7.9 Hz, 2H), 7.69 (t, J = 7.4 Hz,
Scheme 6.

L. Zhang et al. / Journal of Fluorine Chemistry 128 (2007) 755–761
759
1H), 7.57 (m, J = 7.9 Hz, 3H), 7.45 (t, J = 8.5 Hz, 4H), 6.89 (d,
3.1.7. 1-(4-tert-Butylphenyl)-2,2-difluoro-2-
(phenylsulfonyl)ethyl benzoate (3g)
J = 8.5 Hz, 2H), 6.69 (dd, J = 19.2, 5.7 Hz, 1H), 3.79 (s, 3H).
19F NMR: d À104.73 (dd, J = 240.5, 6.2 Hz, 1F), À113.53 (dd,
J = 241.1, 17.2 Hz, 1F). 13C NMR: d 164.060, 160.829,
135.257, 133.628, 133.550, 130.541, 130.155, 129.970,
129.269, 128.898, 128.476, 123.192, 120.072 (dd, J = 296.6,
283.7 Hz), 114.112, 71.310 (dd, J = 30.0, 19.4 Hz), 55.253.
MS (EI, m/z, %): 291 (M+ À SO2Ph, 2.49), 105 (100.00). EA:
calcd. for C22H18F2O5S: C, 61.10; H, 4.20; Found: C, 61.09; H,
4.19.
White solid; mp: 100–102 8C. IR (film): 3064, 2964, 1735,
1601, 1585, 1517, 1265, 1126 cmÀ1 1H NMR: d 8.08 (d,
.
J = 7.4 Hz, 2H), 7.97 (d, J = 7.4 Hz, 2H), 7.68 (t, J = 7.4 Hz,
1H), 7.62–7.50 (m, J = 8.3 Hz, 3H), 7.48–7.43 (m, 4H), 7.38 (d,
J = 8.4 Hz, 2H), 6.72 (dd, J = 20.2, 5.4 Hz, 1H). 19F NMR: d
À103.69 (dd, J = 243.1, 5.1 Hz, 1F), À113.40 (dd, J = 243.1,
18.3 Hz, 1F). 13C NMR: d 164.038, 153.013, 135.227, 133.625,
133.572, 130.533, 130.174, 129.244, 128.883, 128.467,
128.222, 128.175, 125.593, 120.057 (dd, J = 296.7,
283.3 Hz), 71.409 (dd, J = 30.7, 19.2 Hz), 34.673, 31.169.
MS (EI, m/z, %): 317 (M+ À SO2Ph, 1.49), 105 (100.00). EA:
calcd. for C25H24F2O4S: C, 65.49; H, 5.28; Found: C, 65.32; H,
5.60.
3.1.4. (E)-1,1-Difluoro-4-phenyl-1-(phenylsulfonyl)but-3-
en-2-yl benzoate (3d)
IR (film): 3064, 1761, 1601, 1496, 1259, 1063, 697 cmÀ1
.
1H NMR: d 8.09 (d, J = 8.4 Hz, 2H), 8.00 (d, J = 7.8 Hz, 2H),
7.71 (t, J = 7.7 Hz, 1H), 7.58 (q, J = 8.3 Hz, 3H), 7.44 (q,
J = 7.1 Hz, 4H), 7.32 (m, 3H), 6.97 (d, J = 15.5 Hz, 1H), 6.44
(m, J = 7.7 Hz, 1H), 6.28 (q, J = 8.3 Hz, 1H). 19F NMR: d
À106.05 (dd, J = 241.1, 8.46, Hz, 1F), À111.07 (dd, J = 241.1,
14.4 Hz, 1F). 13C NMR: d 164.299, 139.154, 135.388, 135.153,
133.658, 133.424, 130.647, 130.167, 129.334, 128.978,
128.886, 128.658, 128.491, 127.139, 117.358, 120.087 (dd,
J = 293.6, 286.5 Hz), 71.399 (dd, J = 27.9, 21.6 Hz). MS
(MALDI, m/z, %): 451.1 (M+ + Na), 451.1 (100.00). HRMS
(MALDI): calcd. for C23H18F2O4SNa (M+ + Na): 451.0786;
Found: 451.0795.
3.1.8. 2,2-Difluoro-1-(furan-2-yl)-2-(phenylsulfonyl)ethyl
benzoate (3h)
White solid; mp: 91–93 8C. IR (film): 3066, 1739, 1600,
1585, 1502, 1452, 1349, 1249 cmÀ1 1H NMR: d 8.06 (d,
.
J = 8.8 Hz, 2H), 7.98 (d, J = 8.8 Hz, 2H), 7.68 (t, J = 7.6 Hz,
1H), 7.58 (q, J = 7.6 Hz, 3H), 7.45 (t, J = 7.6 Hz, 3H), 6.90 (dd,
J = 17.0, 7.6 Hz, 1H). 6.68 (d, J = 3.8 Hz,1H), 6.41 (m, 1H).
19F NMR: d À105.70 (dd, J = 240.3, 6.7 Hz, 1F), À111.14 (dd,
J = 240.8, 16.6 Hz, 1F). 13C NMR: d 164.061, 144.401,
135.451, 133.795, 133.166, 130.651, 130.271, 129.364,
128.500, 119.442 (t, J = 296.9 Hz), 113.019, 110.834, 65.172
(dd, J = 28.8, 20.6 Hz). MS (EI, m/z, %): 251 (M+ À SO2Ph,
1.17), 105 (100.00). EA: calcd. for C19H14F2O5S: C, 58.16; H,
3.60; Found: C, 58.11; H, 3.55.
3.1.5. 1-(4-(Dimethylamino)phenyl)-2,2-difluoro-2-
(phenylsulfonyl)ethyl benzoate (3e)
White solid; mp: 115–117 8C. IR (film): 3059, 2962, 1731,
1612, 1583, 1451, 1263, 1119 cmÀ1 1H NMR: d 8.06 (d,
.
J = 7.3 Hz, 2H), 7.96 (d, J = 7.8 Hz, 2H), 7.67 (t, J = 7.3 Hz,
1H), 7.60–7.50 (m, J = 7.7 Hz, 3H), 7.46–7.37 (q, J = 7.8 Hz,
4H), 6.69–6.60 (m, 3H), 2.94 (s, 6H). 19F NMR: d À104.19 (dd,
J = 242.2, 7.3 Hz, 1F), À113.02 (dd, J = 241.4, 19.7 Hz, 1F).
13C NMR: d 164.128, 151.386, 135.107, 133.763, 133.441,
130.491, 130.112, 129.667, 129.202, 128.391, 120.332 (dd,
J = 296.2, 283.2 Hz), 118.004, 111.850, 71.669 (dd, J = 29.9,
19.2 Hz), 40.141. MS (EI, m/z, %): 446 (M+ + 1, 2.94), 105
(100.00). EA: calcd. for C23H21F2NO4S: C, 62.01; H, 4.75; N,
3.14; Found: C, 61.90; H, 4.91; N, 2.87.
3.1.9. 1,1-Difluoro-3-methyl-1-(phenylsulfonyl)butan-2-yl
benzoate (3i)
White solid; mp: 78–80 8C. IR (film): 3069, 2970, 1741,
1602, 1582, 1492, 1340, 1259 cmÀ1 1H NMR: d 8.09 (d,
.
J = 7.2 Hz, 2H), 7.97 (d, J = 7.5 Hz, 2H), 7.70 (t, J = 7.2 Hz,
1H), 7.63–7.53 (m, 3H), 7.46 (t, J = 8.0 Hz, 2H), 5.93 (ddd,
J = 18.1, 8.4, 4.2 Hz, 1H), 2.53 (m, 1H), 1.09 (t, J = 7.2 Hz,
6H). 19F NMR: d À105.38 (dd, J = 241.4, 7.9 Hz, 1F), À108.70
(dd, J = 241.7, 17.5 Hz, 1F). 13C NMR: d 164.932, 135.306,
133.530, 133.143, 130.690, 130.145, 129.254, 128.961,
128.467, 121.097 (t, J = 294.8 Hz), 71.991 (dd, J = 25.7,
19 Hz), 28.850, 19.784, 16.871. MS (MALDI, m/z, %): 391.1
(M+ + Na), 391.1 (100.00). HRMS (MALDI): calcd. for
C18H18F2O4SNa (M+ + Na): 391.0786; Found: 391.0796.
3.1.6. 2,2-Difluoro-1-(2-methoxyphenyl)-2-
(phenylsulfonyl)ethyl benzoate (3f)
White solid; mp: 93–95 8C. IR (film): 3071, 2983, 1730,
1601, 1589, 1494, 1341, 1247 cmÀ1 1H NMR: d 8.08 (d,
.
J = 7.1 Hz, 2H), 8.01 (d, J = 7.7 Hz, 2H), 7.68 (t, J = 7.5 Hz,
1H), 7.62–7.52 (m, J = 7.5 Hz, 3H), 7.46–7.37 (q, J = 7.5 Hz,
3H), 7.37–7.27 (m, 2H), 6.93 (t, J = 7.5 Hz, 2H). 3.88 (s, 3H).
19F NMR: d À104.74 (dd, J = 244.8, 3.4 Hz, 1F), À113.98 (dd,
J = 241.7, 20.3 Hz, 1F). 13C NMR: d 163.918, 157.647,
135.154, 133.732, 133.551, 130.985, 130.616, 130.174,
129.225, 129.011, 128.697, 128.466, 120.704, 120.295 (t,
J = 284.4 Hz), 120.156, 111.041, 65.339 (dd, J = 32.0,
18.9 Hz), 55.959. MS (MALDI, m/z, %): 455.1 (M+ + Na),
455.1 (100.00). HRMS (MALDI): calcd. for C22H18F2O5SNa
(M+ + Na): 455.0735; Found: 455.0742.
3.2. Typical procedure for preparation of compounds 4
Under N2 atmosphere, into a 25 mL Schlenk flask containing
3b (2.5 mmol, 1.005 g) in 10 mL of THF at room temperature,
was added dropwise a THF solution (2.83 mL) of (TMS)2NLi
(LHMDS, 1.06 M, 3.0 mmol). The reaction mixture was stirred
for 1 h and quenched with saturated NH4Cl aqueous solution,
and extracted with ether (3Â 25 mL). The combined organic
phase was dried over MgSO4. After the removal of solvents
under vacuum, the crude product was purified by silica gel

760
L. Zhang et al. / Journal of Fluorine Chemistry 128 (2007) 755–761
column chromatography to give product 4b as a white solid
(0.353 g), yield: 54%.
3.2.5. 2,2-Difluoro-1-(2-methoxyphenyl)vinyl benzoate
(4e)
IR (film): 3066, 2941,1748, 1602, 1583, 0496, 1249,
1126 cmÀ1 1H NMR: d 8.12 (d, J = 7.8 Hz, 2H), 7.60 (t,
.
3.2.1. 2,2-Difluoro-1-(naphthalene-2-yl)vinyl benzoate
(4a)
IR (film): 3065, 1733, 1602, 1585, 1511, 1450, 1350,
1262 cmÀ1. 1H NMR: d 8.17 (d, J = 7.8 Hz, 2H), 7.84–7.72 (m,
4H), 7.62 (t, J = 7.9 Hz, 1H), 7.55–7.40 (m, 5H). 19F NMR: d
J = 7.3 Hz, 1H), 7.49–7.42 (q, J = 7.4 Hz, 3H), 7.36 (t,
J = 8.2 Hz, 1H), 7.00–6.91 (q, J = 8.5 Hz, 2H), 3.82 (s, 3H).
19F NMR: d À94.19 (d, J = 48.2 Hz, 1F), À103.62 (d,
J = 48.2 Hz, 1F). 13C NMR: d 163.871, 157.550, 154.00 (dd,
J = 289.4, 283.1 Hz), 133.603, 131.007, 130.806, 130.221,
128.966, 128.510, 120. 487, 111.377, 55.713. MS (EI, m/z, %):
290 (M+, 2.33), 105 (100.00). HRMS (EI): calcd. for
C16H12F2O3: 290.0755; Found: 290.0764.
À91.99 (d, J = 46.8 Hz, 1F), À102.98 (d, J = 48.2 Hz, 1F). 13
C
NMR: d 163.883, 154.567 (t, J = 289.7 Hz), 134.078, 133.034,
132.974, 130.410, 128.773, 128.533, 128.434, 128.286,
127.648, 126.746, 126.609, 125.062 (t, J = 5.2 Hz), 122.840,
122.794, 122.772. MS (EI, m/z, %): 310 (M+, 5.95), 105
(100.00). EA: calcd. for C19H12F2O2: C,73.54; H, 3.90; Found:
C,73.29; H, 4.04.
3.2.6. 1-(4-tert-Butylphenyl)-2,2-difluorovinyl benzoate
(4f)
White solid; mp: 40–41 8C. IR (film): 2972, 1751, 1601,
1585, 1492, 1278, 1138 cmÀ1. 1H NMR: d 8.19 (d, J = 7.5 Hz,
2H), 7.66 (t, J = 7.1 Hz, 1H), 7.52 (t, J = 7.5 Hz, 2H), 7.40 (s,
4H), 1.30 (s, 9H). 19F NMR: d À92.95 (d, J = 49.4 Hz, 1F),
À103.47 (d, J = 49.4 Hz, 1F). 13C NMR: d 163.867, 157.174,
154.283, 151.621, 133.970, 130.343, 128.709, 128.509,
126.405, 125.649, 125.279 (dd, J = 6.1, 3.3 Hz), 34.641,
31.162. MS (EI, m/z, %): 316 (M+, 2.36), 105 (100.00). HRMS
(EI): calcd. for C19H18F2O2: 316.1275; Found: 316.1286.
3.2.2. 2,2-Difluoro-1-phenylvinyl benzoate (4b)
White solid; mp: 18–20 8C. IR (film): 3065, 1749, 1601,
1585, 1500, 1452, 1259, 1135 cmÀ1 1H NMR: d 8.20 (d,
.
J = 6.9 Hz, 2H), 7.65 (t, J = 7.3 Hz, 1H), 7.54–7.46 (q,
J = 8.2 Hz, 4H), 7.41–7.30 (m, J = 6.9 Hz, 3H). 19F NMR: d
À92.55 (d, J = 47.4 Hz, 1F), À103.18 (d, J = 47.6 Hz, 1F). 13
C
NMR: d 163.817, 154.361 (t, J = 289.0 Hz), 134.036, 130.356,
128.881, 128.830, 128.733, 128.680, 128.466, 128.407,
125.520 (dd. J = 6.3, 4.0 Hz). MS (EI, m/z, %): 260 (M+,
0.99), 105 (100.00). HRMS (EI): calcd. for C15H10F2O2:
260.0649; Found: 260.0639.
3.2.7. 2,2-Difluoro-1-(furan-2-yl)vinyl benzoate (4g)
IR (film): 3068, 1751, 1602, 1585, 1494, 1454, 1271 cmÀ1
.
1H NMR: d 8.18 (d, J = 7.6 Hz, 2H), 7.66 (t, J = 6.8 Hz, 1H),
7.52 (t, J = 7.6 Hz, 2H), 7.44 (s, 1H), 6.45 (s, 2H). 19F NMR: d
À94.44 (d, J = 43.7 Hz, 1F), À100.39 (d, J = 43.7 Hz, 1F). 3C
NMR: d 171.743, 149.399, 134.885, 133.827, 130.505,
130.198, 130.039, 128.840, 128.594, 128.481, 123.192 (t,
J = 4.1 Hz), 112.965, 110.865. MS (EI, m/z, %): 250 (M+, 1.84),
105 (100.00). HRMS (EI): calcd. for C13H8F2O3: 250.0442;
Found: 250.0448.
3.2.3. 2,2-Difluoro-1-(4-methoxyphenyl)vinyl benzoate
(4c)
White solid; mp: 44–45 8C. IR (film): 3004, 2844, 1742,
1610, 1574, 1516, 1260, 1114 cmÀ1 1H NMR: d 8.19 (d,
.
J = 8.0 Hz, 2H), 7.66 (t, J = 7.5 Hz, 1H), 7.52 (t, J = 8.0 Hz,
2H), 7.41 (d, J = 8.0 Hz, 2H), 6.91 (d, J = 8.4 Hz, 2H), 3.81 (s,
3H). 19F NMR: d À94.28 (d, J = 52.7 Hz, 1F), À104.89 (d,
J = 52.5 Hz, 1F). 13C NMR: d 163.874, 159.674, 153.993 (dd.
J = 288.7, 286.8 Hz), 133.966, 130.321, 128.701, 128.516,
127.144 (dd. J = 6.1, 4.0 Hz), 121.674, 121.611, 114.196,
55.286. MS (EI, m/z, %): 290 (M+, 2.58), 105 (100.00). EA:
calcd. for C16H12F2O3: C, 66.21; H, 4.17; Found: C, 65.95; H,
4.50.
3.3. Preparation of compound 5
Under N2 atmosphere, into a 50-mL Schlenk flask contain-
ing 2a (2.0 mmol, 0.696 g), CHCl3 (30 mL), PCl5 (6.0 mmol,
1.252 g) at room temperature, was added dropwise pyridine
(12.0 mmol, 0.936 g). The reaction mixture was heated at reflux
temperature for 3 h. After quenched with ice-water, the reaction
mixture was extracted with CHCl3 (3Â 30 mL), and the
combined organic phase was dried over anhydrous MgSO4. The
volatile solvents were removed under vacuum, and the crude
product was purified by silica gel column chromatography to
give product 5 as a white solid (0.592 g), yield: 81%.
3.2.4. 1-(4-(Dimethylamino)phenyl)-2,2-difluorovinyl
benzoate (4d)
White solid; mp: 108–109 8C. IR (film): 3068, 2897, 1744,
1618, 1584, 1529, 1280, 1115 cmÀ1 1H NMR: d 8.18 (d,
.
J = 8.4 Hz, 2H), 7.65 (t, J = 7.8 Hz, 1H), 7.51 (t, J = 7.9 Hz,
2H), 7.33 (d, J = 9.0 Hz, 2H), 6.69 (d, J = 9.0 Hz, 2H), 2.96 (s,
6H). 19F NMR: d À95.92 (d, J = 56.4 Hz, 1F), À106.48 (d,
J = 57.2 Hz, 1F). 13C NMR: d 163.954, 153.780 (dd, J = 287.5,
285.4 Hz), 150.315, 133.797, 130.298, 128.638, 126.821,
126.786, 126.768, 126.727, 112.127, 40.228. MS (EI, m/z,
%): 303 (M+, 13.78), 105 (100.00). EA: calcd. for
C17H15F2NO2: C, 67.32; H, 4.98; N, 4.62; Found: C, 67.21;
H, 5.20; N, 4.41.
3.3.1. 2-(1-Chloro-2,2-difluoro-2-
(phenylsulfonyl)ethyl)naphthalene (5)
White solid; mp: 136–138 8C. IR (film): 3064, 1581, 1509,
1449, 1340, 1157, 1108 cmÀ1. 1H NMR: d 7.98 (s, 1H), 7.83 (d,
J = 8.2 Hz, 5H), 7.68–7.44 (m, 6H), 5.78 (dd, J = 15.7, 10.4 Hz,
1H). 19F NMR: d À102.22 (dd, J = 230.7, 10.2 Hz, 1F),
À105.90 (dd, J = 232.1, 16.1 Hz, 1F). 13C NMR: d 135.310,
133.899, 133.256, 132.694, 130.565, 129.864, 129.379,

L. Zhang et al. / Journal of Fluorine Chemistry 128 (2007) 755–761
761
129.127, 128.776, 128.416, 127.724, 127.422, 126.757,
125.607, 120.179 (t, J = 292.9 Hz), 57.830 (t, J = 21.9 Hz).
MS (EI, m/z, %): 366 (M+, 3.28), 190 (100.00). HRMS (EI):
calcd. for C18H13F2O2ClS: 366.0293; Found: 366.0306.
Program (06QA14063), and the Chinese Academy of Sciences
(Hundreds-Talent Program) for financial support.
References
[1] P. Kirsch, Modern Fluoroorganic Chemistry, Wiley-VCH, Weinheim,
2004.
3.4. Preparation of compound 6
[2] K. Uneyama, Organofluorine Chemistry, Blackwell, New Delhi, 2006.
[3] M.J. Tozer, T.F. Herpin, Tetrahedron 52 (1996) 8619–8683.
[4] J.M. Percy, Top. Curr. Chem. 193 (1997) 131–195.
[5] H. Amii, K. Uneyama, Mg-promoted selective C–F bond cleavage: a
general and efficient access to difluoroenol silyl ethers and their deriva-
tives, in: V.A. Soloshonok (Ed.), Fluorine-containing Synthons, ACS
Symposium Series 911, American Chemical Society, 2005.
[6] M. Yamada, T. Ishihara, T. Ando, Tetrahedron Lett. 24 (1983) 507–510.
[7] F. Jin, Y. Xu, W. Huang, J. Chem. Soc. Perkin Trans. I (1993) 795–799.
[8] T. Brigaud, P. Doussot, C. Portella, J. Chem. Soc. Chem. Commun. (1994)
2117–2118.
Under N2 atmosphere, into a 25-mL Schlenk flask contain-
ing 5 (1.5 mmol, 0.549 g) in 15 mL of THF at room
temperature, was added dropwise a THF solution (1.70 mL)
of (TMS)2NLi (LHMDS, 1.06 M, 1.8 mmol). The reaction
mixture was stirred for 1 h and quenched with saturated NH4Cl
aqueous solution, and extracted with ether (3Â 25 mL). The
combined organic phase was dried over MgSO4. After the
removal of solvents under vacuum, the crude product was
purified by silica gel column chromatography to give product 6
as a white solid (0.182 g), yield: 54%.
[9] H. Amii, T. Kobayashi, Y. Hatamoto, K. Uneyama, Chem. Commun.
(1999) 1323–1324.
[10] We found that 2,2-difluoro enol benzoate 4b can be conveniently purified
by silica gel column chromatography at room temperature without
decomposition, but with the same procedure 1-phenyl-2,2-difluoro enol
silyl ether were readily hydrolyzed to give 2,2-difluoroacetophenone.
Furthermore, we found that 2,2-difluoro enol benzoate 4b was stable
even after stirring with 1N hydrochloric acid at room temperature for 10 h,
while the same treatment of 1-phenyl-2,2-difluoro enol silyl ether resulted
in a full hydrolysis.
3.4.1. 2-(1-Chloro-2,2-difluorovinyl)naphthalene (6)
White solid; mp: 42–44 8C. IR (film): 3061, 2925, 1718,
1627, 1296, 1274, 1193, 1006 cmÀ1. 1H NMR: d 8.00 (s, 1H),
7.84 (m, 3H), 7.61 (d, J = 8.7 Hz, 1H), 7.55–7.49 (m,
J = 3.1 Hz, 2H). 19F NMR: d À82.74 (d, J = 31.3 Hz, 1F),
À88.52 (d, J = 32.7 Hz, 1F). 13C NMR: d 157.079, 154.173,
151.290, 133.070, 132.870, 128.303, 127.641, 127.045,
126.736, 124.824, 124.669 (dd. J = 5.2, 2.2 Hz), 121.026.
MS (EI, m/z, %): 224 (M+, 97.95), 44 (100.00). HRMS (EI):
calcd. for C12H7ClF2: 224.0204; Found: 224.0196.
[11] (a) J.A. Edwards, E.M. Obukhova, V.V. Prezhdo, U.S. Patent 3,705,182
(1972).
(b) G.P. Stahly, J. Fluorine Chem. 43 (1989) 53–66;
(c) J.S. Sabol, J.R. McCarthy, Tetrahedron Lett. 33 (1992) 3101–3104;
(d) D.L. Boger, T.J. Jenkins, J. Am. Chem. Soc. 118 (1996) 8860–8870;
(e) P.J. Serafinowski, C.L. Barnes, Synthesis (1997) 225–228;
(f) J.-D. Ye, X. Liao, J.A. Piccirilli, J. Org. Chem. 44 (2005) 5882–5886;
(g) V. Reutrakul, T. Thongpaisanwong, P. Tuchinda, C. Kuhakarn, M.
Pohmakotr, J. Org. Chem. 69 (2004) 6913–6915.
3.5. Typical procedure for the hydrolysis of compound 4
[12] (a) G.K.S. Prakash, J. Hu, G.A. Olah, J. Org. Chem. 68 (2003) 4457–
4463;
Into a 10-mL Schlenk flask containing 4c (0.2 mmol,
0.058 g), THF (2 mL), H2O (2 mL) at room temperature, was
added KOH (0.3 mmol, 0.017 g). The reaction mixture was
stirred for 12 h, and extracted with ether (3Â 25 mL). The
combined organic phase was dried over MgSO4. After the
removal of solvents under vacuum, the crude product was
purified by silica gel column chromatography to give product 7
as a colorless liquid (0.027 g), yield: 72%.
(b) G.K.S. Prakash, J. Hu, T. Mathew, G.A. Olah, Angew. Chem. Int. Ed.
42 (2003) 5216–5219;
(c) G.K.S. Prakash, J. Hu, Y. Wang, G.A. Olah, Org. Lett. 6 (2004) 4315–
4317;
(d) G.K.S. Prakash, J. Hu, Y. Wang, G.A. Olah, Angew. Chem. Int. Ed. 43
(2004) 5203–5206;
(e) G.K.S. Prakash, J. Hu, Y. Wang, G.A. Olah, Eur. J. Org. Chem. (2005)
2218–2223;
(f) G.K.S. Prakash, Y. Wang, J. Hu, G.A. Olah, J. Fluorine Chem. 126
(2005) 1361–1367;
3.5.1. 2,2-Difluoro-1-(4-methoxyphenyl)ethanone (7)
1H NMR: d 7.99 (d, J = 8.7 Hz, 2H), 6.92 (d, J = 8.7 Hz,
2H), 6.19 (t, J = 53.7 Hz, 1H), 3.83 (s, 3H). 19F NMR: d À121.8
(d, J = 51.8 Hz). The characterization data was consistent with
the previous report [15].
(g) G.K.S. Prakash, J. Hu, Y. Wang, G.A. Olah, J. Fluorine Chem. 126
(2005) 529–534.
[13] (a) Y. Li, J. Hu, Angew. Chem. Int. Ed. 44 (2005) 5882–5886;
(b) C. Ni, J. Hu, Tetrahedron Lett. 46 (2005) 8273–8277;
(c) J. Liu, C. Ni, Y. Li, L. Zhang, G. Wang, J. Hu, Tetrahedron Lett. 47
(2006) 6753–6756;
(d) C. Ni, Y. Li, J. Hu, J. Org. Chem. 71 (2006) 6829–6833;
(e) C. Ni, J. Liu, L. Zhang, J. Hu, Angew. Chem. Int. Ed. 46 (2007) 786–
789.
Acknowledgements
We gratefully acknowledge the National Natural Science
Foundation of China (20502029), Shanghai Rising-Star
[14] R. Anilkumar, D.J. Burton, J. Fluorine Chem. 126 (2005) 1174–1184.
[15] W. Ying, D.D. DesMarteau, Y. Gotoh, Tetrahedron 52 (1996) 15–22.