A new synthesis of α-fluorovinylsulfones utilizing the Peterson olefination methodology

Article abstract of DOI:10.1016/S0022-1139(03)00194-5

α-Fluoro-α-silyl-substituted sulfones 1 are readily prepared from fluoromethyl phenyl sulfone and the appropriate silyl chloride. The use of TBSCl improves both the stability and yield of 1. Lithium derivatives 4 undergo a smooth Peterson olefination reaction with less-enolizable carbonyl compounds to give moderate to good yields of the expected α-fluorovinylsulfones 6, in some cases with high E-stereoselectivity. One-pot reaction with 4 generated in situ from fluoromethyl phenyl sulfone in tetrahydrofuran (THF) also proceeds smoothly, particularly with aldehydes.

Full text of DOI:10.1016/S0022-1139(03)00194-5

Journal of Fluorine Chemistry 124 (2003) 81–88
A new synthesis of a-fluorovinylsulfones utilizing the
Peterson olefination methodology
Noriaki Asakura, Yoshinosuke Usuki*, Hideo Iio
Department of Material Science, Graduate School of Science, Osaka City University,
Sugimoto, Sumiyoshi-ku, Osaka 558-8585, Japan
Received 6 June 2003; received in revised form 7 July 2003; accepted 9 July 2003
Abstract
a-Fluoro-a-silyl-substituted sulfones 1 are readily prepared from fluoromethyl phenyl sulfone and the appropriate silyl chloride. The use of
TBSCl improves both the stability and yield of 1. Lithium derivatives 4 undergo a smooth Peterson olefination reaction with less-enolizable
carbonyl compounds to give moderate to good yields of the expected a-fluorovinylsulfones 6, in some cases with high E-stereoselectivity.
One-pot reaction with 4 generated in situ from fluoromethyl phenyl sulfone in tetrahydrofuran (THF) also proceeds smoothly, particularly
with aldehydes.
# 2003 Elsevier B.V. All rights reserved.
Keywords: a-Fluoro-a-silyl sulfone; Peterson olefination; Monofluorinated building block
1. Introduction
2. Results and discussion
In the past few decades, interest in fluorinated compounds
has increased significantly due to the unique influence of the
fluorine substituent on the chemical, physical, and physio-
logical properties of these compounds [1]. Functionalized
fluoroolefins are particularly important, with current appli-
cations in the synthesis of biologically active materials such
as peptide isosteres and enzyme inhibitors [2]. Several
fluoroolefination methods have been reported (for reviews,
see [3]), and monofluorinated vinylsulfones have been
shown as an attractive approach toward a range of fluor-
oolefins [4–6]. Unsaturated sulfones themselves also have
many synthetic applications [7]. The electron-withdrawing
sulfonyl moiety is a useful functional group for further
transformation, and removal of the sulfonyl group after
completion of the procedure by reductive desulfonylation
provides access to sulfur-free products [8]. Peterson olefina-
tion is a prominent method amongst the numerous reported
techniques for the connective synthesis of alkenes [9–15].
This report describes a new preparation of fluorinated
vinylsulfones by Peterson coupling between a-fluoro-a-silyl
sulfone anions and less-enolizable carbonyl compounds.
a-Fluoro-a-silyl sulfones 1–3 were readily prepared by
deprotonation and subsequent silylation of fluoromethyl
phenylsulfone. The use of TBSCl improved both the stabi-
lity and yield of 1 (Table 1).
Treatment of 1 with 1 eq. of n-BuLi in tetrahydrofuran
(THF) provided the lithiated sulfone 4, which cleanly
reacted with aldehydes to induce an aldol condensation.
The so-formed b-oxidosilane intermediate 5 has been
shown to undergo a syn b-elimination to form the corre-
sponding a-fluorovinylsulfones (6, usually an E/Z mixture)
under basic conditions (Table 2).
The stereochemistry of 6 was assigned by the hydrogen–
fluorine vicinal coupling constants (3JHF). The ‘butterfly’
transition states with chelating control are well established
[13,14], and the formation of a closed four-centered tran-
sition state could be assumed. Of the two configurations
(A and B) of 5, which have the syn alignment of alkoxide
and silicon, 5A, which would lead to the E-isomer, is
preferable in terms of steric factor [16].
A partial separation of E- and Z-isomers was achieved by
silica gel flash column chromatography to give a Z-major
mixture of 6c (E/Z ¼ 1/20), which was isomerized to an
E-major mixture (E/Z ¼ 10/1) using catalytic amounts of
thiophenol and AIBN in benzene under reflux, according to
the Sato protocol (Scheme 1) [17].
* Corresponding author. Tel.: þ81-6-6605-2563; fax: þ81-6-6605-2522.
E-mail address: usuki@sci.osaka-cu.ac.jp (Y. Usuki).
0022-1139/$ – see front matter # 2003 Elsevier B.V. All rights reserved.
doi:10.1016/S0022-1139(03)00194-5

82
N. Asakura et al. / Journal of Fluorine Chemistry 124 (2003) 81–88
Table 1
The aldol condensation of lithiofluoromethyl phenyl sul-
Preparation of a-fluoro-a-silyl sulfones 1–3
fone with benzaldehyde and the following acetylation affor-
ded b-acetoxy-a-fluoro sulfone 7 in good yield (95%) as a
2:3 mixture of diastereomers (Scheme 2).
The configuration of the major isomer 7B is character-
ized by an anti-alignment of the acetoxy group and fluorine
atom, with a smaller hydrogen–fluorine vicinal coupling
constant (3JHF ¼ 10:5 Hz) than that (3JHF ¼ 26:0 Hz)
of minor isomer 7A as shown above, which forms
(Z)-6a through an anti b-elimination upon treatment with
SiCl
Product
Yield (%)
TBSCl
1 (SiR3¼TBS)
2 (SiR3¼TMS)
3 (SiR3¼DPMS)
68
30
18
TMSCl
DPMSCl
Table 2
a-Fluorovinylsulfonylation of aldehydes with 1
RCHO
Product
Yield (%)
E:Z
PhCHO
6a
6b
6c
65
54
34
7:1
iPrCHO
4:1
BnOCH2CH2CHO
3.3:1
Scheme 1.
Scheme 2.

N. Asakura et al. / Journal of Fluorine Chemistry 124 (2003) 81–88
83
Scheme 3.
1,8-diazabicyclo[5,4,0]undec-7-ene (DBU). However, it has
been reported that allyl sulfones are more thermodynami-
cally stable than the corresponding vinyl isomers [18].
Treatment of vinyl sulfone 6c with DBU resulted in exclu-
sive isomerization to allyl sulfone 8 (Scheme 3). This result
suggests that the aldol–acylation–elimination sequence is
not a general method to a-fluorovinylsulfone [4].
condensation with aldehydes. The Peterson olefina-
tion reaction occurred exclusively to give the correspond-
ing a-fluorovinylsulfones (6) in modest to good yields
with E-stereoselectivity. The results are summarized in
Table 3.
However, the reaction of 4 thus prepared with ketones was
not effective (Table 4). In most cases, except cyclohexanone,
The authors then turned their attention toward one-pot
synthesis of 4 as encouraged by the analogous Peterson
olefination with a-silyl phosphorus stabilized carbanion
generated in situ [13,15]. Fluoromethyl phenyl sulfone
was treated with n-BuLi (2 eq.) in THF at À78 8C to afford
gem-dianion, and the subsequent addition of TBSCl
(1 eq.) was effective for the formation of 4 in pure form.
At low temperature in THF, 4 readily underwent aldol
Scheme 4.
Table 3
One-pot preparation of a-fluorovinylsulfones 6 from aldehydes
Entry
Aldehyde
Product
Yield (%) (E:Z)
1
2
3
4
5
6
7
PhCHO
iPrCHO
6a
6b
6c
6d
6e
6f
52 (3.3:1)
41 (4:1)
42 (3.5:1)
48 (7:1)
44 (5:1)
52 (9:1)
36 (20:1)
BnOCH2CH2CHO
CH3CH2CH2CHO
CH3(CH2)6CHO
PhCH2CH2CHO
2-Furaldehyde
6g
Table 4
Reaction of 4 with ketones
Entry
1
Ketone
Product
Yield (%)
55
Cyclohexanone
2
3
Cycloheptanone
Benzophenone
4
Acetophenone
30–60
5
6
7
4-Heptanone
2-Heptanone
2-Heptanone with CeCl3

84
N. Asakura et al. / Journal of Fluorine Chemistry 124 (2003) 81–88
Scheme 5.
the enolization of ketones overcame the aldol condensation
to give a-silyl sulfone 1 as the main product. Interestingly,
McCarthy demonstrated the one-pot Horner–Wittig reaction
of diethyl 1-fluoro-1-(phenylsulfonyl)methane-phosphonate
with ketones to afford the corresponding a-fluorovinylsul-
fones [5,6].
a-Fluorovinylsulfonylation of benzophenone by Peterson
olefination was realized using a stepwise reaction in Et2O.
Treatment of 1 with 1 eq. of n-BuLi in Et2O provided the
lithiated sulfone 4, which cleanly reacted with less-enoliz-
able ketones to induce a Peterson olefination reaction. The
corresponding a-fluorovinylsulfone (6i) was obtained
(Scheme 4).
4.1. Typical procedure for the preparation
of a-fluoro-a-silyl sulfones (1–3)
Under an Ar atmosphere, to a solution of fluoromethyl
phenyl sulfone (1.74 g, 10.0 mmol) in THF (15 ml) was
added n-BuLi (1.55 M solution in hexane; 6.9 ml,
11.0 mmol) at À78 8C. After 30 min stirring at this tem-
perature, to the mixture was added dropwise a solution of
tert-butyldimethylsilyl chloride (1.56 g, 10.0 mmol) in THF
(6 ml). The reaction mixture was allowed to warm to room
temperature and stirred overnight. A solution of pH 7.0
phosphate buffer (15 ml) was poured into the reaction
mixture, and the aqueous layer was extracted with diethyl
ether. The combined organic extracts were washed with
water and brine, dried (Na2SO4) and evaporated under
reduced pressure to afford the crude product, which was
purified by flash column chromatography (10% EtOAc in
hexane) to give 1 (1.97 g, 6.8 mmol; yield 68%).
Reductive removal of the phenylsulfonyl moiety from 6i
was readily achieved by treatment with sodium amalgam in
the presence of NaH2PO4–Na2HPO4 (Scheme 5).
3. Conclusion
4.1.1. tert-Butyldimethylsilyl-fluoro-methyl phenyl
sulfone (1)
a-Fluorovinylsulfones 6 were stereospecifically pre-
pared by the Peterson olefination of less-enolizable carbo-
nyl compounds with a-fluoro-a-silyl sulfones prepared
from fluoromethyl phenyl sulfone and the appropriate silyl
chloride.
4
1H NMR (400 MHz, CDCl3) d 0.30 (d, JHF ¼ 1:2 Hz,
3H), 0.38 (s, 3H), 0.98 (s, 9H), 5.19 (d, 2JHF ¼ 47:1 Hz, 1H),
7.53–7.58 (m, 2H), 7.63–7.67 (m, 1H), 7.92–7.94 (m, 2H);
3
13C NMR (100 MHz, CDCl3) d À7.87 (d, JCF ¼ 3:2 Hz),
3
À6.34 (d, JCF ¼ 4:9 Hz), 17.11, 26.20, 100.36 (d,
1JCF ¼ 216:5 Hz), 128.60, 129.09, 133.86, 138.51; 19F
2
4. Experimental
NMR (283 MHz, CDCl3) d À7.04 (d, JHF ¼ 47:1 Hz); IR
(CH2Cl2) n 3623, 3054, 2985, 2861, 1421, 1267, 1155, 1018,
896 cmÀ1; MS (FAB) m/z 287 [MÀH]À; HRMS (FAB) Calcd
for C13H20O2FSiS [MÀH]À: 287.0937. Found: 287.0954.
All air- and moisture-sensitive reactions were carried out
inflame-dried, argon-flushed, two-necked flaskssealedwith
rubber septa, and the dry solvents and reagents were intro-
duced using a syringe. Tetrahydrofuran was freshly distilled
from sodium benzophenone ketyl. Flash column chromato-
graphy was carried out on a Kanto Chemical silica gel 60N
(spherical, neutral, 40–50 mm), and pre-coated Merck silica
gel plates (Art5715 Kieselgel 60F254, 0.25 mm) were used
for thin-layer chromatography (TLC). Unless mentioned
otherwise, 1H, 13C and 19F nuclear magnetic resonance
(NMR) spectra were recorded in CDCl3 on a JEOL JNM-
LA400 or JEOL JNM-LA300. Coupling constants were
4.1.2. Trimethylsilyl-fluoro-methyl phenyl sulfone (2)
1H NMR (400 MHz, CDCl3) d 0.30 (s, 9H), 5.08 (d,
2JHF ¼ 46:8 Hz, 1H), 7.45–7.50 (m, 2H), 7.54–7.59 (m,
1H), 7.84–7.86 (m, 2H); 13C NMR (100 MHz, CDCl3) d
1
À3.06, 101.11 (d, JCF ¼ 217:2 Hz), 128.26, 129.00,
133.76, 134.66; 19F NMR (283 MHz, CDCl3) d À9.61 (d,
2JHF ¼ 46:8 Hz); IR (CH2Cl2) n 3623, 3055, 2985, 2835,
1444, 1421, 1267, 1155, 1016 cmÀ1; MS (FAB) m/z 245
[MÀH]À; HRMS (FAB) Calcd for C11H13O2FSiS [MÀH]À:
245.0468. Found: 245.0464.
1
determined directly from H, 13C and 19F NMR spectra.
Chemical shifts of 19F NMR were given by d relative to that
of an external trifluoroacetic acid (TFA). Mass spectra were
obtained on a JEOL JMS-700T or JEOL JMS-AX500 spec-
trometer. Infrared (IR) spectra were recorded on a JASCO
FT/IR-700.
4.1.3. Diphenylmethylsilyl-fluoro-methyl phenyl
sulfone (3)
1H NMR (400 MHz, CDCl3) d 0.99 (s, 3H), 5.57 (d,
2JHF ¼ 46:3 Hz, 1H), 7.34–7.55 (m, 9H), 7.60–7.99 (m,

N. Asakura et al. / Journal of Fluorine Chemistry 124 (2003) 81–88
85
3
3
6H); 13C NMR (100 MHz, CDCl3) d À5.35 (d, JCF
¼
(283 MHz, CDCl3) d À130.21 (d, JHF ¼ 33:2 Hz); IR
(CH2Cl2) n 3626, 3055, 2985, 1423, 1333, 1267, 1151,
895 cmÀ1; MS (EI) m/z 228 [Mþ], HRMS (EI) Calcd for
C11H13O2FS: 228.0620. Found: 228.0625. Isomer Z (diag-
nostic peaks only): 1H NMR (400 MHz, CDCl3) d 3.53 (m,
1
3:3 Hz), 100.88 (d, JCF ¼ 218:9 Hz), 127.86, 128.02,
128.16, 128.60, 129.00, 129.81, 130.41, 130.51, 133.91,
135.07, 135.26, 135.28, 137.07, 138.20; 19F NMR
2
(283 MHz, CDCl3) d À5.14 (d, JHF ¼ 46:3 Hz); IR
3
3
(CH2Cl2) n 3070, 3054, 3027, 3012, 1427, 1326, 1153,
1118, 821, 798, 698 cmÀ1; MS (FAB) m/z 369 [MÀH]À;
HRMS (FAB) Calcd for C20H18O2FSiS [MÀH]À: 369.0780.
Found: 369.0776.
1H), 5.62 (dd, JHH ¼ 11:0 Hz, JHF ¼ 22:5 Hz, 1H); 13C
NMR (100 MHz, CDCl3) d 22.81 (d, 4JCF ¼ 2:4 Hz, C-4, C-
5), 24.57 (d, 3JCF ¼ 3:3 Hz, C-3), 126.87 (d, 2JCF ¼ 9:9 Hz,
C-2), 128.20, 129.34, 134.32, 138.45, 150.93 (d,
1JCF ¼ 285:7 Hz, C-1); 19F NMR (283 MHz, CDCl3) d
3
4.2. One-pot procedure for the synthesis of
a-fluorovinylsulfone (6)
À119.61 (d, JHF ¼ 22:5 Hz).
4.2.3. 4-Benzyloxy-1-fluoro-1-phenylsulfonyl-but-1-
ene (6c)
Under an Ar atmosphere, to a solution of fluoromethyl
phenyl sulfone in THF (2 ml) was added n-BuLi (1.55 M
solution in hexane; 1.4 ml, 2.1 mmol) at À78 8C. After
30 min stirring at this temperature, to the mixture was added
dropwise a solution of tert-butyldimethylsilyl chloride
(0.151 g, 1.0 mmol) in THF (1 ml). The mixture was stirred
for 60 min at this temperature, and then a solution of
carbonyl compound (1.0 mmol) in THF (1 ml) was added
slowly. The reaction mixture was allowed to warm to room
temperature and stirred overnight. A solution of pH 7.0
phosphate buffer was then poured into the reaction mixture,
and the aqueous layer was extracted with diethyl ether. The
combined organic extracts were dried (MgSO4) and evapo-
rated under reduced pressure to afford the crude product,
which was then purified by flash column chromatography
(10% EtOAc in hexane).
Isomer E: 1H NMR (400 MHz, CDCl3) d 2.45 (qd,
3
3
4JHF ¼ 2:4 Hz, JHH ¼ 7:6 Hz, 2H), 3.49 (t, JHH
¼
3
7:6 Hz, 2H), 4.43 (s, 2H), 6.32 (dt, JHH ¼ 7:6 Hz,
3JHF ¼ 32:7 Hz, 1H), 7.18–7.29 (m, 5H), 7.41–7.51 (m,
2H), 7.54–7.64 (m, 1H), 7.82–7.98 (m, 2H); 13C NMR
3
(100 MHz, CDCl3) d 25.04 (d, JCF ¼ 2:5 Hz, C-3),
2
67.44, 72.90, 115.61 (d, JCF ¼ 6:6 Hz, C-2), 127.53,
127.65, 128.26, 128.35, 128.45, 128.91, 129.29, 134.24,
1
137.38, 154.81 (d, JCF ¼ 295:0 Hz, C-1); 19F NMR
3
(283 MHz, CDCl3) d À127.67 (d, JHF ¼ 32:7 Hz); IR
(CH2Cl2) n 3626, 3055, 2985, 2866, 1421, 1263, 1167,
1018, 897 cmÀ1; MS (FAB) m/z 319 ½M þ HŠþ, HRMS
(FAB) Calcd for C17H16O3FS ðM þ HÞþ: 319.0795. Found:
319.0805. Isomer Z (diagnostic peaks only): 1H NMR
(400 MHz, CDCl3) d 2.89–2.95 (m, 2H), 3.52–3.55 (m,
3
3
2H), 4.45 (s, 2H), 5.93 (dt, JHH ¼ 8:1 Hz, JHF
¼
4.2.1. 1-Fluoro-1-phenylsulfonyl-styrene (6a)
Isomer E: 1H NMR (400 MHz, CDCl3) d 7.05 (d,
21:7 Hz, 1H); 13C NMR (100 MHz, CDCl3) d 27.60 (C-
3), 65.75, 67.47, 117.81 (d, 2JCF ¼ 7:1 Hz, C-2), 151.11 (d,
1JCF ¼ 270:3 Hz, C-1); 19F NMR (283 MHz, CDCl3) d
3JHF ¼ 34:6 Hz, 1H), 7.31–7.70 (m, 8H), 7.85–8.01 (m,
2H); 13C NMR (100 MHz, CDCl3) d 115.45, 128.49,
À115.95 (d, JHF ¼ 21:7 Hz).
3
3
128.86, 129.37, 130.05, 130.12, 130.31 (d, JCF
1
¼
2:5 Hz, C-3), 134.35, 137.31, 153.42 (d, JCF
¼
4.2.4. 1-Fluoro-1-phenylsulfonyl-pent-1-ene (6d)
1
304:0 Hz, C-1); 19F NMR (283 MHz, CDCl3) d À125.42
(d, 3JHF ¼ 34:6 Hz); IR (CH2Cl2) n 3624, 3055, 2985, 2835,
1423, 1267, 1163, 1018, 897 cmÀ1; MS (EI) m/z 262 [Mþ],
HRMS (EI) Calcd for C14H11O2FS: 262.0464. Found:
262.0438. Isomer Z (diagnostic peaks only): 1H NMR
Isomer E: H NMR (400 MHz, CDCl3) d 0.81–0.95 (m,
3
3
3H), 1.45 (sextet, JHH ¼ 7:3 Hz, 2H), 2.17 (qd, JHH
¼
4
3
7:3 Hz, JHF ¼ 2:2 Hz, 2H), 6.23 (dt, JHH ¼ 7:3 Hz,
3JHF ¼ 32:7 Hz, 1H), 7.54 (t, JHH ¼ 7:6 Hz, 2H), 7.64 (t,
3
3JHH ¼ 7:6 Hz, 1H), 7.91 (d, 3JHH ¼ 7:6 Hz, 2H); 13C NMR
(100 MHz, CDCl3) d 13.31 (C-5), 21.21 (d, 4JCF ¼ 1:6 Hz,
(400 MHz, CDCl3) d 6.90 (d, JHF ¼ 21:9 Hz, 1H); 13C
3
2
3
2
NMR (100 MHz, CDCl3) d 118.92 (d, JCF ¼ 19:0 Hz, C-
C-4), 25.90 (d, JCF ¼ 1:7 Hz, C-3), 118.28 (d, JCF ¼
2), 127.98, 128.63, 129.09, 129.29, 129.33, 129.75 (d,
3JCF ¼ 2:5 Hz, C-3), 134.38, 137.79, 153.02 (d,
1JCF ¼ 290:0 Hz, C-1); 19F NMR (283 MHz, CDCl3) d
7:4 Hz, C-2), 128.27, 129.23, 134.15, 137.48, 154.13 (d,
1JCF ¼ 293:3 Hz, C-1); 19F NMR (283 MHz, CDCl3) d
3
À129.79 (d, JHF ¼ 32:7 Hz). IR (CH2Cl2) n 3623, 3055,
3
À112.35 (d, JHF ¼ 21:9 Hz).
2985, 2873, 1423, 1335, 1265, 1171, 897 cmÀ1. MS (EI) m/z
228 [Mþ]; HRMS (EI) Calcd for C11H13O2FS: 228.0621.
Found: 228.0600. Isomer Z (diagnostic peaks only): 1H
4.2.2. 1-Fluoro-1-phenylsulfonyl-3-methyl-but-1-ene (6b)
1
3
Isomer E: H NMR (400 MHz, CDCl3) d 1.00–1.04 (m,
NMR (400 MHz, CDCl3) d 2.60 (q, JHH ¼ 8:5 Hz, 2H),
6H), 2.70 (m, 1H), 6.10 (dd, 3JHH ¼ 9:8 Hz, 3JHF ¼ 33:2 Hz,
5.82 (dt, JHH ¼ 8:5 Hz, JHF ¼ 22:2 Hz, 1H). 13C NMR
3
3
4
1H), 7.50–7.56 (m, 2H), 7.61–7.67 (m, 1H), 7.88–7.93 (m,
2H); 13C NMR (100 MHz, CDCl3)
(100 MHz, CDCl3) d 22.34 (d, JCF ¼ 2:4 Hz, C-4), 26.07
3
2
d
21.75 (d,
(d, JCF ¼ 3:3 Hz, C-3), 120.39 (d, JCF ¼ 12:4 Hz, C-2),
128.05, 128.98, 134.24, 138.35, 152.15 (d, 1JCF ¼ 271:1 Hz,
C-1). 19F NMR (283 MHz, CDCl3) d À117.28 (d,
3JHF ¼ 22:2 Hz).
3
4JCF ¼ 1:7 Hz, C-4, C-5), 24.89 (d, JCF ¼ 1:7 Hz, C-3),
2
124.50 (d, JCF ¼ 6:6 Hz, C-2), 128.45, 129.32, 134.22,
137.52, 152.74 (d, JCF ¼ 293:2 Hz, C-1); 19F NMR
1

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N. Asakura et al. / Journal of Fluorine Chemistry 124 (2003) 81–88
4.2.5. 1-Fluoro-1-phenylsulfonyl-non-1-ene (6e)
1
4.2.8. (1-Fluoro-1-phenylsulfonyl-ethylidene)cyclohexane
(6h)
Isomer E: H NMR (400 MHz, CDCl3) d 0.82–1.45 (m,
3
13H), 2.19 (qd, JHH ¼ 7:7 Hz, 4JHF ¼ 2:2 Hz, 2H), 6.24
1H NMR (400 MHz, CDCl3) d 1.49–1.62 (m, 6H), 2.22–
2.26 (m, 2H), 2.75–2.79 (m, 2H), 7.51–7.57 (m, 2H), 7.61–
7.67 (m, 1H), 7.90–7.94 (m, 2H); 13C NMR (100 MHz,
3
3
(dt, JHH ¼ 7:8 Hz, JHF ¼ 32:6 Hz, 1H), 7.49–7.55 (m,
2H), 7.63–7.70 (m, 1H), 7.89–7.94 (m, 2H); 13C NMR
(100 MHz, CDCl3) d 13.95 (C-9), 13.99 (C-8), 17.08 (C-
7), 22.46 (C-6), 22.52 (C-5), 24.12 (d, 4JCF ¼ 1:6 Hz, C-4),
3
CDCl3) d 25.66, 26.86, 26.95, 27.23 (d, JCF ¼ 1:6 Hz, C-
3), 27.84 (d, 3JCF ¼ 8:2 Hz, C-7), 127.88, 129.20, 133.69 (d,
27.99 (d, 3JCF ¼ 2:4 Hz, C-3), 118.67 (d, 2JCF ¼ 7:4 Hz, C-
2JCF ¼ 8:2 Hz, C-2), 133.89, 139.43, 145.89 (d, JCF
¼
1
1
2), 128.43, 129.29, 134.18, 137.63, 154.07 (d, JCF
¼
276:7 Hz, C-1); 19F NMR (283 MHz, CDCl3) d À125.97
(s, 1.0F); IR (CH2Cl2) n 3624, 3055, 2985, 2834, 1421, 1267,
1159, 1018, 897 cmÀ1; MS m/z 255 ½M þ HŠþ, HRMS (FAB)
Calcd for C13H16O2FS ðM þ HÞþ: 255.0855. Found:
255.0861.
292:5 Hz, C-1); 19F NMR (283 MHz, CDCl3) d À129.68
(d, 3JHF ¼ 32:6 Hz); IR (CH2Cl2) n 2954, 2931, 2857, 1450,
1334, 1160, 782, 763, 728, 667 cmÀ1; MS (FAB) m/z 285
½M þ HŠþ, HRMS (FAB) Calcd for C15H22O2FS ðM þ HÞþ:
285.1325. Found: 285.1325. Isomer Z (diagnostic peaks
only): 1H NMR (400 MHz, CDCl3) d 2.62 (q, JHH
¼
4.3. Stepwise procedure for synthesis of 2,2-diphenyl-
1-fluoro-1-phenylsulfonyl-ethylene (6i)
3
3
3
7:3 Hz, 2H), 5.83 (dt, JHH ¼ 8:4 Hz, JHF ¼ 22:3 Hz,
1H); 13C NMR (100 MHz, CDCl3) d 24.35 (d, JCF
¼
4
3
3:0 Hz, C-4), 28.93 (d, JCF ¼ 5:8 Hz, C-3), 120.76 (d,
Under an Ar atmosphere, to a solution of 1 (0.343 g,
1.2 mmol) in diethyl ether (5 ml) was added n-BuLi (2.66 M
solution in hexane; 0.49 ml, 1.3 mmol) at À78 8C. After
30 min stirring at this temperature, a solution of benzophe-
none (0.238 g, 1.2 mmol) in diethyl ether (2 ml) was added
dropwise to the mixture. The reaction mixture was allowed
to warm to room temperature and stirred overnight. A
solution of pH 7.0 phosphate buffer (5 ml) was poured into
the reaction mixture, and the aqueous layer was extracted
with diethyl ether. The combined organic extracts were
washed with water and brine, and dried (MgSO4) and
evaporated under reduced pressure to afford the crude
product, which was purified by flash column chromatogra-
phy (5% EtOAc in hexane) to give 6i (0.256 g, 0.75 mmol;
yield 63%).
2JCF ¼ 13:7 Hz, C-2), 128.21, 129.05, 134.28, 138.53,
151.95 (d, JCF ¼ 270:7 Hz, C-1); 19F NMR (283 MHz,
1
3
CDCl3) d À117.40 (d, JHF ¼ 22:3 Hz).
4.2.6. 1-Fluoro-1-phenylsulfonyl-4-phenyl-but-1-ene (6f)
Isomer E: 1H NMR (400 MHz, CDCl3) d 2.43 (qd,
4
3
3JHH ¼ 7:6 Hz, JHF ¼ 2:2 Hz, 2H), 2.66 (t, JHH
¼
3
3
7:6 Hz, 2H), 6.16 (dt, JHH ¼ 7:6 Hz, JHF ¼ 32:4 Hz,
1H), 6.95–7.22 (m, 5H), 7.39–7.46 (m, 2H), 7.52–7.58 (m,
1H),7.75–7.77(m, 2H);13CNMR(100 MHz, CDCl3)d25.81
4
3
(d, JCF ¼ 1:6 Hz, C-4), 34.06 (d, JCF ¼ 1:7 Hz, C-3),
2
117.19 (d, JCF ¼ 6:6 Hz, C-2), 126.39, 128.23, 128.40,
1
128.53, 129.29, 134.20, 137.45, 139.84, 154.38 (d, JCF
¼
294:9 Hz, C-1); 19F NMR (283 MHz, CDCl3) d À128.26 (d,
3JHF ¼ 32:4 Hz); IR (CH2Cl2) n 3066, 3027, 2931, 1450,
1334, 1214, 1160, 1103, 767 cmÀ1; MS (FAB) m/z 291
½M þ HŠþ, HRMS (FAB) Calcd for C16H16O2FS
ðM þ HÞþ: 291.0855. Found: 291.0866. Isomer Z (diagnostic
peaks only): 1H NMR (400 MHz, CDCl3) d 2.69 (t,
1H NMR (400 MHz, CDCl3) d 7.11–7.22 (m, 6H), 7.24–
7.35 (m, 4H), 7.38–7.43 (m, 2H), 7.50–7.56 (m, 1H), 7.73–
7.76 (m, 2H); 13C NMR (100 MHz, CDCl3) d 126.48,
127.19, 127.46, 128.05, 128.26, 128.40, 128.91, 129.33,
3
129.60, 129.66, 130.10 (d, JCF ¼ 3:3 Hz), 133.92 (d,
3JHH ¼ 8:6 Hz, 2H), 2.90 (q, JHH ¼ 8:6 Hz, 2H), 5.75 (dt,
2JCF ¼ 4:1 Hz, C-2), 150.62 (d, JCF ¼ 297:4 Hz, C-1);
3
1
3JHH ¼ 8:6 Hz, 3JHF ¼ 21:9 Hz, 1H); 13C NMR (100 MHz,
CDCl3) d 25.99 (C-4), 35.29 (d, 3JCF ¼ 2:0 Hz, C-3), 119.28
(d, 2JCF ¼ 10:8 Hz, C-2), 150.30 (d, 1JCF ¼ 268:2 Hz, C-1);
19F NMR (283 MHz, CDCl3) d À116.38(d, 3JHF ¼ 21:9 Hz).
19F NMR (283 MHz, CDCl3) d À117.55 (s, 1.0F); IR
(CH2Cl2) n 3624, 3055, 2985, 2835, 1423, 1265, 1018,
897 cmÀ1; MS (FAB) m/z 339 ½M þ HŠþ, HRMS (FAB)
Calcd for C20H16O2FS ðM þ HÞþ: 339.0855. Found:
339.0860.
4.2.7. 2-(2-Furyl)-1-fluoro-1-phenylsulfonylethylene (6g)
Isomer E: 1H NMR (400 MHz, CDCl3) d 6.49 (dd,
4.4. Typical procedure for aldol condensation of
lithiofluoromethyl phenyl sulfone with aldehydes
3
3JHH ¼ 1:7, 3.3 Hz), 6.78 (d, JHH ¼ 3:3 Hz), 7.08 (d,
3JHF ¼ 32:5 Hz), 7.55–7.60 (m, 2H), 7.66–7.70 (m, 1H),
7.97–8.00 (m, 2H); 13C NMR (100 MHz, CDCl3) d 105.63
Under an Ar atmosphere, to a solution of fluoromethyl
phenyl sulfone in THF (5 ml) was added n-BuLi (2.44 M in
hexane; 0.82 ml, 2.0 mmol) at À788C. After 30 min stirring
at this temperature, to the mixture was added dropwise a
solution of benzaldehyde (0.212 g, 2.0 mmol) in THF
(3 ml). The reaction mixture was allowed to warm to
À20 8C and stirred for 4 h, after which acetic anhydride
(0.24 ml, 2.5 mmol) was dropped into the mixture. The
reaction mixture was allowed to warm to room temperature
4
2
(d, JCF ¼ 4:1 Hz, C-4), 112.53, 115.96 (d, JCF ¼ 9:1 Hz,
C-2), 128.59, 129.47, 134.42, 137.50, 145.04 (d,
1
3JCF ¼ 4:1 Hz, C-3), 145.09, 151.70 (d, JCF ¼ 304:0 Hz,
C-1); 19F NMR (283 MHz, CDCl3) d À124.48 (d,
3JHF ¼ 32:5 Hz); IR (CH2Cl2) n 3624, 3055, 2985, 1421,
1267, 1161, 1018, 897 cmÀ1; MS (FAB) m/z 253 ½M þ HŠþ,
HRMS (FAB) Calcd for C12H10O3FS ðM þ HÞþ: 253.0335.
Found: 253.0354.

N. Asakura et al. / Journal of Fluorine Chemistry 124 (2003) 81–88
87
and stirred overnight. Water was poured into the reaction
mixture, and the aqueous layer was extracted with Et2O. The
combined organic extracts were dried (Na2SO4) and evapo-
rated under reduced pressure to afford the crude product,
which was purified by flash column chromatography (10%
EtOAc in hexane) to give 2-acetoxy-2-phenyl-1-fluoro-1-
phenylsulfonylethane (0.611 g, 1.9 mmol; yield 95%) as a
2:3 mixture of diastereomers.
3JHF ¼ 16:1 Hz). IR (CH2Cl2) n 3055, 1699, 1421, 1267,
1018 cmÀ1. MS (EI) m/z 320 [Mþ]; HRMS (EI) Calcd for
C17H17O3FS: 320.0882. Found: 320.0886.
4.6. Typical procedure for reductive desulfonylation
A 0.188 g weight of 6i (0.56 mmol) was dissolved in
methanol–THF (1:2, 6 ml) under an Ar atmosphere. After
addition of anhydrous sodium hydrogen phosphate (0.202 g,
1.7 mmol) and anhydrous disodium hydrogen phosphate
(0.340 g, 2.2 mmol), the reaction mixture was cooled to
À78 8C. A 5% sodium amalgam (0.640 g, 1.4 mmol) was
added in several portions with vigorous stirring. The reac-
tion mixture was allowed to warm to room temperature and
stirred overnight. The solution was then decanted from the
solid residue, which was extracted with diethyl ether and
pentane. The combined organic extracts were dried
(Na2SO4) and evaporated under reduced pressure to afford
the crude product, which was purified by flash column
chromatography (hexane) to give 2,2-diphenyl-1-fluor-
oethylene (0.0491 g, 0.25 mmol; yield 45%). 1H NMR
1
Diastereomer A: H NMR (400 MHz, CDCl3) d 1.86 (s,
3H), 5.26 (dd, 2JHF ¼ 45:1 Hz, 3JHH ¼ 2:2 Hz, 1H), 6.49 (dd,
3
3JHF ¼ 26:0 Hz, JHH ¼ 2:2 Hz, 1H), 7.29–7.38 (m, 5H),
7.49–7.58 (m, 2H), 7.63–7.70 (m, 1H), 7.87 (d,
3JHH ¼ 7:9 Hz, 2H); 13C NMR (100 MHz, CDCl3) d
2
1
20.32, 70.00 (d, JCF ¼ 15:7 Hz), 102.17 (d, JCF
¼
232:1 Hz), 127.10, 127.92, 128.66, 129.14, 129.19, 134.43,
134.57, 136.22, 168.55; 19F NMR (283 MHz, CDCl3) d
À192.77 (dd, 2JHF ¼ 45:1 Hz, 3JHF ¼ 26:0 Hz). IR (CH2Cl )
n 3055, 1736, 1699, 1267, 1018 cmÀ1. MS (EI) m/z 262 [Mþ2];
HRMS (EI) Calcd for C14H11O2FS: 262.0464. Found:
262.0437. Diastereomer B (diagnostic peaks only): 1H
NMR (400 MHz, CDCl3) d 2.13 (s, 3H), 5.39 (dd, JHF
2
¼
3
3
2
46:4 Hz, JHH ¼ 7:0 Hz, 1H), 6.28 (dd, JHH ¼ 7:0 Hz,
(400 MHz, CDCl3) d 6.96 (d, JHF ¼ 83:4 Hz, 1H), 7.23–
3JHF ¼ 11:0 Hz, 1H), 7.32–7.38 (m, 5H), 7.56 (t,
7.25 (m, 2H), 7.29–7.39 (m, 8H); 13C NMR (100 MHz,
3
2
3JHH ¼ 7:6 Hz, 2H), 7.69 (t, JHH ¼ 7:6 Hz, 1H), 7.91 (d,
CDCl3) d 126.22 (d, JCF ¼ 5:8 Hz, C-2), 127.75, 127.79,
3JHH ¼ 7:6 Hz, 2H); 13C NMR (100 MHz, CDCl3) d 20.82,
128.14, 128.19, 128.49, 128.64, 128.68, 129.72, 129.76,
1
2
1
70.66 (d, JCF ¼ 24:8 Hz), 100.56 (d, JCF ¼ 223:0 Hz),
128.07, 128.57, 129.23, 129.42, 129.62, 133.70, 134.73,
135.40, 168.77; 19F NMR (283 MHz, CDCl3) d À183.54
(dd, 2JHF ¼ 46:4 Hz, 3JHF ¼ 11:0 Hz).
135.12, 136.94, 137.03, 145.76 (d, JCF ¼ 267:7 Hz, C-
2
1); 19F NMR (283 MHz, CDCl3) d À128.93 (d, JHF
¼
83:4 Hz, 1.0F); IR (CH2Cl2) n 3626, 3055, 2985, 2835,
1421, 1267, 897 cmÀ1; MS (EI) m/z 198 [Mþ], HRMS
(EI) Calcd for C14H11F: 198.0845. Found: 198.0853.
4.5. Typical procedure for isomerization to allylsulfones
with 1,8-diazabicyclo[5,4,0]undec-7-ene (DBU)
Acknowledgements
Under an Ar atmosphere, to a solution of 6c (0.262 g,
0.82 mmol) in methanol (3 ml) was added DBU (0.149 g,
0.98 mmol) at 0 8C. The reaction mixture was allowed to
warm to room temperature and stirred overnight. After
removing the solvents, a solution of sat NH4Cl aq (3 ml)
was poured into the reaction mixture, and the aqueous layer
was extracted with Et2O. The combined organic extracts
were washed with brine, and dried (Na2SO4) and evaporated
under reduced pressure to afford the crude product, which
was then purified by flash column chromatography (10%
EtOAc in hexane) to give 4-benzyloxy-1-fluoro-1-phenyl-
sulfonyl-2-butene 8 (0.227 g, 0.71 mmol; yield 87%).
1H NMR (400 MHz, CDCl3) d 4.07–4.10 (m, 2H), 4.52 (s,
Thanks are extended to the Analytical Division of Osaka
City University, for mass spectra measurements.
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d
À175.40 (d, JHF ¼ 47:0 Hz,

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