Highly stereoselective and one-pot synthesis of tetra-substituted monofluoroalkenes with aldehydes and fluorobis(phenylsulfonyl)methane

Article abstract of DOI:10.1002/cjoc.201300365

A highly stereoselective synthesis of tetrasubstituted monofluoroalkenes with aldehydes and fluorobis(phenylsulfonyl)methane (FBSM) in one pot has been developed. The reaction was amenable to para- and meta-substituted aryl aldehydes, 2-naphthaldehyde, and cinnamaldehyde, giving phenylsulfonyl- substituted monofluoroalkenes in 40%-86% yields with 98/2-99/1 Z/E ratios. The presence of the sulfonyl group enables the further transformation of the products into more useful monofluoroalkenes. Highly stereoselective and one-pot synthesis of tetrasubstituted monofluoroalkenes with fluorobis(phenylsulfonyl) methane (FBSM) as the fluoroolefination reagent has been developed. This protocol is amenable to the transformation of non-enolizable aldehydes with less sterically demanding substituents. For enolizable aldehydes and sterically hindered aromatic aldehydes, the reaction furnishes carbonyl addition products. Copyright

Full text of DOI:10.1002/cjoc.201300365

FULL PAPER
DOI: 10.1002/cjoc.201300365
Highly Stereoselective and One-Pot Synthesis of
Tetra-substituted Monofluoroalkenes with Aldehydes
and Fluorobis(phenylsulfonyl)methane
Xiao Shen, Chuanfa Ni, and Jinbo Hu*
Key Laboratory of Organofluorine Chemistry, Shanghai Institute of Organic Chemistry,
Chinese Academy of Sciences, Shanghai 200032, China
A highly stereoselective synthesis of tetrasubstituted monofluoroalkenes with aldehydes and fluorobis(phenyl-
sulfonyl)methane (FBSM) in one pot has been developed. The reaction was amenable to para- and meta-substituted
aryl aldehydes, 2-naphthaldehyde, and cinnamaldehyde, giving phenylsulfonyl-substituted monofluoroalkenes in
40%－86% yields with 98/2－99/1 Z/E ratios. The presence of the sulfonyl group enables the further transformation
of the products into more useful monofluoroalkenes.
Keywords olefination, aldehydes, nucleophilic addition, sulfones, fluorine
Introduction
monofluoroalkenes by olefination of aldehydes with
fluorobis(phenylsulfonyl)methane (FBSM) in one pot.
The selective incorporation of fluorine atoms or
fluorinated moieties into organic molecules can often
lead to great changes in their solubility, lipophilicity,
metabolic stability, and chemical reactivity.[1] Therefore,
fluorinated compounds have been widely used in phar-
maceutical, agrochemical, and material sciences.[1,2]
Among various fluorinated motifs contained in these
fluorinated compounds, the monofluoroalkene is of par-
ticular interest. The monofluoroalkene moiety has been
widely used as the peptide bond isostere in the design of
protease inhibitors[1a,3] because of its similar charge dis-
tribution and dipole moment to that of amide bond. In
addition, monofluoroalkenes can be used as fluorinated
building blocks for further functionalization.[4]
Many methods have been developed towards the
synthesis of monofluoroalkenes,[5] including the elimi-
nation reactions of vicinal halofluorides, fluorohydrins,
fluorosulfoxides and fluorocarboxylates, the addition-
elimination processes from gem-difluoroalkenes, and
the fluoroolefination between fluorinated sulfoximines
and nitrones.[6] The carbonyl compound-based methods,
such as Witting reaction,[7] Horner-Wadsworth-
Emmons reaction,[8] Peterson olefination,[9] and Julia-
Kocienski olefination,[10] have also been used to synthe-
size monofluoroalkenes; however, the control of the Z/E
selectivity in these one-pot reactions still remains a
challenging task, especially for the synthesis of tetra-
substituted monofluoroalkene. Herein, we report a
highly stereoselective synthesis of tetra-substituted
Scheme 1 Highly stereoselective preparation of tera-substituted
monofluoroalkene in three steps[11f]
(1) LiHMDS, CH2Cl2
OH
O
-78 oC, 30 min
SO2Ph
+
FBSM
Ph
(2) CF3COOH, -94 oC
SO2Ph
Ph
H
F
1a
92%
2a
OBz
OBz
(1) BzCl, THF
LiHMDS
SO2Ph
SO2Ph
Ph
Ph
THF, 0 oC
(2) LiHMDS, THF
-78 oC
SO2Ph
F
F
81%
80%
3
4a
Z/E = 99/1
FBSM was independently developed by Shibata’s[11b]
and our group[11a] in 2006, and it has been successfully
used as a monofluoromethylating agent in many nu-
cleophilic fluoroalkylation reactions by tackling the
“negative fluorine effect”.[11,12] The addition reaction of
aldehydes and FBSM, which was asserted to be inac-
cessible due to the high preference for retro-aldol type
reaction,[13] was successfully tackled by us in 2011 us-
ing a lithium-oxygen coordination strategy (Scheme
1).[11f] When the addition product (2) was reacted with
benzoyl chloride (BzCl), compound 3 was afforded
(Scheme 1). Upon treatment of compound 3 with lith-
ium hexamethyldisilazide (LiHMDS), monofluoroal-
kene 4a was obtained with very high Z/E selectivity
(99/1) (Scheme 1). Encouraged by the preliminary result,
*
E-mail: jinbohu@sioc.ac.cn; Tel.: 0086-021-54925174; Fax: 0086-021-64166128
Received April 28, 2013; accepted June 9, 2013; published online July 5, 2013.
Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/cjoc.201300365 or from the author.
878
© 2013 SIOC, CAS, Shanghai, & WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
Chin. J. Chem. 2013, 31, 878—884

Highly Stereoselective and One-Pot Synthesis of Tetra-substituted Monofluoroalkenes
we made a further investigation on the scope and limita-
tion of this stereoselective monofluoroolefination reac-
tion. In addition, for the convenience of synthesis, we
developed a one-pot procedure, which could furnish
monofluoroolefins 4 without the isolation of the inter-
mediates 2 and 3.
hyde (1h), giving the corresponding alkene 4h in 86%
yield and 98/2 Z/E selectivity (Table 1, Entry 8). How-
ever, the reaction was largely affected by the position of
substituent on the aromatic ring. The yield of mono-
fluoroalkenes decreased when the bromo substituent
was changed from para- to meta-position (Table 1, En-
tries 4 and 5). When 2-bromobenzaldehyde (1i) was
used as the substrate, the intermediate 6 was obtained in
65% yield without the formation of the desired mono-
fluoroolefin (Table 1, Entry 9). We proposed that the
strong steric interaction between compound 6 and
LiHMDS probably hinders the approach of the base to
the benzylic hydrogen, thus no deprotonation takes
place. Aliphatic aldehyde 1j was also not a suitable sub-
strate for the monofluoroolefination reaction, and the
intermediate 7 was afforded in 55% yield (Table 1, En-
try 10). The failure of this reaction presumably arises
from the relatively weak stabilization effect of the alkyl
substituent on the carbanion, which renders the depro-
tonation of 7 to be much more difficult than that of the
aryl-substituted ones (Scheme 2). The (Z)-configuration
of compound 4g was confirmed by its X-ray crystal
structure analysis (Figure 1),[15] and those of the other
monofluoroalkenes were assigned by analogy. The
highly stereoselective formation of the (Z)-isomer
probably results from the steric repulsion between the
aryl group and the phenylsulfonyl group, which renders
the anti-elimination of hydrogen and one sulfonyl group
from the staggered conformer A to be much more fa-
vored than from the similar conformer B (Scheme 3).
Results and Discussion
FBSM could be easily prepared according to the re-
ported procedures.[14] At the outset, we chose 4-meth-
oxybenzaldehyde (1c) as the model substrate to test the
possibility of synthesizing monofluoroalkene 4c in one
pot (Eq. 1). The mixture of aldehyde 1c (1.5 equiv.) and
FBSM (1.0 equiv.) in THF was treated with LiHMDS
(1.2 equiv.) for 0.5 h, followed by adding BzCl (1.5
equiv.). After 3 h, the solution was allowed to warm to 0
℃, and another portion of LiHMDS (1.2 equiv.) was
added to achieve the β-elimination. When the reaction
was completed, the monofluoroalkene 4c was given in a
yield of 58% with the Z/E ratio of 99/1. Increasing the
amount of LiHMDS used in the third step to 1.5 equiv.,
the yield of 4c was improved to 70% without the loss of
the Z/E selectivity. It is interesting to find that, when
tosyl chloride (TsCl) was used instead of BzCl to pro-
tect the addition product, no tosylate could be obtained.
The chlorination of FBSM occurred to afford product 5
in 42% yield (Eq. 2).
1) LiHMDS (1.2 equiv.),
THF, -78 oC, 0.5 h
CHO
FBSM
2) BzCl (1.5 equiv.),
MeO
Scheme 2 Stabilization effect of the substituents on the carban-
ions
THF, -78 oC, 3 h
1c
1.5 equiv.
3) LiHMDS (n equiv.),
THF, 0 oC, 1 h
OBz
OBz
CF(SO2Ph)2
LiHMDS
LiHMDS
OBz
H
(a)
(b)
Ar
CF(SO2Ph)2
Ar
SO2Ph
(1)
stabilized by the aryl group
F
MeO
4c
n = 1.2, 58%, Z/E = 99/1
n = 1.5, 70%, Z/E = 99/1
OBz
OBz
H
Ph
CF(SO2Ph)2
not stabilized
Ph
CF(SO2Ph)2
1) LiHMDS (1.2 equiv.),
THF, -78 oC, 0.5 h
CHO
FBSM
(2)
(PhSO2)2CFCl
MeO
2) TsCl (1.5 equiv.),
THF, -78 oC, 3 h
5
1c
42%
1.5 equiv.
With the optimized reaction conditions in hand, we
examined the substrate scope of the monofluoroolefina-
tion reaction with FBSM. The results are shown in Ta-
ble 1. It was found that a wide range of aromatic alde-
hydes were transformed to monofluoroalkenes in mod-
erate to good yields (40%－83%) with 99/1 Z/E selec-
tivity (Table 1, Entries 1－6). 2-Naphthaldehyde (1g)
can also undergo the monofluoroolefination reaction,
affording compound 4g in 86% yield with 99/1 Z/E se-
lectivity (Table 1, Entry 7). To our delight, the current
reaction conditions were also amenable to cinnamalde-
Figure 1 ORTEP drawing for compound 4g.[15]
Chin. J. Chem. 2013, 31, 878—884
© 2013 SIOC, CAS, Shanghai, & WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
www.cjc.wiley-vch.de
879

Shen, Ni & Hu
FULL PAPER
Table 1 Monofluoroolefination of aldehydes with FBSM
OBz
OBz
CF(SO2Ph)2
6, 7
1) LiHMDS, THF, -78 oC, 0.5 h
SO2Ph
or
RCHO
(PhSO2)2CHF
(FBSM)
R
R
2) BzCl, THF, -78 oC, 3 h
3) LiHMDS, THF, 0 oC, 1 h
1
F
4
Entry
1
RCHO (1)
Products (4－7)
Yielda/%
72
Z/Eb
OBz
CHO
SO2Ph
99/1
F
1a
4a
OBz
CHO
SO2Ph
2
3
4
5
6
55
70
83
40
60
99/1
99/1
99/1
99/1
99/1
F
Me
Me
1b
4b
OBz
CHO
SO2Ph
MeO
F
MeO
1c
4c
OBz
CHO
SO2Ph
Br
Br
F
Br
Br
1d
4d
OBz
CHO
CHO
SO2Ph
F
1e
4e
OBz
SO2Ph
Cl
F
Cl
1f
4f
OBz
CHO
CHO
SO2Ph
SO2Ph
7
86
73
65
55
99/1
98/2
－
F
1g
4g
OBz
8
F
1h
4h
OBz
CF(PhSO2)2
CHO
Br
9
Br
1i
6
OBz
CF(PhSO2)2
CHO
10
－
1j
7
a Isolated yield. b Determined by 19F NMR.
880
www.cjc.wiley-vch.de
© 2013 SIOC, CAS, Shanghai, & WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
Chin. J. Chem. 2013, 31, 878—884

Highly Stereoselective and One-Pot Synthesis of Tetra-substituted Monofluoroalkenes
Scheme 3 Rationalization of the preference of (Z)-isomers
standard. 19F NMR spectra were taken on a BRUKER
AM-300 spectrometer (282 MHz) or Varian 400-MR
spectrometer (376 MHz) using CFCl3 as external stan-
dard. 13C NMR spectra were recorded in CDCl3 on a
BRUKER AM-300 spectrometer (101 MHz) with TMS
as internal standard. IR spectra were obtained with a
Nicolet iN 10MX spectrometer. MS (ESI) were obtained
on Shimadzu LCMS-2010EV mass spectrometer. MS
(EI) were obtained on Waters Micromass GCT Premier
mass spectrometer. HRMS (ESI) were obtained on
FTMS-7 mass spectrometer. HRMS (MAILDI) were
obtained on IonSpec 4.7 mass spectrometer. All the
solvents were redistilled before use.
H
H
SO2Ph
F
F
PhO2S
Ar
Ar
OBz
OBz
SO2Ph
A
SO2Ph
B
favored
disfavored
BzO
BzO
Ar
SO2Ph
F
F
Ar
SO2Ph
(E)-isomer
(Z)-isomer
To demonstrate the synthetic utility of the aforemen-
tioned highly stereoselective monofluoroolefination
protocol, product 4a was transformed to organotin
compound 8 in 93% yield and 96/4 Z/E selectivity by
using the reported procedure (Eq. 3).[11f] When com-
pound 8 was treated with I2 in CH2Cl2 at room tempera-
ture for 1 h, the iodinated product 9 was obtained in
93% yield. Furthermore, the stereospecific Stille cou-
pling reaction with benzoyl chloride efficiently con-
verted 8 into fluorinated α,β-unsaturated ketone deriva-
tive 10 in 89% yield (Scheme 4).
General procedure for monofluoroolefination of aryl
aldehydes with FBSM
Under N2, to a mixture of FBSM (94 mg, 0.3 mmol)
and benzaldehyde 1a (48 mg, 0.45 mmol) in dry THF (1
mL) was added LiHMDS (1 mol•L－ in THF, 0.36 mL,
1
0.36 mmol) at 78 ℃. The solution was stirred at 78 ℃
for 0.5 h, followed by adding a solution of BzCl (64 mg,
0.45 mmol) in dry THF (1 mL). After 3 h, the solution
was allowed to warm to r.t. and LiHMDS (1 mol•L－1 in
THF, 0.45 mL, 0.45 mmol) was added. The mixture was
reacted at r.t. for another 1 h, then was quenched with an
excess of saturated NH4Cl aqueous solution, followed
by extraction with ethyl ether. The organic phase was
washed with brine and then dried over anhydrous
MgSO4. After the solution was filtered and the solvent
was evaporated under vacuum, the residue was sub-
jected to silica gel column chromatography using petro-
leum ether/ethyl acetate (V/V, 10/1) as eluent to give
product 4a (82 mg, 72%).
OBz
OBz
(n-Bu)3SnH, AIBN (cat.)
SO2Ph
SnnBu3
(3)
Ph
Ph
Benzene, reflux
93%
F
F
4a, Z/E = 99/1
8, Z/E = 96/4
Scheme 4 Synthetic application of compound 8
OBz
F
I2
I
Ph
CH2Cl2, r.t., 1 h
93%
OBz
9, Z/E = 96/4
(Z)-2-Fluoro-1-phenyl-2-(phenylsulfonyl)vinyl
Sn(Bu-n)3
Ph
1
benzoate (4a) White solid. m.p. 117－119 ℃; H
F
OBz O
BzCl
NMR (300 MHz, CDCl3) δ: 8.47 (d, J＝7.2 Hz, 2H),
8.27 (d, J＝7.3 Hz, 2H), 7.98－7.74 (m, 8H), 7.65 (br,
3H); 19F NMR (282 MHz, CDCl3) δ: 138.4 (s, 1F); 13C
NMR (101 MHz, CDCl3) δ: 164.15 (d, J＝2.4 Hz),
149.28 (d, J＝292.1 Hz), 140.80 (d, J＝28.4 Hz),
138.45, 134.70, 134.38, 131.15, 130.60, 129.78 (d, J＝
8, Z/E = 96/4
Ph
Ph
Pd(PPh3)4 (cat.), CuI,
THF, reflux, 4 h
89%
F
10, Z/E = 4/96
Conclusions
5.4 Hz), 129.44, 128.88, 128.90, 128.68, 128.33, 127.53
(d, J＝7.7 Hz). MS (ESI) m/z: 400 (M＋NH4 ). The
In conclusion, we have successfully developed a
highly stereoselective reaction for the synthesis of tetra-
substituted monofluoroalkenes with aldehydes and
FBSM in one pot. The reaction was amenable to para-
and meta-substituted aryl aldehydes, 2-naphthaldehyde,
and cinnamaldehyde, giving monofluoroalkenes in
moderate to good yields (40%－86%) with excellent
stereoselectivities (Z/E＝98/2－99/1). The presence of
the sulfonyl group in the product afforded the conven-
ience to prepare more useful monofluoroalkene com-
pounds.
＋
characterization data were consistent with reference.[11f]
(Z)-2-Fluoro-2-(phenylsulfonyl)-1-p-tolylvinyl
benzoate (4b) White solid. m.p. 84－85 ℃; 1H NMR
(300 MHz, CDCl3) δ: 8.20 (d, J＝7.4 Hz, 2H), 8.00 (d,
J＝7.6 Hz, 2H), 7.67 (t, J＝7.1 Hz, 2H), 7.60－7.46 (m,
6H), 7.18 (d, J＝8.1 Hz, 2H), 2.33 (s, 3H); 19F NMR
(282 MHz, CDCl3) δ: 139.38 (s, 1F); 13C NMR (101
MHz, CDCl3) δ: 164.16 (d, J＝2.5 Hz), 148.78 (d, J＝
290.6 Hz), 141.70, 141.02 (d, J＝28.3 Hz), 138.60,
134.54, 134.26, 130.59, 129.58, 129.37, 128.83, 128.64,
128.44, 127.45 (d, J＝8.1 Hz), 126.91 (d, J＝5.5 Hz),
21.50; IR (film) ν: 3479, 2922, 1751, 1609, 1449, 1347,
1244, 1148, 1019, 817, 705, 592, 567, 487 cm−1. MS
(ESI) m/z: 414 (M＋NH4＋). HRMS (ESI) calcd for
C22H17FNaO4S (M＋Na＋) 419.0724, found 419.0726.
Experimental
1H NMR spectra were recorded in CDCl3 on a
BRUKER AM-300 spectrometer (300 MHz) or Varian
400-MR spectrometer (400 MHz) with TMS as internal
Chin. J. Chem. 2013, 31, 878—884
© 2013 SIOC, CAS, Shanghai, & WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
www.cjc.wiley-vch.de
881

Shen, Ni & Hu
FULL PAPER
(Z)-2-Fluoro-1-(4-methoxyphenyl)-2-(phenyl-
sulfonyl)vinyl benzoate (4c) White solid. m.p. 80－
81 ℃; H NMR (300 MHz, CDCl3) δ: 8.21 (d, J＝7.3
(Z)-2-Fluoro-1-(naphthalen-2-yl)-2-(phenylsul-
fonyl)vinyl benzoate (4g) White solid. m.p. 116－117
℃; H NMR (300 MHz, CDCl3) δ: 8.13 (d, J＝7.5 Hz,
1
1
Hz, 2H), 7.99 (d, J＝7.5 Hz, 2H), 7.68 (s, 2H), 7.60 (t,
J＝7.3 Hz, 6H), 6.89 (d, J＝8.8 Hz, 2H), 3.81 (s, 3H);
19F NMR (282 MHz, CDCl3) δ: −141.0 (s, 1F). 13C
NMR (101 MHz, CDCl3) δ: 164.11 (d, J＝2.6 Hz),
161.62 (d, J＝2.2 Hz), 148.09 (d, J＝288.9 Hz), 140.81
(d, J＝28.2 Hz), 138.65, 134.40, 134.20, 130.52, 129.28,
129.22 (d, J＝8.4 Hz), 128.77, 128.53, 128.38, 121.87
(d, J＝5.6 Hz), 114.29, 55.37; IR (film) ν: 3067, 2840,
1749, 1604, 1512, 1449, 1347, 1248, 1184, 1148, 1020,
2H), 7. 98 (s, 1H), 7.92 (d, J＝7.6 Hz, 2H), 7.66 (t, J＝
9.4 Hz, 3H), 7.55－7.52 (m, 3H), 7.42 (t, J＝7.7 Hz,
4H), 7.35 (t, J＝7.3 Hz, 2H); 19F NMR (282 MHz,
CDCl3) δ: 138.63 (s, 1F); 13C NMR (101 MHz, CDCl3)
δ: 164.31 (d, J＝2.5 Hz), 149.50 (d, J＝291.9 Hz),
141.07 (d, J＝28.2 Hz), 138.53, 134.70, 134.38, 134.23,
132.72, 130.69, 129.52, 128.97, 128.78, 128.74, 128.46,
128.39 (d, J＝3.3 Hz), 128.12, 127.78, 127.16 (d, J＝
5.6 Hz), 127.01, 123.62, 123.54; IR (film) ν: 3445, 3063,
2918, 2842, 1749, 1635, 1448, 1346, 1230, 1146, 1039,
817, 703, 587, 473 cm−1; MS (ESI) m/z: 450 (M＋
NH4＋). HRMS (ESI) calcd for C25H17FNaO4S (M＋
Na＋): 455.0724, found 455.0717.
834, 706, 591, 512, 437 cm−1. MS (ESI) m/z: 430.2 (M
＋
＋NH4 ). HRMS (MALDI) calcd for C22H17FNaO5S (M
＋Na＋) 435.0673, found 435.0688.
(Z)-1-(4-Bromophenyl)-2-fluoro-2-(phenylsul-
fonyl)vinyl benzoate (4d) White solid. m.p. 113－
114 ℃; 1H NMR (300 MHz, CDCl3) δ: 8.19 (d, J＝7.4
Hz, 2H), 7.99 (d, J＝7.6 Hz, 2H), 7.69 (t, J＝7.1 Hz,
2H), 7.64－7.39 (m, 8H); 19F NMR (282 MHz, CDCl3)
δ: 137.28 (s, 1F); 13C NMR (101 MHz, CDCl3) δ: 164.1
(d, J＝2.5 Hz), 149.50 (d, J＝293.4 Hz), 139.82 (d, J＝
28.5 Hz), 138.21, 134.74, 134.44, 132.15, 130.61,
129.44, 129.01, 128.93, 128.88, 128.75, 128.11, 125.4
(d, J＝2.5 Hz); IR (film) ν: 3468, 2924, 1746, 1643,
(1Z,3E)-1-Fluoro-4-phenyl-1-(phenylsulfonyl)-
buta-1,3-dien-2-yl benzoate (4h) White solid. m.p.
1
146－147 ℃; H NMR (300 MHz, CDCl3) δ: 8.27 (d,
J＝7.3 Hz, 2H), 7.98 (d, J＝7.6 Hz, 2H), 7.70 (dd, J＝
14.5, 7.3 Hz, 2H), 7.58 (t, J＝7.0 Hz, 4H), 7.46－7.38
(m, 2H), 7.36－7.28 (m, 3H), 7.06－6.81 (m, 2H); 19F
NMR (282 MHz, CDCl3) δ: 139.72 (s, 1F); 13C NMR
(101 MHz, CDCl3) δ: 164.02 (d, J＝2.5 Hz), 147.83 (d,
J＝291.6 Hz), 140.78 (d, J＝29.9 Hz), 138.30, 136.54,
136.48, 134.87, 134.67, 134.35, 130.69, 129.91, 129.41,
128.92, 128.73, 128.32, 127.78, 115.15; IR (film) ν:
3851, 3064, 2922, 1741, 1268, 1447, 1348, 1244, 1147,
1486, 1348, 1247, 1151, 1143, 1006, 842, 756, 711, 681,
＋
591, 561 cm−1; MS (ESI) m/z: 478 (M＋NH4 ). HRMS
＋
(MAIDI) calcd for C21H14BrFNaO4S (M ＋ Na
)
482.9672, found 482.9670.
1062, 969, 859, 745, 683, 587, 447 cm−1; MS (ESI) m/z:
＋
(Z)-1-(3-Bromophenyl)-2-fluoro-2-(phenylsul-
fonyl)vinyl benzoate (4e) White solid. m.p. 108－109
℃; H NMR (300 MHz, CDCl3) δ: 8.20 (d, J＝8.0 Hz,
426 (M＋NH4 ). HRMS (ESI) calcd for C23H17FNaO4S
(M＋Na＋): 431.0724, found 419.0737.
1
1-(2-Bromophenyl)-2-fluoro-2,2-bis(phenylsul-
fonyl)ethyl benzoate (6) White solid. m.p. 222－223
2H), 7.99 (d, J＝7.9 Hz, 2H), 7.78－7.63 (m, 3H), 7.70
－7.60 (m, 6H), 7.25 (t, J＝7.9 Hz, 1H); 19F NMR (282
MHz, CDCl3) δ: 136.51 (s, 1F); 13C NMR (101 MHz,
CDCl3) δ: 164.07 (d, J＝2.7 Hz), 149.85 (d, J＝294.3
Hz), 139.23 (d, J＝28.3 Hz), 138.08, 134.85, 134.50,
134.04, 131.82 (d, J＝5.4 Hz), 130.65, 130.40, 130.34,
129.49, 128.91, 128.78, 128.06, 126.11 (d, J＝7.5 Hz),
122.94. IR (film) ν: 3472, 2923, 2852, 1760, 1746, 1562,
1
℃; H NMR (300 MHz, CDCl3) δ: 8.31 (d, J＝7.5 Hz,
2H), 7.95 (d, J＝7.5 Hz, 5H), 7.66 (d, J＝7.2 Hz, 3H),
7.53 (t, J＝7.9 Hz, 6H), 7.43 (d, J＝7.9 Hz, 1H), 7.36－
7.21 (m, 1H), 7.20－7.07 (m, 2H); 19F NMR (282 MHz,
CDCl3) δ: −137.08 (s, 1F); 13C NMR (101 MHz, CDCl3)
δ: 164.10, 137.05, 135.48, 131.41 (d, J＝1.8 Hz),
133.90, 132.67, 131.95, 131.82, 131.71, 131.42, 131.40,
130.81, 130.64, 129.42, 128.69, 128.56, 128.52, 127.06,
124.07, 112.44 (d, J＝272.1 Hz), 72.43 (d, J＝26. 4 Hz).
IR (film) ν: 3071, 1934, 1731, 1583, 1468, 1355, 1257,
1447, 1347, 1152, 1020, 800, 707, 567 cm−1; MS (ESI)
＋
m/z: 478 (M ＋ NH4 ). HRMS (ESI) calcd for
C21H14BrFNaO4S (M＋Na＋) 482.9672, found 482.9690.
(Z)-1-(4-Chlorophenyl)-2-fluoro-2-(phenylsul-
fonyl)vinyl benzoate (4f) White solid. m.p. 107－109
1093, 775, 686, 551, 525 cm−1. MS (ESI) m/z: 620 (M＋
＋
NH4 ). HRMS (ESI) calcd for C27H20BrFNaO6S2 (M＋
℃; H NMR (400 MHz, CDCl3) δ: 8.20 (d, J＝7.6 Hz,
Na＋): 624.9761, found 624.9775.
1
2H), 8.00 (d, J＝7.7 Hz, 2H), 7.69 (t, J＝7.2 Hz, 2H),
7.63－7.42 (m, 6H), 7.36 (d, J＝8.6 Hz, 2H); 19F NMR
(376 MHz, CDCl3) δ: −137.63 (s); 13C NMR (101 MHz,
CDCl3) δ: 164.8 (d, J＝2.5 Hz), 149.5 (d, J＝294.8 Hz),
139.8 (d, J＝28.3 Hz), 138.2, 137.2, 134.8, 134.5, 130.6,
129.5, 129.2, 128.9, 128.9 (d, J＝8.1 Hz), 128.8, 128.3
(d, J＝5.2 Hz), 128.1; IR (film) ν: 3474, 3068, 2922,
1751, 1640, 1588, 1489, 1447, 1350, 1249, 1150, 1113,
1044, 1019, 840 741, 725, 630, 614, 589, 475 cm−1; MS
(ESI) m/z: 434 (M＋NH4＋), 439 (M＋Na＋). HRMS
(ESI) calcd for C21H14ClFNaO4S (M＋Na＋) 439.0178,
found 439.0173.
1-Fluoro-4-phenyl-1,1-bis(phenylsulfonyl)butan-
2-yl benzoate (7) White solid, m.p. 204－205 ℃; H
1
NMR (300 MHz, CDCl3) δ: 8.01 (d, J＝7.3 Hz, 2H),
7.91 (d, J＝7.9 Hz, 2H), 7.76－7.54 (m, 5H), 7.54－
7.39 (m, 6H), 7.34－7.11 (m, 5H), 5.85 (d, J＝9.8 Hz,
1H), 3.30－2.37 (m, 4H); 19F NMR (282 MHz, CDCl3)
δ: 138.37 (s, 1F); 13C NMR (101 MHz, CDCl3) δ:
165.42, 139.95, 135.82, 135.31, 135.17, 133.58, 131.16,
130.29, 128.95, 128.91, 128.78, 128.53, 128.45, 126.27,
112.29 (d, J＝278.2 Hz), 70.86 (d, J＝19.2 Hz), 31.99,
31.23; IR (film) ν: 3448, 3068, 1973, 1736, 1583, 1449,
1351, 1264, 1172, 1096, 1030, 965, 735, 716, 586, 565,
882
www.cjc.wiley-vch.de
© 2013 SIOC, CAS, Shanghai, & WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
Chin. J. Chem. 2013, 31, 878—884

Highly Stereoselective and One-Pot Synthesis of Tetra-substituted Monofluoroalkenes
＋
518, 452 cm−1; MS (ESI) m/z: 570 (M＋NH4 ). HRMS
(ESI) calcd for C29H25FNaO6S2 (M＋Na＋): 575.0969,
found 575.0956.
(46 mg, 0.18 mmol) in CH2Cl2 (2 mL) at r.t. After 1 h,
the reaction was quenched by adding saturated Na2SO3
aqueous solution (2 mL), followed by extraction with
ethyl ether. The organic phase was washed with brine
and then dried over anhydrous MgSO4. After the solu-
tion was filtered and the solvent was evaporated under
vacuum, the residue was subjected to silica gel column
chromatography using petroleum ether as eluent to give
yellow oil (51 mg, 73%).
Procedure for chlorination of FBSM in the presence
of aldehyde 1c
Under N2, to a mixture of FBSM (157 mg, 0.5 mmol)
and 4-methoxybenzaldehyde 1c (107 mg, 0.75 mmol) in
dry THF (2 mL) was added LiHMDS (1 mol•L－ in
1
THF, 0.6 mL, 0.6 mmol) at 78 ℃. The solution was
stirred at 78 ℃ for 0.5 h, followed by adding a solution
of TsCl (147 mg, 0.75 mmol) in dry THF (1 mL). After
3 h, the reaction was quenched with an excess of satu-
rated NH4Cl aqueous solution, followed by extraction
with CH2Cl2. The organic phase was washed with brine
and then dried over anhydrous MgSO4. After the solu-
tion was filtered and the solvent was evaporated under
vacuum, the residue was subjected to silica gel column
chromatography using petroleum ether/ethyl acetate
(V/V, 4/1) as eluent to give product 5 (73 mg, 42%).
(Z)-2-Fluoro-2-iodo-1-phenylvinyl benzoate (9)
1H NMR (300 MHz, CDCl3) δ: 8.21 (d, J＝7.3 Hz, 2H),
7.68 (t, J＝7.4 Hz, 1H), 7.61－7.47 (m, 4H), 7.44－7.32
(m, 3H); 19F NMR (282 MHz, CDCl3) δ: 96.93 (s, 1F);
13C NMR (101 MHz, CDCl3) δ: 163.87, 141.32 (d, J＝
29.9 Hz), 134.12, 130.49, 130.42, 129.26, 128.79,
128.63, 126.45, 126.37, 107.74 (d, J＝329.4 Hz); IR
(film) ν: 1748, 1600, 1495, 1451, 1243, 1138, 1104,
1043, 1020, 764,705, 646, 597 cm−1; MS (EI) m/z: 105
(100, [Bz]＋), 241 (16.66, [M−I]＋). HRMS (EI) calcd for
C15H10FO2 ([M−I]＋): 241.0665, found 241.0666.
Chlorofluorobis(phenylsulfonyl)methane
(5)
White solid. 1H NMR (300 MHz, CDCl3) δ: 8.07 (d, J＝
7.7 Hz, 4H), 7.81 (t, J＝7.5 Hz, 2H), 7.64 (t, J＝7.7 Hz,
4H); 19F NMR (282 MHz, CDCl3) δ: 107.58 (s); 13C
NMR (101 MHz, CDCl3) δ: 136.26, 133.19, 131.58,
129.36, 118.60 (d, J＝329.7 Hz); IR (film) ν: 3061,
1580, 1449, 1367, 1190, 1078, 846, 684, 558 cm−1; MS
Procedure for preparation of compound 10
Under N2, the solution of compound 8 (79 mg, 0.15
mmol), BzCl (26 mg, 0.18 mmol), Pd(PPh3)4 (16 mg,
0.015 mmol), and CuI (29 mg, 0.15 mmol) in dry THF
(3 mL) was refluxed for 4 h. The mixture was directly
subjected to silica gel column chromatography using
petroleum ether/ethyl acetate (V/V, 10/1) as eluent to
give compound 10 (46 mg, 89%).
(ESI) m/z: 348.7 (M＋H＋). HRMS (ESI) calcd for
＋
C13H10ClFNaO4S2 (M ＋ Na ): 370.9585, found
370.9597.
2-Fluoro-3-oxo-1,3-diphenylprop-1-en-1-yl ben-
zoate (10) Yellow solid. Z/E＝4/96, m.p. 93－95 ℃;
1H NMR (300 MHz, CDCl3) δ: 8.03 (d, J＝8.4 Hz, 2H),
7.85 (d, J＝7.0 Hz, 2H), 7.77 (dd, J＝6.6, 3.0 Hz, 2H),
7.60 (t, J＝7.5 Hz, 1H), 7.54－7.35 (m, 8H); 19F NMR
(282 MHz, CDCl3) δ: 119.06 (s, 0.04F), 132.96 (s,
0.96F); 13C NMR (101 MHz, CDCl3) δ: 186.96, 186.67,
164.27, 148.94 (d, J＝262.6 Hz), 141.77 (d, J＝33.1
Hz), 136.57, 136.55, 133.90, 133.11, 130.97, 130.92,
130.58, 130.49, 130.31, 129.10 (d, J＝4.4 Hz), 128.88,
128.76, 128.58, 128.51, 128.46, 127.73 (d, J＝8.3 Hz);
IR (film) ν: 3473, 3066, 2020, 1749, 1675, 1616, 1596,
1492, 1447, 1332, 1274, 1241, 1174, 1128, 983, 774,
706, 641, 553, 447 cm−1; MS (EI) m/z: 105 (100, [Bz]＋),
346 (3.28, M＋). HRMS (EI) calcd for C22H15FO3 (M＋):
346.1005, found 346.1007.
Procedure for preparation of organotin reagent 8
Under N2, a mixture of compound 4a (356 mg, 0.93
mmol), nBu3SnH (0.45 mL, 1.71 mmol), and AIBN (14
mg, 0.08 mmol) in dry benzene (10 mL) was refluxed
for 5 h. The solution was cooled to r.t., and saturated KF
aqueuous solution (10 mL) was added. After 0.5 h, the
mixture was extracted with ethyl ether. The organic
phase was washed with brine and then dried over anhy-
drous MgSO4. After the solution was filtered and the
solvent was evaporated under vacuum, the residue was
subjected to silica gel column chromatography using
petroleum ether as eluent to give product 8 (250 mg,
93%).
2-Fluoro-1-phenyl-2-(tributylstannyl)vinyl ben-
1
zoate (8) Colorless oil. Z/E＝96/4. H NMR (300
MHz, CDCl3) δ: 8.16 (d, J＝8.4 Hz, 2H), 7.65 (t, J＝7.4
Hz, 1H), 7.59 (d, J＝7.9 Hz, 2H), 7.51 (t, J＝7.8 Hz,
2H), 7.34 (t, J＝7.6 Hz, 2H), 7.26 (t, J＝7.1 Hz, 1H),
1.55－1.42 (m, 6H), 1.31－1.17 (m, 6H), 1.06－0.98 (m,
6H), 0.83 (t, J＝7.3 Hz, 9H); 19F NMR (282 MHz,
CDCl3) δ: 117.26 (s, 0.04F), 128.94 (s, 0.96F); MS (EI)
m/z: 355 (100, M−nBu−OBz), 475 (M−nBu). The char-
acterization data were consistent with reference.[11f]
Acknowledgement
Support of our work by the National Natural Science
Foundation of China (Nos. 20825209 and 21202189),
the National Basic Research Program of China (Nos.
2012CB215500 and 2012CB821600), the Chinese
Academy of Sciences, and the Syngenta PhD Student-
ship (to X.S.) is gratefully acknowledged.
Procedure for preparation of compound 9
References
Under N2, to a solution of compound 8 (79 mg, 0.15
mmol) in dry CH2Cl2 (1 mL) was added a solution of I2
[1] (a) Uneyama, K. Organofluorine Chemistry, Blackwell, Oxford,
Chin. J. Chem. 2013, 31, 878—884
© 2013 SIOC, CAS, Shanghai, & WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
www.cjc.wiley-vch.de
883

Shen, Ni & Hu
FULL PAPER
2006; (b) Kirsch, P. Modern Fluoroorganic Chemistry, Wiley-VCH,
Weinheim, 2004.
[2] (a) Muller, K.; Faeh, C.; Diederich, F. Science 2007, 317, 1881; (b)
Jeschke, P. ChemBioChem 2004, 5, 570; (c) Pagliaro, M.; Ciriminna,
R. J. Mater. Chem. 2005, 15, 4981; (d) Wang, J.; Liu, H. Chin. J.
Org. Chem. 2011, 31, 1785.
[3] Taguchi, T.; Yanai, H. In Fluorine in Medicinal Chemistry and
Chemical Biology, Ed.: Ojima, I., Blackwell Publishing Inc, Oxford,
2009, p. 257.
[4] For selected examples, see (a) Wong, O. A.; Shi, Y. A. J. Org. Chem.
2009, 74, 8377; (b) Zhou, S.; Kem, E. R.; Gullen, E.; Cheng, Y.-C.;
Drach, J. C.; Tamiya, S.; Mitsuya, H.; Zemlicka, J. J. Med. Chem.
2006, 49, 6120.
[5] For an excellent review, see Landelle, G.; Bergeron, M.; Tur-
cotte-Savard, M.-O.; Paquin, J.-F. Chem. Soc. Rev. 2011, 40, 2867.
[6] (a) Michel, D.; Schlosser, M. Synthesis 1996, 1007; (b) Du, Z.;
Haglund, M. J.; Pratt, L. A.; Erickson, K. L. J. Org. Chem. 1998, 63,
8880; (c) Purrington, S. T.; Pittman, J. H. Tetrahedron Lett. 1987, 28,
3901; (d) Elkik, E. Bull. Soc. Chim. Fr. 1967, 1569; (e) Huang,
X.-H.; He, P.-Y.; Shi, G.-Q. J. Org. Chem. 2000, 65, 627; (f)
Prakash, G. K. S.; Chacko, H.; Vaghoo, S.; Shao, N.; Gurung, L.;
Mathew, T.; Olah, G. A. Org. Lett. 2009, 11, 1127; (g) Zhang, W.;
Huang, W.; Hu, J. Angew. Chem., Int. Ed. 2009, 48, 9858.
[7] Burton, D. J.; Cox, D. G. J. Am. Chem. Soc. 1983, 105, 650.
[8] Tsai, H.-J. Tetrahedron Lett. 1996, 37, 629.
Aissa, C. Eur. J. Org. Chem. 2009, 1831; (c) Kocienski, P. J.; Bell,
A.; Blakemore, P. R. Synlett 2000, 365; (d) Blakemore, P. R.; Cole,
W. J.; Kocienski, P. J.; Morley, A. Synlett 1998, 26; (e) Baudin, J. B.;
Hareau, G.; Julia, S. A.; Ruel, O. Tetrahedron Lett. 1991, 32, 1175.
[11] For selected reactions with FBSM as a reagent, see (a) Ni, C.; Li, Y.;
Hu, J. J. Org. Chem. 2006, 71, 6829; (b) Fukuzumi, T.; Shibata, N.;
Sugiura, M.; Yasui, H.; Nakamura, S.; Toru, T. Angew. Chem., Int.
Ed. 2006, 45, 4973; (c) Ni, C.; Zhang, L.; Hu, J. J. Org. Chem. 2008,
73, 5699; (d) Prakash, G. K. S.; Wang, F.; Shao, N.; Mathew, T.;
Rasul, G.; Haiges, R.; Stewart, T.; Olah, G. A. Angew. Chem., Int.
Ed. 2009, 48, 5358; (e) Zhang, S.; Zhang, Y.; Ji, Y.; Li, H.; Wang,
W. Chem. Commun. 2009, 4886; (f) Shen, X.; Zhang, L.; Zhao, Y.;
Zhu, L.; Li, G.; Hu, J. Angew. Chem., Int. Ed. 2011, 50, 2588; (g)
Shen, X.; Ni, C.; Hu, J. Helv. Chim. Acta 2012, 95, 2043.
[12] For negative fluorine effect, see (a) Zhang, W.; Ni, C.; Hu, J. Top.
Curr. Chem. 2012, 308, 25; (b) Ni, C.; Hu, J. Synlett 2011, 770; (c)
Shen, X.; Zhang, W.; Ni, C.; Gu, Y.; Hu, J. J. Am. Chem. Soc. 2012,
134, 16999; (d) Shen, X.; Zhang, W.; Zhang, L.; Luo, T.; Wan, X.;
Gu, Y.; Hu, J. Angew. Chem., Int. Ed. 2012, 51, 6966.
[13] Furukawa, T.; Goto, Y.; Kawazoe, J.; Tokunaga, E.; Nakamura, S.;
Yang, Y.; Du, H.; Kakehi, A.; Shiro, M.; Shibata, N. Angew. Chem.,
Int. Ed. 2010, 49, 1642.
[14] Ni, C.; Zhang, L.; Hu, J. J. Org. Chem. 2009, 74, 3767.
[15] CCDC 936444 (4g) contains the supplementary crystallographic data
for this paper. These data can be obtained free of charge from the
Cambridge Crystallographic Data Centre via www. ccdc.cam.ac.uk/
data_request/cif.
[9] Lin, J.; Welch, J. T. Tetrahedron Lett. 1998, 39, 9613.
[10] (a) Zhu, L.; Ni, C.; Zhao, Y.; Hu, J. Tetrahedron 2010, 66, 5089; (b)
(Cheng, F.)
884
www.cjc.wiley-vch.de
© 2013 SIOC, CAS, Shanghai, & WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
Chin. J. Chem. 2013, 31, 878—884