Palladium-mediated heck-type reactions of [(Bromodifluoromethyl)sulfonyl] benzene: Synthesis of α-alkenyl- and α-heteroaryl-substituted α,α-difluoromethyl phenyl sulfones

Article abstract of DOI:10.1002/ejoc.201200613

Palladium-catalyzed Heck-type reactions of [(bromodifluoromethyl)sulfonyl] benzene (1) with styrene derivatives and heteroaromatic compounds successfully gave α-alkenyl- and α-heteroaryl-substituted α,α- difluoromethyl phenyl sulfones, respectively. Palladium-catalyzed Heck-type reactions of [(bromodifluoromethyl)sulfonyl]benzene (1) are reported. Both styrene derivatives and heteroaromatic compounds gave PhSO₂CF ₂-substituted products in moderate to good yields.

Full text of DOI:10.1002/ejoc.201200613

Job/Unit: O20613
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FULL PAPER
DOI: 10.1002/ejoc.201200613
Palladium-Mediated Heck-Type Reactions of [(Bromodifluoromethyl)-
sulfonyl]benzene: Synthesis of α-Alkenyl- and α-Heteroaryl-Substituted α,α-
Difluoromethyl Phenyl Sulfones
Nakin Surapanich,[a] Chutima Kuhakarn,[a] Manat Pohmakotr,[a] and Vichai Reutrakul*[a]
Keywords: Synthetic methods / Cross coupling / Heck reaction / Palladium / Fluorine
Palladium-catalyzed Heck-type reactions of [(bromodifluoro- α-heteroaryl-substituted α,α-difluoromethyl phenyl sulfones,
methyl)sulfonyl]benzene (1) with styrene derivatives and
heteroaromatic compounds successfully gave α-alkenyl- and
respectively.
heteroaromatic substrates underwent a facile fluoroalkyl-
ation with [(bromodifluoromethyl)sulfonyl]benzene (1) in
the presence of a Pd0 catalyst and base. The optimization
of the reaction conditions and investigation of the scope of
the substrates are presented as well.
Introduction
It is well known that the introduction of fluorine atoms
into organic molecules can have profound effects on their
physical, chemical, biological, and therapeutic proper-
ties.[1,2] Of particular interest is the introduction of the gem-
difluoromethylene moiety into organic molecules.[3,4] Incor-
porating a difluoromethylene unit into certain molecules
has shown to enhance several biological activities, such as,
antitumor,[5] antibiotic,[6] anti-HIV-1-RT,[7] and enzyme in-
hibitor activities.[8] However, because of the exceptional
characteristic effects of fluorine, fluorinated substrates or
reagents frequently exhibit unusual and unique properties,
which often make them incompatible with existing synthetic
methods.[9] In this respect, there has been an increasing
interest in the invention of synthetic methods for the incor-
poration of the fluorine atom, CF2, and CF3 units into or-
ganic compounds.[10] Radical,[11] carbene,[12] carbanion,[13]
fluorocarbocation,[14] and transition metal-mediated fluoro-
alkylation[15] reactions involving readily available sources of
gem-difluorinated compounds have been reported. These
reactive intermediates have considerably extended the scope
of fluorine research.
Scheme 1.
Results and Discussion
Our preliminary investigation focused on the palladium-
catalyzed reaction of 1 with p-chlorostyrene (2a). Various
palladium precursors were evaluated to understand the ef-
fect of the catalyst on the reaction (see Table 1). We were
pleased that this reaction proceeded by using Pd(PPh3)4 as
a catalyst (10 mol-%) in toluene (100 °C, 24 h) to provide
an 8% yield of the desired coupling product 3a (see Table 1,
Entry 1). The yield of 3a was further improved to 60% by
increasing the catalyst loading to 35 mol-% and the equiva-
lents of 2a from 1.5 to 3.0 equiv. (see Table 1, Entry 2). The
palladium(II) species including Pd(OAc)2, PdCl2(PhCN)2,
and PdCl2 in the presence of a phosphane ligand led to
inferior results, and the yields of the desired product 3a
ranged from 0 to 40% (see Table 1, Entries 3–7). In some
cases, the reduced product 4 was obtained as the sole prod-
uct (see Table 1, Entries 8–10). The reported highly active
air- and moisture-stable palladacycle XPhos-(phen-
ethylamine)palladium(II) chloride[16] (XPhos = 2-dicyclo-
hexylphosphanyl-2Ј,4Ј,6Ј-triisopropylbiphenyl) was also
employed. Unfortunately, under these reaction conditions,
no desired product 3a was observed. From the results
shown in Table 1, Pd(PPh3)4 served as an optimal catalyst
In continuation of our ongoing research in developing
methodologies for the introduction of the gem-difluoro-
methylene moiety into an organic molecule by using both
radical and carbanion methodologies,[11m,13l] we sought to
develop a new approach for transferring the gem-difluoro-
methylene building block into olefins through a Heck-type
reaction (see Scheme 1). Herein, we report that a variety of
styrene derivatives, vinyl ethers, vinyl sulfides, and a few
[a] Department of Chemistry and Center of Excellence for
Innovation in Chemistry (PERCH-CIC), Faculty of Science,
Mahidol University,
Rama 6 Road, Bangkok 10400, Thailand
E-mail: vichai.reu@mahidol.ac.th
Homepage: http://www.perch-cic.org
Supporting information for this article is available on the
WWW under http://dx.doi.org/10.1002/ejoc.201200613.
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FULL PAPER
Table 1. Palladium-mediated fluoroalkylation of 4-chlorostyrene for promoting the Heck-type coupling of [(bromodifluoro-
(2a) with [(bromodifluoromethyl)sulfonyl]benzene (1) in the pres-
methyl)sulfonyl]benzene (1) with p-chlorostyrene (2a).
ence of different Pd precursors.[a]
After identifying an appropriate catalyst, we further ex-
amined other essential reaction parameters with respect to
reagent stoichiometry, types of bases, solvents, and reaction
temperature. The results are summarized in Table 2. When
the reaction was carried out in the absence of potassium
carbonate, a lower yield of 3a (35% yield) was obtained (see
Table 2, Entry 2). Lowering or increasing the stoichiometric
amount of p-chlorostyrene (2a) led to slightly lower yields
of 3a (see Table 2, Entries 3–4). No improvement was ob-
served when the reaction was carried out using 40 mol-%
of Pd(PPh3)4 or under refluxing conditions (see Table 2, En-
tries 5–6). When a series of bases such as Ag2CO3, KOAc,
KF, KHCO3, Na2CO3, CaCO3, Cs2CO3, and Et3N were
screened, K2CO3 proved to be the optimal base (see Table 2,
Entry 1 vs Entries 7–14). The reaction in strong, polar,
aprotic solvents such as DMF (dimethylformamide) and
CH3CN gave the reduced product 4 as the sole product,
and no detectable amount of the desired product 3a was
observed (see Table 2, Entries 15–16). Also, the reaction
performed in 1,4-dioxane did proceed, but gave product 3a
in a lower yield (35% yield, see Table 2, Entry 17). Ad-
ditionally, using commercially available 15% PTS (PEG-
600R/tocopherol-based diester of sebacic acid)/H2O as the
solvent[17] in the presence of Pd(PPh3)4 (35 mol-%) and
Et3N (3 equiv.) at 100 °C resulted in consumption of com-
pound 1, yet, the desired product 3a was not detected. In
view of a recent report[18] on the success of the Heck reac-
Entry
Pd precursor
Ligand[c]
Temp. [°C],
time [h]
% Yield[d]
3a
4
1[b]
2
3
4
5
6
7
8
9
Pd(PPh3)4
Pd(PPh3)4
Pd(OAc)2
PdCl2(PhCN)2
PdCl2
PdCl2
PdCl2
PdCl2
PdCl2
–
–
100, 24
100, 4
100, 4
100, 10
100, 24
8
60
40
35
37
12
–
–
PPh3
PPh3
PPh3
–
–
–
–
–
P(C6H4CF3)3 reflux, 6
P(o-tolyl)3
reflux, 24
100, 24
100, 5
P(2-furyl)3
–
–
–
16
72
74
[e]
P(Cy)3
10
PdCl2
P(Bu)3
100, 5
[a] Except for Entry 1, all other reactions were performed by em-
ploying the reaction conditions: 2a (3 equiv.), 1 (1 equiv.), Pd pre-
cursor (35 mol-%), K2CO3 (1.5 equiv.). [b] Reagents and condi-
tions: 2a (1.5 equiv.), 1 (1 equiv.), Pd(PPh3)4 (10 mol-%), K2CO3
(1.5 equiv.). [c] Ligand loading (140 mol-%). [d] Isolated yields
based on 1. [e] Cy = cyclohexyl.
Table 2. Optimization of Pd(PPh3)4-mediated fluoroalkylation of 4-chlorostyrene (2a) with [(bromodifluoromethyl)sulfonyl]benzene (1).[a]
Entry
2a
[equiv.]
Pd(PPh3)4
[mol-%]
Base
[equiv.]
Solvent
Temp. [°C],
time [h]
% Yield[b]
3a
4
1
2
3
4
5
6
7
8
3.0
3.0
1.5
5.0
3.0
3.0
3.0
3.0
3.0
3.0
3.0
3.0
3.0
3.0
3.0
3.0
3.0
35
35
35
35
40
35
35
35
35
35
35
35
35
35
35
35
35
K2CO3, 1.5
–
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
DMF
100, 4
100, 18
100, 4
100, 4
100, 4
reflux, 4
100, 18
100, 4
100, 4
100, 4
100, 4
100, 4
100, 4
100, 4
100, 19
reflux, 19
100, 4
60
35
49
52
56
44
9
45
44
55
42
31
39
23
–
–
–
–
–
–
–
–
–
–
–
–
–
30
25
40
50
–
K2CO3, 1.5
K2CO3, 1.5
K2CO3, 1.5
K2CO3, 1.5
Ag2CO3, 1.5
KOAc, 3.0
KF, 3.0
KHCO3, 3.0
Na2CO3, 1.5
CaCO3, 1.5
Cs2CO3, 1.5
Et3N, 2.0
9
10
11
12
13
14
15
16
17
K2CO3, 1.5
K2CO3, 1.5
K2CO3, 1.5
CH3CN
1,4-dioxane
–
35
[a] Reagents and conditions: 2a (3 equiv.), 1 (1 equiv.), Ph(PPh3)4 (35 mol-%). [b] Isolated yields based on 1.
2
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Heck-Type Reactions of [(Bromodifluoromethyl)sulfonyl]benzene
tion in ionic liquids, both [BMIM][BF4] and [BMIM][PF6] Heck-type reaction between [(bromodifluoromethyl)sulf-
(BMIM = 1-butyl-3-methylimidazolium) were employed as onyl]benzene (1) and a variety of structurally diverse sub-
a reaction medium. Unfortunately, compounds 1 and 2a de- strates including styrene derivatives, vinyl ethers, a vinyl
composed under the reaction conditions, and no desired sulfide (see Table 3), and heteroaromatic compounds (see
product 3a was observed.
Table 4).
For styrene derivatives, the reaction efficiency depended
From the results shown in Tables 1 and 2, the optimum
reaction conditions used a toluene solution of compound 1 on the nature and the position of the substituent on the
(1 equiv.) and the alkene (3 equiv.) in the presence of aromatic ring. Styrene derivatives bearing an electronega-
Ph(PPh3)4 (35 mol-%) and K2CO3 (1.5 equiv.), as the reac- tive halogen atom at the para position of the phenyl moiety
tion mixture stirred at 100 °C for 4 h. Although the neces- gave the corresponding products in good yields. For in-
sity of a high catalyst loading cannot be clearly explained stance, p-chlorostyrene and p-fluorostyrene were smoothly
at this stage, the use of high loadings of Pd(PPh3)4 in a converted into the corresponding products 3a and 3b in 60
Heck-type reaction with a fluorinated substrate has been and 54% yields, respectively. However, m-chlorostyrene, m-
reported.[19] By employing the optimized reaction condi- fluorostyrene, and m-nitrostyrene yielded the corresponding
tions, we next evaluated the scope of Pd0/K2CO3-mediated adducts 3c, 3d, and 3e in the lower yields of 40, 25, and
Table 3. Palladium-mediated Heck-type reactions of styrene derivatives and vinyl ethers with [(bromodifluoromethyl)sulfonyl]benzene
(1).[a,b]
[a] Reagents and conditions: 2 (3 equiv.), 1 (1 equiv.), Pd(PPh3)4 (35 mol-%), K2CO3 (1.5 equiv.), toluene, 100 °C, 4 h. [b] Isolated yields
based on 1.
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N. Surapanich, C. Kuhakarn, M. Pohmakotr, V. Reutrakul
FULL PAPER
Table 4. Palladum-mediated coupling reaction of [(bromodifluoro-
methyl)sulfonyl]benzene (1) with heteroaromatic compounds
(6).[a,b]
Finally, the reaction of [(bromodifluoromethyl)sulfonyl]-
benzene (1) with selected heteroaromatic compounds was
evaluated (see Table 4). When 1-methylpyrrole and 1-benz-
ylpyrrole were subjected to the reaction conditions, high
yields of corresponding products 7a and 7b were obtained
in 73 and 69% yields, respectively. 1-Phenylpyrrole gave a
moderate yield (38% yield) of the corresponding product
7c. Significantly lower yields were observed when 2-meth-
ylfuran and N-methylindole were employed as substrates.
Thiophene led to an inseparable mixture of isomeric prod-
ucts 7f and 7fЈ in a 31% combined yield.
From a mechanistic aspect, each step of the catalytic cy-
cle should follow the well-known Heck reaction, which has
precedent and is well documented in the literature.[21] How-
ever, previous works by Chen[22] and Burton[23] also re-
ported that the addition of a perfluoroalkane and α,α-di-
fluoro phosphonates to alkenes mediated by tetrakis(tri-
phenylphosphane)palladium proceeded through a Pd0 sin-
gle-electron-transfer-initiated (SET-initiated) radical reac-
tion. To probe the possible radical mechanism,[24] a scav-
enging experiment with a radical inhibitor was carried out.
The addition of 3,5-di-tert-butyl-4-hydroxytoluene (BHT,
1 equiv.) to the reaction of 1 and p-chlorostyrene under our
standard reaction conditions led to a slightly lower yield of
3a (from 60–56% yield). The result implies that the mech-
anistic pathway of the present reaction may not proceed
through a radical mechanism. Additionally, the reactions of
1 with p-chlorostyrene mediated by alternative SET-initia-
[11m–11o]
tors, including Cu[25] and Et3B/O2
were also at-
[a] Reagents and conditions: 6 (3 equiv.), 1 (1 equiv.), Pd(PPh3)4
(35 mol-%), K2CO3 (1.5 equiv.), toluene, 100 °C, 4 h. [b] Isolated
yields based on 1.
tempted. However, the desired coupling product 3a was not
observed, and compound 1 was recovered in the range of
60–90% yields. It is worth noting that our results are com-
plementary to the work reported by Hu et al. on the free
8%, respectively, and o-chlorostyrene led to only a trace radical (phenylsulfonyl)difluoromethylation of terminal alk-
amount of the desired product 3f. Simple styrene and p- enes with iododifluoromethyl phenyl sulfone.[11o] However,
methylstyrene gave moderate yields of the corresponding that work required a two-step process to achieve the Heck-
products. Low yields were observed when styrene was sub- type product, whereas our methodology provides a more
stituted with electron-releasing groups. p-Acetoxystyrene direct route for the difluoromethylation of styrene deriva-
(2j) and p-methoxystyrene (2k) gave the corresponding ad- tives, enol ethers, vinyl sulfide, pyrrole derivatives, and thio-
ducts in 17 and 16% yields, respectively. In addition, β- phene, albeit in moderate to good yields. Finally, to gain
vinylnaphthalene yielded product 3l in low yield (17%). In more insight into the role of the sulfonyl moiety in this
the case of the 1,1-diphenylethylene substrate, an approxi- transformation, the reactions of p-chlorostyrene (2a) with
mate 1:1 inseparable mixture of adduct 3m and the re- bromodifluoro(phenylsulfanyl)methane (8) and [(bromodi-
ductive Heck product 5 was obtained. Attempts to carry fluoromethyl)sulfinyl]benzene (10) were carried out under
out the reaction of 1,1-diphenylethylene under the reductive our standard reaction conditions. To our surprise, the de-
Heck conditions[20] led to a 1:1 mixture of compounds 3m sired products 9a and 11a were not detected from these re-
and 5 in lower yields (36% combined yields). When 3,4- actions (see Scheme 2). These results imply that apart from
dihydro-2H-pyran and tert-butyl vinyl ether were used as the strong electron-withdrawing effect of the sulfonyl moi-
substrates, 3n and 3o were obtained in 41% and 45% yields, ety, the coordination of the lone pair of electrons on the
respectively. A separable mixture of trans- and cis-3p was oxygen atom of the sulfonyl group to the palladium metal
isolated, when vinyl sulfide was used as a substrate. The center helps to stabilize the intermediate formed, and the
extension of the present synthetic methodology to aliphatic stabilized six-membered palladacycle complex 12 may play
alkenes, namely allylbenzene and allyl phenyl sulfide, as an important role in facilitating the course of the coupling
well as electron-deficient alkenes, such as acrylonitrile, n- reaction. In the present work, the inefficiency of the reac-
butyl acrylate, and tert-butyl acrylate, was also carried out. tion with some substrates could be partially explained by
Unfortunately, in all cases, the starting [(bromodifluoro- the inherently weak PhS(O2)–CF2¯ bond, according to the
methyl)sulfonyl]benzene (1) was destroyed, and the corre- recent computational studies based on density functional
sponding coupling adducts were not observed.
theory (DFT).[13m]
4
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Heck-Type Reactions of [(Bromodifluoromethyl)sulfonyl]benzene
Experimental Section
1
General: H and 13C NMR spectroscopic data were recorded with
either a Bruker DPX-300 (300 MHz) or a Bruker Advance-500
(500 MHz) spectrometer, using CDCl3 or [D6]acetone as the sol-
vent. 1H NMR chemical shifts are reported in ppm, using tet-
ramethylsilane (TMS) as an internal standard. 13C NMR chemical
shifts are reported in ppm, using the residual non-deuterated sol-
vent peak as an internal standard. NMR spectroscopic data are
reported as 1H NMR chemical shifts, measured in parts per million
(ppm) downfield from the tetramethylsilane signal (δ), multiplicity,
observed coupling constant (J) in Hertz (Hz), and proton count.
Multiplicities are reported as singlet (s), broad (br.), broad singlet
(br. s), doublet (d), doublet of doublets (dd), doublet of doublets
of doublets (ddd), doublet of triplets (dt), triplet (t), triplet of dou-
blets (td), quartet (q), quintet (quin), and multiplet (m). IR spectra
were recorded with a Perkin–Elmer EX FT-IR system spectrome-
ter. High resolution mass spectra were recorded with a Bruker
Micro TOF spectrometer at the Faculty of Science, Mahidol Uni-
versity. Melting points were determined with a Sanyo/Gallenkamp
apparatus. Column chromatography was performed with Merck sil-
ica gel 60 (no. 7734). Preparative layer chromatography (PLC) was
performed with Merck silica gel 60 F254 (no. 7747). Analytical TLC
was performed with Merck TLC aluminium sheet silica gel 60 F254
(no. 5554) with 0.2 mm thickness. All of the chemicals were pur-
chased from Fluka Aldrich and Acros organics and were used with-
out prior purification. All of the solid compounds were recrys-
tallized from a hexane/chloroform mixture.
Scheme 2.
The synthetic utility of coupling products 3 and 7 for
the syntheses of CF2H-substituted compounds was briefly
investigated (see Scheme 3). An attempted reductive desulf-
onylation reaction of PhSO2CF2-bearing adduct 3a using
Mg/HOAc/NaOAc[11o,13r] afforded CF2H-substituted prod-
uct 13a in 59% yield. However, compound 7a was found to
be inert under similar reaction conditions. It is worth noting
that the CF2H-substituted olefins and heteroaromatic com-
pounds are classes of biologically important compounds.[1]
General Procedure for the Pd-Catalyzed Reaction of [(Bromodi-
fluoromethyl)sulfonyl]benzene (1): An oven-dried round-bottom
flask with a magnetic stir bar was charged with Pd(PPh3)4
(202.2 mg, 0.17 mmol, 35 mol-%), [(bromodifluoromethyl)sulf-
onyl]benzene (1, 135.7 mg, 0.5 mmol, 1.0 equiv.), and K2CO3
(103.7 mg, 0.75 mmol, 1.5 equiv.). The reaction flask was capped
with a rubber septum, evacuated, and then backfilled with argon
gas. A solution of the styrene derivative or heteroaromatic com-
pound (1.5 mmol, 3 equiv.) in toluene (2.5 mL) was added through
the septum by using a syringe. The resulting mixture was heated at
100 °C and vigorously stirred for 4 h. The mixture was then cooled
to room temperature. The reaction was filtered through a plug of
Celite, which was washed with ethyl acetate (50 mL). The solution
was concentrated in vacuo, and the resulting residue was purified
by silica gel column chromatography to yield the gem-difluorinated
compound.
Scheme 3.
Conclusions
(E)-1-Chloro-4-[3,3-difluoro-3-(phenylsulfonyl)prop-1-en-1-yl]benz-
ene (3a): According to the general procedure, 4-chlorostyrene (2a,
207.9 mg, 1.5 mmol) was employed, and purification by column
chromatography (silica gel, hexanes/EtOAc, 9.8:0.2) gave the title
compound (98.6 mg, 60 % yield) as a white solid; m.p. 103.0–
104.8 °C. Rf = 0.25 (silica gel, hexanes/EtOAc, 9.8:0.2). IR (KBr):
In conclusion, we developed a system that allows the alk-
ylation of [(bromodifluoromethyl)sulfonyl]benzene (1) by
structurally different styrene derivatives, vinyl ethers, and
heteroaromatic compounds through palladium-mediated
Heck-type reactions to give the corresponding products in
moderate to good yields. The obtained PhSO2CF2-contain-
ing compounds can be transformed into the biologically im-
portant CF2H-substituted olefins. To the best of our knowl-
edge, our results represent the first case of the palladium-
mediated oxidative addition of the (phenylsulfonyl)di-
fluoromethylene group to olefins. It should be mentioned
that the first case of a similar oxidative addition of a di-
fluoromethylation mediated by a Rh complex was also re-
cently reported.[26] Further exploration of the synthetic ap-
plications of the obtained PhSO2CF2-containing com-
pounds is underway in our laboratory.
ν
max = 3031 (C–H of aromatic), 1650 (C=C), 1589, 1493, and 1449
˜
(aromatic), 1343 and 1163 (SO2), 1077 (C–F) cm–1 1H NMR
.
(500 MHz, CDCl3): δ = 8.06 (d, J = 7.6 Hz, 2 H), 7.80 (m, 1 H),
7.65 (m, 2 H), 7.45 (m, 2 H), 7.40 (m, 2 H), 7.18 (dt, J = 16.2,
2.2 Hz, 1 H), 6.39 (dt, J = 16.2, 11.8 Hz, 1 H) ppm. 13C NMR
(125 MHz, CDCl3): δ = 140.9 (t, JC,F = 8.7 Hz, CH), 136.3 (C),
135.3 (CH), 132.8 (C), 132.0 (C), 130.8 (2 CH), 129.3 (2 CH), 129.2
(2 CH), 129.0 (2 CH), 121.3 (t, JC,F = 281.7 Hz, CF2), 113.0 (t,
JC,F = 22.2 Hz, CH) ppm. 19F NMR (470 MHz, CDCl3): δ =
–101.29 (d, JF,H = 11.7 Hz, CF2) ppm. HRMS (ESI-TOF): calcd.
for C15H11ClF2O2SNa [M + Na]+ 351.0034; found 351.0072.
(E)-1-[3,3-Difluoro-3-(phenylsulfonyl)prop-1-en-1-yl]-4-fluorobenz-
ene (3b): According to the general procedure, 4-fluorostyrene (2b,
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N. Surapanich, C. Kuhakarn, M. Pohmakotr, V. Reutrakul
(aromatic), 1357 and 1160 (SO2), 1113 (C–F) cm–1 1H NMR
FULL PAPER
183.2 mg, 1.5 mmol) was employed, and purification by column
.
chromatography (silica gel, hexanes/EtOAc, 9.8:0.2) gave the title (500 MHz, CDCl3): δ = 8.36 (t, J = 1.8 Hz, 1 H), 8.26 (dd, J = 8.1,
compound (84.2 mg, 54 % yield) as a white solid; m.p. 107.0– 1.4 Hz, 1 H), 8.03 (d, J = 7.5 Hz, 2 H), 7.81–7.77 (m, 2 H), 7.66
109.1 °C. Rf = 0.22 (silica gel, hexanes/EtOAc, 9.8:0.2). IR (KBr):
(m, 2 H), 7.61 (t, J = 8.1 Hz, 1 H), 7.28 (dt, J = 16.2, 2.1 Hz, 1
ν
max = 3058 (C–H of aromatic), 1650 (C=C), 1600, 1578, and 1509
H), 6.55 (dt, J = 16.2, 11.5 Hz, 1 H) ppm. 13C NMR (125 MHz,
˜
(aromatic), 1341 and 1240 (SO2), 1090 (C–F) cm–1
.
1H NMR CDCl3): δ = 148.7 (C), 139.7 (t, JC,F = 8.5 Hz, CH), 135.5 (CH),
(500 MHz, CDCl3): δ = 8.05 (d, J = 7.5 Hz, 2 H), 7.79 (m, 1 H),
135.2 (C), 133.3 (CH), 132.6 (C), 130.8 (2 CH), 130.0 (CH), 129.4
7.66 (m, 2 H), 7.50 (m, 2 H), 7.19 (dt, J = 16.2, 2.1 Hz, 1 H), 7.11 (2 CH), 124.7 (CH), 122.4 (CH), 120.9 (t, JC,F = 282.5 Hz, CF2),
(m, 2 H), 6.34 (dt, J = 16.3, 11.8 Hz, 1 H) ppm. 13C NMR
(125 MHz, CDCl3): δ = 163.7 (d, JC,F = 212.5 Hz, CF), 141.0 (t,
JC,F = 9.0 Hz, CH), 135.3 (CH), 132.9 (C), 130.8 (2 CH), 129.8
116.1 (t, JC,F = 22.3 Hz, CH) ppm. 19F NMR (470 MHz, CDCl3):
δ = –101.67 (d, JF,H = 11.2 Hz, CF2) ppm. HRMS (ESI-TOF):
calcd. for C15H11F2NO4SNa [M + Na]+ 362.0275; found 362.0327.
(C), 129.7 (d, JC,F = 8.6 Hz, 2 CH), 129.2 (2 CH), 121.4 (t, JC,F
281.7 Hz, CF2), 116.1 (d, JC,F = 21.9 Hz, 2 CH), 112.1 (t, JC,F
=
=
(E)-[3,3-Difluoro-3-(phenylsulfonyl)prop-1-en-1-yl]benzene (3g): Ac-
cording to the general procedure, styrene (2g, 156.2 mg, 1.5 mmol)
was employed, and purification by column chromatography (silica
gel, hexanes/EtOAc, 9.2:0.8) gave the title compound (60.0 mg,
41% yield) as a white solid; m.p. 112.8–114.4 °C. Rf = 0.22 (silica
22.5 Hz, CH) ppm. 19F NMR (470 MHz, CDCl3): δ = –101.15 (d,
JF,H = 11.8 Hz, CF2), –109.36 (quin, JF,H = 8.5, 4.7 Hz, CF) ppm.
HRMS (ESI-TOF): calcd. for C15H11F3O2SNa [M + Na]+
335.0330; found 335.0280.
gel, hexanes/EtOAc, 9.2:0.8). IR (KBr): ν
= 3071 (C–H of aro-
˜
max
(E)-1-Chloro-3-[3,3-difluoro-3-(phenylsulfonyl)prop-1-en-1-yl]benz-
ene (3c): According to the general procedure, 3-chlorostyrene (2c,
207.9 mg, 1.5 mmol) was employed, and purification by column
matic), 1649 (C=C), 1580, 1499, and 1447 (aromatic), 1338 and
1165 (SO2), 1092 (C–F) cm–1. 1H NMR (500 MHz, CDCl3): δ =
8.05 (d, J = 7.7 Hz, 2 H), 7.79 (m, 1 H), 7.65 (m, 2 H), 7.51 (m, 2
chromatography (silica gel, hexanes/EtOAc, 9.8:0.2) gave the title H), 7.42 (m, 3 H), 7.22 (dt, J = 16.2, 2.2 Hz, 1 H), 6.42 (dt, J =
compound (65.7 mg, 40% yield) as a white solid; m.p. 85.5–86.5 °C.
R = 0.25 (silica gel, hexanes/EtOAc, 9.8:0.2). IR (KBr): ν
16.2, 11.9 Hz, 1 H) ppm. 13C NMR (125 MHz, CDCl3): δ = 142.3
(t, JC,F = 8.5 Hz, CH), 135.2 (CH), 133.5 (C), 132.9 (C), 130.8 (2
CH), 130.3 (CH), 129.2 (2 CH), 128.9 (2 CH), 127.8 (2 CH), 121.5
(t, JC,F = 282.0 Hz, CF2), 112.3 (t, JC,F = 22.2 Hz, CH) ppm. 19F
NMR (470 MHz, CDCl3): δ = –101.24 (d, JF,H = 11.7 Hz,
CF2) ppm. HRMS (ESI-TOF): calcd. for C15H12F2O2SNa [M +
=
max
˜
f
3077 (C–H of aromatic), 1652 (C=C), 1566, 1473, and 1449 (aro-
matic), 1345 and 1169 (SO2), 1093 (C–F) cm–1 1H NMR
.
(500 MHz, CDCl3): δ = 8.05 (d, J = 7.5 Hz, 2 H), 7.80 (m, 1 H),
7.66 (t, J = 7.7 Hz, 2 H), 7.50 (s, 1 H), 7.42–7.34 (m, 3 H), 7.17
(dt, J = 16.2, 2.2 Hz, 1 H), 6.44 (dt, J = 16.2, 11.7 Hz, 1 H) ppm. Na]+ 317.0424; found 317.0448.
13C NMR (125 MHz, CDCl3): δ = 140.8 (t, JC,F = 9.0 Hz, CH),
(E)-1-[3,3-Difluoro-3-(phenylsulfonyl)prop-1-en-1-yl]-4-methylbenz-
135.38 (C), 135.36 (CH), 135.0 (C), 132.9 (C), 130.8 (2 CH), 130.3
(CH), 130.2 (CH), 129.3 (2 CH), 127.7 (CH), 126.0 (CH), 121.2 (t,
JC,F = 281.8 Hz, CF2), 114.1 (t, JC,F = 22.2 Hz, CH) ppm. 19F
NMR (470 MHz, CDCl3): δ = –101.49 (d, JF,H = 11.7 Hz,
CF2) ppm. HRMS (ESI-TOF): calcd. for C15H11ClF2O2SNa [M +
Na]+ 351.0034; found 351.0111.
ene (3h): According to the general procedure, 4-methylstyrene (2h,
177.2 mg, 1.5 mmol) was employed, and purification by column
chromatography (silica gel, hexanes/EtOAc, 9.2:0.8) gave the title
compound (80.0 mg, 52 % yield) as a white solid; m.p. 130.7–
132.6 °C. Rf = 0.25 (silica gel, hexanes/EtOAc, 9.2:0.8). IR (KBr):
ν
˜
= 3071 (C–H of aromatic), 2923 (C–H of aliphatic), 1645
max
(E)-1-[3,3-Difluoro-3-(phenylsulfonyl)prop-1-en-1-yl]-3-fluorobenz- (C=C), 1606, 1514, and 1450 (aromatic), 1334 and 1164 (SO2), 1075
ene (3d): According to the general procedure, 3-fluorostyrene (2d,
183.2 mg, 1.5 mmol) was employed, and purification by column
chromatography (silica gel, hexanes/EtOAc, 9.8:0.2) gave the title
(C–F) cm–1. 1H NMR (500 MHz, CDCl3): δ = 8.04 (d, J = 7.7 Hz,
2 H), 7.78 (m, 1 H), 7.64 (t, J = 7.6 Hz, 2 H), 7.40 (d, J = 8.1 Hz,
2 H), 7.23 (d, J = 8.0 Hz, 2 H), 7.17 (dt, J = 16.2, 2.0 Hz, 1 H),
compound (39.0 mg, 25 % yield) as a white solid; m.p. 104.0– 6.35 (dt, J = 16.1, 12.0 Hz, 1 H), 2.39 (s, 3 H) ppm. 13C NMR
105.1 °C. Rf = 0.25 (silica gel, hexanes/EtOAc, 9.8:0.2). IR (KBr): (125 MHz, CDCl3): δ = 142.2 (t, JC,F = 8.8 Hz, CH), 140.7 (C),
ν
max = 3089 and 3066 (C–H of aromatic), 1650 (C=C), 1585, 1486,
135.1 (CH), 133.0 (C), 130.8 (C), 130.7 (2 CH), 129.6 (2 CH), 129.2
(2 CH), 127.8 (2 CH), 121.7 (t, JC,F = 281.2 Hz, CF2), 111.1 (t, JC,F
= 22.0 Hz, CH), 21.4 (CH3) ppm. 19F NMR (470 MHz, CDCl3): δ
˜
and 1449 (aromatic), 1337 and 1170 (SO2), 1098 (C–F) cm–1. 1H
NMR (500 MHz, CDCl3): δ = 8.02 (d, J = 7.8 Hz, 2 H), 7.78 (m,
1 H), 7.64 (t, J = 7.8 Hz, 2 H), 7.38 (m, 1 H), 7.27 (d, J = 8.3 Hz, = –101.04 (d, JF,H = 11.7 Hz, CF2) ppm. HRMS (ESI-TOF): calcd.
1 H), 7.18 (br. s, 1 H), 7.15–7.07 (m, 3 H), 6.39 (dt, J = 16.2,
11.7 Hz, 1 H) ppm. 13C NMR (125 MHz, CDCl3): δ = 163.0 (d,
JC,F = 245.5 Hz, CF), 141.0 (t, JC,F = 8.8 Hz, CH), 135.7 (d, JC,F
= 7.8 Hz, 1 C), 135.3 (CH), 132.8 (C), 130.8 (2 CH), 129.3 (2 CH),
for C16H14F2O2SNa [M + Na]+ 331.0580; found 331.0605.
(E)-Methyl 4-[3,3-Difluoro-3-(phenylsulfonyl)prop-1-en-1-yl]-
benzoate (3i): According to the general procedure, methyl 4-vinyl-
benzoate (2i, 243.0 mg, 1.5 mmol) was employed, and purification
by column chromatography (silica gel, hexanes/EtOAc, 8:2) gave
the title compound (29.6 mg, 17% yield) as a white solid; m.p.
126.0–127.3 °C. Rf = 0.27 (silica gel, hexanes/EtOAc, 8:2). IR
123.8 (CH), 121.2 (t, JC,F = 282.1 Hz, CF2), 117.2 (d, JC,F
21.1 Hz, CH), 114.3 (d, JC,F = 22.1 Hz, CH), 114.0 (t, JC,F
=
=
22.1 Hz, CH) ppm. 19F NMR (470 MHz, CDCl3): δ = –101.48 (d,
JF,H = 11.7 Hz, CF2), –112.23 (q, JF,H = 8.9, 8.4, 6.1 Hz, CF).
HRMS (ESI-TOF): calcd. for C15H11F3O2SNa [M + Na]+
335.0330; found 335.0389.
(KBr): ν
= 3066 (C–H of aromatic), 2958 (C–H of aliphatic),
˜
max
1720 (C=O), 1646 (C=C), 1449, 1432, and 1415 (aromatic), 1334
and 1162 (SO2), 1095 (C–O), 1004 (C–F) cm–1 1H NMR
.
(E)-1-[3,3-Difluoro-3-(phenylsulfonyl)prop-1-en-1-yl]-3-nitrobenz- (500 MHz, CDCl3): δ = 8.06 (d, J = 8.3 Hz, 2 H), 8.04 (d, J =
ene (3e): According to the general procedure, 3-nitrostyrene (2e,
223.7 mg, 1.5 mmol) was employed, and purification by column
chromatography (silica gel, hexanes/EtOAc, 8.5:1.5) gave the title
compound (13.6 mg, 8 % yield) as a yellow solid; m.p. 154.2–
7.6 Hz, 2 H), 7.81 (m, 1 H), 7.66 (m, 2 H), 7.58 (d, J = 8.3 Hz, 2
H), 7.26 (dt, J = 16.2, 2.2 Hz, 1 H), 6.52 (dt, J = 16.2, 11.8 Hz, 1
H), 3.78 (s, 3 H) ppm. 13C NMR (125 MHz, CDCl3): δ = 166.3
(C), 140.1 (t, JC,F = 9.0 Hz, CH), 137.7 (C), 135.3 (CH), 132.8 (C),
155.8 °C. Rf = 0.20 (silica gel, hexanes/EtOAc, 8.5:1.5). IR (KBr): 131.5 (C), 130.8 (2 CH), 130.1 (2 CH), 129.3 (2 CH), 127.7 (2 CH),
ν
max = 3090 (C–H of aromatic), 1650 (C=C), 1528, 1478, and 1448
121.2 (t, JC,F = 281.7 Hz, CF2), 115.1 (t, JC,F = 22.3 Hz, CH), 52.2
˜
6
www.eurjoc.org
© 0000 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim Eur. J. Org. Chem. 0000, 0–0

Job/Unit: O20613
/KAP1
Date: 05-09-12 18:35:42
Pages: 11
Heck-Type Reactions of [(Bromodifluoromethyl)sulfonyl]benzene
(CH3) ppm. 19F NMR (470 MHz, CDCl3): δ = –101.53 (d, JF,H
11.7 Hz, CF2) ppm. HRMS (ESI-TOF): calcd. for C17H14F2O4SNa
[M + Na]+ 375.0479; found 375.0531.
=
inseparable mixture of 3m and 5 (152.1 mg, 82% yield) as a white
solid. R = 0.25 (silica gel, hexanes/EtOAc, 9.2:0.8). IR (KBr): ν
˜
f
max
= 3066 and 3028 (C–H of aromatic), 1619 (C=C), 1582, 1492, and
1
1448 (aromatic), 1333 and 1162 (SO2), 1073 (C–F) cm–1. H NMR
(E)-4-[3,3-Difluoro-3-(phenylsulfonyl)prop-1-en-1-yl]phenyl Acetate
(3j): According to the general procedure, 4-vinylphenyl acetate (2j,
243.2 mg, 1.5 mmol) was employed, and purification by column
chromatography (silica gel, hexanes/EtOAc, 8.2:1.8) gave the title
compound (30.0 mg, 17 % yield) as a yellow solid; m.p. 112.0–
113.8 °C. Rf = 0.20 (silica gel, hexanes/EtOAc, 8.2:1.8). IR (KBr):
(500 MHz, CDCl3): δ = 7.98 (d, J = 7.5 Hz, 4 H), 7.75 (m, 2 H),
7.60 (m, 4 H), 7.45–7.22 (m, 20 H), 6.37 (t, J = 14.8 Hz, 1 H), 4.52
(t, J = 7.3 Hz, 1 H), 3.26 (td, J = 18.2, 7.3 Hz, 2 H) ppm. 13C
NMR (125 MHz, CDCl3): δ = 156.1 (t, JC,F = 4.5 Hz, 1 C), 142.8
(C), 140.5 (C), 137.2 (C), 135.2 (CH), 135.0 (CH), 133.0 (C), 132.0
(C), 130.7 (CH), 129.6 (CH), 129.2 (CH), 129.15 (CH), 129.13
(CH), 129.10 (CH), 128.6 (CH), 128.4 (CH), 128.2 (CH), 128.0
ν
= 3071 (C–H of aromatic), 1759 (C=O), 1649 (C=C), 1601,
˜
max
1508, and 1447 (aromatic), 1334 and 1167 (SO2), 1204 (C–O), 1087
(C–F) cm–1. 1H NMR (500 MHz, CDCl3): δ = 8.04 (d, J = 7.6 Hz,
2 H), 7.78 (m, 1 H), 7.64 (m, 2 H), 7.52 (d, J = 8.6 Hz, 2 H), 7.21–
7.13 (m, 3 H), 6.37 (dt, J = 16.1, 11.9 Hz, 1 H), 2.32 (s, 3 H) ppm.
13C NMR (125 MHz, CDCl3): δ = 169.0 (C=O), 152.1 (C), 141.1
(t, JC,F = 8.8 Hz, CH), 135.1 (CH), 132.8 (C), 131.2 (C), 130.7 (2
(CH), 127.6 (CH), 127.4 (CH), 126.7 (CH), 124.1 (t, JC,F
287.5 Hz, CF2), 121.2 (t, JC,F = 284.0 Hz, CF2), 110.6 (t, JC,F
=
=
19.6 Hz, CH), 44.1 (CH), 34.1 (t, JC,F = 18.7 Hz, CH2) ppm. 19F
NMR (470 MHz, CDCl3): δ = –94.39 (d, JF,H = 15.0 Hz, CF2),
–102.06 (t, JF,H = 18.3 Hz, CF2) ppm. HRMS (ESI-TOF): calcd.
for C21H16F2O2SNa [M + Na]+ 393.0737; found 393.0700. HRMS
(ESI-TOF): calcd. for C21H18F2O2SNa [M + Na]+ 395.0893; found
395.0848.
CH), 129.2 (2 CH), 128.9 (2 CH), 122.1 (2 CH), 121.4 (t, JC,F
=
F
281.7 Hz, CF2), 112.6 (t, JC,F = 22.1 Hz, CH), 21.0 (CH3) ppm. 19
NMR (470 MHz, CDCl3): δ = –101.37 (d, JF,H = 11.2 Hz,
CF2) ppm. HRMS (ESI-TOF): calcd. for C17H14F2O4SNa [M +
Na]+ 375.0479; found 375.0503.
5-[Difluoro(phenylsulfonyl)methyl]-3,4-dihydro-2H-pyran (3n): Ac-
cording to the general procedure, 3,4-dihydro-2H-pyran (2n,
126.2 mg, 1.5 mmol) was employed, and purification by column
chromatography (silica gel, hexanes/EtOAc, 9.2:0.8) gave the title
compound (56.6 mg, 41% yield) as a white solid; m.p. 85.8–86.9 °C.
(E)-1-[3,3-Difluoro-3-(phenylsulfonyl)prop-1-en-1-yl]-4-methoxybenz-
ene (3k): According to the general procedure, 1-methoxy-4-vinyl-
benzene (2k, 201.3 mg, 1.5 mmol) was employed, and purification
by column chromatography (silica gel, hexanes/EtOAc, 8:2) gave
the title compound (25.9 mg, 16% yield) as a white solid; m.p.
130.0–131.8 °C. Rf = 0.30 (silica gel, hexanes/EtOAc, 8:2). IR
R = 0.20 (silica gel, hexanes/EtOAc, 9.2:0.8). IR (KBr): ν
=
˜
f
max
3068 (C–H of aromatic), 2999 and 2923 (C–H of aliphatic), 1649
(C=C), 1581, 1475, and 1446 (aromatic), 1328 and 1164 (SO2), 1087
1
(C–F) cm–1. H NMR (500 MHz, CDCl3): δ = 8.01 (m, 2 H), 7.76
(KBr): ν
= 3078 (C–H of aromatic), 2937 (C–H of aliphatic),
˜
max
(m, 1 H), 7.63 (m, 2 H), 6.98 (t, J = 1.4 Hz, 1 H), 4.11 (t, J =
5.3 Hz, 2 H), 2.41 (t, J = 6.2 Hz, 2 H), 1.97 (quin, J = 6.2, 5.3 Hz,
1646 (C=C), 1605, 1514, and 1449 (aromatic), 1333 and 1161 (SO2),
1086 (C–O), 1036 (C–F) cm–1. 1H NMR (500 MHz, CDCl3): δ =
8.04 (d, J = 7.2 Hz, 2 H), 7.77 (m, 1 H), 7.64 (m, 2 H), 7.46 (m, 2
H), 7.15 (dt, J = 16.1, 2.1 Hz, 1 H), 6.93 (m, 2 H), 6.25 (dt, J =
16.2, 12.0 Hz, 1 H), 3.85 (s, 3 H) ppm. 13C NMR (125 MHz,
CDCl3): δ = 161.3 (C), 141.7 (t, JC,F = 8.6 Hz, CH), 135.1 (CH),
133.2 (C), 130.7 (2 CH), 129.5 (2 CH), 129.2 (2 CH), 126.4 (C),
1 H) ppm. 13C NMR (125 MHz, CDCl3): δ = 151.0 (t, JC,F
=
10.6 Hz, CH), 134.8 (CH), 133.4 (C), 130.6 (2 CH), 129.1 (2 CH),
122.7 (t, JC,F = 283.6 Hz, CF2), 100.6 (t, JC,F = 21.2 Hz, 1 C), 66.4
(CH2), 21.0 (CH2), 19.0 (t, JC,F = 2.8 Hz, CH2) ppm. 19F NMR
(470 MHz, CDCl3): δ = –101.79 (s, CF2) ppm. HRMS (ESI-TOF):
calcd. for C12H12F2O3SNa [M + Na]+ 297.0373; found 297.0439.
121.8 (t, JC,F = 281.5 Hz, CF2), 114.3 (2 CH), 109.6 (t, JC,F
=
22.0 Hz, CH), 55.3 (CH3) ppm. 19F NMR (470 MHz, CDCl3): δ =
–100.70 (d, JF,H = 12.2 Hz, CF2) ppm. HRMS (ESI-TOF): calcd.
for C16H14F2O3SNa [M + Na]+ 347.0529; found 347.0606.
(E)-(3-tert-Butoxy-1,1-difluoroallylsulfonyl)benzene (3o): According
to the general procedure, tert-butylvinyl ether (2o, 500.8 mg,
5.0 mmol, 10 equiv.) was employed, and purification by column
chromatography (silica gel, hexanes/EtOAc, 9.2:0.8) gave the title
compound (65.8 mg, 45% yield) as a yellow liquid. Rf = 0.25 (silica
(E)-2-[3,3-Difluoro-3-(phenylsulfonyl)prop-1-enyl]naphthalene (3l):
According to the general procedure, 2-vinylnaphthalene (2l,
231.3 mg, 1.5 mmol) was employed, and purification by column
chromatography (silica gel, hexanes/EtOAc, 9.2:0.8) gave the title
compound (29.2 mg, 17 % yield) as a yellow solid; m.p. 135.5–
137.8 °C. Rf = 0.25 (silica gel, hexanes/EtOAc, 9.2:0.8). IR (Nujol
gel, hexanes/EtOAc, 9.2:0.8). IR (KBr): ν
= 3071 (C–H of aro-
˜
max
matic), 2977 (CH of aliphatic), 1657 (C=C), 1584, 1478, and 1449
(aromatic), 1337 and 1163 (SO2), 1115 (C–O), 1070 (C–F) cm–1. 1H
NMR (500 MHz, CDCl3): δ = 8.05 (d, J = 7.2 Hz, 2 H), 7.75 (m,
1 H), 7.61 (m, 2 H), 7.03 (dt, J = 12.1, 2.0 Hz, 1 H), 5.17 (td, J =
12.7, 12.2 Hz, 1 H), 1.35 (s, 9 H) ppm. 13C NMR (125 MHz,
CDCl3): δ = 153.3 (t, JC,F = 10.2 Hz, CH), 134.8 (CH), 133.3 (C),
130.6 (2 CH), 129.1 (2 CH), 122.8 (t, JC,F = 280.6 Hz, CF2), 91.7
(t, JC,F = 22.7 Hz, CH), 79.8 (C), 27.9 (CH3) ppm. 19F NMR
(470 MHz, CDCl3): δ = –97.80 (d, JF,H = 12.7 Hz, CF2) ppm.
HRMS [APCI (atmospheric pressure chemical ionization)-TOF]:
calcd. for C17H27F2O4S [M + tBuOH]+ 365.1593; found 365.1578.
mull): νmax = 3061 (C–H of aromatic), 1644 (C=C), 1583, and 1450
˜
(aromatic), 1343 and 1164 (SO2), 1072 (C–F) cm–1 1H NMR
.
(500 MHz, CDCl3): δ = 8.05 (d, J = 7.3 Hz, 2 H), 7.88–7.82 (m, 4
H), 7.76 (m, 1 H), 7.65–7.61 (m, 3 H), 7.51 (m, 2 H), 7.35 (dt, J =
16.1, 2.1 Hz, 1 H), 6.50 (dt, J = 16.1, 11.9 Hz, 1 H) ppm. 13C NMR
(125 MHz, CDCl3): δ = 142.3 (t, JC,F = 9.0 Hz, CH), 135.2 (CH),
134.2 (C), 133.2 (C), 133.1 (C), 131.0 (C), 130.8 (2 CH), 129.6
(CH), 129.2 (2 CH), 128.7 (CH), 128.5 (CH), 127.7 (CH), 127.3
(CH), 126.7 (CH), 123.2 (CH), 121.6 (t, JC,F = 281.7 Hz, CF2),
112.5 (t, JC,F = 22.1 Hz, CH) ppm. 19F NMR (470 MHz, CDCl3):
δ = –101.08 (d, JF,H = 11.7 Hz, CF2) ppm. HRMS (ESI-TOF):
calcd. for C19H14F2O2SNa [M + Na]+ 367.0580; found 367.0643.
(E)-[3,3-Difluoro-3-(phenylsulfonyl)prop-1-enyl](phenyl)sulfane
(trans-3p) and (Z)-[3,3-Difluoro-3-(phenylsulfonyl)prop-1-enyl]-
(phenyl)sulfane (cis-3p): According to the general procedure, phen-
yl(vinyl)sulfane (2p, 204.3 mg, 1.5 mmol) was employed, and purifi-
cation by preparative thin layer chromatography (hexanes/EtOAc,
[3,3-Difluoro-3-(phenylsulfonyl)prop-1-ene-1,1-diyl]dibenzene (3m)
and [3,3-Difluoro-3-(phenylsulfonyl)propane-1,1-diyl]dibenzene (5): 9.2:0.8) gave (E)-[3,3-difluoro-3-(phenylsulfonyl)prop-1-enyl]-
According to the general procedure, 1,1-diphenylethylene (2m,
270.0 mg, 1.5 mmol) was employed, and purification by column
chromatography (silica gel, hexanes/EtOAc, 9.2:0.8) gave a 1.2:1
(phenyl)sulfane (trans-3p, 70.7 mg, 43 % yield) and (Z)-[3,3-di-
fluoro-3-(phenylsulfonyl)prop-1-enyl](phenyl)sulfane (cis-3p,
43.3 mg, 26% yield). Data for trans-3p: yellow liquid; Rf = 0.25
Eur. J. Org. Chem. 0000, 0–0
© 0000 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
7

Job/Unit: O20613
/KAP1
Date: 05-09-12 18:35:42
Pages: 11
N. Surapanich, C. Kuhakarn, M. Pohmakotr, V. Reutrakul
FULL PAPER
(silica gel, hexanes/EtOAc, 9.2:0.8). IR (neat): ν
= 3062 (C–H
compound (63.0 mg, 38 % yield) as a white solid; m.p. 117.4–
˜
max
of aromatic), 1600 (C=C), 1583, 1478, and 1448 (aromatic), 1338 118.5 °C. Rf = 0.30 (silica gel, hexanes/EtOAc, 9.2:0.8). IR (KBr):
1
and 1164 (SO2), 1091 (C–F) cm–1. H NMR (500 MHz, CDCl3): δ
= 7.98 (m, 2 H), 7.76 (m, 1 H), 7.62 (m, 2 H), 7.51–7.43 (m, 5 H),
7.25 (dt, J = 15.2, 1.9 Hz, 1 H), 5.57 (dt, J = 15.2, 11.8 Hz, 1
H) ppm. 13C NMR (125 MHz, CDCl3): δ = 143.2 (t, JC,F = 9.0 Hz,
CH), 135.1 (CH), 133.1 (C), 133.1 (2 CH), 130.7 (2 CH), 130.0 (C),
129.8 (2 CH), 129.3 (CH), 129.2 (2 CH), 120.9 (t, JC,F = 282.7 Hz,
CF2), 109.2 (t, JC,F = 23.5 Hz, CH) ppm. 19F NMR (470 MHz,
CDCl3): δ = –99.85 (d, JF,H = 12.2 Hz, CF2) ppm. HRMS (ESI-
TOF): calcd. for C15H12F2O2S2Na [M + Na]+ 349.0144; found
349.0013. Data for cis-3p: yellow liquid; Rf = 0.17 (silica gel, hex-
ν
= 3123 and 3104 (C–H of aromatic), 1596, 1531, 1496, and
˜
max
1448 (aromatic), 1341 and 1169 (SO2), 1073 (C–F) cm–1. H NMR
(500 MHz, CDCl3): δ = 7.85 (d, J = 7.8 Hz, 2 H), 7.69 (m, 1 H),
7.53 (m, 2 H), 7.41 (m, 5 H), 6.93 (t, J = 2.1 Hz, 1 H), 6.83 (m, 1
H), 6.36 (m, 1 H) ppm. 13C NMR (125 MHz, CDCl3): δ = 139.6
(C), 134.9 (CH), 133.1 (C), 130.7 (2 CH), 129.8 (t, JC,F = 1.8 Hz,
CH), 129.0 (2 CH), 128.5 (CH), 128.4 (2 CH), 127.7 (2 CH), 119.7
(t, JC,F = 284.0 Hz, CF2), 117.7 (t, JC,F = 27.8 Hz, 1 C), 117.2 (t,
JC,F = 5.6 Hz, CH), 109.3 (CH) ppm. 19F NMR (470 MHz,
CDCl3): δ = –92.60 (s, CF2) ppm. HRMS (ESI-TOF): calcd. for
C17H13F2NO2SNa [M + Na]+ 356.0533; found 356.0550.
1
anes/EtOAc, 9.2:0.8). IR (KBr): ν
= 3062 (C–H of aromatic),
˜
max
1698 (C=C), 1478 and 1447 (aromatic), 1342 and 1155 (SO2), 1085
(C–F) cm–1. 1H NMR (500 MHz, CDCl3): δ = 8.08 (d, J = 7.4 Hz,
2 H), 7.78 (m, 1 H), 7.65 (m, 2 H), 7.44–7.36 (m, 5 H), 7.15 (dt, J
= 11.1, 2.7 Hz, 1 H), 5.75 (td, J = 15.5, 11.2 Hz, 1 H) ppm. 13C
NMR (125 MHz, CDCl3): δ = 145.1 (t, JC,F = 4.8 Hz, CH), 135.2
(CH), 134.2 (t, JC,F = 2.7 Hz, 1 C), 133.0 (C), 131.2 (2 CH), 130.9
(2 CH), 129.4 (2 CH), 129.2 (2 CH), 128.4 (CH), 121.8 (t, JC,F
= 283.8 Hz, CF2), 109.2 (t, JC,F = 23.2 Hz, CH) ppm. 19F NMR
(470 MHz, CDCl3): δ = –99.83 (d, JF,H = 15.0 Hz, CF2) ppm.
HRMS (ESI-TOF): calcd. for C15H12F2O2S2Na [M + Na]+
349.0144; found 349.0189.
2-[Difluoro(phenylsulfonyl)methyl]-5-methylfuran (7d): According to
the general procedure, 2-methylfuran (6d, 410.5 mg, 5.0 mmol,
10 equiv.) was employed, and purification by column chromatog-
raphy (silica gel, hexanes/EtOAc, 9.2:0.8) gave the title compound
(39.3 mg, 29% yield) as a yellow solid; m.p. 83.8–85.4 °C. Rf = 0.17
(silica gel, hexanes/EtOAc, 9.2:0.8). IR (KBr): ν
= 3132 (C–H
˜
max
of aromatic), 1580, 1546, and 1448 (aromatic), 1343 and 1171
(SO2), 1124 (C–O), 1081 (C–F) cm–1. 1H NMR (500 MHz, CDCl3):
δ = 8.01 (m, 2 H), 7.79 (m, 1 H), 7.64 (m, 2 H), 6.86 (m, 1 H), 6.16
(m, 1 H), 2.37 (m, 3 H) ppm. 13C NMR (125 MHz, CDCl3): δ =
157.2 (C), 137.5 (t, JC,F = 28.9 Hz, 1 C), 135.2 (CH), 132.9 (C),
130.7 (2 CH), 129.2 (2 CH), 117.3 (t, JC,F = 282.7 Hz, CF2), 117.1
(t, JC,F = 3.1 Hz, CH), 107.8 (CH), 13.6 (CH3) ppm. 19F NMR
(470 MHz, CDCl3): δ = –102.15 (s, CF2) ppm. HRMS (ESI-TOF):
calcd. for C12H10F2O3SNa [M + Na]+ 295.0216; found 295.0177.
2-[Difluoro(phenylsulfonyl)methyl]-1-methyl-1H-pyrrole (7a): Ac-
cording to the general procedure, 1-methyl-1H-pyrrole (6a,
121.7 mg, 1.5 mmol) was employed, and purification by column
chromatography (silica gel, hexanes/EtOAc, 8.5:1.5) gave the title
compound (99.1 mg, 73 % yield) as a yellow solid; m.p. 102.9–
104.0 °C. Rf = 0.27 (silica gel, hexanes/EtOAc, 8.5:1.5). IR (KBr):
2-[Difluoro(phenylsulfonyl)methyl]-1-methyl-1H-indole (7e): Accord-
ing to the general procedure, 1-methyl-1H-indole (6e, 196.8 mg,
1.5 mmol) was employed, and purification by column chromatog-
raphy (silica gel, hexanes/EtOAc, 9.2:0.8) gave the title compound
(38.5 mg, 24% yield) as a white solid; m.p. 127.5–129.0 °C. Rf =
ν
= 3130, and 3093 (C–H of aromatic), 1581, 1534, and 1485
˜
max
(aromatic), 1337 and 1162 (SO2), 1065 (C–F) cm–1 1H NMR
.
(500 MHz, CDCl3): δ = 7.98 (m, 2 H), 7.76 (m, 1 H), 7.62 (m, 2
H), 6.81 (t, J = 2.2 Hz, 1 H), 6.57 (m, 1 H), 6.18 (m, 1 H), 3.86 (s,
3 H) ppm. 13C NMR (125 MHz, CDCl3): δ = 135.0 (CH), 133.1
(C), 132.8 (C), 130.6 (2 CH), 129.2 (CH), 129.1 (2 CH), 120.0 (t,
JC,F = 282.3 Hz, CF2), 116.7 (t, JC,F = 24.6 Hz, 1 C), 116.4 (t, JC,F
= 4.8 Hz, CH), 108.3 (CH), 36.0 (CH3) ppm. 19F NMR (470 MHz,
CDCl3): δ = –96.8 (s, CF2) ppm. HRMS (ESI-TOF): calcd. for
C12H11F2NO2SNa [M + Na]+ 294.0376; found 294.0362.
0.22 (silica gel, hexanes/EtOAc, 9.2:0.8). IR (KBr): ν
= 3058
˜
max
(C–H of aromatic), 2925 (C–H of aliphatic), 1580, 1529, and 1470
(aromatic), 1337 and 1167 (SO2), 1054 (C–F) cm–1 1H NMR
.
(500 MHz, CDCl3): δ = 8.02 (d, J = 7.7 Hz, 2 H), 7.8 (m, 1 H),
7.69–7.62 (m, 3 H), 7.42 (m, 2 H), 7.21 (m, 1 H), 6.96 (s, 1 H), 4.01
(s, 3 H) ppm. 13C NMR (125 MHz, CDCl3): δ = 139.7 (C), 135.3
(CH), 132.8 (C), 130.8 (2 CH), 129.2 (2 CH), 126.0 (C), 124.7 (CH),
123.7 (t, JC,F = 27.5 Hz, 1 C), 122.1 (CH), 120.7 (CH), 120.0 (t,
JC,F = 277.5 Hz, CF2), 110.0 (CH), 109.1 (t, JC,F = 5.5 Hz, CH),
31.7 (t, JC,F = 3.6 Hz, CH3) ppm. 19F NMR (470 MHz, CDCl3): δ
= – 9 6 . 8 ( s, C F 2 ) ppm. H RM S ( ES I- TO F) : c al cd . for
C16H13F2NO2SNa [M + Na]+ 344.0533; found 344.0531.
1-Benzyl-2-[difluoro(phenylsulfonyl)methyl]-1H-pyrrole (7b): Ac-
cording to the general procedure, 1-benzyl-1H-pyrrole (6b,
235.8 mg, 1.5 mmol) was employed, and purification by column
chromatography (silica gel, hexanes/EtOAc, 9.2:0.8) gave the title
compound (119.8 mg, 69 % yield) as a brown solid; m.p. 75.7–
76.8 °C. Rf = 0.30 (silica gel, hexanes/EtOAc, 9.2:0.8). IR (KBr):
2-[Difluoro(phenylsulfonyl)methyl]thiophene (7f) and 3-[Difluoro-
(phenylsulfonyl)methyl]thiophene (7fЈ): According to the general
procedure, thiophene (6f, 841.4 mg, 10.0 mmol, 10 equiv.) was em-
ployed, and purification by column chromatography (silica gel,
hexanes/EtOAc, 9.2:0.8) gave a 5.2:1 inseparable mixture of 7f and
7fЈ (85.0 mg, 31% yield) as a yellow solid. Rf = 0.25 (silica gel,
ν
= 3127 and 3060 (C–H of aromatic), 1584, 1536, 1487, and
˜
max
1446 (aromatic), 1325 and 1159 (SO2), 1016 (C–F) cm–1. H NMR
(500 MHz, CDCl3): δ = 8.0 (d, J = 7.5 Hz, 2 H), 7.77 (m, 1 H),
7.62 (m, 2 H), 7.38–7.30 (m, 3 H), 7.16 (d, J = 7.1 Hz, 2 H), 6.84
(t, J = 2.2 Hz, 1 H), 6.64 (m, 1 H), 6.26 (m, 1 H), 5.40 (s, 2 H) ppm.
13C NMR (125 MHz, CDCl3): δ = 137.4 (C), 135.0 (CH), 133.1
(C), 130.7 (2 CH), 129.2 (CH), 128.7 (2 CH), 128.4 (CH), 127.7
(CH), 127.1 (2 CH), 120.0 (t, JC,F = 282.8 Hz, CF2), 117.0 (t, JC,F
= 29.6 Hz, 1 C), 116.5 (t, JC,F = 4.8 Hz, CH), 109.1 (CH), 52.3
(CH2) ppm. 19F NMR (470 MHz, CDCl3): δ = –95.85 (s,
CF2) ppm. HRMS (ESI-TOF): calcd. for C18H15F2NO2SNa [M +
Na]+ 370.0689; found 370.0667.
1
hexanes/EtOAc, 9.2:0.8). IR (KBr): νmax = 3113 and 3065 (C–H of
˜
aromatic), 1581, 1526, and 1447 (aromatic), 1339 and 1170 (SO2),
1094 (C–F) cm–1. 1H NMR (500 MHz, CDCl3): δ = 8.05 (m, 4 H),
7.82–7.77 (m, 2 H), 7.67–7.62 (m, 6 H), 7.57 (m, 1 H), 7.47 (m, 1
H), 7.34 (dd, J = 5.2, 1.3 Hz, 1 H), 7.19 (m, 1 H) ppm. 13C NMR
(125 MHz, CDCl3): δ = 135.3 (CH), 135.2 (CH), 132.7 (C), 132.5
(C), 131.9 (t, JC,F = 5.0 Hz, CH), 131.4 (CH), 130.9 (2 CH), 130.8
(2 CH), 129.7 (t, JC,F = 6.1 Hz, CH), 129.3 (2 CH), 129.2 (2 CH),
127.6 (CH), 127.1 (CH), 127.0 (t, JC,F = 27.0 Hz, 1 C), 126.2 (t,
JC,F = 3.5 Hz, CH), 120.7 (t, JC,F = 283.7 Hz, CF2), 120.3 (t, JC,F
= 282.8 Hz, CF2) ppm. 19F NMR (470 MHz, CDCl3): δ = –92.6 (s,
2-[Difluoro(phenylsulfonyl)methyl]-1-phenyl-1H-pyrrole (7c): Ac-
cording to the general procedure, 1-phenyl-1H-pyrrole (6c,
214.8 mg, 1.5 mmol) was employed, and purification by column
chromatography (silica gel, hexanes/EtOAc, 9.2:0.8) gave the title
8
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© 0000 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 0000, 0–0

Job/Unit: O20613
/KAP1
Date: 05-09-12 18:35:42
Pages: 11
Heck-Type Reactions of [(Bromodifluoromethyl)sulfonyl]benzene
P. Bey, M. Kolb, B. Neises, D. Schirlin, J. Med. Chem. 1990,
CF2), –97.5 (s, CF2) ppm. HRMS (ESI-TOF): calcd. for
C11H8F2O2S2Na [M + Na]+ 296.9831; found 296.9922.
33, 394–407; c) H. L. Sham, D. A. Betebenner, N. Wideburg,
A. C. Saldivar, W. E. Kohlbrenner, A. Craig-Kennard, S. Vasa-
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D. W. Norbeck, FEBS Lett. 1993, 329, 144–146; d) H. L.
Sham, C. Zhao, K. C. Marsh, D. A. Betebenner, S. Q. Lin, E.
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Bernstein, B. J. Kosmider, E. P. Vacek, C. A. Veale, B. C.
Gomes, Bioorg. Med. Chem. Lett. 1994, 4, 2175–2178; g) A. M.
Doherty, I. Sircar, B. E. Kornberg, J. Quin III, R. T. Winters,
J. S. Kaltenbronn, M. D. Taylor, B. L. Batley, S. R. Rapundalo,
M. J. Ryan, C. A. Painchaud, J. Med. Chem. 1992, 35, 2–14; h)
M. Eda, A. Ashimori, F. Akahoshi, T. Yoshimura, Y. Inoue,
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Reductive Desulfonylation Reaction of (E)-1-Chloro-4-[3,3-difluoro-
3-(phenylsulfonyl)prop-1-en-1-yl]benzene (3a):
A round-bottom
flask with a magnetic stir bar was charged with compound 3a
(105.7 mg, 0.32 mmol) and DMF (5 mL) followed by the addition
of HOAc/NaOAc (1:1) buffer solution (8 mol/L, 2.5 mL). Magne-
sium turnings (115.5 mg, 4.8 mmol) were added in portions. After
stirring at room temperature for 5 h, water (15 mL) was added, and
the resulting solution was extracted with EtOAc (3ϫ20 mL). The
combined organic phases were dried with MgSO4 and concentrated
in vacuo. The crude product was purified by silica gel column
chromatography using hexanes as the eluent to give product 13a
(35.5 mg, 59%) as a colorless liquid. IR (neat): ν
= 3031 (C–H
˜
max
of aromatic), 1658 (C=C), 1490 and 1448 (aromatic), 1138 (C–F)
1
cm–1. H NMR (500 MHz, CDCl3): δ = 7.37 (d, J = 8.6 Hz, 2 H),
7.34 (d, J = 8.6 Hz, 2 H), 6.83 (m, 1 H), 6.23 (m, 2 H) ppm. 13C
NMR (125 MHz, CDCl3): δ = 135.7 (t, JC,F = 11.8 Hz, CH), 135.2
(C), 132.9 (C), 129.0 (2 CH), 128.4 (2 CH), 121.5 (t, JC,F = 23.7 Hz,
CH), 115.0 (t, JC,F = 232.7 Hz, CF2) ppm. 19F NMR (470 MHz,
CDCl3): δ = –110.04 (m, CF2) ppm. HRMS (ESI-TOF): calcd. for
C9H8ClF2 [M + H]+ 189.0283; found 189.0306.
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Acknowledgments
The authors thank the Center of Excellence for Innovation in
Chemistry (PERCH-CIC), The Office of the Higher Education
Commission, and Mahidol University under the National Research
Universities Initiative for financial support. Dr. Winai Ieasuwan is
thanked for preliminary works.
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N. Surapanich, C. Kuhakarn, M. Pohmakotr, V. Reutrakul
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Received: May 10, 2012
Published Online: ᭿
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Eur. J. Org. Chem. 0000, 0–0

Job/Unit: O20613
/KAP1
Date: 05-09-12 18:35:42
Pages: 11
Heck-Type Reactions of [(Bromodifluoromethyl)sulfonyl]benzene
Heck-Type Reaction
N. Surapanich, C. Kuhakarn,
M. Pohmakotr, V. Reutrakul* ......... 1–11
Palladium-Mediated Heck-Type Reactions
of [(Bromodifluoromethyl)sulfonyl]benz-
ene: Synthesis of α-Alkenyl- and α-Het-
Palladium-catalyzed Heck-type reactions
of [(bromodifluoromethyl)sulfonyl]benzene
(1) are reported. Both styrene derivatives
and heteroaromatic compounds gave
PhSO2CF2-substituted products in moder-
ate to good yields.
eroaryl-Substituted
Phenyl Sulfones
α,α-Difluoromethyl
Keywords: Synthetic methods / Cross cou-
pling / Heck reaction / Palladium / Fluor-
ine
Eur. J. Org. Chem. 0000, 0–0
© 0000 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
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