Efficient synthesis of racemic and chiral alkenyl sulfoxides by palladium-catalyzed Suzuki coupling

Article abstract of DOI:10.1016/j.tet.2010.06.050

Alkenyl sulfoxide derivatives are obtained in high yields through a palladium-catalyzed Suzuki/Miyaura cross-coupling reaction of racemic and chiral 1-halo sulfoxides with aryl and alkenyl boronic acids. Chiral substrates react with no loss of optical purity and high optical yields. The reaction takes place with different palladium catalysts, such as Pd(PPh₃)₄ or Pd(OAc)₂/DABCO. Although nitrogen ligands like DABCO lead to an active palladium catalyst, they are less effective than the phosphine ones.

Full text of DOI:10.1016/j.tet.2010.06.050

Tetrahedron 66 (2010) 6901e6905
Contents lists available at ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Efficient synthesis of racemic and chiral alkenyl sulfoxides by palladium-catalyzed
Suzuki coupling
*
Gisela Mancha, Ana B. Cuenca, Nuria Rodríguez, Mercedes Medio-Simón , Gregorio Asensio
Departamento de Química Orgánica, Universidad de Valencia, Avenida Vicent Andrés Estellés s/n, 46100 Burjassot, Valencia, Spain
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 6 May 2010
Received in revised form 16 June 2010
Accepted 17 June 2010
Available online 25 June 2010
Alkenyl sulfoxide derivatives are obtained in high yields through a palladium-catalyzed Suzuki/Miyaura
cross-coupling reaction of racemic and chiral 1-halo sulfoxides with aryl and alkenyl boronic acids. Chiral
substrates react with no loss of optical purity and high optical yields. The reaction takes place with
different palladium catalysts, such as Pd(PPh3)4 or Pd(OAc)2/DABCO. Although nitrogen ligands like
DABCO lead to an active palladium catalyst, they are less effective than the phosphine ones.
Ó 2010 Elsevier Ltd. All rights reserved.
Keywords:
Palladium
Cross-coupling
Boronic acids
Sulfoxides
Suzuki reaction
1. Introduction
explore the cross-coupling methodology using halovinyl sulfoxides
as suitable starting materials. Moreover, halovinyl sulfoxides may
Alkenyl sulfoxides are useful synthetic intermediates in organic
chemistry,1 and are widely used as dienophiles,2 dipolarophiles,3
Michael acceptors,4 substrates for Claisen rearrangements,5 as
well as in transition metal-catalyzed processes, such as Heck6 or
Pauson/Khand reactions.7 Besides, specific applications like key
building blocks in the synthesis of fine chemicals, such as alkaloid
aspidoespermidina1c or antibiotic TAN-1085,8 have been described.
Because of their valuable intermediacy, especially in asymmetric
synthesis, different approaches for the synthesis of this class of
compounds are known. Among them, the oxidation of the corre-
sponding sulfides,9 the condensation of carbonyl compounds,10 the
hydrogenation of alkynyl sulfoxides11 and the Andersen synthesis12
are the most representative. However, these procedures approve to
be rather complicated and usually require the use of multi-step
protocols or expensive reagents. Nevertheless, continued efforts
made in this field have resulted in new strategies for the regio- and
stereoselective synthesis of some interesting alkenyl sulfoxides.1a
Surprisingly, transition-metal catalyzed cross-coupling methodol-
ogies13 have scarcely been applied to prepare alkenyl sulfoxides
despite the substrates containing this functional group proving
efficient partners for different types of coupling reactions.14,15 The
synthetic interest of the target alkenyl sulfoxides prompted us to
be envisaged as synthetic equivalents of vinyl bromides if the sul-
finyl moiety is removed.16
Although atomic economy is indeed a drawback in this approach,
the high toxicity of vinyl bromides justifies the search of safer al-
ternatives. In order to outline the reactivity profile of this class of
compounds in cross-coupling reactions, simple halovinyl sulfoxides
1aed can be selected as representative substrates (Chart 1). Even
though 2-bromovinyl sulfoxide 1c has been used in Stille and
Sonogashira17 cross-coupling processes, there are no precedents of
the participation of 1-bromovinyl sulfoxide 1a in cross-coupling
reactions in the literature. Stille coupling processes with 1-iodovinyl
derivative 1b, as described in the literature, proceeds with moderate
yields,17 but the analogous bromovinyl derivative 1a does not react
in the same coupling reaction.17 As far as we know, this is the only
work on the behavior of 1-bromovinyl sulfoxide 1a in a cross-cou-
pling process in the literature. Therefore, those precedents relating
to the structurally similar compounds 1-iodovinyl sulfoxide (1b) and
Sulfoxide X1 X2 Stille Sonogashira
X2
(S)-1a Br
H
H
no
yes
no
no
:
(S)-1b
(R)-1c
(R)-1d
I
p-Tol
S
X1
H
H
Br yes
yes
yes
yes
O
I
* Corresponding author. Fax: þ34 963544939; e-mail address: mercedes.medio@
uv.es (M. Medio-Simón).
Chart 1. Resume of reactivity of 1- and 2-halovinyl sulfoxides according to Ref. 17.
0040-4020/$ e see front matter Ó 2010 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2010.06.050

6902
G. Mancha et al. / Tetrahedron 66 (2010) 6901e6905
2-bromovinyl sulfoxide (1c) deal with only Stille-type coupling re-
actions.17 Nowadays however, we considered that the use of orga-
notin compounds is not the first choice of organometallic partners in
coupling processes owing to the usual difficulties in the work up and
the subsequent isolation of the coupled products, and given the
toxicity of these reagents. In contrast, the organoboron derivatives
used in Suzuki cross-coupling reactions are not toxic, are not air- and
water-sensitive, and the only limitation is their lower reactivity as
transmetallating reagents. This disadvantage is overcome by the
addition of a base18 to activate the transmetallation step. In addition,
our previous experience with related bromomethyl sulfoxides has
proved that Suzuki-type couplings lead to better results than other
organometallic compounds.15 Consequently, the preparation of
alkenyl sulfoxides using the 1-bromovinyl sulfoxide 1a reaction as
an electrophile partner in a transition-metal catalyzed cross-cou-
pling process remains unexplored. These facts prompted us to ex-
plore the reactivity of 1-bromovinyl sulfoxides in cross-coupling
reactions.
a variety of aryl and alkenyl boronic acids to afford the corre-
sponding styrene and diene derivatives 3ael. Very high yields of
the cross-coupled products 3 were obtained from the aryl boronic
acids activated by electron donor substituents 2b and 2c (Table 1,
entries 2 and 3). o-Substituted boronic acids with moderate steric
hindrance (2f and 2g) (Table 1, entries 6 and 7) also gave
satisfactory results. With crowded o-substituted aryl boronic acid
2h (Table 1, entry 8), the yield of the coupled product 3eh was still
good (68%). As expected the aryl boronic acids containing electron
withdrawing groups (2d, 2e, 2i, and 2j) were less effective. Yet even
in these less favorable cases, the corresponding cross-coupling
products were obtained with good (Table 1, entries 4 and 10) to
moderate yields (Table 1, entries 5 and 9).
Alkenyl boronic acids 2k and 2l were also tested in the cross-
coupling reaction. The corresponding dienes, 3ek and 3el, were
obtained with excellent yields, as detected by 1H NMR of the crude
reaction mixture. However, the low stability of diene 3el did not
allow its isolation and complete characterization. These results
show that 1-bromovinyl sulfoxide 1e is a suitable partner in the
cross-coupling process that can react efficiently with aryl and
alkenyl boronic acids under mild conditions (65 ꢀC, 3 h) using Pd
(PPh3)4, the most common palladium catalyst. Under our condi-
tions, CsF efficiently promotes the transmetallation of boronic
acids. We also tested other usual inorganic bases and alcoholic/
aqueous solvents employed in Suzuki-type couplings.20 Neverthe-
less in this case, bases such as NaOH, NaHCO3, K3PO4, and solvents
like CH3OH or the mixture CH3OH/H2O were ineffective given the
occurrence of Michael-type additions of hydroxyl or alkoxy anions
to vinyl sulfoxide 1e. In addition, Cs2CO3 prompted the formation of
sulfenic acid derivatives by the decomposition of 1e, resulting in
lower coupling product yields.
2. Results and discussion
Racemic bromosulfoxide 1e was selected as a benchmark sub-
strate for screening experiments. The synthesis of bromovinyl
sulfoxides, such as 1e by consecutive bromination, and DBU
dehydrobromination from the corresponding commercially avail-
able vinyl sulfoxide, have been previously reported,19 although
experimental details were not provided. In our study, good yields
were attained by the slow addition of the starting material over
a long period (18 h) and by carefully controlling the temperature
(see the Experimental section) to avoid the formation of significant
amounts of 1-bromovinyl sulfide.
Despite the fact that phosphines are the most common ligands
in palladium cross-coupling processes in homogeneous media, the
problems associated with their incompatibilities with air and
aqueous solvents prompted us to test other palladium catalytic
systems.21 Nitrogen ligands are an alternative to phosphine ligands
given their economy and availability.22 However, they are less ef-
fective for both the stabilization of the Pd(0) species (which pre-
cludes the inactivation of metal, such as black palladium) and the
activation of the oxidative addition and reductive elimination steps.
Even though, palladium-nitrogen catalysts are still effective when
applied to substrates that do not require forcing reaction condi-
tions. Along these lines, DABCO23 has recently been described as
a suitable ligand for the palladium-catalyzed Suzuki synthesis of
biaryls. Nevertheless, the cross-coupling of vinyl sulfoxide 1e with
aryl boronic acids 2aed (Table 1, entries 13e16, method B) was less
productive under the Pd(OAc)2/DABCO catalyst and prolonged re-
action times were required to achieve moderate conversions. A
further decrease of catalyst activity was observed with the less
reactive electron-deficient boronic acid 2d (Table 1, entry 16), in
which case the cross-coupled product was obtained with merely
a 23% yield. While the inactivated phenyl boronic acid 2a gave
a moderate yield (Table 1, entry 13), boronic acids 2b and 2c, con-
taining electron donor substituents, produced high coupling
product yields (Table 1, entries 14 and 15).
Next we assayed the cross-coupling reaction using a heteroge-
neous catalyst given its advantages, these being easy product
separation and recycling possibilities. Some commercial heteroge-
neous catalysts, such as FibrecatÒ and Pd EncatÒ, were checked with
1-bromovinyl sulfoxide 1e, but none effectively promoted Suzuki
reaction.
Thanks to the efficiency of palladium-catalyzed cross-coupling,
we extended the method to chiral sulfoxides. The preparation of
the required enantiopure bromosulfoxide (S)-1a, which entailed
following the same procedure for the synthesis of racemic 1e, took
place with only a moderate optical yield (66% ee). It is likely that
Bromovinyl sulfoxide 1e was tested in palladium-catalyzed
Suzuki/Miyaura cross-coupling reactions (see Table 1). As a first
experiment, the reaction of 1-bromovinyl sulfoxide 1e with phenyl
boronic acid 2a took place under mild conditions to give the cross-
coupled product 3ea with a high yield (Table 1, entry 1). The gen-
erality of this reaction allowed us to couple this substrate with
Table 1
Palladium-catalyzed Suzuki cross-coupling of racemic bromosulfoxide 1e with
boronic acids
Pd/L, CsF
+
RB(OH)2
S
Br
THF
S
R
O
O
3ea-el
1e
2a-l
Entry
2
R
Method
3 (Yield)a
1
2
3
4
5
6
7
8
a
b
c
d
e
f
g
h
i
j
k
l
a
b
c
d
C6H5
A
A
A
A
A
A
A
A
A
A
A
A
B
B
B
B
84
89
85
75
53
90
87
68
68
80
4-MeOC6H4
4-MeC6H4
4-CF3C6H4
3-NO2C6H4
2-MeOC6H4
2-MeC6H4
2-(tBuCONH)C6H4
2-CF3C6H4
2-BrC6H4
trans-1-Hexen-1-yl
trans-Styryl
C6H5
4-MeOC6H4
4-MeC6H4
4-CF3C6H4
9
10
11
12
13
14
15
16
85
b
43
78
70
23
a
Isolated yields, A: Pd(PPh3)4 (10 mol %), 65 ꢀC, 3 h, B: Pd (OAc)2/DABCO
(10 mol %), 85 ꢀC, 18 h.
b
conversion >90%, unstable product.

G. Mancha et al. / Tetrahedron 66 (2010) 6901e6905
6903
failure lies in slow bromination because of the
p
-deficient character
142.6. [
a
]
25 þ68.0 (c 1.35, CHCl3) (lit17
[
a
]
25 þ68.2 (c 1.35, CHCl3));
D
D
of the vinyl sulfoxide, which allows bromination at the sulfur atom
with concomitant racemization. Then we prepared 1-iodovinyl
sulfoxide (S)-1b, which we accomplished with both good chemical
and optical yields.17 The palladium-catalyzed cross-coupling re-
actions of iodovinyl sulfoxide, with a representative neutral, elec-
tron-rich and electron-deficient aryl boronic acids, afforded the
corresponding 1,1-substituted vinylsulfoxides (R)-3ba, (R)-3bb, and
(R)-3bd with good yields in an enantiomerically pure form under
the previously optimized conditions (Scheme 1).
HPLC (tR:39.3 min); HRMS (E.I.) m/z (Mþ) 291.9414 (calcd for
C9H10OSI 291.9418).
3.3. Synthesis of 1-bromo phenyl vinyl sulfoxide (1e)
A solution of phenyl vinyl sulfoxide (1 equiv, 50 mmol) in carbon
tetrachloride (50 mL) was added dropwise to a solution of bromine
(2 equiv, 100 mmol) in carbon tetrachloride (85 mL) cooled at
ꢂ20 ꢀC in an N2 atmosphere over an 18-h period. The mixture was
stirred at ꢂ20 ꢀC for 1 h and then DBU (2 equiv, 100 mmol) dis-
solved in carbon tetrachloride (30 ml) was added, and the mixture
was stirred at room temperature for 30 min. The organic layer was
washed with Na2S2O3 aqueous satd (50 mL), dried over anhydrous
Na2SO4, and concentrated to dryness. The crude material was pu-
rified by flash column chromatography (hexane/ethyl acetate 30:1)
:
Pd(PPh3)4
CsF, THF
Ar
:
p-Tol
ArB(OH)
+
2
S
Ar
p-Tol
S
O
I
O
(R)-3 (yield) (ee)a
a
1b
(S)-
(>99%ee)
to yield sulfoxide 1a (65%) colorless oil. 1H NMR (CDCl3)
J¼3.2 Hz, 1H), 6.83 (d, J¼3.2 Hz, 1H), 7.44e7.47 (m, 3H), 7.62e7.65
(m, 2H); 13C NMR (CDCl3) 122.2, 125.8, 129.2, 132.0, 136.0, 141.4;
HMRS m/z 229.9392 (calcd for C8H7BrOS 229.9400).
d 6.15 (d,
[α]D=+68.2
Ph
3ba (79) (>99)
3bb
p-MeOC6H4
p-CF3C6H4
(73) (>99)
(67) (>99)
3bd
aHPLC column
3.4. Palladium-catalyzed Suzuki/Miyaura reaction. General
procedure A
Scheme 1. Palladium-catalyzed Suzuki cross-coupling of chiral sulfoxide
(S)-1b with boronic acids.
A mixture of 1-bromo phenyl vinyl sulfoxide 1e (1 equiv,
0.4 mmol), boronic acid 2 (2eq, 0.8 mmol), CsF (4 equiv, 1.6 mmol),
and Pd(PPh3)4 (10 mol %, 0.04 mmol) was added to a flask fitted
with degassed and dry THF (6 mL). After being refluxed for 3 h, the
reaction mixture was cooled to room temperature, diluted with
ethyl acetate (5 mL) and filtered over CeliteÒ. Then the solution
was evaporated under reduced pressure. The crude material was
purified by flash column chromatography (hexane/ethyl acetate
20:1).
To conclude, despite other reports in the bibliography about the
lack of reactivity of bromovinyl sulfoxides,17 they are an effective
partner for palladium-catalyzed coupling with aryl or alkenyl bo-
ronic acids. The synthesis of the alkenyl and dienyl sulfoxide de-
rivatives described herein constitutes a new and valuable route for
these compounds with high yields. The transformation is also
demonstrated to be efficient for the conversion of enantiopure
halovinyl sulfoxides in the corresponding arylated derivatives
without modifying optical purity. These results show the compat-
ibility of palladium catalysis with the presence of a chiral sulfinyl
moiety in substrates.
3.4.1. [1-(Phenylsulfinyl)vinyl]benzene (3ea). Yield: 84%, oil; 1H
NMR (CDCl3) 5.84 (s, 1H), 6.17 (s, 1H), 7.12e7.36 (m, 10H); 13C
NMR (CDCl3) 116.2, 125.1, 127.5, 128.5, 128.8, 129.0, 131.0, 133.5,
142.6, 154.2; HRMS (E.I.) m/z (Mþ) 228.0617 (calcd for C14H12OS
228.0608).
3. Experimental section
3.1. General methods and materials
3.4.2. 1-Methoxy-4-[(1-phenylsulfinyl)vinyl]benzene (3eb). Yield:
89%, oil; 1H NMR (CDCl3) 3.70 (s, 3H), 5.77 (s, 1H), 6.11 (s, 1H), 7.07
(d, J¼8.7 Hz, 2H), 7.73 (d, J¼8.7 Hz, 2H), 7.22e7.38 (m, 5H); 13C NMR
(CDCl3) 55.2, 113.9, 115.2, 125.1, 125.8, 128.8, 128.9, 131.0, 142.8,
153.7, 160.1; HRMS (E.I.) m/z (Mþ) 258.0725 (calcd for C15H14O2S
258.0714).
Proton magnetic resonance and carbon magnetic resonance
were recorded at 300 MHz and 75 Hz, respectively, with a Bruker
AC-300. Chemical shifts are reported in
d parts per million in re-
lation to the TMS peak at 0.0 ppm (1H spectra) and to the CDCl3
peak at 77.0 ppm (13C spectra). High resolution mass spectra were
determined on a Fisons VG Autospec instrument. All the melting
points were recorded with a Cambridge Instruments apparatus.
Reactions were monitored by analytical thin layer chromatography
using commercial aluminum sheets pre-coated (0.2 mm layer
thickness) with silica gel 60 F254 (E. Merck), and visualization was
done with short wavelength UV light (254 nm). Product purifica-
tion by flash chromatography was performed using E. Merck Silica
Gel (230e400 mesh). The HPLC tests were carried out with a Chir-
acel IC column (25ꢁ0.46 cm) and hexane: 2-propanol 50:50 as el-
uents (flow 1.0). Commercial reagents were supplied by Aldrich,
except Pd(PPh3)4 (Johnson Matthey), and they were used without
further purification.
3.4.3. 1-Methyl-4-[(1-phenylsulfinyl)vinyl]benzene
(3ec). Yield:
2.25 (s, 3H), 5.82 (s, 1H), 6.16 (s, 1H),
85%; oil; 1H NMR (CDCl3)
d
7.00e7.04 (m, 4H), 7.26e7.30 (m, 3H), 7.37e7.40 (m, 2H); 13C NMR
(CDCl3) 21.2, 115.6, 125.1, 127.3, 128.8, 129.2, 131.0, 139.0, 142.8,
154.1; HRMS (E.I.) m/z (Mþ) 242.0751 (calcd for C15H14OS
242.0765).
3.4.4. 1-Trifluoromethyl-4-[(1-phenylsulfinyl)vinyl]benzene (3ed).
Yield: 75%; mp55e57 ꢀC; 1H NMR (CDCl3)
d 5.91 (s, 1H), 6.23 (s, 1H),
7.19e7.37 (m, 7H), 7.44e1.47 (m, 2H); 13C NMR (CDCl3) 115.5, 120.1
(q, J¼223.2 Hz), 125.1, 125.4 (q, J¼3.8 Hz), 127.9, 129.0, 130.9 (q,
J¼32.7 Hz), 131.4, 137.0, 141.9, 153.3; 19F NMR (CDCl3)
d
ꢂ73.2;
3.2. Preparation of starting materials
HRMS (E.I.) m/z (Mþ) 296.0456 (calcd for C15H11F3OS 296.0482).
3.2.1. (þ)-1-Iodo-1-[(S)-p-tolylsulfinyl]ethane ((S)-1b)17. Yield 85%;
white solid; mp 82e83 ꢀC; 1H NMR (CDCl3) 2.34 (s, 3H), 6.52 (d,
J¼2.9 Hz, 1H), 7.30 (d, J¼7.9 Hz, 2H), 7.39 (d, J¼2.9 Hz, 2H), 7.54 (d,
J¼8.2, 2H); 13C NMR (CDCl3) 21.5, 116.8, 125.8, 129.9, 130.4, 138.8,
3.4.5. 1-Nitro-3-[(1-phenylsulfinyl)vinyl]benzene (3ee). Yield: 53%;
1H NMR (CDCl3) 5.92 (d, J¼0.7 Hz, 1H), 6.27 (d, J¼0.7 Hz, 1H),
7.22e7.44 (m, 7H), 7.85 (t, J¼1.9 Hz, 1H), 8.01 (ddd, J¼8.1, 2.2, and
1.3 Hz 1H); 13C NMR (CDCl3) 119.6, 112.5, 123.7, 125.1, 129.2, 129.5,

6904
G. Mancha et al. / Tetrahedron 66 (2010) 6901e6905
131.7, 133.5, 141.7, 148.0, 152.7; HRMS (E.I.) m/z (Mþ) 273.0448
(calcd for C14H11NO3S 273.0459).
J¼272 Hz), 125.5 (q, J¼3.8 Hz), 127.8, 130.3, 130.9 (JCeF¼32.6 Hz),
25
137.3, 138.8, 142.1, 153.4; 19F NMR (CDCl3; 75.5 MHz) ꢂ92.9. [
a]
D
þ71.7 (c 1.4, CHCl3); HPLC (tR: 8.0 min); HRMS (E.I.) m/z (Mþ)
3.4.6. 1-Methoxy-2-[(1-phenylsulfinyl)vinyl]benzene
(3ef). Yield:
3.58 (s, 3H), 5.75 (s, 1H), 6.32 (s, 1H),
310.0637 (calcd for C16H13F3OS 310.0639).
90%; oil; 1H NMR (CDCl3)
d
6.70e6.78 (m, 3H), 7.16e7.30 (m, 6H); 13C NMR (CDCl3) 55.3, 110.7,
117.5, 120.3, 122.4, 125.1, 128.4, 130.4, 130.6, 130.8, 143.0, 152.3,
157.7; HRMS (E.I.) m/z (Mþ) 258.0725 (calcd for C15H14O2S
258.0714).
3.5. Phosphine-free Suzuki/Miyaura coupling. General
procedure B
A mixture of 1-bromo phenyl vinyl sulfoxide 1e (1 equiv,
0.4 mmol), aryl boronic acid 2 (2q, 0.8 mmol), Pd(OAc)2 (10 mol %),
DABCO (20 mol %), CsF (3 equiv) was added to a flask fitted with
degassed and dry THF (6 mL), and was stirred at 80 ꢀC for the re-
quired time and was monitored by TLC. The reaction mixture was
cooled to room temperature, diluted with ethyl acetate (5 mL) and
filtered over CeliteÒ. Then the solution was evaporated under re-
duced pressure. The crude material was purified by flash column
chromatography (hexane/ethyl acetate 20:1).
3.4.7. 1-Methyl-2-[(1-phenylsulfinyl)vinyl]benzene (3eg). Yield: 87%
; oil; 1H NMR (CDCl3)
d 1.80 (s, 3H), 5.90 (s, 1H), 6.29 (s, 1H), 6.74
(dd, J¼7.4 and 1.1 Hz,1H), 6.95e7.02 (m, 2H), 7.08e7.29 (m, 6H); 13C
NMR (CDCl3) 19.0, 116.9, 124.8, 125.4, 128.6, 128.9, 129.9, 130.1,
131.0, 132.2, 137.0, 141.9, 154.0; HRMS (E.I.) m/z (Mþ) 242.0776
(calcd for C15H14OS 242.0765).
3.4.8. 1-(Pivaloylamino) 2-[(1-phenylsulfinyl)vinyl]benzene (3eh).
Yield: 68%; oil; 1H NMR (CDCl3) 1.13 (s, 9H), 5.74 (s, 1H), 6.36 (s, 1H),
6.47 (dd, J¼7.7 Hz, 1H), 6.81 (td, J¼7.6 Hz, 1H), 7.19e7.31 (m, 6H),
7.88 (dd, J¼8.3 and 0.8 Hz, 1H), 8.42 (s, br s); 13C NMR (CDCl3) 27.5,
39.6, 122.8, 123.4, 123.7, 124.1, 124.6, 128.9, 129.8, 130.3, 131.3, 136.7,
141.0, 153.4, 177.1; HRMS (E.I.) m/z (Mþ) 327.1299 (calcd for
C19H21NO2S 327.1293).
Acknowledgements
Financial support by the Spanish Dirección General de Inves-
tigación Científica y Técnica Consolider Ingenio 2010 (CSD2007-
00006), (CTQ2007-65720) and the Generalitat Valenciana (G.M.
grant) is gratefully acknowledged. We gratefully acknowledge
SCSIE (Universidad de Valencia) for access to the instrumental
facilities.
3.4.9. 1-Trifluoromethyl-2-[(1-phenylsulfinyl)vinyl]benzene (3ei).
Yield: 80%; mp 77e80 ꢀC; 1H NMR (CDCl3)
d 5.78 (s, 1H), 6.36 (s,
1H), 6.72 (d, J¼7.5 Hz, 1H), 7.23e7.35 (m, 7H), 7.55 (d, J¼7.6 Hz, 1H);
13C NMR (CDCl3) 119.2, 123.4 (q, J¼274.2 Hz), 126.5 (q, J¼5.3 Hz),
127.8 (q, J¼5.3 Hz), 128.7, 129.0, 129.7 (q, J¼30.4 Hz), 131.1, 131.4,
Supplementary data
Supplementary data associated with this article can be found in
the online version at doi:10.1016/j.tet.2010.06.050. These data in-
clude MOL files and InChIKeys of the most important compounds
described in this article.
131.8, 134.6, 141.5, 152.1; 19F NMR (CDCl3)
d
ꢂ68.1; HRMS (E.I.) m/z
(Mþ) 296.0468 (calcd for C15H11F3OS 296.0482).
3.4.10. 1-Bromo-2-[(1-phenylsulfinyl)vinyl]benzene
(3ej). Yield:
80%; oil; 1H NMR (CDCl3) 5.71 (s, 1H), 6.33 (s, 1H), 6.66e6.69 (m,
1H), 6.98e7.05 (m, 2H), 7.18e7.29 (m, 5H), 7.35e7.40 (m, 1H); 13C
NMR (CDCl3) 119.0, 123.5, 125.0, 126.9, 128.76, 130.2, 131.3, 131.4,
132.9, 133.9, 141.7, 153.7; HRMS (E.I.) m/z (Mþ) 305.9720 (calcd for
C14H11BrOS 305.9713).
References and notes
1. (a) Brebion, F.; Goddard, J.-P.; Fensterbank, L.; Malacria, M. Org. Lett. 2008, 10,
1917; (b) .Viso, A.; Fernandez de la Pradilla, R.; Urena, M.; Colomer, I. Org. Lett.
2008, 10, 4775; (c) Marino, J. P.; Rubio, M. B.; Cao, G.; de Dios, A. J. Am. Chem. Soc.
2002, 124, 13398; (d) Loughlin, W. A.; Rowen, C. C.; Healy, P. C. J. Chem. Soc.,
Perkin Trans.
2 2002, 296; (e) Midura, W. H.; Krysiak, J. A.; Cypryk, M.;
Mikolajczyk, M.; Wieczorek, M. W.; Filipczak, A. D. Eur. J. Org. Chem. 2005, 653;
(f) Craig, D.; Daniels, K.; MacKenzie, A. R. Tetrahedron Lett. 1991, 32, 6973.
2. (a) Fernández de la Pradilla, R.; Baile, R.; Tortosa, M. Chem. Commun. 2003,
2476; (b) Carreño, M. C.; Urbano, A.; Di Vitta, C. Chem.dEur. J. 2000, 6, 906; (c)
Carreño, M. C.; Urbano, A.; Di Vitta, C. Chem. Commun. 1999, 817; (d) Carretero,
J. C.; García-Ruano, J. L.; Martín-Cabrejas, L. M. Tetrahedron: Asymmetry 1997, 8,
2215; (e) Yuste, F.; Ortiz, B.; Israel Pérez, J.; Rodríguez-Hernández, A.; Sánchez-
Obregón, R.; Walls, F.; García Ruano, J. L. Tetrahedron 2002, 58, 2613.
3. (a) Garcia Ruano, J. L.; Fraile, A.; Martin, M. R.; Gonzalez, G.; Fajardo, C. J. Org.
Chem. 2008, 73, 8484; (b) García Ruano, J. L.; Fraile, A.; Martín, M. R.; Núñez, A.
J. Org. Chem. 2006, 71, 6536.
4. (a) Wedel, T.; Gehring, T.; Podlech, J.; Kordel, E.; Bihlmeier, A.; Klopper, W.
Chem.dEur. J. 2008, 14, 4631; (b) Fernández de la Pradilla, R.; Manzano, P.;
Montero, C.; Priego, J.; Martínez-Ripoll, M.; Martínez-Cruz, L. A. J. Org. Chem. 2003,
68, 7755; (c) Fernández de la Pradilla, R.; Buergo, M. V.; Manzano, P.; Montero, C.;
Priego, J.; Viso, A.; Cano, F. H.; Martínez-Alcázar, M. P. J. Org. Chem. 2003, 68, 4797;
(d) Fernández de la Pradilla, R.; Fernández, J.; Manzano, P.; Méndez, P.; Priego, J.;
Tortosa, M.; Viso, A.; Martínez-Ripoll, M.; Rodríguez, A. J. Org. Chem. 2002, 678,
8166; (e) Loughlin, W. A.; McCleary, M. A. Org. Biomol. Chem. 2003, 1, 1347; (f)
Fernández de la Pradilla, R.; Castro, S.; Manzano, P.; Martín-Ortega, M.; Priego, J.;
Viso, A.; Rodríguez, A.; Fonseca, I. J. Org. Chem. 1998, 63, 4954.
3.4.11. (E)-1(Octa-1,3-dien-2-ylsulfinyl)benzene (3ek). Yield: 85%;
oil; 1H NMR (CDCl3) 0.68 (t, J¼7.1 Hz, 3H), 0.95e1.158 (m, 4H),
1.84e1.91 (m, 2H), 5.58 (s, 1H), 5.79e5.85 (m, 3H), 7.12 (s, 1H),
7.30e7.35 (m, 3H), 7.49e7.53 (m, 2H); 13C NMR (CDCl3) 13.8, 22.0,
30.7, 32.7, 115.2, 122.1, 125.5, 129.0, 131.1, 136.9, 143.4, 151.1; HRMS
(E.I.) m/z (Mþ) 234.1064 (calcd for C8H7BrOS 234.1078).
3.4.12. (R)-1-Methyl-4-(1-phenylvinylsulfinyl)benzene ((R)-3ba).
Yield 79%; white solid; mp 105e109 ꢀC; 1H NMR (CDCl3) 2.24 (s,
3H), 5.84 (s, 1H), 6.17 (s, 1H), 7.04 (d, J¼8.0 Hz, 2H), 7.10e7.14 (m,
2H), 7.18e7.20 (m, 3H), 7.25 (d, J¼8.2 Hz, 2H); 13C NMR (CDCl3) 21.3,
116.1, 125.4, 127.4, 128.5, 128.9, 129.6, 133.7, 139.4, 141.6, 154.3. [a]
D
þ117 (c 1.27, CHCl3); HPLC (tR: 13.8 min); HRMS (E.I.) m/z (Mþ)
242.0760 (calcd for C15H14OS 242.0765).
3.4.13. (R)-1-Methyl-4-(1-(p-tolylsulfinyl)vinil)benzene ((R)-3bb).
Yield 73%; white solid; mp 99e103 ꢀC; 1H NMR (CDCl3) 2.30 (s, 6H),
5.88 (s, 1H), 6.20 (s,1H), 7.05e7.13 (m, 6H), 7.32 (d, J¼8.2 Hz, 2H); 13C
NMR (CDCl3) 21.2, 21.4, 115.5, 125.4, 127.3, 129.2, 129.6, 130.9, 138.9,
5. (a) Fernandez de la Pradilla, R.; Montero, C.; Tortosa, M.; Viso, A. Chem.dEur. J.
2009, 15, 697; (b) Fernández de la Pradilla, R.; Montero, C.; Tortosa, M. Org. Lett.
2002, 4, 2373.
6. (a) Díaz Buezo, N.; de la Rosa, J. C.; Priego, J.; Alonso, I.; Carretero, J. C. Chem.d
Eur. J. 2001, 7, 3890; (b) Díaz, N.; Carretero, J. C. J. Am. Chem. Soc. 1998, 120, 7129.
7. Rodríguez Rivero, M.; Alonso, I.; Carretero, J. C. Chem.dEur. J. 2004, 10, 5443.
8. Mori, K.; Ohmori, K.; Suzuki, K. Angew. Chem., Int. Ed. 2009, 48, 5633.
9. (a) Baciocchi, E.; Gerini, M. F.; Lapi, A. J. Org. Chem. 2004, 69, 3586; (b) Craig, D.;
Daniels, K.; Marsh, A.; Dainford, R.; Smith, A. M. Synlett 1990, 531; (c)
Mikolajczyk, M.; Perlikowska, W. O.; Melanczuk, J.; Crzstau, H. J.; Perraudarcy,
A. Synlett 1991, 913.
139.6, 141.6, 154.1. [
a
]
þ77.6 (c 1.39, CHCl3); HPLC (tR: 12.4 min);
D
HRMS (E.I.) m/z (Mþ) 256.0921 (calcd for C16H16OS 256.0921).
3.4.14. (R)-1-Methyl-4-(1-(4-(trifluoromethyl)phenyl)vinylsulfinyl)
benzene ((R)-3bd). Yield 67%; Orange oil; 1H NMR (CDCl3) 2.31 (s,
3H), 5.98 (s, 1H), 6.33 (s, 1H), 7.14 (d, J¼7.9 Hz, 2H), 7.29e7.34 (m,
4H), 7.52 (d, J¼8.09 Hz, 2H); 13C NMR (CDCl3) 21.4, 118.3, 123.1 (q,
10. Mikolajczyck, M.; Perlikowska, W.; Omelanczuk, J.; Cristau, H. J.; Perraud-Darcy,
A. J. Org. Chem. 1998, 83, 9716.

G. Mancha et al. / Tetrahedron 66 (2010) 6901e6905
6905
11. (a) Huang, X.; Duan, D.; Zheng, W. J. Org. Chem. 2003, 68, 1938; (b) Zhong, O.;
Guo, M.-P.; Huang, X. J. Chem. Res., Synop. 2000, 588; (c) Zhong, P.; Huang, X.;
Guo, M.-P. Tetrahedron 2000, 56, 8921.
12. (a) Hogg, D. R. In The Chemistry of Sulfenic Acids and their Derivatives; Patai, S.,
Ed.; John Wiley: Chischester UK, 1990; p 361; (b) Van den Breok, L. A. G. M.;
Delbresine, L. P. C.; Ottenheim, J. C. J. In The Chemistry of Sulfenic Acids and their
Derivatives; Patai, S., Ed.; John Wiley: Chischester, UK, 1990; p 701; (c) Kosugi,
H.; Kitaoka, M.; Tagami, K.; Takahashi, A.; Uda, H. J. Org. Chem. 1987, 52, 1078;
(d) Posner, G. H.; Tang, P. W. J. J. Org. Chem. 1978, 43, 4131; (e) Cardellicchio, C.;
Fiandenese, V.; Naso, F. J. Org. Chem. 1992, 57, 1718.
13. (a) Transition Metal for Organic Synthesis; Be ller, M., Bolm, C., Eds.; Wiley-VCH:
Weinheim, 2004; Vol. 1; (b) Tsuji, J. Transition Metal Reagents and Catalysts;
Wiley: Chichester, UK, 2000.
14. (a) Colobert, F.; Valdivia, V.; Choppin, S.; Leroux, F. R.; Fernandez, I.; Alvarez, E.;
Khiar, N. Org. Lett. 2009, 11, 5130; (b) Broutin, P.-E.; Colobert, F. Org. Lett. 2005, 7,
3737.
16. (a) García-Ruano, J. L. Top. Curr. Chem. 1999, 204, 1; (b) Carreño, M. C. Chem. Rev.
1995, 95, 1717.
17. Paley, R. S.; de Dios, A.; Estroff, L. A.; Lafontaine, J. A.; Montero, C.; McCulley, D.
J.; Rubio, M. B.; Ventura, M. P.; Weers, H. L.; Fernández de la Pradilla, R.; Castro.,
S.; Dorado, R.; Morente, M. J. Org. Chem. 1997, 62, 6326.
18. Miyaura, N.; Suzuki, A. Chem. Rev. 1995, 95, 2457.
19. Cardellicchio, C.; Fiandanese, V.; Naso, F.; Scilimati, A. Tetrahedron Lett. 1992, 33,
5121.
20. Miyaura, N. Cross-Coupling Reactions; Springer: Berlin Heidelberg, 2002.
21. (a) Jackstell, R.; Gómez Andreu, M.; Frisch, A.; Selvakumar, K.; Zaft, A.; Klein, H.;
€
Spanenberg, A.; Rottger, D.; Betel, O.; Karch, R.; Beller, M. Angew. Chem., Int. Ed.
2002, 41, 986; (b) Fürstner, A.; Leitner, A. Synlett 2001, 290; (c) McGuiness, D. S.;
Cavell, K. J. Organometallics 2000, 41, 595; (d) Zim, D.; Gruber, A. S.; Ebelling, G.;
Dupont, J.; Monteiro, A. I. Org. Lett. 2000, 2, 2881; (e) Botella, L.; Nájera, C. Angew.
Chem.,Int. Ed.2002, 41,179;(f)Reetz, M.T.;deVries, J.G.Chem. Commun. 2004,1559.
22. (a) Grasa, G. A.; Hillier, A. C.; Nolan, S. P. Org. Lett. 2001, 3, 1077; (b) Grasa, G. A.;
Singh, R.; Stevens, E. D.; Nolan, S. P. J. Organomet. Chem. 2003, 687, 269.
23. (a) Li, J.-H.; Liang, Y.; Wang, D.-P.; Liu, W.-J.; Xie, Y.-X.; Yin, D.-L. J. Org. Chem.
2005, 70, 2832; (b) Li, J.-H.; Zhu, Q.-M.; Xie, Y.-X. Tetrahedron 2006, 62, 10888;
(c) Li, J.-H.; Zhang, X.-D.; Xie, Y.-X. Synthesis 2005, 804.
15. (a) Rodríguez, N.; Cuenca, A.; Ramírez de Arellano, C.; Medio-Simón, M.;
Asensio, G. Org. Lett. 2003, 5, 1705; (b) Rodríguez, N.; Cuenca, A.; Ramírez de
Arellano, C.; Medio-Simón, M.; Peine, D.; Asensio, G. J. Org. Chem. 2004, 69,
8070.