Palladium-catalyzed desulfitative Mizoroki-Heck coupling reactions of sulfonyl chlorides with olefins in a nitrile-functionalized ionic liquid

Article abstract of DOI:10.1055/s-2006-944198

Aryl and alkenyl sulfonyl chlorides can be used in Heck-Mizoroki-type couplings with mono- and disubstituted olefins in a nitrile-functionalized ionic liquid, viz. [C₃CNpy] [Tf₂N]. Advantages over previously reported methods include: (1) use of a cheap catalyst source, PdCl₂, (2) ability to handle the catalyst in air, (3) reduced reaction times, (4) elimination of phase-transfer catalysts due to the high solubility of the inorganic base in the ionic liquid, and (5) facile recycling of the ionic liquid-palladium catalyst. The yields of coupling products remain in the same range as the reactions conducted in organic solvents. Palladium nanoparticles, characterized using transmission electron microscopy, have been identified in the ionic liquid following the Heck-Mizoroki type coupling reactions. Georg Thieme Verlag Stuttgart.

Full text of DOI:10.1055/s-2006-944198

LETTER
3155
Palladium-Catalyzed Desulfitative Mizoroki–Heck Coupling Reactions of
Sulfonyl Chlorides with Olefins in a Nitrile-Functionalized Ionic Liquid
M
izoroki–Hec
r
kCoupl
i
n
ctions of Su
i
C
v
hlorides
w
it
a
hOlefins s Reddy Dubbaka,a Dongbin Zhao,b Zhaofu Fei,b Chandra M. Rao Volla,a Paul J. Dyson,*b Pierre Vogel*a
a
Laboratory of Glycochemistry and Asymmetric Synthesis, Swiss Federal Institute of Technology (EPFL), BCH 1015 Lausanne,
Switzerland
Fax +41(21)6939375; E-mail: pierre.vogel@epfl.ch
b
Laboratory of Organometallic and Medicinal Chemistry, Swiss Federal Institute of Technology (EPFL), BCH 1015 Lausanne,
Switzerland
Received 21 December 2005
aware, ionic liquids (ILs) have not been used in transition-
metal-catalyzed reactions using sulfonyl chlorides as re-
actants.
Abstract: Aryl and alkenyl sulfonyl chlorides can be used in Heck–
Mizoroki-type couplings with mono- and disubstituted olefins in a
nitrile-functionalized ionic liquid, viz. [C3CNpy][Tf2N]. Advan-
tages over previously reported methods include: (1) use of a cheap
catalyst source, PdCl2, (2) ability to handle the catalyst in air, (3)
reduced reaction times, (4) elimination of phase-transfer catalysts
due to the high solubility of the inorganic base in the ionic liquid,
and (5) facile recycling of the ionic liquid-palladium catalyst. The
yields of coupling products remain in the same range as the reac-
tions conducted in organic solvents. Palladium nanoparticles, char-
acterized using transmission electron microscopy, have been
identified in the ionic liquid following the Heck–Mizoroki type
coupling reactions.
In the last few years ionic liquids have proven to be highly
useful solvents in catalysis and also in organic synthesis.11
There are several reports on Stille,12 Suzuki–Miyaura,13
Sonogashira–Hagihara,14 cross-coupling reactions and
regioselective Heck arylations15 with aryl halides under
ionic liquids. Various benefits have been noted, including:
(i) assisting in the activation of the catalyst, (ii) improve-
ment of the stability of the catalyst, (iii) excellent immo-
bilization and recyclability, (iv) facilitating product
isolation, and (v) influencing the selectivity of the reac-
tion.
Key words: Mizoroki–Heck reaction, ionic liquids, palladium,
sulfonyl chlorides, nanoparticles
Following our previous studies that have shown nitrile-
functionalized ionic liquids to be highly effective solvents
for conducting various C–C cross-coupling reactions,16
we selected N-butyronitrile pyridinium bis(trifluoro-
methylsulfonyl)imide (IL 1, Scheme 2) for the reactions
described herein together with PdCl2 (1 mol%), as the pre-
catalyst since it can be handled in air and is comparatively
cheap (this precatalyst, in IL 1 was as active as
Herrmann’s catalyst17 in organic solvent, see below).
Dissolution of PdCl2 in IL 1 results in the formation of the
complex shown in Scheme 2.
Transition-metal-catalyzed C–C bond-forming reactions
are among the most useful and versatile methods in or-
ganic synthesis.1,2 In recent years, various methodologies
have been developed, such as Mizoroki–Heck protocol,
that permit the cross-coupling of a large variety of
reactants (Scheme 1).3
metal cat.
Ar
Ar–X +
R
R
X : I, Br, Cl, N2+X–, OTf,
SO2Cl, COCl, etc.
(CH2)3CN
(CH2)3CN
Tf2N
N
Cl(CH2)3CN
N
R : Ar, Alkyl
Li[Tf2N]
N
Cl
Scheme 1 Substrates for general Mizoroki–Heck-type reactions
1
(CH2)3CN
Tf2N
The Mizoroki–Heck arylation of alkenes is of high
synthetic utility,1,2 and aryl chlorides and alkenes can be
coupled under decarbonylative conditions.3 We have
shown that the readily available sulfonyl chlorides
(RSO2Cl, R = aryl, alkenyl, methallyl,4 benzyl) undergo
desulfitative Stille and carbonylative Stille,5 Suzuki–
Miyaura,6 Sonogashira–Hagihara7 and Negishi8 cross-
coupling reactions and Mizoroki–Heck arylations.9 The
sulfonyl chlorides are generally more reactive than corre-
sponding bromides and chlorides.7,8,10 As far as we are
(CH2)3CN
PdCl2
2 Tf2N
N
PdCl2
N
2
1
Scheme 2 Synthesis of N-butyronitrile pyridinum and their
palladium complex
Our exploratory experiments started with the coupling of
1-naphthalenesulfonyl chloride (1.5 mmol) with butyl
acrylate (3.5 mmol) in the presence of PdCl2 (1 mol%),
Me(Oct)3NCl (15 mol%), and K2CO3 (2.25 mmol) in IL 1
(2 mL). All materials were handled in air although the
reaction was subsequently conducted under a blanket of
nitrogen. After 1.5 hours at 140 °C (cf. 4 h to achieve the
SYNLETT 2006, No. 18, pp 3155–3157
0
3
.1
1
.2
0
0
6
Advanced online publication: 29.06.2006
DOI: 10.1055/s-2006-944198; Art ID: S12705ST
© Georg Thieme Verlag Stuttgart · New York

3156
S. Reddy Dubbaka et al.
LETTER
same conversion in m-xylene in the presence of a phase- reactions in ILs and often they can be isolated and/or
transfer agent)9 the coupling product was extracted from reused.19 The palladium nanoparticles isolated from IL 1
IL 1 using diethyl ether. Starting material was not detected have a narrow size disparity (1.5–4.5 nm), similar to those
in the extract and the yield of the product (90%) was isolated following Stille coupling reactions reported
estimated by GC using an external standard. The IL was previously.16 As shown in Figure 1, three ILs employed in
recharged with starting materials (as above) and after two catalysis (entries 2, 5, and 7 from Table 1) were selected
hours at 140 °C the product was isolated in 85% yield for TEM analysis. From the figure it is clear that the
following extraction into diethyl ether. IL 1 was charged palladium nanoparticles are well dispersed and separated;
with further starting materials (third batch) and the reac- nanoparticle aggregates are not observed. Nanoparticle
tion was repeated with only a slight decrease in catalytic aggregation during a catalytic process in ILs has been ob-
activity, viz. 82% yield.
served previously,20 but with the nitrile functionalized IL
1, no such detrimental effect was observed. TEM analysis
of the ionic liquids taken after the first recyle shows that
the palladium nanoparticles remain unchanged. It is not
unreasonable to assume that the nitrile group on the IL
provides a stabilizing effect. The EDX spectrum shows
that the nanoparticles are composed of palladium.
The same reaction was conducted in the absence of
Me(Oct)3NCl which resulted in the same catalytic ac-
tivity.
Using these optimized conditions the desulfitative cou-
pling of electron-rich, electron-neutral and electron-poor
sulfonyl chlorides with various olefins was conducted, see
Table 1. We also prepared a 1,3-diene in the reaction of
trans-b-styrenesulfonyl chloride with styrene under these
conditions (entry 10).
TEM analysis of the IL solutions after catalysis reveals
that palladium nanoparticles were formed during the
process (Figure 1). Transition-metal nanoparticles have
been implicated as catalysts or catalyst reservoirs in many
Table 1 Palladium-Catalyzed Desulfitative Mizoroki–Heck-Type
Reactions of Various Sulfonyl Chlorides with Terminal Alkenes in IL
118
1 mol% PdCl2
1–1.5 equiv K2CO3
R
R-SO2Cl +
R1
2.5 equiv
R1
N
1 equiv
N
Tf2N
140 °C, 1–2 h
Entry
R
R1
Yield (%)a
90
1
2
1-Naphthyl
COOn-Bu
Ph
1-Naphthyl
80 (78)
75 (70)
80
3
4-Methylphenyl
4-Methylphenyl
4-Acetylphenyl
4-Methoxyphenyl
3-Cyanophenyl
COOn-Bu
Ph
4
5
COOn-Bu
COOn-Bu
COOn-Bu
70
6
75b
7
70b
8
(4-Trifluoromethyl)phenyl SO2Ph
50b
9
Trifluoromethyl
COOn-Bu
Ph
35c
10
(E)-PhCH=CH
90 (86)
Figure 1 TEM images of nanoparticles in ionic liquids taken from
catalytic system and graphs showing nanoparticle size distribution (1
for entry 2, 2 for entry 5, and 3 for entry 7).
a Yields of coupling products determined by GC using diphenyl-
methane as a external standard, see general procedure, value in paren-
theses corresponds to the isolated yield.
b At 140 °C for 3 h.
c Using a microwave oven at 150 °C for 2 h.
Synlett 2006, No. 18, 3155–3157 © Thieme Stuttgart · New York

LETTER
Mizoroki–Heck Coupling Reactions of Sulfonyl Chlorides with Olefins
3157
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In conclusion, we have demonstrated for the first time that
desulfitative Mizoroki–Heck-type arylation of alkenes
can be performed using sulfonyl chlorides in an IL. In
addition, TEM analysis of nanoparticles extracted from
the catalysis solution shows that palladium nanoparticles,
which presumably act as catalyst reservoirs, are formed. It
appears that a stabilizing effect on the nanoparticles is im-
parted by the nitrile-functionalized IL 1. Such functional-
ized ionic liquids may well prove to be decisive in
transferring ionic liquids from the laboratory to produc-
tion-scale processes in C–C bond-forming reactions. The
[C3CNpy][Tf2N] ionic liquid described herein can be
prepared from relatively inexpensive precursors, which
provides further incentive for its deployment on a larger
scale.
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Acknowledgment
We thank the Swiss National Science Foundation (Grant 200020-
108105) and the ‘Secrétariat d’Etat à l’Education et à la Recherche’
(Grant SER No. 03.0738) for financial support.
References and Notes
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(18) General Procedure for Desulfitative Palladium-
Catalyzed Mizoroki–Heck Reaction of Sulfonyl
Chlorides with Monosubstituted Olefins
To a Schlenk tube, the sulfonyl chloride (1 equiv, 1.5 mmol),
PdCl2 (1 mol%, 0.015 mmol), K2CO3 (1.5 equiv, 2.25
mmol), Me(Oct)3NCl (15 mol%, 0.23 mmol) and IL 1 (2
mL) were added. After the mixture was flushed with
nitrogen, the olefin (2.0 equiv, 3.0 mmol) was added. The
reaction mixture was heated at 140 °C for 1–2 h. After
cooling to r.t., the product was extracted with Et2O (3 × 15
mL). The combined extracts were washed with brine and
H2O and then dried with Na2SO4. The coupling product was
obtained after removal of solvent. An external standard
(diphenylmethane, 0.6 mmol) was used for GC analysis. The
ionic liquid phase was washed with Et2O and placed under
vacuum for 18 h prior to the next catalytic cycle.
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Synlett 2006, No. 18, 3155–3157 © Thieme Stuttgart · New York