Enhanced product selectivity in the Mizoroki-Heck reaction using a supercritical carbon dioxide-liquid biphasic system

Article abstract of DOI:10.1039/b006846m

Arylation of ethylene catalysed by Pd complexes bearing triphenyl phosphite ligands proceeds efficiently in a scCO₂-liquid biphasic system to give a mixture of arylated products; the selectivity of monoarylated products, styrene derivatives, can be improved by increasing the CO₂ pressure, where the monoarylated products are effectively extracted from the liquid reaction phase into the scCO₂ phase to prevent over-reactions to diarylated products.

Full text of DOI:10.1039/b006846m

Enhanced product selectivity in the Mizoroki–Heck reaction using a
supercritical carbon dioxide–liquid biphasic system
Yoshihito Kayaki, Yushi Noguchi and Takao Ikariya*
Graduate School of Science and Engineering, Tokyo Institute of Technology and CREST, Japan Science and
Technology Corporation, O-okayama, Meguro-ku, Tokyo 152-8552, Japan. E-mail: tikariya@o.cc.titech.ac.jp
Received (in Cambridge, UK) 23rd August 2000, Accepted 2nd October 2000
First published as an Advance Article on the web 31st October 2000
Arylation of ethylene catalysed by Pd complexes bearing
triphenyl phosphite ligands proceeds efficiently in a scCO2–
liquid biphasic system to give a mixture of arylated products;
the selectivity of monoarylated products, styrene deriva-
tives, can be improved by increasing the CO2 pressure, where
the monoarylated products are effectively extracted from the
liquid reaction phase into the scCO2 phase to prevent over-
reactions to diarylated products.
There has been extensive interest in supercritical fluids (SCFs)
as reaction media for molecular catalysis.1 Their unique
physical properties tuned by a small change in the pressure and
temperature allows improved performance of molecular cata-
lysts in terms of the reaction rates and selectivities.2 Besides
these benefits for catalysis, the use of SCFs can also offer great
opportunities to solve the frequently encountered problem of
efficient separation of the molecular catalysts by controlling the
pressure of the media.3 Recently, a biphasic reaction system
consisting of a supercritical fluid phase and a solvent phase
including H2O was examined for the purpose of separating and
recycling metal catalysts.4 In the case where CO2-insoluble
substrates form the liquid phase under supercritical or sub-
critical CO2 conditions, the high volatility of CO2 allows it to
help selectively remove the CO2-soluble product from the
reaction phase, resulting in a solvent-free reaction. However,
the catalyst performance in such a multiphase system has not
been systematically investigated except for a recent report on
solvent-free synthesis under subcritical CO2 conditions.5,6 We
now report Mizoroki–Heck arylation of ethylene in a CO2–
liquid biphasic system in which monoarylated products can be
preferentially obtained in condensed CO2 where the selectivity
is controllable by a change in the pressure of CO2.
The arylation of ethylene with aryl halides has been well
investigated in liquid solvents.7 In a single reaction phase, the
initial products, styrene derivatives are subject to further
reaction with aryl halides to afford stilbenes and 1,1-diphenyl-
ethylenes, resulting in a significant decrease in the selectivity
for the monoarylation. If one of the desired products, styrene in
this case, has high solubility in scCO2 compared to that of the
byproducts, the use of scCO2 will enable the separation of the
initial product from the liquid phase8 to suppress the subsequent
reactions of styrene (Fig. 1).
Fig. 1 Schematic illustration of phases during a scCO2–liquid biphasic
Mizoroki–Heck reaction. At the initial stage of the reaction, aryl halide,
amine and some amine·HX salt are precipitated as a liquid containing the Pd
catalyst. At the final stage of the reaction, an excess amount of amine and
amine·HX salt form a liquid phase and monoarylated product is extracted
into the scCO2 phase. Ar = aryl group, X = I, Br in this case.
PdCl2{P(OC6H5)3}2 (1) is the best choice of catalyst for the
arylation because of its excellent activity10 and suitable
solubility (discussed later) under the reaction conditions at
130 °C and 100 atm.‡ Although complex 1 has been found to
partially dissolve in scCO2 under the same conditions,11 it
should stay in the liquid phase rather than the scCO2 phase
because of its higher solubility in the liquid substrates phase.
The reaction of iodobenzene with ethylene (10 atm) catalysed
by the P(OC6H5)3–Pd complex 1 (substrate/catalyst = 1000+1)
at 130 °C in the presence of N(C2H5)3 as a base proceeded
rapidly to an almost quantitative conversion under solvent-free
conditions (without CO2). As listed in Table 1, styrene was
obtained in 57% selectivity along with (E)-stilbene and
1,1-diphenylethylene in 31 and 11% yields, respectively.
Notably, as illustrated in Fig. 2, the selectivity for the styrene
formation was remarkably improved with an increase in the
pressure of CO2 above the critical pressure of 73 atm to attain
over 80% at 100 atm and the same temperature. Further increase
in the pressure above 100 atm resulted in the selectivity
approaching 100% albeit with a significant drop in the yield.
The decrease in the total efficiency at higher CO2 pressures was
We first examined the phase behaviour of iodobenzene,
ethylene, N(C2H5)3 and styrene under subcritical and super-
critical CO2 conditions.† A visual inspection of these com-
pounds in a window-equipped 50 mL reactor vessel confirmed
that 1.0 mmol of styrene was completely dissolved in scCO2
under 100 atm at 130 °C whereas some droplets of iodobenzene
were observed under the same conditions. In the presence of
subcritical CO2 gas, these materials, except ethylene, precipitate
to form the liquid phase where a neat reaction can be performed.
Thus, the significant difference in the solubility of these
compounds in scCO2 should allow one to extract styrene
preferentially from the liquid phase, leading to the efficient
control of the styrene formation.9
a
Table 1 Mizoroki–Heck reaction of iodobenzene with C2H4 in scCO2
Conv. Styrene Yield 1,1-Diphenylethylene+
Run Medium
(%)
(Sel.) (%)
(E)-stilbene
1
2
3
4
5
6
7
—
95
54 (57)
64 (65)
68 (69)
68 (71)
82 (83)
29 (92)
18 (99)
2.8+1
4+1
3.4+1
1.8+1
3.3+1
N.d.
CO2, 25 (atm) > 99
CO2, 50
CO2, 75
CO2, 100
CO2, 125
CO2, 150
> 99
95
> 99
32
19
N.d.
a Reaction was conducted at 130 °C for 18 h, in a 50 mL reaction vessel
containing 10 mmol of Pd catalyst 1, iodobenzene and triethylamine.
Iodobenzene+1+N(C2H5)3 = 1,000+1+1,400.
The screening experiments with Pd catalyst bearing tertiary
phosphine
or
phosphite
ligands
revealed
that
DOI: 10.1039/b006846m
Chem. Commun., 2000, 2245–2246
This journal is © The Royal Society of Chemistry 2000
2245

ethylene under neat conditions without CO2 to give products in
moderate selectivity as shown in Table 2 (Run 1). Using
CH3CN as a liquid solvent, the reaction proceeded to 74%
conversion after 96 h to give the monoarylated product in 82%
selectivity (Runs 2 and 3). In contrast to these liquid phase
reactions, the outcome of the reaction in the scCO2–liquid
biphasic system was significantly improved, the styrene
selectivity increasing from 68 to 88% at near complete
conversion after 18 h (Run 4).13
In conclusion, the arylation of ethylene catalysed by Pd
complex with phosphite ligands selectively afforded mono-
arylated products in the scCO2–liquid biphasic system. A
combination of the rapid reaction in the liquid phase and the
extraction of the product with scCO2 provided a significant
improvement in the product selectivity.
Notes and references
† Safety warning: Operators of high-pressure equipment should take proper
precautions to minimize the risk of personal injury.
‡ Standard procedure for the arylation: The reactor was charged with argon
gas and was placed in the oven at 130 °C before introduction of reagents. A
mixture of the substrate (1.0 mmol), base (1.4 mmol) and DMF (0.01 mL)
solution of Pd catalyst (0.01 mmol) was added into the reactor with a syringe
through an opening against the flow of CO2. Subsequently, C2H4 (10 atm)
was introduced, and then CO2 (0–150 atm) was added with an HPLC pump.
After stirring for 18 h, the reactor was cooled in a bath of methanol with dry
ice. The mixture of C2H4 and CO2 was vented, and the reactor was slowly
warmed to rt. The yields of products were determined by GC analyses.
Fig. 2 Selectivity and conversion profile as a function of the CO2 pressure
for the reaction of iodobenzene 2a and ethylene catalysed by Pd complex 1
in condensed CO2. Condition: C6H5I+N(C2H5)3+Pd catalyst
=
1000+1400+1, C2H4 10 atm.
mainly due to the disappearance of the liquid phase since
everything dissolved in the scCO2, where the homogeneous
reaction in scCO2 possibly occurred. In fact, separate experi-
ments showed that the arylation using CO2-soluble trialkyl
phosphite–Pd catalysts12 in the homogeneous scCO2 phase did
not provide turnover numbers higher than those obtained in the
liquid phase. These results, in addition to the phase behaviour
discussed above, clearly indicate that below 100 atm of CO2
pressure the reaction occurs rapidly mainly in the liquid phase
to give the initial product styrene, which is effectively extracted
in the scCO2 phase because of its reasonably high vapor
pressure (430 mmHg at 125 °C) and high solubility in scCO2
under the reaction conditions. The use of supercritical or even
subcritical gaseous CO2 might help to separate the desired
product from the liquid reaction phase into the scCO2 or vapor
phase to avoid further reactions which may produce undesired
multiarylated products.
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A remarkable advantage of this biphasic system can be
demonstrated by the reaction of p-bromotoluene substrate/
catalyst = 100) and ethylene (10 atm) catalysed by complex 1
in the presence of (DBU) and 1-ethylpiperidine (Table 2). A
mixture of these bases serves as an efficient promoter for the
less reactive bromoarenes possibly because of their strong
basicity. Although the reaction of the bromoarene proceeded
much more slowly than that of iodoarene, it reacted with
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Heitz, W. Brügging, L. Freund, M. Gailberger, A. Greiner, H. Jung, U.
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9 A similar reaction–extraction system consisting of water and super-
critical butene phases is now being used at Idemitsu Petrochemical Co.
in Japan. The hydration of butene proceeds in an aqueous phase to give
butan-2-ol, which can be extracted by supercritical butene. T. Yamada
and T. Muto, Sekiyu Gakkaishi, 1991, 34, 201.
Table 2 Pd-catalysed reaction of p-bromotoluene and ethylene in scCO2 and
other mediaa
10 Some examples of the catalytic activity of PdCl2L2 complexes under the
same conditions (conversion after 18 h), L = CH3CN 13%, P(OC2H5)3
44%, P(n-C4H9)3 52%, P(OC6H5)3 94%, T. Ikariya, to be published.
11 Some examples of the solubility of PdCl2L2 complexes (mol L21 at 200
atm and 80 °C): L = P(n-C4H9)3 5.6 3 1023; P(OC2H5)3 8.8 3 1024
;
CH3CN 2.5 3 1025; P(OC6H5)3 7.5 3 1025. T. Ikariya, to be
published.
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Commun., 1999, 1235.
13 The homogeneous Mizoroki–Heck reaction of aryl iodides and activated
olefins such as methyl acrylate in scCO2 has been studied by several
groups. However, there are no examples of simple bromoarene as the
substrate; (a) M. A. Carroll and A. B. Holmes, Chem. Commun., 1998,
1395; (b) D. K. Morita, D. R. Pesiri, S. A. David, W. H. Glaze and W.
Tumas, Chem. Commun., 1998, 1397; (c) N. Shezad, R. S. Oakes, A. A.
Clifford and C. M. Rayner, Tetrahedron Lett., 1999, 40, 2221.
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Chem. Commun., 2000, 2245–2246