Palladium catalysed allylation reactions in ionic liquids

Article abstract of DOI:10.1039/a903323h

Palladium catalysed allylic alkylation and amination reactions have been demonstrated to proceed readily in the room temperature ionic liquid 1-butyl-3-methylimidazolium tetrafluoroborate ([bmim][BF₄]) with easy catalyst/solvent recycling and n

Full text of DOI:10.1039/a903323h

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Palladium catalysed allylation reactions in ionic liquids
Weiping Chen, Lijin Xu, Craig Chatterton and Jianliang Xiao*
Leverhulme Centre for Innovative Catalysis, Department of Chemistry, University of Liverpool, Liverpool, UK
L69 7ZD. E-mail: j.xiao@liv.ac.uk
Received (in Cambridge, UK) 26th April 1999, Accepted 24th May 1999
Palladium catalysed allylic alkylation and amination reac-
tions have been demonstrated to proceed readily in the room
temperature ionic liquid 1-butyl-3-methylimidazolium tetra-
fluoroborate ([bmim][BF4]) with easy catalyst/solvent re-
cycling and no need to generate separately the carbanion
nucleophiles.
temperature, and the reaction started by adding the substrates
and K2CO3. H NMR monitoring showed that the alkylation
1
was complete after 5 h reaction time at ambient temperature.
The initial rate was slightly lower, due perhaps to the
dissolution of the substrates and base or to the formation of
active Pd0 species at the beginning of the reaction. A few
variables have been identified to be important for the success of
the alkylation in [bmim][BF4] (Table 1). (i) As with allylic
alkylations in molecular solvents,13 no reaction takes place in
the ionic liquid without PPh3. (ii) The reaction rate decreases
markedly when the molar ratio of PPh3+Pd(OAc)2 is less than
4+1. Thus, with 3 equiv. (relative to palladium acetate) of PPh3,
the conversion of the acetate was only 50% after 15 h reaction
time and, with 1 equiv. of PPh3, a much lower conversion of
13% was observed. (iii) The reaction is slower without initial
heating of Pd(OAc)2 and PPh3 in [bmim][BF4]. Thus, heating of
Pd(OAc)2 and PPh3 with the substrates in the absence of
[bmim][BF4] followed by reaction in the ionic liquid at ambient
temperature for 15 h afforded only a 68% conversion. As a base,
K2CO3 and DBU are equally effective but, in the case of the
latter, the reaction mixture is homogeneous. K2CO3 only partly
dissolves in [bmim][BF4] under the reaction conditions. The
quantity of palladium used can be lowered to 0.2 mol% without
affecting the 100% conversion for reactions carried out
overnight.
Using the procedures developed for dimethyl malonate, the
alkylation was extended to the active methylene compounds B–
F. The results are summarised in Table 2. All the reactions were
completed with 100% conversion within the time indicated
when using DBU as the base. The lower yield obtained with the
acetylacetone C was partly due to double alkylation. Alkylation
of the amido malonate F was sluggish at room temperature, but
the reaction proceeded smoothly at 50 °C to give the product
with 86% isolated yield. For the reactions involving methyl
acetoacetate B and methyl cyanoacetate D, the product was a
1:1 mixture of two diastereomers. Replacing DBU with K2CO3
resulted in lower conversions for the substrates B–F under
identical conditions; the reason is not immediately clear.
Using similar procedures, we also tested the amination of
1,3-diphenylallyl acetate. The amination by pyrrolidine pro-
Room temperature ionic liquids consisting of 1,3-dialkylimida-
zolium cations and their counter ions have attracted growing
interest in the last few years.1–8 These ionic liquids offer an
attractive alternative to conventional organic liquids for clean
synthesis, as they are easy to recycle and possess no effective
vapor pressure. As with water and perfluoro solvents, they also
offer the potential for easy catalyst/product separation, owing to
their limited miscibility with many common organic liquids. A
few types of catalytic reactions have been carried out in these
and related ionic liquids; recent examples include Friedel–
Crafts reactions,1,4 Diels–Alder reactions,2 alkylations,3 olefin
dimerisation and oligomerisation,5–7,9 hydrogenation,8 Heck
reaction10 and hydroformylation.11 We report herein the first
examples of palladium catalysed allylic alkylation and amina-
tion reactions in the ionic liquid [bmim][BF4]. [bmim][BF4] has
a liquid range down to 281 °C. It is miscible with polar
compounds such as lower alcohols but immiscible with less
polar compounds such as toluene and Et2O. Many organome-
tallic compounds have been found to display good solubility in
this liquid.
Palladium(0) catalysed allylic alkylations of soft carbon
nucleophiles represent a very useful tool for organic synthesis.12
As summarised by Hegedus, the alkylation reactions are usually
conducted by mixing stabilised carbanions with a substrate-
catalyst mixture in THF and then heating the resultant mixture
at reflux.13 The carbanions are generated separately using bases
such as NaH in dipolar solvents like THF. Catalyst and solvent
recycling, which will undoubtedly be difficult with conven-
tional solvents, has rarely been addressed for these reactions.14
Prompted by Seddon’s recent report on in situ generation of
anions in the alkylaton of indole and 2-naphthol in
[bmim][PF6],3 we examind the room temperature, one-pot
alkylation of the active methylene compounds A–F by 1,3-di-
phenylallyl acetate in [bmim][BF4] (Scheme 1). The results are
presented below.
Table 1 Palladium catalysed allylic alkylations in [bmim][BF4] under
various conditionsa
The alkylation of dimethyl malonate A by 3-acetoxy-
1,3-diphenylprop-1-ene was investigated first. The catalyst or
catalyst precursor was formed by heating Pd(OAc)2 (2 mol%,
based on the acetate) with PPh3 (8 mol%) in [bmim][BF4] at 80
°C for 20 min. The ionic liquid was then cooled to ambient
PPh3/Pd(OAc)2 t/h
Conversion (%)
0
1
2
3
4
4
4
48
15
15
15
5
0
13
36
50
OAc
Ph
Nu
100
68b
100c
Pd(OAc)2/PPh3, base
[bmim][BF4]
+
NuH
15
15
Ph
Ph
Ph
a
O
General reaction conditions: 1.0 mmol of 3-acetoxy-1,3-diphenylprop-
CO2Me COMe
CO2Me CO2Me
CN
COMe
O
O
CO2Et
CO2Et
1-ene, 2 mol% Pd(OAc)2, 1.5 mmol of dimethyl malonate and 2.0 mmol of
K2CO3 in 1 ml of [bmim][BF4] at ambient temperature. Before starting the
reaction, Pd(OAc)2 and PPh3 were heated at 80 °C for 20 min in the ionic
NuH =
AcHN
CO2Me
COMe
b
liquid. Pd(OAc)2, PPh3 and the substrates were heated at 80 °C before
O
c
introducing the base and ionic liquid at ambient temperature. 0.2 mol%
A
B
C
D
E
F
Pd(OAc)2.
Scheme 1
Chem. Commun., 1999, 1247–1248
1247

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Table 2 Palladium catalysed allylations in [bmim][BF4] with various
attractive ‘greener’ alternative to the conventional processes
where volatile organic solvents are frequently employed and
catalyst reuse is difficult to implement.
We are indebted to the EPSRC and the University of
Liverpool Graduates Association (Hong Kong) for postdoctoral
research fellowships (W. C. and L. X.), and to the Leverhulme
Centre for Innovative Catalysis for a LCIC studentship (C. C.).
nucleophilesa
NuH
Base
t/h
Yield (%)b
A
B
C
D
E
F
K2CO3
DBU
DBU
DBU
DBU
DBU
5
15
15
14
15
12
91
87c
54
88c
79
86d
Notes and references
1 A. Stark, B. L. MacLean and R. D. Singer, J. Chem. Soc., Dalton Trans.,
1999, 63.
2 T. Fischer, A. Sethi, T. Welton and J. Woolf, Tetrahedron Lett., 1999,
40, 793.
a The reaction conditions were the same as the general reaction conditions
given in Table 1, unless otherwise indicated. All the reactions completed
with 100% conversion. b Isolated yield. c The product was a 1:1 mixture of
two diastereomers. d Reaction was carried out at 50 °C.
3 M. J. Earle, P. B. McCormac and K. R. Seddon, Chem. Commun., 1998,
2245.
4 C. J. Adams, M. J. Earle, G. Roberts and K. R. Seddon, Chem.
Commun., 1998,2097.
5 L. C. Simon, J. Dupont and R. F. de Souza, Appl. Catal. A: Gen., 1998,
175, 215.
6 J. E. L. Dullius, P. A. Z. Suarez, S. Einloft, R. F. de Souza, J. Dupont,
J. Fischer and A. DeCian, Organometallics, 1998, 17, 815.
7 Y. Chauvin, H. Olivier, C. N. Wyrvalski, L. C. Simon and R. F. de
Souza, J. Catal., 1997, 165, 275.
8 A. L. Monteiro, F. K. Zinn, R. F. de Souza and J. Dupont, Tetrahedron:
Asymmetry, 1997, 8, 177.
9 B. Ellis, W. Keim and P. Wasserscheid, Chem. Commun., 1999, 337.
10 W. A. Herrmann and V. P. W. Bohm, J. Organomet. Chem., 1999, 572,
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references therein.
ceeded readily to give the corresponding 1,3-diphenylallyl-
amine with 100% conversion. Unlike the alkylations, no
additional base is required in this transformation.
Catalyst separation/recycling appears to be difficult under the
conditions established above, because the organic compounds
and the ionic liquids form a homogeneous mixture and so
catalyst separation via phase separation is not feasible. Further,
extraction of the products with solvents of various polarity
resulted in significant leaching of palladium species out of the
ionic liquid. However, replacing PPh3 with the hydrophilic
phosphine P(m-C6H4SO3Na)3 led to effective recycling of the
catalyst-containing ionic liquid phase; the catalyst along with
the ionic liquid was reused three times without losing activity in
the alkylation of dimethyl malonate. The product was extracted
with toluene after each cycle of the reaction.
In summary, we have demonstrated that allylic alkylation and
amination can effectively be performed in the room temperature
ionic liquid [bmim][BF4] with the additional benefit of easy
catalyst/solvent recycling. Ionic liquids like this provide an
ideal environment where ionic intermediates may be generated
in situ and stabilised therein. Reactions in such media offer an
13 L. S. Hegedus, in Organometallics in Synthesis, ed. M. Schlosser,
Wiley, Chichester, 1994.
14 R. Kling, D. Sinou, G. Pozzi, A. Choplin, F. Quignard, S. Busch, S.
Kainz, D. Koch and W. Leitner, Tetrahedron Lett., 1998, 39, 9439.
Communication 9/03323H
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Chem. Commun., 1999, 1247–1248