A comparative study of some Pd-catalysed Heck reactions in polar- and aqueous biphasic media

Article abstract of DOI:10.1081/SCC-100104429

A comparative study of some Pd-catalysed reactions was carried out making use of various ligands and catalyst precursors in polar polar/aqueous biphasic media, the results of which assist in the judicious selection of the appropriate reaction conditions f

Full text of DOI:10.1081/SCC-100104429

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A COMPARATIVE STUDY OF SOME Pd-CATALYSED HECK
REACTIONS IN POLAR- AND AQUEOUS BIPHASIC MEDIA
D. Bradley G. Williams a , Henriëtte Lombard a & Cedric W. Holzapfel a
a Department of Chemistry and Biochemistry , Rand Afrikaans University , P.O. Box 524,
Auckland Park, 2006, South Africa
Published online: 09 Nov 2006.
To cite this article: D. Bradley G. Williams , Henriëtte Lombard & Cedric W. Holzapfel (2001) A COMPARATIVE STUDY
OF SOME Pd-CATALYSED HECK REACTIONS IN POLAR- AND AQUEOUS BIPHASIC MEDIA, Synthetic Communications: An
International Journal for Rapid Communication of Synthetic Organic Chemistry, 31:13, 2077-2081, DOI: 10.1081/
SCC-100104429
To link to this article: http://dx.doi.org/10.1081/SCC-100104429
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SYNTHETIC COMMUNICATIONS, 31(13), 2077–2081 (2001)
A COMPARATIVE STUDY OF SOME
Pd-CATALYSED HECK REACTIONS IN
POLAR- AND AQUEOUS BIPHASIC MEDIA
D. Bradley G. Williams,* Henriette Lombard,
and Cedric W. Holzapfel
Department of Chemistry and Biochemistry,
Rand Afrikaans University, P.O. Box 524,
Auckland Park, 2006, South Africa
ABSTRACT
A comparative study of some Pd-catalysed reactions was car-
ried out making use of various ligands and catalyst precursors
in polar polar/aqueous biphasic media, the results of which
assist in the judicious selection of the appropriate reaction
conditions for such Heck reactions.
The advent of palladium catalysed reactions in aqueous or biphasic
media has brought about a flurry of activity in the area. Various groups
have worked in this sphere, and have made some decisive contributions.
Primary among these are the contributions to water-soluble ligands.1
Although most of the ligands revolve around suphonated aryl phosphines,2
some other solutions to the problem of the solubilisation of the ligands have
been forthcoming. These include cationic ammonium-based systems3 and
*Corresponding author. E-mail: dbgw@na.rau.ac.za
2077
Copyright & 2001 by Marcel Dekker, Inc.
www.dekker.com

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WILLIAMS, LOMBARD, AND HOLZAPFEL
carboxylated ligands.4 The recent seminal work of Beletskaya has shown
that the need for polar ligands in aqueous reactions is not an absolute.5 In
these latter cases, Pd(OAc)2 was used without a ligand in pure water or in
DMF/H2O or HMPA/H2O mixtures. We herein wish to present a compara-
tive study of various reaction conditions (including the presence or absence
of ligands) on the outcome of a few Heck reactions in polar or biphasic
solvents. This study was carried out as part of our interest in Pd-mediated
reactions,6 and with the intention of extending some of this work to aqueous
reaction media. However, we could find no comparative study in which
certain reaction parameters were directly compared, and thus believed
that such a study would contribute to the knowledge base of those in, or
entering, this field.
As a basic reaction, we selected the Heck reaction between iodo-
benzene and butyl acrylate (Scheme 1).7 Various combinations of polar
solvent, solvent-water mixtures, ligand and added base were tested. The
results are shown in Table 1. (The arrangement in the table is primarily
on the basis of catalyst, and secondarily on the basis of solvent.) The
table shows that DMF or DMF/H2O are almost invariably the solvents
of choice for this reaction, and that the origin of the catalyst [Pd(OAc)2
vs. Pd(dba)2] made little difference to the yield of the reaction in most cases.
(In some cases, however, Pd(OAc)2 proved to be the superior catalyst pre-
cursor.)
Scheme 1.
A similar reaction set was attempted with bromobenzene without
much success, presumably due to the lack in reactivity of the bromo-sub-
strate under our reaction conditions. As a result, we made use of 4-bromo-
benzonitrile as a substrate in subsequent reactions (Scheme 2).8 (It is well
known that electron-withdrawing substituents on the aryl halide enhance
the rate of oxidative addition of the substrate to the Pd atom.)
Scheme 2.

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Table 1. Reaction Conditionsa and Isolated Yields for the Heck Reaction
Yield
Entry
Solvent
Ligand
Pd-catalyst
Base
(%)
1
2
MeOH
TPPTSb 20%
TPPTS 20%
None
TPPTS 20%
TPPTS 20%
None
TPPTS 10%
TPPTS 10%
TPPTS 20%
TPPTS 20%
None
Pd(dba)2
Pd(dba)2
Pd(dba)2
Pd(dba)2
Pd(dba)2
Pd(dba)2
Pd(dba)2
Pd(dba)2
Pd(dba)2
Pd(dba)2
Pd(dba)2
Pd(dba)2
Pd(dba)2
NEt3
NEt3
K2CO3
NEt3
NEt3
K2CO3
NEt3
NEt3
NEt3
NEt3
NEt3
NEt3
K2CO3
NEt3
NEt3
K2CO3
NEt3
NEt3
K2CO3
NEt3
NEt3
NEt3
NEt3
NEt3
NEt3
K2CO3
78
55
5
MeOH/H2O
MeOH
3CN
CH3CN/H2O
CH3CN/H2O
DMF
DMF/H2O
DMF
DMF/H2O
DMF
3
4CH
5
6
7
8
9
10
11
12
13
14MeOH
15
16
17
18
19
20
21
22
23
24DMF
25
26
23
75
53
80
75
65
73
75
76
23
40
55
15
38
58
35
58
85
76
80
98
95
73
DMF/H2O
DMF/H2O
None
None
TPPTS 20%
Pd(OAc)
2
MeOH/H2O
MeOH
CH3CN
CH3CN/H2O
CH3CN/H2O
DMF
DMF/H2O
DMF
DMF/H2O
TPPTS 20%
None
TPPTS 20%
TPPTS 20%
None
TPPTS 10%
TPPTS 10%
TPPTS 20%
TPPTS 20%
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
None
Pd(OAc)
2
DMF/H2O
DMF/H2O
None
None
Pd(OAc)2
Pd(OAc)2
a Standard reaction conditions: iodobenzene, butyl acrylate (1 eq.), solvent (mixtures
are 1:1 v/v), base (1.5 eq.), catalyst (0.1 eq.), 80ꢀC, 24h.
b TPPTS ¼ trisodium 3,30,300-phosphinidyne(benzenesulphonic acid).
The results of those reactions are displayed in Table 2. Reactions were
carried out in DMF or in DMF/H2O due to superiority of these solvents
over the others tested. It is clear from the table that higher reaction tem-
peratures were required to effect a satisfactory reaction. The difference in
yield when increasing the temperature from 90 to 100 to 110ꢀC was the most
striking feature displayed in this comparison. Of equal mention is the lack of
reactivity of the substrate in the absence of ligand (Entries 6–8).

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WILLIAMS, LOMBARD, AND HOLZAPFEL
Table 2. Outcome of the Reactiona of 4-bromobenzonitrile and Butyl Acrylate
Under Pd-catalysis
Temp.
ꢀC
Yield
(%)
Entry
Solvent
DMF
DMF
DMF
TPPTS 20%
DMF/H2O
DMF
Ligand
Pd-catalyst
1
2
TPPb 20%
TPP 20%
TPP 20%
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
90
100
110
110
110
110
110
110
29
74
83
64
48
10
5
3
4DMF
5
6
7
8
Pd(OAc)
2
TPPTS 20%
None
None
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(dba)2
DMF/H2O
DMF
None
4
a Standard reaction conditions: bromobenzonitrile, butyl acrylate (1 eq.), solvent
(mixtures are 1:1 v/v), base (1.5 eq.), catalyst (0.1 eq.), 24h.
b TPP ¼ triphenylphosphine.
The results detailed above shed some light on the influence of certain
variations in the reaction conditions on the Heck reaction in a polar or
polar/aqueous medium. It seems as though DMF is universally the solvent
of choice, and Pd(OAc)2 the catalyst of choice. It is important to note that,
while the elegant work of Beletskaya has shown that the presence of a ligand
is not necessary in some cases, the current work indicates that a ligand is
essential to a successful reaction when working with bromo substrates in
polar or aqueous biphasic media. In this regard, some sensitivity in the
reaction was shown with regard to the specific ligand employed (compare
TPP and TPPTS, Table 2).
ACKNOWLEDGMENTS
We are indebted to SASOL, South Africa, for financial support of
this work.
REFERENCES
1. Cornils, B. and Herrmann, W.A. eds., Aqueous-Phase Organometallic
Catalysis: Concepts and Applications, Wiley-VCH, 1998.
2. Genet, J.P. and Savignac, M. J. Organomet. Chem. 1999, 576, 305.
3. Mohr, B.; Lynn, D.M. and Grubbs, R.H. Organometallics 1996,
15, 4317.

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Pd-CATALYZED HECK REACTIONS
2081
4. Jegorov, A. and Podlaha, J. Catal. Lett. 1991, 9, 9.
5. Bumagin, N.A.; More, P.G.; Beletskaya, I.P. J. Organomet. Chem.
1989, 371, 397.
6. van Heerden, F.R.; Huyser, J.J.; Williams, D.B.G. and Holzapfel, C.W.
Tetrahedron Lett. 1998, 39, 5281. Holzapfel, C.W. and Williams,
D.B.G. Tetrahedron 1995, 51(31), 8555.
7. This product has been previously prepared: Manfred, T.R.;
Breinbauer, T.R. and Wanniger, K. Tetrahedron Lett. 1996, 37, 4499.
Miyazaki, F.; Yamaguchi, K. and Shibasaki, M. Tetrahedron Lett.
1999, 40, 7379.
8. This Heck product has been previously prepared: Beller, M.; Fisher, H.;
Klaus, K. and Herrmann, W.A. J. Organomet. Chem. 1996, 250, 257.
Herrmann, W.A.; Brossmer, C.; Oefele, K.; Priermeier, T.; Beller, M.
and Fisher, H. Angew. Chem. Int. Ed. Engl. 1995, 37, 1844.
Received in the Netherlands September 19, 2000

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