Palladium/tetraphosphine catalysed Heck reaction with ortho-substituted aryl bromides

Article abstract of DOI:10.1055/s-2001-18752

The tetraphosphine cis,cis,cis-1,2,3,4-tetrakis(diphenylphosphinomethyl)cyclopentane associated to [PdCl(C₃H₅)]₂ catalyses the Heck reaction of butyl acrylate with a wide range of sterically demanding aryl bromides, furnis

Full text of DOI:10.1055/s-2001-18752

1980
LETTER
Palladium/Tetraphosphine Catalysed Heck Reaction with ortho-Substituted
Aryl Bromides
P
alladium/Tetraphosph
a
ine
c
atalys
r
e
d
H
eck
i
Reacti
e
Laboratoire de Synthèse Organique associé au CNRS, Faculté des Sciences de St-Jérôme, Avenue Escadrille Normandie-Niemen,
13397 Marseille Cedex 20, France
Fax +33(491)983865; E-mail: henri.doucet@lso.u-3mrs.fr; E-mail: m.santelli@lso.u-3mrs.fr
Received 24 July 2001
1,2,3,4-tetrakis(diphenylphosphino-methyl)cyclopentane
Abstract: The tetraphosphine cis,cis,cis-1,2,3,4-tetrakis(diphe-
or tedicyp 19a (Figure). The presence of four phosphines
close to the metal centre seems to increase the coordina-
tion of the ligand to the metal and therefore increases the
nylphosphinomethyl)cyclopentane associated to [PdCl(C3H5)]2 ca-
talyses the Heck reaction of butyl acrylate with a wide range of
sterically demanding aryl bromides, furnishing the addition product
in high yields. Turnover numbers as high as 630–89000 have been stability of the catalyst. A very high efficiency has been
observed in allylic substitution,9 and for Suzuki cross-
obtained using ortho-substituted aryl bromides and 43–2600 with
di-ortho-substituted aryl bromides in the presence of this catalyst.
coupling using tedicyp as the ligand.10 We have also re-
Key words: catalysis, palladium, tetraphosphine, Heck reaction,
aryl bromides
ported recently the first results obtained for Heck reac-
tions.11 For example, a TON of 210000000 for the
reaction of 3,5-bistrifluoromethylbromobenzene with bu-
tyl acrylate acid was observed. While Pd/tedicyp provided
The Heck reaction is one of the most widely used palladi- an efficient method for accomplishing Heck reaction, we
um-catalysed methodology in organic synthesis.1 Howev- felt that important challenges remained, including demon-
er this reaction is sensitive to the steric effects of the strating the broader scope particularly with respect to ster-
substituents which are on the aryl halide and on the olefin. ically demanding substrates. In this paper, we wish to
Most catalysts do not effectively couple hindered sub- report the efficiency of this ligand for the Heck reaction
strates. With hindered aryl bromides low reaction rates are using ortho and di-ortho-substituted aryl bromides.
often observed, and with sterically hindered olefins the re-
action is even slower. In general, fast decomposition of
Ph2P
PPh2
Ph2P
the catalysts occurs. A few ligands have been employed
PPh2
with sterically hindered aryl bromides. The most popular
ones are triphenylphosphine2 or tri-ortho-tolylphosphine.3
Even if the catalysts formed by association of these
Tedicyp 1
ligands with palladium complexes are quite efficient in
terms of yield of adduct, the efficiency in terms of ratio
substrate/catalyst is low. In general 1–10% of these cata-
lysts must be used. In recent years a few more robust cat-
alysts have been prepared and tested with these substrates.
For example, Herrmann et al. have reported that the
palladacycle4 [Pd(o-tol)(OAc)]2 is efficient for the reac-
tion of 2-bromotoluene with n-butyl acrylate.5 Very re-
cently, Fu et al. described that the ligand P(t-Bu)3 is also
an efficient catalyst for sterically hindered substrates even
at room temperature.6 A few other ligands also led to use-
ful catalysts.7 If monophosphines or palladacycles have
been successfully used for the reaction with sterically hin-
dered aryl bromides, to the best of our knowledge, the ef-
ficiency of tetraphosphines ligands has not yet been
demonstrated.
Figure
First, we studied the influence of the presence of one
ortho substituent at the aryl bromide on the rate of the re-
action. For this study, based on our previous results,11
DMF was chosen as the solvent and potassium carbonate
as the base. The reactions were performed at 130 °C in the
presence of a ratio 1/2 of [Pd(C3H5)Cl]2/tedicyp as cata-
lyst. Although this catalyst is quite air-stable,11 the reac-
tions were performed under argon. As illustrated in the
Table, using these conditions, we observed that the cou-
pling of 2-methylbromobenzene with n-butyl acrylate in
the presence of 0.01% catalyst led to the addition adduct
in 78% yield (TON 7800) (Scheme). A slightly higher re-
action rate was obtained using similar conditions with 1-
bromonaphthalene (TON 43000). With 2-bromobiphenyl,
2-bromoanisole or 2,4-dimethoxy-bromobenzene lower
reaction rates were observed (TONs 630–2100). On the
other hand, in the presence of activated aryl bromides
such as 2-fluorobromobenzene, 2-trifluoromethylbro-
mobenzene, 2-bromobenzaldehyde, 2-bromobenzonitrile
or 2-bromonitrobenzene high reaction rates are observed
(2500–89000). Next, we turned our attention to the reac-
tion with 2-bromophenol, and we also observed very high
The nature of phosphine ligands has an important effect
on the rate of transition-metal catalysed reactions. In order
to find more efficient palladium catalysts we have pre-
pared a new tetrapodal8 phosphine ligand, cis,cis,cis-
Synlett 2001, No. 12, 30 11 2001. Article Identifier:
1437-2096,E;2001,0,12,1980,1982,ftx,en;G15601ST.pdf.
© Georg Thieme Verlag Stuttgart · New York
ISSN 0936-5214

LETTER
Palladium/Tetraphosphine catalysed Heck Reaction
1981
Table Palladium/tedicyp catalysed Heck Reaction12
reaction rates. However, with this substrate we also ob-
served the formation of an important amount of coumarin,
which comes from the cyclisation of n-butyl 2-hydroxy-
cinnamate. A longer reaction time led to complete trans-
formation on this hydroxycinnamate into coumarin. This
cyclisation is not palladium-catalysed: in absence of pal-
ladium, using similar reaction conditions (DMF, K2CO3,
130 °C), the cyclisation also proceeds. The Heck reaction
was also performed using 2-bromoaniline. With this sub-
strate relatively high reaction rates were also observed,
however several side products were formed.
Aryl
Ligand
Ratio
Time (h) Yield (%)
bromide
substrate–
catalyst
2-methyl-bro-
mobenzene
1
1
1
1000
10000
100000
20
20
48
100a
78
14a
1-bromo-
naphthalene
1
1
10000
100000
72
20
91
43a
2-bromo-
biphenyl
1
1
1
1000
1000
10000
20
48
20
57a
95
8a
Next, we tried to evaluate the difference of reaction rate
between mono- and di-ortho-substituted aryl bromides
and we were pleased to find that the reaction proceeds ef-
ficiently even on very hindered aryl bromides, although
lower reaction rates were observed than with mono-ortho-
substituted aryl bromides. For example, with 9-bromoan-
thracene, 1-bromo-2-methylnaphthalene and 1-bromo-2-
methoxynaphthalene TONs of 450–2600 were obtained.
A very significant steric effect was observed in the pres-
ence of the extremely sterically demanding aryl bromides
1-bromo-2,6-dimethylbenzene and 1-bromo-2,4,6-triiso-
propylbenzene. For these substrates TONs of 380 and 43
were obtained, respectively.
2-bromo
anisole
1
1
1000
10000
48
20
72
21a
2,4-dimethoxy-
bromobenzene
1
1000
20
63
2-fluoro-bro-
mobenzene
1
1
1
10000
10000
100000
20
48
20
66a
94
7a
2-trifluorometh-
yl-bromobenzene
1
1
1
1000
10000
10000
20
20
48
90
62a
97a
Finally, in order to present a simple procedure using a
commercially available ligand, we performed a few reac-
tions with dppe. Palladium catalyst prepared with dppe as
ligand is less active than with 1 by a factor of ten; however
the system [Pd(C3H5)Cl]2/dppe (ratio 1/2) is much more
stable and efficient than the popular but unstable catalyst
Pd(PPh3)4. With dppe good yields were obtained with 2-
bromobenzaldehyde or 2-bromobenzonitrile in the pres-
ence of 0.1% catalyst.
2-bromo-benzal- dppe
1000
1000
10000
20
20
48
88
98a
72
dehyde
1
1
2-bromo-benzo- dppe
1000
10000
100000
1000000
20
20
20
20
95
100a
89
nitrile
1
1
1
7a
2-bromo-nitro-
benzene
dppe
1
1
1000
1000
10000
20
20
20
48a
92
25a
R1
R1
O
O
2-bromophenol
1
1
10000
100000
20
20
82b
40b
O
[Pd], K2CO3
+
nBu
Br
nBu
32c
O
2-bromoaniline
1
1000
20
R2
R2
9-bromo-an-
thracene
1
1
1000
10000
20
20
62
Scheme
22a
1-bromo-2-meth-
yl-naphthalene
1
1
1000
10000
20
20
92
In conclusion, the tedicyp/palladium complex shows high
catalytic activity and yields in the Heck reaction of steri-
cally hindered aryl bromides. The system exhibits unprec-
edented turnovers with such substrates. This catalyst is
more efficient than the complexes formed with triphe-
nylphosphine ligand or simple diphosphines such as dppe.
This high activity comes from the high stability, even at
high temperature, of this catalyst. This stability probably
result from the presence of the four diphenylphosphi-
noalkyl groups stereospecifically bound to the same face
of the cyclopentane ring, which seems to increases the co-
ordination of the ligand to the metal and prevents precipi-
tation of the catalyst. The Heck reaction of ortho- and di-
ortho-substituted bromobenzene derivatives can be per-
formed with as little as 0.001% catalyst. Further applica-
tions of the tedicyp ligand will be reported in due course.
26a
1-bromo-2-meth-
oxynaphthalene
1
1000
20
45
2,6-dimethyl-
bromobenzene
1
1
1
100
500
500
48
20
48
95a
46a
76
2,4,6-triiso-
propylbromo-
benzene
1
1
50
100
72
20
86
40a
Conditions: catalyst see ref.9a, ArBr (1 equiv), n-butyl acrylate
(2 equiv), K2CO3 (2 equiv), DMF, 130 °C, isolated yields.
a GC yield.
b The formation of coumarin was also observed.
c The formation of several side products was observed.
Synlett 2001, No. 12, 1980–1982 ISSN 0936-5214 © Thieme Stuttgart · New York

1982
M. Feuerstein et al.
LETTER
(5) (a) Herrmann, W. A.; Brossmer, C.; Öfele, K.; Reisinger, C.-
P.; Priermeier, T. Angew. Chem., Int. Ed. Engl. 1995, 107,
17. (b) Herrmann, W. A.; Brossmer, C.; Reisinger, C.-P.;
Reirmeier, T.; Öfele, K.; Beller, M. Chem.–Eur. J. 1997, 3,
1357.
Acknowledgement
M. F. is grateful to the Ministère de la Recherche for a grant. We
thank the CNRS for providing financial support.
(6) (a) Littke, A.; Fu, G. J. Org. Chem. 1999, 64, 10. (b)Littke,
A.; Fu, G. J. Am. Chem. Soc. 2001, 123, 6989.
References
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(1) For reviews on the palladium-catalysed Heck reaction see:
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Katritzky, A. R.; Meth-Cohn, O.; Rees, C. W., Eds.;
Academic Press: London, 1985, 2. (b) Heck, R. F. Vinyl
Substitution with Organopalladium Intermediates, In
Comprehensive Organic Synthesis, Vol. 4; Trost, B. M.;
Fleming, I., Eds.; Pergamon: Oxford, 1991. (c) Malleron,
J.-L.; Fiaud, J.-C.; Legros, J.-Y. Handbook of Palladium-
Catalyzed Organic Reactions; Academic Press: London,
1997. (d) Reetz, M. T. Transition Metal Catalyzed
Reactions; Davies, S. G.; Murahashi, S.-I., Eds.; Blackwell:
Oxford, 1999. (e) Herrmann, W. A.; Böhm, V.; Reisinger,
C.-P. J. Organomet. Chem. 1999, 576, 23. (f) Beletskaya,
I.; Cheprakov, A. Chem. Rev. 2000, 100, 3009.
(2) (a) Melpolder, J.; Heck, R. F. J. Org. Chem. 1976, 41, 265.
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N. Tetrahedron Lett. 1998, 39, 9793. (b) Miyazaki, F.;
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(12) As a typical experiment, the reaction of 2,4,6-triiso-
propylbromobenzene (0.28 g, 1 mmol), n-butyl acrylate
(0.26 g, 2 mmol) and K2CO3 (0.28 g, 2 mmol) at 130 °C
during 20 h in dry DMF (1 mL) in the presence of cis,cis,cis-
1,2,3,4-tetrakis(diphenylphosphinomethyl)cyclopentane/
[PdCl(C3H5)]2 complex (0.02 mmol) under argon affords the
corresponding adduct after evaporation and filtration on
silica gel (ether/pentane: 1/5) in 86% (0.36 g) isolated yield.
1H NMR ( 300 MHz, CDCl3): = 7.90 (d, J = 16.5 Hz, 1 H),
7.01 (s, 2 H), 5.92 (d, J = 16.5 Hz, 1 H), 4.21 (t, J = 6.8 Hz,
2 H), 3.10 (sept., J = 6.8 Hz, 2 H), 2.88 (sept., J = 6.9 Hz, 1
H), 1.70 (m, 2 H), 1.44 (m, 2 H), 1.25 (d, J = 6.9 Hz, 6 H),
1.18 (d, J = 6.9 Hz, 12 H), 0.96 (t, J = 7.3 Hz, 3 H).
Synlett 2001, No. 12, 1980–1982 ISSN 0936-5214 © Thieme Stuttgart · New York