Efficient heck vinylation of aryl halides catalyzed by a new air-stable palladium-tetraphosphine complex

Full text of DOI:10.1021/jo015645b

J . Org. Chem. 2001, 66, 5923-5925
5923
Efficien t Heck Vin yla tion of Ar yl Ha lid es
Ca ta lyzed by a New Air -Sta ble
P a lla d iu m -Tetr a p h osp h in e Com p lex
Marie Feuerstein, Henri Doucet,*,† and
Maurice Santelli*,‡
F igu r e 1. Tedicyp (1).
Sch em e 1
Laboratoire de Synthe`se Organique associe´ au CNRS,
Faculte´ des Sciences de Saint J e´roˆme, Avenue Escadrille
Normandie-Niemen, 13397 Marseille Cedex 20, France
m.santelli@lso.u-3mrs.fr
Received March 22, 2001
The Heck reaction is one of the most widely used
palladium-catalyzed methodologies in organic synthesis.
Several ligands such as phosphines, phosphites, carbenes,
or thioethers have been successfully employed for this
reaction.1-3 In the phosphine ligand series, some inter-
esting results have been described with very simple
phosphine ligands such as PPh3 or dppe which largely
compete with palladacycles.4,5 For example, Herrmann
et al. have reported recently that the system Pd(OAc)2/
PPh3 is extremely efficient for the reaction of activated
aryl bromides with n-butyl acrylate (turnover number
(TON): 1 000 000).6,7 However, to the best of our knowl-
edge, the efficiency of tetraphosphines for Heck reaction
has not yet been demonstrated. In this paper we wish to
report on the efficiency of a new tetraphosphine ligand
for the Heck reaction.
the new tetrapodal8 phosphine ligand, cis,cis,cis-1,2,3,4-
tetrakis(diphenylphosphinomethyl)cyclopentane or Te-
dicyp (1) (Figure 1)9 in which the four diphenylphos-
phinoalkyl groups are stereospecifically bound to the
same face of the cyclopentane ring, in several catalyzed
reactions. We have reported recently the first results
obtained in allylic substitution9,10 and in Suzuki cross-
coupling11 using 1 as ligand. For example, a TON of
9 800 000 for the addition of dimethyl sodiummalonate
to allyl acetate had been observed.9
In this paper, we wish to describe the results obtained
for the catalyzed Heck vinylation of aryl halides using
our tetraphosphine 1 as ligand. First, to compare 1 with
other classical ligands, several experiments have been
performed using identical conditions in the presence of
PPh3, P(o-tolyl)3, and dppe. This comparison has been
carried out with one of the less reactive aryl bromides:
4-bromoanisole (2) (Scheme 1, Table 1). Herrmann et al.
had obtained low TON’s with this substrate (<100) in
the presence of palladacycles or with the system
Pd(OAc)2/P(o-tolyl)3.6 We observed a similar tendency
when [PdCl(C3H5)]2 was used as catalyst precursor
(Scheme 1, Table 1). In the presence of 0.1 mol % of this
complex and without added ligand, only 2% conversion
was observed. When PPh3 or P(o-tolyl)3 was used as the
ligand, slightly higher conversions and TON’s of 270 and
150 were observed, respectively. In the presence of the
diphosphine dppe much better results were obtained
(TON 3800). Finally in the presence of 1 a TON of 82 000
has been obtained in the presence of 0.001 mol % of
catalyst. The complex formed by association of Tedicyp
(1) and [PdCl(C2H5)]2 seems to be more stable and less
sensitive to temperature and poisoning than the com-
The nature of the phosphine ligand on complexes has
a tremendous influence on the stability of the catalysts
and on the rate of catalyzed reactions. To find more stable
and more efficient palladium catalysts, we have prepared
† E-mail: henri.doucet@lso.u-3mrs.fr.
‡ Fax: 04 91 98 38 65.
(1) For reviews on the palladium-catalyzed Heck reaction, see: (a)
Heck, R. F. Palladium Reagents in Organic Syntheses; Katritzky, A.
R., Meth-Cohn O., Rees, C. W., Eds.; Academic Press: London, 1985;
p 2. (b) Heck, R. F. Vinyl Substitution with Organopalladium Inter-
mediates. 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 Reac-
tions; Academic Press: London, 1997. (d) Reetz, M. T. Transition Metal
Catalyzed Reactions; Davies, S. G., Murahashi, S.-I., Eds.; Blackwell
Sci.: Oxford, 1999. (e) Beletskaya, I.; Cheprakov, A. Chem. Rev. 2000,
100, 3009.
(2) For a review on palladacycles in Heck reactions, see: Herrmann,
W. A.; Bo¨hm, V.; Reisinger, C.-P. J . Organomet. Chem. 1999, 576, 23.
(3) For recent examples of Heck reactions catalyzed by palladacycles,
see: (a) Albisson, D.; Bedford, R.; Scully, P. N. Tetrahedron Lett. 1998,
39, 9793. (b) Littke, A.; Fu, G. J . Org. Chem. 1999, 64, 10. (c) Miyazaki,
F.; Yamaguchi, K.; Shibasaki, M. Tetrahedron Lett. 1999, 40, 7379.
(d) Ohff, M.; Ohff, A.; Milstein, D. Chem. Commun. 1999, 357. (e)
Brunel, J .-M.; Hirlemann, M.-H.; Heumann, A.; Buono, G. Chem.
Commun. 2000, 1869. (f) Gai, X.; Grigg, R.; Ramzan, I.; Sridharan,
V.; Collard, S.; Muir, J . Chem. Commun. 2000, 2053. (g) Brunel, J .-
M.; Heumann, A.; Buono, G. Angew. Chem., Int. Ed. 2000, 39, 1946.
(h) Gruber, A.; Zim, D.; Ebeling, G.; Monteiro, A.; Dupont, J . Org. Lett.
2000, 2, 1287.
(4) (a) Cabri, W.; Candiani, I.; Bedeschi, A. J . Org. Chem. 1992, 57,
3558. (b) Heck, R. F. Acc. Chem. Res. 1979, 12, 146.
(5) Qadir, M.; Mo¨chel, T.; Hii (Mimi), K. K. Tetrahedron 2000, 56,
7975.
(8) For a review on the preparation of polypodal diphenylphosphine
ligands, see: Laurenti, D.; Santelli, M. Org. Prep. Proc. Int. 1999, 31,
245.
(9) Laurenti, D.; Feuerstein, M.; Pe`pe, G.; Doucet, H.; Santelli, M.
J . Org. Chem. 2001, 66, 1633.
(10) Feuerstein, M.; Laurenti, D.; Doucet, H.; Santelli, M. Chem.
Commun. 2001, 43.
(11) Feuerstein, M.; Laurenti, D.; Bougeant C.; Doucet, H.; Santelli,
M. Chem. Commun. 2001, 325.
(6) (a) Herrmann, W. A.; Brossmer, C.; Reisinger, C.; Riermeier, T.;
O¨ fele, K.; Beller, M. Chem. Eur. J . 1997, 3, 1357. (b) Herrmann, W.
A.; Brossmer, C.; O¨ fele, K.; Reisinger, C.; Riermeier, T.; Beller, M.;
Fisher, H. Angew. Chem., Int. Ed. Engl. 1995, 34, 1844.
(7) For examples on the influence of ammonium salts, see: (a)
J effery, T. Tetrahedron 1996, 52, 10113. (b) J effery, T. Tetrahedron
Lett. 1985, 26, 2667. (c) J effery, T. Chem. Commun. 1984, 1287.
10.1021/jo015645b CCC: $20.00 © 2001 American Chemical Society
Published on Web 07/18/2001

5924 J . Org. Chem., Vol. 66, No. 17, 2001
Notes
Ta ble 1. P a lla d iu m -Ca ta lyzed Heck Rea ction of
4-Br om oa n isole 2 w ith Bu tyl Acr yla te 19a
and a TON of 210 000 000 have been obtained. With
nonactivated bromobenzene 9, a reasonable TON (87 000)
was observed. When we used ortho-substituted aryl
bromides such as 2-fluorobromobenzene (11) or 2-meth-
ylbromobenzene (12), lower TON’s were obtained. We
noticed a similar decelerating effect with 2,4-dimethoxy-
bromobenzene (13). Finally, heteroaromatic substrates
such as 3-bromopyridine (15) or 3-bromoquinoline (16)
led to TON’s of 96 000 and 960 000, respectively. A lower
TON was obtained in the course of the vinylation of
3-bromothiophene (17).
turnover
substrate-catalyst frequencies turnover yield of
b
ligand
ratio
(h-1
)
numbers 20 (%)c
no ligand
1 000
1 000
1 000
1
13
7
20
270
150
2
PPh3
27
15
P(o-tolyl)3
dppe
dppe
1
1
1
1 000
10 000
10 000
49
980
98
125
390
2 100
2 900
3 800
9 700
82 000
240 000
38d
97d
82e
24f,g
100 000
1 000 000
These results indicate that, as expected, both the
electronic factors and the steric hindrance of the aryl
bromides are important factors for the rate of this
reaction. An electron-withdrawing substituent generally
increases the TOF of the reaction, and lower reaction
rates are observed in the presence of bulky substrates.
Nevertheless, reasonable TOF’s are observed even with
electron-donating substituents on the aryl bromide in the
presence of this catalyst. The catalytically active species
with the ligand 1 appears to be much less sensitive to
electronic factors than most of the catalysts which have
been used so far for this reaction. These results suggests
that, in the presence of this catalyst, the rate-determining
step of the reaction is the insertion of the olefin into the
aryl-palladium intermediate rather than the oxidative
addition of the aryl bromide.
Since Pd(OAc)2 alone is an active catalyst for Heck
reactions when aryl iodides are used, we did not focus
our attention on these substrates. Nevertheless, we
checked that 1 is also active for the coupling of 19 to
iodobenzene 18. In the presence of 0.000001 mol % of
catalyst, 99% conversion was observed after 20 h. On the
other hand, reactions using aryl chlorides as substrates
led to very slow reactions rates. For example, with
4-nitrochlorobenzene conversion was only 32% in the
presence of 0.2% catalyst.
Next we performed some reactions in air12 and surpris-
ingly we observed that the catalyst retains activity even
under air. Substrates 4, 7, and 18 led to TON’s of
980 000, 100 000 and 1 000 000, respectively. Moreover,
aryl bromide 10 led to a TON of 78 000 000. However,
the catalyst solution is not totally air-stable, and after
several hours some decomposition is observed.
In conclusion, the Tedicyp-palladium complex ob-
tained by addition of Tedicyp to [Pd(C3H5)Cl]2 provides
a convenient catalyst for the Heck vinylation of aryl
halides. This catalyst seems to be more stable and less
sensitive to poisoning than the complexes formed with
mono- and diphosphine ligands and appears to be more
efficient than most of the palladacyles. This stability
probably comes from the presence of the four diphen-
ylphosphinoalkyl groups stereospecifically bound to the
same face of the cyclopentane ring. All four phosphines
probably cannot bind at the same time to the same
palladium center, but the presence of these four phos-
phines on the ligand close to the metal center along with
steric factors seem to increase the coordination of the
ligand to the palladium complex. In the presence of this
catalyst, the Heck vinylation of aryl bromides can be
performed with as little as 0.000001 mol % of catalyst.
aConditions: catalyst: [Pd(C3H5)Cl]2/ligand 1/2, 4-bromoanisole
(2) (10 mmol), butyl acrylate (19) (20 mmol), K2CO3 (20 mmol),
b
DMF, 130 °C, 20 h, under argon. TOF calculated between initial
d
g
time and 20 h. c GC yields. 40 h. e 72 h. f 96 h. Addition of
cetyltrimethylammonium bromide (1 mmol).
Ta ble 2. Heck Olefin a tion of Ar yl Ha lid es w ith 19 Usin g
1 a s Liga n d a
turnover
aryl
halide T (h)
substrate-catalyst
frequencies yield
b
ratio
product
(h-1
)
(%)c
3
3
4
4
4
5
5
6
7
7
7
8
9
20
72
20
20
72
16
20
48
20
20
20
72
72
96
20
40
72
20
20
20
72
20
48
20
48
20
20
20
100 000
1 000 000
1 000 000
1 000 000
10 000 000
100 000
1 000 000
100 000
100 000
100 000
1 000 000
100 000
10 000
100 000
21
21
22
22
22
23
23
24
25
25
25
26
27
27
28
28
28
29
30
31
32
32
33
34
34
35
27
27
99
46
19 000
48 500
49 000
42 000
6 250
22 000
3 100
5 000
5 000
6 000
1 900
155
97
98e
25
100
44
59
100
100e
12
81
95
9
1 100
87d
100
78e
21
10
10
10
11
12
13
14
14
15
16
16
17
18
18
100 000 000
100 000 000
1 000 000 000
1 000
5 000 000
1 625 000
3 800 000
26
52
75
44
91
1 000
1 000
10 000
100 000
37
22
2 150
4 400
19 000
27 500
170
43
100 000
96
1 000 000
1 000 000
10 000
1 000 000
100 000 000
38e
96
34
50 000
4 950 000
100e
99
a
Conditions: catalyst: [Pd(C3H5)Cl]2/ligand 1/2, aryl bromide
(10 mmol), butyl acrylate (19) (20 mmol), K2CO3 (20 mmol), DMF,
b
130 °C, under argon. TOF calculated between initial time and
d
20 h. c GC or NMR yields. Addition of cetyltrimethylammonium
bromide (1 mmol). e Reactions performed in air.
plexes formed with classical mono- or diphosphines. In
general, no deposition of palladium is observed during
the reaction. Moreover, these reactions have been per-
formed without addition of tetraalkylammonium salts
which are generally used to avoid precipitation of the
palladium. In the presence of 10 mol % of cetyltrimethyl-
ammonium bromide, an even higher activity has been
observed (TON: 240 000).
These results prompted us to investigate the vinylation
of other aryl bromides (Scheme 1, Table 2). A high
activity has been observed for activated aryl bromides
such as 3 to 7. TON’s as high as 59 000-2 500 000 have
been achieved with these substrates. With 3,5-bistrifluoro-
methylbromobenzene (10), a very high reactivity has been
observed. With this substrate, a TOF of 5 000 000 h-1
(12) For examples of Heck reactions performed in air, see: (a) Ohff,
M.; Ohff, A.; van der Boom, M. E.; Milstein, D. J . Am. Chem. Soc. 1997,
119, 11687. (b) Bergbreiter, D.; Osburn, P.; Liu, Y.-S. J . Am. Chem.
Soc. 1999, 121, 9531. (c) Peris, E.; Loch, J .; Mata, J .; Crabtree, R. Chem.
Commun. 2001, 201.

Notes
J . Org. Chem., Vol. 66, No. 17, 2001 5925
catalyst concentration was obtained by successive dilution with
anhydrous DMF. 31P NMR (162 MHz, CDCl3) δ 25 (w ) 80 Hz),
19.4 (w ) 110 Hz).
So we believe that this catalyst is among the most active
and stable ones reported so far.
(E)-3-(4-methoxyphenyl)acrylic Acid Butyl Ester (20).13 The
reaction of bromoanisole 2 (1.87 g, 10 mmol), K2CO3 (2.76 g, 20
mmol), and butyl acrylate 19 (2.56 g, 20 mmol) at 130 °C during
40 h in anhydrous DMF (10 mL) in the presence of the Tedicyp-
palladium complex (0.001 mmol) under argon affords the cor-
responding coupling product 20 after extraction with dichlo-
romethane, separation, drying (MgSO4), evaporation, and filtration
on silica gel (diethyl ether/pentane: 1/2) in 96% (2.25 g) isolated
yield. 1H NMR (300 MHz, CDCl3): δ ) 7.55 (d, J ) 16.0 Hz,
1H), 7.37 (d, J ) 8.7 Hz, 2H), 6.80 (d, J ) 8.7 Hz, 2H), 6.21 (d,
J ) 16.0 Hz, 1H), 4.12 (t, J ) 6.8 Hz, 2H), 3.69 (s, 3H), 1.60 (tt,
J ) 6.8, 6.8 Hz, 2H), 1.33 (qt, J ) 7.3, 6.8 Hz, 2H), 0.87 (q, J )
7.3 Hz, 3H).
Exp er im en ta l Section
Gen er a l. All reactions under argon were run using vacuum
lines in Schlenk tubes in oven-dried glassware. To avoid
contamination with palladium residues, the reactions were
performed in brand new Pyrex tubes for chromatography
inserted in Schlenk tubes with new stirring bars; dry DMF was
added in the Schlenk tube for the transmission of the temper-
ature of the oil bath to the Pyrex tubes. Reactions in air were
performed in brand new Pyrex tubes for chromatography with
new stirring bars. DMF analytical grade (99.8%) and butyl
acrylate (99+) were not distilled before use. Some of the aryl
halides were distilled before use. Potassium carbonate (99+) was
used without drying. The reactions were followed by GC and
NMR for high boiling point substrates and by GC for low boiling
point substrates. 1H (400 or 300 MHz) spectra were recorded in
CDCl3 solutions. Chemical shift (δ) are reported in ppm relative
to CDCl3. Flash chromatography was performed on silica gel
(230-400 mesh).
Ack n ow led gm en t. M.F. is grateful to the MEN for
a grant.
Su p p or tin g In for m a tion Ava ila ble: Experimental pro-
cedures, 1H NMR data for all compounds. This material is
available free of charge via the Internet at http://pubs.acs.org.
P r ep a r a tion of th e P d -Ted icyp Ca ta lyst. An over-dried
40-mL Schlenk tube equipped with a magnetic stirring bar under
an argon atmosphere was charged with [Pd(η3-C3H5)Cl]2 (30 mg,
81 µmol) and Tedicyp (140 mg, 162 µmol). Anhydrous THF (10
mL) was added, the solution was stirred at room temperature
for 10 min, and the THF was evaporated. The appropriate
J O015645B
(13) Stephan, M. S.; Teunissen, A. J . J . M.; Verzijl, G. K. M.; de
Vries, J . G. Angew. Chem., Int. Ed. 1998, 37, 662-690.