Remarkable dendritic effect in the polymer-supported catalysis of the heck arylation of olefins

Article abstract of DOI:10.1021/ol0340181

(Matrix presented) Phosphine-palladium complexes, immobilized on polystyrene, demonstrated a remarkable increase in catalytic activity and selectivity in the Heck reaction upon the introduction of a dendritic spacer between the support and phosphine. For some reactions an up to 5-fold increase in yield is observed.

Full text of DOI:10.1021/ol0340181

ORGANIC
LETTERS
2003
Vol. 5, No. 8
1197-1200
Remarkable Dendritic Effect in the
Polymer-Supported Catalysis of the
Heck Arylation of Olefins
Adi Dahan and Moshe Portnoy*
School of Chemistry, Raymond and BeVerly Sackler Faculty of Exact Sciences,
Tel AViV UniVersity, 69978 Tel AViV, Israel
portnoy@post.tau.ac.il
Received January 7, 2003
ABSTRACT
Phosphine−palladium complexes, immobilized on polystyrene, demonstrated a remarkable increase in catalytic activity and selectivity in the
Heck reaction upon the introduction of a dendritic spacer between the support and phosphine. For some reactions an up to 5-fold increase
in yield is observed.
Immobilization of analogues of homogeneous catalysts via
covalent attachment to a support is one of the possible ways
to prepare well-defined heterogeneous catalytic systems, a
task of great economic and environmental importance.1
Unfortunately, along with the advantages of the heteroge-
neous catalysts, a substantial decrease in activity and
selectivity is frequently observed. Herein we report results
suggesting that one possible way to overcome these draw-
backs is the introduction of a dendritic template between the
support and catalyst. Our study of the intermolecular Heck
reaction with supported dendritic catalysts reveals a remark-
able positive dendritic effect on the catalysis.
reports, a positive dendritic influence was apparent.4b,f Alper
and co-workers investigated the Heck reaction using the
silica-bound PAMAM-bis(diphenylphosphinomethyl)amine
catalytic system (PAMAM ) polyamidoamine dendron), but
the ineffective palladium complexation to the dendritic
ligands prevented conclusive investigation of the dendritic
effect in this reaction.4d
Heck olefin arylation, one of the most widely used reac-
tions in synthetic organic chemistry, was successfully ac-
complished in solution with aryl iodides, bromides, and even
chlorides, using a variety of catalytic systems.5,6 Heteroge-
(3) For positive dendritic effects in solution, see: (a) Lee, J.-J.; Ford,
W. T.; Moore, J. A.; Li, X. Macromolecules 1994, 27, 4632. (b) Breinbauer,
R.; Jacobsen, E. N. Angew. Chem., Int. Ed. 2000, 39, 3604. (c) Ropartz,
L.; Morris, R. E.; Foster, D. F.; Cole-Hamilton, D. J. Chem. Commun. 2001,
361. (d) Francavilla, C.; Drake, M. D.; Bright, F. V.; Detty, M. R. J. Am.
Chem. Soc. 2001, 123, 52.
Soluble dendrimers with peripherally attached catalytic
units were applied to a variety of reactions.2,3 Surprisingly,
only a few efforts were devoted to the investigation of
catalysis on dendronized insoluble supports.4 In two of these
(4) (a) Bourque, S. C.; Maltais, F.; Xiao, W.-J.; Tardif, D.; Alper,
H.; Arya, P.; Manzer, L. E. J. Am. Chem. Soc. 1999, 121, 3035. (b)
Bourque, S. C.; Alper, H.; Manzer, L. E.; Arya, P. J. Am. Chem. Soc.
2000, 122, 956. (c) Arya, P.; Rao, N. V.; Singkhonrat, J.; Alper, H.;
Bourque, S. C.; Manzer, L. E. J. Org. Chem. 2000, 65, 1881. (d) Alper,
H.; Arya, P.; Bourque, S. C.; Jefferson, G. R.; Manzer, L. E. Can. J. Chem.
2000, 78, 920. (e) Antebi, S.; Arya, P.; Manzer, L. E.; Alper, H. J. Org.
Chem. 2002, 67, 6623. (f) Chung, Y.-M.; Rhee, H.-K. Chem. Commun.
2002, 238.
(1) (a) Leadbeater, N. E.; Marco, M. Chem. ReV. 2002, 102, 3217. (b)
McNamara, C. A.; Dixon, M. J.; Bradley, M. Chem. ReV. 2002, 102, 3275.
(c) de Miguel, Y. R. J. Chem. Soc., Perkin Trans. 1 2000, 4213. (d) de
Miguel, Y. R.; Brule´, E.; Margue, R. G. J. Chem. Soc., Perkin Trans. 1
2001, 3085.
(2) (a) Oosterom, G. E.; Reek, J. N. H.; Kamer, P. C. J.; van Leeuwen,
P. W. N. M. Angew. Chem., Int. Ed. 2001, 40, 1828. (b) Astruc, D.; Chardac,
F. Chem. ReV. 2001, 101, 2991. (c) van Heerbeek, R.; Kamer, P. C. J.; van
Leeuwen, P. W. N. M.; Reek, J. N. H. Chem. ReV. 2002, 102, 3717.
(5) Beletskaya, I. P.; Cheprakov, A. V. Chem. ReV. 2000, 100, 3009.
10.1021/ol0340181 CCC: $25.00 © 2003 American Chemical Society
Published on Web 03/27/2003

neous catalysis, however, was performed almost entirely with
iodides or electron-deficient bromides,7,8 mainly using metal
palladium adsorbed on an inorganic support.9 It is notable
that although in solution phosphines are the most popular
ligands for Heck catalysis, on solid support only a few phos-
phorus-based systems have been reported.10 The reactivities
of these systems were limited to iodides, and only the funda-
mental study by Hallberg and co-workers exposed the need
for multiple phosphine ligation to Pd as a tool for effective
bromoarene olefination with a supported catalyst.11 Unfor-
tunately, such coordination modes result in severe cross-
linking of the polymer, which frequently has a negative effect
on the catalytic activity. With this notion in mind, we found
it imperative to investigate catalytic systems that are based
on ligands derived from dendronized polymeric support.
Looking for an alternative to the potentially coordinating
amide-type linkage, mostly used in the backbone of the
dendritic templates prepared on solid support,4,12 we recently
developed an alternative, efficient route to poly(aryl benzyl
ether) dendronized polystyrene resins G1-G3 (Figure 1).13,14
Scheme 1a
a Reagents and conditions: DIC, DMAP, DMF.
Incubation of resins 1 with Pd(dba)2 in deoxygenated THF
at room temperature for 4 h yielded reddish brown resins
2a-2d (Scheme 2).16 Gel-phase 31P NMR demonstrated
Scheme 2. Complexation of 1 with Pd(dba)2
1
quantitative complexation of the phosphines with Pd. H
NMR spectra of the TFA-cleaved solutions of 2a-2d
revealed that, for each two phosphine groups, one molecule
of dibenzylideneacetone is present. Thus, the most probable
structure of the Pd complexes on the supports is (phosphine)2-
Pd(dba), and accordingly, the loading of the active catalyst
on support was calculated.17
The reaction of bromobenzene with methyl acrylate,
chosen as a model for the Heck reaction with catalysts
2a-2d, was performed under two different temperature
regimes: at 120 °C for 14 h and at 80 °C for 72 h (Scheme
3). In some experiments, the bromobenzene homocoupling
Figure 1. Dendronized support (Gn).
Ligands 1a-1d (Scheme 1) that are based on such support
have already been used for the study of the Co-catalyzed
intramolecular Pauson-Khand reaction, demonstrating a
positive dendritic effect on the catalysis.15
(6) For polyamine-based soluble dendritic catalyst for this reaction, see:
(a) Reetz, M. T.; Lohmer, G.; Schwickardi, R. Angew. Chem., Int. Ed. Engl.
1997, 36, 1526. (b) Reetz, M. T. Top. Catal. 1997, 4, 187.
Scheme 3. Heck Reaction with 2 as Catalyst
(7) (a) Kivaho, J.; Hanaoka, T.; Kubota, Y.; Sugi, Y. J. Mol. Catal. A
1995, 101, 25. (b) Zhao, F.; Bhanage, B. M.; Shirai, M.; Arai, M. Chem.
Eur. J. 2000, 6, 843. (c) Biffis, A.; Zecca, M.; Basato, M. Eur. J. Inorg.
Chem. 2001, 1131. (d) Davies, I. W.; Matty, L.; Hughes, D. L.; Reider, P.
J. J. Am. Chem. Soc. 2001, 123, 10139. (e) Zhao, F.; Shirai, M.; Ikushima,
Y. Arai, M. J. Mol. Catal. A 2002, 180, 211.
(8) For rare examples of supported systems capable of unactivated
bromoarene olefination, see: (a) Buchmeiser, M. R.; Wurst, K. J. Am. Chem.
Soc. 1999, 121, 11101. (b) Schwarz, J.; Bo¨hm, V. P. W.; Gardiner, M. G.;
Grosche, M.; Herrman, W. A.; Hieringer, W.; Raudaschl-Sieber, G. Chem.
Eur. J. 2000, 6, 1773. (c) Dell’Anna, M. M.; Mastrorilli, P.; Muscio, F.;
Nobile, C. F.; Surranna, G. P. Eur. J. Inorg. Chem. 2002, 1094.
(9) For rare metal palladium catalysts capable of unactivated bromoarene
olefination, see: (a) Ko¨hler, K.; Wagner, M.; Djakovitch, L. Catal. Today
2001, 66, 105 and references therein. (b) Mehnert, C. P.; Ying, T. Y. Chem.
Commun. 1997, 2215. (c) Ko¨hler, K.; Heidenreich, R. G.; Krauter, J. G.
E.; Pietsch, J. Chem. Eur. J. 2002, 8, 622.
byproduct, biphenyl 5, is obtained. The results of the model
reaction, summarized in Table 1, demonstrate a remarkable
improvement in the catalyst performance upon dendroniza-
tion of the support. Although at 120 °C, the conversions of
the dendronized resins is only marginally better than that of
(12) (a) Lebreton, S.; Monaghan, S.; Bradley, M. Aldrichim. Acta 2001,
34, 75. (b) Klein Gebbink, R. J. M.; Kruithof, C. A.; van Klink, G. P. M.;
van Koten, G. ReV. Mol. Biol. 2002, 90, 183.
(13) Dahan, A.; Portnoy, M. Macromolecules 2003, 36, 1034.
(14) For first route to such dendrons on polymer see: Basso, A.; Evans,
B.; Pegg, N.; Bradley, M. Chem. Commun. 2001, 697.
(15) Dahan, A.; Portnoy, M. Chem. Commun. 2002, 2700.
(16) Loading of phosphine groups: 1a, 0.89 mmol/g; 1b, 0.82 mmol/g;
1c, 1.12 mmol/g; 1d, 0.70 mmol/g
(10) (a) Wang, P.-W.; Fox, M. A. J. Org. Chem. 1994, 59, 5358. (b)
Villemin, D.; Jaffre`s, P. A.; Nechab, B.; Courivaud, F. Tetrahedron Lett.
1997, 38, 6581. (c) Riegel, N.; Darcel, C.; Ste´phan, O.; Juge´, S. J.
Organomet. Chem. 1998, 567, 219.
(11) Andersson, C.-M.; Karabelas, K.; Hallberg, A.; Andersson, C. J.
Org. Chem. 1985, 50, 3891.
1198
Org. Lett., Vol. 5, No. 8, 2003

Table 1. Heck Reaction of Methyl Acrylate (3a)a
Table 2. Heck Reaction of Styrene (3b)a
conversion
(%)
yield of 4a
selectivity
conversion
(%)
yield of 4b
selectivity
entry
catalyst
(%)
(4a :5)
catalyst
(%)
(4b:5)
1
2
3
4
5
6
7
8
9
2a b
2bb
2cb
2d b
2a c
2bc
2cc
2d c
6c,d
95
100
100
100
20
11
66
100
84
75
81
86
97
18
11
66
100
82
3.8
4.3
6.1
32
9.0
2a b
2bb
2cb
2d b
2a c
2bc
2cc
2d c
100
100
100
100
99
73
100
100
66
67
68
91
67
56
81
89
1.9
2.0
2.1
10
2.0
3.3
4.3
8.1
22
>130
>200
41
a Using 0.5 mmol of bromobenzene, 0.6 mmol of styrene, 0.65 mmol of
triethylamine, and 2 (0.0125 mmol of Pd) in 1 mL of NMP. b At 120 °C,
14 h. c At 80 °C, 72 h.
a Using 0.5 mmol of bromobenzene, 0.6 mmol of methyl acrylate, 0.65
mmol of triethylamine, and 2 (0.0125 mmol of Pd) in 1 mL of N-
methylpyrrolidone (NMP). b At 120 °C, 14 h. c At 80 °C, 72 h. d 6: Pd(dba)2
+ 2 p-MeO2CC6H4PPh2.
Scheme 4. Heck Reaction of Butyl Vinyl Ether with 2 as
the catalyst derived from the Wang resin (2a), the selectivity
of the formation of the Heck versus the homocoupling
product consistently improves from 2a to 2d (an 8-fold
increase is achieved, entries 1 and 4). This increase in selec-
tivity is reflected in the substantially higher yield reached
using the third-generation-derived 2d as compared with its
nondendronized analogue.
Catalyst
The difference in the reactivity within the 2a-2d series
of catalysts is even more dramatic at 80 °C (Table 1, entries
5-8). The second- and third-generation-derived catalysts are
superior to their nondendronized analogue in all parameters.
Although there is a notable decrease in the activity of 2b, as
compared with that of 2a, the activity increases significantly
for 2c and even further for 2d, rendering for the latter a
quantitative conversion. The selectivity of the catalysis is
also significantly improved upon the increase of the dendron
generation and, for 2c and 2d, no biphenyl is observed.
Notably, the conversion and selectivity achieved with 2d are
markedly higher than those obtained with 6, the nondendritic
homogeneous analogue of ligands 2a-2d, prepared in situ
from Pd(dba)2 and the methyl ester of the 4-(diphenylphos-
phino)benzoic acid (entries 8 and 9).18
When styrene is examined as a substrate, the trends in
activity and selectivity of the catalysts are very similar to
those of methyl acrylate (Table 2), although the magnitude
of the effect is somewhat smaller.
To determine whether the observed effects are limited only
to the electron-deficient olefinic substrates, we examined the
performance of 2a-2d in the Heck reaction with butyl vinyl
ether as a substrate (Scheme 4, Table 3).
Table 3. Heck Reaction of Butyl Vinyl Ether (3c)a
conversion
(%)
yield
selectivity
catalyst
(7 + 8 + 9, %)
([7 + 8 + 9]:5)
2a b
2bb
2cb
2d b
2a c
2bc
2cc
2d c
100
100
100
100
55
49
54
77
58
58
75
83
46
41
46
72
1.4
1.4
3.0
4.9
5.1
5.1
5.8
14
a Using 0.5 mmol of bromobenzene, 0.6 mmol of butyl vinyl ether, 0.65
mmol of triethylamine, and 2 (0.0125 mmol of Pd) in 1 mL of NMP. b At
120 °C, 14 h. c At 80 °C, 72 h.
similar to those obtained for substrates 3a and 3b. At both
temperatures, 2d is clearly superior to 2a. According to the
regio- and stereoselectivity data, summarized in Table 4, the
proportion of the R-arylated product 7 increases as the
generation number of the polymer template increases. The
decrease in the ratio â-arylation/R-arylation for butyl vinyl
ether can be attributed to the higher portion of the olefin
insertion occurring through cationic intermediates (enforcing
R-arylation) versus neutral intermediates (yielding mixtures
of R- and â-arylated enol ethers).19 This change in the
distribution between the two alternative catalytic pathways
may result from the more polar environment of the catalytic
units in higher generation catalysts. Alternatively, or ad-
ditionally, the reason for this change may be associated with
For this substrate, the regioselectivity and stereoselectivity
are important issues, as three productsscis- and trans-1,2-
disubstituted 8 and 9 as well as 1,1-disubstituted 7 (undergo-
ing partial hydrolysis to acetophenone (10))sare formed. The
trends observed for the conversion to Heck products (7-9)
and selectivity toward these products (versus 5) are very
(17) Loading of palladium: 2a, 0.38 mmol/g; 2b, 0.36 mmol/g; 2c, 0.47
mmol/g; 2d, 0.31 mmol/g
(18) Although monodentate phosphine is used for preparation of 6, the
minimal chelate size on dendronized resins is 20 atoms and thus chelate
effects are not likely to be responsible for the observed phenomenon.
(19) Cabri, W.; Candian, I. Acc. Chem. Res. 1995, 28, 2.
Org. Lett., Vol. 5, No. 8, 2003
1199

derived complexes as the source of the effect. First, the ratio
between products 9 (trans) and 8 (cis) in the reaction of 3c
(Table 4), which is known to be sensitive to the nature of
the catalyst,22 is more characteristic of the phosphine-
palladium catalysts. Additionally, when we performed the
reaction of 3a at 80 °C for 14 h, it exhibited a more
pronounced positive dendritic effect than that of the afore-
mentioned 3-day experiments.
In conclusion, the novel supported dendron-based catalysts
were successfully employed in the Heck reaction of bro-
mobenzene. The systems we prepared exhibit a truly remark-
able positive dendritic effect, demonstrating superiority even
over their homogeneous nondendritic analogue, although
more work has to be done in order to fully elucidate the
origins of the effect, improve the catalyst stability, and further
increase its activity. The proposed architecture demonstrates
a promising solution toward boosting the activity and
selectivity of supported catalytic systems.
Table 4. Regio- and Stereoselectivity in Heck Reaction of
Butyl Vinyl Ether (3c)
yield of
yield of
regio-
stereo-
selectivity
9/ 8c
â-arylation R-arylation
catalyst (8 + 9, %) (7 + 10, %) ([8 + 9]/[7 + 10])
selectivity
2a a
2ba
2ca
2d a
2a b
2bb
2cb
2d b
33
31
40
42
37
30
29
44
25
27
35
41
9
10
17
28
1.3
1.2
1.1
1.0
4.1
3.0
1.7
1.6
2.4
2.6
3.0
3.0
2.6
2.6
2.8
3.0
1
a At 120 °C, 14 h. b At 80 °C, 72 h. c Determined by H NMR.
the increased local loading of phosphines in higher generation
dendrons.
Precipitation of metallic palladium occurs during the
reaction, and thus the possibilities of the catalysis being
performed by Pd metal nanoparticles, stabilized inside the
dendritic matrix,20 or the dendritic effect being merely the
reflection of a reduced decomposition rate of the higher
generation-derived complexes21 cannot be ruled out at this
stage of the research.
Acknowledgment. This research was partially supported
by a grant from the Ministry of Science, Israel.
Supporting Information Available: General procedures
for complexation and for catalysis. This material is available
free of charge via the Internet at http://pubs.acs.org.
OL0340181
However, some preliminary experimental data may point
to the higher intrinsic reactivity of the higher-generation-
(21) As observed in ref 6a.
(22) According to ref 11, phosphine-Pd complexes as catalysts yield a
ca. 2.5:1 ratio, while the “naked” Pd catalysts form 1:1 product mixtures.
(20) Zhao, M.; Crooks, R. M. Angew. Chem., Int. Ed. 1999, 38, 364.
1200
Org. Lett., Vol. 5, No. 8, 2003