LETTER
Heck Reaction in Water with Amphiphilic Resin-Supported Pd-Phosphine Complexes
2047
Table 2 Reaction of Various Aryl Halides (1a–h) with Alkenes (2,
12–15)a
Acknowledgment
This work was partially supported by a Grant-in-Aid for Creative
Scientific Research (No. 13GS0024), Japan Society for the Promo-
tion of Science, a Grant-in-Aid for Scientific Research, the Ministry
of Education and Science, Japan, the Asahi Glass Science Founda-
tion, the Toray Foundation and the Sumitomo Foundation.
Entry
ArX
1a
1a
1a
1b
1c
Alkene
Temp (°C)
Product Yield (%)b
1
2
2
2
2
2
2
2
2
2
25
25
80
25
25
25
50
50
50
3a
3a
3a
3b
3c
3d
3e
3f
96
93
52
93
95
98
98
99
97
2c
3c
4
References
(1) Visiting graduate student from Gifu University.
(2) For reviews, see: (a) Li, C.-J.; Chan, T.-H. Organic
Reactions in Aqueous Media; Wiley-VCH: New York,
1997. (b) Grieco, P. A. Organic Synthesis in Water; Kluwer
Academic Publishers: Dordrecht, 1997.
(3) For reviews, see: (a) Bailey, D. C.; Langer, S. H. Chem. Rev.
1981, 81, 109. (b) Shuttleworth, S. J.; Allin, S. M.; Sharma,
P. K. Synthesis 1997, 1217. (c) Burgess, K.; Porte, A. M.
Adv. Catal. Proc. 1997, 2, 69. (d) Shuttleworth, S. J.; Allin,
S. M.; Wilson, R. D.; Nasturica, D. Synthesis 2000, 1035.
(e) Dörwald, F. Z. Organic Synthesis on Solid Phase; Wiley-
VCH: Weinheim, 2000.
(4) Uozumi, Y.; Hayashi, T. Solid-Phase Palladium Catalysis
for High-throughput Organic Synthesis, In Handbook of
Combinatorial Chemistry; Nicolaou, K. C.; Hanko, R.;
Hartwig, W., Eds.; Wiley-VCH: Weinheim, 2002, 531–584.
(5) (a) Uozumi, Y.; Danjo, H.; Hayashi, T. Tetrahedron Lett.
1997, 38, 3557. (b) Uozumi, Y.; Danjo, H.; Hayashi, T. J.
Org. Chem. 1999, 64, 3384. (c) Uozumi, Y.; Watanabe, T.
J. Org. Chem. 1999, 64, 6921. (d) Danjo, H.; Tanaka, D.;
Hayashi, T.; Uozumi, Y. Tetrahedron 1999, 55, 14341.
(e) Uozumi, Y.; Nakazono, M. Adv. Synth. Catal. 2002, 344,
274. (f) Uozumi, Y.; Kobayashi, Y. Heterocycles 2003, in
press.
5
6
1d
1e
7d
8
1f
9
1g
3g
10
11
1h
1a
2
80
25
3h
16
92
59
12
12
1a
13
50
17
92
13
14
1a
1a
14
15
50
25
18e
19
93f
48
a All reactions were carried out in water with shaking in the presence
of 10 mol% palladium of PS-PEG resin-supported catalyst 4 and 3
equiv of KOH. The ratio of 1 (mol)/2 (mol)/H2O (L) = 1.0/2.0/2.5
unless otherwise noted.
b Isolated yield.
c The ratio of 1a/2 = 2.0/1.0.
(6) For recent examples of the Heck reaction in water, see:
(a) Amengual, R.; Genin, E.; Michelet, V.; Savignac, M.;
Genet, J.-P. Adv. Synth. Catal. 2002, 344, 393.
d Toluene (10 vol% to H2O) was used as a co-solvent (see ref.14).
e Including 8% of 18 .
f GC yield (internal standard: biphenyl).
(b) Mukhopadyay, S.; Rothenberg, G.; Joshi, A.; Baidossi,
M.; Sasson, Y. Adv. Synth. Catal. 2002, 344, 348.
(c) Genet, J.-P.; Savignac, M. J. Organomet. Chem. 1999,
576, 305; and references cited therein.
along with its regioisomer 20 (15%) (entry 14), where
a new chiral carbon center was generated via the catalytic
pathway. Taking into account of possible extension to
asymmetric carbon-carbon bond forming catalysis in wa-
ter, this reaction system is quite interesting though the
chemical yield was moderate.16
(7) One isolated example of a water-based Heck reaction using
an amphiphilic resin-supported palladium catalyst was
reported in ref. 5c.
(8) Loading of Pd (mmol/g) of the supported catalysts: 4: 0.32,
5: 0.32, 6: 0.33, 7: 0.61, 8: 0.55, 9: 0.32, 10: 0.33, 11: 0.52.
(9) (a) Bayer, E.; Rapp, W. In Chemistry of Peptides and
Proteins, Vol. 3; Voelter, W.; Bayer, E.; Ovchinikov, Y. A.;
Iwanov, V. T., Eds.; Walter de Gruter: Berlin, 1986, 3.
(b) Rapp, W. In Combinatorial Peptide and Nonpeptide
Libraries; Jung, G., Ed.; VCH: Weinheim, 1996, 425.
(c) Du, X.; Armstrong, R. W. J. Org. Chem. 1997, 62, 5678.
(d) Gooding, O. W.; Baudert, S.; Deegan, T. L.; Heisler, K.;
Labadie, J. W.; Newcomb, W. S.; Porco, J. A. Jr.; Eikeren,
P. J. Comb. Chem. 1999, 1, 113.
(10) PEGA resin is a copolymerisate of acrylamidopropyl(2-
aminopropyl)polyethylene glycol and N,N-dimethylacryl-
amide crosslinked with bis(2-acrylamidopropyl)poly-
ethylene glycol, see: Meldal, M. Tetrahedron Lett. 1992, 33,
3077.
Recyclability of the PS-PEG resin supported palladium
catalyst 4 was examined for the subsequent reaction of 1a
and 2. Thus, after the first reaction, which gave 93% yield
of 3a (Table 2, entry 2), the catalyst resin was recovered
by filtration and successively subjected to a second series
of the reaction under the same conditions to afford 95% of
3a. The average yield of 5 continuous runs was 92%.
In summary, an amphiphilic PS-PEG resin-supported
palladium-phosphine complex 4 was identified as the best
immobilized catalyst to promote the Heck reaction in
water to give quantitative yields of the Heck products of
various aryl halides and alkenes. Further studies toward
asymmetric Heck reaction in water using amphiphilic
resin-supported chiral catalysts17 are now in progress and
will be reported in due course.
(11) Purchased from Argonaut Technologies, San Carlos, CA,
USA.
Synlett 2002, No. 12, 2045–2048 ISSN 0936-5214 © Thieme Stuttgart · New York