Remarkable rate enhancement of palladium-catalyzed allylic alkylation in water using a colloidal dispersion system

Article abstract of DOI:10.1016/S0040-4039(00)01027-3

The rate of palladium-catalyzed allylic alkylation was dramatically enhanced in a colloidal dispersion system created by a neutral surfactant, Triton X-100, in water. (C) 2000 Elsevier Science Ltd.

Full text of DOI:10.1016/S0040-4039(00)01027-3

Tetrahedron Letters 41 (2000) 6115±6119
Remarkable rate enhancement of palladium-catalyzed allylic
alkylation in water using a colloidal dispersion system
-
Shu Kobayashi,* William W.-L. Lam and Kei Manabe
Graduate School of Pharmaceutical Sciences, The University of Tokyo, Hongo, Bunkyo-ku, Tokyo 113-0033, Japan
Received 29 May 2000; revised 14 June 2000; accepted 16 June 2000
Abstract
The rate of palladium-catalyzed allylic alkylation was dramatically enhanced in a colloidal dispersion
system created by a neutral surfactant, Triton X-100, in water. # 2000 Elsevier Science Ltd. All rights
reserved.
Keywords: palladium; colloidal dispersions; surfactants; allylic alkylation; aqueous reactions.
Recently, organic transformations in aqueous media, particularly in water, have received much
attention, because water is easily available, economical, and harmless to the environment.1 We
and others have reported that several reactions such as Mukaiyama aldol reactions,2 allylation
reactions,3 Mannich-type reactions,4 Michael reactions,5 Diels±Alder reactions,6 and a-amino
phophonate synthesis7 can be realized by surfactant-aided Lewis acid or Brùnsted acid catalysis
in water. Transition metal-catalyzed hydrogenation8 and hydroformylation9 and several palladium-
catalyzed reactions10 in water have been performed in the presence of surfactants. These results
prompted us to study other catalytic organic transformations in aqueous media.
Palladium-catalyzed carbon carbon bond-forming reactions have been intensively studied as
one of the most ecient reactions in organic synthesis.11 The reactions are usually performed
under very mild conditions with a small amount of the catalyst. In the last decade, several palladium-
catalyzed reactions in aqueous media have been developed.1,10,12 Sinou et al. and Genet et al.
have reported that palladium-catalyzed allylic substitution reactions can be performed in a
homogeneous or a two-phase aqueous±organic medium using an in situ generated catalyst from
Pd(OAc)2 and a water-soluble monophosphine ligand (TPPTS: trisodium salt of tri(m-sulfonato-
phenyl)phosphine).13 However, their procedures su€er from high catalyst loading, high
reaction temperatures, and long reaction times. Therefore, a more ecient catalytic system is
highly desirable. Quite recently, Bergbreiter et al. and Uozumi and Hayashi et al. have
demonstrated that polymer-supported amphiphilic palladium phosphine complexes showed high
* Corresponding author. Fax: +81 3 5684 0634; e-mail: skobayas@mol.f.u-tokyo.ac.jp
0040-4039/00/$ - see front matter # 2000 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(00)01027-3

6116
activity to promote allylic substitution reactions in water.14 Here we report that palladium-
catalyzed allylic alkylation reactions proceeded rapidly in the presence of a nonionic surfactant in
water without using organic solvents.
The reaction of allyl acetate with b-ketoester 1 was selected as a model reaction (Table 1). On
the basis of our recent work on surfactant-aided acid catalysis, we tested several surfactants for
the model reaction in the presence of Pd(PPh3)4 and potassium carbonate as a base in water.
Indeed, the surfactants greatly a€ected the rate of the reaction. Although an anionic surfactant,
sodium dodecyl sulfate (SDS) a€orded the desired product 2 in a low yield (entry 1), use of a
cationic surfactant, cetyltrimethylammonium bromide (CTAB), resulted in a good yield (entry 2).
Furthermore, when a neutral surfactant, Triton X-100 [4-(C8H17)C6H4(OCH2CH2)nOH], was
used, the reaction was dramatically accelerated and completed in 5 min to provide the product in
an excellent yield (entry 3). It should be noted that the nonionic surfactant gave much better
results than the cationic and anionic surfactants, and that only 1 mol% Pd was required for the
reaction. In addition, an expensive, water-soluble phosphine ligand was not needed. The reaction
mixture was a white, colloidal dispersion, which should be essential for the ecient catalysis (vide
infra).
Table 1
Palladium-catalyzed allylic alkylation in water
Encouraged by this observation, we carried out a detailed study on the reaction pro®le under
di€erent conditions using b-ketoester 1 as a substrate (Fig. 1). One of the most typical reaction
protocols using N,O-bis(trimethylsilyl)acetamide (BSA) as a base in toluene (Fig. 1B) was selected
as a reference. As shown in Fig. 1, the reaction in our surfactant-aided system (Fig. 1,A) proceeded
signi®cantly rapidly compared to the reaction in toluene. Over 50% yield of the product was
isolated after 1 min and the reaction was basically over in 5±6 min. It should be noted that the
same reaction in aqueous media containing mixtures of MeCN and H2O using either typical
Pd(PPh3)4 (Fig. 1C) or water-soluble Pd(TPPTS)411 (Fig. 1 D) proceeded relatively slowly. These
results clearly show that our colloidal dispersion system enables rapid allylic alkylation reactions
much more e€ectively than other reaction systems.
Under the optimized conditions with Triton X-100 as a surfactant, various substrates smoothly
reacted with both simple and substituted allyl acetates15 to give the corresponding products in
good to excellent yields as shown in Table 2. Although the reaction times in Table 2 were 45 min
to 2 h, the reactions completed in shorter periods of time in most cases. As for nucleophiles, not

6117
Figure 1. Palladium-catalyzed reaction of allyl acetate (1 equiv.) with 1 (1.1 equiv.) at 30ꢀC under several conditions.
(A) Pd(PPh3)4 (1 mol%), Triton X-100 (5 mol%), K2CO3 (1.1 equiv.), H2O; (B) Pd(PPh3)4 (1 mol%), BSA (1.1 equiv.),
toluene; (C) Pd(PPh3)4 (1 mol%), K2CO3 (1.1 equiv.), H2O/MeCN (1/2); (D) Pd(OAc)2 (2 mol%), TPPTS (18 mol%),
K2CO3 (1.1 equiv.), H2O/MeCN (1/1). The yields are based on allyl acetate
only b-ketoesters (entries 1±7), but also a b-diester (entry 8), a b-diketone (entry 9), and an
a-nitroester (entry 10) worked well. It is noted that an a-unsubstituted b-ketoester gave the
monoallylated product preferentially (entry 7) with a small amount of the diallylated compound
(5%). It is also worthy to mention that a,b-unsaturated enones could be used without forming
any base-catalyzed conjugate addition products (entries 3 and 4).
A typical reaction procedure is as follows. To a 20 mL two-necked ¯ask containing Pd(PPh3)4
(1 mol%) was added an aqueous solution of Triton X-100 (5 mol% in 1 mL H2O) at ambient
temperature. An allylic acetate (0.50 mmol) was then introduced to the mixture. After stirring for
15 min, a substrate (1.1 equiv.) was added to give a white turbid mixture. An aqueous solution of
ꢀ
K2CO3 (1.1 equiv. in 0.5 mL H2O) was then added at 30 C. After stirring for 5 min to 2 h
(depending on the substrates), the reaction was quenched with a saturated aqueous solution of
NH4Cl. After a usual work-up, the combined organic extracts were dried (Na2SO4), ®ltered, and
concentrated in vacuo. The residue was then puri®ed by preparative TLC or column
chromatography (SiO2, ether/hexane) to a€ord the desired product.
In summary, we have developed an ecient palladium-catalyzed allylic alkylation system in
water using a surfactant. In this reaction, colloidal dispersion systems formed rapidly in water.
While the advantages of organic transformation in water are now well recognized, most organic
substances are insoluble in water and, as a result, water does not function as a reaction medium in
many cases. The use of surfactant-aided Lewis acid or Brùnsted acid catalysts enabled several
organic reactions in water using stable colloidal dispersions, and this paper has shown that this
idea can be successfully applied to palladium-catalyzed allylic alkylation. It is noted that a
nonionic surfactant was much more e€ective than a cationic or an anionic surfactant, and that the
reactions proceeded rapidly without using high temperature, and the desired products were obtained
in high yields. This colloidal dispersion system may be applicable to other palladium-catalyzed
organic transformations.

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Table 2
Palladium-catalyzed allylic alkylation in a colloidal dispersion systema
Acknowledgements
This work was partially supported by CREST, Japan Science Technology Corporation (JST),
and a Grant-in-Aid for Scienti®c Research from the Ministry of Education, Science, Sports, and
Culture, Japan. W.W.L.L. thanks JSPS (Japan Society for Promotion of Science) for a post-
doctoral research fellowship.

6119
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