Preparation and application of a polymer-supported chiral π-allylpalladium catalyst for the allylation of imines

Article abstract of DOI:10.1016/S0040-4039(99)02032-8

The polymer-supported chiral π-allylpalladium catalyst 8 was applied to the asymmetric allylation reaction of imines 9 with allyltributylstannane. The catalyst was very stable and could be reused several times with high catalytic activity, although the enantioselectivity was not necessarily high.

Full text of DOI:10.1016/S0040-4039(99)02032-8

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 41 (2000) 131–134
Preparation and application of a polymer-supported chiral
π-allylpalladium catalyst for the allylation of imines
Ming Bao, Hiroyuki Nakamura and Yoshinori Yamamoto ∗
Department of Chemistry, Graduate School of Science, Tohoku University, Sendai 980-8578, Japan
Received 23 September 1999; accepted 26 October 1999
Abstract
The polymer-supported chiral π-allylpalladium catalyst 8 was applied to the asymmetric allylation reaction
of imines 9 with allyltributylstannane. The catalyst was very stable and could be reused several times with high
catalytic activity, although the enantioselectivity was not necessarily high. © 1999 Elsevier Science Ltd. All rights
reserved.
Keywords: polymer support; palladium catalyst; imines; catalytic asymmetric allylation.
In catalytic asymmetric synthesis, polymer-supported chiral catalysts offer the following advantages
over the usual homogeneous catalysts; easy recovery and potential recycling of expensive chiral catalysts,
simplified product purification and the possibility of carrying out the desired transformation in a
continuous-flow system. Although many examples of asymmetric reactions with chiral transition-metal
catalysts that employ polymer-supported chiral ligands containing P, N and O atoms have been given
over recent years,1,2 to the best of our knowledge, asymmetric reactions with polymer-supported chiral
π-allylpalladium catalysts have not been reported so far. We recently reported the asymmetric allylation
reaction of imines with allyltributylstannane catalyzed by the chiral π-allylpalladium catalyst 1 (Fig. 1,
1). Mechanistic studies revealed that the unsymmetrical bis-π-allylpalladium complex 2 is a reactive
intermediate for this allylation; the allyl group reacts as a nucleophile with an imine and the other
sterically bulky chiral π-allyl group acts as a nontransferable π-allyl ligand (Fig. 1, 2).3 It occurred
to us that if a nontransferable chiral π-allyl ligand is bound to a polymer and another π-allyl group is
transferred as a nucleophile selectively to imines (Fig. 1, 3), we may carry out the polymer-supported
catalytic asymmetric allylation of imines. It was thought that the reaction of a chloromethylated polymer
resin with a chiral source containing a hydroxyl group, which afterwards can be converted to a bis-π-
allylpalladium species, would be suitable to make a polymer-bound chiral reagent (Fig. 1, 4).
According to this design, we chose estrone as a chiral source, which was bound to the PS/DVB copoly-
mer with a chloromethylated functionality (Scheme 1).4 To a mixture of chloromethylated polystyrene
∗
Corresponding author. Tel: +81 22 217 6581; fax: +81 22 217 6784; e-mail: yoshi@yamamoto1.chem.tohoku.ac.jp
0040-4039/00/$ - see front matter © 1999 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(99)02032-8
tetl 15960

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Fig. 1.
5 (2.685 g; Cl, 0.97 mmol/g) and estrone (7.042 g, 10 equiv.) in 30 mL of o-dichlorobenzene were
added a 40% solution of tetrabutylammonium hydroxide (0.3 mL) and aqueous solution of NaOH (1.6
g, 5 mL H2O). The mixture was placed in an oil bath at 80°C and stirred magnetically for 3 days.
After filtration the resulting polymer was washed repeatedly with methanol, water, THF:H2O (3:1),
THF, acetone, dichloromethane and methanol, and then dried overnight at 60°C under vacuum. Chlorine
analysis showed no chlorine present in the product. The resulting polymer 6 indicated a new infra-red
band at 1740 cm−1 (C_O); cf. 1720 cm−1 (C_O for estrone). The polymer-supported exoethylidene 7
was prepared by treating the polymer 6 with excess of triphenylphosphonium ethyl bromide (10 equiv.)
and tBuOK (9.5 equiv.) in THF under reflux for 41 h. The product 7 was filtered off, washed, and dried
as described above. The strong C_O band at 1740 cm−1 disappeared in the infra-red spectrum of 7.
The polymer-supported exoethylidene 7 (0.97 g, 0.5 mmol) and palladium trifluoroacetate (166 mg,
0.5 mmol) were stirred at ambient temperature in 5 mL THF for 6 h, and then tetra-n-butylammonium
chloride (153 mg, 0.55 mmol) was added. The resulting mixture was left under stirring for 1 h. It was then
filtered, washed as described above, and dried overnight under vacuum at room temperature.5 Thus, the
yellow polymer-supported chiral π-allylpalladium catalyst 8 was prepared. ICP analysis indicated that
the ratio of Pd was 4.6 wt%; if the exoethylidene group attached to the polymer resin was completely
converted to the π-allylpalladium functionality the ratio should be 7.5 wt% indicating that there would
be free ethylidene groups in the resulting polymer.
Scheme 1.
We tested this catalyst 8 in the asymmetric allylation of imines 9 with allyltributylstannane. The results
are summarized in Table 1. Since the catalyst 8 swelled better in THF than in DMF, THF was chosen as
a solvent.6 DMF was an effective solvent for the imine allylation reaction with chiral π-allylpalladium
catalyst 1.3 The allylation reaction of 9a using 1.2 equiv. allyltributylstannane in THF at 0°C gave 10a in
76% yield with 42% ee (entry 1). Although the allylation of 9b gave a very good yield (91%), a lower ee
was observed (13%; entry 2); the enantioselectivity was the same as that using the chiral π-allylpalladium
catalyst 1. The reactions of 9c and 9d were very sluggish, giving the corresponding homoallylamines 10c
and 10b in low yields with 38 and 35% ee, respectively (entries 3 and 4). The allylation reaction of 9e

133
Table 1
Asymmetric allylation of imines 9 catalyzed by polymer-supported chiral π-allylpalladium catalyst 8
gave 10e in 77% yield with 26% ee. The imines prepared from aliphatic aldehydes (9f and 9g) gave 10f
and 10g in very good yields (89 and 98%) with 38 and 36% ee, respectively (entries 6 and 7). These results
clearly indicate that the polymer-supported chiral π-allylpalladium catalyst 8 is effective for the catalytic
allylation reaction of imines with allyltributylstannane, the catalytic activity of which is comparable to
that using the homogeneous chiral π-allylpalladium catalyst 1, although the enantioselectivity obtained
with 8 is lower than that with the homogeneous system.
A representative procedure for the allylation reaction of imines is as follows. To a mixture of polymer-
supported chiral π-allylpalladium catalyst 8 (94 mg, 0.04 mmol Pd) and the imine 9a (78 mg, 0.4 mmol)
in 2 mL THF at 0°C was added allyltributylstannane (159 mg, 0.48 mmol). The mixture was stirred for
140 h, and then filtered. The reaction progress was monitored by TLC, and the allyltributylstannane
disappeared after 140 h. The catalyst was washed with THF, and the filtrates were combined. The
solvent was removed under reduced pressure, and the crude product was purified by silica gel column
chromatography (hexane:ethyl acetate=5:1), giving 10a in 76% yield. The optical purity was determined
by HPLC analysis using a chiral column.
We next investigated the stability of the catalyst in order to recycle it. The results of repeated use of the
catalyst for the allylation of 9a are summarized in Table 2. Using the fresh catalyst 8, 10a was obtained
in 76% yield with 42% ee (run 1). The use of the recovered catalyst gave 10a in 78% yield with 47%
ee (run 2). Again, the catalyst was recovered and used repeatedly. Essentially, same yields and ees were
Table 2
Recycle use of the catalyst 8 for the allylation of 9aa

134
obtained by the use of the catalyst recovered either from the reaction of run 2 or from that of run 3.
It is interesting that even a slightly higher ee was obtained by the use of the recovered catalyst. These
results clearly indicate that the polymer-supported chiral π-allylpalladium catalyst is very stable and can
be used repeatedly.
In summary, we have prepared the polymer-supported chiral π-allylpalladium catalyst 8 for the first
time. The catalyst was very stable and can be reused with high catalytic activity for allylation reaction of
imines, although the enantioselectivities were not necessarily high.
References
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