Catalytic asymmetric allylic alkylation in water with a recyclable amphiphilic resin-supported P,N-chelating palladium complex

Full text of DOI:10.1021/ja005866j

J. Am. Chem. Soc. 2001, 123, 2919-2920
2919
Scheme 1
Catalytic Asymmetric Allylic Alkylation in Water
with a Recyclable Amphiphilic Resin-Supported
P,N-Chelating Palladium Complex
Yasuhiro Uozumi* and Kazutaka Shibatomi†
Institute for Molecular Science (IMS), Nishi-Gonaka 38
Myodaiji, Okazaki 444-8585, Japan
Faculty of Pharmaceutical Sciences, Nagoya City UniVersity
Mizuho-ku, Nagoya 467-8603, Japan
ReceiVed December 9, 2000
Highly enantioselective reactions in water with recyclable
immobilized chiral catalysts are an important goal in synthetic
organic chemistry.1,2 We recently reported that several palladium-
catalyzed reactions,3 including π-allylic substitution,3a,d carbonyla-
tion,3c the Heck reaction,3c and Suzuki-Miyaura cross-coupling,3b
took place in water4 by use of palladium-phosphine complexes
bound to an amphiphilic polystyrene-poly(ethylene glycol) graft
copolymer (PS-PEG) resin.5 These encouraging results prompted
us to design new chiral complexes supported on the amphiphilic
PS-PEG resin, which would exhibit catalytic activity as well as
enantioselectivity in water in several types of transition metal-
catalyzed asymmetric organic transformations.6 We describe
herein the design and preparation of a new P,N-chelate chiral
ligand bound to PS-PEG resin and its use for palladium-catalyzed
asymmetric allylic substitution in water, in which enantioselec-
tivity up to 99/1 was achieved.
by a sequence of reactions shown in Scheme 1, was immobilized
on PS-PEG-NH2 resin9 to give the PS-PEG resin-supported chiral
P,N-chelate ligand (R,S)-2 (Scheme 1).10 Formation of a palladium
complex of the P,N-chelate ligand was performed by mixing
[PdCl(η3-C3H5)]2 in toluene at room temperature for 10 min to
give the PS-PEG supported P,N-chelate complex 2-Pd in quan-
titative yield. Following the same procedure, PS-PEG resin-
supported complexes 3-Pd and 4-Pd were also prepared.
To explore the enantiocontrolling potential of the resin-
supported complexes in water,11 we elected to study palladium-
catalyzed asymmetric allylic substitution of cyclic substrates,
which is still a major challenge even with homogeneous chiral
catalysts.12 We were very pleased to find that high stereoselectivity
was achieved in water when the PS-PEG resin-supported catalyst
2-Pd was used for allylic substitution of the cyclic substrates with
dialkyl malonate (Scheme 2). Thus, the reaction of methyl
cyclopentenyl carbonate (5) and dimethyl malonate (8a) was
catalyzed by 2-Pd in aqueous lithium carbonate at 40 °C to give
68% isolated yield of the allylic alkylated adduct (S)-9a with
enantiomeric excess of 92% (Table 1, entry 1).13 The reactions
with diethyl malonate (8b) in place of 8a afforded approximately
During our studies on the design of new chiral reagents,7 highly
functionalized optically active bicyclic amines having a pyrrolo-
[1,2-c]imidazolone framework were identified as effective chiral
agents through a diversity-based approach to new chiral amine
catalysts.8 The results indicated that a novel P,N-chelate chiral
ligand having the pyrrolo[1,2-c]imidazolone skeleton as a basic
chiral unit would be readily immobilized on the PS-PEG resin to
achieve highly enantioselective heterogeneous catalysis in water
(Scheme 1). (3R,9aS)-(2-Aryl-3-(2-diphenylphosphino)phenyl)-
tetrahydro-1H-imidazo[1,5-a]indole-1-one (1), which was readily
prepared from (S)-indoline-2-carboxylic acid, 4-{3-(methoxy-
carbonyl)propyl}aniline, and 2-(diphenylphosphino)benzaldehyde
* Address correspondence to this author at the Institute for Molecular
Science.
† Nagoya City University.
(1) For examples, see: (a) Anastas, P. T.; Williamson, T. C., Eds. Green
Chemistry; ACS Symp. Ser. 626; American Chemical Society: Washington:
DC, 1996, and references therein. (b) Li, C.-J.; Chan, T.-H. Organic Reactions
in Aqueous Media; Wiley: New York, 1997. (c) Grieco, P. A., Ed. Organic
Synthesis in Water; Kluwer Academic Publishers: Dordrecht, The Netherlands,
1997.
(2) For a review, see: De Vos, D. E.; Vankelecom, I. F. J.; Jacobs, P. A.,
Eds. Chiral Catalyst Immobilization and Recycling; Wiley-VCH: Weinheim,
2000.
(3) (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.
(4) For a review, see: Herrmann W. A.; Kohlpaintner, C. W. Angew. Chem.,
Int. Ed. Engl. 1993, 32, 1524.
(5) Recently, palladium-catalyzed reactions in water with polymer-supported
palladium-phosphine complexes have been reported, see: Bergbreiter, D.
E.; Liu, Y.-S. Tetrahedron Lett. 1997, 38, 7843.
(6) As a preliminary result, we have reported PS-PEG supported MOP
ligands which achieved asymmetric π-allylic substitution of 1,3-diphenylpro-
penyl acetate in water with up to 84% ee: Uozumi, Y.; Danjo, H.; Hayashi,
T. Tetrahedron Lett. 1998, 39, 8303.
(7) (a) Uozumi, Y.; Hayashi, T. J. Am. Chem. Soc. 1991, 113, 9887. (b)
Hayashi, T.; Iwamura, H.; Naito, M.; Matsumoto, Y.; Uozumi, Y. J. Am. Chem.
Soc. 1994, 116, 775. (c) Uozumi, Y.; Kato, K.; Hayashi, T. J. Am. Chem.
Soc. 1997, 119, 5063.
(8) (a) Uozumi, Y.; Mizutani, K.; Nagai, S.-I. Tetrahedron Lett. 2001, 42,
407. (b) Uozumi, Y.; Yasoshima, K.; Miyachi, T.; Nagai, S.-I. Tetrahedron
Lett. 2001, 42, 411.
(9) (a) Rapp, W. In Combinatorial Peptide and Nonpeptide Libraries; Jung,
G., Ed.; VCH, Weilheim, 1996; p 425. (b) Du, X.; Armstrong, R. W. J. Org.
Chem. 1997, 62, 5678. (c) 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) The solid-phase reactions were monitored by 13C and 31P MAS NMR
studies; see Supporting Information.
(11) For recent examples of nonasymmetric palladium-catalyzed allylic
substitutions in water, see: (a) Safi, M.; Sinou, D. Tetrahedron Lett. 1991,
32, 2025. (b) Geneˆt, J. P.; Blart, E.; Savignac, M. Synlett 1992, 715. (c) Blart,
E.; Geneˆt, J. P.; Safi, M.; Savignac, M.; Sinou, D. Tetrahedron 1994, 50,
505. (d) Sigismondi, S.; Sinou, D. J. Mol. Catal. A: Chem. 1997, 38, 3557.
(e) Kobayashi, S.; Lam, W. W.-L.; Manabe, K. Tetrahedron Lett. 2000, 41,
6115.
(12) Earlier reported catalyst systems that give greater than 90% ee with
cyclic substrates: (a) Trost, B. M.; Bunt, R. C. J. Am. Chem. Soc. 1994, 116,
4089. (b) Knu¨hl, G.; Sennhenn, P.; Helmchen, G. J. Chem. Soc., Chem.
Commun. 1995, 1845. (c) Kudis, S.; Helmchen, G. Angew. Chem., Int. Ed.
1998, 37, 3047. (d) Gilbertson, S.; Xie, D. Angew. Chem., Int. Ed. 1999, 38,
2750. (e) Evans, D. A.; Campos, K. R.; Tedrow, J. S.; Michael, F. E.; Gagne´,
M. R. J. Am. Chem. Soc. 2000, 122, 7905. (f) Saito, A.; Achiwa, K.; Tanaka,
K.; Morimoto, T. J. Org. Chem. 2000, 65, 4227.
10.1021/ja005866j CCC: $20.00 © 2001 American Chemical Society
Published on Web 02/28/2001

2920 J. Am. Chem. Soc., Vol. 123, No. 12, 2001
Communications to the Editor
Scheme 2
counterpart in organic solvent.14 Other PS-PEG supported cata-
lysts, 3-Pd and 4-Pd, were examined for the allylic substitution
of 12 with 8b. The catalysts 3-Pd and 4-Pd, which lack the fused
aromatic moiety on their pyrroloimidazolone ring system, gave
13b with much lower selectivity (23% ee in 55% yield, and 32%
ee in 44% yield, respectively) (entries 10 and 11).
It is noteworthy that the immobilized complex 2-Pd is less
catalytically active in an organic solvent. Thus, the alkylation of
12 with 8b in dichloromethane in the presence of N,O-bis-
(trimethylsilyl)acetamide (BSA) and lithium acetate gave 35%
yield of the adduct 13b with 87% ee, whereas the reaction
proceeded smoothly in aqueous lithium carbonate (entries 9 and
12). In the aqueous media, the organic substrates (e.g., 12 and 8)
must diffuse into the hydrophobic PS matrix to form the highly
concentrated reaction sphere that should react with ionic species
(e.g., aqueous alkaline) through the interfacial PEG region15
exhibiting higher reactivity than those in an organic solvent.
The PS-PEG supported catalyst 2-Pd was effective for the
asymmetric allylic alkylation of both cyclic and acyclic substrates
in water.12a,e The reactions of 1,3-diphenylpropenyl acetate (14)
and pivalate (15) were catalyzed by 2-Pd under the same reaction
conditions to give 16 of 91% ee and 94% ee, respectively.16
The recycle experiments were examined for the asymmetric
substitution of 6 with 8b catalyzed by 2-Pd. After the first run
giving 91% ee of the adduct 10b (Table 1, entry 5), the reaction
mixture was filtered and the catalyst-resin was rinsed twice with
THF.17 The recovered resin-supported catalyst 2-Pd was succes-
sively subjected to a second and a third series of the reactions to
give 10b of 90% ee in 70% yield (second run) and of 90% ee in
65% yield (third run).
Table 1. Catalytic Asymmetric Alkylation of Allylic Esters in
Water by Use of PS-PEG Resin-Supported Pd Complexesa
allylic nucleo-
yield
catalyst product (%)b (config)d
% eec
entry
ester
phile
1
2
3
5
5
6
6
6
7
7
12
12
12
12
12
14
15
8a
8b
8a
8b
8b
8a
8b
8a
8b
8b
8b
8b
8a
8a
2-Pd
2-Pd
2-Pd
2-Pd
2-Pd
2-Pd
2-Pd
2-Pd
2-Pd
3-Pd
4-Pd
2-Pd
2-Pd
2-Pd
9a
9b
68
67
71
78
60
84
94
71
80
55
44
35
86
50h
92 (S)
92 (S)
89 (S)
89 (S)
91 (S)
97 (S)
98 (S)
90 (S)
90 (S)
23 (S)
32 (S)
87 (S)
91 (S)
94 (S)
10a
10b
10b
11a
11b
13a
13b
13b
13b
13b
16
4
5e
6
7
8
9
10
11
12f
13e
14e,g
In summary, we have developed an immobilized palladium
complex of a P,N-chelate chiral ligand on an amphiphilic PS-
PEG resin, which catalyzed the asymmetric π-allylic substitution
of both cyclic and acyclic substrates in water with enantioselec-
tivity of up to 98% ee. The catalyst was recovered by simple
filtration and was reused without any loss of activity and
stereoselectivity. To the best of our knowledge, this is the first
successful work on immobilized recyclable asymmetric catalysis
in water.
16
a All reactions were carried out at 40 °C for 12 h in 0.9 M aqueous
Li2CO3 under N2 unless otherwise noted. The ratio of cyclic substrate
(mol)/nucleophile (mol)/catalyst (Pd equiv)/H2O (L) ) 1.0/3.0/0.3/5.0.
b Isolated yield. c For 9a,b: determined by NMR shift experiment with
use of Eu(hfc)3. For 10-13: determined by GC analysis with use of a
chiral stationary phase capillary column (Cyclodex CB).For 16a,b:
determined by HPLC analysis with use of a chiral stationary phase
column (Dicel OD-H; hexane/i-PrOH ) 98/2). d See Supporting
Information. e Carried out at 25 °C. f Carried out in dichloromethane.
g 5 mol % Pd of 2-Pd complex was used. h 35% of 15 was recovered.
Acknowledgment. This work was supported by a Grant-in-Aid for
Scientific Research, the Ministry of Education, Japan.
Supporting Information Available: Characterization data and
experimental procedures for compounds 1, 2, 2-Pd, 9a, 9b, 10a, 10b,
11a, 11b, 13a, and 13b (PDF). This material is available free of charge
via the Internet at http://pubs.acs.org.
the same results (67% yield, 92% ee (S)) (entry 2). The
six-membered substrate 6 also underwent asymmetric alkylation
with 8a and 8b to afford the corresponding alkylated adducts 10a
and 10b with enantioselectivity of 89% ee (entries 3 and 4). The
best results were obtained for the reactions of cycloheptene ester
7 with 8a and 8b giving 11a and 11b under otherwise similar
conditions where the chemical yields and enantiomeric purities
were increased to 84% yield, 97% ee (S) (for 11a) and 94% yield,
98% ee (S) (for 11b) (entries 6 and 7).
The alkylation of the racemic cis-5-carbomethoxy-2-cyclohex-
enyl methyl carbonate (12) with 8b gave 90% ee of 13b in 80%
yield as a single diastereoisomer having the cis-configuration,
demonstrating that the reaction pathway of allylic substitution in
water is essentially the same as that of the homogeneous
JA005866J
(14) Hayashi, T.; Yamamoto, A.; Hagihara, T.; Ito, Y. Tetrahedron Lett.
1986, 27, 191.
(15) PEG itself is known to be a phase-transfer catalyst to transport an
ionic species to a less-polar organic phase, see: (a) Dehmlow, E. V.; Dehmlow,
S. S. Phase Transfer Catalysis; VCH: Weinheim, 1993. (b) Starks, C. M.;
Liotta, C. L.; Halpern, M. Phase-Transfer Catalysis; Chapman & Hall: New
York, 1994. (c) Halpern, M. E., Ed. Phase-Transfer Catalysis, Mechanism
and Synthesis; American Chemical Society: Washington, DC, 1997.
(16) Quite recently, asymmetric π-allylic substitutions in water have been
reported, in which the allylic substrate was limited to 1,3-diphenylpropenyl
acetate. (a) Hashizume, T.; Yonehara, K.; Ohe, K.; Uemura, S. J. Org. Chem.
2000, 65, 5197. (b) Rabeyrin, C.; Nguefack, C.; Sinou, D. Tetrahedron Lett.
2000, 41, 7461.
(17) 31P NMR (MAS NMR, 162 MHz, chloroform-d) of the recovered resin
catalyst; 24 ppm (singlet). It has been reported that a PS-PEG resin-supported
palladium-phosphine complex was stable during 30 continuous runs (see, ref
3c).
(13) The remaining starting material was not detected on 1H NMR and
GC analyses of the crude mixture.