Asymmetric Allylic Amination in Water Catalyzed by an Amphiphilic Resin-Supported Chiral Palladium Complex

Article abstract of DOI:10.1021/ol036264i

(Matrix presented) Catalytic asymmetric allylic amination of cycloalkenyl carbonates (methyl cyclohexen-2-yl carbonate, methyl cyclohepten-2-yl carbonate, methyl 5-methoxycarbonylcyclohexen-2-yl carbonate, methyl cyclohexenyl carbonate, tert-butyl 5-methoxycarbonyloxy-1,2,5,6- tetrahydropyridinedicarboxylate) with dibenzylamines ((C₆H ₅CH₂)₂NH, (C₆H₅CH ₂)(4-CH₃OC₆H₄CH₂)NH, (4-CH₃OC₆H₄CH₂)₂NH) was achieved in water under heterogeneous conditions by use of a palladium complex of (3R,9aS)-3-[2-(diphenylphosphino)phenyl]-2-phenyltetrahydro-1H-imidazo[1,5-a] indole-1-one anchored on polystyrene-poly(ethylene glycol) copolymer resin to give the corresponding cycloalkenylamines with high enantiomeric selectivity (90-98% ee).

Full text of DOI:10.1021/ol036264i

ORGANIC
LETTERS
2004
Vol. 6, No. 2
281-283
Asymmetric Allylic Amination in Water
Catalyzed by an Amphiphilic
Resin-Supported Chiral Palladium
Complex
Yasuhiro Uozumi,* Hirotaka Tanaka, and Kazutaka Shibatomi
Institute for Molecular Science (IMS), Myodaiji, Okazaki 444-8585, Japan
uo@ims.ac.jp
Received November 20, 2003
ABSTRACT
Catalytic asymmetric allylic amination of cycloalkenyl carbonates (methyl cyclohexen-2-yl carbonate, methyl cyclohepten-2-yl carbonate, methyl
5-methoxycarbonylcyclohexen-2-yl carbonate, methyl cyclohexenyl carbonate, tert-butyl 5-methoxycarbonyloxy-1,2,5,6-tetrahydropyridinedi-
carboxylate) with dibenzylamines ((C H CH ) NH, (C H CH )(4-CH OC H CH )NH, (4-CH OC H CH ) NH) was achieved in water under heterogeneous
6
5
2 2
6
5
2
3
6
4
2
3
6
4
2 2
conditions by use of a palladium complex of (3R,9aS)-3-[2-(diphenylphosphino)phenyl]-2-phenyltetrahydro-1H-imidazo[1,5-a]indole-1-one anchored
on polystyrene−poly(ethylene glycol) copolymer resin to give the corresponding cycloalkenylamines with high enantiomeric selectivity
(90−98% ee).
Aqueous1 and heterogeneous switching2 of a given catalytic
organic reaction are becoming important research subjects
to provide risk-free and environmentally benign processes,
as well as efficient methods for product purification and
catalyst recycling. Recently, we reported that rhodium- and
palladium-phosphine complexes, bound to an amphiphilic
polystyrene-poly(ethylene glycol) copolymer (PS-PEG)
resin, catalyzed various organic transformations in water
under heterogeneous conditions, where the advantages of
both aqueous and heterogeneous switching were combined
in one system.3 On the other hand, development of transition-
metal-catalyzed asymmetric transformations has emerged as
one of the most exciting and challenging subjects in the
domain of modern synthetic chemistry.4 The asymmetric
(1) 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. (c)
Herrmann, W. A.; Kohlpaintner, C. W. Angew. Chem., Int. Ed. Engl. 1993,
32, 1524.
(2) 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) Shuttleworth, S. J.; Allin, S. M.; Wilson, R. D.; Nasturica, D.
Synthesis 2000, 1035. (d) Do¨rwald, F. Z. Organic Synthesis on Solid Phase;
Wiley-VCH: Weinheim, 2000. (e) Ley, S. V.; Baxendale, I. R.; Bream, R.
N.; Jackson, P. S.; Leach, A. G.; Longbottom, D. A.; Nesi, M.; Scott, J. S.;
Storer, R. I.; Taylor, S. J. J. Chem. Soc., Perkin Trans. 1 2000, 3815. (f)
Leadbeater, N. E.; Marco, M. Chem. ReV. 2002, 102, 3217. (h) McNamara,
C. A.; Dixon, M. J.; Bradley, M. Chem. ReV. 2002, 102, 3275.
(3) For studies on polymer-supported palladium catalysts reported by
the author’s group, see: (a) Uozumi, Y.; Danjo, H.; Hayashi, T. Tetrahedron
Lett. 1997, 38, 3557 (π-allylic substitution). (b) Danjo, H.; Tanaka, D.;
Hayashi, T.; Uozumi, Y. Tetrahedron 1999, 55, 14341 (π-allylic substitu-
tion). (c) Uozumi, Y.; Danjo, H.; Hayashi, T. J. Org. Chem. 1999, 64, 3384
(cross-coupling). (d) Uozumi, Y.; Watanabe, T. J. Org. Chem. 1999, 64,
6921 (carbonylation reaction). (e) Uozumi, Y.; Nakai, Y. Org. Lett. 2002,
4, 2997 (Suzuki coupling). (f) Uozumi, Y.; Kimura, T. Synlett 2002, 2045
(Heck reaction). (g) Hocke, H.; Uozumi, Y. Synlett 2002, 2049 (Wacker
reaction). (h) Uozumi, Y.; Kobayashi, Y. Heterocycles 2003, 59, 71
(Sonogashira reaction).
10.1021/ol036264i CCC: $27.50 © 2004 American Chemical Society
Published on Web 12/18/2003

catalytic protocol performed in water under heterogeneous
conditions would approach the realization of what may be
considered an ideal asymmetric reaction.5,6 In an earlier study,
we found that the asymmetric π-allylic alkylation of cy-
cloalkenyl esters with dialkyl malonates was efficiently
catalyzed in water by an immobilized palladium complex
coordinated with a novel chiral ligand, (3R,9aS)-3-[2-
(diphenylphosphino)phenyl]-2-phenyltetrahydro-1H-imidazo-
[1,5-a]indole-1-one, bound to an amphiphilic PS-PEG resin
(1), which was designed and prepared with a view for use
in several transition-metal-catalyzed reactions in water, to
give optically active cycloalkenyl dialkyl malonates of up
to 98% ee.7 With these results in hand, we were eager to
examine the asymmetric π-allylic amination reaction. In
contrast to the vast amount of research on the asymmetric
π-allylic substitution of acyclic esters (e.g., 1,3-diphenyl-
propenyl acetate) with malonate nucleophiles, only scattered
attention has been focused on cyclic substrates with amine
nucleophiles.8 Here we wish to report the results of our
research showing that the palladium-catalyzed asymmetric
amination of cycloalkenyl esters forming optically active
cyclic allylamines was achieved in water by use of the PS-
PEG resin-supported chiral imidazoindole phosphine ligand
1, with a stereoselectivity of up to 98% ee.
Scheme 1
(7a), whose enantiomeric purity was determined by HPLC
analysis with a chiral stationary phase column (CHIRALCEL
OJ) to be 94% ee (Scheme 1) (Table 1, entry 1). The allylic
amination with benzyl(4-methoxybenzyl)amine (6b) or di-
(4-methoxybenzyl)amine (6c) also proceeded with high
stereoselectivity under similar reaction conditions to give
92% ee of 7b or 90% ee of 7c, respectively (entries 2 and
Figure 1. Resin-supported chiral imidazoindole phosphine.
Table 1. Asymmetric Amination of Cycloalkenyl Esters in
Water Catalyzed by Polymeric Catalyst 1a
Amination of the methyl cyclohexenyl carbonate (2) with
5 equiv of dibenzylamine (6a) was carried out in water at
25 °C with shaking for 24 h in the presence of 8 mol % of
the palladium complex of 1 (1-Pd), which was prepared by
mixing 1 and [PdCl(η3-C3H5)]2 just prior to use. The reaction
mixture was filtered, and the catalyst resin was rinsed with
THF to extract the desired product. The crude mixture
obtained from the extract was chromatographed to give 90%
isolated yield of (S)-N,N-dibenzyl(cyclohexen-2-yl)amine
entry
allylic ester
amine
product
yield (%)b
% eec
1
2
3
4
5
6
7
8
2
2
2
3
3
3
4
4
4
5
5
5
6a
6b
6c
6a
6b
6c
6a
6b
6c
6a
6b
6c
7a
7b
7c
8a
8b
8c
9a
9b
9c
10a
10b
10c
90
77
75
91
82
89
61
80
85
89
99
59
94
92
90
98
97
96
90
96
95
95
93
94
(4) For a recent review on asymmetric π-allylic substitution, see: (a)
Acemoglu, L.; Williams, J. M. J. Handbook of Organopalladium Chemistry,
p 1945;Negishi, E., Ed.; Wiley, New York, 2002. (b) Trost, B. M.; Crawley,
M. L. Chem. ReV. 2003, 103, 2921.
(5) For recent reviews on heterogeneous asymmetric catalysis, see: (a)
Chiral Catalyst Immobilization and Recycling; De Vos, D. E., Vankelecom,
I. F. J., Jacobs, P. A., Eds.; Wiley-VCH: Weinheim, 2000. (b) Fan, Q.-H.;
Li, Y.-M.; Chan, A. S. C. Chem. ReV. 2002, 102, 3385.
(6) For a review on asymmetric catalysis in water, see: Lindstro¨m, U.
M. Chem. ReV. 2002, 102, 2751.
(7) (a) Uozumi, Y.; Danjo, H.; Hayashi, T. Tetrahedron Lett. 1998, 39,
8303. (b) Uozumi, Y.; Shibatomi, K. J. Am. Chem. Soc. 2001, 123, 2919.
(c) Shibatomi, K.; Uozumi, Y. Tetrahedron: Asymmetry 2002, 13, 1769.
9
10
11
12
a All reactions were carried out at 25 °C for 24 h in water under a nitrogen
atmosphere. The ratio of cycloalkenyl ester (mol)/amine (mol)/catalyst (Pd
equiv)/H2O (L) ) 1.0/5.0/0.08/5.0. b Isolated yield. c Determined by HPLC
analysis with use of a chiral stationary phase column. Absolute configuration
of the products was assigned as shown in Scheme 1 (see Supporting
Information).
282
Org. Lett., Vol. 6, No. 2, 2004

3). The N-methoxybenzyl groups of 7b and 7c were readily
removed by the standard CAN oxidation cleavage to give
secondary and primary amines, respectively, opening access
to differently N-substituted amines (see Supporting Informa-
tion). Higher stereoselectivity was observed when cyclohep-
tenyl carbonate (3) was used as the substrate (entries 4-6).
Thus, amination of 3 with 6a-c gave N,N-dibenzyl(cyclo-
heptenyl)amine (8a), N-benzyl-N-4-methoxy benzyl(cyclo-
hepten-2-yl)amine (8b), and N,N-di(4-methoxybenzyl)-
(cyclohepten-2-yl)amine (8c), whose chemical yields and
enantiomeric purities were 91% yield, 98% ee (8a); 82%
yield, 97% ee (8b); and 89% yield, 96% ee (8c).
Scheme 2
The cyclohexenyl ester 4 bearing a methoxycarbonyl group
with the cis configuration also underwent π-allylic substitu-
tion with the dibenzylamines 6a-c to give the corresponding
allylamines 9a-c having the cis configuration with high
enantioselectivity ranging from 90% to 96% ee (entries 7-9).
The aminopiperidines 10a-c were also prepared optically
active from the tetrahydropyridyl carbonate 5 under similar
conditions (entries 10-12) with 93-95% enantiomeric
excess.
It is interesting that, under these conditions, the π-allylic
amination does not take place in organic solvent. Thus, the
reaction of the cycloheptenyl carbonate 3 with 5 equiv of
6a in the presence of 8 mol % palladium of the PS-PEG
resin-supported 1-Pd complex was carried out in dichloro-
methane and showed no catalytic activity at 25 °C, whereas
the same system in water proceeded smoothly to give 91%
yield of the cycloheptenylamine 8a (Scheme 2). Furthermore,
the homogeneous catalytic system using imidazoindolephos-
phine 11, which lacks PS-PEG supports, gave only 6% of
8a in dichloromethane. In terms of catalytic efficiency, a
heterogeneous catalyst generally should be inferior to its
homogeneous counterpart. The hydrophobic organic sub-
strates must diffuse into the polystyrene matrix in water to
construct a highly concentrated reaction sphere to provide a
significant increase in reactivity.
The recycling experiments were examined for the amina-
tion of the cycloheptenyl ester 3 with 1 equiv of dibenzyl-
amine 6a. After the first use of the polymeric chiral catalyst
to give 98% ee of 8a, the recovered resin catalyst was taken
on to a second and third use without any additional charge
of palladium and exhibited no loss of its catalytic activity
or stereoselectivity (Scheme 3).
Scheme 3
Acknowledgment. We thank the JSPS (Creative Scien-
tific Research, no. 13GS0024; GRANT-in-AID for Scientific
Research, no.15205015), the MEXT (Scientific Research on
Priority Areas, nos. 412 and 420), and the Toray Foundation
for financial support of this work.
(8) For asymmetric π-allylic substitution of cycloalkenyl esters with high
stereoselectivity, see: (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.;
Gangne, M. R. J. Org. Chem. 1999, 64, 2994. (f) Evans, D. A.; Campos,
K. R.; Tedrow, J. S.; Michael, F. E.; Gangne, M. R. J. Am. Chem. Soc.
2000, 122, 7905. (g) Saitoh, A.; Achiwa, K.; Tanaka, K.; Morimoto, T. J.
Org. Chem. 2000, 65, 4227. (h) Hou, D.-R.; Reibenspies, J. H.; Burgess,
K. J. Org. Chem. 2001, 66, 206. (i) Hamada, Y.; Sakaguchi, K.; Hara, O.
Tetrahedron Lett. 2001, 42, 1297. (j) Xiao, L.; Weissensteiner, W.; Mereiter,
K.; Widhalm, M. J. Org. Chem. 2002, 67, 2206. (k) Agarkov, A.; Uffman,
E. W.; Gilbertson, S. R. Org. Lett. 2003, 5, 2091.
Supporting Information Available: Characterization and
experimental procedures for compounds 7-10 (PDF). This
material is available free of charge via the Internet at
http://pubs.acs.org.
OL036264I
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