Oxoammonium resins as metal-free, highly reactive, versatile polymeric oxidation reagents

Article abstract of DOI:10.1002/1521-3773(20010417)40:8<1436::AID-ANIE1436>3.0.CO;2-X

Polymer-supported oxidation of alcohols was conducted very efficiently by employing oxoammonium salts, the reactive intermediates in TEMPO oxidations (TEMPO = 2,2,6,6-tetramethylpiperidinoxyl). These highly reactive salts (see scheme; X = Br, C1) could be prepared and isolated on the polymeric support, and were used for the conversion of single compounds as well as of complex mixtures of alcohols.

Full text of DOI:10.1002/1521-3773(20010417)40:8<1436::AID-ANIE1436>3.0.CO;2-X

COMMUNICATIONS
[
6] For the synthesis of the N-SES-activated imine, see a) W. R. McKay,
G. R. Proctor, J. Chem. Soc. Perkin Trans. 1 1981, 2435 ± 2442; b) for
the synthesis of SES-Cl, see M. Weinreb, C. E. Chase, P. Wipf, S.
Venkatraman, Org. Synth. 1997, 75, 161 ± 169; SES ˆ 2-(trimethylsi-
lyl)ethanesulfonyl.
Oxoammonium Resins as Metal-Free, Highly
Reactive, Versatile Polymeric Oxidation
Reagents**
Steffen Weik, Graeme Nicholson, Günther Jung, and
Jörg Rademann*
[
7] The imines were prepared by using the methods described in
reference [6a] and by F. Chemla, V. Hebbe, J.-F. Normant, Synthesis
2000, 75 ± 77.
[
8] B. Nyasse, L. Grehn, H. L. S. Maia, L. S. Monteiro, U. Ragnarsson, J.
Org. Chem. 1999, 64, 7135 ± 7139.
Complex organic molecules can be constructed either in
solution or attached to an insoluble polymeric support.
Polymer-assisted solution-phase (PASP) synthesis[ offers a
highly attractive supplement to these concepts by exploiting
[
9] a) TcBoc imines were prepared by treatment of N-silylimine with the
corresponding chloroformate: R. Kupfer, S. Meier, E.-U. Würthwein,
Synthesis 1984, 688 ± 690; b) The Boc-protected imine (Boc ˆ tert-
butoxycarbonyl) was prepared using the method described by: A. M.
Kanazawa, J.-N. Denis, A. E. Greene, J. Org. Chem. 1994, 59, 1238 ±
1±3]
the virtues of both traditional approaches. Polymeric re-
[4, 5]
agents
can be used in high excess and are removed by
1
240; TcBoc ˆ 1,1-dimethyl-2,2,2-trichloroethoxycarbonyl.
10] Compare entry 1 or entry 6 with our previous best results with sulfide
, which was 55% yield, 97% ee, and 3:1 d.r.[3] Note this result used
filtration, the products can be easily analyzed and further
transformed in solution. They are especially suitable for
parallel combinatorial synthesis.[ They allow preparation of
complex libraries by multistep syntheses in solution, they can
be utilized in automated and in flow-through systems, and
finally they can be employedÐas will be demonstrated
hereinÐto transform single compounds as well as complex
[
1
6, 7]
stoichiometric amounts of 1 and cannot be easily scaled up (see
citation [3] in ref. [5]). Antilla and Wulffꢁs process (ref. [1d]) is
complementary to ours as it uses preformed diazoesters and give
cis aziridines (ours uses diazoalkanes/diazoalkenes and gives trans -
aziridines).
[
[
[
11] The ketone-derived imine was prepared using the method described
by: H.-J. Cristau, J.-M Lambert, J.-L. Pirat, Synthesis 1998, 1167 ±
[8]
mixtures.
1170.
The oxidation of alcohols to carbonyl compounds is one of
the most relevant transformations in organic synthesis, owing
to the large diversity of products that can be obtained from
aldehyde and ketone precursors.[ Common oxidative agents
for this transformation include dimethyl sulfoxide
12] a) G. W. Spears, K. Nakanishi, Y. Ohfune, Synlett 1991, 91 ± 92;
b) D. Tanner, P. Somfai, Bioorg. Med. Chem. Lett. 1993, 3, 2415 ±
2418.
9]
13] J. G. Knight, S. W. Ainge, A. M. Harm, S. J. Harwood, H. I. Maughan,
D. R. Armour, D. M. Hollinshead, A. A. Jaxa-Chamiec, J. Am. Chem.
Soc. 2000, 122, 2944 ± 2945.
14] Compare entry 2 with our previous best result with sulfide 1, which
gave 38% yield, 4:1 d.r., and 97% ee.
15] The 1-pyrrolidineacetic acid a-methylene-2,5-dioxo-ethyl ester was
prepared from ethyl propiolate and succinimide by the method
described by: B. M. Trost, G. R. Dake, J. Am. Chem. Soc. 1997, 119,
(
DMSO),[ periodinanes as well as various heavy-metal
10]
[11]
[
[12]
reagents, the latter usually based on either chromium or
ruthenium oxides.[ There are several examples of polymer-
supported oxidation reagents, including heavy-metal oxides
13]
[
[14]
[15, 16]
bound to ion-exchange resins.
One resin of this type has
7595 ± 7596.
been recently employed in a reaction sequence leading to
heterocyclic compounds.[ However, low reactivity with non-
benzylic alcohols, potential persistence of highly toxic heavy
metals in the products as well as overoxidation of aldehydes
limits the use of solid-supported metal oxides in parallel
syntheses.
Herein we report on the generation of oxoammonium
halides as oxidizing reactive species on a solid support and on
the use of this reagent in the oxidation of single alcohols and
of complex compound collections. Oxoammonium salts have
been postulated as reactive intermediates in oxidations
employing the 2,2,6,6-tetramethylpiperidine 1-oxyl radical
[
16] 2-Propenoic acid 2-[bis[(1,1-dimethylethoxy)carbonyl]amino]-methyl
ester was prepared from serine and Boc-ON by the method described
by: P. M. T. Ferreira, H. L. S. Maia, L. S. Monteiro, Tetrahedron Lett.
17]
1
998, 39, 9575 ± 9578. We have found that this acrylate can be prepared
in one step from serine methyl ester and (Boc) O.
17] W. Kuni, O. Koichiro, U. Kiitiro, Chem. Lett. 1987, 10, 2029 ±
032.
2
[
[
[
2
18] C. Alcaraz, M. D. Fern a ndez, M. P. de Frutos, J. L. Marco, M.
Bernab e , Tetrahedron 1994, 50, 12443 ± 12456.
19] We have found from crossover experiments relating to aziridination
that betaine formation is irreversible. Thus, the diastereoselectivity is
controlled by nonbonding interactions that lead to the betaine.
(
TEMPO), which is commonly employed under phase-trans-
fer conditions with, for example, sodium hypochlorite as
activating oxidant in the aqueous phase.[
18, 19]
Recently
TEMPO has been used in solution together with a polymer-
attached oxidizing agent[ and as a catalyst on silica. No
reports were found about using oxoammonium salts on
insoluble, crosslinked polymers, which would allow the
20]
[21]
[*] Dr. J. Rademann, Dipl.-Chem. S. Weik, G. Nicholson,
Prof. Dr. G. Jung
Institut für Organische Chemie, Universität Tübingen
Auf der Morgenstelle 18, 72076 Tübingen (Germany)
Fax : (‡49)7071-295560
E-mail: joerg.rademann@uni-tuebingen.de
[
**] J.R. gratefully acknowledges generous support from Prof. M. E.
Maier, Tübingen, the Strukturfonds of the Universität Tübingen, and
Merck KGaA, Darmstadt, Germany.
1436
ꢀ WILEY-VCH Verlag GmbH, D-69451 Weinheim, 2001
1433-7851/01/4008-1436 $ 17.50+.50/0
Angew. Chem. Int. Ed. 2001, 40, No. 8

COMMUNICATIONS
integration in common polymer-assisted solution-phase syn-
CH OH
CH OH
2
CH OH
2
2
CH2OH
[
22]
thesis operations.
We decided to synthesize and employ
reactive oxoammonium salts in a water-free system with the
intention of generating a highly reactive oxidation agent that
avoids over-oxidation to the acid due to the absence of oxygen
3a
4a
5
a
NO2
a
6
OtBu
OH
COOMe
[
23]
donors.
OH
CH2OH
The 4-hydroxy-2,2,6,6-tetramethylpiperidine 1-oxyl radical
was coupled to 1% divinylbenzene polystyrene resin by employ-
ing sodium hydride as base (Scheme 1). Elemental analysis of
O
7a
8a
O
9a
_
X
CH2OH
OH
O·
O
N
N+
Method A – C
10a
11a
O
O
O
1
2
HO
3
R1
_
X
+
N
CH2OH
R1
R2
R2
OH
CH OH
2
O
H
12a
1
– 2 h, CH2Cl2
O_
H
14a
13a
– 22a
OH
O
O
HO
OH
O
+
OH
+
R1
R2
1
5a
16a
N
H
_
X
3– 22b
O
HO
O
OH
Scheme 1. Oxoammonium resin 2 was prepared in a three-step procedure
from chloromethylated polystyrene resin and was employed in the
17a
oxidation of alcohols 3a ± 22a. Oxidation of resin 1 was effected by Br
2
,
2
Cl , or NCS/HCl (Methods A ± C).
OH
OH
the resulting resin 1 revealed a loading of 0.93 mmolg� 1 of the
radical; the presence of the free radical electron was proved
by ESR spectroscopy, which displayed the characteristic
H
OH
18a
OH
21a
19a
20a
1
4
triplet signal due to coupling with the N nucleus. Likewise,
the high-resolution magic angle spinning (HR-MAS) NMR
spectrum displayed significant line broadening, which can be
attributed to enhanced relaxation of the nuclear magnet-
ization through interaction with the persistent electron spins.
Oxidation of the radical was performed with elemental
bromine, chlorine, and N-chlorosuccinimide/HCl (Methods
A ± C; Scheme 1). Following oxidation, the resulting resin 2
displays a strong absorption at 1700 cm in the attenuated
total reflection IR spectrum (FT-ATR-IR), presumably
characteristic for the NˆO double bond of the reactive
2
2a
HO
�
1
mass spectra and the NIST spectral library, or by NMR
analysis.
First, alcohol 9a was treated with various amounts of 2.
Complete conversion within 1 h was achieved with three
equivalents of 2 (Figure 1). Results of the oxidation (Table 1)
can be summarized as follows: Clean and fast quantitative
conversion of the starting alcohols was observed in general,
only in the case of alcohol 17a was the starting material
detected after the reaction. All benzylic or allylic alcohols
yielded aldehyde or ketone products in very good purities.
The same was found for open-chain primary and secondary
alcohols. Representative yields for less volatile products such
as aldehydes 9b, 10b, or 20b were determined by weight and
were around 90%; the identity of the products was confirmed
intermediate. The oxidation is accompanied by a distinct color
change from colorless to a bright orange-red in case of
chloride as counterion and brown-red in case of bromide.
We investigated the reactivity of reagent 2 towards a
selection of 20 different alcohols 3a ± 22a, representing the
categories of benzylic, allylic, primary as well as secondary
aliphatic alcohols. Comparing the different counterions,
chloride was more reactive than bromide and led to fewer
�
side products, presumably due to the presence of the Br3 ion
in the case of bromine oxidation. Various temperatures were
tested; all comparative reactions were conducted at room
temperature (Table 1). Analysis and quantification of all
reactions were conducted by GC either with a flame-ioniza-
tion detector (FID) or a mass-sensitive detector (EI-MS,
[24]
by NMR analysis (250 MHz, CDCl ).
3
Very easily enolizable primary ketones obtained from
cyclohexanol (19a), 1-phenylpropan-2-ol (21a), and choles-
terol (22a) could be further converted to the diones, 19c, 21c,
and 22c, respectively (Scheme 2). In this reaction the primary
7
0 eV). Compounds were identified by comparison with pure
samples, by software-based structure assignment using the
Angew. Chem. Int. Ed. 2001, 40, No. 8
ꢀ WILEY-VCH Verlag GmbH, D-69451 Weinheim, 2001
1433-7851/01/4008-1437 $ 17.50+.50/0
1437

COMMUNICATIONS
Table 1. Results of the oxidation of the alcohols 3a ± 22a.
O
Starting Main
Product
GC-EI-MS-analysis
alcohol product[ purity [%] (characteristic signals [m/z])
a]
[b]
O
OH
O
OH
‡
3
4
5
6
7
8
9
0a
1a
2a
3a
4a
5a
6a
7a
8a
9a
0a
1a
2a
a
a
a
a
a
a
a
3b
4b
5b
6b
7b
> 95
> 95
> 95
> 95
85
> 95
> 95
> 95
83
106 [M ], 105, 77, 51
7
c
11c
11d
14c
‡
178 [M ], 163, 121, 93, 77, 65, 57, 41
‡
164 [M ], 133, 119, 105, 77, 51
‡
151 [M ], 150, 105, 77, 51
O
O
‡
O
O
132 [M ], 104, 78, 63, 51
O
O
O
O
O
O
‡
8b
9b
134 [M ], 105, 77, 51
O
‡
150 [M ], 149, 121, 91, 63
21c
‡
15c
1
1
1
1
1
1
1
1
1
1
2
2
2
10b
11d
12b
13b
14c
15c
16b
17c
18b
19c
20b
21c
22c
132 [M ], 131, 103, 77, 51
17c
1
9c
‡
150 [M ], 135, 122, 107, 95, 91, 82, 77, 54, 39
‡
90
134 [M ], 105, 91, 78, 65, 51, 39
[
c]
‡
72
60[
65
> 95
30[e]
90
85
> 95
76
79
124 [M ], 106, 95, 91, 80, 67, 55
d]
‡
154 [M ], 139, 136, 121, 111, 95, 84, 81, 71, 55, 41
‡
86 [M ], 56, 42, 41, 39
96, 86, 81, 70, 57, 55, 44, 41
146, 102, 86, 73, 58, 45, 43, 32
22c
O
‡
114 [M ], 99, 85, 71, 58, 43, 39
O
‡
112 [M ], 97, 83, 70, 55, 51, 43, 39
‡
Scheme 2. Secondary oxidation products obtained from alcohols by treat-
152 [M ], 137, 108, 95, 81, 69, 55, 41
‡
ment with resin 2.
148 [M ], 105, 77, 51, 43
‡
398 [M ], 383, 370, 356, 285, 243, 137
[
a] Ketones or aldehydes obtained in the primary oxidation are designated as oxidation product, for example, cyclohexanone is transformed
compounds 3b ± 22b. [b] In accordance with EI mass spectra from the NIST
spectral library. Further products see Scheme 2. [c] Decarbonylated by-product.
[
[25]
to the final diketone product via an enolized intermediate.
In contrast, diols (15a, 17a) are converted to lactones (15c,
7c) in the secondary oxidation step. Interestingly, cascade-
d] 20% 14b. [e] Mainly recovered diol.
1
like reactions were observed with terpene alcohols such as
geraniol (11a) and citronellol (14a). Monitoring by GC-MS
revealed that with an excess of reagent 2, the primary
oxidation products, the open-chain terpene aldehydes (11b,
1
4b) were cyclized in an ene-type reaction to furnish the
[26]
secondary alcohols (11c, 14c). For the geraniol system the
secondary product could be further oxidized to yield the
terpene ketone 11d in good purity.
Finally, a compound collection consisting of 15 alcohols
(
3a ± 10a, 12a, 13a, 15a, 16a, 18a ± 20a) was employed to
investigate the feasibility of converting complex mixtures
2 2
Figure 1. GC analysis (FID) of the reaction of 9a in CH Cl )
(1 mgmL 1
�
for 1 h with one, two, and three equivalents of the polymeric oxoammo-
Figure 2. GC analysis (FID) of a mixture of 15 alcohols (top) and the
nium salt 2.
product mixture obtained following oxidation with resin 2 (bottom).
1438
ꢀ WILEY-VCH Verlag GmbH, D-69451 Weinheim, 2001
1433-7851/01/4008-1438 $ 17.50+.50/0
Angew. Chem. Int. Ed. 2001, 40, No. 8

COMMUNICATIONS
of chemically diverse alcohols (Figure 2). The mixture
suspended in dry DMF (40 mL) in a 100 mL round-bottom flask.
2,2,6,6-Tetramethylpiperidine 1-oxyl (3.57 g, 20.7 mmol) was added
slowly, the flask was sealed with a drying tube, and stirred for 3 h.
Chloromethylated divinylbenzene (1%)/polystyrene (loading
�
1
(1 mgmL per alcohol) was analyzed by GC-FID as well as
GC-MS. In the starting mixture all alcohols could be
separated and identified by their mass spectra. Following
treatment with resin 2 for 2 h, GC analysis revealed the
complete disappearance of all of the alcohol precursors. All
but one of the expected aldehyde, ketone, lactone, or dione
products could be separated and identified; 8b and 12b co-
eluted, whereas 16b was not detected at all. The concen-
tration of products with a low-boiling point eluting early in the
GC was reduced, whereas the concentration of the high-
boiling aldehydes and ketones remained stable in the complex
mixture.
� 1
1
.07 mmolg , 100 ± 200 mesh, 2 g, 2.14 mmol) was added and the
reaction was agitated for three days at room temperature. The resin
was filtered and thoroughly washed with water, water/DMF (1/1),
DMF, THF, CH
2
Cl
2
, and MeOH and dried in vacuo. Loading:
�
1
0
.93 mmolg . Chlorine content: 0.07%. b) Oxidation to oxoammo-
nium resin 2 (Method C; Scheme 1). N-Chlorosuccinimide (6 equiv)
was dissolved in CH Cl , 4m HCl in dioxane was added (5 equiv).
2
2
After 5 min the solution was added to resin 1 (1 equiv) swollen in dry
CH Cl . Agitation for 15 min was followed by filtration of the resin
and washing with dry CH Cl . Half-life time (t1/2) of the activated form
was about one week when stored in vacuo at 48C. c) Oxidation of
2
alcohols. Alcohols 3a ± 22a (1 equiv) were dissolved in dry CH Cl .
2
2
2
2
2
In summary, the reported polymer-bound oxoammonium
reagent should be of great value in polymer-supported
transformations in solution, in automated parallel synthesis
operations, and in flow-through reactors in up-scaled produc-
tion processes. Herein we have only considered the preformed
oxoammonium salts as reactive species. The potential of the
TEMPO ± resin should, however, be exploitable as well as in
Freshly prepared oxoammonium resin 2 (5 equiv as calculated from
the loading of resin 1) was added and agitated at room temperature for
1
h for the primary alcohols and 2 h for the secondary alcohols. The
resin was filtered and washed with CH Cl , the washings were
2
2
employed for analysis by GC, using a 25 m  0.32 mm Permabond SE
54 (d ˆ 1.0 m) fused silica capillary. Temperature program: 508C,
f
�
1
2 min isotherm, 58Cmin to 2008C. H
5
2
was used as carrier gas (p
i
ˆ
0 kPa) for FI detection and He for GC-MS in the EI-mode (70 eV).
Purities are reported in Table 1. Exemplified yields for 10 mg alcohol,
after reaction for 1 h, washing with CH Cl
ration of the solvent at room temperature: 9b: 8.9 mg, 90%; 10b:
8.7 mg, 88%; 20b: 9.2 mg, 91%. The identity of the isolated products
situ generated oxoammonium salt, obtained by one of the
2
2
(4 Â 3 mL), and evapo-
II
available regeneration systems (e.g. Cu /O ), in multiple
2
phases, or by electrochemical means.
was confirmed by NMR analysis (250 MHz, CDCl
25] D. H. Hunter, D. H. R. Barton, W. J. Motherwell, Tetrahedron Lett.
984, 25, 603 ± 606.
26] Y. Nakatami, K. Kawashima, Synthesis 1978, 147 ± 148.
3
).
Received: October 4, 2000
Revised: January 26, 2001 [Z15900]
[
[
1
[
[
1] S. W. Kaldor, M. G. Siegel, Curr. Opin. Chem. Biol. 1997, 1, 101 ± 106.
2] D. L. Flynn, R. V. Devraj, W. Naing, J. J. Parlow, J. J. Weidner, S. L.
Yang, Med. Chem. Res. 1998, 8, 219 ± 243.
[
3] S. V. Ley, I. R. Baxendale, R. M. Bream, P. S. Jackson, A. G. Leach,
D. A. Longbottom, M. Nesi, J. S. Scott, R. I. Storer, S. J. Taylor, J.
Chem. Soc. Perkin Trans. 1 2000, 23, 3815 ± 4195.
Thwarting b-Hydride Elimination: Capture of
the Alkylpalladium Intermediate of an
[
[
[
[
[
[
4] S. J. Shuttleworth, S. M. Allin, P. K. Sharma, Synthesis 1997, 1217 ±
1
239.
5] S. J. Shuttleworth, S. M. Allin, R. D. Wilson, D. Nasturica, Synthesis
000, 1035 ± 1074.
Asymmetric Intramolecular Heck Reaction**
2
Martin Oestreich, Philip R. Dennison,
Jeremy J. Kodanko, and Larry E. Overman*
6] Combinatorial ChemistryÐSynthesis, Analysis, Screening (Ed.: G.
Jung), Wiley-VCH, Weinheim, 1999.
7] Combinatorial Peptide and Nonpeptide Libraries (Ed.: G. Jung),
VCH, Weinheim, 1996.
8] J. Rademann, J. Smerdka, G. Jung, P. Grosche, D. Schmid, Angew.
Chem. 2001, 113, 390 ± 393; Angew. Chem. Int. Ed. 2001, 39, 381 ± 385.
9] Comprehensive Organic Synthesis, Vol. 1 and 2 (Ed.: B. M. Trost),
Pergamon, Oxford, 1991.
Dedicated to Professor Dieter Hoppe
on the occasion of his 60th birthday
The asymmetric intramolecular Heck reaction[1, 2] has
proven to be one of the most efficient methods for enantio-
selective construction of quaternary carbon centers.[ We
[
[
[
[
[
[
10] A. J. Mancuso, D. Swern, Synthesis 1981, 165 ± 185.
3]
11] D. B. Dess, J. C. Martin, J. Org. Chem. 1983, 48, 4156 ± 4158.
12] E. J. Corey, J. W. Suggs, Tetrahedron Lett. 1975, 2647 ± 2650.
13] A. I. Meyers, K. Higashiyama, J. Org. Chem. 1987, 52, 4592 ± 4597.
14] A. Akelah, D. C. Sherrington, Chem. Rev. 1981, 81, 557 ± 587.
15] G. Gardillo, M. Orena, S. Sandri, Tetrahedron Lett. 1976, 17, 3985 ±
[‡]
[*] Prof. Dr. L. E. Overman, Dr. M. Oestreich, Dr. P. R. Dennison,
J. J. Kodanko
Department of Chemistry
University of California, Irvine
3988.
[
[
16] B. Hinzen, S. V. Ley, J. Chem. Soc. Perkin Trans. 1 1997, 1907 ± 1910.
17] M. Caldarelli, J. Habermann, S. V. Ley, J. Chem. Soc. Perkin Trans. 1
5
16 Rowland Hall, Irvine, CA 92697-2025 (USA)
Fax : (‡1)949-824-3866
1
999, 107 ± 110.
18] P. L. Anelli, C. Biffi, F. Montanari, S. Quici, J. Org. Chem. 1987, 52,
559 ± 2562.
19] P. L. Anelli, S. Banfi, F. Montanari, S. Quici, J. Org. Chem. 1989, 54,
970 ± 2972.
E-mail: leoverma@uci.edu
[
[
‡
[
] NMR analyses
2
[**] This research was supported by the National Institutes of Health
(
grant GM-12389). M.O. thanks the Deutsche Forschungsgemein-
2
schaft (DFG) for an Emmy Noether fellowship (Oe 249/1-1). NMR
and mass spectra were determined at the University of California,
Irvine with instruments purchased with the assistance of the NSF and
NIH shared instrumentation programs. We are grateful to Dr.
Joseph W. Ziller and Dr. John Greaves for their assistance with
X-ray structure and mass spectrometric analyses.
[
[
[
20] G. Sourkouni-Argirusi, A. Kirschning, Org. Lett. 2000, 2, 3781 ± 3784.
21] C. Bolm, T. Pey, Chem. Commun. 1999, 1795 ± 1796.
22] A. E. J. de Nooy, A. C. Besemer, H. van Bekkum, Synthesis 1996,
1
153 ± 1174.
23] M. F. Semmelhack, C. R. Schmid, D. A. Cortes, Tetrahedron Lett.
986, 27, 1119 ± 1122.
[
[
1
24] Experimental details: a) Preparation of TEMPO resin 1. Sodium
Supporting information for this article is available on the WWW under
http://www.angewandte.com or from the author.
hydride (1.28 g, stabilized with paraffin oil, 60%, 32.1 mmol) was
Angew. Chem. Int. Ed. 2001, 40, No. 8
ꢀ WILEY-VCH Verlag GmbH, D-69451 Weinheim, 2001
1433-7851/01/4008-1439 $ 17.50+.50/0
1439