Tuning the regioselectivity in the palladium(II)-catalyzed isomerization of alkylidene cyclopropyl ketones: A dramatic salt effect

Article abstract of DOI:10.1002/anie.200390073

Useful building blocks are formed in this [PdCl₂(CH₃CN)₂]-catalyzed regioselective isomerization reaction of alkylidene cyclopropyl ketones, in which a dramatic salt effect was observed. In the presence of Nal, the reactio

Full text of DOI:10.1002/anie.200390073

Angewandte
Chemie
Communications
From a starting material of alkylidene cyclopropyl ketones, it is possible
to make both two types of useful organic building block (furans and
4H-pyrans) regioselectively, by a simple adjustment of the reaction
conditions. For more information, see the communication by S. Ma
and J. Zhang.
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Regioselective Cyclization
in 51% yield (entry 2, Table 1).The reaction can also be
carried out in CH3CN or DMF to afford the product in very
low yields (entries 3 and 4, Table 1).The best results were
obtained using two equivalents of sodium iodide as the
additive in refluxing acetone, under the catalysis of 5 mol%
[PdCl2(CH3CN)2] (Conditions A; entry 5, Table 1).Other
salts such as tetra(n-butyl)ammonium iodide, tetra(n-but-
yl)ammonium bromide, and lithium bromide also showed a
similar effect, albeit that 2a was formed in lower yields
(entries 6 8, Table 1).
This transformation is general and some of the typical
results are summarized in Table 2.The reactions of 1 under
Conditions A afforded the corresponding polysubstituted
furans 2 in good yields (Table 2).The reaction of 1d with
20 mol% of sodium iodide afforded the corresponding
product 2d in a lower yield (compare entries 3 and 4,
Table 2).The reaction of 1 f for 20.5 h afforded the furan 2 f
in 80% yield, while 4-octylidene-4, 5-dihydrofuran Z-3 f was
formed in 55% yield together with 2 f (15%; Scheme 2)
within 1 h, which indicates that the reaction proceeded
through the intermediacy of 3 f.The stereochemistry of Z-
3 f was determined by an NOE study.
Tuning the Regioselectivity in the Palladium(ii)-
Catalyzed Isomerization of Alkylidene
Cyclopropyl Ketones:A Dramatic Salt Effect**
Shengming Ma* and Junliang Zhang
In the last three decades, methylenecyclopropanes (MCPs)
have been studied with numerous mechanistic,[1] biological[2]
and synthetic interests.[3] Especially, mounting attention has
been paid to the transition-metal-catalyzed reactions of
MCPs.[4,5] Various reaction pathways, including oxidative
[4,6]
ꢀ
addition of the distal or proximal C C bond
and regiose-
lective hydrometalation[7,8] or carbometalation[9,10] of the C C
bond, have been observed in the transition-metal-catalyzed
reactions of MCPs.Although the chloropalladation reaction
of MCPs with stoichiometric [PdCl2(PhCN)2] has been
studied,[11] no catalyzed reaction has been reported
(Scheme 1).During our systematic study of allene chemis-
¼
Furthermore, it is surprising for us to observe that the
[PdCl2(CH3CN)2]-catalyzed reaction of 1g in acetone at RT in
the absence of NaI (Conditions B) afforded the 4H-pyran 4g
in 91% yield (Scheme 3), of which the structure was
determined by a X-ray diffraction study of the corresponding
hydroboration oxidation product 5g.[16]
Scheme 1. Two possible modes of halometalation reactions of MCPs.
This transformation is also general and the results are
summarized in Table 3.In the presence of
5 mol%
try,[12] we have been interested in the chemistry of its
analogues, MCPs.Herein, we disclose a dramatic salt effect [13]
in the palladium(ii)-catalyzed regioselective cycloisomeriza-
tion reaction of the alkylidene cyclopropyl ketones 1 giving
the corresponding furan or 4H-pyran derivatives initiated
[PdCl2(CH3CN)2], the reaction of the alkylidene cyclopropyl
ketone 1b at RT in acetone gave the 4H-pyran 4b in 80%
yield (entry 1, Table 3).In some cases, benzene is a better
solvent.For example, the reaction of 1d in benzene afforded
4d in 80% yield, while the same reaction in acetone afforded
4d in 69% yield (entries 3 and 4, Table 3).The reaction of 1e,
which contains the TBS-protected hydroxy group (TBS ¼ tert-
butyldimethylsilyl), gave 4e in 85% yield in benzene (entry 5,
Table 3).The presence of the electron-withdrawing group R 2
¼
with the regioselective halopalladation of the C C bond of
MCPs.
We initially examined the reaction of the methylenecy-
clopropyl ketone 1a[14] in the presence of a catalytic amount
of [PdCl2(CH3CN)2].After numerous trial and error attempts,
fortunately we observed the [PdCl2(CH3CN)2]-catalyzed
regioselctive isomerization of 1a with two equivalents of
sodium iodide in THF afforded 2-phenyl-4-methylfuran 2a[15]
[*] Prof. S. Ma, Dr. J. Zhang
State Key Laboratory of Organometallic Chemistry
Shanghai Institute of Organic Chemistry, Chinese Academy of
Sciences
Scheme 2. The PdII-catalyzed cycloisomerization reaction of 1 f under
Conditions A.
354 Fenglin Lu, Shanghai 200032 (P.R. China)
Fax: (þ86)21-6416-6128
E-mail: masm@pub.sioc.ac.cn
[**] Financial support from the National Science Foundation of China,
the Major State Basic Research Development Program (Grant No.
G2000077500), the Chinese Academy of Sciences, and the Shanghai
Municipal Committee of Science and Technology are greatly
appreciated. S.M. is the recipient of the 1999 Qiu Shi Award for
Young Chinese Scientific Workers issued by the Hong Kong Qiu Shi
Foundation of Science and Technology (1999 2003)
Scheme 3. The PdII-catalyzed isomerization reaction of 1g under Con-
ditions B and the subsequent hydroboration oxidation reaction.
a) 5 mol% [PdCl2(CH3CN)2], acetone, RT, 15 min; b) 1. BH3¥SMe2,
THF, 08C!RT, 1 h; 2. NaOH H2O2, 08C!RT, 6 h.
Supporting information for this article is available on the WWW
under http://www.angewandte.org or from the author.
184
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Table 1: Palladium(ii)-catalyzed regioselective isomerization of 1a into 2a.
of 1 is shown in Scheme 4. In the
presence of NaI, the iodide anion
(Iꢀ) attacks the palladium(ii)-coor-
¼
dinated C C bond to afford the
palladium intermediate 7 (path a),
then b decarbopalladation involv-
Entry
Additive
Solvent
CH2Cl2
T [8C]
t [h]
Yield [%][a]
0
ꢀ
1
2
3
4
5
6
7
8
LiCl
NaITHF
NaICH
NaIDMF
NaIacetone
Bu4NIacetone
Bu4NBr
LiBr
RT
10
70
10
5
ing the proximal C C bond of the
reflux
3CN
70
reflux
reflux
51
10
9
80
61
10
10
complex 7 would give the delocal-
ized intermediate 8, which would
undergo the intramolecular endo-
5
9
¼
mode insertion of the C C bond
[b]
10
reflux
reflux
acetone
acetone
57[b]
63
into the oxy-palladium bond fol-
lowed by b halide elimination to
produce the catalytically active pal-
ladium(ii) species and 3, which
would furnish the furan 2 upon
aromatization (cycle A).In the ab-
sence of NaI the reaction would go
through cycle B.The regioselective
[a] 5 mol% of catalyst was used. [b] 10 mol% of catalyst was used.
Table 2: Palladium(ii)-catalyzed regioselective isomerization of ketones 1, which leads to furans 2.[a]
chloropalladation[11] of the C C
¼
bond of the alkylidene cyclopro-
pane ketone 1 (path b) would af-
ford the palladium intermediate 11,
which would undergo b decarbopal-
ladation to afford the delocalized
intermediate 12.Subsequent intra-
molecular endo-mode insertion of
Entry
1
t
[h]
Yield of 2
[%]
R1
R2
R3
1
2
3
4
5
6
7
C7H15
C4H9
Bn
CO2Et
CO2Et
CO2Et
1d
CO2Et
COMe
H
Me (1b)
Me (1c)
Me (1d)
10
14
13.5
24
26
74 (2b)
74 (2c)
78 (2d)
65(2d)[b]
82 (2e)
80 (2 f)[c]
77 (2h)
TBSO(CH2)3
C7H15
H
Me (1e)
Me (1 f)
C6H5(CH2)2 (1h)
¼
the C C bond into the oxygen
20.5
12
palladium bond of the intermedi-
ate 12 would afford a cyclic palla-
dium intermediate 13, which would
undergo b-hydride elimination hy-
dropalladation with an opposite
regioselectivity to afford the palla-
dium intermediate 14.Finally, b-
halide elimination of 14 would pro-
duce the 4H-pyran 4 and regenerate
the palladium(ii) species (path c).
The intermediate 13 might also un-
dergo a-halide elimination[17] to
afford a carbene intermediate 15
and regenerate palladium(ii) spe-
cies (path d).The carbene inter-
mediate 15 would undergo intramo-
lecular 1, 2-migration of hydrogen
to afford the 4H-pyran 4.
[a] Unless otherwise specified, the reaction was carried out using 1 (0.25 1.5 mmol) in the presence of 5
mol% [PdCl2(CH3CN)2] and 2 equiv of sodium iodide in 2 mL of acetone under reflux (Conditions A).
[b] The reaction was carried out in the presence of 0.2 equiv of sodium iodide in 0.5 mL of acetone under
reflux. [c] See the text.
Table 3: Palladium(ii)-catalyzed regioselective isomerization of the ketones 1, which leads to the 4H-
pyrans 4.[a]
Entry
1
R2
t
Yield of 4
[%]
R1
R3
[min]
1
2
3
4
5
6
7
8
C7H15
C4H9
Bn
CO2Et
CO2Et
CO2Et
1d
CO2Et
COMe
SO2Ph
H
Me (1b)
Me (1c)
Me (1d)
15
15
15
10
10
40
15
15
80 (4b)
75 (4c)
69 (4d)
80 (4d)[b]
85 (4e)[b]
60 (4 f)
91 (4g)
70 (4i)[b]
TBSO(CH2)3
C7H15
C4H9
Me (1e)
Me (1 f)
Me (1g)
Ph (1i)
In conclusion, a dramatic salt
effect was observed in the pallad-
ium(ii)-catalyzed regioselective cy-
cloisomerization of alkylidene cy-
clopropyl ketones 1.In the presence
of two equivalents of sodium iodide
or other salts the reaction provides
the furans 2 through distal-bond
cleavage, while in the absence of
C8H17
[a] Unless otherwise specified, all reactions were carried out using 1 (0.5 mmol) in the presence of
5 mol% [PdCl2(CH3CN)2] in 2 mL of acetone at RT (Conditions B). [b] The solvent used was benzene.
is not necessary because the reaction of 1i was also good,
affording 4i in 70% yield (entry 8, Table 3).
A plausible rationale for the dramatic salt effect of NaI in
the palladium(ii)-catalyzed regioselective cycloisomerization
salt, the polysubstituted 4H-pyrans 4 were formed by prox-
imal-bond cleavage.Further studies into the scope, mecha-
nism, and synthetic applications of this reaction are being
carried out in our laboratory.
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185

Communications
Chem. Soc. 1989, 111, 7285; d) A.Brandi, A.Goti, Chem. Rev.
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[4] For a recent review, see: I.Nakamura, Y.Yamamoto, Adv. Synth.
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[5] For reviews, see: a) P.Binger, H.M.B¸ch,
Top. Curr. Chem.
1987, 135, 77; b) T.Ohta, H.Takaya in Comprehensive Organic
Synthesis, Vol. 5 (Ed.: B. M. Trost, I. Fleming, L. A. Paquette),
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118, 10676; b) A.G.Bessmertnykh, K.A.Blinov, Y.K.Grishin,
N.A.Donskaya, E.V.Tveritinova, N.M.Yur©eva, I.P.Belet-
skaya, J. Org. Chem. 1997, 62, 6069.
[8] a) N.Tsukada, A.Shibuya, I.Nakamura, Y.Yamamoto,
Chem. Soc. 1997, 119, 8123; b) I.Nakamura, H.Itagaki, Y.
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J. Am.
Scheme 4. A plausible mechanism for the PdII-catalyzed isomerization
reaction of 1.
Experimental Section
[9] a) G.Fournet, G.Balme, J.J.Barieux, J.Gorÿ,
Tetraherdron
Conditions A; synthesis of 2b: [PdCl2(MeCN)2] (17 mg, 0.65 mmol)
was added to a solution of 1b (356 mg, 1.3 mmol) and sodium iodide
(400 mg, 2.7 mmol) in acetone (5 mL). The mixture was then stirred
under reflux for 14 h.Evaporation of the solvent and chromatography
on silica gel (petroleum ether/ether 100:1) afforded pure 2b (256 mg,
74%) as a liquid. 1H NMR (300 MHz, C6D6): d ¼ 6.81 (s, 1H), 4.03 (q,
J ¼ 7.2 Hz, 2H), 2.61 (t, J ¼ 7.5 Hz, 2H), 2.37 (s, 3H), 1.60 1.46 (m,
2H), 1.38 1.10 (m, 10H), 0.97 (t, J ¼ 7.2 Hz, 3H), 0.84 ppm (t, J ¼ 7.
2 Hz, 3H); 13C NMR (75.4 MHz, C6D6): d ¼ 164.10, 160.06, 137.63,
126.76, 113.51, 59.57, 32.25, 30.08, 29.96, 29.87, 29.73, 25.17. 23.03,
14.31, 14.26, 14.24 ppm; MS (70 eV): m/z (%): 266 (1.14) [Mþ], 168
(100) [MþꢀC7H14]; IR (neat): n˜ ¼ 1716, 1607, 1559 cmꢀ1; HRMS calcd
for C16H26O3: 266.18819, found: 266.18641.
1988, 44, 5809, 5821; b) S.Br‰se, A.de Meijere, Angew. Chem.
1995, 107, 2741; Angew. Chem. Int. Ed. Engl. 1995, 34, 2545.
[10] a) R.Grigg, P.Kennewell, A.Teasdale, V.Sridharan,
Tetrahe-
dron Lett. 1993, 34, 153; b) K.H.Ang, S.Br‰se, A.G.Steinig,
F.E.Meyer, A.Llebaria, K.Voigt, A.de Meijere,
1996, 52, 11503.
Tetrahedron
[11] a) R.Noyori, H.Takaya, Chem. Commun. 1969, 525; b) P.R.
Clemens, R.P.Hughes, L.D.Margerum, J. Am. Chem. Soc. 1981,
103, 2428; c) T.A.Albright, P.R.Clemens, R.P.Hughes, D.E.
Hunton, L.D. Margerum, J. Am. Chem. Soc. 1982, 104, 5369;
d) B.K.Dallas, R.P.Hughes, K.Schumann,
J. Am. Chem. Soc.
1982, 104, 5380, and references therein.
[12] For some of the most recent results from this group, see: a) S.
Ma, S.Wu, Chem. Commun. 2001, 441; b) S.Ma, S.Zhao, J. Am.
Chem. Soc. 2001, 123, 5578; c) S.Ma, Z.Shi, Chem. Commun.
2002, 540; d) S.Ma, W.Gao, Synlett 2002, 65; e) S.Ma, S.Yin, L.
Li, F.Tao, Org. Lett. 2002, 4, 505; f) S.Ma, N.Jiao, S.Zhao, H.
Hou, J. Org. Chem. 2002, 67, 2837; g) S.Ma, D.Duan, Y.Wang, J.
Comb. Chem. 2002, 4, 239; h) S.Ma, Z.Yu, Angew. Chem. 2002,
114, 1853; Angew. Chem. Int. Ed. 2002, 41, 1775.
[13] For reviews, see: a) E.M.Vogl, H.Grˆger, M.Shibasaki, Angew.
Chem. 1999, 111, 1671; Angew. Chem. Int. Ed. 1999, 38, 1570;
b) K.Fagnou, M.Lautens, Angew. Chem. 2002, 114, 26; Angew.
Chem. Int. Ed. 2002, 41, 26.
[14] 1a, 1h, and 1i were prepared according to the following
reference except that the corresponding N,N-dimethyl amide
was used instead of the lithium carboxulates, see: E.W.Thomas,
J.R.Szmuszkovicz, J. Org. Chem. 1990, 55, 6054; other starting
MCPs were prepared by the rhodium-catalyzed cyclopropana-
tion reaction of the diazo compounds with allenes, see: C.Cheng,
T.Shimo, K.Somekawa, M.Baba, Tetrahedron 1998, 54, 2031.
[15] The structure of 2a was determined by the comparison with the
authentic sample, which was synthesized according to the
following reference: Y.Wakabayashi, Y.Fukuda, H.Shiragami,
K.Utimoto, H.Nozaki, Tetrahedron 1985, 41, 3655.For 1H NMR
spectroscopic data of 2a, see: H.Hagiwara, H.Uda, J. Chem.
Soc. Perkin Trans. 1 1984, 91.
Conditions B; synthesis of 4b: [PdCl2(MeCN)2] (6 mg, 5 mol%)
was added to a solution of 1b (133 mg, 0.50 mmol) in acetone (2 mL).
The mixture was then stirred at RT for 15 min.Evaporation of the
solvent and chromatography on silica gel (petroleum ether/ether
100:1) afforded pure 4b (106 mg, 80%) as an air-sensitive liquid.
1H NMR (300 MHz, CDCl3): d ¼ 4.65 (t, J ¼ 3.6 Hz, 1H), 4.14 (q, J ¼
6.9 Hz, 2H), 2.90 2.80 (m, 2H), 2.20 (t, J ¼ 0.9 Hz, 3H), 1.99 (t, J ¼
6.9 Hz, 2H), 1.50 1.30 (m, 2H), 1.30 1.20 (m, 8H), 1.25 (t, J ¼ 6.9 Hz,
3H), 0.87 ppm (t, J ¼ 6.6 Hz, 3H); 13C NMR (75.4 MHz, CDCl3): d ¼
168.16, 160.95, 150.23, 100.27, 97.33, 59.81, 32.58, 31.76, 29.04, 28.94,
26.35, 22.62, 21.92, 19.13, 14.31, 14.05 ppm; MS (70 eV): m/z (%): 266
(7.89) [Mþ], 43 (100) [C3H7þ]; IR (neat): n˜ ¼ 1720, 1637, 761 cmꢀ1
;
HRMS calcd for C16H26O3: 266.18819, found 266.1857.
Received: July 29, 2002 [Z19842]
[1] MG. .Lazzara, JJ..Harrison, M.Rule, EF. .Hilinski, JA. .
Berson, J. Am. Chem. Soc. 1982, 104, 2233.
[2] a) C.H. Hassall, K. Reyle, P. Feng,
b) C.H. Hassall, K. Reyle, Biochem. J. 1955, 60, 344; c) J.A.
Carbon, W.B.Martin, L.R.Swett, J. Am. Chem. Soc. 1958, 80,
Nature 1954, 173, 356;
1002; d) N.D.Lenn, Y.Shih, M.T.Stankovich, H.Liu,
J. Am.
[16] X-ray data for compound 5g: C16H22O4S, Mr ¼ 310.40, mono-
clinic, space group P2(1)/c, MoKa, final R indices [I > 2s(I)],
R1 ¼ 0.0553, wR2 ¼ 0.1280, a ¼ 17.931(4), b ¼ 8.4053(16), c ¼
10.938(2) ä, a ¼ 90, b ¼ 94.494(3), g ¼ 908, V¼ 1643.5(5) ä3,
Chem. Soc. 1989, 111, 3065.
[3] a) R.Noyori, N.Hayashi, M.KatÙ, J. Am. Chem. Soc. 1971, 93,
4948; b) B.M.Trost, Angew. Chem. 1986, 98, 1; Angew. Chem.
Int. Ed. Engl. 1986, 25, 1; c) S.Yamago, E.Nakamura, J. Am.
186
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Chemie
TTFþC, and TTF2þ) and for this reason TTF derivatives have
T¼ 293 K, Z ¼ 4, reflections collected/unique: 9438/3824 (Rint
¼
found widespread use in materials chemistry.[9] Progress in
synthetic TTF chemistry[9] has revolutionized the possibilities
for the incorporation of TTF into macrocyclic, molecular, and
supramolecular structures and has transformed complicated
systems, such as TTF cyclophanes,[9] TTF catenanes,[9] and
TTF rotaxanes/pseudorotaxanes[9,10] from chemical curiosities
into a vibrant area of modern-day research.In the context of
electrochemically active sensors, TTF has already been used
as the redox-active unit in a number of cation responsive
receptors.[11] However, to our knowledge, no anion receptor
incorporating TTF as the redox-active unit has been reported.
We have recently developed an efficient synthesis of the
parent pyrrolo[3,4-d]TTF-ring system.[12] With this building
block in hand, we have prepared the first example of a single
molecule in which the anion-receptor abilities of the calix[4]-
pyrrole system were coupled to the favorable redox proper-
ties of the TTF core through direct annulation of one TTF
unit to the upper rim of the calix[4]pyrrole skeleton.
0.0457), no observation [I > 2s(I)] 3824, parameters 257.CCDC-
190370 (5g) contains the supplementary crystallographic data
for this paper.These data can be obtained free of charge via
www.ccdc.cam.ac.uk/conts/retrieving.html (or from the Cam-
bridge Crystallographic Data Centre, 12, Union Road, Cam-
bridge CB21EZ, UK; fax: (þ 44)1223-336-033; or deposit
@ccdc.cam.ac.uk).
[17] S.Ma, B.Xu, B.Ni, J. Org. Chem. 2000, 65, 8532.
Electrochemical Sensors
Mono-Tetrathiafulvalene Calix[4]pyrrole in the
Electrochemical Sensing of Anions**
Herein, we report the synthesis of the first calix[4]pyrrole
incorporating a TTF unit.Furthermore, we describe our
1H NMR spectroscopic and electrochemical studies on the
recognition abilities of this novel mono-TTF calix[4]pyrrole 4
system towards anions.
Kent A. Nielsen, Jan O. Jeppesen,* Eric Levillain,
and Jan Becher*
Dedicated to Professor J. Fraser Stoddart
on the occasion of his 60th birthday
Our preparation of the mono-TTF calix[4]pyrrole 4 is
outlined in Scheme 1.The tripyrrane dialdehyde 1 was
prepared according to a literature procedure[13] by the
condensation of pyrrole and acetone followed by a Clezy
formylation.The reduction of the formyl groups with NaBH 4/
LiBr in anhydrous THF/MeOH produced the bishydroxyme-
thyltripyrrane 2 in 76% yield.The tripyrrane 2 was used
immediately after purification by means of flash column
chromatography on account of the low stability of the
compound.Treatment of equal quantities of 2 and the newly
developed pyrrolo TTF 3 with a catalytic amount of BF3¥Et2O
in anhydrous MeCN, gave the mono-TTF calix[4]pyrrole 4 as
yellow crystals after purification by means of column
chromatography (yield 21%).[14]
The advent of supramolecular chemistry[1] has stimulated the
contemporary chemist©s interest in the development of
chemosensors capable of recognizing specific chemical spe-
cies.[2] Calix[4]pyrroles[3]–first synthesized in the 19th Cen-
tury by Baeyer[4]–contain four pyrrole NH hydrogen-bond
functionalities and have recently been studied for possible use
as receptors for anionic and neutral substrates.[5] They have
been used to prepare optical anion sensors[6] and anion-
selective high-performance liquid-chromatography (HPLC)
supports.[7] However, only a few electrochemically active
sensors based on calix[4]pyrroles have been reported.[8]
Electrochemically active sensors, designed to permit the
detection of substrates by binding-induced changes in the
redox properties, are generally composed of a receptor unit,
which works by the covalent association of a substrate-
recognition functionality, and an electrochemical-signaling
capacity (redox-active unit).The redox-active tetrathiafulva-
lene[9] (TTF) unit can exist in three stable redox states (TTF0,
[*] Dr. J. O. Jeppesen, Prof. J. Becher, K. A. Nielsen
Department of Chemistry
Odense University (University of Southern Denmark)
Campusvej 55, 5230 Odense M (Denmark)
Fax: (þ45)66-158-780
E-mail: joj@chem.sdu.dk
jbe@chem.sdu.dk
Dr. E. Levillain
Ingÿnierie Molÿculaire et Matÿriaux Organiques
CNRS UMR 6501, Universitÿ d©Angers
2 Bd Lavoisier, 49045 Angers (France)
[**] We gratefully acknowledge the University of Odense for a Ph.D
scholarship to K.A.N., financial support from Carlsbergfondet to
J.O.J, and the French Embassy Copenhagen for a travel grant to J.B.
Scheme 1. Synthesis of the mono-TTF calix[4]pyrrole 4.
Angew. Chem. Int. Ed. 2003, 42, No. 2
¹ 2003 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
1433-7851/03/4202-0187 $ 20.00+.50/0
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