Practically perfect asymmetric autocatalysis with (2-alkynyl-5- pyrimidyl)alkanols

Article abstract of DOI:10.1002/(SICI)1521-3773(19990301)38:5<659::AID-ANIE659>3.0.CO;2-P

Extremely high enantioselectivity (> 99.5% ee) and chemical yield (> 99%) are achieved in an asymmetric autocatalytic reaction. A (5- pyrimidyl)alkanol with a tert-butylethynyl group at its 2-position (1) is a very efficient asymmetric autocatalyst in the enantioselective alkylation in Equation (1).

Full text of DOI:10.1002/(SICI)1521-3773(19990301)38:5<659::AID-ANIE659>3.0.CO;2-P

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[8] J. Pan, D. Charych, Langmuir 1997, 13, 1365 ± 1367.
these enzymes cleave at the hydrophilic head-group region
(phosphate ester) of DMPC. The significance of the detection
system described is that it both mimics the natural membrane
interface, and also provides a visual reporting component (the
conjugated polymer) for the rapid detection of biocatalysis.
The simple, one-step detection method for enzymatic
catalysis and inhibition allows convenient adaptation to the
high-throughput screening of catalytic inhibitors. In addition,
this method may be applied to detect deadly neurotoxins that
have enzyme-like activities (for example, b-bungarotoxin).
Future efforts are geared towards the study of factors that
affect enzyme recognition and activity, parameters that
influence reorganization of the conjugated polymer mem-
brane, and adaptation of the colorimetric method to other
enzyme systems.
[9] Q. Cheng, R. C. Stevens, Chem. Phys. Lipids 1997, 87, 41 ± 53.
[10] Q. Cheng, R. C. Stevens, Adv. Mater. 1997, 9, 481 ± 483.
[11] K. Faid, M. Leclerc, Chem. Commun. 1996, 24, 2761 ± 2762.
[12] R. M. Kini, Venom Phospholipase A2 Enzymes, Wiley, Chichester,
1997.
[13] M. Waite, The Phospholipases, Plenum, New York, 1987.
[14] J. S. Bomalaski, M. A. Clark, Arthritis Rheum. 1993, 36, 190 ± 198.
[15] F. Ramirez, M. K. Jain, Proteins Struct. Funct. Genet. 1991, 9, 229 ± 239.
[16] E. A. Dennis, P. Y. K. Wong, Phospholipase A2: Role and Function in
Inflammation, Plenum, New York, 1990.
[17] M. H. Gelb, M. K. Jain, O. G. Berg, FASEB J. 1994, 8, 916 ± 924.
[18] H.-K. Lin, M. H. Gelb, J. Am. Chem. Soc. 1993, 115, 3932 ± 3942.
[19] C. Ehnholm, T. Kuusi, Methods Enzymol. 1986, 129, 716 ± 738.
[20] T. Bayburt, B.-Z. Yu, I. Street, F. Ghomashchi, F. Laliberte, H. Perrier,
Z. Wang, R. Homan, M. K. Jain, M. H. Gelb, Anal. Biochem. 1995,
232, 7 ± 23.
[21] L. J. Reynolds, L. L. Hughes, E. A. Dennis, Anal. Biochem. 1992, 204,
190 ± 197.
[22] D. W. Grainger, A. Reichert, H. Ringsdorf, C. Salesse, D. E. Davies,
J. B. Lloyd, Biochim. Biophys. Acta 1990, 1022, 146 ± 153.
[23] S.-K. Wu, W. Cho, Anal. Biochem. 1994, 221, 152 ± 159.
[24] R. Dua, S.-K. Wu, W. Cho, J. Biol. Chem. 1995, 270, 263 ± 268.
[25] V. M. Mirsky, C. Krause, K. D. Heckmann, Thin Solid Films 1996, 284,
939 ± 941.
Experimental Section
Figure 2a: The polymerized vesicles composed of 40% DMPC/60% PDA,
1mm total lipid, were diluted 1:10 in 50mm Tris buffer (pH 7.0) to a final
volume of 0.5 mL in a standard cuvette, and the spectra were recorded with
[26] G. Wegner, J. Polym. Sci. Part B 1971, 9, 133 ± 144.
[27] H. Ringsdorf, B. Schlarb, J. Venzmer, Angew. Chem. 1988, 100, 117 ±
162; Angew. Chem. Int. Ed. Engl. 1988, 27, 113 ± 158.
[28] I. C. P. Smith, I. H. Ekiel, Phosphorous-31 NMR. Principles and
Applications, Academic Press, Orlando, 1984.
[29] R. Jelinek, S. Y. Okada, S. Norvez, D. Charych, Chem. Biol. 1998, 5,
619 ± 629.
[30] M. K. Jain, W. Tao, J. Rogers, C. Arenson, H. Eibl, B.-Z. Yu,
Biochemistry 1991, 30, 10256 ± 10268.
[31] M. Jain, unpublished results.
[32] M. F. Rubner, D. J. Sandman, C. Velazquez, Macromolecules 1987, 20,
1296 ± 1300.
[33] M. Wenzel, G. H. Atkinson, J. Am. Chem. Soc. 1989, 111, 6123 ± 6127.
[34] Y. Tomioka, N. Tanaka, S. Imazeki, J. Chem. Phys. 1989, 91, 5694 ±
5700.
a
Hewlett Packard Spectrophotometer (model 9153C). Bee venom
phospholipase A2 (Sigma) was dissolved in a buffer (pH 8.9) of 10mm
Tris, 150mm NaCl, and 5mm CaCl2 to yield a final concentration of
1.4 mg mL 1. 50 mL of this solution was added to the cuvette and the
spectrum recorded after 60 min.
Figure 2b: 5 mL of the 1.4 mgmL 1 solution of PLA2 was added to 50 mL of
DMPC/DPA vesicles (0.1mm final total lipid concentration). The experi-
ment was carried out in a standard 96-well plate with a UVmax kinetic
microplate reader (Molecular Devices). The absorption of the vesicle
solution was monitored as a function of time at 620 and 490 nm. The data
was then plotted as colorimetric response (CR) versus time to yield the
color response curves. Colorimetric response is defined here as the
percentage change in the absorption at 620 nm relative to the total
absorption maxima.[6]
Figure 2c: 5 mL of 40% DTPC/PDA vesicles diluted with 45 mL of 50mm
Tris pH 7.0 and 5 mL of 6mm DTNB were incubated with 10 mL of
1.4 mg mL PLA2. The absorbance at 412 nm was monitored over time.
[35] Y. Tomioka, N. Tanaka, S. Imazeki, Thin Solid Films 1989, 179, 27 ± 31.
[36] H. Kitano, N. Kato, N. Ise, J. Am. Chem. Soc. 1989, 111, 6809 ± 6813.
1
Figure 4b: MJ33 was added to 5 mL of unpolymerized 40% DMPC/PDA
vesicles (0.015 mol ratio of MJ33 in the substrate interface) in 40 mL of
50mm Tris (pH 7.0) and 5 mL of a solution of 50mm Tris, 150mm NaCl, and
5mm CaCl2 (pH 8.9). The mixture was incubated at room temperature for
20 min and polymerized prior to measuring the absorption at 490 and
620 nm. 5 mL of a 1.4 mgmL solution of PLA2 was added and the
colorimetric response recorded as above. For Zn2‡ inhibition the enzyme
was dissolved in 10mm Tris, 150mm NaCl, and 0.1mm ZnCl2 at pH 8.9.
Practically Perfect Asymmetric Autocatalysis
with (2-Alkynyl-5-pyrimidyl)alkanols
1
Takanori Shibata, Shigeru Yonekubo, and Kenso Soai*
Received: July 14, 1998 [Z12143IE]
German version: Angew. Chem. 1999, 111, 678 ± 682
Organic synthesis plays a central role in natural and
technical sciences, and the development of organic reactions
that proceed with perfect chemo- and stereoselectivity is an
important goal for organic chemists.[1] Reactions that are
catalyzed by enzymes in living organisms proceed with
extremely high chemo- and stereoselectivities. Enzymes are,
however, macromolecules that consist of thousands of amino
Keywords: biosensors ´ conjugation ´ enzyme catalysis ´
enzyme inhibitors ´ vesicles
[1] I. Levesque, M. Leclerc, Chem. Mater. 1996, 8 , 2843 ± 2849.
[2] C. Galiotis, R. J. Young, D. N. Batchelder, J. Polym. Sci. Polym. Phys.
Ed. 1983, 21, 2483 ± 2494.
[3] M. J. Marsella, R. J. Newland, P. J. Carroll, T. M. Swager, J. Am.
Chem. Soc. 1995, 117, 9842 ± 9848.
[4] H. Tanaka, M. A. Gomez, A. E. Tonelli, M. Thakur, Macromolecules
1989, 22, 1208 ± 1215.
[5] D. Charych, Q. Cheng, A. Reichert, G. Kuziemko, M. Stroh, J. O.
Nagy, W. Spevak, R. C. Stevens, Chem. Biol. 1996, 3, 113 ± 120.
[6] A. Reichert, J. O. Nagy, W. Spevak, D. Charych, J. Am. Chem. Soc.
1995, 117, 829 ± 830.
[7] D. H. Charych, J. O. Nagy, W. Spevak, M. D. Bednarski, Science 1993,
261, 585 ± 588.
[*] Prof. Dr. K. Soai, Dr. T. Shibata, S. Yonekubo
Department of Applied Chemistry
Faculty of Science, Science University of Tokyo
Kagurazaka, Shinjuku-ku, Tokyo 162 ± 8601 (Japan)
Fax : (‡ 81)3-3235-2214
E-mail: ksoai@ch.kagu.sut.ac.jp
[**] This work was supported by a Grant-in-Aid for Scientific Research
from the Ministry of Education, Science, Sports, and Culture, the
Kurata Foundation, and the SUT Grant for Research Promotion.
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acids. It is a challenging problem in asymmetric synthesis to
design a chiral catalyst that exhibits extremely high enantio-
selectivity.[2] Although highly enantioselective reactions
(>90% ee) are known these days, it is much more difficult
to develop an enantioselective reaction that gives greater than
99.5% ee, even in non-autocatalytic asymmetric synthesis. In
general, it is difficult to achieve a reaction with an extremely
high ee value (>99.5%) because the difference in Gibbs free
energy (DDG=) between the transition states that give the R
and S isomers kinetically increases exponentially with the
increase in enantioselectivity.[3] We have studied asymmetric
autocatalysis,[4, 5] where the catalyst and product have the
same structure and configuration.
N
N
tBu
CHO
20 mol% 2, > 99.5% ee
1
N
N
asymmetric autocatalyst
+
(2)
tBu
*
solvent, 0 ˚C, 3 h
OH
iPr2Zn
2
X equiv.
with 99.1% ee (Table 1, entry 1). When cumene was used as
the solvent instead of toluene the ee value increased to 99.3%
(entry 2). The ee value reached in excess of 99.5% when a
cumene solution of diisopropylzinc was used (entry 4). The
use of 1.7 equivalents of diisopropylzinc gave (S)-2 with a
We previously reported the first highly enantioselective
autocatalytic reaction,[5b] but even this reaction did not
achieve perfect enantioselectivity: when a pyrimidylalkanol
with a high ee value was used as an asymmetric autocatalyst,
the ee value of the resulting pyrimidylalkanol remained at up
to 98.2% and the chemical yield was no greater that 80%, as a
result of the formation of by-products and the recovery of
unreacted aldehyde. We report here an unprecedented
practically perfect asymmetric autocatalytic reaction that
gives extremely high enantioselectivity (>99.5% ee) and
almost quantitative chemical yield (>99%).
First, to find a better asymmetric autocatalyst, several
5-pyrimidylalkanols that possessed an alkynyl group at their
2-positions were used as asymmetric autocatalysts in the
enantioselective alkylation with diisopropylzinc (2.2 equiv)
[Eq. (1)]. Differences in selectivity were clarified by the use
Table 1. Asymmetric autocatalytic reaction as shown in Equation (2) with
(S)- and (R)-2 with >99.5% ee.
Entry
X
Solvent
Asym. autocat.
and product
ee [%]
Newly formed
product
yield [%]
ee [%]
1
2
3
4
5
6
2.2 toluene[a]
2.2 cumene[a]
99.3 (S)
99.4 (S)
98
98
99
99
> 99
> 99
99.1 (S)
99.3 (S)
99.1 (S)
> 99.5 (S)
> 99.5 (S)
> 99.5 (R)
2.2 tert-butylbenzene[a] 99.3 (S)
2.2 cumene[b]
1.7 cumene[b]
1.7 cumene[b]
> 99.5 (S)
> 99.5 (S)
> 99.5 (R)
[a] With 1m iPr2Zn in toluene. [b] With 1m iPr2Zn in cumene.
greater than 99.5% ee and induced a further increase in yield
(>99%; entry 5). (R)-Pyrimidylalkanol ((R)-2), with the
opposite configuration, is also an extremely efficient asym-
metric autocatalyst (entry 6). We utltimately achieved a
practically perfect asymmetric autocatalytic reaction in terms
of either configurations (>99.5% ee, >99% yield).
Under the best reaction conditions (Table 1, entry 5), the
reaction was performed successively, with the products of one
round serving as the reactants for the next entry (Table 2).
Even after ten rounds, all the asymmetric autocatalytic
reactions proceeded perfectly (>99%, >99.5% ee). In our
reaction, the factor by which the amount of (S)-2 multiplied
relative to the amount of (S)-2 initially used as an asymmetric
N
N
N
N
R
R
CHO
S
OH
20 mol%
asymmetric autocatalyst
N
N
+
(1)
R
S
OH
toluene, 0 ˚C
iPr2Zn
(R = nBu, tBu, Me3Si, iPr3Si, Ph)
of (2-alkynylpyrimidyl)alkanols with a low ee value. An
alkanol, including the catalyst, with 21.2% ee was obtained
from the use of a pyrimidylalkanol with an n-butyl group on
the alkyne with 5.8% ee. The introduction of a tert-butyl or
trimethylsilyl group was much more effective (5.5 !69.6% ee
for a tert-butyl and 8.4 !74.2% ee for a trimethylsilyl group).
On the other hand the introduction of a more bulky
triisopropylsilyl group reduced the catalytic activity (8.6 !
8.8% ee). A phenyl group was also effective (5.9 ! 47.3%ee),
but less than a tert-butyl group. These results imply that a
moderate electron-withdrawing effect that arises from the
alkynyl group and the appropriate bulkiness of the alkyne are
indispensable for a practically perfect asymmetric autocata-
lyst. Thus, 1-(2-tert-butylethynyl-5-pyrimidyl)-2-methyl-1-prop-
anol was found to be a very efficient asymmetric autocatalyst.
The enantioselective isopropylation of 2-(tert-butylethy-
nyl)pyrimidine-5-carbaldehyde (1) with diisopropylzinc (in
toluene) and the enantiomerically pure (>99.5% ee) (S)-
pyrimidylalkanol (S)-2 as an asymmetric autocatalyst was
performed in toluene [Eq. (2)]. This reaction resulted in the
formation of (S)-pyrimidylalkanol (S)-2 in 98% yield and
N
tBu
CHO
2
N
> 99.5% ee
1
N
N
asymmetric autocatalyst
+
(3)
tBu
*
cumene, 0 ˚C, 3 h
OH
iPr2Zn
2
>99%, >99.5% ee
autocatalyst (entry 1) was approximately 103 in five rounds
(entry 5) and approximately 107 in ten rounds (entry 10), with
no deterioration of the catalyst. Thus, in the present asym-
metric autocatalytic reaction, the factor by which a chiral
molecule multiplies is practically unlimited.
In this asymmetric autocatalytic reaction, only one product
(catalyst) is obtained. Therefore, if this product can be
converted into important chiral synthetic intermediates, the
significance of this scheme is surely enhanced. In fact, we
previously reported that chiral 5-pyrimidylalkanols can be
transformed into a-hydroxycarboxylic acid derivatives with-
out racemization.[6]
660
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Table 2. Consecutive asymmetric autocatalytic reaction[a] shown in Equa-
tion (3). The compounds 2a ± k only distinguish in which round the catalyst
is used.
[1] D. Seebach, Angew. Chem. 1990, 102, 1363 ± 1409; Angew. Chem. Int.
Ed. Engl. 1990, 29, 1320 ± 1367.
[2] a) Catalytic Asymmetric Synthesis (Ed.: I. Ojima), VCH, Weinheim,
1993; b) A. Togni, L. M. Venanzi, Angew. Chem. 1994, 106, 517 ± 548;
Angew. Chem. Int. Ed. Engl. 1994, 33, 497 ± 526.
[3] a) J. D. Morrison, H. S. Mosher, Asymmetric Organic Reaction,
Prentice-Hall, Englewood Cliffs, New Jersey, 1971, chap. 1, pp. 28 ±
49; b) Y. Izumi, A. Tai, Stereo-Differentiating Reactions, Academic
Press, New York, 1977, chap. 7, pp. 178 ± 184.
[4] Short reviews, see a) K. Soai, T. Shibata, Yuki Gosei Kagaku Kyokaishi
(J. Synth. Org. Chem. Jpn.) 1997, 54, 994 ± 1005; b) C.Bolm, A. Seger, F.
Bienewald, Organic Synthesis Highlights III (Eds.: J. Mulzer, H.
Waldmann), WILEY-VCH, Weinheim, 1998, pp. 79 ± 83; c) C.Bolm,
F. Bienewald, A. Seger, Angew. Chem. 1996, 108, 1767 ± 1769; Angew.
Chem. Int. Ed. Engl. 1996, 35, 1657 ± 1659.
[5] a) K. Soai, T. Shibata, H. Morioka, K. Choji, Nature 1995, 378, 767 ±
777; b) T. Shibata, H. Morioka, T. Hayase, K. Choji, K. Soai, J. Am.
Chem. Soc. 1996, 118, 471 ± 472; c) T. Shibata, K. Choji, H. Morioka, T.
Hayase, K. Soai, Chem. Commun. 1996, 751 ± 752; d) T. Shibata, K.
Choji, T. Hayase, Y. Aizu, K. Soai, Chem. Commun. 1996, 1235 ± 1236;
e) T. Shibata, H. Morioka, S. Tanji, T. Hayase, Y. Kodaka, K. Soai,
Tetrahedron Lett. 1996, 37, 8783 ± 8786; f) T. Shibata, T. Hayase, J.
Yamamoto, K. Soai, Tetrahedron: Asymmetry 1997, 8, 1717 ± 1719.
[6] a) K. Soai, S. Tanji, Y. Kodaka, T. Shibata, Enantiomer 1998, 3, 241 ±
243; b) S. Tanji, Y. Kodaka, T. Shibata, K. Soai, Heterocycles in press.
[7] M. Hird, K. J. Toyne, G. W. Gray, Liq. Cryst. 1992, 14, 741 ± 761.
[8] J. W. Goodby, M. Hird, R. A. Lewis, K. J. Toyne, Chem. Commun. 1996,
2719 ± 2720.
Entry Asym. Autocat.
Product
Amplified factor[b]
ee [%]
yield [%] ee[%]
1
2
3
4
5
6
7
8
9
> 99.5 (2a)
> 99.5 (2b)
> 99.5 (2c)
> 99.5 (2d)
> 99.5 (2e)
> 99.5 (2 f)
> 99.5 (2g)
> 99.5 (2h)
> 99.5 (2j)
> 99.5 (2k)
> 99
> 99
> 99
> 99
> 99
> 99
> 99
> 99
> 99
> 99
> 99.5 (2b)
6
> 99.5 (2c)
> 99.5 (2d)
> 99.5 (2e)
> 99.5 (2 f)
> 99.5 (2g)
> 99.5 (2h)
> 99.5 (2i)
> 99.5 (2k)
> 99.5 (2l)
62
63
64
65 ꢀ8 Â 103
66
67
68
69
10
610 ꢀ6 Â 107
[a] Molar ratio 1:iPr2Zn (in cumene):catalyst 2 ˆ 1.0:1.7:0.2. [b] The factor
by which the amount of 2 has multiplied based on the amount of 2 used as
an asymmetric autocatalyst in entry 1.
Experimental Section
Entry 5, Table 1: A solution of 1 (94.2 mg, 0.50 mmol) in cumene (5.0 mL)
was added at 08C to a mixture of (S)-2 (23.3 mg, 0.10 mmol, >99.5% ee) in
cumene (12.0 mL) and iPr2Zn (0.85 mL of a 1m solution in cumene,
0.85 mmol) that had been stirred for 15 min at 08C. The reaction mixture
was stirred for 3 h at 08C, then quenched by the addition of 1m hydrochloric
acid (3 mL) and saturated aqueous NaHCO3 (9 mL) at 08C. The mixture
was filtered through celite and the filtrate was extracted with ethyl acetate
(4 Â 15 mL). The extract was dried over anhydrous sodium sulfate and
evaporated under reduced pressure. Cumene was removed by flash column
chromatography (SiO2, hexane, then hexane/ethyl acetate, 3/1) to give pure
2 (138.8 mg). HPLC analysis of the obtained 2 on a column with a chiral
stationary phase (Daicel Chiralcel OD, eluent 3% 2-propanol in hexane,
flow rate 1.0 mLmin 1, 254 nm UV detector, retention time 18.1 min for
(S)-2, 26.9 min for (R)-2) showed that it had an enantiomeric purity of
>99.5% ee. The newly formed (S)-alcohol (138.8 23.3 ˆ 115.5 mg, 99.2%
yield) had an enantiomeric purity of >99.5% ee.
[9] T. Rho, Y. F. Abuh, Synth. Commun. 1994, 24, 253 ± 256.
A Functionalized Heterocubane with Extensive
Intermolecular Hydrogen Bonds**
Musa A. Said, Herbert W. Roesky,*
Carsten Rennekamp, Marius Andruh,
Hans-Georg Schmidt, and Mathias Noltemeyer
Preparation of 2-alkynylpyrimidine-5-carbaldehydes (Scheme 1): Com-
mercially available 2-hydroxypyrimidine hydrochloride was halogenated to
form 5-bromo-2-chloropyrimidine by the improved procedure.[7] Halogen
exchange occurred at the 2-position by the reaction with hydroiodic acid to
give 5-bromo-2-iodopyrimidine, which was then coupled with alkynes to
give 2-alkynyl-5-bromopyrimidines in 80 ± 99%.[8] Lithiation of the bro-
mides by n- or tert-butyllithium and the subsequent formylation[9] by ethyl
formate gave the 2-alkynylpyrimidine-5-carbaldehydes in 25 ± 60%.
Dedicated to Professor Alan H. Cowley
on the occasion of his 65th birthday
The use of inorganic cage compounds as molecular building
blocks for the rational design of materials is an attractive and
challenging avenue for the materials chemist. One example is
the silicate cage compounds (RSiO1.5)n (R ˆ organic or
inorganic group), which are potentially a very useful class of
compounds.[1±6] They have been used as three-dimensional
building block units for the synthesis of new materials, such as
precursors for ceramics and models in various fields.[1, 3, 4] In
addition, an exciting structural organization of the cubic
silicate species [Si8O20]8 was achieved recently with various
N
N
N
a, b
N
N
c
I
Br
HO
Cl
Br
• HCl
N
N
N
N
N
N
N
d
e
+
R
I
Br
R
Br
R
CHO
(R =nBu, tBu, Me3Si, iPr3Si, Ph)
Scheme 1. Synthesis of 2-alkynylpyrimidine-5-carbaldehydes. a) Br2, H2O;
b) POCl3, PhNMe2, 55% over two steps; c) 57% HI, CH2Cl2, 93%; d) 1 ± 2
mol% [Pd(PPh3)4], 2 ± 4 mol% CuI, iPr2NH, 80 ± 99%; e) nBuLi or tBuLi
then HCO2Et, THF or Et2O, 25 ± 60%.
[*] Prof. Dr. H. W. Roesky, Dr. M. A. Said, Dipl.-Chem. C. Rennekamp,
Dr. M. Andruh, H.-G. Schmidt, Dr. M. Noltemeyer
Institut für Anorganische Chemie der Universität
Tammannstrasse 4, D-37077 Göttingen (Germany)
Fax: (‡49)551-393-337
E-mail: hroesky@gwdg.de
Received: October 15, 1998 [Z12530IE]
German version: Angew. Chem. 1999, 111, 749 ± 751
[**] This work was supported by the Deutsche Forschungsgemeinschaft,
the Witco GmbH, and the Volkswagen Foundation. M.A.S. thanks the
Alexander-von-Humboldt foundation, Bonn, for a research fellow-
ship. C.R. is grateful to the Fonds der Chemischen Industrie for a
fellowship.
Keywords: aldehydes ´ alkylations ´ asymmetric synthesis ´
autocatalysis ´ zinc
Angew. Chem. Int. Ed. 1999, 38, No. 5
ꢀ WILEY-VCH Verlag GmbH, D-69451 Weinheim, 1999
1433-7851/99/3805-0661 $ 17.50+.50/0
661