Expeditious 'on-water' cycloaddition between N-substituted maleimides and furans

Article abstract of DOI:10.1055/s-0034-1378560

Cycloaddition reactions between N-alkyl and N-aryl-substituted maleimides and furan derivatives have been carried out using the 'on-water' methodology. Transformations are faster and products can easily be isolated by simple workup protocols, often in qua

Full text of DOI:10.1055/s-0034-1378560

LETTER
▌2179
letter
Expeditious ‘On-Water’ Cycloaddition between N-Substituted Maleimides
and Furans
‘On-Water’ Cycloadditions
María Victoria Gil, Verónica Luque-Agudo, Emilio Román,* José Antonio Serrano
Departamento de Química Orgánica e Inorgánica, Facultad de Ciencias, Universidad de Extremadura, Avda. de Elvas, s/n, 06071 Badajoz, Spain
Fax +34(924)271149; E-mail: roman@unex.es
Received: 23.05.2014; Accepted after revision: 04.07.2014
described on moving from organic solvents to aqueous
Abstract: Cycloaddition reactions between N-alkyl and N-aryl-
conditions.6,7
substituted maleimides and furan derivatives have been carried out
using the ‘on-water’ methodology. Transformations are faster and
products can easily be isolated by simple workup protocols, often in
quantitative yields.
The Diels–Alder cycloaddition plays a key role in synthe-
ses of cantharidin (1) and norcantharidin (2, Figure 1), as
well as some of their derivatives; those two compounds
have similar biological activity, the former being the most
effective ingredient in the preparation of several healing
products used in ancient Chinese medicine and against
certain malignant tumors worldwide. Some derivatives of
exo-5,6-dehydronorcantharidin (3) also exhibit pharma-
cological activity.8 Currently, the use of these compounds
in clinical practice is replacing cantharidin due to their
lower toxicity and greater ease of synthesis.9
Key words: cycloaddition, heterocycles, green chemistry
Synthetic organic chemistry is currently experiencing nu-
merous innovations to develop environmentally friendly
procedures that avoid the use of toxic or hazardous re-
agents, leading to safer and more efficient protocols. This
so-called ‘green chemistry’ takes into account economic
and ecological considerations, such as energy consump-
tion, atom efficiency, and sustainability of chemical pro-
cesses.1 In this context, considerable research is devoted
to alternative reaction media, such as solvent-free condi-
tions, ionic liquids, or water, to reduce or eliminate the use
of traditional organic solvents and the processing thereof.
Among these options, the use of water as the supporting
medium for a reaction opens up new and advantageous
ways to perform organic transformations. By using this
methodology, there have been in the last decades numer-
ous reactions which not only have shown remarkable in-
creases in both rates and yields when compared with the
same processes in common organic solvents, but also they
were more chemo-, regio-, and enantioselective; thus in-
creasing the importance of those reactions performed in
aqueous media.2
O
O
O
O
O
O
O
O
O
O
O
N-R
O
O
O
O
1
2
3
4
Figure 1 Pharmacologically active cantharidin (1) and related prod-
ucts
The unsaturated oxabicycle 3 is the immediate precursor,
via 2, of a series of norcantharimides 4, which have shown
moderate to good cytotoxicity in anticancer evaluation,10
as well as good antiplasmodial activity.11 The presence of
the imide moiety is a structural requisite for several im-
portant bioactive molecules showing antitumor, antiviral,
analgesic, sedative, and fungicide properties.9b,12 Herein
we report highly efficient Diels–Alder reactions between
furan derivatives and three maleimides, by using the envi-
ronmentally benign ‘on-water’ protocol.
Sharpless et al.3 coined the term ‘on-water’ reactions for
those processes involving water-insoluble reactants in
which a vigorous stirring of the reaction medium gener-
ates aqueous emulsions or suspensions in the absence of
organic cosolvents. From an environmental point of view,
this methodology where water plays the roles of reaction
medium and catalyst is one of the most recent and prom-
ising innovations in organic synthesis.4
Reactions between N-phenyl-, N-ethyl-, and N-tert-butyl-
maleimides (5a–c) with furan, 2-methylfuran, and 2,5-di-
methylfurans (6a–c) were carried out either at ambient
temperature or at 65 °C. In all cases, the reagents were in-
soluble or only slightly soluble in water, forming an aque-
ous suspension after vigorous magnetic stirring. An
excess of furan or derivatives were used to dissolve the
solid maleimides 5a and 5b, whereas stoichiometric
amounts of the same furans were employed with liquid
maleimide 5c. Under both temperature conditions, N-phe-
nyl- and N-ethylmaleimides (5a and 5b) afforded mix-
tures of the corresponding endo- and exo-Diels–Alder
adducts 7–12 (Scheme 1 and Table 1) in quantitative
yields, although for 5c, the yields are of product obtained
after achieving equilibrium at 25 °C. With the exception
Literature reports about organic reactions that occur ‘on
water’ are rapidly growing in number and this area has
been reviewed.5 Pericyclic reactions, such as Diels–Alder
cycloadditions, are among the most frequently cited,
probably because these processes were the first for which
substantial changes in selectivities and accelerations were
SYNLETT 2014, 25, 2179–2183
Advanced online publication: 13.08.2014
0
9
3
6
-
5
2
1
4
1
4
3
7
-
2
0
9
6
DOI: 10.1055/s-0034-1378560; Art ID: st-2014-d0448-l
© Georg Thieme Verlag Stuttgart · New York

2180
M. V. Gil et al.
LETTER
R2
O
R2
O
N
O
O
+
+
R1
R2
R3
O
O
N
R3
R3
O
N
O
R1
R1
R1
O
R3
R2
6a, R2 = R3 = H
6b, R2 = H, R3 = Me
6c, R2 = R3 = Me
5a, R1 = Ph
5b, R1 = Et
5c, R1 = t-Bu
7a
8a
9a
10a
11a
12a
13a
14a
15a
Ph
Ph
Ph
Et
Et
Et
t-Bu
t-Bu
t-Bu
H
H
Me
H
H
Me
H
H
H
7b
8b
9b
10b
11b
12b
13b
14b
15b
Me
Me
H
Me
Me
H
Me
Me
Me
Scheme 1
of the cycloaddition between 5c and 9, reaction times Compound exo-11b was prevalent in the mixture of
were shorter at 65 °C.
11a/11b. This behavior could be explained by considering
that the exo adducts are compounds of thermodynamic
control. It should be noted that 7b and 8b were obtained
quantitatively; thus, the former was resulting from heating
the mixture of 7a + 7b at 95–100 °C, whereas the latter
was obtained directly from the cycloaddition at 65 °C. The
imide-oxabicycle 7b has been used as starting material for
the preparation of perhydroisoindoles showing broad
pharmacological activity.13 Adducts 7a, 8a, 9a,b, 10a,
11b, and 12a were isolated in pure form by preparative
thin-layer chromatography, having been used compounds
10a and 10b as monomers in the alternating copolymer-
ization with cyclooctene, via ring-opening metathesis of
copolymers with polar tailorable functionalities linked by
nonpolar spacers.14 Similarly, the treatment of furans 6a–
c with N-tert-butylmaleimide (5c) led to the correspond-
ing cycloadducts as endo–exo mixtures, from which
13a,b, 14b, and 15a,b could be isolated by PTLC.
Table 1 Diels–Alder Reactions between Furans 6a–c, 9 and Ma-
leimides 5a–c[29]
Imide Diene Time
(h)a,b
Yield
(%)a,b
Product(s)
Ratio
endo/exo
5a
5b
5c
6a
6b
6c
9
3.0a
1.5b
0.6a
0.3b
1.0a
0.5b
1.5a
0.25b
quant.a,b
quant.a,b
quant.a,b
quant.a,b
7a/7b[24]
8a/8b
1.6:1a
1.6:1b
1.3:1a
0:1b
9a/9b
16a[26]
5:1a
1.2:1b
0:1a
0:1b
6a
6b
6c
9
3.0a
quant.a,b
quant.a,b
quant.a,b
quant.a,b
10a/10b
11a/11b
12a/12b
19b[27]
6:1a
1.0b
1.4:1b
1.5:1a
1:1.7b
6.5:1a
3.5:1b
2.5a
1.0b
0.6a
The outcomes of the reaction between furfural N,N-di-
methylhydrazone (9) and maleimides 5a–c (Scheme 2 and
Table 1) were different from those described above. Thus,
either at room temperature or at 65 °C, the treatment of 9
with 5a led quantitatively to the exo adduct 16a, whereas
with 5b the phthalimide 19b was exclusively obtained
and, in the case of 5c, the product consisted of a mixture
of 20c and 21c.
0.25b
0.45a
0.25b
6a
6b
6c
9
51a
38c
37b
61c
56c
82c
30b
37c
37b
13a/13b[25]
14a/14b
1:1.6a
0:1b
26b
51a
23b
15a/15b
1:8a
20c/21c[28]
0:1b
1.3a
2.3:1a
1:2.5b
2:1a
1.0b
0.6a
1.0b
Heating of an aqueous suspension of 16a in water at 95–
100 °C for 50 minutes gave phthalimide 17a in 94% yield.
The conversion of 18b into 19b proceeded spontaneously
under the reaction conditions at 25 °C for 27 minutes or
by heating either at 65 °C for 15 minutes.
0:1b
a Results from reactions at r.t.
b Results from reactions at 65 °C.
c Incomplete reactions: conversion rates are calculated when equilib-
rium is reached.
Treatment of hydrazone 9 with N-tert-butylmaleimide
(5c) yielded a 2:1 mixture of cycloadduct 20c and
phthalimide 21c (Table 1); however, after stirring for six
hours at room temperature, the ratio 20c/21c became
1:6.1. When this reaction was performed at 65 °C, only
phthalimide 21c was obtained. We propose that the for-
mation of phthalimides through ring opening of exo-7-ox-
abicycle followed by dehydration is aided by electron
donation from the hydrazono substituent assisting in the
rupture of the oxygen bridge;15 however, no cycloadduct
At 25 °C, the adducts from olefins 5a or 5b were predom-
inantly endo, whereas an increase in exo adducts was ob-
served when the cycloadditions were carried out at 65 °C.
At this temperature, only the exo products 8b, 13b, and
14b were formed in the cycloadditions of 5a and 6b, 5c
and 6a, or 5c and 6b, respectively.
Synlett 2014, 25, 2179–2183
© Georg Thieme Verlag Stuttgart · New York

LETTER
‘On-Water’ Cycloadditions
2181
O
O
N
O
Me
N
N
R
+
N
R
O
O
N
R
O
Me
O
O
9
N
N
N
5a, R = Ph
5b, R = Et
5c, R = t-Bu
Me
N
Me
Me
Me
R
16a
18b
20c
Ph
Et
17a
19b
21c
t-Bu
Scheme 2 ‘On-water’ cycloadditions between maleimides 5a–c and furfural N,N-dimethylhydrazone (9)
18b could be detected by 1H NMR analysis of the reaction The cycloaddition of 5a and 6b has been described at
mixture of 9 and 5b.
room temperature for 24 hours, in a 4:1 mixture of tolu-
ene–benzene, under 11 kbar pressure. The product was
obtained in 85% yield, as a 1:1.6 mixture of 8a/8b.20
It should be noted that the ‘on-water’ reaction between
furfural N,N-dimethylhydrazone (9) and maleimide (5a)
led quantitatively to exo adduct 16a. The structure of the The reaction of N-phenylmaleimide (5a) with 2,5-dimeth-
latter is of great interest either in itself or as immediate ylfuran (6c) occurred in 90 minutes at 0 °C on K10 mont-
precursor of products with potential biological activity;12 morillonite and in the absence of organic solvents;18 the
furthermore, phthalimides 17a, 19b, and 21c are closely product was obtained in 77% yield, as a 2.3:1 mixture of
related to compounds which are useful for preventing or 9a and 9b. When microwave irradiation was used, the
treating diseases or conditions related to an abnormally same mixture of adducts was produced quantitatively af-
high level or activity of tumor necrosis factor α in mam- ter 15 minutes (2.3:1 ratio). No pure products were isolat-
mals.16
ed.
In order to highlight the improvements we have achieved A recent patent reported21 two Diels–Alder reactions of
by using the ‘on-water’ methodology, a comparison fol- N-maleimide propionic acid and N-(2-hydroxyethyl)ma-
lows between our results and those reported in previous leimide with 2,5-dimethylfuran, leading to 3.5:1 and 4:1
syntheses for some of the products described herein or mixtures of exo/endo adducts 22b/22a and 23b/23a, re-
other with similar structures. Thus, the reaction between spectively (Figure 2). In the first case, the yield was quan-
N-phenylmaleimide (5a) and furan 6a has been de- titative after stirring for six hours in acetonitrile at 60 °C;
scribed17 by dissolving the maleimide in furan, without whereas in the second case no yield was reported, the re-
any additional organic solvent; the mixture was allowed to action being carried out in the same solvent under argon
stand for at least 20 hours and, after ten days, crystalliza- at 65 °C overnight. All of the four adducts could be isolat-
tion of adducts 7a and 7b took place as a mixture that was ed in pure form.
filtered and washed with diethyl ether (88% yield, 36:64
respective ratio). The same reaction was conducted in
solutions in diethyl ether, in benzene, or in CDCl3; in the
latter case, the process was monitored by H NMR and
O
R2
O
N
O
R2
O
1
R1
R3
R3
N
gave 86% conversion after seven days at 0 °C, with an
exo–endo ratio of 36:49; 89% conversion after seven days
at room temperature, with an exo–endo ratio of 48:41 and
91% conversion after 20 days at room temperature, with
an exo–endo ratio of 68:23 (equilibrium ratio). In addi-
tion,18 the solventless reaction between 5a and 6a on K10
montmorillonite at 0 °C for 24 hours gave 85% of a 1.3:1
mixture of 7a and 7b and, when additional microwave ir-
radiation was used, 80% of the same mixture of adducts
was produced after 15 minutes (1.5:1 ratio). No pure prod-
ucts were isolated.
O
R1
O
R1
R2
R3
22a CH2CH2COOH
23a CH2CH2OH
24a Me
Me
Me
H
Me
Me
H
22b
23b
24b
Figure 2 Structures for cycloadducts 22a–24b
The cycloaddition between N-methylmaleimide and furan
has been described in refluxing benzene22 for 15 hours, af-
fording 24a and 24b as a mixture that crystallized from di-
ethyl ether (96% yield, ratio 3:2). When the same process
was carried out in tetrahydrofuran at room temperature for
48 hours, the endo-adduct 24a was isolated in 61% yield
by fractional crystallization from the mixture of the ad-
ducts.23
Products from reactions involving stoichiometric quan-
tities of 2-substituted furans and N-propyl, N-isobutyl,
N-phenyl, or N-tert-butylmaleimides have been used as
model compounds for the preparation of polymers.19 The
processes were carried out at 55 °C for 24–48 hours, in
chloroform, the products being purified by silica gel col-
umn chromatography.
The reaction of N-ethylmaleimide (5b) with hydrazone 9
has been reported15 under stirring for 16 hours in chloro-
© Georg Thieme Verlag Stuttgart · New York
Synlett 2014, 25, 2179–2183

2182
M. V. Gil et al.
LETTER
(11) Bajsa, J.; McCluskey, A.; Gordon, C. P.; Stewart, S. G.; Hill,
T. A.; Sahu, R.; Duke, S. O.; Tekwani, B. L. Bioorg. Med.
Chem. Lett. 2010, 20, 6688.
(12) Göksu, G.; Öcal, N.; Kaufmann, D. E. Molecules 2010, 15,
1302.
form at room temperature, resulting in 90% of solid
phthalimide 19b after extraction with diethyl ether. No 1H
NMR signals were detected for a hypothetical adduct pre-
cursor of this compound. Analogues of 19b, with (2,6-di-
oxopiperidin-3-yl) as a substituent on the imide nitrogen
have synthesized in a two-step thermal reaction for eight
hours with solvent and catalyst.16
(13) Göksu, G.; Gül, M.; Öcal, N.; Kaufmann, D. E. Tetrahedron
Lett. 2008, 49, 2685.
(14) Ilker, M. F.; Coughlin, E. B. Macromolecules 2002, 35, 54.
(15) Potts, K. T.; Walsh, E. B. J. Org. Chem. 1988, 53, 1199.
(16) Muller, G. W.; Saindane, M.; Ge, C.; Kothare, M. A.;
Cameron, L. M.; Rogers, M. E. US 20080064876 A1, 2008.
(17) Cooley, J. H.; Williams, R. V. J. Chem. Educ. 1997, 74, 582.
(18) Avalos, M.; Babiano, R.; Bravo, J. L.; Cintas, P.; Jiménez, J.
L.; Palacios, J. C. Tetrahedron Lett. 1998, 39, 9301.
(19) Canadell, J.; Fischer, H.; De With, G.; Van Benthem, R. A.
T. M. J. Polym. Sci., Part A: Polym. Chem. 2010, 48, 3456.
(20) Jarosz, S.; Mach, M.; Szewczyk, K.; Skóra, S.; Ciunik, Z.
Eur. J. Org. Chem. 2001, 2955.
In conclusion, the results described in this paper show that
the use of the ‘on-water’ protocol clearly improves previ-
ously reported procedures in one or more of the following
aspects: no organic solvent as the reaction medium or
during workup is required; no catalyst is needed; reaction
times are shorter; yields are higher; the protocol is safer
and more energy economical; and reaction conditions are
milder. Therefore, this protocol meets the requirements to
be considered ‘green chemistry’.
(21) Grandas, A. N.; Sánchez, A.; Pedroso, E. US 20130158248
A1, 2013.
(22) Anderson, W. K.; Miowsky, A. S. J. Org. Chem. 1985, 50,
5423.
Acknowledgment
(23) Goh, Y. W.; Pool, B. R.; White, J. M. J. Org. Chem. 2008,
73, 151.
V. Luque-Agudo acknowledges financial support of this work by a
grant from the Plan de Iniciación a la Investigación, Desarrollo Tec-
nológico e Innovación 2013 of the University of Extremadura.
(24) General Procedure for Cycloadditions between N-
Phenyl- or N-Ethylmaleimides 5a,b and Furans 6a–c
A) In a 10 mL round-bottom flask the maleimide (ca. 0.5 g)
was dissolved in the minimum quantity of furan 6a–c (0.5–
1.7 mL); H2O (3 mL) was added, and the resulting mixture
was subjected to vigorous magnetic vigorous at 25 °C. After
the time specified in Table 1, 1H NMR spectroscopic
analysis and TLC (EtOAc–hexane, 1:1) revealed the absence
of starting materials and appearance of the respective
cycloadducts. The products either immediately precipitated,
from the reaction medium or after overnight storage in the
refrigerator, and were filtered and washed on the filter with
cold H2O. In the case of reaction between 5b and 6b, the
reaction mixture was diluted with brine (5 mL), extracted
with CH2Cl2 (3 × 5 mL), the combined extracts dried over
MgSO4, filtered, and evaporated to afford an oil that
crystallized after 24 h into the freezer. Then, the solid was
collected by filtration and washed on the filter with cold
H2O.
Supporting Information for this article is available online
at
http://www.thieme-connect.com/products/ejournals/journal/
10.1055/s-00000083.SunpfgIpi
o
o
nr
i
References and Notes
(1) Gawande, M. B.; Bonifácio, V. D. B.; Luque, R.; Branco, P.
S.; Varma, R. S. Chem. Soc. Rev. 2013, 42, 5522.
(2) (a) Lindström, U. M. Chem. Rev. 2002, 102, 2715. (b) Li,
C.-J. Chem. Rev. 2005, 105, 3095. (c) Horváth, I. T. Green
Chem. 2008, 10, 1024. (d) Candeias, N. R.; Branco, L. C.;
Góis, P. M. P.; Alfonso, C. A. M.; Trindade, A. F. Chem.
Rev. 2009, 109, 2703.
(3) Narayan, S.; Muldoon, J.; Finn, M. G.; Fokin, V. V.; Kolb,
H. C.; Sharpless, K. B. Angew. Chem. Int. Ed. 2005, 44,
3275.
(4) (a) Jung, Y.; Marcus, R. A. J. Am. Chem. Soc. 2007, 129,
5492. (b) Beattie, J. K.; McErlean, C. S. P.; Phippen, C. B.
W. Chem. Eur. J. 2010, 16, 8972. (c) Mellouli, S.;
Bousekkine, L.; Theberge, A. B.; Huck, W. T. S. Angew.
Chem. Int. Ed. 2012, 51, 7981.
(5) (a) Chanda, A.; Fokin, V. V. Chem. Rev. 2009, 109, 725.
(b) Butler, R. N.; Coyne, A. G. Chem. Rev. 2010, 110, 6302.
(c) Simon, M. O.; Li, C.-J. Chem. Soc. Rev. 2012, 41, 1415.
(6) (a) Rideout, D. C.; Breslow, R. J. Am. Chem. Soc. 1980, 102,
7816. (b) Breslow, R.; Maitra, U.; Rideout, D. C.
Tetrahedron Lett. 1983, 24, 1901. (c) Breslow, R. In
Structure and Reactivity in Aqueous Solution, ACS
Symposium Series 568; Cramer, C. J.; Truhlar, D. G., Eds.;
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(7) Grieco, P. A.; Garner, P.; He, Z. Tetrahedron Lett. 1983, 24,
1987.
Yields were quantitative and, in all cases, analytically pure
samples of each one of the adducts could be isolated by
preparative TLC. The exo adduct 7b was the only product
obtained after refluxing an aqueous suspension of a mixture
of 7a and 7b for 45 min.
B) Following the same procedure above, reactions were
complete after stirring at 65 °C for times specified in Table
1. Then, the adducts, which precipitated in the reaction
mixture, were filtered and collected as indicated above.
(25) General Procedure for Cycloadditions between N-tert-
Butylmaleimide 5c and Furans 6a–c
In a 10 mL round-bottom flask, N-tert-butylmaleimide (5c,
0.2 mL, 1.38 mmol) was mixed with an equimolar quantity
of the furans 6a–c (0.10–0.15 mL), H2O was added (3 mL),
and the resulting suspension was subjected to magnetic
vigorous stirring at 25 °C. After times specified in Table 1,
1H NMR and TLC (EtOAc–hexane, 1:2) analyses showed no
further progress of the reaction with the mixture still
containing unreacted starting materials. Except for the
reaction between 5c and 6a, the products precipitated and
were collected by filtration and washed on the filter with
cold H2O. In this case, workup of the reaction mixture was
the same as indicated in ref. 24. Adducts 13a and 13b were
separated by preparative TLC.
(8) Hart, M. E.; Chamberlin, A. R.; Walkom, C.; Sakoff, J. A.;
McCluskey, A. Bioorg. Med. Chem. Lett. 2004, 14, 1969.
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Chem. 2005, 42, 13.
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Synlett 2014, 25, 2179–2183
© Georg Thieme Verlag Stuttgart · New York

LETTER
‘On-Water’ Cycloadditions
2183
(26) 1-[(E)-2,2-Dimethylhydrazono]-7-oxabicyclo[2.2.1]hept-
5-ene-2,3-exo-dicarboxy-N-phenylimide (16a) and 4-
[(E)-2,2-Dimethylhydrazono]-2-phenylisoindoline-1,3-
dione (17a)
dimethyl hydrazone (9, 0.5 mL, 3.77 mmol) led
quantitatively to ethylisoindoline 19b as a solid that was
filtered and washed on the filter with cold H2O.
(28) 1-[(E)-2,2-Dimethylhydrazono]-7-oxabicyclo[2.2.1]hept-
5-ene-2,3-exo-dicarboxy-N-tert-butylimide (20c) and 4-
[(E)-2,2-Dimethylhydrazono]-2-tert-butylisoindoline-
1,3-dione (21c)
Following the two methods A and B as described above,
cycloaddition of N-phenylmaleimide (5a) and furfural
N,N-dimethylhydrazone (9) led quantitatively to adduct 16a
as a yellow solid that was filtered and washed on the filter
with cold H2O. By refluxing a suspension of 16a (0.85 g) in
H2O (25 mL) for 50 min, this compound was converted
quantitatively into phenylisoindoline 17a, isolated by
filtration as an yellow-orange solid and recrystallized from
EtOH.
Following the general procedure above described for the
reactions of furans with N-tert-butyl maleimide (5c),
treatment of the latter compound (0.2 mL, 1.38 mmol) with
furfural N,N-dimethylhydrazone (9, 0.185 mL, 1.39 mmol)
led to an equilibrium mixture (see Table 1) from which 37%
yield of the title compounds were isolated by filtration and
washing on the filter with cold H2O.
(27) 4-[(E)-2,2-Dimethylhydrazono]-2-ethylisoindoline-1,3-
dione (19b)
(29) For 1H NMR and 13C NMR spectra of all compounds see the
Supporting Information.
Following methods A and B as described above, treatment of
N-ethylmaleimide (5b, 0.4 g, 3.20 mmol) and furfural N,N-
© Georg Thieme Verlag Stuttgart · New York
Synlett 2014, 25, 2179–2183

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