Oxidative coupling reactions of 1,3-diarylpropene derivatives to dibenzo[a,c]cycloheptenes by PIFA

Article abstract of DOI:10.1002/ejoc.201100918

The oxidative cyclization reactions of a variety of α- benzylcinnamates can be selectively performed with hypervalent iodine as an oxidant. The dibenzo[a,c]cycloheptenes were isolated in up to 55 % yield. When an oxo substrate is applied, the yield was significantly increased. With this synthetic approach, a central intermediate for the synthesis of metasequirin-B was obtained in three steps from very simple starting materials. For this transformation, both aryl moieties have to be activated.

Full text of DOI:10.1002/ejoc.201100918

FULL PAPER
DOI: 10.1002/ejoc.201100918
Oxidative Coupling Reactions of 1,3-Diarylpropene Derivatives to
Dibenzo[a,c]cycloheptenes by PIFA
Kristina Hackelöer,[a] Gregor Schnakenburg,[b] and Siegfried R. Waldvogel*[a,c]
Keywords: Oxidation / Cyclization / C–C coupling / Hypervalent iodine / Dibenzo[a,c]cycloheptene
The oxidative cyclization reactions of a variety of α-benzyl- thetic approach, a central intermediate for the synthesis of
cinnamates can be selectively performed with hypervalent
iodine as an oxidant. The dibenzo[a,c]cycloheptenes were
isolated in up to 55% yield. When an oxo substrate is ap-
plied, the yield was significantly increased. With this syn-
metasequirin-B was obtained in three steps from very simple
starting materials. For this transformation, both aryl moieties
have to be activated.
drugs act as vascular disrupting agents on existing blood
vessels, which feed a solid tumor causing a tumor ischemia
and necrosis. In particular, these potential drugs are of
interest for the nonsurgical treatment of advanced cancer
states.[6] Consequently, access to the dibenzo[a,c]cyclo-
heptene skeleton is highly desired.
Introduction
Several natural products exhibiting seven-membered ring
systems with annulated benzo moieties are known among
the cycloneolignans and alkaloids,[1] the most prominent
example of which is colchicine.[2] This natural product and
its related compounds, such as allocolchicine, have experi-
enced significant medicinal and biological interest because
of their pharmacological potential.[3] According to their
known mode of action, colchicine and its analogues bind
to the β-subunit of the protein tubulin in the protofila-
ments, which results in the destabilization of the microtu-
bules.[4] This efficiently inhibits the formation of the mitotic
spindle in eukaryotic cells and is of potential interest for
applications in cancer therapy. The high toxicity of col-
chicine limits its application and creates a demand for struc-
tural analogues. Metasequirin-B is the only known natu-
rally occurring norcycloneolignan with a dibenzocyclo-
heptene skeleton fused with a tetrahydrofuran (THF) sys-
Figure 1. Structure of allocolchicine and metasequirin-B.
Common synthetic strategies exploit an early construc-
tem. This natural product is found in the heartwood of tion of the biaryl moiety. Subsequently, the central seven-
Metasequoia glyptostroboides.[5] The similar architecture of membered ring is accomplished. This approach to tricyclic
metasequirin-B to allocolchicine suggests an interesting compounds usually requires several steps and is less flexible
pharmacological profile (Figure 1). These compounds are for molecular variations.[7] An oxidative cyclization ap-
considered as vascular disrupting agents because of the proach via diaryl substrates seems to be ideal because of its
tubulin-binding mechanism, whereas antiangiogenesis atom-economic nature. It is noteworthy that this technology
has received less attention due to the low yields that are
usually observed for such reactions.[8] The only example of
[a] Kekulé Institute for Organic Chemistry and Biochemistry,
Bonn University,
an unsaturated diaryl substrate has been achieved by the
toxic reagent thallium(III) trifluoroacetate (TTFA) and was
not extended to a general method.[9] When 1,3-diarylprop-
anes are available, MoCl5 is a powerful oxidant providing
a collection of dihydrodibenzo[a,c]cycloheptenes with dif-
ferent substitution patterns.[10]
For the oxidative coupling reaction, MoCl5 is a versatile
and easy to handle reagent.[11–13] The performance of this
reagent can be enhanced when Lewis acids are used to bind
Gerhard-Domagk-Strasse 1, 53121 Bonn, Germany
[b] X-ray Analysis Department, Institute for Inorganic Chemistry,
Bonn University,
Gerhard-Domagk-Strasse 1, 53121 Bonn, Germany
[c] Institute for Organic Chemistry, Johannes Gutenberg
University Mainz,
Duesbergweg 10-14, 55128 Mainz, Germany
Fax: +49-6131-39-26777
E-mail: waldvogel@uni-mainz.de
Supporting information for this article is available on the
WWW under http://dx.doi.org/10.1002/ejoc.201100918.
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Oxidative Coupling of 1,3-Diarylpropene Derivatives by PIFA
Scheme 1. Oxidant-dependant reaction pathway: (a) MoCl5, TiCl4 then R1CH2COR, NEt3; (b) PIFA, BF3·OEt2.
hydrogen chloride.[14] If α-benzylcinnamic acid derivatives 2 For the oxo substrates 9 a two-step sequence including
are subjected to this reagent mixture, overoxidation occurs, benzoylation and Knoevenagel condensation was ap-
and an oxidative domino coupling follows resulting in the plied.[18] Standard conditions resulted in yields of up to
formation of 1 (Scheme 1). An intermediate tropylium spe- 84% for the substituted ethyl benzoylacetates 8 and up to
cies is postulated, which allows the installation of a carbon 89% for the ethyl α-benzoylcinnamates 9.[19]
side chain.[15]
Here we report an oxidative coupling protocol, which
Results and Discussion
stops at the intramolecular arylation product 3. The
method of choice is based on Kita’s hypervalent iodine rea-
gent phenyliodine(III) bis(trifluoroacetate) (PIFA).[16]
Other reagents, such as FeCl3 or 2,3-dichloro-5,6-dicyano-
1,4-benzoquinone, resulted either in no conversion, com-
plete decomposition, or in the case of MoCl5, proceeded
with further C–H functionalization.[15] The unusually high
oxidation power was also found by King et al.[12,13] Sub-
strates 2 and 6 are readily prepared by a benzylation/ole-
The tetramethoxy substrate 6a exhibits optimal acti-
vation in both aryl moieties for the oxidation coupling pro-
cess. The product 3a with the seven-membered ring system
was isolated in 55% yield (Table 1, Entry 1). The reaction
was conducted at low temperature for 1.5 h and then at
room temperature for 0.5 h prior to workup. The molecular
structure was verified by X-ray analysis of a suitable single
crystal. The central seven-membered ring is strongly bent
and shows a boat-type conformation (Figure 2), and the bi-
aryl axis is tilted by about 38°.
The location of the electron-releasing methoxy groups is
important. In 6b only a single methoxy group is present on
the cinnamate, whereas the intramolecular coupling partner
exhibits both methoxy groups. Compared to 6a, the reactiv-
ity of 6b is significantly decreased. The desired dibenzo[a,c]-
cycloheptene 3b was obtained in 31% yield (Entry 2). A
reversed substitution pattern with two methoxy groups on
the cinnamate and one on the benzyl moiety was beneficial
for the oxidative arylation. The electron-withdrawing nature
of the ester functionality is partially compensated and re-
sulted in 51% yield for 6c, and 29% of the starting material
was recovered (Entry 3).
fination sequence starting with phosphonoacetate
4
(Scheme 2). The introduction of the benzyl moiety was best
performed in N,N-dimethylformamide (DMF) in the pres-
ence of K2CO3 and the corresponding benzyl chloride de-
rivative. Yields for the α-phosphono-dihydrocinnamates 5
are up to 68%. The synthesis of the product can be easily
conducted on a 0.1 m scale (Supporting Information). Suit-
able conditions for the Horner–Wadsworth–Emmons ole-
fination employ sodium hydride in toluene. However, our
previously elaborated protocol for the synthesis of α-aryl-
cinnamates could not be employed in the synthesis of 6.[17]
The limits of this transformation were elucidated by vari-
ation of the molecular structure. Further methoxy groups
on the cinnamate portion led to another reaction pathway.
Spirocyclohexadienone derivative 10 was isolated in 59%.
The loss of the methyl group occurs on the benzyl moiety
(Entry 4). The architecture of 10 was elucidated by X-ray
analysis of a suitable single crystal (Figure 3).
Most probably, the steric strain caused by the formation
of the seven-membered ring system adjacent to the methoxy
substitutions is too high. Consequently, the six-membered
ring is preferred. If the benzyl fragment is not equipped
with an electron-releasing group, no cyclization reaction
was detected (Entry 5). Shifting the ester group adjacent to
the benzo ring in 6f is rewarded by a lower yield and a
mixture of atropisomers, as these groups exhibit limited ro-
Scheme 2. Synthesis of the substrates: (a) K2CO3, benzyl chloride
derivative, DMF, room temp.; (b) NaH, benzaldehyde derivative,
toluene, 50 °C; (c) LDA, benzoyl chloride derivative; THF, –70 °C;
(d) pyridine, AcOH, benzaldehyde derivative, benzene, reflux.
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K. Hackelöer, G. Schnakenburg, S. R. Waldvogel
FULL PAPER
Table 1. Oxidative cyclization by PIFA/BF3·OEt2 (optimized condi-
tions).
Figure 2. Molecular structure of 3a obtained by X-ray analysis.
Figure 3. Molecular structure of 10 obtained by X-ray analysis.
tational freedom at the seven-membered ring (Entry 6). In-
stallation of an additional oxo group on the substrate is
beneficial to the oxidative coupling process. Despite its elec-
tron-withdrawing nature, yields are increased compared to
the methylene-equipped congeners. The products have some
aromatic stabilization from the central tropylium system.
Substrate 9a is oxidatively arylated to 3e in 84% yield.
Upon crystallization from ethyl acetate, some loss of prod-
uct occurs (Entry 7). When 9b is treated in an analogous
way, the dibenzo[a,c]cycloheptenone 3f is obtained in 51%
yield (Entry 8). As 6b represents the nonoxygenated equiva-
lent of 9b, the influence of the oxo function is remarkable.
The molecular structure of 3f was elucidated by X-ray
analysis of a suitable single crystal. Two competing effects
have an influence on the structure: first, stabilization is
achieved by formation of a central tropylium-like system
leading to a more planarized core; secondly, the steric strain
caused by the set of substituents arranged around the
seven-membered ring system will disfavor the generation of
the central tropylium-like system. The molecular structure
of 3f exhibits a strongly planarized central ring system (Fig-
ure 4), and the birayl axis is tilted by about 28°.
[a] Method A: –40 °C to room temp.; Method B: –20 °C to room
temp. [b] First, reaction time at low temperature, then additional
reaction time at room temp. given. [c] Ratio of isomers 2:1. [d]
After crystallization from ethyl acetate.
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Oxidative Coupling of 1,3-Diarylpropene Derivatives by PIFA
1
yielded 2.06 g (54%) of the desired product. H NMR (300 MHz,
3
3
CDCl3): δ = 1.15 (t, J4,3 = 7.1 Hz, 3 H), 1.34 (t, J6,5 = 7.1 Hz, 3
3
H), 1.35 (t, J8,7 = 7.1 Hz, 3 H), 3.07–3.27 (m, 3ϫ 1 H), 3.77 (s, 3
H), 4.05–4.22 (m, 3ϫ 2 H), 6.80 (d, 3J12,11 = 9.0 Hz, 2ϫ 1 H), 7.10
(d, J11,12 = 9.0 Hz, 2ϫ 1 H) ppm. 13C NMR (75 MHz, CDCl3): δ
3
= 14.0 (s), 16.3 (d, 3J8,P = 6.1 Hz), 16.4 (d, 3J6,P = 6.1 Hz), 32.0 (d,
2J9,P = 4.4 Hz), 48.0 (d, J1,P = 128.5 Hz), 55.2 (s, C-14), 61.3 (s),
1
2
2
62.7 (d, J7,P = 6.9 Hz), 62.8 (d, J5,P = 6.5 Hz), 113.9 (s), 129.6
3
2
(s), 130.6 (d, J10,P = 16.6 Hz), 158.3 (s), 168.5 (d, J2,P = 4.6 Hz)
ppm. MS (EI, 70 eV): m/z (%) = 344 (38) [M]·+, 299 (10) [M –
C2H5O]+, 271 (63) [M – C2H5O – CO]+, 243 (8) [M – C2H5O –
CO – C2H4]+, 206 (100) [M – OP(OC2H5)2 – H]·+, 161 (82)
[M – OP(OC2H5)2 – H – OC2H5]+, 134 (35) [C9H10O]+, 121 (58)
[C8H9O]+, 91 (7) [C6H3O]+, 77 (69) [C6H5]+. HRMS (EI): calcd.
for C17H27O7P [M]·+ 344.1389; found 344.1387.
Ethyl (2E)-3-(3,4-dimethoxyphenyl)-2-(4-methoxybenzyl)prop-2-eno-
ate (6c): To 5c (450 mg, 1.30 mmol) and 3,4-dimethoxybenzalde-
hyde (249 mg, 1.50 mmol) in anhydrous toluene (10 mL) was added
NaH (57 mg, 60% in mineral oil, 1.43 mmol) in several portions
with stirring at room temperature. The mixture was then stirred at
room temperature for 4 d. The solvent was removed under reduced
pressure, and the residue was taken up in ethyl acetate (20 mL) and
washed with water (10 mL). The separated aqueous fraction was
extracted with ethyl acetate (3ϫ 15 mL). The combined organic
fractions were washed with brine (25 mL) and dried with MgSO4.
Removal of the solvent under reduced pressure and purification by
column chromatography on silica (cyclohexane/ethyl acetate, 4:1)
yielded a 4:1 mixture of (E)/(Z) isomers (430 mg, 90%) as a yellow
solid. The major product is (E) isomer. (E)-6c: RF (SiO2; cyclohex-
ane/ethyl acetate, 4:1) = 0.33. 1H NMR (500 MHz, CDCl3): δ =
Figure 4. Molecular structure of 3f obtained by X-ray analysis.
A substrate with a trimethoxyphenyl moiety (9c) still
gives access to the seven-membered ring system. Although
the yield is low, the attack adjacent to the carbonyl group
is efficiently inhibited (Entry 9). Extension of this method
to a substrate with a coupling partner without an activating
group results in no conversion as deactivation by the at-
tached carbonyl group is too high (Entry 10).
Conclusions
3
1.28 (t, J5,4 = 7.1 Hz, 3 H), 3.66 (s, 3 H), 3.78 (s, 3 H), 3.88 (s, 3
The cyclization reaction to dibenzo[a,c]cycloheptenes
and dibenzo[a,c]cycloheptenones by oxidative biaryl cou-
pling is best achieved by the use of hypervalent iodine rea-
gents. The Kita-type protocol allows the formation of the
central seven-membered ring in good to acceptable yields.
The benzo rings fused at a and c disfavor a planar geome-
try. However, the use of substrates with an oxo functionality
results in significantly better yields. The starting materials
are readily prepared and can be constructed in a modular
fashion. However, for both classes of substrates both aryl
moieties have to be activated by at least one methoxy group
in order to be suitable for oxidative cyclization. The central
intermediate for the synthesis of metasequirin-B was ob-
tained in three steps from very simple starting materials
with this synthetic approach.
3
H), 3.95 (br. s, 2ϫ 1 H), 4.23 (q, 3J4,5 = 7.1 Hz, 2 H), 6.83 (d, J9,8
≈ 3J5Ј,6Ј = 8.8 Hz, 3ϫ 1 H), 6.90 (d, 4J2Ј,6Ј = 2.7 Hz, 1 H), 7.00 (dd,
3
3J6Ј,5Ј = 9.0 Hz, 4J6Ј,2Ј = 2.7 Hz, 1 H), 7.13 (d, J8,9 = 8.8 Hz, 1 H),
7.87 (br. s, 1 H) ppm. 13C NMR (125 MHz, CDCl3): δ = 14.2, 32.3,
55.1, 55.5, 55.8, 60.7, 110.9, 112.3, 113.9, 122.9, 128.7, 128.9, 131.4,
140.4, 148.6, 149.5, 157.9, 168.4 ppm. (Z)-6c: 1H NMR (400 MHz,
3
CDCl3): δ = 1.06 (t, J5,4 = 7.1 Hz, 3 H), 3.66 (br. s, 2ϫ 1 H), 3.77
3
(s, 3 H), 3.84 (s, 3 H), 3.86 (s, 3 H), 4.07 (q, J4,5 = 7.1 Hz, 2 H),
3
6.51 (br. s, 1 H), 6.76–6.90 (m, 5ϫ 1 H), 7.17 (d, J8,9 = 8.4 Hz,
2ϫ 1 H) ppm. 13C NMR (101 MHz, CDCl3): δ = 13.8, 40.6, 55.2,
55.7, 55.8, 60.5, 110.6, 111.4, 113.8, 121.4, 130.0, 130.0, 131.1,
132.9, 133.6, 148.3, 148.8, 158.2, 169.5 ppm. MS (EI, 70 eV): m/z
(%) = 356 (100) [M]·+, 327 (5) [M – C2H5]+, 311 (10) [M –
C2H5O]+, 282 (70) [M – C2H5O – CO – H]·+, 267 (30) [M –
C2H5O – CO – H – CH3]+, 251 (11) [M – C2H5O – CO – H –
OCH3]+, 236 (13) [M – C2H5O – CO – H – OCH3 – CH3]·+, 210
(13), 189 (17) [M – C2H5O – CO – H – OCH3 – OCH3 – OCH3]+,
165 (18) [C13H10]+, 145 (10) [C10H9O]+, 121 (11) [C8H9O]+, 77 (66)
[C6H5]+. HRMS (EI): calcd. for C21H24O5 [M]·+ 356.1624; found
356.1620. C21H24O5 (356.42): calcd. C 70.77, H 6.79; found C
70.96, H 6.98.
Experimental Section
General Remarks: See Supporting Information.
Ethyl 2-(Diethoxyphosphoryl)-3-(4-methoxyphenyl)propanoate (5b):
Ethyl (diethoxyphosphoryl)acetate (4, 5 g, 22.3 mmol), 1-(chlo-
romethyl)-4-methoxybenzene (1.75 g, 11.15 mmol), and K2CO3
(2.31 g, 16.73 mmol) in anhydrous DMF (50 mL) were stirred at
room temperature for 3 d. Water (300 mL) was added, and the
Ethyl (2E)-2-(3,4-Dimethoxybenzoyl)-3-(3,4-dimethoxyphenyl)prop-
2-enoate (9a): The Knoevenagel condensation was carried out with
ethyl 3-(3,4-dimethoxyphenyl)-3-oxopropanoate (8, 600 mg,
2.38 mmol), 3,4-dimethoxybenzaldehyde (395 mg, 2.38 mmol),
AcOH (0.03 mL, 0.48 mmol), and piperidine (0.02 mL, 0.24 mL) in
aqueous layer was extracted with ethyl acetate (5ϫ 30 mL). The benzene (20 mL) with a Dean–Stark apparatus. After 4 h of heating
combined organic fractions were washed with water (50 mL) and
brine (50 mL), dried with MgSO4, filtered, and concentrated under
reduced pressure. Excess 4 was removed by distillation under high
vacuum (56 °C, 0.4 mbar, 120 °C). The crude benzylation product
was purified by distillation (62 °C, 2.5ϫ10–6 mbar, 170 °C), which
to reflux, the mixture was allowed to cool to ambient temperature
before water (20 mL) was added. The separated aqueous fraction
was extracted with tert-butyl methyl ether (TBME) (3ϫ 20 mL),
and the combined organic fractions were washed with 1 n HCl (2ϫ
20 mL), satd. NaHCO3 (20 mL), and brine (20 mL), and dried with
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MgSO4. Removal of the solvent under reduced pressure and purifi-
cation by column chromatography on silica (cyclohexane/ethyl
acetate, 2:1) yielded a single diastereomer (840 mg, 88%) as a yel-
low solid. RF (SiO2; cyclohexane/ethyl acetate, 2:1) = 0.17. 1H
with the Kompetenzzentrum der Integrierten Naturstoff-For-
schung (University of Mainz).
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NMR (400 MHz, CDCl3): δ = 1.20 (t, 3J5,4 = 7.1 Hz, 3 H), 3.61 (s,
3
3 H), 3.82 (s, 3 H), 3.90 (s, 3 H), 3.91 (s, 3 H), 4.22 (q, J4,5
=
7.1 Hz, 2 H), 6.74 (d, 3J5Ј,6Ј = 8.4 Hz, 1 H), 6.80 (d, 3J11,12 = 8.4 Hz,
1 H), 6.84 (d, J2Ј,6Ј = 2.1 Hz, 1 H), 6.99 (dd, J6Ј,5Ј = 8.5, J6Ј,2Ј
4
3
4
=
3
4
2.0 Hz, 1 H), 7.50 (dd, J12,11 = 8.4, J12,8 = 2.0 Hz, 1 H), 7.61 (d,
4J8,12 = 2.0 Hz, 1 H), 7.85 (s, 1 H) ppm. 13C NMR (100 MHz,
CDCl3): δ = 14.1, 55.5, 55.8, 56.0, 56.0, 61.3, 110.0, 110.2, 110.8,
112.3, 124.9, 124.9, 125.8, 128.8, 129.6, 142.0, 148.7, 149.3, 150.9,
154.0, 165.4, 194.6 ppm. MS (EI, 70 eV): m/z (%) = 400 (83)
[M]·+, 354 (60) [M – C2H5O – H]·+, 326 (75) [M – C2H5O – H –
CO]·+, 299 (30) [M – C2H5O – CO – CO]+, 165 (100) [C9H9O3]+.
HRMS (EI): calcd. for C22H24O7 [M]·+ 400.1522; found 400.1521.
C22H24O7 (400.43): calcd. C 65.99, H 6.04; found C 65.27, H 6.08.
Ethyl
2,3,9,10-Tetramethoxy-5H-dibenzo[a,c][7]annulene-6-carb-
oxylate (3a): The oxidative coupling was carried out under an inert
gas with a solution of 9a (158 mg, 0.41 mmol) in anhydrous dichlo-
romethane (6 mL) at –20 °C.
A solution of PIFA (194 mg,
0.45 mmol) and BF3·OEt2 (0.21 mL, 0.82 mmol) in anhydrous
dichloromethane (6 mL) was prepared separately and added by sy-
ringe to the chilled substrate over a period of 20 min. After the
mixture had been stirred for 1.5 h, it was warmed to ambient tem-
perature, and stirring was continued for another 30 min. The reac-
tion was quenched by the addition of satd. NaHCO3 solution
(10 mL). The separated aqueous fraction was extracted with ethyl
acetate (3ϫ 10 mL). The combined organic fractions were washed
with brine (10 mL) and dried with anhydrous MgSO4. The crude
product was purified by flash column chromatography on silica
(cyclohexane/ethyl acetate, 3:1), which yielded 86 mg (55%) of the
desired product as a slightly yellow solid. Single crystals of 3a were
obtained by diffusion of n-heptane to a solution of 3a in dichloro-
methane at ambient conditions. RF (SiO2; cyclohexane/ethyl acet-
ate, 3:1) = 0.22. M.p. 146 °C (CH2Cl2/n-heptane). 1H NMR
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3
(300 MHz, CDCl3): δ = 1.34 (t, J13,12 = 7.1 Hz, 3 H), 2.74 (br. s,
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1 H), 3.81–3.86 (m, 1 H), 3.89 (s, 3 H), 3.91 (s, 3 H), 3.94 (s, 3 H),
3
3.99 (s, 3 H), 4.26 (q, J12,13 = 7.1 Hz, 2 H), 6.85 (s, 1 H), 6.91 (s,
1 H), 6.99 (s, 1 H), 7.15 (s, 1 H), 7.58 (s, 1 H) ppm. 13C NMR
(75 MHz, CDCl3): δ = 14.3, 31.4, 55.9, 55.9, 56.0, 56.2, 60.7, 110.4,
111.7, 112.3, 112.6, 127.3, 129.8, 131.0, 133.2, 134.2, 136.5, 147.5,
147.6, 148.9, 149.2, 166.1 ppm. MS (EI, 70 eV, 120 °C): m/z (%) =
384 (70) [M]·+, 355 (30) [M – C2H5]+, 339 (10) [M – C2H5O]+, 311
(100) [M – C2H5 – CO2]+, 267 (17) [C16H11O4]+, 225 (7), 181 (8),
152 (9). HRMS (EI): calcd. for C22H24O6 [M]·+ 384.1573; found
384.1574. C22H24O6 (384.43): calcd. C 68.10, H 5.99; found C
68.32, H 6.19.
CCDC-827036 (for 3a), -827037 (for 3f), and -827038 (for 10) con-
tain the supplementary crystallographic data for this paper. These
data can be obtained free of charge from The Cambridge Crystallo-
graphic Data Centre via www.ccdc.cam.ac.uk/data_request/cif.
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K. H. thanks the Degussa Stiftung and the Jürgen Manchot Stif-
tung for granting fellowships. S. R. W. appreciates the collaboration
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© 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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Received: June 23, 2011
Published Online: September 2, 2011
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