Installation of amine moieties into a polycyclic anodic product derived from 2,4-dimethylphenol

Article abstract of DOI:10.1002/chem.201102722

When 2,4-dimethylphenol is anodically treated, a dehydrotetramer with four contiguous stereocentres is readily obtained on a multi-gram scale. The substitution of a 2,4-dimethyl-phenoxy fragment by several amines was demonstrated, and the best results were obtained with primary amines. Optically pure α-chiral aliphatic amines yield diastereomeric mixtures that can be separated in most cases. The basic amine causes a partial hemiketal-opening of the bisbenzofuran moiety leading to an equilibrium within an α,β-unsaturated cyclohexenone. This dynamic behaviour occurs on the time scale of NMR spectroscopy and is also found by X-ray analysis providing a consistent picture.

Full text of DOI:10.1002/chem.201102722

FULL PAPER
DOI: 10.1002/chem.201102722
Installation of Amine Moieties into a Polycyclic Anodic Product Derived
from 2,4-Dimethylphenol
Joaquin Barjau,[a] Jan Fleischhauer,[a] Gregor Schnakenburg,[b] and
Siegfried R. Waldvogel*[a]
Abstract: When 2,4-dimethylphenol is
anodically treated, a dehydrotetramer
with four contiguous stereocentres is
readily obtained on a multi-gram scale.
Optically pure a-chiral aliphatic
amines yield diastereomeric mixtures
that can be separated in most cases.
The basic amine causes a partial hemi-
ketal-opening of the bisbenzofuran
moiety leading to an equilibrium
within an a,b-unsaturated cyclohexe-
none. This dynamic behaviour occurs
on the time scale of NMR spectroscopy
and is also found by X-ray analysis pro-
viding a consistent picture.
The substitution of
a 2,4-dimethyl-
Keywords: amination · chiral reso-
lution · diastereoselectivity · hemi-
ketal formation · polycycles
phenoxy fragment by several amines
was demonstrated, and the best results
were obtained with primary amines.
Introduction
Enantiomerically pure compounds are especially valuable in
modern organic synthesis. Resolution of racemic mixtures
and stereoselective reactions of chiral or prochiral starting
materials are the two major routes to obtain optical enrich-
ment.[1]
Scheme 1. Dehydrotetramer rac-2 obtained by anodic treatment of 1 and
Even though asymmetric approaches offer distinct advan-
tages, diastereomer-mediated resolution is still the method
of choice for large-scale enantiomer separations,[2c] mainly
due to the robustness of the processes and the availability of
various natural and synthetic agents.[1,2] Synthetic challenges
thereby often consist in the generation of multiple well-de-
fined stereogenic centers, for example, by using domino ap-
proaches[3] or multicomponent sequences.[4] The electron-
rich 2,4-dimethylphenol 1 was shown to be a potent starting
material in electro-organic synthesis[5] and can be converted
easily and efficiently to polycyclic dehydrotetramer rac-2
(Scheme 1).[6] This step appears to be a complexity-generat-
ing reaction and confirms electrochemically induced oxida-
tive couplings of phenols as a powerful methodology in di-
versity-oriented synthesis.[7] In subsequent studies, com-
pound 2 was identified as a promising platform for the syn-
thesis of structurally diverse polycycles, providing a diversi-
its reactivity.
ty-oriented compound library.[7] Starting from 1, eleven
different scaffolds can be obtained through highly chemo-,
regio- and stereoselective reaction sequences in only two
synthetic steps. We assume that the unique combination of
hydrogen-bonding interactions and 1,3-diaxial repulsions for
the attack from the lower side is responsible for the high
degree of diastereoselectivity in these substitution reactions
(Figure 1).[8]
Dehydrotetramer 2 represents the key intermediate that
provides
a
densely functionalized cyclohexene core
[a] J. Barjau, Dr. J. Fleischhauer, Prof. Dr. S. R. Waldvogel
Institute of Organic Chemistry
Johannes Gutenberg-University Mainz
Duesbergweg 10–14, 55128 Mainz (Germany)
Fax : (+49)6131-39-26777
E-mail: waldvogel@uni-mainz.de
[b] Dr. G. Schnakenburg
Institute of Inorganic Chemistry
Friedrich-Wilhelms-University Bonn
Gerhard-Domagk-Strasse 1, 53121 Bonn (Germany)
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/chem.201102722.
Figure 1. Key interactions for the stereoselective substitution of the phen-
oxy moiety in dehydrotetramer 2.
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Results and Discussion
Upon oxidative treatment, phenols can undergo the forma-
tion of polycycles instead of the anticipated ortho–ortho
coupling reaction. The most common structural motif is the
so called Pummererꢁs ketone, which is obtained as a result
of an ortho–para coupling and a subsequent 1,4-addition.[11]
In particular, 2,4-dimethylphenol is prone to the formation
of this architecture. When anodic protocols are applied, the
generation of larger dehydro-oligomers is observed.[6a] De-
rivative 2 seems to be the key intermediate for most of the
pentacyclic architectures found. When using an undivided
cell equipped with platinum electrodes and Ba(OH)2·8H2O
in methanol as electrolyte, 2 can be readily obtained by elec-
trolysis under constant current control. Compound 2 precipi-
tates during the electrolysis and can be isolated in almost
pure fashion by simple filtration (Scheme 1).[6b] This simple
protocol yields up to 24 g of 2 per run (52% yield), provid-
ing significant amounts for subsequent reactivity studies.
The complex central ring of 2 is formed in exclusive stereo-
selectivity. The proposed mechanism suggests the Pummer-
erꢂs ketone derivative as an intermediate in the formation of
2.[6] Since the derivative of Pummererꢂs ketone is obtained
as a mixture of enantiomers, dehydrotetramer 2 is provided
as a racemate. Diastereomer-mediated resolution with enan-
tiomerically enriched auxiliaries seemed to be the best way
to separate the generated diastereomers. In initial studies,
the hydroxyl group of the hemiketal was successfully modi-
fied by silylation or opened up by O-acylation of the phe-
nolic portion.[7] Several resolving agents including (ꢀ)-cam-
phanic acid chloride were found to be unsuitable for resolv-
ing racemic 2.
Therefore, the displacement of the 2,4-dimethylphenoxy
moiety by a removable auxiliary should be a viable route.
We decided to expand the amination reaction of 2 and to in-
troduce aliphatic amines with stereogenic information. To
the best of our knowledge, no similar transformation has
been previously reported. To explore the scope of this reac-
tion, compound 2 was initially treated with pyrrolidine and
CsF as fluoride source in acetonitrile heated to reflux,
whereby the expected tertiary amine 3a was obtained in
63% yield (Scheme 3). X-ray diffraction experiments of
suitable single crystals confirmed the anticipated structure.
Remarkably, in the solid state 3a is obtained in the ring-
opened cyclohexenone form. One reason for this observa-
tion is the formation of hydrogen bonding between the basic
pyrrolidine nitrogen (protonated moiety: pKa 10.46[12a]) and
the neighbouring hydroxyl hydrogen of the weak acid
Scheme 2. Formation of carbocation 2a and its reaction pathways, leading
to nucleophilic substitution (3) and semipinacol-type rearrangement
product 4.
equipped with four contiguous stereocentres. Treatment
with Lewis or Brønsted acids cleaves the 2,4-dimethylphe-
noxy moiety, generating the tertiary carbocation 2a. This in-
termediate opens up the possibility to introduce molecular
variation into the scaffold by simply switching the reaction
conditions (Scheme 2). In general, the central scaffold can
be conserved at low temperatures and the generated carbo-
cation 2a can be used for the selective conversion with nu-
cleophiles.[7,8] Raising the temperature changes the reactivi-
ty, and skeletal rearrangement (as typically expected for car-
bocations) becomes dominant. This pathway yields complex
architectures such as spirocycle 4 in a highly selective
manner.[7]
The molecular structure of 2 seems to be a promising plat-
form for the synthesis of natural product analogues.[7]
Hence, its modification might open an easy access to novel
pharmacologically active structures. For instance, spiropen-
tacycle 4 contains a central cyclopenta[b]benzofuran moiety,
which has been regarded as the biologically active compo-
nent in natural products of the rocaglamide family.[9] In pre-
vious studies, the stereospecific substitution of one phenoxy
fragment by an amino group was achieved. This amination
reaction was found upon treatment of 2 with NH4F in aceto-
nitrile at 808C.[7] An intramolecular hydrogen-bonding be-
tween the hydroxy group of the hemiketal (donor) and the
phenol ether moiety (acceptor) of 2 might decrease the
LUMO energy level of the latter,[10a] activating it towards
nucleophilic substitution (Figure 1). Their arrangement at
the same side of the central cyclohexene ring forms an ideal
docking site for incoming nucleophiles. On the other hand,
one methyl group at the cyclohexene points to the other
side of the molecule and leads to 1,3-diaxial repulsions.
Both effects are responsible for the high diastereoselectivity
in nucleophilic substitution reactions (Figure 1).[7,8] When no
good nucleophiles enter the reaction scene, several rear-
rangements of the backbone have been observed resulting
in complex molecular architectures.[7] Herein, we present
the nucleophilic substitution of the 2,4-dimethylphenoxy
moiety using optically pure a-chiral aliphatic or benzylic
amines and subsequent resolution of the diastereomeric spe-
cies.
Scheme 3. Formation of amino derivative 3a and its rearrangement to
spiropentacycle 4.
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Installation of Amine Moieties into a Polycyclic Anodic Product
FULL PAPER
phenol (pKa 10.59[12b]). Therefore, 3a exhibits intramolecular
hydrogen bonding from the phenol donor to the pyrrolidine
acceptor with a bond distance dACTHNUGRTNEUNG(O···N)=2.685(2) ꢃ. Terti-
ary amine 3a turned out to be unstable under prolonged
preparative and harsh analytical conditions. Thermal impact
upon gas chromatography or column chromatography on
silica cleaves off the pyrrolidine ring. The generated carbo-
cation undergoes a semipinacol rearrangement to finally
yield spirolactone 4. This pathway provides an access to the
initially targeted structure 4.
Scheme 4. Reaction of 2 with optically pure amines under formation of
substitution products, equilibrating between cyclohexenone (6–13) and
hemiketal form (6’–13’).
Initial experiments using l-proline ethyl ester or amino al-
cohol (ꢀ)-ephedrine did not lead to the desired products, in-
stead, compound 5 was predominantly obtained. Pentacycle
5 was first isolated as a minor component during the electro-
chemical oxidation of 1[6a] and can also be obtained in high
yields after treating 2 with NaCN.[7] Since a-substituted sec-
ondary amines exhibit an enhanced steric demand, they are
non-suitable substrates for this substitution reaction on the
densely functionalized polycycle 2. Therefore, we focused
our investigations on optically pure primary amines, furnish-
ing optically pure polycycles 6–13 (Scheme 4). Substoichio-
metric amounts of CsF (30 mol%) and lower temperatures
(558C) were found to be milder reaction conditions. Further
studies using other alkali fluorides also led to a nucleophilic
replacement of the phenolether moiety by the amine, but
neither the yield nor the reaction rate could be increased.
We initially anticipated an activation of the nucleophile
through hydrogen bonding by fluoride, as previously report-
ed in fluoride-catalysed N-alkylation reactions.[12] When
using Cs2CO3, the amination reaction occurred as well, re-
vealing that the fluoride acts mostly as a base.
From mechanistic rationale these results indicated that
derivatives 3 and 5 originate from a common intermediate
derived from 2, which might be explained by the following
assumption (Scheme 5): Under basic conditions, the hemike-
tal moiety 2 will be deprotonated and opened up to give the
stabilized a,b-unsaturated system 2c. Extrusion of the 2,4-
dimethylphenolate yields the ortho-quinone methide 2d.
ortho-Quinone methides have been suggested as synthetic
Scheme 5. Mechanistic rationale for the amination reaction to yield nucleophilic substitution products as exemplified on derivative 3, and an alternative
pathway for the formation of 5.
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S. R. Waldvogel et al.
intermediates in multiple mechanistic pathways.[14] In nature,
this facile activation of the benzylic position by tautomeriza-
tion takes place without enzymatic intervention. Compound
2d represents a key intermediate in our mechanistic ration-
ale and determines the reaction pathway. Additionally, com-
pound 2d is a highly conjugated p-system containing two di-
poles that compensate each other and a lower steric demand
compared with the starting material. If nucleophilic amines
(Table 1) are present, a 1,4-addition followed by protonation
mixture of diastereoisomers that were assigned by means of
NMR spectroscopy, MS, HRMS, EA, RP-HPLC as well as
X-ray analysis of suitable single crystals (Figures 2 and 3
and the Supporting Information). The results of these stud-
Table 1. Scope of the substitution reaction with optically pure amines.
Entry
Amine
Diastereo-
isomers
Yield
[%][a]
Ratio of ketone
to hemiketal
6a
6b
38
41
0:1[b]
1:1[b]
1
2
[c]
7a
7b
37
44
–
[c]
–
8a
8b
42
42
1:0.38[d]
1:0.47[d]
3
4
9a
9b
39
42
1:0.36[b]
1:0.63[b]
10a
10b
40
42
0.22:1[d]
0:1[d]
5
6
11a
11b
30
37
1:0.31[d]
1:0.5[d]
7
8
12a/b
13a/b
75
77
1:0.4[e]
1:0.13[d]
Figure 2. Molecular structures of diastereoisomers 6a’ (top) and of 6b’
(bottom) obtained by X-ray analysis (different crystals).
[a] Refers to isolated product yields. [b] Ratio determined at ꢀ208C.
[c] Ratio could not be determined due to strong signal broadening.
[d] Ratio determined at 208C. [e] Ratio determined at 258C.
ies are listed in Table 1. The isolated overall yields of iso-
meric pairs of 6–13 are fairly good and range from 67 to
84%. We were able to explore the scope of this approach
and successfully separate the diastereoisomers 6–11 (in
yields ranging from 30–44%). In case of 12 and 13 it is pos-
sible to introduce optically pure amine moieties, but resolu-
tion of the generated diastereomers was found to be impos-
sible. Moreover, we were able to separate both diastereoiso-
mers by analytical reversed-phase high-performance liquid
chromatography (RP-HPLC), but failed to separate them
when applying column chromatography.
provides amino derivatives 3 and 6–13 with exclusive stereo-
selectivity. In the absence of suitable nucleophiles, the loss
of the proton in the vinylogous position induces a domino-
type ring-opening/ring-closure sequence (2d!2e) to finally
furnish pentacycle 5.
To elucidate the scope of this transformation and explore
the possibilities for the separation of the diastereomeric
products, we introduced different primary aliphatic as well
as benzylic amines as nucleophiles.
By using a twofold excess of the amine component and
applying the mild reaction conditions, we were able to re-
place the phenoxy moiety. Filtration over silica as stationary
phase and cyclohexane/ethyl acetate (9:1) as eluent allowed
us to remove polar side products such as 2,4-dimethylphenol
(1) and the excess of amine. Subsequent column chromatog-
raphy on silica with a less polar eluent system (e.g., cyclo-
hexane/ethyl acetate 20:1) led to the desired compounds as
The structure of two representative pairs of diastereoiso-
mers 6a–b and 9a–b were confirmed in chloroform at
ꢀ208C by assigning their NMR chemical shifts by using rou-
tine techniques (1H, 13C, HMBC, HSQC, NOESY). In addi-
tion, the relative configuration of the diastereomeric pair of
6 was proven by single-crystal analysis of suitable crystals
(Figure 2). In contrast to the trends found by NMR experi-
ments (see the Supporting Information) and to the X-ray
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Installation of Amine Moieties into a Polycyclic Anodic Product
FULL PAPER
structure of 3a, which exists in the cyclohexenone form, in
the solid state these molecules exist in form of their hemike-
tals 6a’/b’. Thereby, hydrogen bonding of the amine proton
to the adjacent dihydrobenzofurane moiety (6a’, d
2.737(2) ꢃ) as well as from the hemiketal hydroxyl group to
the amine nitrogen (6a’, d(O···N)=2.611(2) ꢃ) was ob-
served (Figure 2).
ACHTUNGTRENN(UNG N···O)=
AHCTUNGTRENNUNG
As proven by NMR measurements, the amino derivatives
coexist in an equilibrium between their carbonyl (6–13) and
hemiketal form (6’–13’, Scheme 4 and the Supporting Infor-
mation). Both, the cyclohexenone and the hemiketal form
of each diastereoisomer can be clearly distinguished due to
their characteristic shifts. The benzylic proton of the amine
moiety for instance, shows a characteristic quartet signal in
the 1H NMR spectrum between d=3.5 and 4.5 ppm. In
13C NMR spectra, the a,b-unsaturated cyclohexenone ring
of 3 exhibits a weak broadened signal for the carbonyl
group at approximately d=205 ppm, whereas the carbon of
the hemiketal causes a sharp signal at higher field (ca. d=
1
106 ppm). Due to the different H NMR signals it is possible
to estimate the relative ratio of both equilibrating forms. In
addition, the carbonyl derivatives exhibit significantly higher
molecular flexibility. This in turn will impede the formation
of regularly ordered molecules and might explain the pre-
ferred crystallisation of hemiketal derivatives 6’–13’ from
this equilibrium. Structure elucidations by using NMR tech-
niques clearly reveal that the hemiketal forms are the less
dominant ones in solution (except entries 1 and 5 of
Table 1), even if they are preferred in the solid state.
The combination of steric repulsions of the substituents at
the amine portion and reduced degrees of freedom of the
phenoxy substituent are probably the two major reasons for
the strong broadening of the NMR signals observed. Since
electron-rich 2,4-dimethylphenol is less acidic than phenol
(pKa 10.59[12b]) its acidity is comparable to that of hemiketal
hydroxyl groups (pKa of similar compounds ranges from 9.6
for malvedin-3-glucoside[12c] to 10.4 for a-((b-hydroxy-
Figure 3. Molecular structures of hemiketal 12a’ (top) and its diastereo-
meric keto derivative 12b (bottom) obtained by X-ray analysis. Both
compounds were found in same unit cell, but separated here for clarity.
five-membered cycle exhibiting a hydrogen bond, which
points from the nitrogen to the adjacent benzofuran moiety
(12b, dACTHNURTGNEU(GN N···O)=2.676(5) ꢃ). No p-interactions and a signifi-
cantly decreased ring strain (angle 105.958) were identified
in derivative 12b. The hydrogen bonds of hemiketal in 12a’
are shortened in comparison to those of keto form 12b and
are energetically preferred. This might be another directing
force for the preferred crystallisation of the hemiketal
forms. There are a number of competing electronic and
steric effects that are almost balanced and allow a shift of
equilibrium by a subtle impact. Consequently, the NMR
spectra are remarkable complex. In particular, the NMR
spectra of the diastereomeric pair 7a/b were strongly broad-
ened. In this case an additional repulsion by an ortho-me-
thoxy group on the benzylic amine moiety with the sur-
rounding substituents might be responsible for this behav-
iour. These observations are in agreement with previous
studies in which the ring-opening/ring-closure dynamics of
related dibenzofuran systems[15] and acyclic substrates[12d]
have been studied.
ACHTUNGTRENNUNG
ethyl)amino)deoxybenzoines[12d]). In addition, a hindered ro-
tation of the phenoxy moiety seems likely due to different
competing hydrogen bonding possibilities.
Crystallisation of the diastereomeric keto and hemiketal
form of 12a’/b occurred in one unit cell, which gives a direct
comparison of both competing forms (Figure 3). In the hem-
iketal form 12a’, two five-membered ring systems estab-
lished by hydrogen bonding between hydroxyl oxygen of
hemiketal and the amino group (12a’,
2.636(5) ꢃ) as well as the amino substituent and the benzo-
furan moiety (12a’, d(N···O)=2.654(4) ꢃ) were observed. In
dACTHNGUTERN(UNG O···N)=
AHCTUNGTRENNUNG
addition, a weak p-interaction between the benzofuran
moiety and the benzylic amine substituent (d=3.886 ꢃ) was
detected. On the other hand, a significantly higher aberra-
tion of the ideal tetrahedral angle (100.498), leading to an
increased ring strain of hemiketal dihydrobenzofuran
moiety was found. In contrast, the keto form 12b exhibits a
six-membered ring with hydrogen bonding between the hy-
droxyl group of the 2,4-dimethylphenol moiety and the
We investigated these dynamic effects and measured
1H NMR spectra of 6a–b and 9a–b at temperatures ranging
1
from ꢀ20 to 508C. Figure 4 depicts the H NMR spectra of
derivative 6a’, in which the temperature was increased in
10 K increments from ꢀ20 to 208C. This is one of the few
amine nitrogen (12b, dACTHNUTRGNEU(GN O···N)=2.982(8) ꢃ) as well as a
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14789

S. R. Waldvogel et al.
the
amine
component
(0.4 equiv) at 408C and the re-
action progress was monitored
by RP-HPLC. Unfortunately,
the low enantiomeric ratios of
approximately 3:1, even at low
conversion rates, caused us to
stop further studies to achieve
optical enrichment by using
this approach. Surprisingly, all
attempts to rearrange the mo-
lecular scaffold of amino deriv-
atives 6–13 failed. Despite the
instability of 3 towards acidic
media (Scheme 3), the treat-
ment of 6–13 with H2SO4 or
trifluoromethanesulfonic acid
(TfOH) did not induce the for-
mation of spiropentacycle 4.
Figure 4. Variable-temperature 1H NMR spectra (CDCl3, ꢀ20 to 208C) of 6a’ and the assignment of the most
important signals. As can be seen by its inspection, even at ambient temperatures a strong signal broadening is
clearly observed.
Conclusion
The dehydrotetramer (2) of
2,4-dimethylphenol has been
examples in which the hemiketal form was observed exclu-
sively. At higher temperatures, broadening of the signals
was observed. Conformational changes in the central cyclo-
hexene ring are translated in broadening of signals of hydro-
gen atoms at positions 7 and 12a. The portion of the amine
moiety closer to the pentacyclic scaffold experiences re-
stricted rotation, probably due to steric hindrance. Thus, sig-
nals assigned to protons at positions 1’, 2’, and 1 are close
and appear broadened. In contrast, free rotation of the tert-
butyl substituent causes a sharp signal.
In those cases where both species, hemiketal and ketone,
are in equilibrium, the NOESY spectra showed exchange
peaks for the corresponding protons of each species (posi-
tive and negative signals). Further correlation, observed in
HSQC and HMBC experiments, helped to differ among
conformer signals. As expected, lowering the temperature
led to sharpened signals, even if line broadening is still ob-
servable. As indicated by integrating the 1H NMR signals,
the concentration of hemiketal form increases successively
by lowering the temperature which confirms that they are
energetically preferred in the solid state.
shown to be a powerful starting material for the synthesis of
optically pure polycyclic scaffolds. The amination reaction
using suitable enantiomerically pure alkyl and benzylic
amines takes place in the course of a nucleophilic substitu-
tion of 2,4-dimethylphenoxy leading to diastereomeric prod-
ucts. The diastereomeric pairs can be separated in most
cases displaying a dynamic equilibrium between the hemike-
tal and the a,b-unsaturated cyclohexenone form, in which
the latter dominates in solution. These dynamic effects were
observed by NMR spectroscopy and in solid state providing
a consistent picture. The amination products are stable to-
wards acidic treatment and show a remarkably dynamic be-
haviour. The equilibrium can be easily shifted. The conver-
sion is accompanied by a significant structural change.
Therefore, these unique scaffolds might adapt and bind to a
given environment. The biological profile of these com-
pounds will be reported in due course.
Kinetic racemate resolution of rac-2[16] as a methodology
to obtain the enantiomerically enriched dehydrotetramer 2
was also studied. This strategy would pave the way to opti-
cally pure polycycles in our diversity-oriented synthesis
strategy.[7] Since we expected hydrogen bonding to the ap-
proaching amine in the course of the substitution process, a
preferential conversion of one enantiomer of 2 might take
place. In the field of catalysis, this type of interaction has
been successfully used in bis-functionalised substrates pos-
sessing hydrogen bonding donor and acceptors.[10] Thus,
compound 2 was treated with catalytic amounts of CsF and
Experimental Section
Representative procedure for the synthesis of 6–12: A suspension of 2
(482 mg, 1 mmol), CsF (45.6 mg, 0.3 mmol) and the corresponding amine
(2.0 mmol) in CH3CN (10 mL) was stirred for 3 h at 558C. After comple-
tion of the reaction, the solvent was evaporated under reduced pressure
and the residue was adsorbed on silica. Both diastereomers were isolated
by subsequent filtration trough a silica gel plug using a mixture of cyclo-
hexane:ethyl acetate (9:1). Resolution of diastereomers was afforded by
column chromatography on silica using n-hexane/ethyl acetate (20:1) as
eluent.
Further details of the synthetic procedures, structural and analytical data
can be found in the Supporting Information.
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Installation of Amine Moieties into a Polycyclic Anodic Product
FULL PAPER
[7] J. Barjau, G. Schnakenburg, S. R. Waldvogel, Angew. Chem. Int. Ed.
2011, 50, 1415–1419; Angew. Chem. 2011, 123, 1451–1455.
[8] J. Barjau, G. Schnakenburg, S. R. Waldvogel, Synthesis 2011, 2054–
2061.
Acknowledgements
Donation of optically pure amines by Prof. Dr. K. Ditrich, BASF SE, is
highly appreciated. J.B. thanks the DAAD-La Caixa program for a fel-
lowship. Support by the SFB 813 Chemistry at Spin Centers is highly ap-
preciated. The collaboration with the Kompetenzzentrum der Integriert-
en Naturstoff-Forschung (University of Mainz) was helpful. The authors
thank Dr. J. Liermann for the NMR measurements and Dr. D. Scholl-
meyer for the X-ray diffraction experiments of 6b.
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Received: August 31, 2011
Published online: November 24, 2011
Chem. Eur. J. 2011, 17, 14785 – 14791
ꢀ 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
14791