Synthesis of rigid receptors based on triphenylene ketals

Article abstract of DOI:10.1002/ejoc.200500108

The synthesis of rigid receptors based on triphenylene ketals, including some improved procedures, is described in detail. Since chemical transformations are strongly influenced by the rigid character and steric bulkiness of the receptors, the constructio

Full text of DOI:10.1002/ejoc.200500108

FULL PAPER
Synthesis of Rigid Receptors Based on Triphenylene Ketals
Matthias C. Schopohl,[a] Andreas Faust,[a] Daniela Mirk,[a] Roland Fröhlich,[a]
Olga Kataeva,[b] and Siegfried R. Waldvogel*[a,c]
Keywords: Receptors / Supramolecular chemistry / Synthetic methods / Oxidative coupling reaction / Triphenylene ketals
The synthesis of rigid receptors based on triphenylene ketals,
including some improved procedures, is described in detail.
Since chemical transformations are strongly influenced by
the rigid character and steric bulkiness of the receptors, the
construction of a subunit allowing quicker synthetic develop-
ment is also reported. The preparation of these receptor
structures involves an oxidative trimerization and a subse-
quent repeated isomerization procedure. The scope for the
attachment of sterically demanding affinity groups on the re-
ceptor scaffold and the corresponding subunit is discussed,
and the molecular structures and available space for molecu-
lar recognition of the chirally modified systems are outlined
by some crystal structures.
(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim,
Germany, 2005)
Introduction
Results and Discussion
Initial investigations into the properties of functionalized
triphenylene ketals revealed that the synthesis was easily
performed with conformationally flexible moieties on the
scaffold,[16] but that almost no preorganization was found
because of the conformational freedom of these functional
groups. Consequently, the separation of the two isomeric
triphenylenes turned out to be challenging. Only the pres-
ence of bulky and lipophilic groups on the nonfunction-
alized side of the triphenylene ketals gave access to reason-
able amounts of isomerically pure scaffolds. The introduc-
tion of a bicyclic backbone into the ketal moiety of the
platform should overcome several drawbacks: on the one
hand the functional group would be centered and confor-
mationally locked, which should provide excellent preor-
ganization, be beneficial for molecular recognition, and
suppresses self-aggregation. On the other hand, a defined
location of the polar groups would endow the individual
isomeric triphenylenes with distinct polarities, which should
facilitate efforts at separation. Additionally, a more highly
substituted catechol ketal would promise increased hydro-
lytic stability and would therefore enhance the stabilities of
the receptor structures.
Several common bicyclic ketone structures were evalu-
ated. The crucial step is the ketalization with catechol. Ste-
rically demanding adamantane-derived systems, such as the
Stetter ketone,[20] which would also give rise to functionali-
zation on both sides of the aromatic plane, resisted all
attempts at ketalization. 9-Substituted fluorenones formed
catechol ketals, but these intermediates turned out to be too
labile for further synthetic transformations. Bicyclo[3.3.1]-
nonan-9-one moieties proved to exhibit the subtle balance
between synthetic feasibility and robustness of the resulting
spiroketals.
Groups of appropriate affinity in well defined orienta-
tions are key for high selectivity and association constants
in artificial receptors.[1,2] Concave receptor structures with
rigidly oriented or conformationally locked functional
groups are therefore among the most potent systems for
molecular recognition.[3–14]
Since many target molecules for sensors exhibit C3 or
pseudo-C3 symmetry, complementary scaffolds with three-
fold symmetry are popular.[15] An unusual large and rigid
backbone providing concave and convergent preorganized
functional groups for supramolecular interaction was estab-
lished by us recently.[16] Based on these functionalized tri-
phenylene ketals, the first artificial caffeine receptors were
developed,[17] and chirally modified receptors proved cap-
able of the first enantiofacial discrimination of single het-
erocyclic guest molecules.[18] The binding modes for such
highly dynamic supramolecular aggregates were studied by
different spectroscopic means, providing a highly consistent
picture in solution and in the solid state.[19]
The synthesis of the scaffold and some receptors have
been reported in fragments as preliminary findings. We
therefore present detailed procedures for the synthesis of
these structures here.[16–19]
[a] Westfälische Wilhelms-Universität Münster, Organisch-
Chemisches Institut,
Corrensstr. 40, 48149 Münster, Germany
[b] A. E. Arbuzov Institute of Organic and Physical Chemistry,
Arbuzov-Str. 8, Kazan 420088, Russia
[c] Present address: Kekulé-Institut für Organische Chemie und
Biochemie, Rheinische Friedrich Wilhelms-Universität Bonn,
Gerhard-Domagk-Str. 1, 53121 Bonn, Germany
Fax: +49-228-73 9608
E-mail: waldvogel@uni-bonn.de
Supporting information for this article is available on the
WWW under http://www.eurjoc.org or from the author.
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DOI: 10.1002/ejoc.200500108
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Scheme 1. Synthesis of bicyclic spiroketal 7. a) acrolein, NEt3, DMF, room temp., 16 h, 92%. b) H2SO4, –10 °C Ǟ room temp., 22 h,
77%. c) catechol, pTsOH, toluene, Dean–Stark trap, 22 h, 84%. d) Pd/C, H2 (1 atm), THF, 40 h, 100%.
Table 1. Reaction conditions for addition of 1 to acrolein.
Entry
Reagents
Temperature
Reaction time
Yield
Purity (GC)
1
2
3
Na, EtOH
Al2O3
NEt3, DMF
–78 °C Ǟ room temp.
room temp.
2 h
5 min
16 h
71%
30% (GC)
92%
90%
n.d.[a]
96%
room temp.
[a] Sluggish crude mixture.
The construction of the bicyclic backbone started excess of catechol was employed. The isomeric catechol ket-
with a Michael-type addition of commercially available als 5 and 6 were obtained upon workup as crystalline solids.
ethyl 2-oxocyclohexane-1-carboxylate (1) to acrolein The mother liquor contained the remaining olefinic mixture
(Scheme 1).[21,22] Application of the conditions described by 3/4, which was collected and then exploited for further keta-
Cope and Synerholm,[23] with sodium ethoxide as base, lization processes.
turned out to be difficult due to the sensitivity of aldehyde
The double bond in the bicyclic moiety is fairly inaccess-
2. The workup required a time-consuming purification by ible. Homogeneous reduction under diverse sets of condi-
a short-path distillation, only applicable for small quantities tions was unsuccessful, but heterogeneous catalysts enabled
(Table 1, Entry 1), so alternative procedures for the synthe- a very slow but constantly proceeding hydrogenation reac-
sis of 2 were considered (Table 1). Adsorption of β-keto es- tion. Treatment under high-pressure conditions (up to
ter 1 on aluminium oxide and subsequent treatment with 200 atm H2) did not enhance the reaction rate. The hydro-
acrolein gave only a 30% yield of the desired compound genation process might occur only on the edges and corners
(Entry 2).[24,25] The conjugate addition method of Fujii of the colloidal palladium crystals, higher catalyst loading
et al., with triethylamine as catalyst in DMF, provided alde- and prolonged reaction times therefore being required.
hyde 2 in excellent amounts as well as in splendid quality Thanks to the clean and smooth reduction, the desired
(Entry 3),[26] with the crude 2 exhibiting sufficient purity for compound was directly obtained by crystallization.
the next step and the time-consuming short-path distillation
The key step for the construction of the receptor plat-
therefore no longer being required.
form is oxidative trimerization, yielding a statistical mixture
Aldehyde 2 was then subjected to an aldol condensation of the all-syn (8) and the anti,anti,syn (9) isomers, in which
reaction in concentrated sulfuric acid, resulting in an ole- the undesired less symmetric derivative 9 is the more abun-
finic mixture. The original procedure published by Cope dant (Scheme 2). Initially, this transformation was per-
and Synerholm had delivered only traces of the bicyclic formed by employing MoCl5.[17] Detailed investigations
products,[23] but previous reports mentioned this synthetic into the stoichiometry of the trimerization indicated that
problem and recommended the use of prolonged reaction the molybdenum species reacts as a single-electron oxidant
times.[27] Best yields were obtained if the aldehyde was and that six equivalents of MoCl5 are therefore necessary
added dropwise to concentrated sulfuric acid that had al- for the construction of one triphenylene moiety.[29] A syn-
ready been chilled to –10 °C.[28] Vigorous mixing by a me- thesis on large scales would consequently give significant
chanical stirring device seemed to be essential, since the amounts of molybdenum waste, but this might be avoidable
high viscosities of both reactants impedes the mixing. The by use of an anodic procedure.[30] Electrochemical trimeri-
reaction mixture was slowly brought to ambient tempera- zation could be performed easily even on a 20 g scale and
ture and stirred for a total of 20–22 h in order to provide provided the two isomeric triphenylene ketals in an almost
the best yield. Construction of the catechol moiety was only statistical ratio. The unusually high yields for this transfor-
achieved under acidic conditions with thermal activation. mation are a consequence of the low solubilities of the
Completion of the ketalization reaction was not observed formed triphenylene ketals. Precipitation during the elec-
even when prolonged reaction times were applied or a large trolysis avoids the overoxidation typical of hexamethoxy-
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Synthesis of Rigid Receptors Based on Triphenylene Ketals
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Scheme 2. Access to all-syn triester 8: a) Pt electrodes, 20 °C, 0.1 m NBu4BF4 in H3CCN, 0.45 A·cm–2, 3.1 F, up to 90%. b) Crystallization
from toluene/ethanol (4:1). c) 1. ClCH2CH2Cl, reflux, 2. F3CSO3H, reflux, 15 min., 3. NEt3, then 0 °C.
substituted triphenylenes.[31–33] Unfortunately, this limits to shift the equilibrium towards the desired isomer. Unfor-
the application of the electrochemical procedure to rigid tunately, additives that should form π–π complexes with the
substrates such as 7.[34] Interestingly, the precipitation oc- triphenylene core, such as 1,3,5-trinitrotoluene (TNT) or
curs mainly from solution rather than on the surfaces of the (cyclopentadienyl)iron fragments, did not succeed at all.
platinum electrodes. This trimerization step was performed Furthermore, a template-directed oxidative trimerization
galvanostatically under an inert atmosphere in order to pre- also failed, since no appropriate triple linker to promote the
vent molecular oxygen from being incorporated as peroxide intramolecular oxidative coupling reaction was found.[36]
bridges and reducing product quality.[35] Addition of aque-
ous methanol to the electrolyte allowed an easy workup, bone, saponification of all-syn triester 8 demands hydroxide
since the crude triphenylenes could simply be filtered off. ions without solvent spheres in order to attack poorly ac-
Because of the high steric hindrance of the bicyclic back-
The all-syn (8) and the anti,anti,syn (9) isomers were sep- cessible moieties (Scheme 3). These so-called naked hydrox-
arated by simple crystallization from a toluene/ethanol mix- ide ions are generated in THF from potassium tert-butoxide
ture. The undesired triphenylene ketal 9 can be equilibrated with a stoichiometric amount of water, as described by
to the statistical mixture of 8 and 9 under strongly acidic Gassmann and Schenck.[37] Alternatively, potassium hy-
reaction conditions (Scheme 2). The less symmetric triphen- droxide dissolved in DMSO can be employed, but this is a
ylene ketal 9 exhibits particularly poor solubility behavior, strong oxidant and its application for electron-rich aromatic
its highest solubility being found in hot chlorinated sol- systems is limited.[38] Tricarboxylic acid 10 could be han-
vents, and so only 1,2-dichloroethane was suitable. The loss dled during workup and in solution at ambient temperature
of material was negligible if the isomerization was per- or below without decomposition. The water-containing
formed under strictly anhydrous conditions at elevated tem- crude triacid 10 was carefully dried at 50 °C in high vac-
peratures. Since anhydrous trifluoromethanesulfonic acid is uum. The subsequent Curtius rearrangement was per-
difficult to handle, use of mixtures of the acid and its anhy- formed under mild conditions by employing the nonexplos-
dride is highly recommended. Formation of the cationic tri- ive azide-transfer reagent diphenylphosphoryl azide
phenylene intermediate was indicated by strong coloration (DPPA), introduced to organic synthesis by Shioiri[39] and
of the reaction mixture. The isomerization was quenched at obtainable on multigram scales.[40] DPPA activates the free
elevated temperature by addition of base, and the repetitive carboxylic acid in the presence of base. The initially formed
sequence of isomerization of 9 to the statistical mixture, fol- acyl azide rearranges with the loss of nitrogen upon subse-
lowed by the separation of these isomers, gave access to quent heating to afford the isocyanate, which was trapped
large amounts of 8.
in situ with benzyl alcohol. The prolonged reaction times
In the course of these investigations we also attempted reflect the high steric hindrance due to the bicyclic back-
to favor the all-syn isomer during the isomerization in order bone. The Cbz-protected amine 12 can be purified by col-
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umn chromatography and represents a stable storage form
for the receptor platform. Deprotection was performed with
Pearlman’s catalyst under standard conditions and yielded
the all-syn trisamine 14 as a grey, vitreous solid that should
be stored under inert atmosphere with exclusion of light.
The amino moieties exhibit low nucleophilicity, and trans-
formations with highly reactive compounds such as isocya-
nates require prolonged transformation times, as described
later on.
Scheme 4. Synthesis of subunits: a) 1. KOtBu, THF, H2O, 0 °C,
then reflux, 16 h, 2. 0 °C, conc. HCl, 88%. b) 1. Toluene or ben-
zene, DMF, DPPA, NEt3, 0 °C, 30 min., then reflux, 3 h, 2. BnOH,
reflux, 24–36 h, 92%. c) Pd(OH)2/C, H2, THF, room temp., 48 h,
quantitative.
Some of the employed α-chiral isocyanates in Figure 1
are either commercially available or are known from the
literature, whilst full sets of analytical details are given here
for compounds 21–23.[41–48] Standard procedures starting
from the corresponding optically pure amine included the
formation of the individual ammonium chloride and subse-
quent phosgenation. Distillative workup provided the de-
sired isocyanates.
Scheme 3. Synthesis of the modified all-syn derivatives (anti,anti,
syn compounds): a) 1. KOtBu, THF, H2O, 0 °C, then reflux, 16 h,
2. 0 °C, conc. HCl, 10: 87% (11: 92%). b) 1. Benzene, DMF, DPPA,
NEt3, 0 °C, 30 min., then reflux, 4 h, 2. BnOH, reflux, 36 h, 12:
81% (13: 85%), c) Pd(OH)2/C, H2, THF, room temp., 48 h, 14: 99%
(15: 99%).
These transformations can also be applied to the less
symmetric anti,anti,syn derivatives 9, 11, 13, and 15, analo-
gously with the reported reactions for the all-syn isomer.
Good separation of the isomeric triphenylene compounds
at the stage of the triesters 8/9 is important and advan-
tageous, because the Cbz-protected derivatives 12/13 and
subsequent isomeric compounds turned out to be chro-
matographically inseparable.
The corresponding subunit 18 was also prepared in order
to develop the reaction conditions for the functional group
transformations (Scheme 4). As expected, the yields for the
individual steps were higher than those for the trimerized
Figure 1. Synthesized optically pure isocyanates.
For further enhancement of the steric repulsion a trityl
analogues, and furthermore, purification of these com- substituent was considered instead of a tert-butyl moiety
pounds was also facilitated. Since less synthetic effort is and the corresponding α-chiral isocyanate was devel-
necessary for 18, this particular subunit was exploited to oped.[49] The addition of trityl bromide to diethyl ketene
elucidate optimal reaction conditions for the attachment of acetals is known.[50,51] In order to circumvent use of the
the corresponding hydrogen bonding donor onto the con- mercury catalyst, trityl tetrafluoroborate[52] was used and
cave platform.
the desired trityl ester 29 was obtained in 35% yield. Appli-
Urea groups on the triphenylene scaffold create good af- cation of this transformation to the silylated ester enolate
finity systems for hydrogen bonding to heterocyclic sub- 28,[53] however, doubled the yield of 29 (Scheme 5). Subse-
strates such as caffeine. The first artificial receptor for this quent saponification and resolution of the ester has been
alkaloid compound involved n-hexyl-substituted urea func- described,[54] but procedures using quinine or other stan-
tions,[17] installation of which was accomplished by treat- dard resolution reagents unfortunately failed in our hands,
ment of 14 with the corresponding isocyanates (Scheme 6). so we proceeded with the racemic mixture 30. Curtius re-
For the enantiofacial discrimination of single heterocyclic arrangement under mild conditions with DPPA gave the
guest molecules α-chiral isocyanates were employed. The isocyanate 31, which was treated with the subunit 18 in situ.
efficiency of the chiral interaction with the supramolecular Despite the expected steric hindrance, 32 was obtained in
guest is based on repulsive steric interactions.
excellent yield.
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Synthesis of Rigid Receptors Based on Triphenylene Ketals
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that the protruding trityl moieties would require more space
than provided by the platform. Most probably the preferen-
tial orientation of the urea system would be strongly dis-
torted, so the trityl-modified receptors were not investigated
further.
The depicted α-chiral isocyanates (Figure 1) exhibit in-
creasing steric demand in the vicinity of the nitrogen. The
bulkiness of both reactants, isocyanate as well as scaffold,
results in prolonged reaction times. The urea formation pro-
ceeded constantly without interfering side-reactions
(Scheme 6).
Scheme 5. Synthesis of trityl-substituted receptor subunit 32:
a) Et2O, Ph3CBF4, 0 °C Ǟ room temp., 1 h, 60%. b) KOH, EtOH,
H2O, reflux, 64 h, 67%. c) Acetone, DPPA, 0 °C, 45 min., then tol-
uene, reflux, 3 h. d) NEt3, 18, 0 °C Ǟ room temp., 14 d, 89%.
Scheme 6. Synthesis of chirally modified receptors: a) R-NCO,
NEt3, CH2Cl2, 0 °C Ǟ room temp.
This highly reliable transformation was applied to con-
versions in which both reactants featured sterically hindered
functionalities (Table 2, Entries 7 and 8). The rigid charac-
ter of the substituents on the urea systems might complicate
the purification of the resulting receptors. Compounds 19c
and 19d form almost capsule-like structures without rotat-
able side chains. The obtained receptors have poor solubilit-
ies that impede chromatographic purification, and in the
case of the crude product of 19d no solvent mixture in
which to run analytical characterization in solution could
be found. Mass spectrometric investigations indicated the
existence of the desired receptor, but without a clear set of
data revealing structure and purity, no yield can reliably be
given.
A crystal in which a water molecule was incorporated
into a hydrogen bonding pattern with acetone (Figure 2)
was obtained from acetone and n-hexane. The carbonyl
moiety of another acetone molecule forms a hydrogen bond
with the NH functional groups of the urea on the receptor
subunit, so a mixed solvate was obtained.
The optically pure receptors based on triphenylene ketals
(Table 2) were characterized by one- and two-dimensional
NMR spectroscopic methods as well as by mass spectro-
metric investigations.[55] Correct microanalyses for the re-
ceptors without incorporated solvent molecules were ob-
tained only in one instance, as the receptors possess not
only hydrogen bonding donors in the form of the NH moie-
ties but also a hydrogen bonding acceptor in the carbonyl
function of the urea system. The solvent molecules were
also detected by NMR and therefore allowed for correct
Figure 2. Crystal structure of 32.
The trityl moieties protrude significantly into the space microanalyses.
designed for binding the guest, and treatment of the plat-
The α-chiral substituents on the urea moiety have prefer-
form 14 with 31 resulted in an isomeric mixture of recep- ential conformations in which the differently sized groups
tors. Diagnostic signals in 1H NMR spectroscopic and mass are positioned on opposite sides of the urea moiety. The
spectrometric investigations clearly indicated the antici- readily available (S)-phenethyl system 19a turned out not
pated structure, but molecular modeling studies indicated to be efficient for the enantiofacial differentiation of caf-
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Table 2. Synthesized optically pure receptors based on triphenylene ketals.
[a] Compound 19d was obtained as powder without any means of purification.
feine. After complex formation the phenyl groups should results in only one diastereomeric form, namely the α-
occupy an alignment that provides maximum space to the form.[56] As a result of these assumptions other orientations
guest, and consequently the opposite sides of the urea sys- of the bound guest cannot be excluded and might exist in
tem would exhibit similar steric demand. Only with 1,3,5- solution with high probability.
triacetyl benzene as substrate were suitable crystals for X-
The caffeine complexes of 19b and 19c each reveal a sin-
ray analysis obtained. In the solid state only one form of the gle orientation of the guest in the solid state. The methyl
complex was found, in which the guest is slightly distorted groups on the guest and the phenyl moieties of the receptors
(Figure 3).
are appropriate oriented for CH/π interactions. The dis-
Unfortunately, no caffeine complexes of 19a afforded tances found between the methyl carbons of the caffeine
suitable material for crystallographic investigations, and so and the plane of the corresponding π-system are in the
a para-bromophenethyl analogue of the receptor was con- range of 2.87–4.42 Å. Despite the small energy contribution
structed. The obtained caffeine complex of 19b had a and the weak nature of this attractive interaction,[57] it
strongly disordered receptor arm, with standard deviations might explain the enantiofacial preference in the solid state.
of binding lengths and angles twice as high as those for the Initially, the same preference was anticipated for the 1,3,5-
other two arms. Equal binding lengths were assigned to the triacetyl benzene complexes, but the suitable orientation of
N–C–N bonds of the imidazole moiety of caffeine, which the methyl protons is not possible due to the conforma-
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Synthesis of Rigid Receptors Based on Triphenylene Ketals
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However, no significant increase in the enantiofacial differ-
entiation was observed, since the tertiary C–H parts of the
isopropyl groups pointed into the coordination area for the
guest. By substitution of this unit with an additional methyl
group (see 19g) excellent enantiofacial differentiation both
in solution and in the solid state was observed.[18]
In 19h the C–H unit was substituted by a phenyl group,
and we assumed that the phenyl moieties would turn away
and would be located outside of the receptor. The repulsive
interactions between the arms of the receptor and caffeine
should thus result in a further increase in the enantiofacial
differentiation, since the methyl moieties should come
closer to the moieties of the guest than in the case of 19g.
Surprisingly though, 19h showed relatively poor host–guest
behavior. No suitable crystals with caffeine or another guest
were obtained for analytical diffraction methods. Investi-
gations into the supramolecular properties in solution gave
a less defined interaction. Subsequent simulation of 19h by
molecular dynamics indicates movements of the phenyl
moieties, facilitating the extrusion of the guest and partially
occupying the space in the receptor.
Conclusions
Rigid receptors based on a triphenylene core and a bicy-
clic moiety can be efficiently constructed. The synthesis in-
cludes oxidative trimerization of the corresponding catechol
ketals, followed by a repetitive separation/isomerization se-
quence to provide the desired scaffold for the concave archi-
tectures. The key intermediate for all receptors is the trisam-
ine 14, which can be converted into trisureas with sterically
very demanding chiral isocyanates. Reaction rates decrease
with the steric hindrance, but still allow reliable construc-
tion of such bulky systems. With trityl-substituted benzyl
or 8-phenylmenthyl moieties the available space in the re-
ceptor is not sufficient for supramolecular recognition.
When rigid α-chiral groups are present, the solubility be-
havior becomes poor. Therefore, aliphatic moieties seem to
be beneficial. With the established synthetic pathway for
these receptor structures based on triphenylene ketals, novel
sensors and catalysts are currently being developed and will
be reported in due course.
Figure 3. Molecular structures of triacetyl benzene with 19a (top)
and caffeine complexes of 19b (middle) and 19c (bottom). Left col-
umn: side view of the complexes. Right column: top view.
tional strain of the side chain, so that system is purely based
on steric interactions. However, none of these preferences
was confirmed in solution, indicating the low impact on the
complex dynamic system.
Because of the annulated six-membered ring of the tetra-
lin moiety, both the alkyl groups and the phenylene moiety
are conformationally fixed relative to 19a and 19b, respec-
tively. When caffeine was placed into receptor 19c only the
α-form was found in the crystal structure. This selectivity
seemed to be based on packing effects, because neither mol-
ecular modeling studies nor CD-spectroscopic investi-
gations indicated a preference for one of the two possible
aggregates.[19]
Experimental Section
Receptor 19e was of special interest, because no aromatic
General Remarks: All reagents were used in analytical grades. Sol-
moiety was located in the vicinity of the distal NHs, those vents were desiccated if necessary by standard methods. Column
chromatography was performed on silica gel (particle size 63–
200 μm, Merck, Darmstadt, Germany) with mixtures of cyclohex-
ane or toluene and ethyl acetate as eluents. TLC was performed on
silica gel (60 F254) on glass (Merck, Darmstadt, Germany). Melting
points were determined on a SMP3 Melting Point Apparatus (Stu-
art Scientific, Watford, Herts, UK) and were uncorrected. Micro-
analysis was performed with a Vario EL III instrument (Elementar-
Analysensysteme, Hanau, Germany). NMR spectra were recorded
on Bruker ARX 300 or AMX 400 machines (Analytische Mess-
technik, Karlsruhe, Germany) with TMS as internal standard or
further away from the triphenylene plane. Furthermore, the
tert-butyl moieties extend further into the cavity than the
phenyl group does and, indeed, the repulsive interaction be-
tween the tert-butyl fragments and the N-7 methyl group of
the caffeine produced a distinct enantiofacial differentia-
tion.[18] For further improvement of the discrimination we
introduced α-chiral moieties reaching far into the cavity.
These requirements were met by the two methyl groups of
(–)-menthol-derived substructures, and the six-membered
ring additionally provided higher conformational stability. CDCl3 and [D6]DMSO with δ = 7.26 ppm and δ = 2.49 ppm for
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M. C. Schopohl, A. Faust, D. Mirk, R. Fröhlich, O. Kataeva, S. R. Waldvogel
FULL PAPER
1H NMR, respectively, and δ = 77.0 ppm and δ = 39.7 ppm for 13
C
for subsequent ketalizations. M.p. 94–95 °C. Isomeric ratio: 67:33
NMR, respectively. The NMR spectroscopic data are given in ppm.
Mass spectra were obtained on a MAT8200 instrument (Finnigan–
MAT, Bremen, Germany) for EI, on a QUATTRO LCZ instrument
(Waters-Micromass, Manchester, UK) for ESI, or a LAZARUS
III–DE device (built in the Institute of Organic Chemistry,
Münster, Germany) for MALDI. HRMS data was recorded by the
mass spectrometer MicroTof (Bruker Daltronics, Bremen, Ger-
many). Optical rotary power was determined in a 10 cm cell on a
341 Polarimeter (Perkin–Elmer GmbH, Überlingen, Germany).
(GC). 1H NMR (300 MHz, CDCl3, olefinic mixture): δ = 0.88, 0.89
3
(2×t, JH,H = 7.2 Hz, 6 H, CH3), 1.44–1.88, 2.02–2.14, 2.22–2.44,
2.70–2.80, 3.04–3.10 (5×m, 18 H, CH2), 3.86, 3.88 (2×q, 4 H,
OCH2), 5.52–5.59, 5.69–5.73 (2×m, 2 H, CH), 5.98, 6.08 (2×dt,
3JH,H = 9.9 Hz, 2 H, CH), 6.74–6.77 (br. s, 8 H, arom. H) ppm.
13C NMR (75 MHz, CDCl3, olefinic mixture): δ = 13.4 (CH3), 16.3,
17.0, 25.9, 30.1, 30.5, 31.8, 34.1, 35.7, 36.9, 41.0 (CH2), 48.8, 51.9
(Cq), 60.6, 60.7 (OCH2), 107.9, 108.0, 108.1 (arom. CH), 117.9,
118.1 (OCO), 120.6, 120.8, 120.9 (arom. CH), 125.5, 125.7, 128.0,
129.2 (vinyl-CH), 147.3, 147.5, 147.6 (arom. Cq), 172.2, 173.0
(CO2Et) ppm. MS (EI, 70 eV): m/z (%) = 300 (100) [M]+, 227 (94)
[M – CO2Et]+, 147 (54) [bicyclo-CO]+. C18H20O4 (300.35): calcd.
C 71.98, H 6.71; found C 71.83, H 6.52.
Aldehyde 2: Ethyl 2-oxo-cyclohexane-1-carboxylate (60.0 g,
352 mmol) and acrolein (29.7 g, 35.3 mL, 530 mmol) were dissolved
under argon in DMF (300 mL). Triethylamine (5.3 g, 7.4 mL,
53 mmol) was added, and the reaction mixture was stirred for 16 h
at ambient temperature. The mixture was diluted with diethyl ether
(500 mL) and water (500 mL), and the organic phase was washed
with water (3×250 mL) and brine (100 mL), dried (MgSO4), and
concentrated in vacuo. The obtained yellow oil (67.3 g, 323 mmol,
Bicyclic Spiroketal 7: The olefinic mixture 5/6 (20 g, 66.2 mmol)
was dissolved in THF (300 mL), and palladium on charcoal (10%,
3 g) was added under argon. The suspension was evacuated and
treated with hydrogen (three times). After stirring for 40 h in hydro-
gen (1 atm) at ambient temperature the mixture was filtered
through a silica gel/Celite® pad in order to remove the hetero-
geneous catalyst. The filter cake was washed thoroughly with
dichloromethane and the filtrate was concentrated in vacuo. The
remaining oil crystallized spontaneously, yielding a colorless solid
1
92%) was used without further purification. H NMR (300 MHz,
3
CDCl3): δ = 1.30 (t, JH,H = 7.2 Hz, 3 H, CH3), 1.40–2.70 (m, 12
H, CH2), 4.20 (q, 2 H, OCH2), 9.75 (s, 1 H, CHO) ppm. 13C NMR
(75 MHz, CDCl3): δ = 13.9 (CH3), 22.4, 26.7, 27.3, 36.4, 39.2, 40.8
(CH2), 59.7 (OCH2), 61.3 (C-2), 171.6 (COO), 200.9 (CHO), 207.4
(CO) ppm. MS (EI, 70 eV): m/z (%) = 226.1 (8) [M]+, 208.1 (5)
[M – H2O]+, 170.1 (100) [M – C3H4O]+, 55.0 (50) [C4H7]+.
1
(20.3 g, 66.7 mmol, 100%). M.p. 99–101 °C. H NMR (300 MHz,
3
CDCl3): δ = 0.86 (t, JH,H = 7.2 Hz, 3 H, CH3), 1.60–2.56 (m, 13
H, bicyclo-H), 3.83 (q, 2 H, OCH2), 6.73 (s, 4 H, arom. H) ppm.
13C NMR (75 MHz, CDCl3): δ = 13.9 (CH3), 20.9, 28.7, 32.6 (bicy-
clo-CH2), 38.7 (OCH2), 49.5 (bicyclo-CH), 60.9 (bicyclo-Cq), 108.4
(arom. CH), 119.9 (OCO), 121.1 (arom. CH), 148.2 (arom. Cq),
174.1 (CO2Et) ppm. MS (EI, 70 eV): m/z (%) = 302 (100) [M]+, 229
(54) [M – CO2Et]+, 147 (40) [bicyclo-CO]+. C18H22O4 (302.36):
calcd. C 71.50, H 7.33; found C 71.22, H 7.22.
Olefinic Mixture 3/4: Compound 2 (56.7 g, 250 mmol) was added
directly over 10 minutes to concentrated sulfuric acid that had al-
ready been chilled to –10 °C.[28] During addition the reaction mix-
ture was vigorously stirred with a mechanical stirring device. After
2 h at 0 °C the mixture was allowed to warm to ambient tempera-
ture and stirred for 20 h. The black and viscous mixture was poured
onto ice (1 kg). After extraction with diethyl ether (3×200 mL),
the combined organic layers were washed with water (2×200 mL),
saturated NaHCO3 solution (200 mL), and brine (200 mL), dried
(MgSO4), and concentrated in vacuo. The olefinic mixture was
purified by short-path distillation (Boiling range: 80–82 °C,
0.08 mbar) and yielded a yellow oil that crystallized upon standing
(35.3 g, 170 mmol, 67%). M.p.[23] 46–47 °C. Isomeric ratio: 76:24
all-syn Triester 8 and anti,anti,syn Triester 9: Under an argon atmo-
sphere, 7 (18.1 g, 60 mmol) was dissolved in tetrabutylammonium
tetrafluoroborate in acetonitrile (0.1 m, 150 mL) by slightly heating
and transferred into an undivided standard electrolysis cell[58] with
two platinum sheets as anode and cathode. Galvanostatic electroly-
sis with a current density of 0.05 A·cm–2 was performed at 20 °C.
At the beginning we observed the appearance of a green coloration
that indicates the presence of radical cations. Vigorous stirring is
necessary during the electrolysis; if larger crystalline aggregates of
the crude products are formed, they occasionally have to be re-
moved from the anode. After ca. 18000 C (3.1 F·mol–1) had been
applied the mixture was transferred into a container with dichloro-
methane and the solvents were evaporated to dryness. The residue
was taken up in dichloromethane (250 mL), and methanol/water
(9:1, 800 mL) was added slowly at 0 °C. After the mixture had been
stirred for an additional 30 min the precipitate of crude anti,anti,
syn isomer 9 was filtered off and dried in vacuo and the mother
liquor contained mainly all-syn isomer 8. In order to extract the
remaining all-syn isomer of the precipitate, it was dissolved in tolu-
ene (80 mL) and heated at reflux and, after the system had been
brought to ambient temperature, ethanol (20 mL) was added drop-
wise. Precipitation was observed, and was brought to completion
by keeping the mixture for 12 h at 0 °C; pure anti,anti,syn isomer
was filtered off. The mother liquor was concentrated to a third of
its volume, and water (120 mL) was slowly added. The solid was
filtered off after 10 min. and dissolved in dichloromethane
(200 mL). The organic layer was dried (CaCl2), concentrated, and
adsorbed on silica gel. In order to circumvent cleavage of the ketal
moieties the crude product was purified immediately by column
chromatography (toluene to toluene/ethyl acetate, 95:5).
1
(GC). H NMR (300 MHz, CDCl3, olefinic mixture): δ = 1.29 (t,
3JH,H = 7.2 Hz, 6 H, CH3), 1.61–1.72, 1.84–2.08, 2.30–2.95, 3.38–
3.45 (4×m, 18 H, CH2), 4.22 (q, 4 H, OCH2), 5.55–5.62, 5.64–5.69
3
4
(2×m, 2 H, CH), 5.96, 6.05 (2×dt, JH,H = 9.8, JH,H = 3.6 Hz, 2
H, CH) ppm. 13C NMR (75 MHz, CDCl3, olefinic mixture): δ =
14.0, 14.1 (CH3), 17.5, 18.2, 33.3, 36.0, 36.7, 36.9, 39.4, 39.6 (CH2),
45.5, 47.8 (CHCO), 58.9, 60.2 (Cq), 61.5, 61.6 (OCH2), 126.6,
127.1, 129.3, 130.2 (CH), 171.7, 172.2 (CO2Et), 210.4, 210.5
(CO) ppm. MS (EI, 70 eV): m/z (%) = 208.0 (67) [M]+, 180.0 (23)
[M – CO]+, 162.0 (100) [M – EtOH]+, 134.0 (44) [M – EtOH –
CO] +.
Isomeric Catechol Ketals 5/6: The olefinic mixture 3/4 (35.3 g,
167 mmol) was dissolved in toluene (300 mL). After addition of
catechol (27.9 g, 253 mmol) and p-toluenesulfonic acid (3.0 g,
17.4 mmol), the mixture was heated under reflux, water (3.9 mL)
being collected by a Dean–Stark trap. After concentration of the
crude mixture under reduced pressure, the resulting oil was frac-
tionated with diethyl ether (700 mL) and sodium hydroxide solu-
tion (3%, 200 mL). The organic layer was washed several times
with water (5×200 mL) and brine (200 mL), dried (MgSO4), and
concentrated under reduced pressure. Ethanol (100 mL) was added
to the brown oil and spontaneous crystallization occurred. The ob-
tained crystals were filtered off and washed with methanol (43.2 g,
143 mmol, 84%). We recommend recycling of the mother liquor
2994
© 2005 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
Eur. J. Org. Chem. 2005, 2987–2999

Synthesis of Rigid Receptors Based on Triphenylene Ketals
FULL PAPER
Compound 8: 1.44 g, 1.6 mmol, 8%. M.p. Ͼ340 °C (decomp.). RF
arom. H) ppm. 13C NMR (75 MHz, [D6]DMSO): δ = 19.9, 27.9,
31.8 (bicyclo-CH2), 37.7 (bicyclo-CH), 47.8 (bicyclo-Cq), 101.1
1
= 0.4 (toluene/ethyl acetate, 95:5). H NMR (300 MHz, CDCl3): δ
3
= 0.77 (t, JH,H = 6.9 Hz, 9 H, CH3), 1.75–2.56 (m, 39 H, bicyclo- (arom. CH), 120.2 (bicyclo-OCO), 123.9 (arom. Cq), 147.6 (arom.
H), 3.76–3.84 (m, 6 H, OCH2), 7.69 (br. s, 6 H, arom. H) ppm. 13
C
ketal-C), 174.1 (CO2 H) ppm. MS (ES-): m/z (%) = 847.3 (1) [M +
NMR (75 MHz, CDCl3): δ = 14.0 (CH3), 21.0, 28.9, 32.8 (bicyclo-
CH2), 39.0 (bicyclo-CH), 49.6 (OCH2), 61.0 (bicyclo-Cq), 101.0
(arom. CH), 120.8 (bicyclo-OCO), 124.8 (arom. Cq), 148.3 (arom.
ketal-C), 174.1 (CO2Et) ppm. MS (ES+): m/z (%) = 900.6 (22),
901.6 (20), 902.6 (8), 903.6 (4) [M + H]+, 923.6 (100), 924.6 (55),
925.6 (20), 926.6 (10) [M + Na]+. C54H60O12 (901.05): calcd. C
71.98, H 6.71; found C 71.83, H 6.73.
MeOH]–, 815.8 (26), 815.3 (19) [M – H]–. HRMS: calcd. for
C48H48O12 [M
839.3038/815.3062.
+ –
Na]+/[M H]+ 839.3043/815.3073; found
Cbz-Protected Trisamine 12: Under argon, all-syn 10 (10.0 g,
12.2 mmol) was dissolved in benzene (400 mL) and DMF
(100 mL). Triethylamine (5.7 g, 7.9 mL, 56.0 mmol) and diphenyl-
phosphoryl azide (13.0 g, 10.8 mL, 47.2 mmol) were added at 0 °C.
The reaction mixture was stirred for 30 min. and then heated at
reflux for 4 h. After addition of benzyl alcohol (39.0 g, 37.2 mL,
Compound 9: 13.9 g, 15.4 mmol, 77%. M.p. Ͼ340 °C (decomp.). RF
1
= 0.5 (toluene/ethyl acetate, 95:5). H NMR (400 MHz, CDCl3): δ
3
= 0.76 (t, JH,H = 7.2 Hz, 9 H, CH3), 1.70–2.55 (m, 39 H, bicyclo- 360 mmol) and subsequent heating at reflux for 36 h the reaction
H), 3.77–3.83 (m, 6 H, OCH2), 7.69 (br. s, 6 H, arom. H) ppm. 13
NMR (100 MHz, CDCl3): δ = 13.5, 13.6 (CH3), 20.6, 28.4, 32.4 were evaporated under reduced pressure. Abundant benzyl alcohol
C
mixture was brought to ambient temperature. Volatile components
(bicyclo-CH2), 38.5 (bicyclo-CH), 49.2 (OCH2), 60.6 (bicyclo-Cq),
100.6 (arom. CH), 120.4 (bicyclo-OCO), 124.3 (arom. Cq), 147.8,
147.9 (arom. ketal-C), 173.6, 173.7 (CO2Et) ppm. MS (ES+): m/z
(%) = 923.3 (100), 924.5 (60), 925.3 (20), 926.3 (5) [M + Na]+.
(C54H60O12)2·EtOH (1848.16): calcd. C 71.49, H 6.87; found C
71.51, H 6.59.
and remaining DMF were removed by short-path distillation in
high vacuum (oil bath: 80 °C, 1·10–2 mbar). The viscous residue
was taken up in ethyl acetate (300 mL) and 0.1 m hydrochloric acid
(150 mL). The organic phase was washed with water (200 mL) and
brine (100 mL), dried (MgSO4), and concentrated in vacuo. Purifi-
cation by column chromatography (cyclohexane/ethyl acetate, 9:1)
yielded a yellow solid.
Isomerization of 9: Under an argon atmosphere,
9 (10.0 g,
11.1 mmol) was completely dissolved in 1,2-dichloroethane
(500 mL) by heating at reflux. Trifluoromethanesulfonic acid
(0.1 mL) was added, and the mixture was heated for an additional
15 min. After quenching with triethylamine (0.4 mL), the mixture
was chilled in an ice bath, and then concentrated in vacuo to re-
cover 1,2-dichloroethane. The residue was recrystallized from tolu-
ene/ethanol (4:1, 100 mL) and kept at 0 °C for an additional 12–
14 h. After removal of the solid containing pure 9 by filtration, the
mother liquor was concentrated in vacuo and taken up in dichloro-
methane (200 mL). The organic layer was dried (CaCl2) and purifi-
cation was performed as described above, providing 8 (2.3 g,
2.55 mmol, 23%) as an off-white powder.
Isomer all-syn 12: 11.2 g, 9.9 mmol, 81%. M.p. 268 °C. RF = 0.36
(cyclohexane/ethyl acetate, 6:4). H NMR (300 MHz, CDCl3): δ =
1
1.69–1.77, 2.05–2.31, 2.65–2.70 (3×m, 39 H, bicyclo-H), 4.84 (s, 6
H, OCH2Ph), 7.04–7.08 (m, 15 H, phenyl-H), 7.76 (s, 6 H, arom.
H) ppm. 13C NMR (75 MHz, CDCl3): δ = 21.0, 28.2, 33.7 (bicyclo-
CH2), 38.2 (bicyclo-CH), 57.8, 57.9 (bicyclo-Cq), 65.3, 66.1
(OCH2Ph), 101.6 (arom. CH), 121.2 (bicyclo-OCO), 124.7, 124.9,
126.9, 127.8, 128.0, 128.3, 128.5, 136.4 (arom. Cq, phenyl-CH),
140.9 (phenyl-Cq), 147.4 (arom. ketal-C), 155.0 (CO2Bn) ppm. MS
(ES+): m/z (%) = 1154.7 (100), 1155.7 (80), 1156.7 (35), 1157.7 (15)
[M + Na]+. C69H69N3O12 (1132.30): calcd. C 73.19, H 6.14, N 3.71;
found C 73.08, H 6.32, N 3.38.
all-syn Tricarboxylic Acid 10: Compound 8 (15 g, 16.7 mmol) was
dissolved in THF (400 mL) with use of a mechanical stirrer, and
potassium butoxide (56.1 g, 500 mmol) was added. Addition of
water (4.5 mL, 4.5 g, 250 mmol) at 0 °C resulted in clouding of the
reaction mixture, which was then heated at reflux for 16 h. For
workup the mixture was transferred with additional water into a
large flask, and THF was removed under reduced pressure. The
slurry was diluted with water (500 mL) and ice (800 mL). Careful
addition of concentrated hydrochloric acid brought the mixture to
pH 1, and precipitation of the carboxylic acid occurred. After an
additional 5 min the pH was monitored and adjusted if necessary.
Isomer anti,anti,syn 13: This isomer was obtained by treatment of
11 as described for 12: 11.7 g, 10.4 mmol, 85%. M.p. 265–267 °C.
RF = 0.40 (cyclohexane/ethyl acetate, 75:25). H NMR (400 MHz,
1
CDCl3): δ = 1.70–1.78, 2.06–2.33, 2.66–2.71 (3×m, 39 H, bicyclo-
H), 4.85 (s, 6 H, OCH2Ph), 7.05–7.08 (m, 15 H, phenyl-H), 7.74 (s,
6 H, arom. H) ppm. 13C NMR (100 MHz, CDCl3): δ = 21.0, 28.2,
33.0, 33.3 (bicyclo-CH2), 38.3 (bicyclo-CH), 57.8, 58.0 (bicyclo-Cq),
65.3, 66.1 (OCH2Ph), 101.5, 101.6, 101.6 (arom. CH), 121.1, 121.2
(bicyclo-OCO), 124.7, 124.7, 126.9, 127.6, 127.8, 128.0, 128.0,
128.2, 128.5, 136.4 (phenyl-CH), 140.9 (phenyl-Cq), 147.4, 147.5
(arom. ketal-C), 154.9 (CO2Ph) ppm. MS (ES+) m/z (%) = 1156.6
The aqueous layer was extracted with ethyl acetate (4×500 mL) (42), 1155.5 (37), 1154.5 (14) [M + Na]+. C69H69N3O12 (1132.30):
and the combined organic layers were washed with water (500 mL)
and brine (500 mL), dried (Na2SO4), and concentrated, and the
resulting solid was dried in high vacuum at 50 °C for 12–14 h.
calcd. C 73.19, H 6.14, N 3.71; found C 73.22, H 6.02, N 3.36.
Trisamine 14: Isomer all-syn 12 (6.80 g, 6.00 mmol) was dissolved
in THF (250 mL), and Pearlman’s catalyst (20% Pd(OH)2 on char-
coal, 50% water) was added. The suspension was evaporated and
treated with hydrogen (three times). After stirring for 48 h under
hydrogen (1 atm) at ambient temperature the mixture was filtered
with the aid of a Celite® pad for removing the heterogeneous cata-
1
Isomer all-syn 10: 11.9 g, 14.5 mmol, 87%. M.p. 307 °C. H NMR
(300 MHz, [D6]DMSO): δ = 0.93–2.48 (m, 39 H, bicyclo-H), 7.98
(br. s, 6 H, arom. H) ppm. 13C NMR (75 MHz, [D6]DMSO): δ =
19.8, 28.1, 31.9 (bicyclo-CH2), 37.8 (bicyclo-CH), 47.8 (bicyclo-Cq),
101.2 (arom. CH), 120.3 (bicyclo-OCO), 123.9 (arom. Cq), 147.6 lyst. The filter cake was intensively rinsed with dichloromethane
(arom. ketal-C), 174.3 (CO2 H) ppm. MS (ES+): m/z (%) = 816.5
and the filtrate was concentrated in vacuo. The trisamine was ob-
(20), 817.5 (16), 818.5 (8) [M + H]+, 839.5 (100), 840.5 (48), 841.5 tained as an off-white solid.
(18) [M + Na]+. C48H48O12·2THF (961.10): calcd. C 69.98, H 6.71;
found C 69.94, H 6.68.
Isomer all-syn 14: 4.37 g, 5.97 mmol, 99%. M.p. Ͼ340 °C (de-
1
comp.). RF = 0.0 (ethyl acetate). H NMR (300 MHz, CDCl3): δ =
Isomer anti,anti,syn 11: Compound 9 was treated as for the isomer 0.92–2.39 (m, 39 H, bicyclo-H), 7.70 (br. s, 6 H, arom. H) ppm.
10: 12.6 g, 15.4 mmol, 92%. M.p. 304–308 °C. 1H NMR (300 MHz, 13C NMR (75 MHz, CDCl3): δ = 21.4, 28.4, 36.4 (bicyclo-CH2),
[D6]DMSO): δ = 0.95–2.51 (m, 39 H, bicyclo-H), 7.99 (s, 6 H,
www.eurjoc.org
38.6 (bicyclo-CH), 54.0 (bicyclo-Cq), 100.7 (arom. CH), 122.9 (bi-
2995
Eur. J. Org. Chem. 2005, 2987–2999
© 2005 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

M. C. Schopohl, A. Faust, D. Mirk, R. Fröhlich, O. Kataeva, S. R. Waldvogel
FULL PAPER
cyclo-OCO), 124.4 (arom. Cq), 148.3 (arom. ketal-C) ppm. MS (+)-(1S)-1-(4-Bromophenyl)ethyl Isocyanate (21): Compound 21
(ES+): m/z (%) = 730.6 (100), 731.6 (50), 732.6 (14) [M + H]+.
(C45H51N3O6)2·2HCl·H2O (1550.74): calcd. C 69.71, H 6.89, N
5.42; found C 69.95, H 6.92, N 5.13.
(19.0 g, 84 mmol, 84%) was obtained from (–)-(1S)-(4-bro-
20
20
mophenyl)ethylamine (20.0 g, 100 mmol, [α]
= –20.9, [α]
=
589
578
20
20
20
–21.8, [α]
= –24.9, [α]
= –43.3, [α]
= –70.3 (c = 2.35,
546
436
365
MeOH)), and became solid upon standing (M.p. around room tem-
Isomer anti,anti,syn 15: Isomer 13 was treated as for the isomer 14:
4.38 g, 5.97 mmol, 99%. M.p. Ͼ340 °C (decomp.). RF = 0.0 (ethyl
acetate). 1H NMR (400 MHz, CDCl3): δ = 0.93–2.42 (m, 39 H,
bicyclo-H), 7.72 (s, 6 H, arom. H) ppm. 13C NMR (100 MHz,
CDCl3): δ = 21.6, 28.6, 36.8 (bicyclo-CH2), 38.8 (bicyclo-CH), 54.1
(bicyclo-Cq), 100.7 (arom. CH), 122.9 (bicyclo-OCO), 124.4 (arom.
Cq), 148.3 (arom. ketal-C) ppm. MS (ES+): m/z (%) = 730.5 (4)
[M]+. C45H51N3O6·HCl (780.39): calcd. C 70.80, H 6.97, N 5.18;
found C 71.15, H 7.12, N 4.77.
perature). Boiling range: 123–127 °C (12 mbar). 1H NMR
3
(300 MHz, CDCl3): δ = 1.54 (d, JH,H = 6.9 Hz, 3 H, CH3), 4.70
(q, 1 H, CH), 7.16–7.20, 7.43–7.48 (2×m, 4 H, arom. H) ppm. 13C
NMR (75 MHz, CDCl3): δ = 25.8 (CH3), 53.9 (CH), 121.5 (C–Br),
127.1, 131.7 (arom. CH), 141.3 (arom. Cq) ppm. MS (EI, 70 eV):
m/z (%) = 227.0 (35), 225.0 (36) [M]+, 212.0 (95), 210.0 (100)
[M – CH3]+, 185.0 (14), 183.0 (15) [BrC6H4CNH]+, 146.1 (75) [M –
20
20
20
Br]+, 77.1 (31) [C6H5]+. [α] = +5.0, [α] = +5.3, [α] = +6.0,
589
578
546
20
20
[α]
436
= +10.3, [α]
= +15.3 (c = 2.04, benzene). C9H8BrNO
365
Carboxylic Acid 16: This compound was prepared as described for
10, from 7 (10.0 g, 33 mmol) and potassium butoxide (37.1 g,
330 mmol) in THF (150 mL) with subsequent addition of water
(3.0 g, 3.0 mL, 165 mmol). Workup and drying provided 7.3 g
(26.5 mmol, 88%). M.p. 217 °C. 1H NMR (300 MHz, CDCl3): δ =
1.60–2.60 (m, 13 H, bicyclo-H), 6.77 (br. s, 4 H, arom. H) ppm.
13C NMR (75 MHz, CDCl3): δ = 20.4, 28.2, 32.2 (bicyclo-CH2),
37.4 (bicyclo-CH), 48.5 (bicyclo-Cq), 108.4 (bicyclo-OCO), 119.1,
121.0 (arom. CH), 147.4 (arom. ketal-C), 178.6 (CO2 H) ppm. MS
(EI, 70 eV): m/z (%) = 274 (100) [M]+, 229 (19) [M – CO2H]+, 165
(16) [M – C6H4O2]+, 147 (51) [bicyclo-CO]+, 109 (28) [C6H5O2]+.
C16H16O4 (274.31): calcd. C 70.06, H 6.61; found C 70.10, H 6.33.
(226.07): calcd. C 47.82, H 3.57, N 6.20; found C 47.80, H 3.57, N
6.20.
(+)-(1S)-1,2,3,4-Tetrahydro-1-naphthyl Isocyanate (22): Use of (+)-
20
(1S)-1,2,3,4-tetrahydronaphthylamine (15.0 g, 102 mmol, [α]
=
589
20
20
20
20
+29.5, [α] = +30.9, [α] = +34.9, [α] = +58.0, [α] = +87.9
578
546
436
365
(c = 2.55, MeOH)) yielded 22 (12.7 g, 73 mmol, 72%). B.p. 129 °C
(18 mbar). 1H NMR (400 MHz, CDCl3): δ = 1.72–1.81 (m, 1 H, 3-
H), 1.88–2.05 (m, 3 H, 2-H, 3-H), 2.66–2.74 (m, 1 H, 4-H), 2.76–
3
2.84 (m, 1 H, 4-H), 4.65 (t, JH,H = 5.2 Hz, 3 H, 1-H), 7.05–7.09
(m, 1 H, 6-H), 7.14–7.19 (m, 2 H, 7-H, 8-H), 7.29–7.34 (m, 1 H,
9-H) ppm. 13C NMR (100 MHz, CDCl3): δ = 19.2 (C-2), 28.7 (C-
4), 31.8 (C-2), 53.1 (C-1), 126.2, 127.7, 128.2, 129.2 (arom. CH),
135.9, 136.1 (arom. Cq) ppm. MS (EI, 70 eV): m/z (%) = 173.1 (16)
[M]+, 145.0 (21) [M – CO]+, 130.1 (100) [M – NCO]+, 91.1 (16)
Cbz-Protected Amine 17: This compound was prepared analo-
gously to 12, from 16 (8.0 g, 29.2 mmol) in benzene (200 mL),
DMF (10 mL), triethylamine (6.2 mL, 4.4 g, 43.7), diphenylphos-
phoryl azide (10.4 g, 8.7 mL, 38.0 mmol), and benzyl alcohol
(31.5 g, 30.2 mL, 292 mmol), to give 17 as a colorless, viscous oil
20
20
20
20
[C7H7]+. [α]
+16.9, [α]
= +10.7, [α]
= +11.0, [α]
= +12.1, [α]
=
589
578
546
436
20
= +17.9 (c = 1.15, benzene). C11H11NO (173.21):
365
calcd. C 76.28, H 6.40, N 8.09; found C 76.44, H 6.49, N 7.88.
1
(10.2 g, 26.9 mmol, 92%). H NMR (300 MHz, CDCl3): δ = 1.42–
1.69, 2.09–2.27, 2.69–2.73 (3×m, 13 H, bicyclo-H), 4.95 (s, 2 H,
OCH2Ph), 6.80 (s, 4 H, phenyl-H), 7.21–7.30 (m, 4 H, arom.
H) ppm. 13C NMR (75 MHz, CDCl3): δ = 21.0, 28.1, 28.9, 33.8
(bicyclo-CH2), 37.7 (bicyclo-CH), 57.6 (bicyclo-Cq), 66.2
(+)-(1S)-Indanyl Isocyanate (23): This compound was prepared
20
from (+)-(1S)-aminoindane (15.0 g, 113 mmol, [α]
= +18.1, [α]
589
20
20
20
20
= +18.9, [α] = +21.0, [α] = +31.2, [α] = +37.2 (c = 2.15,
578
546
436
365
MeOH)), providing 23 (15.5 g, 97 mmol, 86%). B.p. 116 °C
(OCH2Ph), 108.9 (bicyclo-OCO), 121.4 (arom. CH), 128.0, 128.2, (21 mbar). 1H NMR (400 MHz, CDCl3): δ = 1.95–2.04 (m, 1 H, 2-
128.5 (phenyl-CH), 137.0 (phenyl-Cq), 147.2 (arom. ketal-C), 156.7
(CO2Bn) ppm. MS (EI, 70 eV): m/z (%) = 379 (27) [M]+, 271 (14)
[M – C6H4O2]+, 136 (8) [C9H14N]+, 91 (100) [PhCH2]+. C23H25NO4
(379.5): calcd. C 72.80, H 6.64, N 3.69; found C 72.81, H 6.71, N
3.76.
H), 2.40–2.48 (m, 1 H, 2-H), 2.73–2.81 (m, 1 H, 3-H), 2.93–3.01
3
(m, 1 H, 3-H), 4.89 (t, JH,H = 7.2 Hz, 1 H, 1-H), 7.17–7.33 (m, 4
H, arom. H) ppm. 13C NMR (100 MHz, CDCl3): δ = 29.9 (C-3),
35.4 (C-2), 58.5 (C-1), 123.5, 124.8, 126.8, 128.3 (arom. CH), 142.2,
142.4 (arom. Cq) ppm. MS (EI, 70 eV): m/z (%) = 159.1 (84) [M]+,
20
20
117.0 (100) [M – NCO]+, 77.0 (27) [C6H5]+. [α] = +28.7, [α]
=
589
578
Amine 18: This compound was prepared analogously to 14, from 17
(10.86 g, 28.6 mmol) and Pearlman’s catalyst (0.60 g, 20% Pd(OH)2
on charcoal, 50% water) in THF (250 mL) under hydrogen (1 atm).
Purification of the crude product could be accomplished by subli-
mation in high vacuum, yielding 18 as an off-white solid (6.44 g,
26.4 mmol, 91%). 1H NMR (300 MHz, CDCl3): δ = 1.64–2.28 (m,
13 H, bicyclo-H), 6.74–6.81 (m, 4 H, arom. H) ppm. 13C NMR
(75 MHz, CDCl3): δ = 21.9, 28.8, 36.8 (bicyclo-CH2), 38.8 (bicyclo-
CH), 54.3 (bicyclo-Cq), 108.6 (bicyclo-OCO), 121.3, 122.2 (arom.
CH), 148.4 (arom. ketal-C) ppm. MS (EI, 70 eV): m/z (%) = 245.2
(42) [M]+, 137.1 (100) [C9H15N]+, 109.1 (48) [C6H5O2]+.
C15H19NO3 (245.3): calcd. C 73.44, H 7.81, N 5.71; found C 73.44,
H 7.80, N 5.43.
+29.6 (c = 1.35, benzene). C10H9NO (159.18): calcd. C 75.45, H
5.70, N 8.80; found C 75.30, H 5.72, N 8.75.
(+)-(2S)-1,2,2-Trimethylpropyl Isocyanate (24): This compound was
prepared
99 mmol, [α]
from
(+)-(2S)-3,3-dimethylbut-2-ylamine
(10.0 g,
20
20
20
20
= +18.1, [α]
= +18.9, [α]
= +21.0, [α]
=
589
578
546
436
20
+31.2, [α] = +37.2 (c = 2.15, MeOH)) as a solution in toluene
365
(8.9 g, 70 mmol, 71%). Boiling range: 108–116 °C. 1H NMR
3
(300 MHz, CDCl3): δ = 0.92 (s, 9 H, C(CH3)3), 1.22 (d, JH,H
=
6.6 Hz, 3 H, CH3), 3.31 (q, 1 H, CH) ppm. 13C NMR (75 MHz,
CDCl3): δ = 18.1 (CH3), 25.9 (C(CH3)3), 60.9 (CH) ppm. MS (EI,
70 eV): m/z (%) = 127.0 (0.2) [M]+, 112 (5) [M – CH3]+, 99.0 (5)
20
20
[M – CO]+, 57.0 (100) [C4H9]+. [α] = +18.4, [α] = +19.3, [α]
589
578
20
20
= +21.9, [α] = +37.7 (c = 11.7, toluene).
546
436
Phosgenation: Phosgenation was performed according to the litera-
ture.[59] The employed optically pure amines were converted into
the corresponding ammonium chlorides, which were subsequently
treated with either phosgene or diphosgene in toluene. Distillative
workup gave the individual isocyanates as colorless liquids.
(rac)-1-Methyl-2,2,2-triphenylethyl Isocyanate (31): A toluene ex-
tract of the reaction mixture for 32 confirmed the existence of the
3
isocyanate. 1H NMR (400 MHz, CDCl3): δ = 1.30 (d, JH,H
=
6.8 Hz, 3 H, CH3), 4.73 (q, 1 H, CH), 7.03–7.27 (m, 15 H,
phenyl) ppm. 13C NMR (75 MHz, CDCl3): δ = 16.3 (CH3), 58.7
(CH), 70.6 (Cq), 126.5, 127.6, 129.6 (phenyl-CH), 144.5 (phenyl-
(–)-(1S)-1-Phenethyl Isocyanate (20): The analytical data were in
agreement with a commercial sample.
2996
© 2005 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
Eur. J. Org. Chem. 2005, 2987–2999

Synthesis of Rigid Receptors Based on Triphenylene Ketals
FULL PAPER
3 H, CH), 4.58 (br. s, 3 H, NHprox), 4.66 (d, JNH,H = 5.6 Hz, 3 H,
Cq). GC-MS (EI+): m/z (%) = 298 (55) [M – CH3]+, 270 (100) [M –
3
HNCO]+, 243 (36) [Ph3C]+.
NHdist), 6.76, 7.05 (2×d, J12,13 = 8.4 Hz, 6 H, phenyl-H), 7.69,
3
7.85 (2×s, 2×3 H, triphenylene-H) ppm. 13C NMR (100 MHz,
CDCl3): δ = 20.9, 21.0 (bicyclo-CH2), 23.5 (CH3), 28.2, 28.3, 34.1,
34.2 (bicyclo-CH2), 38.2 (bicyclo-CH), 50.1 (CH), 57.9 (bicyclo-
Cq), 101.8, 102.0 (triphenylene-CH), 120.5 (C–Br), 121.9 (bicyclo-
OCO), 124.5, 124.6 (triphenylene-Cq), 127.3, 131.5 (phenyl-CH),
143.2 (phenyl-Cq), 147.4, 147.6 (triphenylene-CO), 156.7
(CO) ppm. MS (ES+): m/z (int.) = 1407.4 (11), 1408.4 (9), 1409.4
(11), 1410.4 (9), 1411.4 (5) [M + H]+, 1427.4 (25), 1428.4 (22),
1429.4 (85), 1430.4 (66), 1431.4 (100), 1432.4 (58), 1433.4 (48),
1434.4 (31), 1435.4 (11) [M + Na]+, 1443.4 (16), 1444.4 (11), 1445.4
(51), 1446.4 (40), 1447.4 (65), 1448.4 (43), 1449.4 (38), 1450.4 (20),
Trityl-Modified Subunit 32: 2-Methyl-3,3,3-triphenylpropionic acid
(30, 486 mg, 1.53 mmol) was dissolved in toluene (10 mL), concen-
trated under reduced pressure (3×), and then well dried in vacuo.
The anhydrous acid was dissolved in toluene (20 mL) by gentle
warming. After addition of triethylamine (0.32 mL, 233 mg,
2.30 mmol) and diphenylphosphoryl azide (507 mg, 1.84 mmol) at
ambient temperature and stirring for 15 min., the mixture was
heated at reflux until gas evaporation was no longer observed (2–
3 h) and was then allowed to cool to ambient temperature before
being chilled to 0 °C. Compound 18 (250 mg, 1.02 mmol), and af-
terwards triethylamine (0.14 mL, 103 mg, 1.02 mmol), were added,
and the mixture was stirred for 14 d at ambient temperature. After
fractionation between ethyl acetate (50 mL) and water (75 mL) the
aqueous phase was extracted with ethyl acetate (3×30 mL). The
combined organic layers were washed with brine (2×30 mL), dried
(MgSO4), and concentrated under reduced pressure. Purification
was performed by column chromatography (toluene/ethyl acetate,
9:1 Ǟ 8:2), yielding a colorless solid (510 mg, 0.91 mmol, 89%).
20
20
20
1451.4 (8) [M + K]+. [α] = +44.1, [α] = +46.9, [α] = +53.8,
589
578
546
20
[α] = +96.5 (c = 0.54, CH2Cl2). C72H75Br3N6O9·2EtOAc·PhCH3
436
(1676.46): calcd. C 62.33, H 5.95, N 5.01; found C 62.35, H 5.91,
N 5.21.
(+)-Tetralyl-Substituted Receptor 19c: The compound was obtained
as a gray solid (262 mg, 0.21 mmol, 38%) from all-syn trisamine 14
(400 mg, 0.55 mmol), triethylamine (0.23 mL, 167 mg, 1.65 mmol),
and (+)-(1S)-1,2,3,4-tetrahydronaphthyl isocyanate (22, 372 mg,
1.64 mmol), stirring for 7 d and purification by column chromatog-
raphy (cyclohexane/ethyl acetate, 8.2 Ǟ 6:4). M.p. 240 °C (de-
comp.). RF = 0.20 (cyclohexane/ethyl acetate, 8:2). 1H NMR
(400 MHz, CDCl3): δ = 1.37 (br. s, 12 H, tetralin-CH2), 1.65–1.67,
2.00–2.24 (m, 33 H, bicyclo-H), 2.33 (br. s, 6 H, tetralin-CH2), 2.84
(br. s, 6 H, bicyclo-H), 4.36–4.54 (m, 9 H, tetralin-CHNH and
1
M.p. 107 °C (decomp.). RF = 0.58 (toluene/ethyl acetate, 8:2). H
3
NMR (400 MHz, CDCl3): δ = 0.90 (d, JH,H = 6.4 Hz, 3 H, CH3),
1.49–1.54, 1.60–1.66, 1.91–2.14 (3×m, 11 H, bicyclo-CH2), 2.20
(br. s, 1 H, bicyclo-CH), 2.38–2.41 (m, 1 H, bicyclo-CH2), 4.14 (br.
3
s, 1 H, NHprox), 4.52 (d, JH,H = 10.0 Hz, 1 H, NHdist), 5.54–5.58
(m, 1 H, CH), 6.25 (d (b), 3JH,H = 7.6 Hz, 1 H, catechol-CH); 6.62–
6.75 (m, 3 H, catechol-CH); 7.21–7.35 (m, 15 H, trityl-H) ppm. 13
C
3
NH), 6.61 (d, JH,H = 7.6 Hz, 3 H, tetralin-CarH), 6.66, 6.79 (2×t,
NMR (100 MHz, CDCl3): δ = 18.6 (CH3), 21.1, 21.1, 27.9, 28.0,
32.9, 36.0 (bicyclo-CH2); 38.3 (bicyclo-CH), 48.0 (CH), 57.7 (bicy-
clo-Cq), 61.7 (CPh3), 108.6, 108.6 (catechol-CH), 120.7 (bicyclo-
OCO), 120.9, 121.5 (catechol-CH), 126.0, 126.0, 127.8 (trityl-C),
146.4, 147.3 (catechol-Cq), 156.7 (CO) ppm. MS (MALDI, DHB
matrix): m/z = 559, 560 [M + H]+, 581, 582 [M + Na]+, 597, 598
[M + K]+. (C37H38N2O3)2·H2O (1135.43): calcd. C 78.28, H 6.92,
N 4.83; found C 78.23, H 7.18, N 4.40. HRMS: calcd. for
3
3
3JH,H = 7.2, JH,H = 7.6 Hz, 2×3 H, tetralin-CarH), 6.85 (d, JH,H
= 7.6 Hz, 3 H, tetralin-CarH), 7.63 (br. s, 6 H, triphenylene-
H) ppm. 13C NMR (100 MHz, CDCl3): δ = 19.8 (tetralin-CH2),
21.1, 28.3 (bicyclo-CH2), 29.1, 30.4 (tetralin-CH2), 34.5, 34.6 (bicy-
clo-CH2), 38.3 (bicyclo-CH), 48.0 (tetralin-CHNH), 58.0 (bicyclo-
Cq), 101.6, 101.6 (triphenylene-CH), 121.9 (bicyclo-OCO), 124.6
(triphenylene-Cq), 125.7, 126.6, 128.5, 128.7 (tetralin-CHarom),
137.1, 137.3 (tetralin-Cq), 147.4, 147.4 (triphenylene-CO), 156.9
(CO) ppm. MS (ES+): m/z (int.) = 1271.8 (100), 1272.8 (93), 1273.8
(40), 1274.8 (15), 1275.7 (5) [M + Na]+, 1287.8 (5), 1288.8 (5) [M
[C37H38N2O3
581.2790.
+
H+/Na+] 559.2961/581.2780; found 559.2964/
General Procedure for Synthesis of Optically Pure Receptors (19a–
19h): The all-syn trisamine 14 (1 equiv.) was dissolved in dichloro-
methane (20 mL) and chilled to 0 °C. After addition of triethyl-
amine (3 equiv.) and α-chiral isocyanate (6 equiv.) the reaction mix-
ture was allowed to warm to ambient temperature, stirred for the
given time, and then diluted with ethyl acetate (50 mL) and hydro-
chloric acid (0.2 m, 75 mL). The aqueous phase was extracted with
ethyl acetate (3×75 mL) and the combined organic layers were
washed with brine (2×50 mL), dried (MgSO4), and concentrated
in vacuo. The crude product was purified by column chromatog-
raphy or by crystallization from methanol or ethanol and sub-
sequently dried in high vacuum.
+ K]+. [α] = +40.2, [α] = +42.8, [α] = +49.8, [α] = +104.9
20
20
20
20
589
578
546
436
(c = 0.22, CH2Cl2). (C78H84N6O9)2·2EtOAc·H2O (2693.30): calcd.
C 73.14, H 6.96, N 6.24; found C 73.06, H 6.69, N 6.12.
(+)-(1R,3R,4S)-8-Phenylmenthyl-Substituted Receptor 19h: This
compound was obtained as
a light yellow solid (895 mg,
0.60 mmol, 87%) from all-syn trisamine 14 (500 mg, 0.69 mmol),
triethylamine (0.30 mL, 208 mg, 2.06 mmol), and (–)-(1R,3R,4S)-
8-phenylmenthyl isocyanate (27) (1.06 g, 4.11 mmol), stirring for
8 d, and purification by column chromatography (cyclohexane/
ethyl acetate, 9:1 Ǟ 6:4). M.p. 225 °C (decomp.). RF = 0.27 (cyclo-
1
hexane/ethyl acetate, 7:3). H NMR (400 MHz, CDCl3): δ = 0.40–
3
0.49 (m, 3 H, 14-Ha), 0.68 (d, J15,13 = 6.4 Hz, 9 H, 15-H,), 0.73–
Compounds 19a, 19e, 19f, and 19g are partially known, so their
complete sets of data are given in the Supporting Information (for
Supporting Information see also the footnote on the first page of
this article).
0.83 (m, 3 H, 12-Ha), 0.99 (s, 9 H, 21-/22-H), 1.04–1.08 (m, 3 H,
11-Ha), 1.14 (s, 9 H, 21-/22-H), 1.27–1.36 (m, 3 H, 13-Ha), 1.51–
1.65 (m, 18 H, of which 12 H: bicyclo-CH2 and 6H: 10-Ha, 12-He),
1.77–1.83 (m, 6 H, 11-He, 14-He), 1.96–2.23 (m, 21 H, bicyclo-H),
(+)-(1S)-4-Bromophenethyl-Substituted Receptor 19b: Compound
19b was obtained as a gray solid (348 mg, 0.25 mmol, 92%) from 3.38 (m, 6 H, NH), 6.49 (t, J20,19 = 7.2 Hz, 3 H, 20-H), 6.98 (t,
2.67–2.69 (m, 3 H, 9-Ha), 2.91–2.93 (m, 6 H, bicyclo-CH2), 3.33–
3
3
all-syn trisamine 14 (200 mg, 0.27 mmol), triethylamine (0.12 mL,
83 mg, 0.82 mmol), and (+)-(1S)-1-(4-bromophenyl)ethyl isocya-
nate (21, 372 mg, 1.64 mmol) after stirring for 3 d and purification
by column chromatography (toluene/ethyl acetate, 6:4). M.p.
3J19,18/20 = 7.6 Hz, 6 H, 19-H), 7.11 (d, J18,19 = 7.6 Hz, 6 H, 18-
H), 7.84, 7.89 (2×s, 2×3 H, triphenylene-H) ppm. 13C NMR
(100 MHz, CDCl3): δ = 20.5 (C-21/-22), 20.9, 21.1 (bicyclo-CH2),
21.8 (C-15), 27.1 (C-11), 28.4, 28.5 (bicyclo-CH2), 31.0 (C-13), 31.6
(C-21/-22), 34.0 (bicyclo-CH2), 34.8 (C-12), 35.2 (bicyclo-CH2),
37.8 (bicyclo-CH), 39.4 (C-16), 44.7 (C-14), 51.4 (C-10), 51.8 (C-9),
57.1 (bicyclo-Cq), 101.9, 102.0 (triphenylene-CH), 121.9 (bicyclo-
1
185 °C (decomp.). RF = 0.16 (toluene/ethyl acetate, 6:4). H NMR
3
(400 MHz, CDCl3): δ = 1.10 (d, JH,H = 6.8 Hz, 9 H, CH3), 1.66–
1.71, 1.98–2.29, 2.86–2.91 (3×m, 39 H, bicyclo-H), 4.36–4.39 (m,
Eur. J. Org. Chem. 2005, 2987–2999
www.eurjoc.org
© 2005 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
2997

M. C. Schopohl, A. Faust, D. Mirk, R. Fröhlich, O. Kataeva, S. R. Waldvogel
OCO), 124.7 (C-20), 124.7 (triphenylene-Cq), 125.2 (C-18), 128.2 X-ray Crystal Structure Analysis for 19c with Caffeine: formula
FULL PAPER
(C-19), 147.5, 147.6 (triphenylene-CO), 153.2 (phenyl-Cq), 155.6
(CO) ppm. MS (ES+): m/z (int.) = 1502.2 (78), 1503.2 (70), 1504.2
(46), 1505.2 (18) [M + H]+, 1524.1 (91), 1525.1 (100), 1526.1 (53),
C78H84N6O9·C8H10N4O2,
0.45×0.20×0.20 mm,
23.644(1) Å, β = 90.87(1)°, V = 3784.4(5) Å3, ρcalc = 1.267 g·cm–3,
M
=
=
1443.71, colorless crystal
a
11.243(1), 14.238(1),
b
=
c =
1527.1 (20) [M + Na]+, 1540.0 (18), 1541.0 (15), 1542.0 (8) [M + μ = 0.85 cm–1, empirical absorption correction (0.963 Յ T Յ
K]+. [α]
= +278.0, [α]
= +292.2, [α]
= +340.3, [α] =
0.983), Z = 2, monoclinic, space group P21 (No. 4), λ = 0.71073 Å,
T = 198 K, ω and φ scans, 30634 reflections collected ( h, k, l),
[(sinθ)/λ] = 0.66 Å–1, 16570 independent (Rint = 0.047) and 12402
observed reflections [I Ն 2 σ(I)], 991 refined parameters, R = 0.051,
wR2 = 0.119, max. residual electron density 0.43 (–0.23) e·Å–3, hy-
drogen atoms at nitrogen atoms from difference Fourier calcula-
tions, other calculated and refined as riding atoms.
20
20
20
20
589
578
546
436
+684.5 (c = 0.54, CH2Cl2). C96H120N6O9·EtOAc (1590.12): calcd.
C 75.53, H 8.11, N 5.29; found C 75.35, H 8.03, N 5.25.
X-ray Crystallographic Study: Data sets were collected with Enraf
Nonius CAD4 and Nonius KappaCCD diffractometers, in case of
Mo-radiation equipped with a rotating anode generator. Programs
used: data collection EXPRESS (Nonius B.V., 1994) and COL-
LECT (Nonius B.V., 1998), data reduction MolEN (K. Fair, Enraf–
Nonius B.V., 1990) and Denzo-SMN,[60] absorption correction for
CCD data SORTAV[61,62] and Denzo,[63] structure solution
SHELXS-97,[64] structure refinement SHELXL-97,[65] graphics
SCHAKAL-97 (E. Keller, 1997) and DIAMOND.[66]
CCDC-261423 (for 32), -261424 (for 19a with 1,3,5-triacetylben-
zene), -261425 (for 19b with caffeine), and -261426 (for 19c with
caffeine) contain the supplementary crystallographic data
for this paper. These data can be obtained free of charge at
www.ccdc.cam.ac.uk/conts/retrieving.html
[or
from
the
Cambridge Crystallographic Data Centre, 12 Union Road, Cam-
bridge CB2 1EZ, UK; Fax: +44(1223)336-033, E-mail:
deposit@ccdc.cam.ac.uk].
X-ray
C37H38N2O3·2C3H6O·H2O,
0.30×0.25×0.18 mm,
Crystal
Structure
Analysis
692.87, colorless crystal
13.233(1), 13.129(1),
for
32:
formula
M
=
a
=
b
=
c =
21.811(1) Å, β = 97.78(1)°, V = 3754.5(4) Å3, ρcalc = 1.226 g·cm–3,
μ = 0.81 cm–1, empirical absorption correction (0.976 T Յ 0.986),
Z = 4, monoclinic, space group P21/n (No. 14), λ = 0.71073 Å, T
= 198 K, ω and φ scans, 14468 reflections collected ( h, k, l),
[(sinθ)/λ] = 0.62Å–1, 7624 independent (Rint = 0.034) and 5004 ob-
served reflections [I Ն 2 σ(I)], 477 refined parameters, R = 0.053,
wR2 = 0.133, max. residual electron density 0.34 (–0.32) e·Å–3, hy-
drogen atoms at nitrogen atoms and water from difference Fourier
calculations, other calculated and refined as riding atoms.
Acknowledgments
The work was supported by the Deutsche Forschungsgemeinschaft
and the State of Northrhine-Westfalia (Bennigsen-Foerder-Award).
Some chiral amines were kindly donated by BASF AG. M.C.S. and
D.M. thank the Fonds der Chemischen Industrie for stipends.
[1] J. W. Steed, J. L. Atwood, Supramolecular Chemistry, John
Wiley & Sons, Chichester, 2000.
[2] P. D. Beer, P. A. Gale, D. K. Smith, Supramolecular Chemistry,
Oxford University Press, New York, 1999.
[3] B. J. Postnikova, E. V. Anslyn, Tetrahedron Lett. 2004, 45, 501–
504.
[4] G. Heinrichs, L. Vial, J. Lacour, S. Kubik, Chem. Commun.
2003, 1252–1253.
X-ray Crystal Structure Analysis for 19a with 1,3,5-Triacetylben-
zene: formula C72H78N6O9·C12H12O3·1.5CH2Cl2·2CH3OH, M =
1567.09, yellow crystal 0.35×0.25×0.1 mm, a = 15.347(2), b =
22.926(2), c = 24.639(2) Å, V = 8669.1(15) Å3, ρcalc = 1.201 g·cm–3,
μ = 14.74 cm–1, empirical absorption correction via ψ scan data
(0.627 Յ T Յ 0.809), Z = 4, orthorhombic, space group P212121
(No. 19), λ = 1.54178 Å, T = 223 K, ω/2θ scans, 9617 reflections
collected (+h, –k, +l), [(sinθ)/λ] = 0.62Å–1, 9617 independent and
4351 observed reflections [I Ն 2 σ(I)], 974 refined parameters, R =
0.086, wR2 = 0.226, max. residual electron density 0.65 (–0.39)
e·Å–3, hydrogen atoms at nitrogen atoms from difference Fourier
calculations, other calculated and refined as riding atoms, one
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isotropic thermal displacement parameters, one methanol refined
with split positions, due to the disorder the accuracy of the analysis
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X-ray Crystal Structure Analysis for 19b with Caffeine: formula
C72H75Br3N6O9·C8H10N4O2·3C7H8, M = 1878.71, colorless crystal
0.45×0.30×0.10 mm,
a = 18.464(1), b = 22.110(1), c =
22.449(1) Å, V = 9164.6(8) Å3, ρcalc = 1.362 g·cm–3, μ = 21.66 cm–1,
empirical absorption correction (0.442 Յ T Յ 0.813), Z = 4, ortho-
rhombic, space group P212121 (No. 19), λ = 1.54178 Å, T = 223 K,
ω and φ scans, 40740 reflections collected ( h, k, l), [(sinθ)/λ]
= 0.59 Å–1, 14381 independent (Rint = 0.039) and 12443 observed
reflections [I Ն 2 σ(I)], 1029 refined parameters, R = 0.080, wR2 =
0.226, max. residual electron density 1.11 (–0.67) e·Å–3, hydrogen
atoms at nitrogen atoms from difference Fourier calculations, other
calculated and refined as riding atoms, caffeine was refined with
geometrical constraints and isotropic thermal displacement param-
eters, one toluene with anisotropic thermal parameters, one with
isotropic ones, and the third with a common isotropic one, the
last two also with geometrical constraints; due to the disorder the
accuracy of the analysis is poor.
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2998
© 2005 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
Eur. J. Org. Chem. 2005, 2987–2999

Synthesis of Rigid Receptors Based on Triphenylene Ketals
FULL PAPER
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[56] For further information about the assignment of α and β see
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B. S. Freed, B. E. Kurys, US 4,791,107. Received: February 9, 2005
Eur. J. Org. Chem. 2005, 2987–2999
www.eurjoc.org
© 2005 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
2999