Synthesis and supramolecular structures of molecular clips

Article abstract of DOI:10.1016/S0040-4020(01)00230-7

The syntheses of the novel dimethylene-bridged clips 4a-e and 5b are reported. They selectively bind electron-deficient neutral and cationic aromatic substrates comparable to the tetramethylene-bridged tweezers 1 and 2. The geometry of the noncovalently bound complexes with 4b-d as receptors derived from the single-crystal structure analyses is, however, different from that of the complexes with 2 as receptor. In clip complexes the plane of the included aromatic substrate molecule is orientated almost parallel to the naphthalene side-walls of the clip, whereas in the tweezer complex the substrate is orientated parallel to the central arene spacer-unit. TCNB 19 as substrate is placed inside the cavity of the hydroquinone clip 4c in solution as well as in the cocrystal. In contrast it was found for the cocrystal with the diacetate clip 4b that the TCNB 19, is placed between the naphthalene side-wall of two different clip molecules whereas in solution 19 is included into the cavity of 4b. Finally, 19 forms a (1:2) complex with dinaphthonorbornadiene 20 in solution as well as in the crystalline state. The findings reported here are instructive for the understanding of the weak noncovalent binding forces particularly the arene-arene interaction.

Full text of DOI:10.1016/S0040-4020(01)00230-7

TETRAHEDRON
Pergamon
Tetrahedron 57 32001) ꢀ67ꢀ±ꢀ687
Synthesis and supramolecular structures of
molecular clips
a,p
Frank-Gerrit Kl aÈ rner, Jens Panitzky, Dieter Bl aÈ ser and Roland Boese
a
b
b,p
a
Institut f uÈ r Organische Chemie, Universit aÈ t Essen 45117 Essen, Germany
Institut f uÈ r Anorganische Chemie, Universit aÈ t Essen, 45117 Essen, Germany
b
Received 4 September 2000; accepted 29 November 2000
AbstractÐThe syntheses of the novel dimethylene-bridged clips 4a±e and 5b are reported. They selectively bind electron-de®cient neutral
and cationic aromatic substrates comparable to the tetramethylene-bridged tweezers 1 and 2. The geometry of the noncovalently bound
complexes with 4b±d as receptors derived from the single-crystal structure analyses is, however, different from that of the complexes with 2
as receptor. In clip complexes the plane of the included aromatic substrate molecule is orientated almost parallel to the naphthalene side-
walls of the clip, whereas in the tweezer complex the substrate is orientated parallel to the central arene spacer-unit. TCNB 19 as substrate is
placed inside the cavity of the hydroquinone clip 4c in solution as well as in the cocrystal. In contrast it was found for the cocrystal with the
diacetate clip 4b that the TCNB 19, is placed between the naphthalene side-wall of two different clip molecules whereas in solution 19 is
included into the cavity of 4b. Finally, 19 forms a 31:2) complex with dinaphthonorbornadiene 20 in solution as well as in the crystalline state.
The ®ndings reported here are instructive for the understanding of the weak noncovalent binding forces particularly the arene±arene
interaction. q 2001 Elsevier Science Ltd. All rights reserved.
1
. Introduction
de®cient aromatic and aliphatic substrates as well as organic
cations via a clipping mechanism whereas electron-rich
arenes or anions are not bound by 1 or 2. This high selec-
tivity has been correlated with markedly negative molecular
electrostatic potentials 3MEPs) calculated for the concave
sides of 1 and 2 by using semi-empirical and quantum
The processes of molecular recognition and self-assembly
are of central importance in many areas of biological and
supramolecular chemistry, e.g. in enzyme±substrate bind-
ing or antigen±antibody recognition as well as in the design
1
10
of new materials by molecular self-assembly. Both
chemical methods. When analogous calculations were
processes depend on speci®c, mostly noncovalent recep-
tor±substrate interactions. Besides the relatively strong
and therefore often dominating hydrogen bonding, ion-
performed for the electron-de®cient substrates, the comple-
mentary nature of their electrostatic potentials to those
inside the cavity of 1 or 2 became evident suggesting the
relatively strong receptor±substrate binding to be predomi-
nantly of electrostatic nature. In order to investigate the
effect of the receptor topology on the substrate speci®ty
the number of methylene bridges shall be reduced from
2
ꢀ
4
pairing, and the hydrophobic effects in aqueous media,
the noncovalent interactions of arenes with other aromatic
5
units 3p±p or arene±arene interaction) or with positively
6
charged ions 3cation±p interaction) seem to be particularly
1
1
important for the formation of supramolecules. The design
of ef®cient synthetic receptors with the ability of selective
substrate binding requires precise control of their topologi-
cal and electronic properties. Besides the frequently used
cyclic and, hence, well preorganized receptors of the cyclo-
four in the molecular tweezers 1 and 2 to three in 3 and
two in 4 and 5. We call the new receptor molecules 3, 4, and
5 molecular clips because they form complexes by clipping
the substrates between their two side arms. From the calcu-
lation of electrostatic potential surfaces 3EPSs, Scheme 1)
we expect the trimethylene- and dimethylene-bridged clips
3±5 to selectively bind electron-de®cient substrates
comparable to the tetramethylene-bridged tweezers 1 and
2. But due to their more open cavities the clips 3±5 are
expected to be less speci®c to the shape and size of the
substrate than 1 and 2. Here we report the synthesis of the
dimethylene-bridged clips 4 and 5 and their binding
properties towards various neutral and cationic aromatic
substrates preferentially in the crystalline state. The receptor
properties of 5 and 4 in solution will be discussed
7
phane-type , noncyclic receptors with cavities of ¯exible
8
size proved to be effective. Recently, we have described
the synthesis of the benzene- and naphthalene-spaced recep-
9
tors 1 and 2 which belong to a family of molecules termed
molecular tweezers due to their concave±convex topology
and propensity to selectively form complexes with electron-
Keywords: molecular clips; synthesis; supramolecular chemistry; single-
crystal structure; analysis.
p
Corresponding authors. Fax: 1201-18ꢀ4252;
e-mail: klaerner@oc1.orgchem.uni-essen.de
1
2
elsewhere.
0040±4020/01/$ - see front matter q 2001 Elsevier Science Ltd. All rights reserved.
PII: S0040-4020301)002ꢀ0-7

ꢀ674
F.-G. Kl aÈ rner et al. / Tetrahedron 57 (2001) 3673±3687
2
1
Scheme 1. Structures and EPSs of molecular tweezers and clips calculated by AM1 are depicted. The color code spans from 225 3red) to 125 kcal mol
21
3blue). The most negative MEPs in kcal mol on the concave and convex side of the parent molecular tweezer 1a and clips 3a, 4a calculated with semi-
empirical AM1, ab initio HF/6-ꢀ1G , and DFT pBP/DN are given in parenthesis.
p
p
p
2
. Synthesis of the dimethylene-bridged clips
a±e and 5b
which can be also used as a precursor of 7 at high tempera-
ture 31508C). In the presence of a dienophile such as maleic
anhydride or N-phenyl maleic imide 7 reacts with these
trapping reagents leading to the corresponding naphthalene
derivatives after double HBr elimination under the condi-
4
First, we tried to synthesize the clip molecule 4b via
repetitive Diels±Alder cycloadditions of o-quinodimethane
1
6
3
2
generated in situ by thermolysis of benzocyclobutene at
tions of reaction. Later in 1986 Paddon-Row and Patney
1
008C) to the bisdienophile 8 followed by oxidative
ꢀ
14
used this method to annelate naphthalene-units to nor-
bornene and norbornadiene systems. In our ®rst experiments
using the conditions 3658C, NaI, DMF) reported by Cava
DDQ aromatization of the tetralene-units in the primary
2:1) Diels±Alder cycloadduct 3DDQÐ2,ꢀ-dichloro-5,6-
1
5
3
16
dicyano-1,4-benzoquinone). The 32:1) Diels±Alder adduct
could be isolated in almost quantitative yield, but the DDQ
oxidation, tried under various conditions, failed up to date,
only decomposition of the starting material has been
observed. The successful synthesis of 4b starts with the in
situ generation of dibromo-o-quinodimethane 7 by 1,4-Br2
elimination from tetrabromo-o-xylene 6 with sodium iodide
as nucleophile. This reaction has been already described by
and Paddon-Row for the reaction of 6 with 8 only 5% of
the desired product 4b could be isolated from a brownish-
black oil. We assume that the reaction of the acetate
functions in the product 4b and the dienophile 8 with the
hydrogen bromide generated during the reaction leads to a
decomposition of 4b and 8, respectively. The yield of 4b
could be improved to 6ꢀ% by the addition of an excess of
triethylamine which binds the HBr as triethylammonium
bromide. 4b Can now be synthesized in 8ꢀ% yield under
the optimized conditions given in Scheme 2and Section 5
which, however, have to be carefully controlled. At higher
1
5
Cava and Shirley in 1960. In the absence of a trapping
reagent 7 formed as an intermediate undergoes an electro-
cyclic ring-closure leading to dibromobenzocyclobutene 11,

F.-G. Kl aÈ rner et al. / Tetrahedron 57 (2001) 3673±3687
ꢀ675
Scheme 2. Synthesis of the naphthalene, benzene-spaced clip 4b, electrocyclic ring-closure of dibromo-o-quinodimethane 7.
temperature and pressure a substantial amount of anti-
con®gurated product 13 3up to 50%) is formed presumably
by HBr-catalyzed rearrangement of one of the benzo-
norbornadiene-units either in the bisdienophile 8 3leading
to 12) or the 31:1) Diels±Alder adduct between 7 and 8
after HBr elimination. 13 can be also prepared by the
reaction of 6 with the anti-con®gurated bisdienophile 12
in 55% yield. The synthesis of the naphthalene naphtha-
lene-spaced clip 5b 3yield: 79%) proceeds analogously to
leads to the hydroquinone clip 4c. The addition of phenyl-
hydrazine prevents the air oxidation of 4c to the correspond-
ing quinone clip which smoothly occurs under the basic
1
2
conditions in the absence of phenylhydrazine. The parent
hydrocarbon clip 4a can be obtained by the esteri®cation of
the hydroquinone 4c to the ditri¯ate 4e with tri¯uoro-
methanesulfonic anhydride followed by the Pd-catalyzed
1
7
reduction of 4e with formic acid. In the synthesis of the
dimethoxy derivative 4d it is not necessary to isolate the
hydroquinone 4c after the hydrolysis of 4b. The methylation
of 4c was performed by addition of methyl iodide and
potassium tert-butoxide to the mixture of hydrolysis. The
structures of all new compounds were assigned by their
spectroscopic data given in the experimental section and
1
4
that of 4b starting from 6 and the bisdienophile 10
Scheme ꢀ).
3
The clip derivatives 4a, 4c±e can be synthesized starting
from 4b 3Scheme 4). Basic hydrolysis of the diacetate 4b
Scheme 3. Synthesis of the anti-con®gurated compound 13 and the naphthalene, naphthalene-spaced clip 5b.

ꢀ676
F.-G. Kl aÈ rner et al. / Tetrahedron 57 (2001) 3673±3687
Scheme 4. Transformation of the diacetate clip 4b to the hydroquinone clip 4c, the dimethoxy-clip 4d, and the parent hydrocarbon clip 4a.
the single-crystal structure analyses discussed in the
following paragraph.
intermolecular slipped face-to-face interactions between
the naphthalene-units and CH±p interactions between the
CH -bridge hydrogen atoms of one clip and the
2
naphthalene-unit of another clip.
3. Single-crystal structures of 4b, 13 and of
supramolecules with the clips 4b, 4c, and 4d as receptors
In solution the dimethylene-bridged clip molecules 4 and 5
function as receptors comparable to the tetramethylene-
bridged tweezers 1 and 2. However, the clips generally
form weaker complexes with aromatic substrates than the
Crystallization of 4b from a mixture of ethanol and
dichloromethane in the presence of pyrazine gave 4b as
colorless plates suitable for a single-crystal structure
analysis shown in Fig. 1. The crystal packing is character-
ized by introducing one methyl group of each molecule into
9
,12
tweezers.
Exceptions are larger substrates such as 2,4-
dinitrophenylhydrazine 314), 2,4-dinitro¯uorobenzene 315),
or 10,10-dicyano-2,4,7-trinitro¯uorenylidene 316) which,
for example, bind to the clip 4b and 4c, respectively, in
chloroform with an signi®cant association constant
Ê
the neighboring cavity, thus expanding the clip by 1.4 A
compared to the empty clip 4b observed in the
cocrystals of 4b and 1,2,4,5-tetracyanobenzene 3TCNB)
2
1
3K
218C) but do not show any association to the tweezer
ˆ2 8 31 4 @ 4b), ꢀ0 315 @ 4b), and 46 M 316 @ 4c),
a
1
9 3Fig. 7) and calculated by semi-empirical AM1 and
p
1
molecules 1 and 2 within the limits of H NMR detection
3Scheme 5).
DFT pBP/DN 3vide infra). This demonstrates that in this
system the methyl group has a repulsive effect in contrast to
the arenes mentioned below.
The single-crystal structure analyses of the complexes
between 4b, 4c, and 4d as receptors and p-dinitrobenzene
17, N-ethyl-4-carbethoxypyridinium triiodide 18, and tetra-
cyanobenzene 19 as substrates provide an explanation to
the question, why the clip molecules 4 are less ef®cient
receptors than the tweezer molecules 1 and 2. The
1
3 Was obtained in two pseudopolymorphic crystalline
forms from recrystallization in acetonitrile, one containing
solvent molecules in the crystal lattice, and the other
one solvent-free. Fig. 2shows that the molecules of 13 are
densely packed in both crystal lattices employing
Figure 1. Single-crystal structure analysis of 4b.

F.-G. Kl aÈ rner et al. / Tetrahedron 57 (2001) 3673±3687
ꢀ677
Figure 2. Single-crystal structure analysis of 13. Solvent-free crystal 3top); the crystal contains 13 and CH CN in a 31:2) ratio 3bottom). Every second line
ꢀ
corresponds to a different level in both crystals.
Scheme 5. Substrates noncovalently bound to the clip molecules 4b and 4c, respectively.

ꢀ678
F.-G. Kl aÈ rner et al. / Tetrahedron 57 (2001) 3673±3687
Figure 3. Single-crystal structure analysis of cocrystals containing complex 17 @ 4d and ethanol 3not shown) in a 31:2) ratio.
single-crystal structure of cocrystals containing the complex
7 @ 4d and ethanol in a 31:2) ratio obtained from the
4d 3Fig. ꢀ). The increase in steric strain resulting from this
1
compression certainly leads to a weakening of the supra-
molecular complex. This conclusion is also supported by the
single-crystal structure of the solvent-free complex 17 @ 4d
obtained by keeping the cocrystals in a mixture of ethanol
and dichloromethane in a sealed ¯ask for a longer period of
time 3about 1.5 years). 17 @ 4d has a remarkably packing
containing four complexes in the asymmetric unit with a
slightly different arrangement of the substrate 17 inside
the cavity of 4d in each complex 3Fig. 4). All of them
obviously correspond to different enthalpies, slightly
above the global minimum, thus paying for a higher packing
density 3Fig. 4).
crystallization of 17 and 4d from ethanol/dichloromethane
shows that the substrate molecule 17 is placed inside the
cavity of 4d with its plane of molecule almost parallel to
the naphthalene side-walls of the receptor contrary to the
geometry of the hitherto known complexes of the tweezer 2
as receptor where the plane of the substrate molecule is
9
arranged parallel to the central naphthalene spacer-unit.
In order to gain attractive noncovalent substrate±receptor
interactions the distance between the naphthalene side-
walls, apparently, have to be compressed from about
Ê Ê
0.0 A in the empty receptor to 7.6 A in the complex 17 @
1
Figure 4. Single-crystal structure analysis of solvent-free complex 17 @ 4d.

F.-G. Kl aÈ rner et al. / Tetrahedron 57 (2001) 3673±3687
ꢀ679
Figure 5. Single-crystal structure analysis of complex 18 @ 4b.
Ê
Similar results are obtained for the complex between the
pyridium salt 18 and diacetate clip 4b. In solution the related
N-ethyl-4-carbmethoxypyridinium iodide forms a relatively
from 10.0 to 8.ꢀ A. Remarkable is the orientation of the
negatively polarized carbonyl oxygen of 4b toward the
positively charged nitrogen atom of substrate 18 3distance
2
1
1
Ê
strong complex with 4b as receptor 321.08C: K ˆ1ꢀ7 M
3O´´´N )ˆꢀ.70 A).
a
CDCl ). The crystals suitable for the single-crystal structure
ꢀ
analyses 3Fig. 5) were obtained by cocrystallization of a
3
Interesting cases are the complexes between tetracyano-
benzene 3TCNB) 19 as substrate and the dimethoxy-, di-
acetoxy-, and dihydroxy-substituted clips 4d, 4b, and 4c
as receptors. In solution no complex formation between
1:10) mixture of 4b and N-ethyl-4-carbmethoxypyridium
iodide from ethanol and dichloromethane at the air. Under
these conditions, apparently, a partial air-oxidation of the
iodide ions to iodine and transester®cation of the carbo-
methoxy group to the carbethoxy group took place leading
to the salt 18 which gave the observed brownish colored
cocrystals of 18 @ 4b. The distance between the two naph-
thalene side walls is again reduced in the complex 18 @ 4b
1
19 and 4d is observed within the limits of H NMR
detection. In the cocrystals obtained from a mixture of
1
2
19 and 4d in chloroform a CHCl molecule is positioned
ꢀ
inside the cavity of 4d whereas 19 is located between two
naphthalene-units outside the cavity of 4d 3Fig. 6).
ꢀ
Figure 6. Single-crystal structure analysis of the cocrystals of 4d, 19, and CHCl in a 31:1:1) ratio.

ꢀ680
F.-G. Kl aÈ rner et al. / Tetrahedron 57 (2001) 3673±3687
Figure 7. Comparison between the structure of the cocrystals of 4b and 19 and the complex 19 @ 4b in solution.
More surprising is the structure of the cocrystals between 19
and 4b obtained from toluene and dichloromethane. In
solution the diacetate clip 4b binds TCNB 19 inside the
cavity whereas in the cocrystal 19 is again located between
two naphthalene-units outside the cavity of 4b which is
empty in this case 3Fig. 7). Evidently, in the crystal the
noncovalent interaction between 19 and the naphthalene-
units of two different clip molecules is stronger than the
The hydroquinone clip 4c forms a much stronger
complex with TCNB 19 than the diacetate clip 4b most
likely because of the additional O±H´´´N hydrogen
bonds 3Fig. 8) and the smaller steric demand of the OH
function in 4c in comparison to that of the more bulky
OAc or OMe substituent in 4b and 4d, respectively. In
this case the substrate 19 is bound inside the cavity of 4c
in both states, in the crystalline state and as well in
solution.
`
intramolecular' interaction between 19 and the two
naphthalene-units of one and the same clip molecule
because in the ®rst 3observed) case no distortion of the
clip geometry is necessary whereas in the second case a
compression of the naphthalene side walls and, hence, an
increase in steric strain is required for an optimal substrate±
receptor interaction. Therefore the geometry of 4b @ 19 is
taken as a reference for the noncomplexed structure, which
also agrees to the geometry found in semi-empirical AM1
Encouraged by the results obtained for the complex forma-
tion between the clips 4b±d and TCNB 19 we studied the
potential receptor properties of dinaphthonorbornadiene
3DNN) 20 which was synthesized by the reaction of nor-
bornadiene with tetrabromo-o-xylene 6 and sodium iodide
1
6
1
in DMF. In the solution-state H NMR spectrum
3500 MHz, CDCl ) of a mixture of TCNB 19 and DNN 20
ꢀ
p
and DFT pBP/DN calculations. In solution, however, the
3
a large complexation-induced up ®eld-shift of the TCNB
protons 3Dd) is observed. The dependence of Dd from the
concentration [20] at a constant concentration [19] can be
2:1) arrangement of 4b and 19 observed in the crystal is
certainly disfavored because of the highly negative
entropy term expected for the formation of a trimolecular
associate.
1
8
best ®tted by the use of the hostest program with the
formation of 32:1) complex between 20 and 19 leading to

F.-G. Kl aÈ rner et al. / Tetrahedron 57 (2001) 3673±3687
ꢀ681
1
Figure 8. Single-crystal structure, association constant, and maximum complexation-induced H NMR shift 3in CDCl
ꢀ
) of the complex 19 @ 4c.
1
Figure 9. Dependence of the complexation-induced H NMR shift 3Ddˆdobs2d
0 ꢀ
) of 19 3500 MHz, CDCl ) from the concentration of [20] at a constant
2ꢀ
concentration [19]
0
ˆꢀ.4£10 M 3d 319)ˆ8.25).
0

Figure 10. Single-crystal structure analysis of the complex 19 @ 2 2´ 0.

F.-G. Kl aÈ rner et al. / Tetrahedron 57 (2001) 3673±3687
Table 1. Crystal data obtained from the X-ray analyses
ꢀ68ꢀ
Compound
4b
13
13´2´CH CN
ꢀ
17 @ 4d´2´EtOH
17 @ 4d
T
meas. 3K)
20ꢀ 32)
29ꢀ 32)
29ꢀ 32)
9.775 31)
15.ꢀ75 3ꢀ)
11.ꢀ55 32)
29ꢀ 32)
17.ꢀ1ꢀ 3ꢀ)
21.817 35)
9.209 32)
22ꢀ 31)
a
a
a
Ê
A 3A)
B 3A)
Ê
C 3A)
a 38)
b 38)
g 38)
V 3A )
Z
r
m 3mm
SG
N
total
u
N
R
N
N
R
wR
14.202 32)
25.481 34)
7.ꢀ68 31)
10.7ꢀ0 32)
8.865 31)
27.421 34)
17.401 35)
18.842 36)
19.806 36)
104.716 37)
92.562 37)
94.68236)
6245 3ꢀ)
8
Ê
110.87 31)
ꢀ
Ê
2666.4 37)
4
2608.ꢀ 37)
4
1594.5 34)
2
ꢀ478 31)
4
1.ꢀ50
2ꢀ
calc 3g cm
)
1.ꢀ021.ꢀꢀ1 59
0.084
Pnma
244ꢀ4
24.99
2ꢀ94
0.09ꢀ
1.2 1.ꢀ57
21
)
0.086
Pbca
16565
24.72
2225
0.0416
1671
181
0.05520.0551
0.1ꢀ8ꢀ
0.081
0.094
Pbcn
22652
24.99
2710
0.0ꢀ27
2156
257
0.0708
0.091
Å
P1
ꢀ1022
25.00
21995
0.0ꢀ77
1ꢀ944
1728
P2
12210
26.46
2761
0.042ꢀ
1
/n
max 38)
indep
merg
obs [4s3F)]
1612
214
20ꢀ8
209
param
1
0.06ꢀ1
0.180ꢀ
0.0612
2
3all data)
0.1544
0.1784
0.212ꢀ
a
Ed's of cell dimensions multiplied by 10 due to a known error in diffractometer software.
up ®eld-shift of the TCNB protons in the complex 19 @
´20 of Ddmaxˆ6.0 which is comparable to that observed
4. Conclusions
2
9
for the 31:1) complex 19 @ 1a 3Dd ˆ5.9). The attempt,
max
The bismethylene-bridged clips 4 reported here preferen-
tially bind electron-de®cient neutral and cationic aromatic
substrates comparable to the tetramethylene-bridged
tweezers 1 and 2. The geometry of the noncovalently
bound complexes with 4b±d as receptors derived from the
single-crystal structure analyses is, however, different from
that of the complexes with 2 as receptors. In the clip
complexes the substrate is placed inside the receptor cavity
with its plane of molecule orientated almost parallel to the
naphthalene side-walls of the receptor whereas in the
tweezer complexes the substrate is orientated parallel to
the central arene spacer-unit.
to ®t the experimental data to the formation of a 31:1)
complex between 19 and 20, leads to an high Ddmaxˆ7.0
3
Fig. 9).
The results determined for the association between 19 and
0 in solution are in good agreement with single-crystal
2
structure of the cocrystals obtained from the crystallization
of a 31:1.ꢀ) mixture of 20 and 19 in toluene. In the crystal-
line state the complex shows an optimal arrangement of the
TCNB molecule between the two DNN molecules without
any distortion of the receptor geometry experiencing attrac-
Ê
tive CH±p 3distance 3CH´´´p)ˆ2.5 A) and slipped face-to-
Ê
face p±p interactions 3distance: ꢀ.4 A between TCNB and
naphthalene, Fig. 10).
The ®ndings, that TCNB 19 is positioned inside the cavity
of the hydroquinone clip 4c in solution as well as in the
Table 2. Crystal data obtained from the X-ray analyses
Compound
18 @ 4b
19, 4d, and ´CHCl
ꢀ
19, 4b
29ꢀ 32)
9.685 3ꢀ)
29.826 39)
12.60ꢀ 3ꢀ)
19 @ 4c
19 @ 2 2´ 0
T
a 3A)
b 3A)
meas. 3K)
24ꢀ 32)
29ꢀ 32)
26ꢀ 32)
29ꢀ 32)
a
Ê
20.ꢀ55 39)
19.055 38)
21.922 39)
9.672 31)
ꢀ0.01ꢀ 31)
12.9ꢀ9 31)
8.20ꢀ 3ꢀ)
19.700 37)
19.702 37)
10.ꢀ78 32)
15.671 32)
12.668 31)
Ê
Ê
c 3A)
a 38)
b 38)
g 38)
V 3A )
Z
rcalc 3g cm
m 3mm
SG
N
total
107.4ꢀ 31)
ꢀ
Ê
850ꢀ 36)
8
ꢀ755.9 35)
4
ꢀ640 32)
4
ꢀ184 32)
4
1966 31)
4
2ꢀ
)
2.255
1.700
1.ꢀ51
0.289
Pnma
12677
24.75
2908
0.044ꢀ
242ꢀ
258
1.286
0.087
Pnma
2ꢀ612
25.00
ꢀ197
0.08ꢀ7
1781
268
1.287
0.081
1.289
0.076
21
)
Pbca
797ꢀ6
2ꢀ.ꢀ6
7485
0.0ꢀ76
Pna2
5864
1
P2
47ꢀ9
27.49
4499
0.0ꢀ50
1
/n
u
max 38)
25.66
5864
0.0994
298ꢀ
4ꢀꢀ
N
indep
R
N
N
merg
obs [4s3F)]
522ꢀ
518
2470
272
param
R
wR
1
0.04620.0690
0.1ꢀ09
0.0971
0.0644
0.2745
0.0579
0.1645
2
3all data)
0.1858
0.1611
a
Ed's of cell dimensions multiplied by 10 due to a known error in diffractometer software.

ꢀ684
F.-G. Kl aÈ rner et al. / Tetrahedron 57 (2001) 3673±3687
crystal whereas in the case of the diacetate clip 4b the
structure of the cocrystals is different from that of
the complex in solution, are particularly instructive for the
understanding of the weak noncovalent binding forces.
Finally, the surprising formation of a 32:1) complex between
dinaphthonorbornadiene 20 and TCNB 19 in the crystal as
well as in solution is a good example which shows the
geometrical orientation in supramolecules affected by
arene±arene interactions 3Tables 1 and 2).
silica gel by using EtOAc/cyclohexane 31:ꢀ) as eluent.
Digestion of the crude product after heating the suspension
in methyl tert-butyl ether 37 mL) gave 4b 31.ꢀ5 g, 8ꢀ%) as a
1
colorless solid. Mp.ꢀ008C; MS m/z 3%): 522 3100) [M ],
480 3ꢀ0) [M 2CH CO]; HRMS m/z 522.182 3calcd for
1
2
2
1
C H O , 522.18ꢀ); IR 3KBr)Uꢀ05ꢀ cm
3CH), ꢀ011
3CH), 2984 3CH), 1766 3CvO), 1211 3C±O); H NMR
ꢀ
6
26
4
1
2
3CDCl ): dˆ2.ꢀ5 3d, 2H, J319i-H, 19a-H)ˆ8 Hz, 19i-H,
ꢀ
20i-H), 2.41 3s, 6H, ±CH ), 2.60 3d, 2H, 19a-H, 20a-H),
ꢀ
4
ꢀ
7
.22 3s, 4H, 6-H, 8-H, 15-H, 17-H), 7.19 3m, 4H, 2-H,
-H, 11-H, 12-H), 7.44 3s, 4H, 5-H, 9-H, 14-H, 18-H),
.51 3m, 4H, 1-H, 4-H, 10-H, 1ꢀ-H); C NMR 3CDClꢀ):
1
ꢀ
5. Experimental
dˆ20.91 3q, ±CH ), 48.04 3d, C-6, C-8, C-15, C-17), 64.9 3t,
ꢀ
C-19, C-20), 120.08 3d, C-5, C-9, C-14, C-18), 125.24 3d,
C-2, C-ꢀ, C-11, C-12), 127.65 3d, C-1, C-4, C-10, C-1ꢀ),
5
.1. General
1
1
ꢀ2.12 3s, C-4a, C-9a, C-1ꢀa, C-18a), 1ꢀ7.18 3s, C-7, C-16),
40.723s, C-6a, C-7a, C-15a, C-16a), 145.78 3s, C-5a, C-8a,
IR: Bio-Rad FTS 1ꢀ5. UV: J1M Tidas FG Cosytec RS 422.
1
1ꢀ
H NMR, C NMR, DEPT, H,H-COSY, C,H-COSY, C,H-
COSY, NOESY, HMQC, HMBC: Bruker AVANCE DRX
C-14a, C-17a), 168.71 3s, CvO).
1
00; H NMR titration experiments: Varian Gemini XL 200;
5
5
.1.3. 7,16-Dihydroxy-ꢀ6a,8a,15a,17a)-6,8,15,17-tetra-
the undeuterated amount of the solvent was used as an inter-
nal standard. Positions of the protons of the methano bridges
are indicated by the letters i 3innen, towards the center of the
molecule) and a 3auûen, away from the center of the
molecule). MS: Fisons Instruments VG ProSpec ꢀ000
hydro-6,17:8,15-dimethanoheptacene 4c. To a stirred
suspension of 4b 30.200 g, 0.ꢀ8 mmol), phenylhydrazine
3
0.050 g, 0.46 mmol), and ethanol 315 mL) under argon at
room temperature aqueous sodium hydroxide 30.5 mL,
5%) was added. The reaction mixture became a clear solu-
1
3
70 eV). All melting points are uncorrected. Column
tion after about ꢀ0 min. After a reaction time of 1 h aqueous
HCl 30.5 mL, 15%) was added, the reaction mixture was
poured into water 350 mL), and cooled for ꢀ0 min in an
ice bath. The solution was ®ltered under argon atmosphere,
the precipitate was dried in vacuo to give 4c 30.160 g, 95%)
as a colorless solid. Mp.ꢀ008C; MS m/z 3%): 4ꢀ8 3100)
chromatography: Silicagel 0.06ꢀ±0.2mm. All solvents
were destilled prior to use.
5
.1.1. 1,4-Dihydro-1,4-methanonaphthalene-5,8-dione
1
4,19
ꢀ
modi®ed procedure).
endo-1,2,ꢀ,4-tetrahydro-1,4-methanonaphthalene-5,8-dione
100 g, 0.57 mol) in MeOH 3600 mL) was added triethyl-
To a cooled solution 3108C) of
1
1
3
[M ]; HRMS m/z [M22H] 4ꢀ6.14ꢀ 3calcd for Cꢀ2H O ,
20 2
1
2
21
amine 31 mL) and stirred for 5 h at 108C. The solution was
allowed to warm up to room temperature and stirred for
further 15 h. The solvent was removed under reduced
pressure on a rotary evaporator at 408C to give the corre-
sponding hydroquinone, which was suspended with
p-benzoquinone 36ꢀ g, 0.58 mol) in chloroform 31.5 L).
The stirred suspension was heated ®rst to 508C for 4 h and
then at 408C for 1 h. The reaction mixture was cooled to
room temperature, the precipitate of hydroquinone was
®ltered off and washed with 100 mL chloroform. The
combined chloroform layers were washed with aqueous
NaOH 3800 mL, 1%), dried over MgSO , and concentrated
4
in a rotary evaporator at 408C in vacuo to give 1,4-dihydro-
1,4-methanonaphthalene-5,8-dione 381 g, 81%) as an
orange solid. Mp 678C.
4ꢀ6.14ꢀ); IR 3KBr)Uꢀꢀ8ꢀ 3OH) cm , ꢀ049 cm 3CH),
2991 3CH), 2968 3CH), 29ꢀ2 3CH), 2860 3CH), 150ꢀ
1
3CvC), 1282 3C±O); H NMR 3CDCl
J319i-H, 19a-H)ˆ8 Hz, 19i-H, 20i-H), 2.5ꢀ 3d, 2H, 19a-H,
20a-H), 4.49 3s, 4H, 6-H, 8-H, 15-H, 17-H), 4.51 3s, 2H,
OH), 7.24 3m, 4H, 2-H, ꢀ-H, 11-H, 12-H), 7.51 3s, 4H, 5-H,
): dˆ2.45 3d, 2H,
ꢀ
2
1
ꢀ
9-H, 14-H, 18-H), 7.54 3m, 4H, 1-H, 4-H, 10-H, 1ꢀ-H);
NMR 3CDCl
C
): dˆ46.69 3d, C-6, C-8, C-15, C-17), 64.623t,
ꢀ
C-19, C-20), 119.52 3d, C-5, C-9, C-14, C-18), 125.16 3d,
C-2, C-ꢀ, C-11, C-12), 127.55 3d, C-1, C-4, C-10, C-1ꢀ),
1ꢀ1.98 3s, C-4a, C-9a, C-1ꢀa, C-18a), 1ꢀ4.ꢀ9 3s, C-6a, C-7a,
C-15a, C-16a), 1ꢀ8.89 3s, C-5a, C-8a, C-14a, C-17a), 146.5ꢀ
3s, C-7, C-16).
5.1.4. 7,16-Dimethoxy-ꢀ6a,8a,15a,17a)-6,8,15,17-tetra-
hydro-6,17:8,15-dimethanoheptacene 4d. A suspension
of 4b 30.500 g, 0.95 mmol), phenylhydrazine 30.100 g,
0.92mmol), powdered KOH 30.ꢀ00 g, 5.26 mmol) in
isopropanol 320 mL) was stirred under argon for 1.5 h at
room temperature. After addition of potassium tert-butoxide
30.100 g, 0.89 mmol) and methyl iodide 30.7 mL,
11.ꢀ1 mmol) the reaction mixture was stirred for further
1.5 h at room temperature, and then poured into aqueous
HCl 340 mL, 1 M). The solution was ®ltered, the precipitate
was puri®ed by column chromatography on silica gel by
using chloroform/n-hexane 31:1) as eluent to give 4d
30.406 g, 91%) as a colorless solid. Mp.2108C 3sublima-
5.1.2. 7,16-Diacetoxy-ꢀ6a,8a,15a,17a)-6,8,15,17-tetra-
hydro-6,17:8,15-dimethanoheptacene 4b. The mixture of
8
31.0 g, ꢀ.1 mmol), tetrabromo-o-xylene
6
310 g,
ꢀ.9 mmol), anhydrous NaI 32ꢀ g, 16ꢀ.1 mmol), anhydrous
2
CaCO 35 g, 50 mmol), and anhydrous dimethyl formamide
ꢀ
375 mL) was stirred under Ar atmosphere for ꢀ0 min at
room temperature and then heated to 558C under vacuum
3
3
100 mbar) for 5 h. The reaction mixture was poured into ice
ꢀ00 g) and the brown mixture, decolorized by the addition
of aqueous sodium hydrogen sul®te, was extracted with
dichloromethane 3ꢀ£50 mL), the combined organic layers
were ®ltered, washed with saturated aqueous sodium hydro-
gen carbonate 350 mL) and water 34£100 mL), dried over
1
1
tion); MS m/z 3%): 466 3100) [M ], 451 340) [M 2CH
],
ꢀ
1
4ꢀ5 37) [M 2OCH
, 466.19ꢀ); IR 3KBr)Uꢀ054 cm
3CH), 2951 3CH), 2920 3CH), 2826 3CH), 1504 3CvC),
]; HRMS m/z 466.198 3calcd for
ꢀ
2
1
MgSO , and concentrated in vacuo in a rotary evaporator.
C
ꢀ4
H
26
O
2
3CH), 2990
4
The residue was puri®ed by column chromatography on

F.-G. Kl aÈ rner et al. / Tetrahedron 57 (2001) 3673±3687
ꢀ685
1
2
1
1
ꢀ
7
1
284 3C±O); H NMR 3CDCl ): dˆ2.ꢀ5 3d, 2H, J319i-H,
12-H), 7.27 3s, 2H, 7-H, 16-H), 7.49 3s, 4H, 5-H, 9-H, 14-H,
18-H), 7.55 3m, 4H, 1-H, 4-H, 10-H, 1ꢀ-H); C NMR
ꢀ
1
ꢀ
9a-H)ˆ8 Hz, 19i-H, 20i-H), 2.47 3d, 2H, 19a-H, 20a-H),
.74 3s, 6H, ±OCH ), 4.47 3s, 4H, 6-H, 8-H, 15-H, 17-H),
ꢀ
3CDCl ): dˆ50.623d, C-6, C-8, C-15, C-17), 65. 72 3t,
ꢀ
.18 3m, 4H, 2-H, ꢀ-H, 11-H, 12-H), 7.44 3s, 4H, 5-H, 9-H,
4-H, 18-H), 7.51 3m, 4H, 1-H, 4-H, 10-H, 1ꢀ-H). C NMR
C-19, C-20), 116.25 3s, C-7, C-16), 119.22 3d, C-5, C-9,
C-14, C-18), 125.01 3d, C-2, C-ꢀ, C-11, C-12), 127.49 3d,
C-1, C-4, C-10, C-1ꢀ), 1ꢀ2.0ꢀ 3s, C-4a, C-9a, C-1ꢀa,
C-18a), 147.05 3s, C-6a, C-7a, C-15a, C-16a), 147.5ꢀ 3s,
C-5a, C-8a, C-14a, C-17a).
1
ꢀ
3
±
CDCl ): dˆ47.50 3d, C-6, C-8, C-15, C-17), 61.28 3q,
ꢀ
OCH ), 64.01 3t, C-19, C-20), 119.41 3d, C-5, C-9, C-14,
ꢀ
C-18), 125.2 3d, C-2, C-ꢀ, C-11, C-12), 127.55 3d, C-1, C-4,
C-10, C-1ꢀ), 1ꢀ2.05 3s, C-4a, C-9a, C-1ꢀa, C-18a), 1ꢀ9.75
3s, C-6a, C-7a, C-15a, C-16a), 145.40 3s, C-5a, C-8a, C-14a,
C-17a), 147.28 3s, C-7, C-16).
5.1.7. 7,18-Diacetoxy-ꢀ6a,9a,16a,19a)-6,9,16,19-tetra-
hydro-6,19:9,16-dimethanooctacene 5b. The mixture of
10 31.16 g, ꢀ.1 mmol), tetrabromo-o-xylene 6 310 g,
2ꢀ.9 mmol), anhydrous NaI 32ꢀ g, 16ꢀ.1 mmol), anhydrous
5
.1.5. 7,16-Bis-tri¯uormethylsulfonoxy-ꢀ6a,8a,15a,17a)-
6
,8,15,17-tetrahydro-6,17:8,15-di-methanoheptacene 4e.
To an argon-swept and magnetically stirred solution of 4c
CaCO 35 g, 50 mmol), and anhydrous dimethyl formamide
ꢀ
375 mL) was stirred under Ar atmosphere for ꢀ0 min at
room temperature and then heated to 558C under vacuum
3100 mbar) for 5 h. The reaction mixture was poured into ice
3ꢀ00 g) and the brown mixture, decolorized by the addition
of aqueous sodium hydrogen sul®te, was extracted with
dichloromethane 3ꢀ£50 mL), the combined organic layers
were ®ltered, washed with saturated aqueous sodium hydro-
gen carbonate 350 mL) and water 34£100 mL), dried over
30.100 g, 0.228), triethylamine 30.5 mL) in chloroform
310 mL) at 08C tri¯uoromethanesulfonic anhydride
30.26 g, 0.92 mmol) was added dropwise. After the addition
was completed, the cooling bath was removed, the mixture
was warmed up to room temperature, and stirred for further
ꢀ
3
0 min. The reaction mixture was poured into ice-water
20 mL), and the layers were separated. The organic layer
was washed with aqueous HCl 32£5 mL, 1 M), dried over
MgSO , and concentrated in vacuo in a rotary evaporator.
4
MgSO , and concentrated in vacuo in a rotary evaporator.
4
Puri®cation of the yellow oil by column chromatography
3silica gel, EtOAc/cyclohexane 1:ꢀ) yielded 5b as colorless
crystals as a colorless solid 31.40 g, 79%). Mp 197±2028C;
The residue was puri®ed by column chromatography on
silica gel by using chloroform/n-hexane 31:1) as eluent
and ®nally by recrystallization from ethanol to give 4e
1
1
MS m/z 3%): 5723ꢀ5) [M ], 5ꢀ0 3ꢀ0) [M 2CH CO], 488
2
1
3100) [M 22 CH CO]; HRMS m/z 572.191 3calcd for
3
tion); MS m/z 3%): 702392) [M ], 569 316) [M 2CF SO ],
0.122 g, 76%) as a colorless solid. Mp.2158C 3sublima-
p
2
1
1
21
C H O , 572.199); IR 3KBr)Uꢀ050 cm
3CH), ꢀ01ꢀ
3CH), 2984 3CH), 1760 3CvO), 1219 3C±O); H NMR
ꢀ
2
40 28
4
1
ꢀ6 3100) [M 22 CF SO ]; HRMS m/z 702.062 3calcd for
1
4
C H F O S , 702.061); IR 3KBr)Uꢀ05ꢀ cm 3CH), ꢀ021
p
ꢀ
2
2
1
2
3CDCl ): dˆ2.47 3d, H, J321i-H, 21a-H)ˆ8 Hz, 21a-H),
ꢀ
4
20
6
6
2
ꢀ
1
CH), 2980 3CH), 29ꢀ9 3CH), 2864 3CH), 1506 3CvC); H
3
2.54 3s, 2H, 22i-H, 22a-H), 2.55 3s, 6H, ±CH ), 2.60 3d,
ꢀ
2
2
NMR 3CDCl ): dˆ2.5ꢀ 3d, 2H, J319i-H, 19a-H)ˆ8 Hz,
H, J321i-H, 21a-H)ˆ8 Hz, 21i-H), 4.44 3s, 2H, 6-H, 19-
ꢀ
1
6
1
5
9i-H, 20i-H), 2.71 3d, 2H, 19a-H, 20a-H), 4.62 3s, 4H,
-H, 8-H, 15-H, 17-H), 7.27 3m, 4H, 2-H, ꢀ-H, 11-H,
2-H), 7.58 3m, 4H, 1-H, 4-H, 10-H, 1ꢀ-H), 7.60 3s, 4H,
H), 4.47 3s, 2H, 9-H, 16-H), 7.27 3m, 4H, 2-H, ꢀ-H, 12-H,
1ꢀ-H), 7.56 3s, 2H, 10-H, 15-H), 7.57 3m, 2H, 11-H, 14-H),
7.58 3s, 2H, 8-H, 17-H), 7.60 3s, 2H, 5-H, 20-H), 7.62 3m,
1
ꢀ
1ꢀ
-H, 9-H, 14-H, 18-H); C NMR 3CDCl ): dˆ48.67 3d,
2H, 1-H, 4-H); C NMR 3CDCl ): dˆ20.90 3q, ±CH ),
ꢀ
ꢀ
ꢀ
C-6, C-8, C-15, C-17), 65.4ꢀ 3t, C-19, C-20), 118.25 3q,
47.97 3d, C-6, C-19), 50.47 3d, C-9, C-16), 62.0 3t, C-21),
62.68 3t, C-22), 11ꢀ.44 3d, C-8, C-17), 119.68 3d, C-10,
C-15), 120.ꢀ7 3d, C-5, C-20), 125.21 3d, C-2, C-ꢀ), 125.24
3d, C-12, C-1ꢀ), 125.50 3s, C-7a, C-17a), 127.55 3d, C-11,
C-14), 127.69 3d, C-1, C-4), 1ꢀ2.21 3s, C-10a, C-14a),
1ꢀ2.29 3s, C-4a, C-20a), 1ꢀ7.09 3s, C-7, C-18), 1ꢀ7.ꢀ9 3s,
C-6a, C-18a), 144.78 3s, C-5a, C-19a), 146.06 3s, C-8a,
C-16a), 147.68 3s, C-9a, C-15a), 168.923s, C vO).
1
C±Fꢀ, J3C±F)ˆꢀ18 Hz), 121.27 3d, C-5, C-9, C-14,
C-18), 125.78 3d, C-2, C-ꢀ, C-11, C-12), 127.84 3d, C-1,
C-4, C-10, C-1ꢀ), 1ꢀ2.19 3s, C-4a, C-9a, C-1ꢀa, C-18a),
1ꢀ6.24 3s, C-7, C-16), 14ꢀ.51 3s, C-6a, C-7a, C-15a,
C-16a), 14ꢀ.74 3s, C-5a, C-8a, C-14a, C-17a).
5.1.6. ꢀ6a,8a,15a,17a)-6,8,15,17-Tetrahydro-6,17:8,15-
dimethanoheptacene 4a. A suspension of 4e 30.294 g,
0
0
.42mmol), 1,ꢀ-bis3diphenylphosphino)propane 30.066 g,
.16 mmol), bis3triphenylphosphino)palladium3II)chloride
5.1.8. 7,16-Diacetoxy-ꢀ6a,8b,15b,17a)-6,8,15,17-tetra-
hydro-6,17:8,15-dimethanoheptacen 13. The mixture of
12 31.0 g, ꢀ.1 mmol), tetrabromo-o-xylene 6 310 g,
3
0.0ꢀ9 g, 0.06 mmol), and formic acid 30.4 mL) in dimethyl
formamide 35 mL) and tri-n-butylamine 31 mL) was stirred
under argon at 1008C for 72h. After addition of aqueous
HCl 3ꢀ0 mL, 1.5 M), the mixture was extracted with methyl
tert-butyl ether 3ꢀ£7 mL), the combined organic layers were
washed with aqueous HCl 3ꢀ£5 mL, 1.5 M), and dried over
2ꢀ.9 mmol), anhydrous NaI 32ꢀ g, 16ꢀ.1 mmol), anhydrous
CaCO 35 g, 50 mmol), and anhydrous dimethyl formamide
ꢀ
375 mL) was stirred under Ar atmosphere for ꢀ0 min at
room temperature and then heated to 558C under vacuum
3100 mbar) for 5 h. The reaction mixture was poured into ice
3ꢀ00 g) and the brown mixture, decolorized by the addition
of aqueous sodium hydrogen sul®te, was extracted with
dichloromethane 3ꢀ£50 mL), the combined organic layers
were ®ltered, washed with saturated aqueous sodium hydro-
gen carbonate 350 mL) and water 34£100 mL), dried over
MgSO . The organic layer was concentrated in vacuo in a
4
rotary evaporator. Puri®cation of the yellow residue by
column chromatography 3silica gel, chloroform/n-hexane
1
Mp.2008C 3sublimation); IR 3KBr)Uꢀ065 cm
:1) yielded 4a as colorless crystals 30.145 g, 85%).
3CH),
992 3CH), 2951 3CH), 2924 3CH), 28ꢀ8 3CH), 1500
2
1
2
MgSO , and concentrated in vacuo in a rotary evaporator.
4
1
2
3
CvC); H NMR 3CDCl ): dˆ2.50 3d, 2H, J319i-H, 19a-
The residue was puri®ed by column chromatography on
silica gel by using EtOAc/cyclohexane 31:ꢀ) as eluent.
Recrystallization of the crude product from toluene gave
ꢀ
H)ˆ8 Hz, 19i-H, 20i-H), 2.58 3d, 2H, 19a-H, 20a-H), 4.28
3
s, 4H, 6-H, 8-H, 15-H, 17-H), 7.2ꢀ 3m, 4H, 2-H, ꢀ-H, 11-H,

ꢀ686
F.-G. Kl aÈ rner et al. / Tetrahedron 57 (2001) 3673±3687
1
3
3 30.89 g, 55%) as a colorless solid. Mp.ꢀ008C; MS m/z
%): 522 377) [M ], 480 3ꢀ8) [M 2CH CO], 4ꢀ8 3100)
a clear yellow solution. The solution was cooled down to
1
1
408C. After 12h under a slight argon stream, yellow needles
of complex 19 @ 4c suitable for single-crystal structure
analysis were obtained.
2
1
1
[
M 22 CH CO], 4ꢀ 310) [CH CO ]; HRMS m/z 522.182
p 2 ꢀ
1
2
3
calcd for C H O , 522.18ꢀ); IR 3KBr)Uꢀ06ꢀ cm 3CH),
ꢀ6 26 4
1
015 3CH), 2991 3CH), 1754 3CvO), 1208 3C±O); H
ꢀ
2
NMR 3CDCl ): dˆ2.ꢀ5 3d, 2H, J319i-H, 19a-H)ˆ8 Hz,
5.2.7. 19 @ 2´20. To a suspension of 20 30.016 g,
0.054 mmol) and 19 30.012g, 0.07 mmol) in toluene
3ꢀ mL) at 408C so much dichloromethane was added that
it became a clear yellow solution. The crystallization
occurred during slow evaporation of the solvent. After
three days, yellow plates of complex 19 @ 2 2´ 0 suitable
for single-crystal structure analysis were obtained.
ꢀ
1
±
2
7
9i-H, 20i-H), 2.47 3d, 2H, 19a-H, 20a-H), 2.49 3s, 6H,
CH ), 4.26 3s, 4H, 6-H, 8-H, 15-H, 17-H), 7.ꢀ4 3m, 4H,
ꢀ
-H, ꢀ-H, 11-H, 12-H), 7.61 3s, 4H, 5-H, 9-H, 14-H, 18-H),
.69 3m, 4H, 1-H, 4-H, 10-H, 1ꢀ-H); C NMR 3CDClꢀ):
1
ꢀ
dˆ20.84 3q, ±CH ), 48.08 3d, C-6, C-8, C-15, C-17), 64.20
ꢀ
3
t, C-19, C-20), 120.18 3d, C-5, C-9, C-14, C-18), 125.ꢀ0 3d,
C-2, C-ꢀ, C-11, C-12), 127.8 3d, C-1, C-4, C-10, C-1ꢀ),
ꢀ2.22 3s, C-4a, C-9a, C-1ꢀa, C-18a), 1ꢀ7.45 3s, C-7,
C-16), 140.66 3s, C-6a, C-7a, C-15a, C-16a), 145.99 3s,
1
5.2.8. 18 @ 4b. To a suspension of 4b 30.025 g,
0.047 mmol) and N-ethyl-4-carbmethoxypyridinium iodide
30.1 g, 0.ꢀ4 mmol) in ethanol 3ꢀ mL) at ꢀ58C so much
dichloromethane was added that it became a clear yellow
solution. The crystallization occurred during slow evapora-
tion of the solvent. After 14 days, brown bricks of complex
C-5a, C-8a, C-14a, C-17a), 168.41 3s, CvO).
5.2. Preparation of crystals suitable for single-crystal
structure analysis
18 @ 4b suitable for single-crystal structure analysis were
obtained.
5
.2.1. 4b. To a suspension of 4b 30.025 g, 0.048 mmol),
pyrazine 30.1 g, 1.25 mmol) and ethanol 3ꢀ mL) at ꢀ58C
was added so much dichloromethane that it became a
clear colorless solution. Crystallization of 4b occurred
during slow evaporation of the solvents. After one week,
colorless plates 4b suitable for single-crystal structure
analysis were obtained.
1
.3. Determination of K by H NMR titration
5
a
In the titration experiments, the total substrate concentration
S] was kept constant whereas the total receptor concentra-
tion [R] was varied. This was achieved by dissolving a
[
0
0
de®ned amount of the receptor R in 0.5 mL of a solvent
containing the substrate concentration [S] . Dd was deter-
5
.2.2. 13. The crystallization of 13 from acetonitrile occur-
ring during slow evaporation of the solvent leads to two
different type of crystals, plates containing only 13 and
needles containing 13 and acetonitril in a 31: 2) ratio.
0
mined from the chemical shift of the pure substrate and the
chemical shift of the substrate measured in the H NMR
1
spectrum 3200 MHz, 218C) of this mixture. Successive addi-
tion of further solution containing [S] led to a dilution of the
5
0
.2.3. 17 @ 4d. To a suspension of 4d 30.025 g,
.048 mmol) and 17 30.01 g, 0.06 mmol) in ethanol
0
concentration [R]0 in the mixture while [S]0 was kept
constant. Measurement of the chemical shift of the substrate
dependent from the concentration [R] afforded the data
3
2mL) at ꢀ5 8C so much dichloromethane was added that
it became a clear orange solution. Crystallization occurred
during slow evaporation of the solvents. After one week,
cocrystals containing complex 17 @ 4d and EtOH in a 31:2)
ratio suitable for single-crystal structure analysis were
obtained as orange needles. The cocrystals containing
ethanol were kept in a sealed ¯ask at room temperature
for about 1.5 years. During this time 17 @ 4d precipitates
as orange plates which do not contain ethanol.
0
pairs Dd and [R] . Fitting of the data to the 31:1) binding
0
isotherm by iterative methods delivered the parameters K
0,21
a
2
and Ddmax
.
5.4. Crystal structure determinations
X-Ray data were collected on a Brucker-SMART 1000
System, except for 19 @ 2 2´ 0, which was measured on a
Siemens P4 diffractometer. Structure solutions and re®ne-
ments were performed with the Siemens shextl-suite of
programs 3Version 5.10), hydrogen atoms were treated as
riding groups with the 1.2-fold of the corresponding
C-atom.
5
0
3
.2.4. 19 and 4b. To a suspension of 4b 30.025 g,
.048 mmol) and 19 30.012g, 0.07 mmol) in toluene
ꢀ mL) at 408C so much dichloromethane was added that
it became a clear yellow solution. The solvents were slowly
evaporated by leaving the ¯ask open. After ꢀ d, yellow
plates of complex 19 @ 4b suitable for single-crystal
structure analysis were obtained.
5.2.5. 19, 4d, and CHCl . Crystallization occurred during
3
slow evaporation of the solvent of a chloroform solution
Acknowledgements
containing 4d 30.04 g, 0.085 mmol) and 19 30.016 g,
0.089 mmol). After one week, yellow bricks containing
complex 19, 4d, and CHCl in a 31:1:1) ratio suitable for
single-crystal structure analysis were obtained.
This work was supported by the Deutsche Forschungsge-
meinschaft 3Sonderforschungsbereich). We are grateful to
Heinz Bandmann for performing the NMR measurements.
We thank Professor Craig Wilcox for the assistance to deter-
ꢀ
5.2.6. 19 @ 4c. To a suspension of 4c 30.025 g, 0.057 mmol)
and 19 30.012g, 0.07 mmol) in toluene 37 mL) at 70 8C
under argon so much chloroform was added that it became
mine Ddmax and K for the formation of 19 @ 2 2´ 0 from the
a
dependence of Dd319) from the concentration of 20 by the
use of the hostest program.

F.-G. Kl aÈ rner et al. / Tetrahedron 57 (2001) 3673±3687
ꢀ687
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8