Preparation of strained axially chiral (1,5)naphthalenophanes by photo-dehydro-diels-Alder reaction

Article abstract of DOI:10.1021/ja109118m

The preparation of 10 (1,5)naphthalenophanes (10a-j) by photo-dehydro-Diels-Alder (PDDA) reaction is described. Owing to hindered rotation around the biaryl axis, compounds 10 are axially chiral and the separation of enantiomers by chiral HPLC was demonst

Full text of DOI:10.1021/ja109118m

ARTICLE
pubs.acs.org/JACS
Preparation of Strained Axially Chiral (1,5)Naphthalenophanes by
Photo-dehydro-Diels-Alder Reaction
Pablo Wessig* and Annika Matthes
Institut f€ur Chemie, Universit€at Potsdam, Karl-Liebknecht-Strasse 24-25, D-14476 Potsdam, Germany
S Supporting Information
b
ABSTRACT: The preparation of 10 (1,5)naphthalenophanes
(10a-j) by photo-dehydro-Diels-Alder (PDDA) reaction is
described. Owing to hindered rotation around the biaryl axis,
compounds 10 are axially chiral and the separation of enantio-
mers by chiral HPLC was demonstrated in three cases (10a,b,
e). The absolute configuration of the isolated enantiomers
could be unambiguously determined by comparison of calcu-
lated and measured circular dichroism (CD) spectra. Further-
more, we analyzed ring strain phenomena of (1,5)naphthalenophanes 10. Depending on the length of the linker units, one can
distinguish three classes of naphthalenophanes. Compounds 10a-c are highly strained (ESTR = 7-31 kcal/mol), and the strain is
caused by small bond angles in the linker unit and deformation of the naphthalene moiety. Another type of strain is observed if the
linker unit becomes relatively long (10g,h) originating from transannular interactions and is comparable with the well-known strain
of medium sized rings. The naphthalenophanes 10d-f with a linker length of 10-14 atoms are only marginally strained. To clearly
discriminate the different sources of strain, we defined two geometrical parameters (average central dihedral angle δC and
naphthalene thickness DN) and demonstrated that they are well-suited to indicate naphthalene deformation of our naphthaleno-
phanes 10 as well as of ten model naphthalenophanes (I-X) with different linker lengths and linking positions.
’ INTRODUCTION
The synthesis of highly strained molecules is enjoying great
interest since many decades and is still a challenge for preparative
chemists.1 This interest has different sources. On the one hand,
many naturally occurring compounds with biological activity
have a highly strained molecular structure, and the total synthesis
of these compounds requires a repertoire of special methods. On
the other hand, highly strained molecules are unique objects for
studying unusual bonding conditions combined with high che-
mical reactivity. Furthermore, strained molecules exhibit uncom-
Figure 1. (1,5)Naphthalenophanes.
mon physical properties and interesting applications as func-
Although (1,5)naphthalenophanes were first described already
tional molecules or in material science may be expected.
more than 70 years ago by L€uttringhaus,5 there are only a limited
Molecular strain originates from bonding conditions (bond
number of reports about synthetic access to this compound class.
length, bond angles, and dihedral angles) that deviate more or
Particularly [k](1,5)naphthalenophanes with smaller linker units as
less from their equilibrium values in unstrained molecules. This
those described in this paper (k e 16) scarcely appear in the
may be due to steric hindrance or cyclic structures prohibiting
literature. Beside the pioneering work by Haenel,6 only 15 other
strain release by molecular topology. In the latter case, one refers
articles were published in the last 80 years.7
to ring strain as a special case of molecular strain. Besides small
To the best of our knowledge, all hitherto reported synthetic
rings (three- and four-membered rings) and unusual connectivity
routes to (1,5)naphthalenophanes are based on linking the
modes (e.g., propellanes or paddlanes), cyclophanes2 are often
positions 1 and 5 of an already existing naphthalene moiety.
characterized by high ring strain.
This approach is limited to naphthalenophanes with low or at
Cyclophanes are molecules consisting of an aromatic unit
best medium ring strain, but it should be difficult to prepare
(e.g., benzene, naphthalene) and a chain (which may contain
target compounds with high ring strain in this way. On the other
further aromatic units) forming a bridge between two nonadja-
hand, photochemical methods are perfectly convenient for the
cent positions of the aromatic unit. If the aromatic unit is a
naphthalene moiety, these compounds are called naphthalenophanes,3
at which the link positions are prefixed in parentheses, e.g.
Received: October 18, 2010
Published: February 7, 2011
(1,5)naphthaleno-phanes A (see Figure 1).4
r
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preparation of highly strained molecules because the excitation
energy usually overcompensates the strain buildup.
neglected here). The ring closure occurs by an attack of one of
the radical centers at the opposite aromatic ring giving cyclic
allene E. In the final step, naphthalenes F are formed by hydrogen
migration (which is mediated by the solvent in most cases,
Scheme 1).8c-8e It should be noted that R should be an acyl
group because the PDDA reaction then takes place at a longer
excitation wavelength (>300 nm) compared with R = alkyl.
On the basis of this mechanism, it should be possible to obtain
(1,5)naphthalenophanes, such as G, by irradiation of compounds
H, in which two arylynones are linked by a chain X (Scheme 1).
As a special feature, compounds G contain a chirality axis
(clarified by an asterisk in Scheme 1) and the enantiomers should
be separable. The unique combination of axial chirality, a
relatively rigid molecular structure and the cavity caused by the
cyclophane structure give reason to expect very interesting
applications of such compounds in the time to come, e.g. as
catalysts or as components in supramolecular assemblies.
Herein we describe the successful synthesis of various
(1,5)naphthalenophanes of type G, which are partly highly
strained. Furthermore, we will report on optical and chiroptical
properties as well as calculations of the ring strain of this new
compound class.
In continuation of our previous work concerning the photo-
dehydro-Diels-Alder (PDDA) reaction,8 we have investigated
whether this reaction provides an access to highly strained
(1,5)naphthalenophanes.9 In contrast to the thermally activated
Diels-Alder reaction, the PDDA reaction does not proceed
concerted but over several intermediates. Starting from an
arylynone B and an alkyne C (which is also an arylynone in
most cases and may be identical with B), a 1,4-diradical D is
formed after photochemical excitation (the role of spin state is
Scheme 1. Photo-dehydro-Diels-Alder Reaction (Left) and
Retrosynthetic Route from (1,5)-Naphthalenophanes G to H
’ RESULTS AND DISCUSSION
1. Synthesis of (1,5)Naphthalenophanes of Type G. Our
three-step sequence to the reactants for the PDDA reaction
commences with 2-iodobenzoic acid 1a, 2-iodophenyl acetic acid
1b (both are commercially available), and 3-(2-iodophenyl)-
propionic acid 1c.10 After esterification with different diols 2, the
obtained diesters 3 are subjected to a twofold Sonogashira-
coupling11 with 3-butyn-2-ol providing the bis-propargyl alco-
hols 4 as a mixture of diastereomers. In the subsequent Dess-
Martin12 or Swern13 oxidation, these diols are converted to bis-
ynones 5. The yields of these three steps are almost always good
to excellent (Scheme 2, Table 1). In the following, the chain
linking the two benzene rings is referred to as “linker”.
Table 1. Yields and Conditions of the Three-Step Synthesis
of Bis-ynones 5a-f
n
m
S-1a S-2a S-3a
M-1b
M-2b
Nc
a
b
c
d
e
f
0
1
0
1
2
2
2
2
4
4
2
4
65
62
36
56
52
44
65
99
81
99
-
69 DIC/DMAP
92 DIC/DMAP
72 DIC/DMAP
Dess-Martin
Dess-Martin
Dess-Martin
6
8
8
69 H2SO4/ DCM Dess-Martin 10
46d DIC/HOBt
Dess-Martin 10
In the case of bis-ynones 5g-j with a longer linker (N = 13-
16), another route proved to be more advantageous. It differs
from the route described for 5a-f in that initially the ynone
moiety is installed and afterward the linker is completed. Starting
89
60 DIC
Swern 12
a Yields in percent of steps 1-3. b Methods M-1, M-2; see Scheme 1.
c Number of chain atoms, N = m þ 2n þ 4. d Steps S-2, S-3.
Scheme 2. Synthesis of Bis-ynones 5a-fa
a For M-1 and M-2, see Table 1.
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with 3-(2-iodophenyl)-propionic acid 1c, the carboxylic group
is protected as tert-butyl ester (6), followed by Sonogashira
coupling with 3-butyn-2-ol (7), Swern oxidation to ynone 8, and
deprotection with trifluoroacetic acid, providing carboxylic acid
9. The bis-ynones 5g-j are obtained by esterification with
different diols (Scheme 3, Table 2).
Upon irradiation (λEXC > 300 nm, pyrex vessel) in tert-butanol
bis-ynones 5 smoothly undergo a PDDA reaction to [k](1,5)-
naphthalenophanes 10 (Scheme 4, k = N þ 2; see Tables 1-3).
It should be mentioned that we used the optimized reaction
conditions previously reported for similar PDDA reactions.8d
Despite the rather low yields, the naphthalenophanes 10 were the
sole isolable products. The remaining amount of the reactants
underwent unselective decomposition.
The structure of products 10 was unambiguously proven by
X-ray structure of compounds 10b and 10g (Figure 2, for
comparison the calculated structure of 10a is also depicted).14
In 10b, a [10](1,5)naphthalenophane, the naphthalene moiety
is strongly distorted indicating a considerable ring strain
whereas the nearly planar naphthalene moiety in the [15]-
(1,5)naphthalenophane 10g verifies a less strained molecular
skeleton. Thus, the distortion of the naphthalene moiety is a
sensitive indicator for ring strain of (1,5)naphthalenophanes
(see section 4).
Table 2. Yields and Conditions of the Synthesis of Bis-ynones
5g-j
R
esterification
DCC/DCM
yields [%]
Na
g
h
i
(CH2)5
(CH2)6
78
33
64
64
13
14
13
16
Boc2O/MgCl2/DCM
Boc2O/MgCl2/DCM
Boc2O/MgCl2/DCM
(CH2)2O(CH2)2
j
(CH2)2(O(CH2)2)2
a Number of chain atoms.
Scheme 3. Synthesis of Bis-ynones 5g-ja
2. UV Absorption and Luminescence Properties. In the
face of the above-mentioned ring strain of (1,5)naphthalenophanes
10 with shorter linkers (k e 10), we investigated the UV absorption
and luminescence properties of these compounds to find out
whether a systematic trend occurs depending on the linker length.
We chose 10a, 10b, and 10e as a typical set of (1,5)naphthaleno-
phanes with increasing k-values (k = 8, 10, 12). As shown in Figure 3,
all three compounds show absorption bands in three regions: (A)
220-260, (B) 280-310, and (C) 330-360 nm. Whereas in the
spectra of 10b and 10e, a clear vibrational fine structure is discernible,
the UV spectrum of 10a is considerably less structured. Furthermore,
the molar extinction coefficient decreases with decreasing linker
length. Particularly remarkable is the decrease of the C-band from log
ε340 = 3.4 (10e) to 2.9 (10a). Obviously, this phenomenon is caused
by a perturbation of the π-conjugation of the naphthalene moiety by
distortion (for details, see the Supporting Information (SI)).
Compounds 10a-j show a negligible luminescence at room
temperature, pointing to a very efficient intersystem crossing
a See Table 2.
Scheme 4. PDDA Cyclization of Bis-ynones 5 to [k](1,5)Naphthalenophanes 10
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Table 3. Yields of [k](1,5)Naphthalenophanes 10
ka
yield [%]
a
8
10
10
12
12
14
15
16
15
18
6
15
16
48
37
38
29
30
41
50
b
c
d
e
f
g
h
i
j
a k = N þ2.
Figure 3. UV spectra of (1,5)naphthalenophanes 10a, 10b, and 10e in
acetonitrile.
Figure 4. n-π overlap, facilitating the ISC to the triplet state.
Figure 2. Calculated structure of 10a (conformer 2, see the SI) and
X-ray crystal structures of 10b and 10g.
(ISC) to the triplet state. This behavior was already previously
observed with compounds having a 1-aryl-2-acyl-naphthalene
substitution pattern.8a An overlap between the lone pair orbitals
of the carbonyl oxygen and the π-system of the aryl ring
obviously facilitates the ISC from S1 (n f π*) to T1 (π f π*)
state by efficient spin-orbit coupling (Figure 4).
By embedding compounds 10 in a frozen EPA matrix (EPA =
diethylether/i-pentane/ethanol 5:2:1) at 77 K, we observed an
intense phosphorescence, which is consistent with the above
postulated efficient ISC. The phosphorescence spectra of 10a,
10b, and 10e are exemplarily depicted in Figure 5. The short-
wavelength 0-0-transition of these spectra is blue-shifted with
increasing length of the linker, i.e. the triplet energy is decreased
with increasing ring strain. This observation is consistent with
the idea that growing distortion of the naphthalene moiety
stabilizes the triplet state because diradical contributions gain
in importance.
Figure 5. Phosphorescence spectra of (1,5)naphthalenophanes 10a,
10b, and 10e in EPA at 77 K.
presence of a chirality axis. In view of the substitution pattern, the
barrier for the rotation around this axis should be high enough at
room temperature to separate the enantiomers.15 To prove this
hypothesis and to investigate the chiroptical properties of the
individual enantiomers, we performed various chiral HPLC runs
on different chiral stationary phases using different solvent
mixtures. The best results were obtained with a Chiralcel
OD-H column and a hexane/i-propanol (100:15) mixture as
mobile phase. The recorded chromatograms for compounds 10a,
10b, and 10e as well as the respective resolution R and separation
factors R are shown in Figure 6 (10h was also separated. For
details, see the SI). The first eluated enantiomers were called E1
The phosphorescence maxima and triplet energies of com-
pounds 10 (except for 10i,j) are summarized in Table 4.
3. Separation of Enantiomers and CD-Spectroscopy. A
special structural feature of (1,5)naphthalenophanes 10 is the
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Table 4. Phosphorescence Maxima and Triplet Energies of
[k](1,5)Naphthalenophanes 10
ka
0-0-transition [nm]
triplet energy [kcal/mol]
a
b
c
d
e
f
8
10
10
12
12
14
15
16
515
511
512
499
498
497
495
495
57.9
58.3
58.2
59.7
59.8
60.0
60.2
60.2
g
h
a For k, see Table 3.
Figure 7. CD-spectra of enantiomers E1 (see Figure 6) of 10a, 10b, and
10e in acetonitrile.
Figure 8. P- and M-enantiomers of 10.
Figure 6. Separation of enantiomers of 10a, 10b, and 10e by chiral
HPLC (R = resolution, R = separation factor, t1, t2 = retention times of
E1, E2, respectively, stationary phase = Chiralcel OD-H, mobile phase =
hexane/i-propanol, 100:15).
4. Molecular Modeling/Calculation of Ring Strain. In the
preceding sections, we concluded from several experimental
results that at least the (1,5)naphthalenophanes with short
linking units should be highly strained. Up to now, there are
only a few reports about ring strain of naphthalenophanes in the
literature.17 Due to the fundamental importance of ring strain for
the physical and chemical properties of this type of compounds,
we decided to undertake a systematic investigation of this
phenomenon by means of quantum chemical calculations. A
powerful method for the calculation of ring strain energy is the
definition of an isodesmic reaction, i.e., a hypothetical reaction in
which the type and number of chemical bonds cleaved in the
reactants are the same as the type and number of bonds formed in
the reaction products.18 In Scheme 5, the isodesmic reactions are
defined that are used for our problem. The isodesmic reactions
are based on the cleavage of one bond of the diol moiety of the
reactants 10 (normally the central bond [10a-f, 10h] or a bond
adjacent to the central atom [10g]) combined with the bond
formation from acetates (J, M, N) to diol diacetates (L, P).
The strain energy ESTR can now be defined by eqs 1 and 2
and the second eluated enantiomers E2. All three compounds were
baseline-separated, and the separation factors are, at least for 10a
and 10b, excellent. With these conditions in hand, we were able to
semipreparatively separate the enantiomers and investigate their
chiroptical properties by means of CD-spectroscopy.
The recorded CD-spectra of first-eluated enantiomers E1 are
depicted in Figure 7. They have in common a strong Cotton
effect around 220 nm, but the sign is negative for the rather
strained (1,5)naphthalenophanes 10a and 10b and positive for
10e. Furthermore, it is conspicuous that the CD spectra of 10b-
E1 and 10e-E1 are nearly perfect mirror images. This suggests
that the E1 enantiomers of 10b and 10e have opposite config-
uration. To assign the absolute configuration to the E1 enantio-
mers of 10a, 10b, and 10e, we calculated the CD spectra at the
density functional theory (DFT) level of theory (TD-B3LYP/6-
311þþG**, 30 excited states; for details, see the SI).16 In
Figure 9, the measured CD spectra are compared with the
calculated CD spectra both of M- and P-enantiomers. (For
definitions of the P- and M-enantiomers, see Figure 8). The
comparison clearly indicates that the E1 enantiomers of 10a and
10b have the same configuration (P) whereas 10e-E1 has the
opposite configuration (M) in accordance with the expectation
from the measured CD-spectra.
ESTR ¼ EðKÞ þ EðLÞ - 2EðJÞ - Eð10a - f, 10hÞ
ESTR ¼ EðPÞ þ EðOÞ - EðMÞ - EðNÞ - Eð10gÞ
ð1Þ
ð2Þ
The DFT calculations of strain energy ESTR (B3LYP/6-31G*; for
details, see the SI) turned out to be in part very expensive because
a large number of conformers have to be considered. The results
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Figure 9. Comparison of the measured (left) and calculated (right) CD spectra of 10a, 10b, and 10e.
of these calculations are summarized in Table 5. For compound
10a with the shortest linker (k = 8), we calculated a strain energy
of 31 kcal/mol, which is clearly higher than the strain energy of
cyclopropane (27.6 kcal/mol)19 and is comparable with the
reported strain energies of [2.2]paracyclophane (32.020b and
30.420g kcal/mol). Tobe et al.20e reported a strain energy of 25-
32.6 kcal/mol for [6](1,3)naphthalenophane, although these
values are based only on semiempirical calculations. On the
other hand, considerably higher strain energies were reported for
[1.1]paracyclophane (90-100 kcal/mol20f) and [4]paracyclophane
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Scheme 5. Isodesmic Reactions for the Calculation of Ring Strain of (1,5)Naphthalenophanes 10
naphthalene moieties from the calculated structures (i.e., remov-
ing the acetyl groups and the linker) and saturated the free
valences with hydrogen atoms. The strain energy of the resulting
puckered naphthalenes was obtained by comparison with the
energy of optimized perfect planar naphthalene geometry. We
found that in the case of highly strained 10a about one-fourth of
the strain energy ESRT arises from naphthalene deformation
(END = 7.1 kcal/mol) whereas three-fourths is caused by the
linker unit. We found a similar situation for (1,5)naphthaleno-
phanes 10b and c, but the contribution of END becomes
considerably higher with the less strained compounds 10d-f
(the apparently inconsistent values 10f are probably due to limits
of the used model).
Because the naphthalene moiety is relatively sensitive to
twisting forces, it should be possible to estimate the strain caused
by naphthalene deformation by evaluating ideally one geome-
trical parameter. We found that two different parameters are
comparably well-suited for this purpose. The first parameter δC is
the average central dihedral angle of the naphthalene moiety as
defined in Figure 10. It should be noted that it is not sufficient to
evaluate only one of the central dihedral angles because the
deformation caused by the (1,5)-bridge leads not only to a twist
around the axis as shown in Figure 10 but also to a small
pyramidalization of atoms 4a and 8a, and therefore, the central
dihedral angles are not identical. The second parameter suitable
for an evaluation of the naphthalene deformation is the thickness
DN. We define the thickness DN as the minimally possible height
of a cuboid surrounding all ten naphthalene carbon atoms. To
evaluate the generalizability of this approach, we extended the
calculations on ten model naphthalenophanes I-X, some of
which are considerably more strained than compounds 10. We
were particularly interested to find out whether (1,5)naphtha-
lenophanes without ester groups (I, II), without o-phenyliden
group (III-V), or naphthalenophanes with other linking posi-
tions (e.g., (1,6)naphthalenophanes VI-VIII or (1,7)naphthal-
enophanes IX, X) also exhibit the empirical correlation found for
naphthalenophanes 10. The suitability of these two parameters
δC and DN is discernible by the excellent correlation with the
naphthalene deformation energy END, as depicted in Figure 11.
(For calculation of END as well as the curve fittings, see the
Table 5. Strain Parameters of [k](1,5)Naphthalenophanes
10a-h and Model Compounds I-X
ka
Nconf
ESTR
END
δC
DN
b
c
d
e
f
a
8
10
10
12
12
14
15
16
8
8
24
31.0
7.1
7.9
2.4
164.2
169.8
172.7
177.0
177.2
178.3
179.6
179.2
162.4
170.4
151.0
157.3
163.7
154.9
165.7
161.1
171.5
176.1
0.39
0.24
0.19
0.07
0.07
0.04
0.02
0.02
0.43
0.23
0.65
0.54
0.41
0.69
0.39
0.53
0.30
0.12
b
c
32
11.8
1.1
3.0
d
32
1.0
e
80
2.4
1.1
f
92
0.0
1.1
g
148
44
7.6
1.0
h
7.0
1.0
I
8.8
II
III
IV
V
10
6
2.8
23.6
14.4
7.7
7
8
VI
VII
VIII
IX
X
6
21.9
7.2
7
8
12.3
6.1
6
8
1.5
a For k of 10a-h, see Table 3. b Number of conformers to be considered
(10a-h only). c Strain energy according to eqs 1 and 2 in kilocalories per
mole (10a-h only). d Naphthalene deformation energy in kilocalories
f
per mole. e Average central dihedral angle in degrees. Thickness of
naphthalene moiety in angstroms. (ESRT, END, δC, and DN were
calculated for the conformer with the lowest energy in each case.)
(91.3 kcal/mol20d). If the linker becomes longer by two atoms
(10b and c), the strain energy is reduced to 7.1 and 11.8 kcal/
mol, respectively, whereas naphthalenophanes 10d-f exhibit
only marginal ring strain. The relatively high strain energy of 7-8
kcal/mol for compounds 10g and h is surprising at first glance.
At this point, we decided to illuminate the origin of the ring
strain energy more precisely. As mentioned in the introduction,
both the deformation of the naphthalene moiety and unfavorable
bonding conditions in the linker unit contribute to the strain
energy.20 To isolate these two parts of strain, we have “cut off” the
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Figure 10. Definition of the average central dihedral angle δC and formulas of the model naphthalenophanes I-X.
comments in the SI). Obviously, the strain energy of the
naphthalene moiety caused by its deformation in naphthaleno-
phanes is mostly independent from the positions of the linker
(provided that they are not in the same benzene ring).
At last, we wish to return to the unexpected strain energies of
(1.5)naphthalenophanes 10g and 10h. The results summarized
in Table 5 indicate that this strain is solely derived from the linker
but not by deformation of the naphthalene moiety. Evaluating
the calculated structures of these compounds as well as the X-ray
structure of 10g reveals that in both cases some short distances of
nonbonded atoms exist which obviously cause the strain. This
phenomenon is closely related to the well-known ring strain of
medium sized cycloalkanes.21
’ CONCLUSION
In summary, we reported on the preparation of ten
(1,5)naphthalenophanes (10a-j) by photo-dehydro-Diels-Al-
der (PDDA) reaction. To the best of our knowledge, it is the first
approach in which the naphthalene moiety is constructed only in
the ring closure step of the cyclophane synthesis. Compounds 10
feature an efficient intersystem crossing (ISC) to the triplet state
upon irradiation and the triplet energies could be determined
from the phosphorescence spectra at 77 K. Due to hindered
rotation around the biaryl axis, compounds 10 are axially chiral
and the separation of enantiomers by chiral HPLC was demon-
strated in three cases (10a,b,e). The absolute configuration of the
isolated enantiomers could be unambiguously determined by
comparison of calculated and measured CD spectra. In the last
part we turned to analyzing ring strain phenomena of (1,5)-
naphthalenophanes 10. Depending on the length of the linker
units, one can distinguish three classes of naphthalenophanes.
Compounds 10a-c are highly strained (ESTR = 7-31 kcal/mol)
and the strain is caused by small bond angles in the linker unit and
deformation of the naphthalene moiety. Another type of strain is
observed if the linker unit becomes relatively long (10g,h)
originating from transannular interactions and is comparable
with the well-known strain of medium sized rings. The naphtha-
lenophanes 10d-f with a linker length of 10-14 atoms are only
Figure 11. Correlation of the naphthalene deformation energy END
with the average central dihedral angle δC (a) and the naphthalene
thickness DN (b) (10a-h [circles], I-V [triangles], VI-VIII [squares],
IX, X [diamonds]).
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ARTICLE
marginally strained. To clearly discriminate the different sources
of strain, we defined two geometrical parameters (average central
dihedral angle δC and naphthalene thickness DN) and demon-
strated that they are well-suited to indicate naphthalene defor-
mation of various (n,m)naphthalenophanes (n = 1, m = 5, 6, 7)
without the necessity of expensive calculations. After the success-
ful application of the PDDA methodology to the synthesis of
(1,5)naphthalenophanes, we are now investigating an extension
of this approach to other substitution patterns and will report on
the results in the near future.
Lee, J. Y.; Menzer, S.; Stoddart, J. F.; Venturi, M.; Williams, D. J. J. Am.
Chem. Soc. 1998, 120, 4295. (j) Rasadkina, E. N.; Nifant’ev, E. E. Russ.
J. Gen. Chem. 1999, 69, 489. (k) Ballardini, R.; Balzani, V.; Becher, J.;
Fabio, A.; Gandolfi, M. T.; Mattersteig, G.; Nielsen, M. B.; Raymo, F. M.;
Rowan, S. J.; Stoddart, J. F.; White, A. J. P.; Williams, D. J. J. Org. Chem.
2000, 65, 4120. (l) Matsuda-Sentou, W.; Shinmyozu, T. Eur. J. Org.
Chem. 2000, 18, 3195. (m) Rasadkina, E. N.; Slitikov, P. V.; Mel’nik,
M. S.; Nifant’ev, E. E. Russ. Chem. Bull. 2004, 53, 376. (n) Mathews, M.;
Tamaoki, N. J. Am. Chem. Soc. 2008, 130, 34. (o) Suzuki, K.; Mori, K.;
Ohmori, K. Angew. Chem., Int. Ed. 2009, 48, 5638.
(8) (a) Wessig, P.; M€uller, G.; K€uhn, A.; Herre, R.; Blumenthal, H.;
Troelenberg, S. Synthesis 2005, 1445. (b) Wessig, P.; M€uller, G. Chem.
Commun. 2006, 4524. (c) Wessig, P.; M€uller, G.; Herre, R.; K€uhn, A.
Helv. Chim. Acta 2006, 89, 2694. (d) Wessig, P.; M€uller, G.; Pick, C.;
Matthes, A. Synthesis 2007, 464. (e) Wessig, P.; M€uller, G. Chem. Rev.
2008, 108 (2008), 2051. (f) Wessig, P.; M€uller, G. Aust. J. Chem. 2008,
61, 569.
(9) Preparation of cyclophanes by Diels-Alder reaction: (a) Cory,
R. M.; McPhail, C. L.; Dikmans, A. J.; Vittal, J. Tetrahedron Lett. 1996, 37,
1983. (b) Maynollo, J.; Kraeutler, B. Fullerene Sci. Tech. 1996, 4, 213.
(c) Layton, M. E.; Morales, C. A.; Shair, M. D. J. Am. Chem. Soc. 2002,
124, 773. (d) Brettreich, M.; Bendikov, M.; Chaffins, S.; Perepichka,
D. F.; Dautel, O.; Duong, H.; Helgeson, R.; Wudl, F. Angew. Chem. Int.
Ed. 2002, 41, 3688. (e) Aly, A. A. Org. Biomol. Chem. 2003, 1, 756.
(f) Minuti, L.; Taticchi, A.; Lanari, D.; Marrocchi, A.; Gacs-Baitz, E.
Tetrahedron: Asymm. 2003, 14, 2775. (g) Franz, D.; Robbins, S. J.; Boere,
R. T.; Dibble, P. W. J. Org. Chem. 2009, 74, 7544Preparation of
cyclophanes by Dehydro-Diels-Alder reaction:. (h) Saito, S.; Salter,
M. M.; Gevorgyan, V.; Tsuboya, N.; Tando, K.; Yamamoto, Y. J. Am.
Chem. Soc. 1996, 118, 3970. (i) Rubin, M.; Sromek, A. W.; Gevorgian, V.
Synlett 2003, 2265. (j) Saito, S.; Yamamoto, Y. Chem. Rev. 2000, 100,
2901. (k) Gevorgyan, V.; Yamamoto, Y. J. Organomet. Chem. 1999, 576,
232.
’ ASSOCIATED CONTENT
S
Supporting Information. Synthetic procedures for all
b
new compounds including analytical data and copies of 13C-
spectra. Details of quantumchemical calculations. CD spectros-
copy, chiral HPLC, and phosphorescence measurements. This
information is available free of charge via the Internet at http://
pubs.acs.org/.
’ AUTHOR INFORMATION
Corresponding Author
*wessig@uni-potsdam.de
’ ACKNOWLEDGMENT
The financial support of this work by the Deutsche For-
schungsgemeinschaft (We1850-5/1-4 and Heisenberg fellow-
ship of P.W.) is gratefully acknowledged.
(10) Kawasaki, N.; Goto, M.; Kawabata, S.; Kometani, T. Tetrahe-
dron Asymm. 2001, 12, 585.
(11) Sonogashira, K.; Tohda, Y.; Hagihara, N. Tetrahedron Lett.
1981, 22, 3815.
(12) Dess, D. B.; Martin, J. C. J. Am. Chem. Soc. 1991, 113, 7277.
(13) Omura, K.; Swern, D. Tetrahedron 1978, 34, 1651.
(14) (a) Single-crystal X-ray diffraction analysis details of 10b were
deposited with the Cambridge Crystallographic Database, CCDC No.
804691. (b) Crystal structure of 10g: Wessig, P.; Matthes, A.; Schilde,
U. Z. Kristallogr. NCS 2010, 225, 744.
(15) Bringmann, G.; Price Mortimer, A. J.; Keller, P. A.; Gresser,
M. J.; Garner, J.; Breuning, M. Angew. Chem., Int. Ed. 2005, 44, 5384.
(16) Bringmann, G.; Gulder, T. A. M.; Reichert, M.; Gulder, T.
Chirality 2008, 20, 628.
(17) (a) Tobe, Y.; Takemura, A.; Jimbo, M.; Takahashi, T.; Kobiro,
K.; Kakiuchi, K. J. Am. Chem. Soc. 1992, 114, 3479. (b) McBride, J. M.;
Keehn, P. M.; Wasserman, H. H. Tetrahedron Lett. 1969, 47, 4147.
(18) Hehre, W. J.; Ditchfield, R.; Radom, L.; Pople, J. A. J. Am. Chem.
Soc. 1970, 92, 4796.
’ REFERENCES
(1) (a) Halton, B. Advances in Strained and Interesting Organic
Molecules. Vol. 8; JAI Press: Stamford, 2000. (b) Strained Hydrocarbons:
Beyond the van’t Hoff and Le Bel Hypothesis; Dodziuk, H., Ed.; Wiley-
VCH: Weinheim, 2009. (c) Hopf, H. Classics in Hydrocarbon Chemistry:
Synthesis, Concepts, Perspectives; Wiley-VCH: Weinheim, 2000.
(2) (a) Modern Cyclophane Chemistry; Gleiter, R., Hopf, H., Eds.;
Wiley-VCH: Weinheim, 2004. (b) Bogdan, N. D.; Grosu, I. Curr. Org.
Chem. 2009, 13, 502.
(3) V€ogtle, F.; Sch€afer, R.; Schunder, L.; Neumann, P. Liebigs Ann.
Chem. 1970, 734, 102.
(4) V€ogtle, F.; Neumann, P. Tetrahedron Lett. 1969, 60, 5329.
(5) (a) L€uttringhaus, A.; Graalheer, H. Liebigs Ann. Chem. 1942, 550,
67. (b) L€uttringhaus, A. Liebigs Ann. Chem. 1937, 528 (181), 203.
(6) (a) Haenel, M. W. Tetrahedron Lett. 1978, 19, 4007. (b) Haenel,
M. W. Chem. Ber. 1978, 111, 1789. (c) Blank, N. E.; Haenel, M. W. Chem.
Ber. 1981, 114, 1520. (d) Haenel, M. W. Chem. Ber. 1982, 115, 1425.
(e) Haenel, M. W.; Lintner, B.; Benn, R.; Rufinska, A.; Schroth, G.;
Krueger, C.; Hirsch, S.; Irngartinger, H.; Schweitzer, D. Chem. Ber. 1985,
118, 4884. (f) Lintner, B.; Schweitzer, D.; Benn, R.; Rufinska, A.; Haenel,
M. W. Chem. Ber. 1985, 118, 4907. (g) Haenel, M. W.; Lintner, B.; Benn,
R.; Rufinska, A.; Schroth, G. Chem. Ber. 1985, 118, 4922.
(7) (a) Corbellini, A.; Albenga, L. Gazz. Chim. Ital. 1931, 61, 111.
(b) Ando, T.; Nakagawa, M. Tetrahedron Lett. 1966, 7, 4437.
(c) Yoshida, M.; Tochiaki, Y.; Tatemitsu, H.; Sakata, Y.; Misumi, S.
Chem. Lett. 1978, 829. (d) Brown, H. S.; Muenchausen, C. P.; Sousa,
L. R. J. Org. Chem. 1980, 45, 1682. (e) Kovac, B.; Allan, M.; Heilbronner,
E. Helv. Chim. Acta 1981, 64, 430. (f) Chang, M. H.; Masek, B. B.;
Dougherty, D. A. J. Am. Chem. Soc. 1985, 107, 1124. (g) Nishimura, J.;
Takeuchi, M.; Takahashi, H.; Ueda, E.; Matsuda, Y.; Oku, A. Bull. Chem.
Soc. Jpn. 1989, 62, 3161. (h) Asakawa, M.; Ashton, P. R.; Dehaen, W.;
L’abbꢀe, G.; Menzer, S.; Nouwen, J.; Raymo, F. M.; Stoddart, J. F.; Tolley,
M. S.; Toppet, S.; White, A. J. P.; Williams, D. J. Chem.—Eur. J. 1997, 3,
772. (i) Amabilino, D.; Ashton, P. R.; Balzani, V.; Boyd, S. E.; Credi, A.;
(19) (a) Dudev, T.; Lim, C. J. Am. Chem. Soc. 1998, 120, 4450.
(b) Wiberg, K. B. Angew. Chem., Int. Ed. 1986, 25, 312.
(20) (a) Allinger, N. L.; Sprague, J. T.; Liljefors, T. J. Am. Chem. Soc.
1974, 96, 5100. (b) Lindner, H. J. Tetrahedron. 1976, 32, 753.
(c) Jenneskens, L. W.; Louwen, J. N.; De Wolf, W. H.; Bickelhaupt, F.
J. Phys. Org. Chem. 1990, 3, 295. (d) Grimme, S. J. Am. Chem. Soc. 1992,
114, 10542. (e) Tobe, Y.; Takemura, A.; Jimbo, M.; Takahashi, T.;
Kobiro, K.; Kakiuchi, K. J. Am. Chem. Soc. 1992, 114, 3479. (f) Tsuji, T.;
Ohkita, M.; Konno, T.; Nishida, S. J. Am. Chem. Soc. 1997, 119, 8425.
(g) Stanger, A.; Ben-Mergui, N.; Perl, S. Eur. J. Org. Chem. 2003, 2709.
(21) Cope, A. C.; Martin, M. M.; McKervey, M. A. Q. Rev. Chem. Soc.
1966, 20, 119.
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