Tolanophane revisited-Resolution and racemization mechanism of a twisted chiral aromatic compound

Article abstract of DOI:10.1002/ejoc.201200765

Enantiomers of tolanophane consisting of two tolane units were resolved by chiral HPLC, contrary to the previous attempts by Staab et al. Racemization took place rapidly at room temperature, and the barrier to enantiomerization was determined to be 93.2 kJ mol^-1 at 283 K. This energy barrier was rationally deduced with a mechanism involving rotations about the single and triple bond axes, as revealed by DFT calculations. A tetrahedrane intermediate resulting from a transannular reaction between the two adjacent triple bonds was ruled out.

Full text of DOI:10.1002/ejoc.201200765

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FULL PAPER
DOI: 10.1002/ejoc.201200765
Tolanophane Revisited – Resolution and Racemization Mechanism of a Twisted
Chiral Aromatic Compound
Shinji Toyota,*[a] Katsutoshi Kawai,[a] Tetsuo Iwanaga,[a] and Kan Wakamatsu[a]
Keywords: Cyclophanes / Alkynes / Chiral resolution / Circular dichroism / Conformation analysis / Density functional
calculations
Enantiomers of tolanophane consisting of two tolane units
were resolved by chiral HPLC, contrary to the previous
attempts by Staab et al. Racemization took place rapidly at
room temperature, and the barrier to enantiomerization was
determined to be 93.2 kJmol–1 at 283 K. This energy barrier
was rationally deduced with a mechanism involving rotations
about the single and triple bond axes, as revealed by DFT
calculations. A tetrahedrane intermediate resulting from a
transannular reaction between the two adjacent triple bonds
was ruled out.
the twisted molecular motif with four o-phenylene units has
been extensively adopted for the design of nonplanar or
helical phenylene oligomers, such as tetraphenylenes and
their larger analogues with acetylene linkers.[6–9]
Introduction
In 1968, Staab et al. reported the first synthesis of tolan-
ophane (1),[1] which consists of two tolane (diphenylethyne)
units (Figure 1).[2,3] X-ray analysis revealed that this mole-
cule had a twisted structure with D2 symmetry and a short
nonbonding distance between the two triple bonds
(2.85 Å).[4] This orientation led to transannular reactions
across the triple bonds on treatment with various reagents,
such as bromine, to form cyclized products.[2,3] Although
the chiral structure suggested the presence of enantiomers,
resolution by HPLC on a chiral stationary phase or the
formation of diastereomeric salts with enantiopure reagents
was unsuccessful. The authors proposed the possibility of
the formation of tetrahedrane intermediate 2 to explain the
facile racemization of the twisted molecule. However, there
was no experimental evidence for the intermediacy: no
isomerization, namely scrambling of substituents, was ob-
served for some substituted tolanophanes. As far as we have
surveyed, no further studies on this simple yet puzzling mo-
lecule have been reported since then.[5] On the other hand,
HPLC with immobilized chiral stationary phases[10] is a
powerful technique to resolve enantiomers of chiral cyclic
oligomers and can be used with a wide variety of eluent
systems.[11] Enantiomers of various cyclic oligomers were
resolved with Daicel CHIRALPAK IA and IC columns,[12]
giving valuable information of the chiroptical properties of
such hydrocarbon samples. These results inspired us to ap-
ply this technique to the resolution of tolanophane in the
hope that it could offer convincing clues to solve a stereo-
chemical problem that had remained unsolved for more
than 40 years. We herein report the structures, the resolu-
tion of enantiomers, and the mechanism of enantiomeriz-
ation of chiral tolanophane in terms of steric congestion
and electronic properties of the triple bonds.
Results and Discussion
Synthesis
Bis(2-bromophenyl)ethyne (3) was prepared by the
double Sonogashira coupling of 1-bromo-2-iodobenzene
and (trimethylsilyl)ethyne in the presence of 1,8-diazabicy-
clo[5.4.0]undec-7-ene (DBU).[13] According to the original
Figure 1. Enantiomers of tolanophane 1 and proposed tetra- procedure,[3] this precursor was treated with BuLi and then
hedrane intermediate 2.
CuCl2 to give 1 in 10% yield (Scheme 1). Although we also
carried out the coupling of 1 under several conditions with
[a] Department of Chemistry, Faculty of Science, Okayama
various solvents, additives, and Ni catalyst, the original
University of Science,
1
method gives the best results as far as we know. The H
NMR spectrum has one set of ABCD signals at δ = 7.3–
7.5, and the 13C NMR spectrum has six aromatic signals
and one alkyne signal. These signal patterns support a sym-
1-1 Ridaicho, Kita-ku, Okayama 700-0005, Japan
Fax: +81-86-256-9457
E-mail: stoyo@chem.ous.ac.jp
Supporting information for this article is available on the
WWW under http://dx.doi.org/10.1002/ejoc.201200765.
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S. Toyota, K. Kawai, T. Iwanaga, K. Wakamatsu
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metric structure on the NMR timescale at room tempera- same helicity and D2 symmetry. Selected structural param-
ture. The alkyne carbon signal of 1 (δ = 94.7 ppm) shifted eters are listed in Table 1. In the acetylene axes, the bond
downfield relative to that of the parent tolane (δ = lengths of the triple and single bonds are 1.20 and 1.43 Å,
89.6 ppm).[14] This deshielding is attributable to the bending respectively. The bond angles at the alkyne carbon atoms
deformation of sp carbon atoms as well as the anisotropic are 171° and 175° in molecules A and B, respectively, and
effect of the nearby triple bond.
indicate small bending deformations. The dihedral angles
between the phenyl groups in the biphenyl moieties, φ1 and
φ2, suggest that molecule B (52°) is less twisted than mole-
cule A (58°). The orientation of the two triple bonds can
be characterized by two parameters: the distances between
their midpoints R and the skew angles between the two axes
ρ. The R values for the two independent molecules are 2.86
and 2.83 Å, which are much shorter than the sum of the van
der Waals radii of sp carbon atoms (ca. 3.4 Å). Molecule A
has a larger skew angle (64.7°) than that of molecule B
(56.2°) as a result of the large twist angles in the rigid ring
system of the former. Close contact between the two triple
bonds is observed in the X-ray structures of tetradehydrodi-
naphtho[10]annulene (4, 2.78 Å, Figure 3) and 5,6,11,12-
tetradehydrodibenzo[a,e]cyclooctene (5, 2.61 Å),[15] where
the R values shown in parentheses are somewhat shorter
than those of 1. In these planar compounds, the two triple
bonds are parallel rather than skewed, corresponding to ρ
= 0.
Scheme 1. Synthesis of 1.
X-ray Analysis
X-ray analysis of 1 was performed at –150 °C with a sin-
gle crystal grown from hexane/dichloromethane. Figure 2
shows the X-ray structures of two independent molecules
where solvent molecules (CH2Cl2) were omitted. The crys-
tallographic parameters of this crystal, which is tetragonal
¯
and in the I4c2 space group, are similar to those of one of
the polymorphs reported by Irngartinger.[4] The asymmetric
unit contains two sets of one-quarter of the whole molecule,
and the symmetric operation gives two molecules with the
Figure 3. Structures of 4 and 5.
Resolution of Enantiomers
We performed chiral HPLC with a racemic sample of 1
by using a Daicel CHIRALPAK IA column. The enantio-
mers were eluted at 29.7 and 37.4 min with hexane/chloro-
Figure 2. X-ray structures of the two independent molecules of 1.
See Table 1 for the definition of dihedral angles φ1 and φ2.
Table 1. Structural parameters of the X-ray structures of 1 and calculated structures of 1 and related isomers at the M05-2/6-31G* level.[a]
Symmetry
1 X-ray A[c] D2
N[b]
ΔE [kJmol–1] ΔG298 K [kJmol–1] r1 [Å]
r2 [Å]
φ1 [°]
φ2 [°]
θ [°]
R [Å]
ρ [°]
–
–
0
1
0
1
3
0
0
–
–
0
–
–
0
1.203
1.191
1.210
1.213
1.213
1.212
1.209
–
1.432
1.441
1.430
1.434
1.434
1.433
1.431
–
57.9
51.7
56.2
–50.1
–48.0
–39.0
0.0
57.9
51.7
56.2
50.1
51.2
51.8
0.0
170.6
174.5
172.7
161.1
161.1, 161.5
162.5, 163.9
169.0
–
–
2.86
2.83
2.86
2.98
2.97
2.92
2.76
–
64.7
56.2
58.9
0.0
6.0
19.4
0.0
–
1 X-ray B[c] D2
1a[d]
1b
1c
D2
C2h
C2
96.2
96.2
96.3
159.9
81.1
–199.1
97.9
87.1
98.7
167.3
86.1
–192.3
1d[e]
1e
C1
D2h
D2d
D2h
2
6
0.0
0.0
0.0
0.0
–
–
–
–
[a] Definitions of structural parameters (see graphic). r1: CϵC bond length, r2: C–C bond length, φ1, φ2: dihedral angles between two
phenyl groups, θ: bond angle at acetylene carbon atoms, R: distance between midpoints of two triple bonds, ρ: skew angle between two
triple bonds. [b] Number of imaginary frequencies. [c] X-ray structures of two independent molecules A and B (see Figure 2). [d] Global
minimum. Reference of ΔE and ΔG. [e] Transition state.
2
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Tolanophane Revisited – Resolution and Racemization Mechanism
form, 10:1, as eluent with almost baseline separation. Pre- show that the unsuccessful resolution reported in the litera-
liminary experiments revealed that the enantiomers under- ture was due to facile racemization at room temperature.[3]
went racemization slowly even at room temperature. By Nevertheless, the enantiomers can be resolved under appro-
chilling the solvent during chromatography, we successfully priate conditions where the exchange becomes slow.
obtained almost enantiopure samples of the enantiomers.
The resolved enantiomers were circular dichroism (CD)
active and their CD curves were mirror images of each
other (Figure 4). The first and second fractions gave nega-
DFT Calculation
tive and positive Cotton effects, respectively, at 265 nm.[16]
In order to obtain information on the racemization
mechanism, structures and energies were calculated for vari-
ous conformations of 1 and related isomers. We adopted
the M05-2X/6-31G* level of theory and basis sets because
it reasonably reproduced the X-ray structures and energies
of π-conjugated compounds.[17] The calculated structures
are shown in Figure 5, and the structural parameters and
other data are compiled in Table 1. The global minimum
structure 1a is close to molecule A of the X-ray structures.
We adopted the dihedral drive technique for dihedral an-
gle φ1 as the variable parameter, and the other structural
parameters were optimized every time with retention of C2
symmetry. The energy increased monotonically with the de-
crease of φ1 from 56° (global minimum) to –50°, and be-
came almost constant at 96 kJmol–1 in the range of –30 to
–50° (Figure 6). The dihedral angle in the other biphenyl
unit φ2 was not affected so much at ca. 50° during the dihe-
dral drive. The calculated structure at φ1 = –50° is 1b, which
has a small bond angle (161°) at the alkyne carbon atoms.
Full optimization from structure 1b gave the less symmetric
structure 1c as the energy minimum, although their energies
Figure 4. CD spectra of enantiomers of 1 in hexane/chloroform,
10:1. Solid line: first fraction. Broken line: second fraction. Gray
lines: decay of CD spectra of first fraction after 1, 2, 3, 4, 6, and
9 h at 10 °C.
The course of racemization could be monitored from the were almost the same. We also calculated the transition
CD spectra measured with an enantiopure sample of the state of the above conformational change to give structure
first eluted enantiomer (Figure 4). The rate of enantiomer- 1d, which was only slightly less stable than 1b and 1c. The
ization was determined by the classical kinetics technique energy difference between 1d and 1a (98.7 kJmol–1) is com-
at 10 °C (see Exp. Sect. for the usage of terms, enantiomer- parable to the observed barrier to enantiomerization. This
ization and racemization). The half-life at this temperature analysis suggests that 1c is located at a very shallow hollow
was ca. 150 min. Kinetic analysis gave the rate constant in the energy profile and its energy is close to that of transi-
(3.82Ϯ0.10)ϫ 10–5 s–1, which corresponds to ΔG϶ tion state 1d. Fully planar structure 1e was much less stable
93.2 kJmol–1 at 283 K. These kinetic data unambiguously than the other nonplanar structures.
Figure 5. Calculated (M05-2X/6-31G*) structures of various conformations of 1, tetrahedrane isomer 2, and cyclobutadiene isomer 6.
See Table 1 for definitions of φ1 and φ2. GM: global minimum, TS: transition state.
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S. Toyota, K. Kawai, T. Iwanaga, K. Wakamatsu
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lecules (9) into cyclobutadiene (10) in a similar manner
(Scheme 2). This process is also symmetrically forbidden
under thermal conditions. The course of the isomerization
of two acetylene molecules to 8 or 10 was thoroughly inves-
tigated by theoretical calculations.[19] The calculations sug-
gested that carbene 11 was a key intermediate in the step-
wise routes of the two processes. However, the conversion
of two acetylene molecules to 11 would require a large
amount of energy (Ͼ 200 kJmol–1).[19a] The above findings
suggest that tetrahedrane 2 and cyclobutadiene 6 are highly
unlikely to be intermediates during the racemization pro-
cess of 1. The observed energy barrier can be rationally ex-
plained by the thermal inversion mechanism by bond rota-
tions (Scheme 3).
Figure 6. Effects of dihedral angle φ1 on the calculated energies
starting from global minimum structure 1a at the M05-2X/6-31G*
level.
Scheme 3. Mechanism of racemization between enantiomers 1a
and 1aЈ by axis rotation.
We also calculated the isomeric structures of 1. Tetrahe-
drane structure 2 was obtained as an energy minimum and
found to be more stable by 12.6 kJmol–1 than transition
state 1d. In general, the conversion from the two alkyne
units into a tetrahedrane structure was not allowed in terms
of MO symmetry, as far as a thermally concerted process
was assumed. Then, a conversion process from two acetyl-
ene molecules in a crossed arrangement (7) into one tetrahe-
drane molecule (8) was analyzed as a model reaction
(Scheme 2). This process is symmetrically not allowed ac-
cording to the calculated orbital correlation diagram (Fig-
ure S4 in Supporting Information). If the conversion from
1 into 2 were to occur through nonconcerted mechanisms
involving such intermediates as radicals and zwitterions,
various side products would be formed. Another possible
isomer is cyclobutadiene because some tetrahedrane deriva-
tives are known to isomerize into cyclobutadiene ana-
logues.[18] In the presence of Fe(CO)5, 1 is converted into a
Fe(CO)3 complex of cyclobutadiene isomer 6.[2,3] The calcu-
lation suggests that cyclobutadiene 6 itself is thermodynam-
ically much more stable than the other structures. This me-
ans that once 6 is formed, it will never revert to the original
tolanophane under ordinary conditions. Then we analyzed
a model conversion process from two parallel acetylene mo-
The barrier to inversion for tolanophane is much lower
than those for tetraphenylene (tetrabenzocyclooctatetraene,
12) and its derivatives without acetylene linkers (ca.
Ͼ330 kJmol–1), which have saddle-shaped twisted struc-
tures (Figure 7).[7] On the contrary, expanded tetraphenyl-
ene 13 with two acetylene linkers and two diacetylene link-
ers undergoes rapid enantiomerization with an energy bar-
rier of 39 kJmol–1.[8a] The dynamic behavior of such pro-
cesses in cyclic compounds with long linkers occurs too
rapidly to allow observation by experimental meth-
ods.[8b,8c,20] These tendencies mean that the barrier is effec-
tively lowered by the insertion of acetylene or diacetylene
linkers between phenylene units in the tetraphenylene sys-
tem, which reduces the molecular strain in the transition
state.[21] The analogous substituted tolanophane 14 with
four meta-phenylene units undergoes rapid interconversion
between diastereomeric conformers.[5b] Therefore, the sub-
Scheme 2. Model processes from two ethyne molecules to tetrahe-
drane 8 and cyclobutadiene 10 and theoretically possible intermedi-
ate 11.
Figure 7. Structures of related compounds 12–14.
4
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Tolanophane Revisited – Resolution and Racemization Mechanism
form, 10:1) λ (Δε) first fraction (5.73ϫ 10–5 molL–1): 237 (–0.56),
248 (+1.98), 266 (–5.33), 304 (–1.01) nm. Second fraction (5.37ϫ
10–5 molL–1): 237 (+0.40), 248 (–2.37), 267 (+5.38), 304
(+1.14) nm. Because of the low sensitivity and the ease of racemiza-
tion, the specific rotations [α] of these enantiomers could not be
measured correctly. However, the first and second fractions showed
positive and negative optical rotations, respectively, at 589 nm. For
the kinetic measurements, all eluents and eluates were cooled in an
ice bath. The first eluate was collected and injected again into the
column, which contained approximately 5% of the second fraction.
The eluate of the first fraction was placed in a CD cell equipped
with a thermostat set at 10 °C. The spectra were measured every
30 min while CD intensity was monitored at 266 nm. The data were
analyzed as a first-order reversible process expressed as Equa-
tion (1), where ke is the rate of enantiomerization.
stitution position has crucial effects on the conformational
distribution and flexibility of the cyclic system.
Conclusions
We were able to resolve the enantiomers of tolanophane
1 and determine the barrier to enantiomerization by classi-
cal kinetics. The relatively low barrier was reasonably eluci-
dated by thermal conformational inversion according to
DFT calculations, and a mechanism via the tetrahedrane
intermediate was ruled out. These findings offer clear evi-
dence to answer the unsolved question raised by Staab et
al. Unfortunately, further studies of this interesting com-
pound, in particular, the interactions between triple bonds
and transannular reactions to form new aromatic com-
pounds and oligomers, were greatly obstructed by the low
yield of the macrocyclization step. The development of an
efficient method for the synthesis of this compound and its
derivatives, for example, by modern cross-coupling reac-
tions, is in progress.
(1)
This rate can be determined from the equation, –1/2 ln([CD]t/
[CD]0) = ket, where t is time (unit: seconds), and [CD]t and [CD]0
are CD intensities at t and 0, respectively. The least-squares fit of
the time and the CD decay gave a rate constant of (3.82Ϯ0.10)ϫ
10–5 s–1 (r = 0.9998) as the slope and the free energy of activation
at 93.2 kJmol–1 at 283 K (see Table S1 in the Supporting Infor-
mation). Racemization is defined as an irreversible conversion from
an enantiopure (or enantioenriched) sample into a racemate.[22]
Therefore, the rate of racemization kr is equal to twice the rate of
enantiomerization ke: kr = 7.64ϫ 10–5 s–1 or ΔG϶ 91.5 kJmol–1 at
283 K for racemization.
Experimental Section
General Methods: NMR spectra were measured with a Varian
Gemini-300 spectrometer (1H: 300 MHz, 13C: 75 MHz). HRMS
were measured with a JEOL MStation-700 spectrometer by the
FAB method. UV spectra were measured with a Hitachi U-3000
spectrometer with a 10 mm cell. CD spectra were measured with a
JASCO J-820 polarimeter with a 10 mm cylindrical cell. GPC was
performed with a Japan Analytical Industry Co. LC-908 recycling
preparative HPLC system with 20 mmφϫ 600 mm JAIGEL-1H,
2H columns.
DFT Calculations: Calculations were carried out with Gaussian
03[23] on a Linux computer. Structures of various conformations
were optimized by hybrid DFT at the M05-2X/6-31G* level of
theory. For the dihedral drive analysis, the structure was optimized
by varying φ1 in the range 56.2° to –50° with retention of C2 sym-
metry. Frequency analyses were performed for all structures and
the number of imaginary frequencies is listed in Table 1.
Synthesis of 1: To a solution of bis(2-bromophenyl)ethyne (3)[13]
(1.00 g, 2.98 mmol) in dry ether (35 mL) was added BuLi (4.13 mL
of 2.6 molL–1 solution in hexane, 6.61 mmol) at –30 °C under N2.
The solution was stirred for 45 min at that temperature. After cool-
ing to –40 °C, CuCl2 (1.40 g, 10.4 mmol) was added. The reaction
mixture was stirred for 30 min at that temperature and then for 2 h
at room temp., and heated to reflux for 2 h. The reaction was
quenched with dilute HCl (20 mL), and the mixture was extracted
with diethyl ether three times. The combined organic solution was
washed with aq. NaHCO3 and then aq. NaCl, dried with MgSO4,
and the solvents evaporated. The residue was roughly separated by
chromatography on silica gel with hexane/chloroform, 8:1 as eluent.
The crude product was further purified by preparative GPC with
chloroform to give the desired product as colorless crystals (51 mg,
10%); m.p. 209–211 °C (lit. 222–223 °C).[3] 1H NMR (400 MHz,
CD2Cl2): δ = 7.32 (m, 4 H), 7.39 (d, J = 7.8 Hz, 4 H), 7.42–7.45
(m, 8 H) ppm. 13C NMR (75 MHz, CDCl3): δ = 94.7 (alkyne),
122.7, 127.0, 128.0, 131.4, 131.7, 143.2 (aromatic) ppm. UV
(CHCl3): λmax (ε) = 222 (71000), 241 (68000) nm. HRMS (FAB)
calcd. for C28H16 [M]+ 352.1252; found 352.1279.
X-ray Analysis: A single crystal was obtained by crystallization
from hexane/dichloromethane. Diffraction data were collected with
a Rigaku RAXIS-RAPID imaging plate diffractometer with Cu-
Kα radiation (λ = 1.54187 Å) to a maximum 2θ value of 68.22° at
–150 °C. The structure was solved by the direct method
(SHELXS97) and refined by the full-matrix least-squares method
(SHELXL97). Non-hydrogen atoms were refined anisotropically.
Hydrogen atoms were included in fixed positions. Formula
¯
2(C28H16)·2(CH2Cl2), M = 874.67, tetragonal, space group I4c2
(#120), a = 12.7198(9), c = 25.791(2) Å, V = 4172.8(5) Å3, Z = 4,
Dc = 1.39 gcm–3, μ(Cu-Kα) = 2.90 mm–1. Number of data 22146,
number of data used 1917 [IϾ2.0σ(I)], R1 = 0.0594, wR2 = 0.1646,
GOF = 1.143.
CCDC-884577 contains the supplementary crystallographic data
for this paper. These data can be obtained free of charge from The
Cambridge Crystallographic Data Centre via www.ccdc.cam.ac.uk/
data_request/cif.
Chiral HPLC and Kinetic Measurement: Chiral HPLC of 1 was
carried out with a Daicel CHIRALPAK® IA column (10 mmφϫ
250 mm) with hexane/chloroform, 10:1, as eluent. A solution of a
racemic sample (ca. 0.50 mg) in the eluent (0.5 mL) was injected
for each batch at a flow rate of 1.0 mLmin–1. The enantiomers
were eluted at 29.7 and 37.4 min. The eluate of each fraction was
used for the CD measurement as obtained. CD (hexane/chloro-
Supporting Information (see footnote on the first page of this arti-
1
cle): H NMR, 13C NMR, and UV spectra, kinetic analysis data,
and DFT calculation data.
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[13] M. J. Mio, L. C. Kopel, J. B. Braun, T. L. Gadzikwa, K. L.
Hull, R. G. Brisbois, C. J. Markworth, P. A. Grieco, Org. Lett.
2002, 4, 3199–3202.
Acknowledgments
This work was partly supported by Grants-in-Aid for Scientific Re-
search on Innovative Areas (Integrated Organic Synthesis) from
The Ministry of Education, Culture, Sports, Science and Technol-
ogy, Japan (MEXT) (grant numbers 22106543 and 24106743) and
by the MEXT-supported Program for the Strategic Research Foun-
dation at Private Universities, 2009–2013. The authors thank Mr.
Kota Sugahara for technical assistance in spectroscopic measure-
ments.
[14] E. Breitmaier, W. Voelter, Carbon-13 NMR Spectroscopy, VCH
Verlagsgesellschaft, Weinheim, Germany, 1989, chapter 4.11.
[15] These compounds are known to undergo facile transannular
reactions across triple bonds, see: a) R. Umeda, D. Hibi, K.
Miki, Y. Tobe, Org. Lett. 2009, 11, 4104–4106; b) R. Destro, T.
Pilati, M. Simonetta, J. Am. Chem. Soc. 1975, 97, 658–659; c)
G. Babu, A. Orita, J. Otera, Chem. Lett. 2008, 37, 1296–1297.
[16] Although we calculated the CD spectrum of 1 by the TDDFT
method at the M05-2X/6–31G* level, we could not clearly pre-
dict the absolute stereochemistry by simply comparing the cal-
culated spectrum with the observed one.
[17] a) Y. Zhao, D. G. Truhlar, Chem. Phys. Lett. 2011, 502, 1–13;
b) Y. Zhao, D. G. Truhlar, Acc. Chem. Res. 2008, 41, 157–167;
c) M. D. Wodrich, C. Corminboeuf, P. R. Schreiner, A. A.
Fokin, P. v. R. Schleyer, Org. Lett. 2007, 9, 1851–1854.
[18] a) G. Maier, Angew. Chem. 1988, 100, 317–341; Angew. Chem.
Int. Ed. Engl. 1988, 27, 309–332; b) S. Rayne, K. Forest, Com-
put. Theor. Chem. 2012, 979, 1–9.
[1] The systematic name is 9,10,19,20-tetradehydrotetrabenzo-
[a,c,g,i]cyclododecene. Tolanophanes are cyclophanes con-
sisting of tolane units. This term was used in the following
articles: a) M. Bauer, M. Nieger, F. Vögtle, Chem. Ber. 1992,
125, 2533–2538; b) H. R. Darabi, K. Jadidi, A. R. Mohebbi,
L. Faraji, K. Aghapoor, S. Shahbazian, M. Azimzadeh, S. M.
Nasseri, Supramol. Chem. 2008, 20, 327–333.
[2] H. A. Staab, E. Wehinger, Angew. Chem. 1968, 80, 240–241;
Angew. Chem. Int. Ed. Engl. 1968, 7, 225–226.
[19] a) D. Cremer, E. Kraka, H. Joo, J. A. Stearns, T. S. Zwier, Phys.
Chem. Chem. Phys. 2006, 8, 5304–5316; b) A. Nemirowski,
H. P. Reisenauer, P. R. Schreiner, Chem. Eur. J. 2006, 12, 7411–
7420; c) G. Maier, J. Neudert, O. Wolf, D. Pappusch, A. Sekigu-
chi, M. Tanaka, T. Matsuo, J. Am. Chem. Soc. 2002, 124,
13819–13826.
[3] H. A. Staab, E. Wehinger, W. Thorwart, Chem. Ber. 1972, 105,
2290–2309.
[4] H. Irngartinger, Chem. Ber. 1973, 106, 761–772.
[5] This compound was cited in the following articles to date; a)
Y. Tobe, R. Umeda, Sci. Synth. 2008, 43, 393–433; b) K. Uts-
umi, T. Kawase, M. Oda, Chem. Lett. 2003, 32, 412–413.
[6] For a review on twisted chiral molecules, see: K. Campbell,
R. R. Tykwinski, in: Carbon-Rich Compounds (Eds.: M. M.
Haley, R. R. Tykwinski), Wiley-VCH, Weinheim, Germany,
2006, chapter 6.
[20] M. A. Heuft, S. K. Collins, A. G. Fallis, Org. Lett. 2003, 5,
1911–1914.
[21] S. Toyota, Chem. Rev. 2010, 110, 5398–5424.
[22] M. Reist, B. Testa, P.-A. Carrupt, M. Jung, V. Schurig, Chiral-
ity 1995, 7, 369–400.
[7] a) H. Huang, T. Stewart, M. Gutmann, T. Ohhara, N. Niimura,
Y.-X. Li, J.-F. Wen, R. Bau, H. N. C. Wong, J. Org. Chem.
2009, 74, 359–369; b) S. M. Bachrach, J. Org. Chem. 2009, 74,
3609–3611.
[8] a) R. Boese, A. J. Matzger, K. P. C. Vollhardt, J. Am. Chem.
Soc. 1997, 119, 2052–2053; b) S. K. Collins, G. P. A. Yap, A. G.
Fallis, Angew. Chem. 2000, 112, 393–396; Angew. Chem. Int.
Ed. 2000, 39, 385–388; c) S. K. Collins, G. P. A. Yap, A. G.
Fallis, Org. Lett. 2000, 2, 3189–3192.
[23] M. J. Frisch, G. W. Trucks, H. B. Schlegel, G. E. Scuseria,
M. A. Robb, J. R. Cheeseman, J. A. Montgomery Jr., T.
Vreven, K. N. Kudin, J. C. Burant, J. M. Millam, S. S. Iyengar,
J. Tomasi, V. Barone, B. Mennucci, M. Cossi, G. Scalmani, N.
Rega, G. A. Petersson, H. Nakatsuji, M. Hada, M. Ehara, K.
Toyota, R. Fukuda, J. Hasegawa, M. Ishida, T. Nakajima, Y.
Honda, O. Kitao, H. Nakai, M. Klene, X. Li, J. E. Knox, H. P.
Hratchian, J. B. Cross, V. Bakken, C. Adamo, J. Jaramillo, R.
Gomperts, R. E. Stratmann, O. Yazyev, A. J. Austin, R.
Cammi, C. Pomelli, J. W. Ochterski, P. Y. Ayala, K. Morok-
uma, G. A. Voth, P. Salvador, J. J. Dannenberg, V. G. Zakrzew-
ski, S. Dapprich, A. D. Daniels, M. C. Strain, O. Farkas, D. K.
Malick, A. D. Rabuck, K. Raghavachari, J. B. Foresman, J. V.
Ortiz, Q. Cui, A. G. Baboul, S. Clifford, J. Cioslowski, B. B.
Stefanov, G. Liu, A. Liashenko, P. Piskorz, I. Komaromi, R. L.
Martin, D. J. Fox, T. Keith, M. A. Al-Laham, C. Y. Peng, A.
Nanayakkara, M. Challacombe, P. M. W. Gill, B. Johnson, W.
Chen, M. W. Wong, C. Gonzalez, J. A. Pople, Gaussian 03, rev.
E.01, Gaussian, Inc., Wallingford CT, 2004.
[9] For reviews, see: a) S. Toyota, Chem. Lett. 2011, 40, 12–18; b)
S. Toyota, Pure Appl. Chem. 2012, 84, 917–929.
[10] a) T. Ikai, Y. Okamoto, Chem. Rev. 2009, 109, 6077–6101; b)
Y. Okamoto, T. Ikai, J. Shen, Isr. J. Chem. 2011, 51, 1096–1106.
[11] a) T. Ishikawa, T. Iwanaga, S. Toyota, M. Yamasaki, Bull.
Chem. Soc. Jpn. 2011, 84, 729–740; b) S. Toyota, T. Kawakami,
R. Shinnishi, R. Sugiki, S. Suzuki, T. Iwanaga, Org. Biomol.
Chem. 2010, 8, 4997–5006; c) T. Ishikawa, T. Shimasaki, H.
Akashi, T. Iwanaga, S. Toyota, M. Yamasaki, Bull. Chem. Soc.
Jpn. 2010, 83, 220–232; d) S. Toyota, H. Onishi, K. Wakam-
atsu, T. Iwanaga, Chem. Lett. 2009, 38, 350–351.
Received: June 8, 2012
[12] CHIRALPAK is a trade name of Daicel Co., Japan.
Published Online: ᭿
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© 0000 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 0000, 0–0

Job/Unit: O20765
/KAP1
Date: 02-08-12 16:47:45
Pages: 7
Tolanophane Revisited – Resolution and Racemization Mechanism
Chiral Cyclophane
S. Toyota,* K. Kawai, T. Iwanaga,
K. Wakamatsu .................................. 1–7
Tolanophane Revisited – Resolution and
Racemization Mechanism of a Twisted
Chiral Aromatic Compound
Enantiomers of Staab’s tolanophane were
finally resolved by chiral HPLC. The facile
racemization is rationally explained by a
bond-rotation mechanism without a tetra-
hedrane intermediate based on DFT calcu-
lations.
Keywords: Cyclophanes / Alkynes / Chiral
resolution / Circular dichroism / Confor-
mation analysis / Density functional calcu-
lations
Eur. J. Org. Chem. 0000, 0–0
© 0000 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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