Planar-chiral [7]orthocyclophanes

Article abstract of DOI:10.1002/anie.201204484

Just plain chiral: The [7]orthocyclophanes 1, having an E-olefinic ansa chain, exhibit planar chirality at ambient temperature and their stereochemical stabilities are highly dependent upon the embedded X group in the ansa chain. Inter- and intramolecular transformations of 1 (where X=NTs) provide a variety of nitrogen-containing chiral molecules in a stereospecific manner. Ts=4-toluenesulfonyl. Copyright

Full text of DOI:10.1002/anie.201204484

Angewandte
Chemie
DOI: 10.1002/anie.201204484
Chirality
Planar-Chiral [7]Orthocyclophanes**
Katsuhiko Tomooka,* Chisato Iso, Kazuhiro Uehara, Masaki Suzuki, Rie Nishikawa-Shimono,
and Kazunobu Igawa
Medium-sized bridged cyclophanes have attracted consider-
able interest because of their unusual conformational, chem-
ical, and spectroscopic properties caused by deformation and
strain in the aromatic ring and in the bridging ansa chain.[1]
Among cyclophanes, meta- or paracyclophanes having
dynamic planar chirality have generated much theoretical
and synthetic interest as unique chiral molecules. In contrast,
their regioisomer, that is, orthocyclophane (A) does not
display planar chirality. It is also expected that 1 can achieve
thermal stability, which 2 does not exhibit (see below). The
details of the study are provided below.
At the outset, we examined the synthesis of the nitrogen-
containing orthocyclophane 1aa (X = NTs, R = H) from the
known diol 3 (Scheme 1). The Mitsunobu reaction of 3 and
TsNHCO2Me proceeded with high group selectivity and
attract much attention owing to its less interesting topology
and lack of planar chirality.[2] However, the introduction of
a properly designed ansa chain, which can be on the outside of
the plane of the benzene ring and decrease the flexibility of
the molecule, may create stable planar chirality, even in
simple orthocyclophanes. Herein we report the design and
synthesis of the planar-chiral [7]orthocyclophanes 1 having an
E alkene in the ansa chain, as well as a detailed stereochem-
ical analysis and a demonstration of their utility in synthesis.
Recently, we discovered a novel class of planar-chiral
heterocycles (2) which consist of a bis(allylic) skeleton and
the heteroatom X (X = O, NTs, SOn; Ts = 4-toluenesul-
fonyl).[3] The chirality of these compounds originates from
the presence of suitably located E and Z alkenes in the nine-
membered ring.[4] On the basis of this stereochemical
phenomenon, we anticipated that the orthocyclophane 1, in
which the Z alkene of 2 is replaced by a benzene ring, may
Scheme 1. Synthesis and X-ray analysis of 1aa: a) TsNHCO2Me, PPh3,
DEAD, THF, ꢀ78!08C, 78%; b) DMP, CH2Cl2, 08C!RT, 84%;
c) (EtO)2POCH2CO2Et, NaH, THF, ꢀ78!08C, 90% [>98% (E)];
d) DIBAL, CH2Cl2, ꢀ788C, quant. [94% (E): The Z isomer was sepa-
rated by silica gel choromatography]; e) PPh3, DEAD, THF, ꢀ78!08C,
90%. DEAD=diethyl azodicarboxylate, DIBAL=diisobutylaluminium
hydride, DMP=Dess–Martin periodinane, THF=tetrhydrofuran,
Ts =4-toluenesulfonyl. For the ORTEP drawing of 1aa the thermal
ellipsoids are shown at 50% probability and the tolyl group has been
omitted for clarity.
provided the amide alcohol 4 as the only product in 78%
yield.[5] The Dess–Martin oxidation of the alcohol moiety of 4
followed by the Horner–Wadsworth–Emmons reaction and
treatment with DIBAL provided the key intermediate (E)-5
in 71% yield (three steps). The intramolecular Mitsunobu
reaction of (E)-5 under a high dilution conditions (ca. 0.01m)
provided the desired cyclic amide 1aa in excellent yield
(90%). It should be noted that only a negligible amount of
dimerized product (< 1%) was formed in this reaction. The
orthocyclophane 1aa afforded a crystal suitable for X-ray
analysis. The analysis reveals that the ansa chain is located on
the outside of the plane of the benzene ring and both the
benzene ring and alkene moieties of the ansa chain form
chiral planes in the solid state (Scheme 1).[6]
[*] Prof. Dr. K. Tomooka, Dr. K. Uehara, Dr. K. Igawa
Institute for Materials Chemistry and Engineering
Kyushu University
Kasuga, Fukuoka 816-8580 (Japan)
E-mail: ktomooka@cm.kyushu-u.ac.jp
Homepage: http://www.cm.kyushu-u.ac.jp/tomooka
C. Iso, Dr. M. Suzuki, R. Nishikawa-Shimono
Department of Applied Chemistry, Tokyo Institute of Technology
Meguro-ku, Tokyo 152-8552 (Japan)
[**] This research was supported by the JSPS KAKENHI (Grant number
22350019 and 23655086), the G-COE Program (Kyushu Univ.),
MEXT Project of Integrated Research on Chemical Synthesis, and
Nagase Science and Technology Foundation. We thank Y. Ishikawa
(Kyushu Univ.) for his technical support and Y. Tanaka (Kyushu
Univ.) for HRMS measurements.
The existence of isolable enantiomers of 1aa in solution
was revealed by HPLC analysis using a chiral stationary
column equipped with a CD spectropolarimeter. As shown in
Figure 1, both enantiomers of 1aa were successfully separated
on an analytical as well as a semi-preparative scale.[7] The
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/anie.201204484.
Angew. Chem. Int. Ed. 2012, 51, 1 – 5
ꢀ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
1
These are not the final page numbers!

.
Angewandte
Communications
show that 1a is a manageable chiral molecule having stable
planar chirality and sufficient thermal stability for standard
handling.
The enantioenriched form of the orthocyclophane can be
obtained not only by HPLC separation but also by our
recently developed asymmetric cyclization method.[11] For
example, the cyclization of the achiral precursor 7 with the d-
glucose-derived alkoxide 8 at ꢀ108C in CH2Cl2 provided (R)-
1ab with 63% ee.[12] The enantiomerically pure form of (R)-
1ab can be obtained from the fractional crystallization of this
enantio-enriched product.
Figure 1. HPLC analysis of 1aa using a chiral stationary column.[7]
At this stage, the basic and important question arises as to
the type of influence the atom X has on the stereochemical
behavior of orthocyclophane 1. In particular, we were
interested in the carbon congener 1b (X = CH2), which was
synthesized by Cope and Fordice in 1967.[13] They carried out
a subtle stereochemical study of 1b, including the preparation
of a platinum complex, recrystallization, and liberation of the
platinum moiety. However, an optically active form of 1b
could not be isolated and, hence, they concluded that 1b
might not have significant planar chirality at ambient temper-
ature.[14] To revisit Copeꢀs historic orthocyclophane 1b and to
gain an insight into the influence of X on stereochemical
behavior, we synthesized 1b and the oxygen congener 1c
(X = O).[15] A stereochemical analysis of these in a manner
similar to that of 1a showed that both 1b and 1c have isolable
enantiomers in solution at ambient temperature (Figure 3).
absolute stereochemistry of 1aa was determined to be R for
the (ꢀ)-isomer, based on the stereochemistry of its [2,3]-
Wittig rearrangement product (see below). The half-lives of
the optical activity (t1/2) for 1aa in n-hexane at 40, 50, and
608C are 6.88, 1.87, and 0.553 hours, respectively. The
activation parameters for the racemization of 1aa are
calculated from an Eyring plot by the analysis of the rate
constants of racemization as DH° = 25.5 kcalmolꢀ1 and
DS° = 0.546 calmolꢀ1 Kꢀ1. This result clearly demonstrates
that 1aa has stable chirality at ambient temperature.[8] In
addition, it was found that the stereochemical stability of this
class of orthocyclophanes is considerably increased by the
introduction of a substituent on the ansa chain.[9] For example,
the half-lives of the optical activity of the methyl-substituted
derivative 1ab (X = NTs, R = Me) in n-heptane at 60, 70, 80,
and 908C are 453, 125, 34.0, and 11.9 hours, respectively, and
the activation parameters for the racemization are DH° =
28.7 kcalmolꢀ1 and DS° = ꢀ3.13 calmolꢀ1 Kꢀ1. The absolute
stereochemistry of the enantiomers of 1aa and 1ab were
determined by transformation to a known compound and X-
ray analysis (Figure 2), respectively.[6]
Figure 2. ORTEP drawing of (R)-1ab. Thermal ellipsoids are shown at
50% probability and the tolyl group has been omitted for clarity.
Figure 3. HPLC analyses of 1b and 1c using a chiral stationary
column.[7]
It is noteworthy that the orthocyclophane 1a (X = NTs,
R = H, Me) differs from the bis(allylic) cycle 2 in terms of
thermal stability. For example, 2a (X = NTs, R1 and R2 = H)
easily converts into the transannular Cope rearrangement
product 6 when heated at 1108C for 1 hour. In sharp contrast,
1aa and 1ab were not changed even when heated at 1108C for
7.5 hours, and were quantitatively recovered.[10] These results
The activation parameters for the racemization of 1b and
1c are calculated from an Eyring plot by the analysis of the
rate constants of racemization as DH° = 22.8 kcalmolꢀ1 and
DS° = ꢀ3.31 calmolꢀ1 Kꢀ1, and DH° = 25.1 kcalmolꢀ1 and
DS° = ꢀ4.62 calmolꢀ1 Kꢀ1, respectively. From these data,
along with the data for 1aa described above, the half-lives
of the optical activity (t1/2) of 1aa, 1b, and 1c at 258C were
calculated. The resulting order of t1/2 is 1c (380 h) > 1aa
(56.7 h) > 1b (4.35 h). This trend is consistent with the reverse
bond length order of C-X (C-O < C-N < C-C).[16] These
results show that the stereochemical stability of 1 is highly
dependent upon the embedded atom X in the ansa chain.
With the chiral orthocyclophanes in hand, we turned our
attention to transforming their planar chirality into central
2
www.angewandte.org
ꢀ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Angew. Chem. Int. Ed. 2012, 51, 1 – 5
These are not the final page numbers!

Angewandte
Chemie
chirality using either inter- or intramolecular reactions.[17]
First, the epoxidation reaction of (S)-1aa (> 98% ee) was
performed using mCPBA and quantitatively provided the
epoxide (3R, 4R)-9 (Scheme 2).[6,12] This result attests to the
provides (3aS, 4R)-10. In contrast, an O C9 bond formation
in B will provide (4aR, 10bS)-12.[19] In another reaction, the
base treatment of (S)-1aa and (S)-1ab with nBuLi in THF at
ꢀ78!ꢀ208C provides the transannular aza-[2,3]-Wittig rear-
rangement products (1R, 2S)-13aa and (1R, 2S)-13ab,
respectively, in excellent yields (13aa: quant., 13ab: 87%)
with high stereoselectivity.[12] These transformations of planar
chirality clearly show that the enantioenriched orthocyclo-
phane 1 could serve as a versatile synthetic precursor for
a variety of chiral nitrogen-containing compounds with
central chirality.
ꢀ
As an example, the asymmetric synthesis of the peptide
(1S, 2S, 2’R)-14, a potent compound for selective agonists of
the melanocortin-4 receptor (MC4R) developed by Bakshi
and colleagues, was carried out (Scheme 3).[20] The pep-
Scheme 3. Asymmetric synthesis of the peptide (1S, 2S, 2’R)-14:
a) nBuLi, THF, ꢀ78!ꢀ208C, quant.; b) LiNaph, THF, ꢀ788C, 98%;
c) NsCl, Et3N, DMAP, CH2Cl2, 08C!RT, 95%; d) O3, MeOH-CH2Cl2,
ꢀ788C then PPh3, ꢀ78!08C, 92%; e) NaClO2, NaH2PO4·2H2O, 2-
methyl-2-butene, tBuOH-H2O, RT, quant.; f) DCC, DMAP, CH2Cl2, 08C,
73%; g) TFA, CH2Cl2-H2O, 08C!RT, quant.; h) EDC·HCl, DMAP,
CH2Cl2, 08C, 41%; i) PhSH, K2CO3, DMF, RT, 74%. Boc=tert-butoxy-
carbonyl, DCC=N,N’-dicyclohexylcarbodiimide, DMAP=4-(dimethyl-
amino)pyridine, EDC=N-[3-(dimethylamino)propyl]-N’-ethylcarbodi-
imide, LiNaph=lithium naphthalenide, Ns=2-nitrobenzenesulfonyl,
TFA=trifluoroacetic acid.
Scheme 2. Transformations of (S)-1aa and (S)-1ab: a) mCPBA, CH2Cl2,
08C!RT, quant.; b) TiCl4, CH2Cl2, 08C, 96%; c) 1. TBSOTf, 2,6-luti-
dine, DMF, RT, 65%; 2) RuO2 (cat.), NaIO4 aq., EtOAc, RT, 92%;
d) BF3·OEt2, CH2Cl2, 08C, (4aR, 10bS)-12 (84%) and (3aS, 4R)-10
(6%); e) nBuLi, THF, ꢀ78!ꢀ208C, (1R, 2S)-13aa from (S)-1aa
(quant.), (1R, 2S)-13ab from (S)-1ab (87%). DMF=N,N’-dimethyl-
formamide, mCPBA=meta-chloroperbenzoic acid, TBS=tert-butyl-
dimethylsilyl, Tf=trifluoromethanesulfonyl.
fact that the epoxidation reaction only occurs from the outer
peripheral face. The epoxide (3R, 4R)-9 would be a suitable
substrate for further transannular reactions. Indeed, a TiCl4-
promoted reaction of (3R, 4R)-9 provided the unique tricyclic
compound (3aS, 4R)-10 in excellent yield (96%), in a stereo-
specific manner.[6,12] The resulting (3aS, 4R)-10 can be trans-
formed into (3aS, 4R)-11, which contains the core structure of
palonosetron, by RuO2-catalyzed oxidation.[18] Interestingly
enough, a similar transannular reaction of (3R, 4R)-9 with
BF3·OEt2 afforded a different tricyclic compound, (4aR,
10bS)-12, as the major product (84%),[6,12] along with
a small amount of (3aS, 4R)-10 (6%). These Lewis acid
promoted reactions should involve the same cationic inter-
mediate B, which is formed by the epoxide cleavage and
subsequent intramolecular Friedel–Crafts reaction. Then, 1,2-
migration of C9 from the C8 position to the C13 position
tide(1S, 2S, 2’R)-14 has a bicyclic cis-b-amino acid moiety,
which can be made from the aza-[2,3]-Wittig rearrangement
product (1S, 2R)-13aa. Our synthesis started from the aza-
[2,3]-Wittig rearrangement of enantiopure (R)-1aa under the
above-mentioned reaction conditions, which provided (1S,
2R)-13aa as a single stereoisomer. The change of the
protective group on the nitrogen atom from the Ts to Ns
group and subsequent oxidation of the vinyl group afforded
the desired cis-b-amino acid derivative (1S, 2S)-15 in excellent
yield.[6,12,21,22] Finally, EDC-promoted condensation of (1S,
2S)-15 and the amine (R)-18, derived from 16 and (R)-17, and
subsequent removal of the Ns group provided (1S, 2S, 2’R)-14
as a single stereoisomer. Thus, the asymmetric synthesis of
(1S, 2S, 2’R)-14 was achieved from the planar-chiral orthocy-
clophane (R)-1aa in seven steps with an overall yield of 26%.
Angew. Chem. Int. Ed. 2012, 51, 1 – 5
ꢀ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.angewandte.org
3
These are not the final page numbers!

.
Angewandte
Communications
[9] The stereochemical stabilizing effect of the methyl substituent in
the (E)-cyclodecene system has been reported: J. A. Marshall,
T. R. Konicek, K. E. Flynn, J. Am. Chem. Soc. 1980, 102, 3287 –
3288. A similar substituent effect is seen in nine-membered
nitrogen cycles; see Ref. [3c].
[10] The observed thermal stability of 1a is understandable as a high
energy request for a benzene-ring dearomatization may prohibit
a Cope rearrangement; see: a) C. D. Hurd, H. T. Bollman, J. Am.
Chem. Soc. 1933, 55, 699 – 702; b) A. C. Cope, L. Field, D. W. H.
MacDowell, M. E. Wright, J. Am. Chem. Soc. 1956, 78, 2547 –
2551.
In summary, the synthesis, stereochemical analysis, and
transformation of the newly designed [7]orthocyclophanes
1 have been described. Incorporation of an E-olefinic ansa
chain into the orthocyclophane contributes to the conforma-
tional rigidity relevant to planar chirality and also provides
unique reactivity and synthetic utility. More detailed studies
on the relationship between the structure and the stereo-
chemical stability of orthocyclophanes and their synthetic
applications are in progress.
[11] K. Tomooka, K. Uehara, R. Nishikawa, M. Suzuki, K. Igawa, J.
Am. Chem. Soc. 2010, 132, 9232 – 9233.
[12] The enantiopurities were determined by HPLC analysis using
a chiral stationary phase. The diastereopurities were determined
by 1H NMR analysis or HPLC analysis. See the Supporting
Information for details.
Received: June 9, 2012
Published online: && &&, &&&&
Keywords: atropisomerism · chirality · cyclophanes ·
.
enantioselectivity · rearrangements
[13] A. C. Cope, M. W. Fordice, J. Am. Chem. Soc. 1967, 89, 6187 –
6191.
[14] Cope and Fordice found that the reaction of 1b with trans-
dichloro(ethylene)[(R)-methylbenzylamine]platinum(II)
affords the corresponding diastereomeric pairs of PtII complexes
and they are separable by the fractional crystallization. How-
ever, the liberation reaction of the diastereomerically pure
complex at room temperature or ꢀ708C provides 1b as an
optically inactive form.
[15] Cyclophanes 1b and 1c were synthesized from the diol 3. Details
of their synthesis and reactions will be reported elsewhere.
[16] a) L. Pauling, The Nature of The Chemical Bond, Cornell
University Press, New York, 1960; b) B. Cordero, V. Gꢂmez,
A. E. Platero-Prats, M. Revꢃs, J. Echeverrꢄa, E. Cremades, F.
Barragꢅn, S. Alvarez, Dalton Trans. 2008, 2832 – 2838, and
references therein.
[17] For reviews on the transformation of macrocyclic compounds,
see: a) A. C. Cope, M. M. Martin, M. A. McKervey, Q. Rev.
Chem. Soc. 1966, 20, 119 – 152; b) W. C. Still, I. Galynker,
Tetrahedron 1981, 37, 3981 – 3996; c) U. Nubbemeyer, Eur. J.
Org. Chem. 2001, 1801 – 1816. For recent reports on stereose-
lective transformation of planar chirality of medium-sized ring
containing central chirality, see: d) A. Sudau, W. Mꢆnch, J. A.
Bats, U. Nubbemeyer, Chem. Eur. J. 2001, 7, 611 – 621; e) M.
Prꢃvost, K. A. Woerpel, J. Am. Chem. Soc. 2009, 131, 14182 –
14183. For recent reports on stereoselective transformation of
sole planar-chiral medium-sized ring, see: f) K. Tomooka, M.
Suzuki, M. Shimada, N. Runyan, K. Uehara, Org. Lett. 2011, 13,
4926 – 4929. and Ref. [3].
[1] For general reviews on cyclophanes, see: a) B. H. Smith, Bridged
Aromatic Compounds, Academic Press, New York, 1964;
b) Cyclophanes, Vols. 1 and 2 (Eds.: P. M. Keehn, S. M. Rose-
nfeld), Academic Press, New York, 1983; c) K. Schlçgl, Top.
Curr. Chem. 1984, 125, 27 – 62; d) F. Diederich, Cyclophanes,
Royal Society of Chemistry, London, 1991; e) F. Vçgtle, Cyclo-
phane Chemistry, Wiley, New York, 1993; f) V. V. Kane, W. H.
de Wolf, F. Bickelhaupt, Tetrahedron 1994, 50, 4575 – 4622;
g) Modern Cyclophane Chemistry (Eds.: R. Gleiter, H. Hopf),
Wiley-VCH, Weinheim, 2004.
[2] For representative studies on orthocyclophanes, see: a) A. G.
Anastassiou, S. S. Libsch, R. C. Griffith, Tetrahedron Lett. 1973,
14, 3103 – 3106; b) G. Bodwell, L. Ernst, M. W. Haenel, H. Hopf,
Angew. Chem. 1989, 101, 509 – 510; Angew. Chem. Int. Ed. Engl.
1989, 28, 455 – 456; c) W. Y. Lee, C. H. Park, Y. D. Kim, J. Org.
Chem. 1992, 57, 4074 – 4079; d) Y. Tobe, M. Kawaguchi, K.
Kakiuchi, K. Naemura, J. Am. Chem. Soc. 1993, 115, 1173 – 1174;
e) E. Lindner, W. Wassing, R. Fawzl, M. Steimann, Angew.
Chem. 1994, 106, 363 – 365; Angew. Chem. Int. Ed. Engl. 1994,
33, 321 – 323; f) S. Mataka, K. Shigaki, T. Sawada, Y. Mitoma, M.
Taniguchi, T. Thiemann, K. Ohga, N. Egashira, Angew. Chem.
1998, 110, 2626 – 2628; Angew. Chem. Int. Ed. 1998, 37, 2532 –
2534.
[3] a) K. Tomooka, N. Komine, D. Fujiki, T. Nakai, S. Yanagitsuru, J.
Am. Chem. Soc. 2005, 127, 12182 – 12183; b) K. Tomooka, M.
Suzuki, M. Shimada, S. Yanagitsuru, K. Uehara, Org. Lett. 2006,
8, 963 – 965; c) K. Tomooka, M. Suzuki, K. Uehara, M. Shimada,
T. Akiyama, Synlett 2008, 2518 – 2522; d) K. Uehara, K.
Tomooka, Chem. Lett. 2009, 38, 1028 – 1029.
[4] For reviews on planar-chiral trans-cycloalkenes, see: a) J. A.
Marshall, Acc. Chem. Res. 1980, 13, 213 – 218; b) M. Nakazaki,
K. Yamamoto, K. Naemura, Top. Curr. Chem. 1984, 125, 1 – 25;
c) E. L. Eliel, S. H. Wilen, L. N. Mander in Stereochemistry of
Organic Compounds, Wiley, New York, 1994, pp. 1172 – 1175.
[5] The exact origin of the group selectivity is not clear at present.
Further studies to clarify the generality and mechanism of the
group selective Mitsunobu reaction are now underway.
[6] The structures of 1aa, 1ab, 9, 10, 12, and 15 were determined by
X-ray crystallography. See the Supporting Information for
details.
[18] For reviews on palonosetron, see: a) G. J. Kilpatrick, K. T.
Bunce, M. B. Tyers, Med. Res. Rev. 1990, 10, 441 – 475; b) S. M.
Grunberg, J. M. Koeller, Expert Opin. Pharmacother. 2003, 4,
2297 – 2303; c) M. A. A. Siddiqui, L. J. Scott, Drugs 2004, 64,
1125 – 1132.
[19] The change of the reaction pathway should be due to the
difference in counter ions of intermediate B.
[20] R. K. Bakshi, Q. Hong, J. T. Olson, Z. Ye, I. K. Sebhat, D. H.
Weinberg, T. MacNeil, R. N. Kalyani, R. Tang, W. J. Martin, A.
Strack, E. McGowan, C. Tamvakopoulos, R. R. Miller, R. A.
Stearns, W. Tang, D. E. Maclntyre, L. H. T. van der Ploeg, A. A.
Patchett, R. P. Nargund, Bioorg. Med. Chem. Lett. 2005, 15,
3430 – 3433.
[21] Amine synthesis using an Ns group, see: a) T. Kan, T. Fukuyama,
J. Synth. Org. Chem. Jpn. 2001, 59, 779 – 789; b) T. Kan, T.
Fukuyama, Chem. Commun. 2004, 353 – 359.
[7] HPLC analyses of 1aa, 1ab, 1b, and 1c were performed with
CHIRALCEL OD-H (4.6 mm ꢁ 250 mm) at room temperature.
See the Supporting Information for details.
[22] Based on the absolute stereochemistry of 15 and the steric
course of the [2,3]-Wittig rearrangement, the absolute stereo-
chemistry of 1aa was determined as R for the (ꢀ)-isomer.
[8] The observed stereochemical stability of 1aa is lower than that
of 2a (X = NTs, R1, R2 = H) (DH° = 26.3 kcalmolꢀ1); see
Ref. [3c]. This difference is reasonably explained by an increase
in the flexibility of the ring due to the introduction of a benzene
ring, which has a longer bond length than that of the Z alkene.
4
www.angewandte.org
ꢀ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Angew. Chem. Int. Ed. 2012, 51, 1 – 5
These are not the final page numbers!

Angewandte
Chemie
Communications
Chirality
K. Tomooka,* C. Iso, K. Uehara,
M. Suzuki, R. Nishikawa-Shimono,
K. Igawa
&&&& — &&&&
Planar-Chiral [7]Orthocyclophanes
Just plain chiral: The [7]orthocyclophanes
1, having an E-olefinic ansa chain, exhibit
planar chirality at ambient temperature
and their stereochemical stabilities are
highly dependent upon the embedded X
group in the ansa chain. Inter- and intra-
molecular transformations of 1 (where
X=NTs) provide a variety of nitrogen-
containing chiral molecules in a stereo-
specific manner. Ts=4-toluenesulfonyl.
Angew. Chem. Int. Ed. 2012, 51, 1 – 5
ꢀ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.angewandte.org
5
These are not the final page numbers!