Synthesis of novel acetylenic cyclophanes with helical chirality: Potential new structures for liquid crystals

Article abstract of DOI:10.1021/ol000199k

(matrix presented) The synthesis of a series of novel acetylenic cyclophanes is described. X-ray crystallographic analysis of the core structure revealed a twisted conformation with helical chirality. Preliminary results suggest that these cyclophanes, wi

Full text of DOI:10.1021/ol000199k

ORGANIC
LETTERS
2000
Vol. 2, No. 20
3189-3192
Synthesis of Novel Acetylenic
Cyclophanes with Helical Chirality:
Potential New Structures for Liquid
Crystals
Shawn K. Collins, Glenn P. A. Yap,† and Alex G. Fallis*
Department of Chemistry, UniVersity of Ottawa, 10 Marie Curie,
Ottawa, Ontario, Canada K1N 6N5
afallis@science.ottawa.ca
Received July 26, 2000
ABSTRACT
The synthesis of a series of novel acetylenic cyclophanes is described. X-ray crystallographic analysis of the core structure revealed a twisted
conformation with helical chirality. Preliminary results suggest that these cyclophanes, with appropriate functionality, have the potential to act
as unique liquid crystalline materials.
The synthesis and design of novel cyclophanes and assorted
cage compounds with novel shapes and geometries continue
to be topics of current interest.1 Earlier, we reported the
synthesis of a new class of cyclophanes connected by
enediyne moieties.2 A number of [1.4]paracyclophanes3 are
known, and recently we described the synthesis of a related
class of phenyl acetylene cyclophanes in which a benzene
ring replaced the double bond.4 The combination of the
number and type of unsaturated linkages in these molecules
creates a twisted conformation that imparts helical chirality.3d,5
This property, which is shared with other D2-symmetric
cyclophanes,6 should allow these molecules to be employed
as novel liquid crystalline materials.7
The design of liquid crystals, dopants, and optically active
materials using chiral aromatic cores has attracted increased
interest.8 Enantiomerically pure optically active materials
† For enquiries regarding X-ray analysis.
(4) Collins, S. K.; Yap, G. P. A.; Fallis, A. G. Angew. Chem., Int. Ed.
2000, 39, 385.
(1) (a) Top. Curr. Chem. 1983, 113. (b) Top. Curr. Chem. 1983, 115.
(c) Cyclophanes; Keehn, P. M., Rosenfeld S. M., Eds.; Academic Press:
New York, 1983; Vols. I, II. (d) Diederich, F. Cyclophanes; Royal Society
of Chemistry: Cambridge, UK, 1991. (e) Vogtle, F. Cyclophane Chemistry;
Wiley: New York, 1993. (f) Top. Curr. Chem. 1994, 172. (g) Bodwell, G.
J. Angew. Chem., Int. Ed. Engl. 1996, 35, 2085. (h) de Meijere, A.; Konig,
B. Synlett 1997, 1221.
(2) Romero, M. A.; Fallis, A. G. Tetrahedron Lett. 1994, 35, 4711.
(3) (a) Heirtzler, F. R.; Hopf, H.; Jones, P. G.; Bubenitschek, P.
Tetrahedron Lett. 1995, 36, 1239. (b) Hopf, H.; Jones, P. G.; Bubenitschek,
P.; Werner, C. Angew. Chem., Int. Ed. Engl. 1995, 34, 2367. (c) Kawase,
T.; Ueda, N.; Darabi, H. R.; Oda, M. Angew. Chem., Int. Ed. Engl. 1996,
35, 1556. (d) Haley, M. M.; Langsdorf, B. L. Chem. Commun. 1997, 1121.
(e) Ohkita, M.; Ando, K.; Suzuki, T.; Tsuji, T. J. Org. Chem. 2000, 65,
4385.
(5) For examples of helical chirality in cyclophanes, see: (a) Boese, R.;
Matzger, A. J.; Vollhardt, K. P. C. J. Am. Chem. Soc. 1997, 119, 2052. (b)
Haley, M. M.; Bell, M. L.; Brand, S. C.; Kimball, D. B.; Pak, J. J.; Wan,
W. B. Tetrahedron Lett. 1997, 38, 7483. Molecular scaffolds: (c) Marsella,
M. J.; Kim, I. T.; Tham, F. J. Am. Chem. Soc. 2000, 122, 974.
(6) Malaba, D.; Djebli, A.; Chen, L.; Zarate, E. A.; Tessier, C. A.;
Youngs, W. J. Organometallics 1993, 12, 1266.
(7) (a) Mizutani, T.; Yagi, S.; Morinaga, Y.; Nomura, T.; Takagishi, T.;
Kitagawa, S.; Ogoshi, H. J. Am. Chem. Soc. 1999, 121, 754. (b) Yang, K.;
Campbell, B.; Birch, G.; Williams, V. E.; Lemieux, R. P. J. Am. Chem.
Soc. 1996, 118, 9557. (c) Chin, E.; Goodby, J. W. J. Am. Chem. Soc. 1986,
108, 4736. (d) Goodby, J. W.; Chin, E.; Leslie, T. M.; Geary, J. M.; Patel,
J. S. J. Am. Chem. Soc. 1986, 108, 4729.
(8) Katz, T. J. Angew. Chem., Int. Ed. 2000, 39, 1921.
10.1021/ol000199k CCC: $19.00 © 2000 American Chemical Society
Published on Web 09/07/2000

containing biphenyl cores have been investigated for use as
liquid crystals9 as well as dopants.10 The best ferroelectric
liquid crystals have an aromatic core adjacent to a chiral
center. Until recently, there were no examples in which the
aromatic core also provided the chirality. However, Katz et
al. constructed racemic helicenes containing long alkyl chains
which form a liquid crystalline phase and assemble in
solution to form helical columns.11 Subsequently, they
prepared the related chiral nonracemic derivatives 1 to
generate the first liquid crystalline columnar mesophase
molecules with a nonracemic helical aromatic core.12 Heli-
cenes have also been assembled with acetylene bridges to
form helical cyclophanes and polymers in order to investigate
their optical properties.13
Scheme 1. Synthesis of Core Structurea
a (a) (i) BuLi, THF, -78 °C, 15 min, (ii) ZnBr2, THF, 0 °C, 15
min, (iii) 1,4-bis(bromoethynyl)benzene, Pd(PPh3)4, reflux, 15 h;
(b) K2CO3, THF, MeOH, H2O, 15 h; (c) Cu(OAc)2 (6 equiv), 3:1
pyridine:Et2O, 4 h.
We envisioned that modification of our acetylenic cyclo-
phanes should also afford compounds that would exhibit
interesting optical properties, and in addition, they might
serve as liquid crystal dopants to induce the type of
polarization observed for smectic liquid crystals.5c,d The
parent ring system represented by the cyclic structure 2
appeared to possess the required geometric constraints to
provide the desired rigid conformation (Figure 1). We wish
diacetylene 4 83%. Dimerization with Cu(OAc)2 in 3:1
pyridine:ether under high dilution conditions gave the
expected dimer in 21% yield. The increase in separation of
the terminal acetylenes eliminated the product resulting from
intramolecular coupling (cf. 10, Scheme 3).3 X-ray crystal-
lographic analysis of the hydrocarbon core revealed the
stereoviews in Figure 2 which confirmed the twisted helical
Figure 1. Helicene (above) and cyclophane (below) core structures.
to report the synthesis of a series of functionalized ben-
zenoid-acetylenic cyclophanes in order to eventually access
their potential optical properties.
Initially we prepared 2 (n ) 1) by the route outlined in
Scheme 1. Lithium-halogen exchange of (2-bromophenyl-
ethynyl)trimethylsilane followed by transmetalation with
ZnBr affords an organozincate that is coupled with 1,4-bis-
(bromoethynyl)benzene15 in the presence of Pd(PPh3)4 to
afford 3 in 49% yield. Removal of the trimethylsilyl
protecting groups with K2CO3 in THF/MeOH/H2O gave the
Figure 2. X-ray crystal structure of the parent cyclophane 2 (n )
1) displaying its twisted nature and the helical chirality inherent in
these compounds. View from the top (above) and from the side
(below).14
(9) Solladie, G.; Hugele, P.; Bartsch, R.; Skoulios, A. Angew. Chem.,
Int. Ed. Engl. 1996, 35, 1533.
(10) Vizitiu, D.; Lazar, C.; Halden, B. J.; Lemieux R. P. J. Am. Chem.
Soc. 1999, 121, 8229.
(11) Nuckolls, C.; Katz, T. J.; Katz, G.; Collings, P. J.; Castellanos, L.
J. Am. Chem. Soc. 1999, 121, 79.
(12) Nuckolls, C.; Katz, T. J. J. Am. Chem. Soc. 1998, 120, 9541.
(13) Fox, J. M.; Lin, D.; Itagaki, Y.; Fujita, T. J. Org. Chem. 1998, 63,
2031.
geometry that was anticipated. This differed significantly
from the special orientation observed with a smaller cyclo-
phane,3 in which a pincer like arrangement of the aromatic
rings resulted in cocrystallization of the solvent (CH2Cl2).
As illustrated, the two central benzene rings are aligned in
a slightly offset but overlapping, superimposed manner,
3190
Org. Lett., Vol. 2, No. 20, 2000

through the central axis with an inter-ring distance of 3.572
Å (Figure 2). The length of the diacetylene “arm” is 13.073
Å, while the spacial separation of the bent top and bottom
phenyl rings is slightly longer at 16.371 Å.
Scheme 3. Synthesis of Diacetylenic Cyclophanesa
Our strategy for the potential liquid crystalline cyclophanes
was based upon the synthetic route above in which a C11-
alkyl chain could be attached by an ether linkage. The first
series examined were cyclophanes related to 2 (n ) 0) in
which the acetylene spacers have been deleted.
These syntheses commenced with the conversion of 2,5-
dibromoaniline to the corresponding phenol via a diazonium
salt intermediate. Attachment of the appropriate side chain
was accomplished in greater than 90% yield by refluxing
the alkyl bromide with the phenol in acetone in the presence
of K2CO3 (Scheme 2). Compounds 5a and 5b were employed
Scheme 2. Synthesis of Acetylenic Cyclophane Precurosorsa
a (a) H2SO4, NaNO2, H2O, reflux 3h; (b) for 5a, 1-bromo-
undecane, K2CO3, acetone, reflux, 15 h; for 5b, methyl 11-
bromoundecanoate, K2CO3, acetone, reflux, 15 h.
a (a) (i) BuLi, THF, -78 °C, 15 min, (ii) ZnBr2, THF, 0 °C, 15
min, (iii) 5a or 5b, Pd(PPh3)4, reflux, 15 h; (b) K2CO3, THF, MeOH,
H2O, 15 h; (c) Cu(OAc)2 (6 equiv), 3:1 pyridine:Et2O, 4 h; (d)
LiOH, H2O, THF, MeOH, 5 h.
as starting materials for the synthesis of both the shortened
(n ) 0) and extended (n ) 1) cyclophanes.
bearing compounds 8b and 9b were subjected to hydrolysis
using LiOH in THF/MeOH/H2O. The corresponding acids
10b and 11b were isolated in yields of 75% and 50%,
respectively. Unfortunately 10b rapidly decomposes to
become a black tar over several hours, while 11b remained
an orange foam which could not be crystallized.
The 13C NMR spectra obtained for the dimers indicated
that a mixture of compounds had been formed. Several
signals appeared as pairs of equal intensity. This is a
consequence of the free rotation of the central benzene ring,
despite the presence of the long chains, and the formation
of the statistical 1:1 mixture of isomers during the dimer-
ization. These dimers were therefore a racemic mixture of
the two different regioisomers.
The next series of compounds were generated by insertion
of an additional acetylene unit between the central and outer
benzene rings of the cyclophanes. Their synthesis (Scheme
4) also began with 5a and 5b. The reaction sequence, via
Sonogashira coupling, paralleled the routes described above
to provide the acetlyene monomers 15, except the cross-
coupling step required the use of (2-iodoophenylethynyl)-
trimethylsilane in place of the bromide (from treatment of
the lithium salt with NIS, 95%). The dimerization was
accomplished under Cu(OAc)2 reaction conditions identical
to those used previously to provide the dimers 16a and 16b
in similar yields of 40-41%. Dimer 16a was a golden yellow
liquid, which solidified into a brittle yellow solid when placed
Construction of the mono- and diacetylenic synthons was
achieved using ZnBr-mediated palladium cross-coupling
methodology described previously (Scheme 3).3,16 Generation
of the organozincate of (2-bromophenylethynyl)trimethyl-
silane followed by addition of 5a or 5b and Pd(PPh3)4
afforded the silyl-protected derivatives 6a and 6b in yields
of 78% and 51%, respectively. Deprotection of the trimeth-
ylsilyl groups gave the diacetylenes 7a and 7b in 100% and
75% yields. Dimerization of 7a or 7b with Cu(OAc)2 under
pseudo high dilution conditions (syringe pump addition) gave
mixtures of both the expected dimers and the “monomer”
products resulting from intramolecular coupling of the
terminal acetylenes.3 Yields of the monomer compounds
were similar and provided the products in 35-45% yield as
yellow gums which blackened over time upon exposure to
air (even when stored under nitrogen) for both series of
compounds. The dimer 9a was obtained in 36% yield, while
9b was obtained in 18% yield. The dimers were obtained as
yellow foams. In an effort to obtain solid samples, the ester-
(14) X-ray data for compound 2 has been deposited with the Cambridge
Crystallographic Data Centre as supplementary publication number CCDC
147868. Copies of the data may be obtained free of charge from CCDC,
12 Union Road, Cambridge CB2 1EZ, UK (fax (+44) 1223-336-033;
e-mail deposit@ccdc.cam.ac.uk).
(15) 1,4-Bis(bromoethynyl)benzene was isolated as a pale yellow solid
prepared in 91% yield by treating 1,4-ethynylbenzene with NBS in acetone
in the presence of a catalytic amount of AgNO3 (15 h).
(16) Sengupta, S.; Snieckus, V. J. Org. Chem. 1990, 55, 5680.
Org. Lett., Vol. 2, No. 20, 2000
3191

liquid, while the remaining portion melted from 48 to 66 °C
to provide a gray opaque solution typical of liquid crystal
behavior. This is likely due to the more polar regioisomer
of 16b but definitive proof will require an single enantio-
merically pure isomer. Unfortunately, the individual isomers
could not be separated. Thus, in the future, modification of
the synthetic sequence to incorporate substituents into the
rigid (corner) phenyl rings would eliminate the current
complication from free rotation of the central benzene rings.
Scheme 4. Synthesis of Extended Acetylenic Cyclophanesa
In summary, we have developed a short, efficient syntheses
of a series of novel, functionalized acetylenic cyclophanes
by Pd- and Cu-mediated coupling reactions. The X-ray
analysis of the extended cyclophane has established the
nature of the hydrocarbon core. This structure differs from
the previously synthesized dimer and suggests that further
synthetic manipulation will generate interesting solid-state
geometries. The synthetic protocol above will also facilitate
the preparation of new derivatives which may possess
unusual optical properties. These methods allow variation
of the chain length, alteration of the position of the alkyl
groups, and modification of the acetylene spacers to control
the helical conformation. In addition, the inclusion of
heteroaromatic rings should permit the capture of metal
ions.17
a (a) Pd(PPh3)2Cl2, CuI, TMSA, DEA, THF, reflux, 15 h; (b)
K2CO3, THF, MeOH, H2O, 15 h; (c) (2-iodophenylethynyl)tri-
methylsilane, Pd(PPh3)2Cl2, CuI, DEA, THF, reflux, 15 h; (d)
Cu(OAc)2 (6 equiv), 3:1 pyridine:Et2O, 4 h.
Acknowledgment. We are grateful to the National
Sciences and Engineering Research Council of Canada for
financial support of this research and to Professor Bob
Lemieux for helpful advice and the use of his equipment. S.
K. Collins thanks NSERC for a Graduate Scholarship. We
also thank the referees for their constructive suggestions.
under vacuum, while compound 16b was obtained as a pale
orange solid. Both dimers exhibited the same 13C NMR effect
as was observed with the standard group of cyclophanes.
Independent examination of the melting range of these
compounds on a hot stage polarizing microscope did not
reveal liquid crystal behavior in the case of 16a. However,
approximately 50% of the sample 16b melted as a clear
OL000199K
(17) (a) Baena, M. J.; Barbera, J.; Espinet, P.; Ezcurra, A.; Ros, M. B.;
Serrano, J. L. J. Am. Chem. Soc. 1994, 116, 1899. (b) van Nostrum, C. F.;
Picken, S. J.; Schouten, A. J.; Notle, R. J. M. J. Am. Chem. Soc. 1995,
117, 9957.
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