Hetero-double-helix formation by an ethynylhelicene oligomer possessing perfluorooctyl side chains

Article abstract of DOI:10.1021/jo8010057

(Chemical Equation Presented) Monomeric to pentameric (P)-ethynylhelicene oligomers possessing perfluorooctyl side chains were synthesized. The circular dichroism (CD) and vapor pressure osomometry (VPO) studies indicated the formation of a helix-dimer for the (P)-pentamer, for example, in trifluoromethylbenzene at 5°C at concentrations above 2 × 10 ^-6 M. Compared with a (P)-pentamer possessing decyloxycarbonyl side chains, the perfluorooctyl (P)-pentamer exhibited lower solubilities in organic solvents, formed a thermodynamically more stable helix-dimer, and exhibited a mirror image CD spectrum. The perfluorooctyl (P)-pentamer formed a hetero-helix dimer with a decyloxycarbonyl (M)-pentamer but not with a (P)-pentamer. It indicated higher stability of the hetero-helix dimer over the homo-helix dimers.

Full text of DOI:10.1021/jo8010057

Hetero-Double-Helix Formation by an Ethynylhelicene Oligomer
Possessing Perfluorooctyl Side Chains
Ryo Amemiya, Nozomi Saito, and Masahiko Yamaguchi*,†
Department of Organic Chemistry, Graduate School of Pharmaceutical Sciences, Tohoku UniVersity, Aoba,
Sendai 980-8578, Japan
yama@mail.pharm.tohoku.ac.jp
ReceiVed May 9, 2008
Monomeric to pentameric (P)-ethynylhelicene oligomers possessing perfluorooctyl side chains were
synthesized. The circular dichroism (CD) and vapor pressure osomometry (VPO) studies indicated the
formation of a helix-dimer for the (P)-pentamer, for example, in trifluoromethylbenzene at 5 °C at
concentrations above 2 × 10-6 M. Compared with a (P)-pentamer possessing decyloxycarbonyl side
chains, the perfluorooctyl (P)-pentamer exhibited lower solubilities in organic solvents, formed a
thermodynamically more stable helix-dimer, and exhibited a mirror image CD spectrum. The perfluorooctyl
(P)-pentamer formed a hetero-helix dimer with a decyloxycarbonyl (M)-pentamer but not with a (P)-
pentamer. It indicated higher stability of the hetero-helix dimer over the homo-helix dimers.
Introduction
reported,2 hetero-double-helices are rare because of the difficulty
in designing two different acyclic compounds that recognize
each other. Lehn used five-coordinate Cu2+ ions to bind
bipyridine oligomers and terpyridine oligomers to form a hetero-
double-helix.3 Huc reported the formation of a hetero-double-
helix between aromatic oligoamides and their N-oxides via
hydrogen bonds and π-π interactions.4 Yashima developed a
double-helical assembly composed of two crescent-shaped
As exemplified by DNA, the double-helix is an essential
molecular structure in biological systems, and structural changes
in response to changes in the environment play important roles
in its functions. A double-helix is constructed by noncovalent
interactions between two acyclic compounds, and homo- and
hetero-double-helices can be formed depending on the affinity
of the two compounds. A homo-double-helix is formed from
two identical compounds, while the formation of a hetero-
double-helix requires two distinct compounds which recognize
each other.
(2) (a) Berl, V.; Huc, I.; Khoury, R. G.; Krische, M. J.; Lehn, J.-M. Nature
2000, 407, 720–723. (b) Berl, V.; Huc, I.; Khoury, R. G.; Lehn, J.-M.
Chem.sEur. J. 2001, 7, 2810–2820. (c) Barboiu, M.; Vaughan, G.; Kyritsakas,
N.; Lehn, M.-J. Chem.sEur. J. 2003, 9, 763–769. (d) Jiang, H.; Maurigot, V.;
Huc, I. Tetrahedron 2004, 60, 10029–10038. (e) Kategiri, H.; Miyagawa, T.;
Furusho, Y.; Yashima, E. Angew. Chem., Int. Ed. 2006, 45, 1741–1744. (f)
Haldar, D.; Jiang, H.; Le´gar, J.-M.; Huc, I. Angew. Chem., Int. Ed. 2006, 45,
5483–5486. (g) Goto, H.; Katagiri, H.; Furusho, Y.; Yashima, E. J. Am. Chem.
Soc. 2006, 128, 7176–7178. (h) Li, J.; Wisner, A.; Jennings, M. C. Org. Lett.
2007, 9, 3267–3269.
Recently, synthetic oligomeric compounds that can form
double-helices have attracted much interest,1 since they exhibit
novel functions that utilize their structural changes and can be
used to promote understanding of the function of double-helical
biomolecules. While several homo-double-helices have been
(3) (a) Hasenknopf, B.; Lehn, J.-M.; Baum, G.; Fenske, D. Proc. Natl. Acad.
Sci. U.S.A. 1996, 93, 1397–1400. (b) Marquis, A.; Smith, V.; Harrowfield, J.;
Lehn, J.-M.; Herschbach, H.; Sanvito, R.; Leise-Wagner, E.; Dorsselaer, A. V.
Chem.sEur. J. 2006, 12, 5632–5641.
(4) Zhan, C.; Le´ger, J.-M.; Huc, I. Angew. Chem., Int. Ed. 2006, 45, 4625–
4628.
† WPI Advanced Institute for Materials Research, Tohoku University, Aoba,
Sendai 980-8577, Japan.
(1) Reviews: (a) Hill, D. J.; Mio, M. J.; Prince, R. B.; Hughes, T. S.; Moore,
J. S. Chem. ReV. 2001, 101, 3893–4011. (b) Albecht, M. Angew. Chem., Int.
Ed. 2005, 44, 6448–6451. (c) Furusho, Y.; Yashima, E. Chem. Rec. 2007, 1, 11.
10.1021/jo8010057 CCC: $40.75
Published on Web 08/26/2008
2008 American Chemical Society
J. Org. Chem. 2008, 73, 7137–7144 7137

Amemiya et al.
SCHEME 1a
a Key: (a) Pd2(dba)3 ·CHCl3, CuI, Ph3P, Mes3P, n-Bu4NI, Et3N, DMF/THF; (b) Bu4NF, THF, 0 °C.
m-terphenyl derivatives5a and their analogues5b,e using aminidium-
carboxylate salt bridges. The formation of a hetero-double-helix
between oligoresolcinols and oligosaccharides has also been
reported.6 Further studies to synthesize hetero-double-helices
are required to develop substances that can exhibit novel
functions.
Previously, we reported the synthesis of optically active
ethynylhelicene oligomers possessing two to nine helicenes
connected by m-phenylene spacers (Scheme 1).7,8 The CD
(CHCl3, 5 × 10-6 M, 25 °C) spectrum of the heptamer (P)-2
was quite different from those of oligomers from dimer to
hexamer and exhibited an extremely strong Cotton effect (the
large absolute values of ∆ꢀ up to several thousands) over the
hexamer with an inverted sign between 300 and 400 nm. Vapor
pressure osmometry (VPO) analysis of (P)-2 (CHCl3, 40 °C)
showed the dimeric structure. These observations indicated that
(P)-2 formed a helix dimer, most probably a double-helix.
Further investigations of (P)-2 revealed that the rate constant
k for the unfolding of the double-helix to random coil was
largely dependent on the aromatic solvents used.8a The k values
differed by 7 orders of magnitude between iodobenzene and
trifluoromethylbenzene, and the log k values exhibited a good
correlation with the absolute hardness η of aromatic molecules,
which were obtained by Pearson employing the ionization
potential and electron affinity.9 Higher unfolding rates were
observed in soft arenes and lower rates in hard arenes. Hard
arenes such as trifluoromethylbenzene and m-difluorobenzene
are strong helix-forming solvents. The results suggest a strong
relationship between the π-π interaction and the HSAB
principle: the π-π interaction is a soft interaction.
Thus, we investigated the effect of the hardness of the arenes
contained in the oligomers. The m-phenylene spacers of (P)-2
were changed from the relatively soft decyloxycarbonylphe-
nylene spacers to hard perfluorooctylphenylene spacers. The
former can be regarded as oligomers containing soft aromatic
moieties, and the manipulation would provide compounds with
an alternating arrangement of soft and hard arenes. We compared
the decyloxycarbonyl compounds and the perfluorooctyl com-
pounds on the basis of homo-double-helix formation. In addition,
the hetero-double-helix formation was examined between the
decyloxycarbonyl compounds and perfluorooctyl compounds.
In this study, perfluorooctyl dimer (P)-3 to pentamer (P)-6
were synthesized, and the CD and VPO studies demonstrated
that the pentamer (P)-6 and the decyloxycarbonyl pentamer
(P)-1 formed stable homo-double-helix in trifluoromethylben-
zene. A notable feature of (P)-6 compared to (P)-1 is that the
screw sense of the homo-double-helix was inverted, despite both
helicenes having the same configuration. (P)-6 formed a hetero-
double-helix with (M)-1 but not with (P)-1. This is a novel
methodology to construct hetero-double-helix using enantio-
meric compounds with different side chains.
Results and Discussion
(5) (a) Tanaka, Y.; Katagiri, H.; Furusho, Y.; Yashima, E. Angew. Chem.,
Int. Ed. 2005, 44, 3867–3870. (b) Ikeda, M.; Tanaka, Y.; Hasegawa, T.; Furusho,
Y.; Yashima, E. J. Am. Chem. Soc. 2006, 128, 6806–6807. (c) Furusho, Y.;
Tanaka, Y.; Yashima, E. Org. Lett. 2006, 8, 2583–2586. (d) Hasegawa, T.;
Furusho, Y.; Katagiri, H.; Yashima, E. Angew. Chem., Int. Ed. 2007, 46, 5885–
5888. (e) Furusho, Y.; Tanaka, Y.; Maeda, T.; Ikeda, M.; Yashima, E. Chem.
Commun. 2007, 3174–3176.
A series of (P)-perfluorooctyl oligomers (P)-3 to (P)-6 were
synthesized by repeating the Sonogashira coupling and depro-
tection by a two-directional method using a building block (P)-9
according to the synthesis of (P)-decyloxycarbonyl oligomers
(Scheme 1).8a The building block (P)-9 was synthesized by
coupling monosilylated helicene (P)-811 and 4 equiv of spacer
(6) Goto, H.; Furusho, Y.; Yashima, E. J. Am. Chem. Soc. 2007, 129, 9168–
9174.
(7) Amemiya, R.; Yamaguchi, M. Chem. Rec. 2008, 8, 116–127.
(8) (a) Sugiura, H.; Nigorikawa, Y.; Saiki, Y.; Nakamura, K.; Yamaguchi,
M. J. Am. Chem. Soc. 2004, 126, 14858–14864. (b) Sugiura, H.; Yamaguchi,
M. Chem. Lett. 2007, 36, 58–59.
(10) See the Supporting Information.
(11) Nakamura, K.; Okubo, H.; Yamaguchi, M. Org. Lett. 2001, 3, 1097–
1099.
(9) Pearson, R. G. J. Org. Chem. 1989, 54, 1423–1430.
7138 J. Org. Chem. Vol. 73, No. 18, 2008

Hetero-Double-Helix Formation by an Ethynylhelicene Oligomer
7, which in turn was synthesized from 3,5-dihydroxyiodoben-
zene.10 The reaction of (P)-diethynylhelicene (P)-1011 and 2
equiv of (P)-9 under the rapid Sonogashira coupling conditions12
yielded the trimer (P)-4 in 77% yield. (P)-4 was treated with
Bu4NF in THF giving the deprotected trimer (P)-12, and the
subsequent coupling gave the pentamer (P)-6 in 36% yield. The
dimer (P)-3 and the tetramer (P)-5 were synthesized in 81%
and 50% yield, respectively, by the sequence of the reactions
starting from 7. The solubility of the oligomers in organic
solvents significantly decreased with the increase in the number
of helicenes, and the yield of the coupling reaction decreased.
Because of the solubility problem, the hexamer could not be
obtained in an acceptable yield.
The solubilities of the pentamers (P)-1 and (P)-6 in organic
solvents were compared. Whereas (P)-1 readily dissolved in
various aromatic solvents, chloroform, and tetrahydrofuran
(THF) at 1 × 10-3 M, (P)-6 was soluble at 1 × 10-3 M in
chloroform, THF, and m-difluorobenzene at 40 °C but only
partially soluble at 5 °C. Under identical conditions, (P)-6 was
partially soluble in toluene, chlorobenzene, fluorobenzene, and
trifluoromethylbenzene. The solubility of (P)-6 was not im-
proved in fluorophilic solvents, such as hexafluorobenzene,
n-perfluorooctane, and perfluoro(2-butyltetrahydrofuran). At 1
× 10-4 M, (P)-6 was soluble only in chloroform, THF,
m-difluorobenzene, toluene, chlorobenzene, and fluorobenzene
at 5 °C. The solubility in trifluoromethylbenzene, a strong helix-
forming solvent, was examined in more detail. At 5 and 60 °C,
(P)-6 dissolved only at concentrations below 2.5 × 10-5 M,
and slow precipitation was observed after 30 min at 5 °C. The
spectroscopic studies of (P)-6 in trifluoromethylbenzene, there-
fore, were conducted within 30 min after cooling the solution
to 5 °C. In addition, reproducibility was checked for all the CD
experiments shown below, and the homogeneity of the solutions
was confirmed. Formation of precipitate resulted in ill reproduc-
ibility of such experiments. The poor solubility of (P)-6
compared to (P)-1 may be related to double-helix formation
with the perfluorootyl group directed to the outside of the helix.
Presumably, the regular arrangement of the side chain strength-
ened the intermolecular aggregation between double-helices
resulting in poor solubility.
The CD studies were conducted on dimer (P)-3 to pentamer
(P)-6 in chloroform and trifluoromethylbenzene, which are weak
and strong helix-forming solvents, respectively. In chloroform,
|∆ꢀ| (the absolute value of ∆ꢀ) of the CD spectra (5 × 10-6 M,
25 °C) of (P)-3 to (P)-6 showed a monotonic increase in
accordance with the number of helicenes on the basis of (P)-3
(Figure 1a). In trifluoromethylbenzene (5 × 10-6 M, 25 °C),
(P)-3, (P)-4, and (P)-5 showed similar spectra to those in
chloroform, whereas (P)-6 showed an obviously different shape:
An increased |∆ꢀ| compared to that in chloroform with the
maxima at 330 and 360 nm (Figure 1b). The CD spectra of
(P)-6 in trifluoromethylbenzene changed depending on temper-
ature. A spectrum similar to that in chloroform was obtained at
60 °C, while it showed an increased |∆ꢀ| at 5 °C over that at 25
°C (Figure 1c). The CD studies suggest the formation of a helical
structure of (P)-6 at 5 °C in trifluoromethylbenzene, most likely
a double-helix, and a random coil at 60 °C.
FIGURE 1. (a) CD spectra (chloroform, 5 × 10-6 M, 25 °C) of (P)-3,
4, 5, and 6. (b) CD spectra (trifluoromethylbenzene, 5 × 10-6 M, 25
°C) of (P)-3, 4, 5, and 6. (c) CD spectra (trifluoromethylbenzene, 5 ×
10-6 M) of (P)-6 at 60, 25, and 5 °C. The spectra were obtained within
30 min of cooling or heating.
spectra of (P)-6 were obtained at concentrations below 2 × 10-6
M, and the CD spectra were obtained within 30 min of cooling
to 5 °C. In order to know the CD spectra in the pure double-
helix state, temperature, time course, and concentration were
examined. The CD (2 × 10-6 M) spectra of (P)-6 were obtained
at various temperatures between -10 and 60 °C. Above 25 °C,
the random coil state was formed. An increase of |∆ꢀ| compared
to that at the random coil state were observed as the temperature
decreased, and a steady state was reached at -10 °C with ∆ꢀ
at 330 nm at approximately +800 cm-1M-1 (Figure 2a). Next,
the ∆ꢀ value at 330 nm was monitored after heating the solution
to 60 °C and then cooling it to -10 °C (Figure 2b). The ∆ꢀ
value reached steady state after 30 min, at a value of ap-
proximately +800 cm-1M-1. The effect of concentration on the
CD spectra was also examined. Very similar CD spectra were
obtained at 5 °C at the concentrations between 5 × 10-6
M
and 2.5 × 10-5 M, reaching a ∆ꢀ value of approximately +800
cm-1 M-1 at 330 nm and an decreased |∆ꢀ| from those was
obtained at 2 × 10-6 M (Figure 2c). The studies indicated a
steady state below a certain temperature and above a certain
concentration providing very similar CD spectra with a ∆ꢀ value
of +800 cm-1 M-1 at 330 nm. It was concluded that the CD
spectra at these steady states in trifluoromethylbenzene represent
the pure helix state.
For the following discussions, it was necessary to know the
CD spectra of (P)-6 in the pure double-helix state. The study
was conducted in trifluoromehylbenzene, which is a strong helix-
forming solvent. Because of the solubility at 5 °C, the CD
The degree of aggregation was investigated by VPO for the
helix state. m-Difluorobenzene was used as a solvent, since (P)-6
(12) Nakamura, K.; Okubo, H.; Yamaguchi, M. Synlett 1999, 549–550.
J. Org. Chem. Vol. 73, No. 18, 2008 7139

Amemiya et al.
FIGURE 4. CD Spectra (trifluoromethylbenzene, 1 × 10-3 M) of (P)-1
at various temperatures.
FIGURE 2. (a) CD spectra (trifluoromethylbenzene, 2 × 10-6 M) of (P)-6
at various temperatures. The spectra were obtained within 30 min of heating
or cooling. (b) Profiles of ∆ꢀ at 330 nm (trifluoromethylbenzene, 2 × 10-6
M) of (P)-6 heated at 60 °C and then cooled to -10 °C. (c) CD spectra
(trifluoromethylbenzene, 5 °C) of (P)-6 at various concentrations. The
spectra were obtained within 30 min of cooling.
FIGURE 5. (a) CD spectra (chloroform, 5 × 10-6 M, 25 °C) of (P)-1
and (P)-6. (b) CD spectra (trifluoromethylbenzene) of (P)-1 (1 × 10-3
M, 0 °C) and (P)-6 (2 × 10-6 M, -10 °C).
10-3 M were measured at different temperatures. Below 25 °C,
typical double-helix spectra were obtained with a ∆ꢀ value at
370 nm at +810 cm-1M-1 (Figure 4), and unfolding was
observed at 60 °C. Thus, both pentamers (P)-6 and (P)-1
possessing perfluorooctyl and decyloxycarbonyl side chains
formed helix-dimers in trifluoromethylbenzene.
The CD spectra of (P)-1 and (P)-6 were compared in the
random coil state and the double-helix state. Although they
showed very similar CD spectra for the random coil state in
chloroform (Figure 5a), nearly mirror-image spectra were
obtained for the double-helix (Figure 5b). This means that (P)-6
also formed double-helix structure similar to (P)-1, but had an
inverted screw sense. This result was quite unexpected, since
(P)-6 and (P)-1 had the same helicene configuration, and differ
only in the structure of the side chains. The result was attributed
to a significant difference in the absolute hardness of the
m-phenylene moieties. It was supposed that the strong hard/
hard interactions between the m-phenylene moieties of (P)-6
compared to (P)-1 changed the mode of interaction at the
backbone, which resulted in a change in the stable helical
conformation (Figure 6). Several single-stranded polymers and
oligomer possessing chiral side chains are known to exhibit
inversion of the helical screw sense13 by the ratio of the R-side
FIGURE 3. Degree of aggregation (m-difluorobenzene, 40 °C) of (P)-6
by VPO at various concentrarions.
was soluble at 1 × 10-3 M at 40 °C in this solvent. At 40 °C,
VPO indicated the dimeric structure at concentrations between
1-3 × 10-3 M (Figure 3), and indicated helix-dimer formation
by (P)-6 in the solution, most probably as the double-helix.
On the basis of the experiments on the pentamer (P)-6 with
perfluorooctyl side chains, comparative studies were conducted
with the original pentamer (P)-1 with decyloxycarbonyl side
chains. It was confirmed that (P)-1 also formed a double helix,
although the use of a strong helix-forming solvent, trifluorom-
ethylbenzene, was required compared to the solvents for the
heptamer (P)-2 previously reported.8 The CDs of (P)-1 at 1 ×
7140 J. Org. Chem. Vol. 73, No. 18, 2008

Hetero-Double-Helix Formation by an Ethynylhelicene Oligomer
FIGURE 6. Proposed effect of hard arenes arranged among soft arenes
in (P)-6.
FIGURE 9. CD spectra of a 1:1 mixture of (P)-1 and (P)-6 (trifluo-
romethylbenzene, total concentration 2.5 × 10-5 M, 5 °C), (P)-1, and
(P)-6 (trifluoromethylbenzene, 1.25 × 10-5 M, 5 °C) obtained within
30 min of cooling. The spectrum calculated by adding those of (P)-1
and (P)-6 is also shown.
Since a new double-helix-forming (P)-6 possessing perfluo-
rooctyl side chains was obtained in this study, the interactions
between (P)-6 and the conventional oligomer (P)-1 were
examined. Experiments were conducted to determine whether
(P)-1 and (P)-6 form heterodimers or a mixture of individual
homodimers. It was also of interest to compare the interactions
of (M)-1 and (P)-6 to examine the chiral recognition phenomena.
Our previous studies revealed that the same configurations were
favored as for the enantiomeric helicenes in noncovalent
interactions.16
FIGURE 7. CD spectra (toluene, 5 °C) of (P)-1 (5 × 10-5 M and 1 ×
10-4 M) and (P)-6 (5 × 10-5 M).
The complexation of (P)-1 and (P)-6 was examined in
trifluoromethylbenzene, in which the total concentration of (P)-1
and (P)-6 was adjusted to 2.5 × 10-5 M, because both formed
a double-helix at 1.25 × 10-5 M at 5 °C (Figure 9). Solutions
of (P)-1 and (P)-6 in trifluoromethylbenzene were prepared and
were mixed in a 1:1 ratio at room temperature. The solution
was then cooled to 5 °C, and the CD spectra were obtained
within 30 min. The 1:1 mixture showed a spectrum similar to
the sum of the spectra10 of each double-helix in trifluorometh-
ylbenzene (1.25 × 10-5 M, 5 °C), which suggested the
formation of homo-double-helices (Figure 9). In order to further
confirm this interpretation, the ratio of (P)-1 to (P)-6 was
changed, keeping the total concentration at 2.5 × 10-5M (Figure
10a), and ∆ꢀ value at 330 and 370 nm were plotted against the
ratio of (P)-1 to (P)-6 (Figure 10b). Both plots were on
approximate straight lines giving the maxima of the ∆ꢀ value
for pure (P)-1 and pure (P)-6. It was therefore concluded that
the structural changes of (P)-1 and (P)-6 were independent and
resulted in the formation of individual homo-double-helices.
CDs were measured in a solvent of less helix-forming
tendency. In toluene (1 × 10-4 M, 5 °C), (P)-6 formed a partial
double-helix, and (P)-1 was random coil. The 1:1 mixture of
(P)-1 and (P)-6 showed a spectrum similar to the sum of both
FIGURE 8. CD spectra (m-difluorobenzene, 1 × 10-4 M) of (P)-1 (5
and 60 °C) and (P)-6 (5 °C).
chain to the S-side chain14 or by external stimuli such as changes
in pH, solvent, and temperature.15 The inversion of a double-
helix depending on solvent has been also reported.5d These
observations of (P)-6 and (P)-1 are another notable example of
such inversions caused by the effect of achiral side chains.
The stability of the double-helix structure was compared
between (P)-6 and (P)-1. In toluene, (P)-6 showed an increase
in |∆ꢀ| compared to the random coil state at 5 × 10-5 M, while
(P)-1 was in the random coil state even at 1 × 10-4 M (Figure
7). In m-difluorobenzene at 1 × 10-4 M, (P)-6 showed a
spectrum with relatively increased |∆ꢀ| over the random coil
state due to a partial double-helix structure, and (P)-1 was
random coil (Figure 8). In general, (P)-6 formed a double-helix
at lower concentrations than (P)-1, indicating that the double-
helix of (P)-6 is more stable than that of (P)-1. It was presumed
that the hard/hard π-π interactions strengthened the binding
and stabilized the double-helix structure of (P)-6, which
possessed alternating soft and hard arene moieties (Figure 6).
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Amemiya et al.
FIGURE 12. (a) CD spectra (trifluoromethylbenzene, 25 °C) of a 1:1
mixture of (M)-1 and (P)-6 (total concentration 5 × 10-6 M, obtained
within 5 min of mixing), (M)-1, and (P)-6 (2.5 × 10-6 M). The spectrum
calculated by adding those of (M)-1 and (P)-6 is also shown. (b) CD
spectrum (trifluoromethylbenzene, 5 × 10-6 M, 25 °C, obtained within
5 min of mixing) of a 1:1 mixture of (M)-1 and (P)-6. CD spectrum of
the precipitate is also shown with an arbitrary scale.
FIGURE 10. (a) CD spectra (trifluoromethylbenzene, total concentra-
tion 2.5 × 10-5 M, 5 °C) of a mixture of (P)-1 and (P)-6 at various
ratio obtained within 30 min of cooling. (b) Plots of ∆ꢀ (trifluorom-
ethylbenzene, total concentration 2.5 × 10-5 M, 5 °C) at 330 and 370
nm against the ratio of (P)-1 to (P)-6. Lines were approximated to the
points.
complex. Although the solution was initially clear, precipitation
occurred and was complete after 2 h. The precipitate was
isolated by centrifugation, and elemental analysis showed a fairly
good agreement with the analysis calculated for a 1:1 complex,
Anal. Calcd: C, 71.29; H, 4.52. Found: C, 68.80; H, 4.71. The
values are intermediate between the calculated analytical data
for (M)-1, C, 86.36; H, 6.96, and for (P)-6, C, 60.14; H, 2.77.
MALDI-TOF MS analysis, m/z 2699.6 and 3634.7, was also
consistent with the complex formation of (M)-1, m/z 2699.0,
and (P)-6, m/z 3635.6. The precipitated solid showed a CD
spectrum similar to that in solution (Figure 12b), and the
complex seemed to possess a similar structure in solution and
in the solid state. The observations suggest the formation of a
chiral 1:1 complex of (M)-1 and (P)-6, probably the hetero-
double-helix. However, once a precipitate was formed, it was
insoluble even at higher temperature in solvents such as
trifluoromethylbenzene, toluene, and chloroform. Therefore, the
solution experiments were conducted within 30 min of mixing
(M)-1 and (P)-6, before the precipitate appeared.
The same experiment was conducted in chloroform (total
concentration 5 × 10-6 M, 25 °C), in which both (M)-1 and
(P)-6 are random coil. The 1:1 mixture again showed an
increased |∆ꢀ| over the calculated spectrum similar to that in
trifluoromethylbenzene after 5 min (Figure 13a), and the
precipitate was complete after 2 h. When the solution stood at
25 °C for 30 min and was then heated at 60 °C for 30 min,
only a small change in the CD spectrum was observed. The
chiral structure was thermally stable than homo-double-helices
of (M)-1 and (P)-6 that were unfolded under the same condition.
The precipitation showed a Cotton effect similar to that in
solution (Figure 13b), and similar to that obtained in a solution
of trifluoromethylbenzene and in the solid state. The results
indicated that (M)-1 and (P)-6 formed a stable hetero-double-
FIGURE 11. CD spectra of a 1:1 mixture of (P)-1 and (P)-6 (toluene,
total concentration 1 × 10-4 M, 5 °C), (P)-1, and (P)-6 (toluene, 5 ×
10-5 M, 5 °C) obtained within 30 min of cooling. The spectrum
calculated by adding those of (P)-1 and (P)-6 is also shown.
spectra (Figure 11), which indicated that only (P)-6 formed a
homo-double-helix. In chloroform (1 × 10-5 M, 5 °C), the 1:1
mixture showed a spectrum corresponding to the random coil.10
Next, we turned our attention to the interactions between
(M)-1 and (P)-6, and experiments were conducted in trifluo-
romethylbenzene at a total concentration of 5 × 10-6 M.
Experiments at low concentrations were conducted compared
to those for the (P)-1/(P)-6 system, because both (M)-1 and (P)-6
were random coil at 2.5 × 10-6 M at 25 °C in this solvent.
Solutions of (M)-1 and (P)-6 in trifluoromethylbenzene (5 x10-6
M) were prepared and mixed in a 1:1 ratio at 25 °C. The mixture
showed much increased |∆ꢀ| compared to the calculated
spectrum within 5 min suggesting the formation of a helical
structure in solution (Figure 12a). The CD spectrum was similar
to those of (M)-1 and (P)-6 in the double-helix-structures (Figure
5b), and suggested a similar structure of the (M)-1/(P)-6
7142 J. Org. Chem. Vol. 73, No. 18, 2008

Hetero-Double-Helix Formation by an Ethynylhelicene Oligomer
FIGURE 13. (a) CD spectra (chloroform, 25 °C) of a 1:1 mixture of
(M)-1 and (P)-6 (total concentration 5 × 10-6 M, obtained within 30
min of mixing), (M)-1, and (P)-6 (2.5 × 10-6 M). The spectrum
calculated by adding those of (M)-1 and (P)-6 is also shown. The 1:1
mixture was heated at 60 °C for 30 min after standing at 25 °C for 30
min, and the CD spectrum was obtained. (b) CD spectrum (chloroform,
5 × 10-6 M, 25 °C, obtained within 30 min of mixing) of a 1:1 mixture
of (M)-1 and (P)-6. CD spectrum of the precipitate is also shown with
an arbitrary scale.
FIGURE 14. (a) CD spectra (chloroform, total concentration 5 × 10-6
M, 25 °C, obtained within 30 min of mixing) of mixtures of (M)-1 and
(P)-6 at various ratios. The spectra of (M)-1 and (P)-6 under the same
conditions are also shown. (b) Plots of ∆ꢀ (chloroform, total concentra-
tion 5 × 10-6 M, 25 °C) at 325 nm against the ratio of (M)-1 to (P)-6.
Approximated lines are also shown.
helix in both solvents, and the formation of hetero-double-helix
was favored over homo-double-helices.
In order to confirm the formation of a hetero-double-helix,
the ratio of (M)-1 to (P)-6 was changed, keeping the total
concentration at 5 × 10-6 M (Figure 14a). The ∆ꢀ values at
330 nm were plotted against the (M)-1/(P)-6 ratio (Figure 14b).
A maximum was obtained at a 1:1 ratio, which indicates the
1:1 stoichiometry of (M)-1 and (P)-6 in the hetero complex.
(M)-1 and (P)-6 formed a hetero-double-helix, while (P)-1
and (P)-6 formed a homo-double-helix (Figure 15). This result
indicates that (P)-6 preferres to complex with (M)-1 rather than
(P)-1 or (P)-6, (M)-1/(P)-6 is a matched pair. The complexation
of the hetero-double-helix (M)-1/(P)-6 was more stable than the
homo-double-helices (P)-6/(P)-6 and (M)-1/(M)-1. These phe-
nomena were in contrast with our previous observations that
helicene derivatives favor interaction with helicenes of the same
configuration rather than the opposite.16 It was also shown in
this study that the (P)-6/(P)-6 complex, (M)-1/(M)-1 complex,
and (M)-1/(P)-6 showed similar CD spectra, which indicates a
similar double-helix structure. (P)-6 may recognize the screw
sense of the double-helix state rather than configuration of
helicene moieties.
In summary, we synthesized dimeric to pentameric ethynyl-
helicene oligomers possessing perfluorooctyl side chains. CD
and VPO studies revealed the formation of double-helix for the
pentamer (P)-6. Compared to the conventional pentamer (P)-1
possessing decyloxycarbonyl side chains, (P)-6 formed a more
stable double-helix with inverted screw sense. It was also found
that (M)-1 and (P)-6 formed a stable hetero-double-helix rather
than homo-double-helices, whereas (P)-1 and (P)-6 formed
homo-double-helices. The investigation of homo- and hetero-
double-helix compounds will lead to the discovery of interesting
supramolecular functions.
FIGURE 15. Heterodouble-helix formation between (P)-6 and (M)-1.
Experimental Section
Pentamer (P)-6. Under an argon atmosphere, a mixture of (P)-9
(59.3 mg, 0.0582 mmol), tris(dibenzylideneacetone)dipalladium(0)
chloroform adduct (6.03 mg, 5.82 × 10-3 mmol), cuprous iodide
(13.3 mg, 0.0698 mmol), tris(2,4,6-trimethylphenyl)phosphine (13.6
mg, 0.0349 mmol), triphenylphosphine (9.16 mg, 0.0349 mmol),
tetrabutylammonium iodide (172 mg, 0.466 mmol), triethylamine
(0.48 mL), N,N-dimethylformamide (1.6 mL), and tetrahydrofuran
(2.0 mL) was freeze-evacuated three times in flask A. In flask B,
a solution of (P)-12 (55.2 mg, 0.0291 mmol) in tetrahydrofuran
(7.0 mL) was freeze-evacuated three times and was added dropwise
to flask A. The mixture was stirred for 24 h at room temperature,
and insoluble materials appeared. The reaction was quenched by
adding saturated aqueous ammonium chloride. The solid was
filtrated and washed with water, methanol, ethyl acetate, and hexane
on the filter. The organic materials in the residual solution were
extracted with toluene. The organic layer was washed with brine
and dried over magnesium sulfate. The filtered solid was dissolved
in toluene and was mixed with the organic layer. The solvent was
evaporated under a reduced pressure, and separation by silica gel
chromatography and recycling gel permeation chromatography gave
(P)-6 (37.8 mg, 0.0104 mmol, 36% from (P)-12): mp 230 °C dec
(toluene-methanol); [R]21D -335 (c 0.05, CHCl3); MALDI TOF-
J. Org. Chem. Vol. 73, No. 18, 2008 7143

Amemiya et al.
13C2H100F68Si2 3634.9, found 3635.6;
twice by this method. The resulting precipitate was put between
12
MS m/z calcd for
C
180
UV-vis (CHCl3, 5 × 10-6 M) λmax (ꢀ) 336 nm (3.5 × 105); CD
the two quartz plates, and the CD spectrum was obtained (Figure
(CHCl3, 5 × 10-6 M) λ (∆ꢀ) 297 nm (-96), 337 nm (89), 389 nm
12
13b): MALDI TOF-MS m/z calcd for (P)-6
C
13CH100F68Si2
181
1
(-245); IR (KBr) 2209, 2151, 1242, 1211, 1150 cm-1; H NMR
12
3633.9, (M)-1
C
13CH184O8Si2 2698.4, found 3634.7, 2699.7;
193
UV-vis (CF3C6H5, 5 × 10-6 M, 25 °C, observed within 5 min of
mixing) λmax (ꢀ) 343 nm (2.6 × 105); CD (CF3C6H5, 5 × 10-6 M,
25 °C, observed within 5 min of mixing) λ (∆ꢀ) 323 nm (705),
368 nm (-856), 396 nm (-397); CD (precipitation obtained from
CF3C6H5, with an arbitrary scale) λ (∆ꢀ) 310 nm (419), 382 nm
(-788), 400 nm (-818). Anal. (C376H284F68O8Si4) Calcd: C, 71.29;
H, 4.52. Found: C, 68.80; H, 4.71. A solution of (P)-6 and (M)-1
in chloroform was treated by the same procedures. The CD spectrum
of the precipitate is shown in Figure 14b: UV-vis (CHCl3, 5 ×
10-6 M, 25 °C, observed within 30 min of mixing) λmax (ꢀ) 337
nm (3.1 × 105); CD (CHCl3, 5 × 10-6 M, 25 °C, observed within
30 min of mixing) λ (∆ꢀ) 326 nm (959), 370 nm (-1213), 397 nm
(-541); CD (precipitation obtained from CHCl3, with an arbitrary
scale) λ (∆ꢀ) 326 nm (554), 372 nm (-1349).
(600 MHz, CDCl3) δ 0.36 (18H, s), 1.92 (6H, s), 1.93 (6H, s),
1.97 (12H, s), 1.98 (6H, s), 7.44 (2H, d, J ) 7.2 Hz), 7.46 (2H, d,
J ) 7.2 Hz), 7.49-7.51 (6H, m), 7.65 (2H, dd, J ) 7.2, 7.8 Hz),
7.70 (2H, dd, J ) 7.2, 7.8 Hz), 7.72-7.75 (6H, m), 7.88-7.90
(4H, m), 7.91 (4H, s), 8.01 (2H, s), 8.08 (2H, s), 8.15 (4H, s), 8.16
(2H, s), 8.20 (2H, s), 8.22 (2H, s), 8.41 (2H, d, J ) 7.8 Hz), 8.49
(2H, d, J ) 7.8 Hz), 8.52-8.53 (6H, m); 13C NMR (150 MHz,
CDCl3, observed at 50 °C) δ 1.00, 23.1, 23.2, 23.3, 29.7, 105-119
(m, br), 119.4, 119.7, 119.8, 120.6, 123.5, 123.6, 123.8, 124.7,
125.0, 125.1, 127.0, 127.2 (2 peaks), 127.3, 129.2, 129.3, 129.4,
129.8, 129.9, 130.1, 130.2, 131.0, 131.1, 131.3, 132.2, 132.3, 137.8;
19F NMR (565 MHz, CDCl3) δ -127.3 (8F, s, br), -123.8 (8F, s,
br), -123.0 (8F, s, br), -122.9 (8F, s, br), -122.5 (8F, s, br),
-122.3 (8F, s, br), -112.2 (8F, t, J ) 12.4 Hz), -81.9 (12F, t, J
) 9.6 Hz). Anal. (C182H100F68Si2) Calcd: C, 60.14; H, 2.77; F, 35.54.
Found: C, 59.85; H, 3.08; F, 35.28.
Pentamer (M)-1. The compound was prepared by the method
discussed for the synthesis of (P)-1:8a [R]20D -455 (c 0.10, CHCl3,).
1H NMR spectrum is shown in the Supporting Information.
Complex of (M)-1 and (P)-6. To a solution of (P)-6 in
trifluoromethylbenzene (5 × 10-6 M, 2 mL) was added a solution
of (M)-1 in trifluoromethylbenzene (5 × 10-6 M, 2 mL) at 25 °C.
The mixture was cooled at 5 °C for 2 h. The precipitate was
separated by centrifugal separator (6400 rpm, 30 min), and the top
liquid layer was removed by decantation. To the resulting solid
was added trifluoromethylbenzene (2 mL), and the solid was
separated again by a centrifugal separator. The solid was washed
Acknowledgment. This work was financially supported by
the Japan Society for Promotion of Science (JSPS).
Supporting Information Available: Synthesis and charac-
terization date of spacer 7, characterization date for (P)-3-5,
11, and 12, CD spectra of (P)-1, (P)-6, and a 1:1 mixture of
1
(P)-1 and (P)-6, H and 13C NMR spectra of new compounds,
1
and H NMR spectra of (M)-1. This material is available free
of charge via the Internet at http://pubs.acs.org.
JO8010057
7144 J. Org. Chem. Vol. 73, No. 18, 2008