Aromatic foldamers with iminodicarbonyl linkers: Their structures and optical properties

Article abstract of DOI:10.1021/jo048233m

(Chemical Equation Presented) Carboxamides possessing naphthalene rings connected by multiple iminodicarbonyl linkers were synthesized. These molecules forced the naphthalene rings to be placed in the positions facing each other, and they form helical fol

Full text of DOI:10.1021/jo048233m

Aromatic Foldamers with Iminodicarbonyl Linkers: Their
Structures and Optical Properties
Hyuma Masu,† Masaki Sakai,‡ Keiki Kishikawa,‡ Makoto Yamamoto,‡
Kentaro Yamaguchi,§ and Shigeo Kohmoto*,†
Graduate School of Science and Technology and Department of Applied Chemistry and Biotechnology,
Faculty of Engineering, Chiba University, 1-33, Yayoi-cho, Inage-ku, Chiba 263-8522, Japan, and
Department of Pharmaceutics, Faculty of Pharmaceutical Science, Tokushima Bunri University Shido,
Sanuki-city, Kagawa 769-2193, Japan
kohmoto@faculty.chiba-u.jp
Received October 7, 2004
Carboxamides possessing naphthalene rings connected by multiple iminodicarbonyl linkers were
synthesized. These molecules forced the naphthalene rings to be placed in the positions facing
each other, and they form helical foldamers both in solution and in the crystalline state. Their
1
folding structures were investigated by single-crystal X-ray analysis and H NMR spectroscopy.
Their absorption and fluorescence spectra showed a red shift as the number of naphthalene moieties
increased. This remarkable change is based on the intramolecular interaction between naphthalene
moieties. Helicity of the foldamer can be controlled by the introduction of chiral auxiliaries at imide
nitrogen atoms, which results in an observation of induced circular dichroism.
Introduction
bonding, electrostatic forces, and hydrophobic forces are
utilized for their construction. Hydrogen bonding is the
major force for foldamers derived from â-peptides.4 It is
also utilized for the construction of folding structures in
the crystalline state.5 Metal or nonmetal complexes are
frequently used to prepare helical structures.6 Aromatic
π-π stacking is efficient for the creation of aromatic
foldamers.7
We have been interested in aromatic foldamers because
the construction of multilayered aromatic structures can
be possible using folding patterns. Unique optical proper-
ties can be expected from these multilayered structures
Oligomers and polymers which adopt specific compact
conformations by folding are named foldamers.1 In solu-
tion, folding structures are very common in biopolymers,2
mostly proteins. The well-defined three-dimensional
structures produced by folding, which furnish the ap-
propriate location of active sites in the molecules, are
responsible for their sophisticated chemical functions.3
In the past decade, attempts have been made extensively
to prepare synthetic foldamers for the exploration of
behavior analogous to that of biopolymers. Hydrogen
† Graduate School of Science and Technology, Chiba University.
‡ Department of Applied Chemistry and Biotechnology, Chiba
University.
(4) (a) Cubberley, M. S.; Iverson, B. L. Curr. Opin. Chem. Biol. 2001,
5, 650-653. (b) Corbin, P. S.; Zimmerman, S. C.; Thiessen, P. A.;
Hawryluk, N. A.; Murray, T. J. J. Am. Chem. Soc. 2001, 123, 10475-
10488. (c) Patch, J. A.; Barron, A. E. Curr. Opin. Chem. Biol. 2002, 6,
872-877. (d) Huck, B. R.; Fisk, J. D.; Guzei, I. A.; Carlson, H. A.;
Gellman, S. H. J. Am. Chem. Soc. 2003, 125, 9035-9037. (e) Jiang,
H.; Le´ger, J.; Dolain, C.; Guionneau, P.; Huc, I. Tetrahedron 2003, 59,
8365-8374.
(5) (a) Moriuchi, T.; Nishiyama, M.; Yoshida, K.; Ishikawa, T.; Hirao,
T. Org. Lett. 2001, 3, 1459-1461. (b) Garric, J.; Le´ger, J.; Grelard, A.;
Ohkita, M.; Huc, I. Tetrahedron Lett. 2003, 44, 1421-1424.
(6) (a) Piguet, C.; Bernardinelli, G.; Hopfgartner, G. Chem. Rev.
1997, 97, 2005-2062. (b) Albrecht, M. Chem. Rev. 2001, 101, 3457-
3497. (c) Thu¨nemann, A. F.; Kubowicz, S.; Burger, C.; Watson, M. D.;
Tchebotareva, N.; Mu¨llen, K. J. Am. Chem. Soc. 2003, 125, 352-356.
§ Tokushima Bunri University.
(1) (a) Gellman, H. S. Acc. Chem. Res. 1998, 31, 173-180. (b) Li, A.
D. Q.; Wang, W.; Wang, L.-Q. Chem.sEur. J. 2003, 9, 4594-4601. (c)
Schmuck, C. Angew. Chem., Int. Ed. Engl. 2003, 42, 2448-2452.
(2) (a) Eaton, W. A.; Mun˜oz, V.; Thompson, P. A.; Henry, E. R.;
Hofrichter, J. Acc. Chem. Res. 1998, 31, 745-753. (b) Hill, R. B.;
Raleigh, D. P.; Lombardi, A.; Degrado, W. F. Acc. Chem. Res. 2000,
33, 745-754. (c) Brooks, C. L., III. Acc. Chem. Res. 2002, 35, 447-
454. (d) Straub, J. E.; Guevara, J.; Huo, S.; Lee, J. P. Acc. Chem. Res.
2002, 35, 473-481. (e) Wang, W.; Wan, W.; Zhou, H.-H.; Niu, S.; Li,
A. D. Q. J. Am. Chem. Soc. 2003, 125, 5248-5249.
(3) (a) Nakano, T.; Okamoto, Y. Chem. Rev. 2001, 101, 4013-4038.
(b) Lan, T.; McLaughlin, L. W. Biochemistry 2001, 40, 968-976.
10.1021/jo048233m CCC: $30.25 © 2005 American Chemical Society
Published on Web 01/22/2005
J. Org. Chem. 2005, 70, 1423-1431
1423

Masu et al.
due to aromatic interactions in a vertical direction.8 A
choice of linker to connect arene moieties might be
important to regulate folding. Several aromatic foldamers
were constructed by connecting arenes with urea,9 guani-
dine,10 or amide11 linkers. These linkers prefer to have a
cis conformation, which promotes the settling of the
molecule in a folding conformation.12 Even methylene
could be a linker to afford π-stacked polyfluorene fol-
damers.13 Folded aromatic hetero duplexes were reported
recently14 in which a donor-acceptor interaction played
an important role. Solvophobically-driven generation of
helical foldamers from phenylene ethynyl oligomers has
been extensively studied by Moore et al.15 A folding,
crowded aromatic was applied for the construction of a
folded columnar superstructure.16
SCHEME 1. Synthesis of Naphthalene-Based
Foldamers
During the course of our study on the photochemical
cycloaddition reaction of aromatic carboxamides in the
solid state,17 we have found that an iminodicarbonyl
group was a nice linker to place two aromatic moieties
in the positions facing each other. Considering this fact,
we planned to use an iminodicarbonyl group as a linker
to prepare aromatic oligomers, and we examined the
folding conformations and optical properties of these
oligomers in both solution and in the crystalline state.
Folding might be operated in a helical way. Therefore,
an introduction of chiral groups could possibly generate
chiral helical foldamers. Efficient induction of chirality
in helical polymers is a current topic.18 It is interesting
to survey chirality amplification effected by multilayered
aromatic structures.19
(7) (a) Marsella, M. J.; Kim, I. T.; Tham, F. J. Am. Chem. Soc. 2000,
122, 974-975. (b) Nakamura, K.; Okubo, H.; Yamaguchi, M. Org. Lett.
2001, 3, 1097-1099. (c) Adams, H.; Hunter, C. A.; Lawson, K. R.;
Perkins, J.; Spey, S. E.; Urch, C. J.; Sanderson, J. M. Chem.sEur. J.
2001, 7, 4863-4878. (d) Cubberley, M. S.; Iverson, B. L. J. Am. Chem.
Soc. 2001, 123, 7560-7563. (e) Zhao, D.; Moore, J. S. J. Org. Chem.
2002, 67, 3548-3554. (f) Huc, I. Eur. J. Org. Chem. 2004, 17-29.
(8) (a) Oda, M.; Nothofer, H.-G.; Lieser, G.; Scherf, U.; Meskers, S.
C. J.; Neher, D. Adv. Mater. 2000, 12, 362-365. (b) Oda, M.; Nothofer,
H.-G.; Scherf, U.; Sˇunjic´, V.; Richter, D.; Regenstein, W.; Neher, D.
Macromolecules 2002, 35, 6792-6798.
(9) (a)Yamaguchi, K.; Matsumura, G.; Kagechika, H.; Azumaya, I.;
Ito, Y.; Itai, A.; Shudo, K. J. Am. Chem. Soc. 1991, 113, 5475-5476.
(b) Jørgensen, M.; Krebs, F. C. J. Org. Chem. 2002, 67, 7511-7518.
(c) Lewis, F. D.; Kurth, T. L.; Hattan, C. M.; Reiter, R. C.; Stevenson,
C. D. Org. Lett. 2004, 6, 1605-1608.
(10) (a) Tanatani, A.; Kagechika, H.; Azumaya, I.; Fukutomi, R.; Ito,
Y.; Yamaguchi, K.; Shudo, K. Tetrahedron Lett. 1997, 38, 4425-4428.
(b) Tanatani, A.; Yamaguchi, K.; Azumaya, I.; Fukutomi, R.; Shudo,
K.; Kagechika, H. J. Am. Chem. Soc. 1998, 120, 6433-6442.
(11) (a) Winkler, J. D.; Piatnitski, E. L.; Mehlman, J.; Kasparec, J.;
Axelsen, P. H. Angew. Chem., Int. Ed. Engl. 2001, 40, 743-745. (b)
Huc, I.; Maurizot, V.; Gornitzka, H.; Le´ger, J.-M. Chem. Commun.
2002, 578-579.
Results and Discussion
Aromatic imides possessing one, two, three, and five
naphthalene rings connected at their R-position with
iminodicarbonyl linkers were prepared by sequential
standard amidation reactions as presented in Scheme 1.
To examine the steric effects of substituents on foldamer
generation, chiral ((S)-1-phenylethyl and (S)-1-(1-naph-
thyl)ethyl), bulky (2-tert-butylphenyl), and long (N-octyl)
substituents were introduced at the nitrogen atoms.
Pentamers 5a and 5b were prepared from the corre-
sponding dimers and naphthalene 1,4-dicarbonyldichlo-
ride. However, a similar procedure was not applicable
for 5c. Pentamer 5c was obtained from the reaction of
4c with 1-naphthoyl chloride. Single crystals were ob-
tained for 3a-3e; however, 5a-5c were obtained as a
powder.
Conformation in the Crystalline State. Single-
crystal X-ray analysis was carried out for monoclinic or
orthorhombic crystals of 3a-3e. General crystallographic
data are shown in Table 1. The X-ray structure of 3a is
presented in Figure 1. The single crystal of 3a contains
a chloroform molecule (the solvent used for recrystalli-
(12) Itai, A.; Toriumi, Y.; Saito, S.; Kagechika, H.; Shudo, K. J. Am.
Chem. Soc. 1992, 114, 10649-10650.
(13) Rathore, R.; Abdelwahed, S. H.; Guzei, I. A. J. Am. Chem. Soc.
2003, 125, 8712-8713.
(14) (a) Gabriel, G. J.; Iverson, B. L. J. Am. Chem. Soc. 2002, 124,
15174-15175. (b) Yanq, X.; Martinovic, S.; Smith, R. D.; Gonq, B. J.
Am. Chem. Soc. 2003, 125, 9932-9933. (c) Zhou, Q.-Z.; Jiang, X.-K.;
Shao, X.-B.; Chen, G.-J.; Jia, M.-X.; Li, Z.-T. Org. Lett. 2003, 5, 1955-
1958. (d) Fedorova, A.; Chaudhari, A.; Ogawa, M. Y. J. Am. Chem.
Soc. 2003, 125, 357-362. (e) Zhao, X.; Jia, M.-X.; Jiang, X.-K.; Wu,
L.-Z.; Li, Z.-T.; Chen, G.-J. J. Org. Chem. 2004, 69, 270-279.
(15) (a) Nelson, J. C.; Saven, J. G.; Moore, J. S.; Wolynes, P. G.
Science 1997, 277, 1793. (b) Cubberley, M.; Iverson, B. J. Am. Chem.
Soc. 2001, 123, 7560-7563. (c) Tanatani, A.; Hughes, T. S.; Moore, J.
S. Angew. Chem., Int. Ed. Engl. 2002, 41, 325-328. (d) Goto, H.;
Heemstra, J. M.; Hill, D. J.; Moore, J. S. Org. Lett. 2004, 6, 889-892.
(16) Zhang, W.; Horoszewski, D.; Decatur, J.; Nuckolls, C. J. Am.
Chem. Soc. 2003, 125, 4870-4873.
(18) (a) Applequist, J.; Bode, K. A.; Appella, D. H.; Christianson, L.
A.; Gellman, S. H. J. Am. Chem. Soc. 1998, 120, 4891-4892. (b)
Yashima, E.; Maeda, K.; Okamoto, Y. Nature 1999, 399, 449-451. (c)
Feringa, B. L.; Delden, R. A.; Koumura, N.; Geertsema, E. M. Chem.
Rev. 2000, 100, 1789-1816. (d) Yu, Z.; Wan, X.; Zhang, H.; Chen, X.;
Zhou, Q. Chem. Commun. 2003, 974-975. (e) Goto, H.; Zhang, H. Q.;
Yashima, E. J. Am. Chem. Soc. 2003, 125, 2516-2523.
(19) Yashima, E.; Maeda, K.; Nishimura, T. Chem.sEur. J. 2004,
10, 42-51.
(17) Kohmoto, S.; Ono, Y.; Masu, H.; Yamaguchi, K.; Kishikawa,
K.; Yamamoto, M. Org. Lett. 2001, 3, 4153-4155.
1424 J. Org. Chem., Vol. 70, No. 4, 2005

Novel Aromatic Foldamers
TABLE 1. Crystallographic Data for Compounds 3a, 3b, 3c, 3d, and 3e
3aa
3bb
3cc
3d
3e
formula
crystal system
space group
a (Å)
C
48H34N2O4‚CHCl3
C
50H38N2O4‚1/2C4H8O
C58H42N2O4‚C4H8O2
orthorhombic
P212121
11.2677(19)
16.808(3)
25.638(4)
90.000
4855.5(14)
90
0.0818
C
54H46N2O4
C
50H54N2O4
monoclinic
C2/c
monoclinic
C2
monoclinic
P21/n
monoclinic
P21/c
18.836 (3)
14.828 (3)
14.441 (3)
99.516 (3)
3978.1 (12)
150
19.550(3)
14.449 (2)
14.925 (2)
96.767 (3)
4186.7 (11)
150
22.015(5)
13.7857(8)
14.917(2)
108.93(2)
4282(1)
298
21.571(4)
10.548(2)
19.756(3)
107.503(3)
4286(1)
273
b (Å)
c (Å)
â (deg)
V (Å3)
T (K)
R (F)
0.0777
0.0908
0.0534
0.0685
a Crystal contains chloroform molecules. b Crystal contains THF molecules. c Crystal contains ethyl acetate molecules.
FIGURE 1. Ball-and-stick presentations for 3a (a) along and (b) perpendicular to the helix axis.
FIGURE 2. Ball-and-stick presentations for 3b, 3c, 3d, and 3e.
zation), which is omitted in Figure 1. The main chain
has a zigzag type structure (Figure 1a). Three naphtha-
lene rings in a main chain are stacked on each other with
a neighboring naphthalene ring and spread out radially
(Figure 1b). The molecule is folded in a helical way. The
X-ray structures of four other trimers, 3b-3e (Figure 2),
show that they have similar folding structures indepen-
dent of substituents at the nitrogen atoms. Because of
the disorders originated in the substituents at the
nitrogen atom, the R-factors for 3b, 3c, and 3e could not
J. Org. Chem, Vol. 70, No. 4, 2005 1425

Masu et al.
TABLE 2. Folding Parameters for 3a, 3b, 3c, 3d, and 3e
Obtained from Their Single Crystal X-ray Structures
3a
3b
3c
3d
3e
d1 (Å)
3.5
3.5
25
3.7
3.7
31
3.8
3.9
31
3.5
3.6
21
3.5
3.6
23
d2 (Å)
θ1 (deg)
θ2 (deg)
φ1 (deg)
φ2 (deg)
25
31
37
23
26
137
137
134
134
129
134
138
139
144
135
be reduced sufficiently in their X-ray analyses even at
low temperature (150 K for 3a and 3b and 90 K for 3c).
Characteristic folding parameters in the crystalline
state are presented in Table 2. The distances between
the naphthalene rings (d1 and d2) are prescribed as the
lengths of centroid to centroid of the benzene rings of
naphthalene moieties directly connected to iminodicar-
bonyl linkers. Angles of plane (θ1 and θ2) are defined as
the degree of inclination between the two naphthalene
π planes. Twisting angles between the naphthalene rings
are designated as φ1 and φ2. They are defined as the
intersected angles created by the two lines joined between
the two centroids of benzene rings of naphthalene
moieties. In all five crystal structures, d1 and d2 are in
the range of 3.5-3.9 Å, which is the typical distance for
π-π stacking.20 The average values of 134-139° for φ1
and φ2 mean that roughly three naphthalene rings are
expected to exist per pitch in longer oligomers.
FIGURE 3. Proton chemical shifts of Ha (the protons at the
central naphthalene rings of 1a, 2a, 3a, and 5a) in CDCl3.
TABLE 3. Chemical Shifts of the Naphthalene Protons
of 3a, 3b, 3d, and 3e
The X-ray structures of foldamers with chiral substit-
uents at the nitrogen atoms, 3b and 3c, showed distinct
differences in their crystal structures. Chiral space
groups C2 and P212121 were observed for 3b and 3c,
respectively. In the crystal structure of 3b, two diaster-
eomeric forms with P- and M-helicity existed in a ratio
of 1:1. In contrast, 3c showed a single helicity in its
crystal structure. It was determined that 3c possessed
M-helicity based on the configuration of the chiral
substituent, (S)-1-(1-naphthyl)ethyl.
Conformation in Solution. To elucidate the confor-
mations of the foldamers in solution, their 1H NMR
spectra were examined. The protons Ha (protons at the
2- and 3-positions of the naphthalene moiety) of 1a were
observed at 7.53 ppm in CDCl3. The corresponding Ha
signals of 2a and 3a were shifted upfield (Figure 3). The
assignment of the proton signals was carried out in the
following way. For 1a and 2a, their signals were assigned
from their coupling patterns. The assignment for 3a was
based on HH-COSY and NOE difference spectroscopic
measurements. Compound 5a showed proton signals that
were too complicated and broad to be assigned. We
tentatively assigned that the signal that appeared in the
highest upfield position might be the proton Ha, which
should be shielded strongly in the folded conformation.
The results suggested that they had folding conforma-
3a
3b
3d
3e
3a
3b
3d
3e
Ha 6.20 6.41 6.37 6.44
Hb 7.37 7.22 7.73 7.46
Hc 7.13 7.07 7.39 7.20
Hd 6.82 6.94 7.27 6.96
He 6.43 6.49 6.37 6.54
Hf 6.97 6.94 7.02 7.10
Hg 7.28 7.38 7.35 7.40
Hh 7.06
Hi 7.09
Hj 7.52 7.68 7.88 7.67
a
a
7.23 7.25
7.30
a
a Due to the overlapping of several peaks, the assignment was
difficult.
tions in solution.21 As the number of naphthalene moi-
eties increases, shielding caused by them should increase
in the folding conformation and the increasing upfield
shifts of the protons at the central naphthalene moiety
were observed. The folded conformation was also con-
firmed from NOE in 3a. The NOEs were observed
between the protons Ha-Hd and Ha-Hj, which attested
its folded conformation in solution. These NOE relations
are shown as arrows in the structure of 3 presented in
1
Table 3. In addition to these H NMR data, assignment
of all the naphthalene ring protons is also useful to
examine their conformation. Table 3 shows the chemical
shifts of the naphthalene ring protons for 3a, 3b, 3d, and
(20) (a) Blatchly, R. A.; Tew, G. N. J. Org. Chem. 2003, 68, 8780-
8785. (b) Aravinda, S.; Shamala, N.; Das, C.; Sriranjini, A.; Karle, I.
L.; Balaram, P. J. Am. Chem. Soc. 2003, 125, 5308-5315.
(21) Krebs, F. C.; Jørgensen, M. J. Org. Chem. 2002, 67, 7511-7518.
1426 J. Org. Chem., Vol. 70, No. 4, 2005

Novel Aromatic Foldamers
signal by that of the opposite helicity. The CD signal of
3c measured at a similar low temperature (218 K, see
Figure 11 in the discussion of CD spectra) was slightly
more intense than the one at 298 K. Therefore, it is hard
to consider that the helical conformational equilibrium
is the major cause of this NMR behavior. E/Z isomeriza-
tion of the imide groups might also be excluded, since
this isomerization would change the shape of the mol-
ecule from the folded conformation to the linear one,
which would cause disappearance of its CD signal.
Moreover, the proton Ha should appear downfield, since
the shielding caused by the folding structure might be
canceled out. However, the peak of Ha at 223 K appeared
in the same chemical shift region as that at room
temperature. The possible explanation for this 1H NMR
behavior might be the restricted rotation of the (S)-1-(1-
naphthyl)ethyl moiety along the C-N bond. At low
temperature, two stable rotamers may exist. This re-
stricted rotation may cause neither the helical confor-
mational change nor the unfolding (E/Z isomerization),
and the folding conformation of the molecule remains
intact.
Absorption and Fluorescence Spectra. UV-vis
absorption and fluorescence spectra of imides were
measured in solution and in the solid state. The series
of compounds with the same substituent at the nitrogen
atom were examined for comparison. Figure 5 shows
those spectra for the benzyl series (1a, 2a, 3a, and 5a).
Compound 1a, with one naphthalene moiety, showed λmax
at 300 nm (chloroform) in its absorption spectrum.
However, for 2a, 3a, and 5a, new absorptions appeared
as shoulders at 331, 344, and 370 nm, respectively. These
new bands might be the results of π-π interaction of
naphthalene moieties in the folding conformations. They
showed red shifts with increasing number of naphthalene
moieties. An increase of molar extinction coefficients was
also observed (1a: λmax ) 295 nm, ꢀmax ) 7 800; 5a: λmax
) 311 nm, ꢀmax ) 13 000). No concentration dependence
was observed on their λmax and ꢀmax (10-5 to 10-4 M). A
similar red shift was observed in their absorption spectra
in the solid state, which were taken in a reflection mode.
This tendency was distinct in the solid state. There is a
characteristic difference between their solution and solid-
state fluorescence spectra. In chloroform, 1a showed its
emission maximum at 402 nm (excitation wavelength:
300 nm). However, 2a, 3a, and 5a exhibited their
emission maxima at nearly the same wavelength, 470
nm, as a single band. In contrast, their fluorescence
spectra in the solid state showed two emission bands.
Compound 1a showed the band at 384 nm together with
a shoulder at 462 nm. Gradual increase of the shoulder
occurred according to the increasing number of naph-
thalene moieties. Finally, this shoulder became the major
emission band of 5a, which was nearly the same as those
of 2a, 3a, and 5a in solution. It is conceivable that
intramolecularly formed excimers between naphthalene
moieties are responsible for those emission bands at 470
nm. Due to their immobility in crystals, an intramolecu-
lar excimer formation might be rather ineffective com-
pared to that in solution, since two naphthalene moieties
are twisted about 130-140° in their crystals. As the
number of naphthalene moieties increases, the prob-
ability of excimer formation might be boosted, which
results in a gradual increase of the excimer emission
FIGURE 4. Variable temperature 1H NMR spectra of (a) the
methyl protons and (b) the proton Ha of 3c in CDCl3.
3e. Assignment for 3c was not possible because of its
complexity. A similar tendency in the order of chemical
shifts was observed for these compounds. The proton Ha
appeared in the highest upfield position followed by He
in the second, and the proton Hj appeared in the lowest
downfield position in all five compounds. The results
indicate that naphthalene moieties are overlapping each
other on their benzene rings when connected with imi-
nodicarbonyl linkers in solution as well as in the solid
state.
A variable temperature 1H NMR study on 3c was
carried out in CDCl3. As the temperature was lowered,
a broadening of most of the signals was observed. Figure
4a shows the measurements for the doublet correspond-
ing to the methyl signal of the (S)-1-(1-naphthyl)ethyl
moiety. Coalescence could not be observed at the tem-
perature measured (down to 223 K). However, the signal
of proton Ha, the most shielded proton in the central
naphthalene ring, finally became two singlet peaks (δ
5.61 and 5.89) in a ratio of 1:1 at 223 K (Figure 4b). The
assignment was difficult for other naphthalene ring
protons. It showed the coalescence temperature at 250
K. The ∆Gq at this temperature was calculated to be 12.0
kcal/mol. The results suggest the existence of two stable
conformations at this temperature. If diastereomerization
(equilibration in helical structures) took place to give the
mixture of M/P-helical structures in a ratio of 1:1, no CD
signal would be observed due to a cancellation of the CD
J. Org. Chem, Vol. 70, No. 4, 2005 1427

Masu et al.
FIGURE 5. Absorption and fluorescence spectra of 1a, 2a,
3a, and 5a: (a) absorption spectra in CHCl3, 40 µM; (b)
fluorescence spectra in CHCl3, 40 µM (excitation wavelength:
300 nm); (c) absorption spectra in the solid state; (d) fluores-
cence spectra in the solid state (excitation wavelength: 300
nm).
FIGURE 6. Absorption and fluorescence spectra of 1b, 2b,
3b, and 5b: (a) absorption spectra in CH3CN, 20 µM; (b)
fluorescence spectra in CH3CN, 20 µM (excitation wave-
length: 260 nm); (c) absorption spectra in the solid state; (d)
fluorescence spectra in the solid state (excitation wavelength:
300 nm).
intensity. Therefore, the emission corresponding to the
excimer becomes almost the sole emission band in 5a. A
similar tendency was observed in acetonitrile and ben-
zene. No solvent effect was observed. Similar results were
obtained for the (S)-1-phenylethyl series (1b, 2b, 3b, and
5b) and the (S)-1-(1-naphthyl)ethyl series (1c, 2c, 3c, and
5c), as shown in Figures 6 and 7.
aromatic substituents at the imide nitrogen atom, the
absorption and fluorescence spectra of the N-octyl deriva-
tive (3e) were investigated (Figure 8). The absorption and
fluorescence spectra of 3e both in solution and in the solid
state were similar to those for 3a, 3b, and 3c. The results
clearly show that the red shifts observed in a series of
foldamers were the result of the stacking of naphthalene
moieties in the folding conformation and not because of
To demonstrate that the red shifts observed in the
absorption and fluorescence spectra are irrelevant to the
1428 J. Org. Chem., Vol. 70, No. 4, 2005

Novel Aromatic Foldamers
FIGURE 8. Absorption and fluorescence spectra of 1e and
3e: (a) absorption spectra in CH3CN, 20 µM; (b) fluorescence
spectra in CH3CN, 20 µM (excitation wavelength: 260 nm);
(c) absorption spectra in the solid state; (d) fluorescence spectra
in the solid state (excitation wavelength: 260 nm).
FIGURE 7. Absorption and fluorescence spectra of 1c, 2c,
3c, and 5c: (a) absorption spectra in CH3CN, 20 µM; (b)
fluorescence spectra in CH3CN, 20 µM (excitation wave-
length: 260 nm); (c) absorption spectra in the solid state; (d)
fluorescence spectra in the solid state (excitation wavelength:
260 nm).
solution and in the solid state for 1b, 2b, 3b, 5b, 1c, 2c,
3c, and 5c. In the (S)-1-phenylethyl series (1b, 2b, 3b,
and 5b), almost no CD signal was observed in acetonitrile
(Figure 9a) and marginal spectra were observed in
chloroform (Figure 9b) in the region corresponding to the
absorption band caused by π-π interactions between
naphthalene moieties. Recently, switching of chiral in-
duction using solid-state-solution-state equilibrium was
the aromatic substituents, (S)-1-phenylethyl or (S)-1-(1-
naphthyl)ethyl moiety, at the imide nitrogen atom.
CD Spectra. Our major interest is chirality amplifica-
tion in foldamers.22 The CD spectra were measured in
(22) (a) Fenniri, H.; Deng, B.-L.; Ribbe, A. E. J. Am. Chem. Soc.
2002, 124, 11064-11072. (b) Inai, Y.; Ishida, Y.; Tagawa, K.; Takasu,
A.; Hirabayashi, T. J. Am. Chem. Soc. 2002, 124, 2466-2473.
J. Org. Chem, Vol. 70, No. 4, 2005 1429

Masu et al.
FIGURE 10. CD spectra of 1c, 2c, 3c, and 5c: (a) in CH3CN,
20 µM; (b) in CH3Cl, 20 µM; (c) in the solid state.
FIGURE 9. CD spectra of 1b, 2b, 3b, and 5b: (a) in CH3CN,
20 µM; (b) in CH3Cl, 20 µM; (c) in the solid state.
reported in helical aromatic oligoamides.23 The equilib-
rium inclined to a stable diastereomer in solution when
crystals composed of two diastereomers of helical oligo-
amides were dissolved. In this case, induction of handed-
ness was observed. Probably the N-substituent, the (S)-
1-phenylethyl group, is not bulky enough to incline the
equilibrium to one of the diastereomers to induce hand-
edness. After dissolving, their two helical diastereomeric
forms might exist nearly in an equivalent amount, which
results in the cancellation of the CD signal. The observa-
tion of weak CD signals in chloroform suggests that a
slight solvent effect on this equilibrium might exist.
The situation is completely different in the (S)-1-(1-
naphthyl)ethyl series (1c, 2c, 3c, and 5c). Parts a and b
of Figure 10 show their CD spectra in acetonitrile and
chloroform, respectively. Similar spectra were observed
for each compound in both solvents. Compound 1c, with
one naphthalene moiety, showed the weak Cotton effect
at 298 nm, presumably due to a chiral (S)-1-(1-naphthyl)-
ethyl group. A marginal CD was observed for 2c. In
contrast to these, rather intense negative Cotton effects
were observed for 3c and 5c which corresponded to the
band caused by π-π interactions between naphthalene
moieties in the UV-vis absorption spectra.24 They showed
a similar spectral pattern. However, 5c showed an extra
negative Cotton effect in a longer wavelength region than
that of 3c. The results were consistent with the UV-vis
spectral behavior of 5c, whose absorption band shifted
∼25 nm compared with that of 3c at a longer wavelength.
The induced CD signals originate in the handedness of
a folding conformation and not in the preferred confor-
mation of the (S)-1-(1-naphthyl)ethyl chromophore based
on the following three reasons: (1) Even though 1c and
2c have the (S)-1-(1-naphthyl)ethyl moiety, they did not
show significant CD signals in a region over 350 nm.
Obviously, this signal was not derived simply from the
(S)-1-(1-naphthyl)ethyl moiety itself. (2) From the X-ray
structure of 3c, it is hard to understand that this (S)-1-
(1-naphthyl)ethyl moiety can have any interaction with
other chromophores. Rather, it is natural to consider that
the CD signals originate in the stacked folding naphtha-
lene moieties, as can be seen in its X-ray structure. (3)
The CD signals in the longer wavelength region correlate
(23) Jiang, H.; Dolain, C.; Le´ger, J.-M.; Gornitzka, H.; Huc, I. J.
Am. Chem. Soc. 2004, 126, 1034-1035.
(24) Snatzke, G. Angew. Chem., Int. Ed. Engl. 1979, 18, 363-377.
1430 J. Org. Chem., Vol. 70, No. 4, 2005

Novel Aromatic Foldamers
to the red shift in the absorption spectra with the
increasing number of naphthalene moieties. This does
not require the (S)-1-(1-naphthyl)ethyl moiety, since a
similar phenomenon was observed with the N-benzyl
moiety in 3a and 5a.
Intensities of the Cotton effects become larger with the
increasing number of naphthalene moieties in acetoni-
trile. The amplification of CD intensities might be due
to the increasing number of folding units, which increases
the number of exciton couplings. Even though both the
(S)-1-phenylethyl and the (S)-1-(1-naphthyl)ethyl series
showed similar absorption bands in their UV-vis spectra,
only the (S)-1-(1-naphthyl)ethyl series were CD-active for
these absorption bands. This difference might originate
in the difference in bulkiness of these chiral substituents.
For comparison to the CD signals in solution, the CD
spectra of both series were investigated in the solid state
(Figures 9c and 10c). The crystalline compound was
grounded minutely and mixed with Nujol. The measure-
ment was carried out using NaCl plates. In the (S)-1-(1-
naphthyl)ethyl series, 3c and 5c showed the same sign
and relatively similar shapes of CD signals in their solid
state as in solution. To examine the effect of annealing,
an acetonitrile solution of 3c was refluxed for 4 h. Since
no spectral change in its CD spectrum was observed
before (immediately after dissolving) and after reflux, the
equilibrium between the two helices might incline to one
of them completely. Therefore, the conformation for 3c
(M-helicity) observed in the X-ray structure is plausible
to be the stable conformation in solution as well.25 From
these results, we can conclude that the helicities that
exist in the crystalline state for the (S)-1-(1-naphthyl)-
ethyl series might be maintained in solution. Since the
same sign of Cotton effect was observed for 5c as for 3c,
5c may possibly have the same helicity (M-helicity) as
that of 3c. However, it is not always ambiguous to
determine the secondary structure by comparing the
similarity of CD signals.26 In the (S)-1-phenylethyl series,
no CD signals were observed for 3b and 5b in a longer
wavelength region, which might be the result of the
existence of two diastereomeric helices in their crystalline
state, as can be seen in the single-crystal X-ray structure
of 3b. This stability is attributed to the multiple π-π
FIGURE 11. Temperature effect on CD spectra of 3c and 5c.
stacking of naphthalene moieties enhanced by iminodi-
carbonyl linkers and to the bulkiness of the (S)-1-(1-
naphthyl)ethyl substituent.
To study the effect of temperature on the folding
conformation, CD spectral measurements of 3c and 5c
were carried out at 218 K and compared with those at
298 K (Figure 11). At 218 K, a slight increase in their
intensities was observed. This may be caused partly by
a volumetric change of the solvent at low temperature.
The results indicate that the helical folding conformation
was preserved at room temperature and that almost no
diastereomerization occurred.
Conclusion
Carboxamides which possess naphthalene chromophores
connected by multiple iminodicarbonyl linkers formed the
helical foldamer both in solution and in the solid state.
Their absorption and fluorescence spectra showed a red
shift as the number of naphthalene rings increased by
the multiple interactions between intramolecular naph-
thalene rings. Helicity of the foldamer could be controlled
by the introduction of a chiral auxiliary at the imide
nitrogen atom. The (S)-1-(1-naphthyl)ethyl substituent
on the nitrogen atom was sufficiently bulky to regulate
the conformational change in equilibration of two helices,
which resulted in the predominance of one helix leading
to induction of a CD signal. The present study contributes
to the designing of chiral foldamers, which is one of the
current topics in the construction of artificial high-order
structures.
(25) (a) Azumaya, I.; Yamaguchi, K.; Okamoto, I.; Kagechika, H.;
Shudo, K. J. Am. Chem. Soc. 1995, 117, 9083-9084. (b) Kohmoto, S.;
Masu, H.; Tatsuno, C.; Kishikawa, K.; Yamamoto, M.; Yamaguchi, K.
J. Chem. Soc., Perkin Trans. 1, 2000, 4464-4468. (c) Tabei, J.; Nomura,
R.; Masuda, T. Macromolecules 2003, 36, 573-577. (d) Sakamoto, M.;
Iwamoto, T.; Nono, N.; Ando, M.; Arai, W.; Mino, T.; Fujita, T. J. Org.
Chem. 2003, 68, 942-946.
Supporting Information Available: Preparation infor-
mation, spectral data, and ORTEP diagrams of the compounds
(PDF and CIF). This material is available free of charge via
the Internet at http://pubs.acs.org.
(26) Gla¨ttli, A.; Daura, X.; Seebach, D.; van Gunstern, W. F. J. Am.
Chem. Soc. 2002, 124, 12972-12978.
JO048233M
J. Org. Chem, Vol. 70, No. 4, 2005 1431