Solvophobically-driven oligo(ethylene glycol) helical foldamers, synthesis, characterization, and complexation with ethane-1,2-diaminium

Article abstract of DOI:10.1021/jo049420n

Oligo(ethylene glycols) 1a-h, which are incorporated with one to eight 2,3-naphthylene units, respectively, have been synthesized and characterized. The conformational changes of the new oligomers have been investigated in chloroform-acetonitrile binary s

Full text of DOI:10.1021/jo049420n

Solvop h obica lly-Dr iven Oligo(eth ylen e glycol) Helica l F old a m er s.
Syn th esis, Ch a r a cter iza tion , a n d Com p lexa tion w ith
Eth a n e-1,2-d ia m in iu m
J un-Li Hou,† Mu-Xin J ia,‡ Xi-Kui J iang,† Zhan-Ting Li,*,† and Guang-J u Chen*,‡
Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, 354 Fenglin Lu,
Shanghai 200032, China, and Department of Chemistry, Beijing Normal University,
Beijing 100875, China
ztli@mail.sioc.ac.cn
Received April 7, 2004
Oligo(ethylene glycols) 1a -h , which are incorporated with one to eight 2,3-naphthylene units,
respectively, have been synthesized and characterized. The conformational changes of the new
1
oligomers have been investigated in chloroform-acetonitrile binary solvents by the UV-vis, H
NMR, and fluorescent spectroscopy. It has been revealed that the naphthalene units in hexamer
1f, heptamer 1g, and octamer 1h are driven by solvophobic interaction to stack in polar solvents.
As a result, compact helical conformations are formed that give rise to a cavity similar to that of
18-crown-6. Shorter oligomers 1b-e exhibit weaker folding tendency. 1H NMR studies reveal that
1f-h are able to complex ammonium or ethane-1,2-diaminium 19, but not secondary ammonium
compounds. The association constants of complexes 1f‚19, 1g‚19, and 1h ‚19 in acetonitrile are
determined to be 3.5((0.4) × 103, 1.0((0.12) × 104, and 2.5((0.4) × 104 M-1, respectively, with the
1H NMR titration method. For comparison, hexamer 22, which incorporates six 1,5-naphthylene
units, is also prepared. The UV-vis and fluorescent investigations show that 22 is also able to fold
in polar solvents, but no helical structure can be produced due to mismatch of the stacking
naphthalene units and consequently there is no obvious complexation between 22 with ethane-
1,2-diaminium ion. The structures of the longest foldamer 1h and its complex with 19 have been
studied with molecular mechanics calculations. This work represents a new approach to building
folding conformations from flexible linear molecules.
In tr od u ction
employed as molecular backbones to build foldamers.
Nevertheless, only a few folding systems have the ability
to perform functions, such as molecular recognition,5
antimicrobial activity,6 R-helix mimicking,7 and molecular
switching.8 Therefore, there is still a strong requirement
to develop novel folding patterns for further exploring
the structure-function relation.
Biomolecules rely on precise combinations of different
noncovalent interactions to produce folded conformations
that are responsible for numerous biological functions
and processes. In recent years, there has been intense
interest in developing foldamers, the synthetic oligomers
that fold into well-defined secondary structures.1 A large
number of heterocycles,2 amino acid derivatives,3 and
oligo(m-phenylene ethynylene) derivatives4 have been
(3) For representative examples, see: (a) Hamuro, Y.; Schneider,
J . P.; DeGrado, W. F. J . Am. Chem. Soc. 1999, 121, 12200. (b) Lucarini,
S.; Tomasini, C. J . Org. Chem. 2001, 66, 727. (c) Zych, A. J .; Iverson,
B. L. Helv. Chim. Acta 2002, 85, 3294. (d) Rueping, M.; Schreiber, J .
V.; Lelais, G.; J aun, B.; Seebach, D. Helv. Chim. Acta 2002, 85, 2577.
(e) J iang, H.; Leger, J .-M.; Huc, I. J . Am. Chem. Soc. 2003, 125, 3448.
(f) Huck, B. R.; Fisk, J . D.; Guzei, I. A.; Carlson, H. A.; Gellman, S. H.
J . Am. Chem. Soc. 2003, 125, 9035. (g) Yang, X.; Martinovic, S.; Smith,
R. D.; Gong, B. J . Am. Chem. Soc. 2003, 125, 9932. (h) Zhao, X.; J ia,
M. X.; J iang, X.-K.; Li, Z.-T.; Chen, G.-J . J . Org. Chem. 2004, 69, 270.
(4) For recent examples, see: (a) Yang, X.; Brown, A. L.; Furukawa,
M.; Li, S.; Gardinier, W. E.; Bukowski, E. J .; Bright, F. V.; Zheng, C.;
Zeng, X. C.; Gong, B. Chem. Commun. 2003, 56. (b) Zhao, D.; Moore,
J . S. J . Am. Chem. Soc. 2003, 125, 16294.
(5) (a) Prince, R. B.; Barnes, S. A.; Moore, J . S. J . Am. Chem. Soc.
2000, 122, 2758. (b) Tanatani, A.; Hughes, T. S.; Moore, J . S. Angew.
Chem., Int. Ed. 2002, 41, 325.
(6) (a) Liu, D. H.; DeGrado, W. F. J . Am. Chem. Soc. 2001, 123,
7553. (b) Porter, E. A.; Weisblum, B.; Gellman, S. H. J . Am. Chem.
Soc. 2002, 124, 7324.
† Chinese Academy of Sciences.
‡ Beijing Normal University.
(1) (a) Bassani, D. M.; Lehn, J .-M.; Baum, G.; Fenske, D. Angew.
Chem., Int. Ed. Engl. 1997, 36, 1845. (b) Seebach, D.; Matthews, J . L.
Chem. Commun. 1997, 2015. (c) Gellman, S. H. Acc. Chem. Res. 1998,
31, 173. (d) Nowick, J . S. Acc. Chem. Res. 1999, 32, 287. (e) Katz, T. J .
Angew. Chem., Int. Ed. 2000, 39, 1921. (f) Cubberley, M. S.; Iverson,
B. L. Curr. Opin. Chem. Biol. 2001, 5, 650. (g) Hill, D. J .; Mio, M. J .;
Prince, R. B.; Hughes, T. S.; Moore, J . S. Chem. Rev. 2001, 101, 3893.
(h) Seebach, D.; Beck, A. K.; Brenner, M.; Gaul, C.; Heckel, A. Chimia
2001, 55, 831. (i) Gong, B. Chem.sEur. J . 2001, 7, 4336. (j) Patch, J .
A.; Barron, A. E. Curr. Opin. Chem. Biol. 2002, 6, 872. (k) Zhao, D.;
Moore, J . S. Chem. Commun. 2003, 807. (l) Sanford, A. R.; Gong, B.
Curr. Org. Chem. 2003, 7, 1649. (m) Schmuck, C. Angew. Chem., Int.
Ed. 2003, 42, 2448.
(2) For recent examples, see: (a) Corbin, P. S.; Zimmerman, S. C.;
Thiessen, P. A.; Hawryluk, N. A.; Murray, T. J . J . Am. Chem. Soc.
2001, 123, 10475. (b) Petitjean, A.; Cuccia, L. A.; Lehn, J .-M.;
Nierengarten, H.; Schmutz, M. Angew. Chem., Int. Ed. 2002, 41, 1195.
(c) Dolain, C.; Maurizot, V.; Huc, I. Angew. Chem., Int. Ed. 2003, 42,
2738. (d) Kolomiets, E.; Berl, V.; Odriozola, I.; Stadler, A.-M.; Kyrit-
sakas, N.; Lehn, J .-M. Chem. Commun. 2003, 2868.
(7) Ernst, J . T.; Becerril, J .; Park, H. S.; Yin, H.; Hamilton, A. D.
Angew. Chem., Int. Ed. 2003, 42, 535.
(8) (a) Barboiu, M.; Lehn, J .-M. Proc. Natl. Acad. Sci. U.S.A. 2002,
99, 5201. (b) Barboiu, M.; Vaughan, G.; Kyritsakas, N.; Lehn, J .-M.
Chem.sEur. J . 2003, 9, 763.
10.1021/jo049420n CCC: $27.50 © 2004 American Chemical Society
Published on Web 08/24/2004
6228
J . Org. Chem. 2004, 69, 6228-6237

Solvophobically-Driven Oligo(ethylene glycol) Helical Foldamers
SCHEME 1
It has been established that in polar solvents nonpolar
aromatic units of linear molecules tend to aggregate or
stack intermolecularly or intramolecularly as a result of
hydrophobic interaction.9 This kind of hydrophobically
driven aromatic stacking is the dominant noncovalent
force for the formation of several elegant folding systems.
For example, Iverson et al. utilized the hydrophobic
interaction to construct a series of peptide-backboned
aedamers in aqueous solution.1f,10 Moore et al. employed
such noncovalent force to induce oligo(m-phenylene eth-
ynylenes) to fold in polar solvents.1g,11 Recently, Li et al.
also reported that a folded state could be produced for
linear phosphoramidites due to intramolecular per-
ylenetetracarboxilic diimide stacking.12 In this paper, we
describe that 2,3-naphthalene-incorporated oligo(ethylene
glycols) can spontaneously acquire stable helical confor-
mations in polar solvent. The new solvophobically driven
helical foldamers have a cavity similar to that of 18-
crown-6 that can complex ammonium or ethane-1,2-
diaminium in acetonitrile.
SCHEME 2
Resu lts a n d Discu ssion
It has been revealed that flexible oligo(ethylene glycols)
with two terminal aromatic donors are able to wrap
themselves around a cation to acquire a folded conforma-
tion in polar solvents.13 Nevertheless, oligo(ethylene
glycols) themselves adopt random, disordered conforma-
tions in polar solvents due to their high hydrophilicity.
We imagined that introducing hydrophobic aromatic
units at suitable positions of the oligo(ethylene glycol)
chain might force the skeleton to fold as a result of the
formation of π-π stacking between adjacent naphtha-
lenes. Therefore, a series of naphthalene-incorporated
oligo(ethylene glycols) 1b-h were designed and synthe-
sized14 with compound 1a as a reference molecule.15 The
The syntheses of 1b-d are straightforward (Scheme
2). Compound 1b was prepared in 80% yield from the
reaction of 2 and 3 in DMF with cesium carbonate as a
base. For preparation of 1c, bromide 4 was first produced
from the reaction of 2 and an excessive amount of 3 under
the reaction conditions for 1b, and subsequent reaction
of 4 with 5 produced 1c in 67% yield. Similarly, 4 was
reacted with an excessive amount of 5 to produce 6 in
60% yield. The latter was then reacted with 3 to afford
1d in 51% yield.
The synthetic routes for 1e and 1f are shown in
Scheme 3. Thus, tosylate 9 was first prepared in 81%
yield from the reaction of 7 and 8 in DMF and then
converted into 10 in 80% yield under similar conditions.
Palladium-catalyzed hydrogenation of 10 afforded 11 in
89% yield. Subsequent reaction of 11 with 4 in DMF also
with cesium carbonate as a base produced 1e in 51%
yield. For the preparation of 1f, 12 was first produced in
76% yield from the reaction of 6 and 9 and was then
deprotected under the catalysis of Pd-C to afford 13 in
86% yield. Treatment of 13 with 3 in hot DMF afforded
1f in 28% yield.
2,3-disubstituted naphthalene unit was chosen, and the
adjacent units were separated with a -OCH2CH2OCH2-
CH2O- chain because molecular modeling revealed that
π-π stacking between adjacent units would induce the
formation of a helical structure, which produces a cavity
similar to that of 18-crown-6, as shown in Scheme 1.
(9) (a) J iang, X.-K. Acc. Chem. Res. 1988, 21, 362. (b) Tung, C.-H.;
Wang, Y.-M. J . Am. Chem. Soc. 1990, 112, 6322. (c) J iang, X.-K. Pure
Appl. Chem. 1994, 66, 1621. (d) J iang, X.-K.; J i, G.-Z.; Li, Z.-T. Acta
Chim. Sinica 2000, 58, 601.
(10) Lokey, R. S.; Iverson, B. L. Nature 1995, 375, 303.
(11) Nelson, J . C.; Saven, J . G.; Moore, J . S.; Wolynes, P. G. Science
1997, 277, 1793.
(12) Wang, W.; Li, L.-S.; Helms, G.; Zhou, H.-H.; Li, A. D. Q. J . Am.
Chem. Soc. 2003, 125, 1120.
(13) Vo¨gtle, F.; Weber, E. Angew. Chem., Int. Ed. Engl. 1979, 18,
753.
(14) A 1,2-dioxybenzene-incorporated oligo(ethylene glycol) deriva-
tive similar to 1d has been reported; see: Vo¨gtle, F.; Heimann, U.
Chem. Ber. 1978, 111, 2757.
(15) Cisak, A.; Kusztal, D.; Brzezinska, E. J . Chem. Soc., Perkin
Trans. 2 2001, 538.
For the preparation of 1g (Scheme 4), bromide 14 was
first produced in 74% yield from the reaction of 6 and an
excessive amount of 3. Subsequent reaction of 14 with
11 afforded 1g in 51% yield. The synthesis of 1h began
with the preparation of 15 (Scheme 4). Compound 5 was
first treated with an excessive amount of 9 in DMF to
produce 15, which was then reacted with an excessive
amount of 3 to afford 16. Subsequent reaction of 16 with
6, followed by palladium-catalyzed hydrogenation of
intermediate 17, produced 18 in good yield. Finally, 18
was reacted with 3 in DMF to afford 1h in 44% yield.
J . Org. Chem, Vol. 69, No. 19, 2004 6229

Hou et al.
SCHEME 3
SCHEME 4
Compounds 1b-h are soluble in chloroform, a typical
nonpolar solvent, and acetonitrile, a typical polar solvent.
Therefore, the chloroform-acetonitrile binary solvent
systems were chosen for the investigation of the folding
behavior of the oligomers. The UV-vis study was first
performed to exclude any important intermolecular in-
teraction, the relation of the absorbance with the con-
centration of the oligomers was first investigated in
acetonitrile. The representative results are provided in
Figure 1. It can be found that, for all the oligomers, the
absorbance is linearly dependent on the concentration
within the specific concentration range ((0.45 to 2.4) ×
10-5 M for 1h ). That is, Beer’s law behavior is observed.
The experiment ruled out any important intermolecular
interactions within or below the concentration range.
Similar results were also observed in chloroform. Since
it has been well established that chloroform is a “benign”
solvent for nonpolar aromatic moieties,1g,3h,11 it is reason-
able to assume that Beer’s law should also be observed
for the oligomers in mixtures of chloroform and acetoni-
trile within or below the above concentration range.
The hypochromic effect of the oligomers was then
investigated in the chloroform-acetonitrile mixtures.
Previous studies have demonstrated that this intramo-
lecularly aromatic stacking-induced effect is a powerful
indicator of the folding conformation of the artificial and
natural systems.3h,10-12,16 The UV-vis spectra of all the
compounds 1a -h were recorded in the solvents with
increasing acetonitrile content at the fixed chromophore
(2,3-dioxynaphthalene ) Np) concentration of 5.0 × 10-5
M, which corresponds to a concentration of 6.3 × 10-6
M
for the longest 1h . The results are provided in Figure 2.
It was found that the hyperchromic effect was first
produced and the ꢀNp (apparent molar extinction coef-
ficient for one Np unit of a molecule) is linearly increased
with Φ (Φ is volume fraction of acetonitrile in the binary
solvent system9a) for 1a in all the solvent systems.17 This
solvent polarity-induced hyperchromic effect became
F IGURE 1. Plot of the absorbance (323 nm) vs [1] in
acetonitrile at 25 °C. Similar linear results were also observed
for oligomers 1b, 1d , 1f, and 1g, which are not shown.
(16) Cantor, C. R.; Schimmel, P. R. Biophysical Chemistry: Free-
man: New York, 1980.
6230 J . Org. Chem., Vol. 69, No. 19, 2004

Solvophobically-Driven Oligo(ethylene glycol) Helical Foldamers
F IGURE 4. Chemical shift of the CH3 signal vs the Np
number of oligomers 1 ([Np] ) 3.0 mM) in CDCl3 (b) and CD3-
CN (9) at 25 °C. The curves are drawn only as guides for the
eye.
F IGURE 2. Plot of the apparent molar extinction coefficient
ꢀNp (323 nm, [Np] ) 5.0 × 10-5 M) of oligomers 1 against Φ at
25 °C, highlighting the folding-induced hypochromic effect of
the longer oligomers in solvents of high Φ. The curves are
drawn only as guides for the eye.
F IGURE 5. Fluorescence spectra of (a) 1h in MeCN, (b) 1a
in MeCN, (c) 1h in CHCl3, and (d) 1a in CHCl3 at 25 °C ([Np]
) 2.7 × 10-6 M, λex ) 280 nm).
F IGURE 3. Partial 1H NMR spectrum (400 MHz) of oligomers
1 ([Np] ) 3.0 mM) in CD3CN at 25 °C, highlighting the folding-
induced upfield shifting of both the aromatic and aliphatic
proton signals.
the more polar solvent system (see the Supporting
Information).
weakened gradually from the short 1b in solvents of Φ
> 0.8 and vanished for the long 1e-h when Φ g 0.5.
Because there was no important intermolecular interac-
tion at the low concentration of the oligomers investi-
gated, this ꢀNp derivation, a new hypochromic effect, of
oligomers 1b-h , compared to 1a in solvents of high Φ
values, should be generated as a result of the intramo-
lecular stacking between the adjacent naphthalene units,
which induced the folding of the linear oligo(ethylene
glycol) backbones. The fact that the above hypochromic
effect occurred at lower Φ values for the longer oligomers
suggests that the longer oligomers have greater folding
ability. This observation might be attributed to their
increased hydrophobicity and implies that the stacking
is cooperative. The terrace exhibited by 1f-h within the
area of high Φ values appears to indicate that these
longer oligomers adopt completely folding conformation
in highly polar solvents.
1H NMR spectra provide more evidence that longer
oligomers 1 adopt folded conformations in polar solvents.
Compounds 1g and 1h are not soluble in DMSO. How-
1
ever, shorter compounds 1b-f are soluble, and the H
NMR spectra of these compounds in DMSO-d6 revealed
remarkable upfield shifting for all signals compared to
those of 1a at the identical [Np] (2.0 mM). The spectra
of all oligomers 1 in CD3CN were recorded, and the
representative results are presented in Figure 3. It can
be seen that pronounced upfield shifting was also exhib-
ited for all the peaks of 1b-h compared to those of 1a .
1H NMR dilution investigations (3-0.5 mM) revealed no
important intermolecular interaction (<0.03 ppm);18,19
therefore, the upfield shifting should be produced as a
result of intramolecular naphthalene stacking and (oli-
goethylene glycol) skeleton folding. The lowered resolu-
tion of the aromatic proton peaks of the longer oligomers
also supported the folding state of the skeleton.20 Al-
The UV-vis and fluorescent properties of the oligomers
are also investigated in the CHCl3-DMSO binary solvent
system. Very similar results are obtained, which show
that similar folding conformation could be generated in
(18) (a) Corbin, P. S.; Zimmerman, S. C.; Thiessen, P. A.; Hawryluk,
N. A.; Murray, T. J . J . Am. Chem. Soc. 2001, 123, 10475. (b) Zhao, X.;
Wang, X.-Z.; J iang, X.-K.; Chen, Y.-Q.; Chen, G.-J .; Li, Z.-T. J . Am.
Chem. Soc. 2003, 125, 15128.
(19) Assuming a 1:1 self-association mode, we determined the Kassoc
of the longest oligomer 1h to be approximately 52 M-1 by using the
1H NMR dilution method with the sharp methyl signal as probe, which
means that <4% of the compound existed as homodimer when [Np] )
3.0 mM.
(17) (a) J affe, H. H.; Orchin, M. Theory and Applications of
Ultraviolet Spectroscopy; J ohn Wiley & Sons: New York, 1962. (b)
Suzuki, H. Electronic Absorption Spectroscopy of Organic Molecules;
Academic Press: New York, 1967.
J . Org. Chem, Vol. 69, No. 19, 2004 6231

Hou et al.
F IGURE 6. Excimer emission spectrum of oligomers 1 (a) in chloroform and (b) in acetonitrile at 25 °C. λex ) 280 nm. [Np] ) 2.7
× 10-6 M.
though accurate chemical shifts could not be obtained for
the naphthalene and methylene signals, the methyl
signal of all oligomers was sharp. A plot of the chemical
shift of the methyl signal versus the naphthalene number
of the oligomers is shown in Figure 4. It can be found
that the shifts were nearly unchanged (<0.008 ppm) for
1b-h compared to that of 1a in CDCl3. However,
pronounced upfield shifting was displayed for the oligo-
mers and the shifting was increased with the lengthening
of the oligomers (ca. -0.12 ppm for 1h ) in CD3CN. The
increased upfield shifting observed for the longer oligo-
mers should reflect stronger stacking and a correspond-
ingly more compact folding state, which is also consistent
with the above UV-vis observations.
The fluorescent study also supports the folded confor-
mations for long oligomers in polar solvents. The fluo-
rescent spectra of 1h and 1a in chloroform and aceto-
nitrile at the identical [Np] are shown in Figure 5. It can
be seen that in chloroform both compounds exhibited
F IGURE 7. Plot of the excimer intensity at 367 nm vs Φ in
chloroform and acetonitrile at 25 °C. λex ) 280 nm, [Np] ) 2.7
× 10-6 M. The curves are drawn as guides for the eye.
similar spectra with comparable emission strength. In
7). Within the area of low Φ (e ca. 0.2), the excimer
intensity of the oligomers was increased linearly with the
increase of Φ. However, the excimer emission of the
longer oligomers became stronger than the shorter ones
and finally unchanged at high Φ (ca. 0.78 for 1h ), while
the emission of the shorter compounds 1b and 1c
contrast, a remarkable hyperchromic effect was exhibited
for 1h in acetonitrile.17 A similar hyperchromic effect was
also observed for 1b-g at the fixed [Np], which was
increased with the lengthening of the oligomers. Because
the UV-vis experiments have established that no im-
portant intermolecular aggregations exist for all the
exhibited just a slight strengthening even at very high
oligomers at the concentration, the hyperchromic effect
Φ. This is very similar to that revealed by the above UV-
vis investigations (Figure 2), supporting that the longer
oligomers have greater folding tendency in polar solvents.
should also be attributed to intramolecular aromatic
stacking and chain folding.10 The normalized excimer
emission spectra of 1b-h at the identical [Np] in
The terrace observed in Figure 7 for 1f,g within the area
chloroform and acetonitrile, produced by subtracting the
of high Φ is also consistent with a completely folding
conformation for these oligomers. This is well in ac-
cordance with the above UV-vis result.
Crystals of 1c suitable for X-ray analysis were grown
from DMSO by evaporation of the solution. Figure 8
shows the X-ray structure, in which the two flexible
spectrum of 1a from that of 1b-h ,9b respectively, are
given in Figure 6. It can be seen that all the oligomers
exhibited a very weak emission band with λmax at ca. 348
nm in chloroform, and the shorter oligomers 1b and 1c
also displayed weak excimer emission band at λmax ) 348
and 358 nm, respectively, in acetonitrile. In contrast, the
aliphatic chains are pointed away from the central
longer oligomers 1d -h produced stronger excimer emis-
naphthalene. One ending naphthalene is located nearly
sion in acetonitrile, which was increased with the length-
perpendicular to another ending naphthalene (the angle
ening of the oligomers. This result also indicates that
between the two planes is ca. 84°).
more compact folding states were generated for the longer
Numerous attempts to crystallize the longer oligomers
oligomers in polar solvent.
were not successful. To obtain more insight for the
The influence of the solvent polarity on the excimer
structure of the folding oligomers, molecular mechanics
emission of the oligomers was also investigated in
calculation with the compass force field was carried out
chloroform and acetonitrile at the identical [Np] (Figure
for the longest 1h .21 The structure of the energy-
minimized conformation is presented in Figure 9, which
reveals a cavity with depth of ca. 10 Å and width of ca.
2.8 Å. The width of the cavity is very close to that of
(20) Extensive intramolecular aromatic stackings usually lead to
lowered resolution of the 1H NMR spectra of folding molecules, see
refs 10 and 11.
6232 J . Org. Chem., Vol. 69, No. 19, 2004

Solvophobically-Driven Oligo(ethylene glycol) Helical Foldamers
F IGURE 8. X-ray structure of 1c.
F IGURE 11. J ob’s plots of the chemical shift of the CH2
protons of 19 vs [1]/[1] + [19] in CD3CN at 25 °C ([1] + [19] )
3.0 mM).
-
studies between 1f-h and NH3+CH2CH2NH3+2CF3SO3
(19) were then performed in CD3CN. As examples, the
results of 1f and 1h are provided in Figure 10. It can be
found that adding 1 equiv of 19 to the solutions of 1f and
1h led to important splitting of the spectrum of the
oligomers. The NH signal of 19 disappeared, while its
CH2 signal shifted upfield remarkably (-0.20 and -0.31
ppm, respectively). The upfield shift was obviously gener-
ated due to complexation of 19 by the oligomers, the
naphthalene units of which produced an important
deshielding effect to the CH2 group of 19. In addition,
the resolution of the resonances of 19 was also moder-
ately increased upon addition of the guest, and the H-1
and H-4 protons of the naphthalene units displayed six
identifiable signals, although most of the signals could
not be assigned completely (the peak of the aromatic
protons adjacent to the MeO group could be assigned with
the NOESY experiment). These observations suggest that
a more compact conformation was formed for 19 after
complexation. Similar result was also observed for 1g. A
J ob’s plot study revealed a 1:1 binding mode for the
complexes (Figure 11).25a Quantitative studies were
preformed by titrating 19 with the oligomers and observ-
ing the changes of the CH2 signal. The results are
provided in Figure 12. By fitting to a nonlinear binding
F IGURE 9. Energy-minimized structure of octamer 1h ,
showing a cavity similar to that of 18-crown-6.
dibenzo-18-crown-6, the cavity of which has been esti-
mated to be 2.68-2.86 Å.22,23
It has been established that dibenzo-18-crown-6 could
complex ammonium or alkylammonium.24 Therefore, a
binding study was also carried out between the longer
oligomers 1f-h and ammoniums. Adding 2 equiv of
ammonium perchlorate to the solution of 1f-h in CD3-
CN (1.5 mM) induced important shifting of the signals
of the 1H NMR spectrum of the oligomers. A similar
result was not revealed when n-Bu4N+ ClO4 (5 equiv)
-
was added. Therefore, the spectral shifting should result
from complexation between the oligomers and ammo-
1
nium ion but not from the salt effect. Since the H NMR
spectrum of the mixtures was of low resolution, quantita-
tive binding study could not be performed. The binding
1
F IGURE 10. Partial H NMR spectrum (400 MHz) of (a) 1h , (b) 1h + NH3+CH2CH2NH3+ 2CF3SO3- (19), (c) 19, (d) 1f + 19, and
(e) 1f in CD3CN at 25 °C (1.5 mM).
J . Org. Chem, Vol. 69, No. 19, 2004 6233

Hou et al.
SCHEME 5
F IGURE 12. Chemical shift changes of the CH2 proton of 19
(6.9 × 10-4 M) with the concentrations of 1f (9), 1g (b), and
1h (2) in CD3CN at 25 °C.
folding conformation was formed for 1f in acetonitrile due
to its strong complexation toward 19.
Mixing 1.0 equiv of 20 and 1f, 1g, or 1h in CD3CN (1.5
mM) did not induce the 1H NMR signals of both com-
pounds to change notably. Similar results were also
observed for the systems of 21 and the oligomers. These
observations indicate that the oligomers cannot complex
the cationic guests, which are consistent with the fact
that 18-crown-6 derivatives could not efficiently complex
secondary ammoniums.27
F IGURE 13. Energy-minimized structure of complex 1h ‚19.
equation appropriate for a 1:1 binding model,18,25 associa-
tion constants (Kassoc) of 3.5((0.4) × 103, 1.0((0.12) × 104,
and 2.5((0.4) × 104 M-1 were determined for complexes
1f‚19×e2 1g‚19×e2 and 1h ‚19, respectively.26 The binding
mode of complex 1h ‚19 was also investigated by molec-
ular modeling, and an energy-minimized structure was
produced (Figure 13), which shows that the dicationic
guest is twined by the oligomer.
1
A 2D H NMR experiment in CD3CN revealed inter-
molecular NOEs between the ethylene protons of 1f and
the methylene protons of 19, providing additional evi-
dence that a stable complex 1f‚19 was formed in the polar
solvent (see the Supporting Information). Strong in-
tramolecular NOEs were also observed between the H-1
and H-4 signals of the naphthalene units and the OCH2
signals of 1f in the presence of 19. These OCH2 groups
should be those directly linked to the naphthalene units.
Similar NOEs were remarkably weaker or even not
observed at an identical concentration of 1f in the absence
of 19. These results also indicate that a more compact
To examine if the location of the ethylene glycol chain
at the 2,3-positions of the naphthalene unit in the
oligomers is indispensable for the formation of the 18-
crown-6-like folding state, hexamer 22 was also synthe-
sized (Scheme 5). In brief, 24 was first prepared from
the alkylation of 23 and then reacted with 25 to yield
26. Compound 26 was then converted to 27 by palladium-
catalyzed hydrogenation followed by a further alkylation
reaction. By repeating the same reaction procedures, 27
was converted to 22 in moderate yield.
UV-vis studies in chloroform and acetonitrile revealed
remarkable hypochromic effect, starting from Φ ) 0.58,
for 22 at [Np] ) 2.7 × 10-6 M,28 while its excimer
(21) Berkert, U.; Allinger, N. L. Molecular Mechanics; ACS Mono-
graph 177; American Chemical Society: Washington, D.C., 1982.
(22) Izatt, R. M.; Bradshaw, J . S.; Nielsen, S. A.; Lamb, J . D.;
Christensen, J . J . Chem. Rev. 1985, 85, 271.
(23) Dalley, N. K. In Synthetic Multidentate Macrocyclic Compounds;
Izatt, R. M., Christensen, J . J ., Eds.; Academic Press: New York, 1978.
(24) (a) Nagano, O.; Kobayashi, A.; Sasaki, Y. Bull. Chem. Soc. J pn.
1978, 51, 790. Bovill, M. J .; Chadwick, D. J .; Sutherland, I. O.; Watkin,
D. J . Chem. Soc., Perkin Trans. 2 1980, 1529. (c) Pears, D. A.; Stoddart,
J . F.; Fakley, M. E.; Allwood, B. L.; Williams, D. J . Acta Crystallogr.
1988, C44, 1426. (d) Trueblood, K. N.; Knobler, C. B.; Lawrence, D.
S.; Stevence, R. V. J . Am. Chem. Soc. 1982, 104, 1355.
(25) (a) Conners, K. A. Binding Constants: The Measurement of
Molecular Complex Stability; Wiley: New York, 1987. (b) Wilcox, C.
S. In Frontiers in Supramolecular Organic Chemistry and Photochem-
istry; Schneider, H. J ., Du¨rr, H., Eds.; VCH: New York, 1991; p 123.
(26) Other more complicated binding patterns could not be excluded.
Nevertheless, good results were obtained by assuming the simple 1:1
binding mode.
(27) Pedersen, C. J . J . Am. Chem. Soc. 1967, 89, 7017.
6234 J . Org. Chem., Vol. 69, No. 19, 2004

Solvophobically-Driven Oligo(ethylene glycol) Helical Foldamers
Exp er im en ta l Section
Ma ter ia ls a n d Meth od s. Melting points are uncorrected.
All reactions were performed under an atmosphere of dry
1
nitrogen. The H NMR spectra were recorded on a 400 or 600
M Hz spectrometer in the indicated solvents, chemical shifts
are expressed in parts per million relative to the residual
solvent protons as internal standards. Chloroform (δ ) 7.26
ppm) and TMS (δ ) 0.00 ppm) were used as an internal
standard for CDCl3 and CD3CN, respectively. Elemental
analysis was carried out at the SIOC analytic center. Unless
otherwise indicated, all starting materials were obtained from
commercial suppliers and were used without further purifica-
tions. DMF was dried following standard procedures before
use. Silica gel (10-40 µ) was used for all column chromatog-
raphy. For the 1H NMR titration method, see ref 18b.
Compound 1a was prepared according to the reported method.15
Com p ou n d 1b. To a stirred suspension of 230 (0.25 g, 1.44
mmol) and cesium carbonate (0.56 g, 1.73 mmol) in DMF (10
mL) was added a solution of 331 (0.17 g, 0.72 mmol) in DMF
(2 mL). The mixture was stirred at 80 °C for another 3 h, and
the solvent was removed under reduced pressure. The result-
ing residue was triturated with chloroform (100 mL). The
organic phase was washed with water (30 mL × 2) and brine
(30 mL) and dried over sodium sulfate. After removal of the
solvent in vacuo, the crude product was purified by column
chromatography (hexane/CH2Cl2 1:3) to afford 1b as a white
F IGURE 14. Plot of the excimer intensity for compound 22
at 367 nm vs Φ in chloroform and acetonitrile at 25 °C (λex
)
280 nm, [Np] ) 2.7 × 10-6 M).
intensity of the same concentration was increased and
reached a platform at Φ ) ca. 0.75 (Figure 14). These
results are very similar to those observed for 1f, indica-
tive of a folding conformation and intramolecular stack-
ing taking place for 22. However, adding up to 10 equiv
of ammonium perchlorate or 19 to its solution in CD3CN
did not cause any pronounced shifting of its 1H NMR
spectrum (<0.01 ppm). The result reveals that aromatic
stacking within 22 did not produce a helical conforma-
tion, but might give rise to a folding state similar to that
of the “aedamer” reported by Iverson.10,29 Molecular
modeling also revealed that other kinds of isomers of the
long oligomers could not produce folding conformations
with a cavity through efficient aromatic stacking.
1
powder (0.24 g, 80%). Mp: 108-110 °C. H NMR (CDCl3): δ
7.64-7.67 (m, 4 H), 7.34-7.30 (m, 4 H), 7.17 (s, 2 H), 7.10 (s,
2 H), 4.35 (t, J ) 5.1 Hz, 4 H), 4.10 (t, J ) 5.7 Hz, 4 H), 3.95
(s, 6 H). 13C NMR (75 MHz, CDCl3): 149.7, 148.6, 129.3, 129.0,
126.3, 126.2, 124.2, 124.1, 108.0, 106.5, 69.8, 68.2, 55.8. MS
(ESI): m/z 436 [M + NH4]+, 441 [M + Na]+. Anal. Calcd for
C
26H26O5: C, 74.61; H, 6.27. Found: C, 74.66; H, 6.17.
Com p ou n d 4. This compound was prepared from the
reaction of 2 and excessive amount of 3 (4.0 equiv) on the basis
of the method described for 1b. The crude product was purified
by column chromatography (EtOAc/hexanes 1:15) to give the
required product as a white powder (77%). Mp: 55-57 °C. 1H
NMR (CDCl3): δ 7.70-7.66 (q, J ) 3.5 Hz, 2 H), 7.35-7.32
(m, 2 H), 7.17 (s, 1 H), 7.13 (s, 1 H), 4.32 (t, J ) 4.5 Hz, 2 H),
4.02-3.98 (m, 5 H), 3.94 (t, J ) 6.6 Hz, 2 H), 3.53 (t, J ) 6.6
Hz, 2 H). MS (ESI): m/z 342 [M + NH4]+, 347 [M + Na]+.
Anal. Calcd for C15H17BrO3: C, 55.40; H, 5.27. Found: C, 55.75;
H, 5.26.
Com p ou n d 1c. This compound was prepared as a white
powder (67%) from the reaction of 2 equiv of 4 and 1 equiv of
5 on the basis of the method described for 1b. Mp: 116-120
°C. 1H NMR (CD3CN): δ 7.72-7.63 (m, 6 H), 7.35-7.20 (m,
12 H), 4.28 (t, J ) 4.2 Hz, 4 H), 4.22 (t, J ) 4.2 Hz, 4 H),
3.98-3.95 (m, 8 H), 3.89 (s, 6 H). 13C NMR (75 MHz, CDCl3):
δ 149.7, 149.0, 148.6, 129.3, 129.0, 126.3, 126.3, 126.2, 124.2,
124.2, 124.0, 108.5, 108.0, 106.4, 69.8, 69.8, 68.5, 68.2, 55.7.
MS (ESI): m/z 666 [M + NH4]+, 671 [M + Na]+. Anal. Calcd
for C40H40O8: C, 74.04; H, 6.23. Found: C, 74.06; H, 6.18.
Com p ou n d 6. This compound was prepared as a white
powder (60%) from the reaction of 4 and an excess amount of
5 (4.0 equiv) on the basis of the method described for 1b. Mp:
96-99 °C. 1H NMR (CDCl3): δ 7.68-7.63 (m, 4 H), 7.35-7.31
(m, 4 H), 7.25-7.12 (m, 4 H), 6.84 (s, 1 H), 4.39-4.34 (m, 4
H), 4.08-4.06 (m, 4 H), 3.96 (s, 3 H). MS (ESI): m/z 422 (M +
NH4)+, 427 (M + Na)+. Anal. Calcd for C25H24O5: C, 74.24; H,
5.98. Found: C, 74.15; H, 5.95.
Con clu sion s
We have demonstrated that structurally flexible 2,3-
naphthylene-incorporating oligo(ethylene glycols) can
adopt folding conformation in polar solvents as a result
of solvophobically driven intramolecular aromatic stack-
ing. The folding conformations of the oligomers have been
supported by the UV-vis, 1H NMR, fluorescent spectros-
copy, and molecular modeling study. The long oligomers
exhibt greater ability to fold and their folding states can
produce a cavity with a width similar to that of 18-crown-
6, which can complex ammonium or ethane-1,2-diamin-
ium ion.
For a long time, ethylene glycols have been regarded
as a kind of disordered oligomers in both polar and
nonpolar solvents.13 The present investigation demon-
strates that, by introducing additional functional units
at specific positions, the compact and ordered conforma-
tion could be induced from the otherwise flexible materi-
als. A noticeable feature of the new kind of foldamers is
that a cavity with relatively width could be produced,
while the depth of the cavity could be controlled by
regulating the length of the oligomers. Further works will
focus on introducing chiral side chains to the ethylene
glycol chain, which is envisioned to induce the chiral bias
of the corresponding oligomers, and constructing longer
oligomers or polymers of the same skeleton, which should
give rise to nanoscale of tubes.
Com p ou n d 1d . This compound was prepared as a white
powder (51%) from the reaction of 1 equiv of 3 and 2 equiv of
6 on the basis of the method described for 1b. Mp: 146-148
°C. 1H NMR (acetone-d6): δ 7.69-7.61 (m, 8 H), 7.28-7.22
(m, 16 H), 4.28-4.21 (m, 12 H), 4.04-3.93 (m, 12 H), 3.88 (s,
(28) At such a low concentration, intermolecular interaction could
be ruled out. The concentration is within the concentration range where
the Bill’s law is observed.
(30) Ansink, H. R. W.; Zelvelder, E.; Cerfontain, H. Recl. Trav. Chim.
Pays-Bas 1993, 112, 216.
(31) Illuminati, G.; Mandolini, L.; Masci, B. J . Am. Chem. Soc. 1981,
103, 4142.
(29) Nguyen, J . Q.; Iverson, B. L. J . Am. Chem. Soc. 1999, 121, 2639.
J . Org. Chem, Vol. 69, No. 19, 2004 6235

Hou et al.
6 H). 13C NMR (75 MHz, CDCl3): δ 149.9, 148.9, 148.6, 129.3,
129.0, 126.3, 126.3, 126.3, 126.2, 124.2, 124.1, 124.0, 108.5,
108.4, 107.9, 106.4, 69.8, 69.8, 69.7, 68.5, 68.4, 68.2, 55.7. MS
(ESI): m/z 896 [M + NH4]+, 901 [M + Na]+. HRMS (ESI): m/z
901.3531, calcd for C54H54O11Na 901.3558. Anal. Calcd for
of 13 on the basis of the method described for 1b. Mp: 170-
172 °C. 1H NMR (DMSO-d6): δ 7.69-7.60 (m, 12 H), 7.31-
7.24 (m, 24 H), 4.16 (m, 20 H), 3.88 (m, 20 H), 3.82 (s, 6 H).
13C NMR (75 MHz, CDCl3): δ 149.3, 148.5, 148.3, 128.9, 128.9,
128.7, 126.2, 126.1, 123.9, 123.8, 108.0, 107.9, 107.3, 106.5,
69.0, 68.9, 68.0, 67.7, 55.3. MS (MALDI-TOF): m/z 1361 [M
C
54H54O11: C, 73.79; H, 6.19. Found: C, 73.50; H, 6.02.
Com p ou n d 9. To a stirred suspension of compound 732 (1.00
+ Na]+. HRMS (MALDI): m/z 1361.5451, calcd for C82H82O17
-
Na 1361.5444. Anal. Calcd for C82H82O17: C, 73.52; H, 6.17.
Found: C, 73.19; H, 6.24.
g, 4.0 mmol) and cesium carbonate (1.43 g, 4.40 mmol) in DMF
(40 mL) was added a solution of ditosylate 833 (8.28 g, 20.0
mmol) in DMF (25 mL). The reaction mixture was stirred at
100 °C for 3 h, and the solvent was removed under reduced
pressure. The resulting residue was triturated with chloroform
(300 mL), and the organic phase was washed with water (50
mL × 3) and brine (50 mL) and dried over sodium sulfate.
Upon removal of the solvent in vacuo, the crude product was
subjected to column chromatography (EtOAc/hexane 1:4) to
produce 9 as a white gel (1.60 g, 81%). 1H NMR (CDCl3): δ
7.77 (d, J ) 8.4 Hz, 2 H), 7.65 (q, J ) 4.5 Hz, 2 H), 7.47 (d, J
) 7.5 Hz, 2H), 7.38-7.32 (m, 7 H), 7.20 (s, 1 H), 7.13 (s, 1 H),
5.20 (s, 1 H). MS (ESI): m/z 493 [M + H]+, 510 [M + NH4]+.
Anal. Calcd for C28H28O6S: C, 68.27; H, 5.73. Found: C, 68.28;
H, 5.94.
Com p ou n d 10. This compound was prepared as a white
powder (80%) from the reaction of 1 equiv of 5 and 2 equiv of
9 (2.0 equiv) on the basis of the method described for 9. Mp:
120-122 °C. 1H NMR (acetone-d6): δ 7.70-7.64 (m, 6 H),
7.56-7.53 (m, 4 H), 7.38-7.27 (m, 18 H), 5.21 (s, 4 H), 4.28-
4.21 (m, 8 H), 4.02-3.97 (m, 8 H). MS (ESI): m/z 818 [M +
NH4]+, 823 [M + Na]+. Anal. Calcd for C52H48O8: C, 77.96; H,
6.05. Found: C, 78.13; H, 6.02.
Com p ou n d 11. A suspension of 10 (0.80 g, 1.00 mmol),
Pd-C (10%, 0.10 g) in dichloromethane (90 mL), and methanol
(10 mL) was stirred under an atmosphere of hydrogen (1 atm)
at 40 °C for 12 h. The solid was filtered off, and the filtrate
was concentrated in vacuo. The crude product was then
purified by column chromatography (CH2Cl2/CH3OH 500:1) to
obtain 11 as a white powder (0.56 g, 89%). Mp: 62-63 °C.1H
NMR (CD3OD): δ 7.65-7.61 (m, 2 H), 7.54-7.50 (m, 4 H),
7.27-7.16 (m, 12 H), 7.09 (s, 2 H), 4.24-4.12 (m, 8 H), 3.97-
3.91 (m, 8 H). MS (ESI): m/z 638 [M + NH4]+, 643 [M + Na]+.
Anal. Calcd for C38H36O8: C, 73.52; H, 5.85. Found: C, 73.52;
H, 6.22.
Com p ou n d 14. This compound was prepared as a white
powder (74%) from the reaction of 6 and an excessive amount
of 3 (5.0 equiv) on the basis of the method described for 1d .
Mp: 67-69 °C. 1H NMR (CDCl3): δ 7.63-7.68 (m, 4 H), 7.34-
7.30 (m, 4 H), 7.18 (s, 1 H), 7.17 (s, 1 H), 7.13 (s, 1 H), 7.10 (s,
1 H), 4.35-4.31 (m, 4 H), 4.24 (t, J ) 4.5 Hz, 2 H), 4.13-4.06
(m, 4 H), 3.95-3.90 (m, 7 H), 3.50 (t, J ) 6.0 Hz, 2 H). MS
(ESI): m/z 572 [M + NH4]+, 577 [M + Na]+. Anal. Calcd for
C
29H31BrO6: C, 62.71; H, 5.63. Found: C, 62.38; H, 5.41.
Com p ou n d 1g. This compound was prepared as a white
solid (51%) from the reaction of 11 (1.0 equiv) and 14 (2.2
equiv) on the basis of the method described for 1b. Mp: 162-
164 °C.1H NMR (DMSO-d6): δ 7.68-7.59 (m, 12 H), 7.28-
7.21 (m, 24 H), 4.13 (m, 24 H), 3.88 (m, 24 H), 3.81 (s, 6 H).
13C NMR (75 MHz, CDCl3): δ 149.3, 148.5, 148.3, 128.9, 128.7,
128.7, 126.2, 126.1, 123.9, 123.8, 107.9, 107.3, 106.5, 69.0, 68.9,
68.0, 67.6, 66.4, 55.3. MS (MALDI-TOF): m/z 1591 [M + Na]+.
HRMS (MALDI-TOF): m/z 1591.6402, calcd for C96H96O20Na
1591.6387. Anal. Calcd for C96H96O20
Found: C, 73.02; H, 6.32.
: C, 73.45; H, 6.16.
Com p ou n d 15. A suspension of 5 (0.37 g, 2.32 mmol), 9
(1.14 g, 2.32 mmol), and NaHCO3 (0.20 g, 2.32 mmol) in DMF
(40 mL) was stirred at 100 °C for 2 h and then poured into ice
(200 g). The precipitate formed was filtered, washed with water
thoroughly, and dried in vacuo. After recrystallization from
ethyl acetate and hexanes (1:2), the desired compound was
obtained as a gray powder (0.83 g, 74%). Mp: 122-124 °C. 1H
NMR (CDCl3): δ 7.67-7.62 (m, 4 H), 7.48 (d, J ) 6.6 Hz, 2
H), 7.35-7.28 (m, 7 H), 7.22 (s, 1 H), 7.18 (s, 1 H), 7.11 (s, 1
H), 6.74 (s, 1 H), 5.21 (s, 2 H), 4.35 (t, J ) 4.2 Hz, 2 H), 4.25
(t, J ) 4.2 Hz, 2 H), 4.06-4.03 (m, 4 H). MS (ESI): m/z 498
[M + NH4]+, 503 [M + Na]+. Anal. Calcd for C31H28O5: C,
77.48; H, 5.87. Found: C, 76.91; H, 5.86.
Com p ou n d 1e. This compound was prepared as a white
powder (51%) from the reaction of 4 and 11 on the basis of
the method described for 1b. Mp: 154-156 °C. 1H NMR (CD3-
CN): δ 7.64-7.58 (m, 10 H), 7.29-7.25 (m, 10 H), 7.17-7.13
(m, 10 H), 4.18-4.12 (m, 16 H), 3.87 (m, 16 H), 3.83 (s, 6 H).
13C NMR (75 MHz, CDCl3): δ 149.7, 148.9, 148.6, 129.3, 129.0,
126.3, 126.3, 126.2, 124.2, 124.2, 124.1, 124.0, 108.5, 107.9,
106.4, 69.8, 69.8, 69.8, 68.5, 68.4, 68.2, 55.7. MS (MALDI-
TOF): m/z 1131 [M + Na]+. Anal. Calcd for C68H68O14: C,
73.61; H, 6.19. Found: C, 73.24; H, 6.41.
Com p ou n d 16. This compound was prepared as a white
powder (81%) from the reaction of 15 and 3 (5.0 equiv) on the
basis of the method described for 1b. Mp: 87-89 °C. 1H NMR
(CDCl3): δ 7.66-7.64 (m, 4 H), 7.51-7.48 (d, J ) 7.8 Hz, 2
H), 7.36-7.31 (m, 7 H), 7.21 (s, 1 H), 7.18 (s, 1 H), 7.12 (s, 1
H), 5.21 (s, 2 H), 4.36 (t, J ) 4.5 Hz, 2 H), 4.26-4.21 (m, 4 H),
4.11-4.09 (m, 4 H), 3.92-3.86 (m, 4 H), 3.46 (t, J ) 6.3 Hz, 2
H). MS (ESI): m/z 648 [M + NH4]+, 653 [M + Na]+. Anal. Calcd
for C35H35BrO6: C, 66.56; H, 5.59. Found: C, 66.59; H, 5.67.
Com p ou n d 17. This compound was prepared as a white
powder (79%) from 6 and 16 on the basis of the method
Com p ou n d 12. This compound was prepared as a white
gel (76%) from the reaction of 6 and 9 on the basis of the
method described for 9. 1H NMR (acetone-d6): δ 7.69 (m, 6
H), 7.56 (m, 2 H), 7.36-7.22 (m, 15 H), 5.21 (s, 2 H), 4.26 (m,
8 H), 4.01 (m, 8 H), 3.88 (s, 3 H). MS (ESI): m/z 742 [M +
NH4]+, 747 [M + Na]+. HRMS (ESI): m/z 747.2930, calcd for
described for 1b. Mp: 82-84 °C. 1H NMR (acetone-d6):
δ
7.70-7.20 (m, 29 H), 5.19 (s, 2 H), 4.26-4.19 (m, 12 H), 4.01-
3.92 (m, 12 H), 3.86 (s, 3 H). MS (ESI): m/z 972 [M + NH4]+.
Anal. Calcd for C60H58O11: C, 75.45; H, 6.12. Found: C, 75.31;
H, 6.20.
C
46H44O8Na 747.2928. Anal. Calcd for C46H44O8: C, 76.22; H,
Com p ou n d 18. This compound was prepared from 17 on
the basis of the method described for 11 as a white powder
(89%). Mp: 78-80 °C.1H NMR (acetone-d6): δ 8.03 (s, 1 H),
7.61-7.66 (m, 8 H), 7.29-7.18 (m, 16 H), 4.28-4.23 (m, 12
H), 4.02-3.95 (m, 12 H), 3.87 (s, 3 H). MS (ESI): m/z 882 [M
+ NH4]+, 887 [M + Na]+. Anal. Calcd for C53H52O11: C, 73.58;
H, 6.07. Found: C, 73.34; H, 6.07.
Com p ou n d 1h . This compound was prepared as a white
powder (44%) from the reaction of 3 and 18 (2.2 equiv) on the
basis of the method described for 1b. Mp: 174-176 °C. 1H
NMR (DMSO-d6): δ 7.64-7.55 (m, 16 H), 7.25-7.17 (m, 32
H), 4.10 (m, 28 H), 3.82 (m, 28 H), 3.78 (s, 6 H). 13C NMR (75
MHz, CDCl3): δ 148.5, 148.3, 128.8, 128.7, 125.8, 125.6, 123.5,
123.4, 108.6, 108.5, 107.8, 106.7, 68.8, 68.1, 67.8, 55.2. MS
6.12. Found: C, 76.01; H, 6.20.
Com p ou n d 13. This compound was prepared as a white
powder (86%) from 12 on the basis of the method described
for 11. Mp: 64-66 °C. 1H NMR (acetone-d6): δ 7.59-7.47 (m,
6 H), 7.19-7.06 (m, 12 H), 4.21-4.11 (m, 8 H), 3.92-3.84 (m,
8 H), 3.75 (s, 3 H). MS (ESI): m/z 652 [M + NH4]+, 657 [M +
Na]+. HRMS (ESI): m/z 657.2441, calcd for C39H3O8Na 657.2458.
Com p ou n d 1f. This compound was prepared as a white
powder (56%) from the reaction of 1 equiv of 3 and 2.2 equiv
(32) Weber, E.; Ko¨hler, H.-J .; Reuter, H. Chem. Ber. 1989, 122, 959.
(33) Bradshaw, J . S.; Huzthy, P.; McDaniel, C. W.; Zhu, C. Y.; Dalley,
N. K.; Izatt, R. M.; Lifson, S. J . Org. Chem. 1990, 55, 3129.
6236 J . Org. Chem., Vol. 69, No. 19, 2004

Solvophobically-Driven Oligo(ethylene glycol) Helical Foldamers
(MALDI-TOF): m/z 1821 [M + Na]+, 1837 [M + K]+. HRMS
purify and, without purification, treated with dibromide 3 in
hot DMF in the presence of cesium carbonate. Compound 27
was obtained after workup and column chromatography (CH2-
Cl2/MeOH 100:1) as a white powder (45% for two steps). Mp:
(MALDI-TOF): m/z 1821.7296, calcd for
C110H110O23Na
1821.7330.
Com p ou n d 24. A solution of 2334 (2.50 g, 10.0 mmol) and
cesium carbonate (3.90 g, 12.0 mmol) in DMF (100 mL) was
stirred at room temperature for 30 min. A solution of 3 (16.6
g, 50.0 mmol) in DMF (100 mL) was then added. The solution
was then stirred at 80 °C for 12 h. Upon removal of the solvent
under reduced pressure, the resulting residue was triturated
with chloroform (200 mL). After normal workup, the crude
product was purified by column chromatography (hexane/CH2-
Cl2 1:5) to afford compound 24 as a white powder (2.60 g, 65%).
1
78-80 °C. H NMR (CDCl3): δ 7.92-7.88 (m, 6 H), 7.52 (d, J
) 6.9 Hz, 2 H), 7.42-7.28 (m, 9 H), 6.89-6.83 (m, 6 H), 5.24
(s, 2 H), 4.36-4.34 (m, 8 H), 4.17-4.14 (m, 8 H), 3.99 (s, 3 H).
MS (ESI): m/z 725 [M + H]+. HRMS (ESI): m/z 747.2930,
calcd for C46H44O8Na 747.2928.
Com p ou n d 22. This compound was prepared as a white
powder (40%) by hydrogenation of 27 and treatment of the
crude product with 3 by using the procedures described for
27. Mp: 178-180 °C. 1H NMR (CDCl3): δ 7.78-7.73 (m, 12
H), 7.30-7.24 (m, 12 H), 4.32-4.28 (m, 20 H), 4.09-4.04 (m,
20 H), 3.96 (s, 1 H). 13C NMR (75 MHz, CDCl3): δ 148.4, 148.3,
128.7, 128.8, 128.7, 126.2, 126.1, 123.7, 123.4, 107.9, 107.3,
106.5, 69.1, 68.8, 68.0, 67.5, 55.3. MS (MALDI-TOF): m/z 1356
[M + NH4]+, 1361 [M + Na]+. HRMS-MS (MALDI): m/z
1361.5451, calcd for C82H82O17Na 1361.5444.
1
Mp: 74-76 °C. H NMR (CDCl3): δ 7.94 (d, J ) 8.4 Hz, 1 H),
7.88 (d, J ) 8.4 Hz, 1 H), 7.55-7.52 (m, 2 H), 7.45-7.34 (m, 5
H), 6.93 (d, J ) 7.5 Hz, 1H), 6.87 (d, J ) 7.5 Hz, 1 H). MS
(ESI): m/z 401 [M + H]+. Anal. Calcd for C21H21BrO3: C, 62.85;
H, 5.27. Found: C, 63.19; H, 5.01.
Com ou n d 26. This compound was prepared as a white
powder (88%) from the reaction of 2535 and 24 (2.2 equiv) on
1
the basis of the method described for 24. Mp: 54-56 °C. H
Ack n ow led gm en t. We thank the Ministry of Sci-
ence and Technology (G2000078100), the National
Natural Science Foundation, and the State Laboratory
of Bio-Organic and Natural Products Chemistry of
China for financial support.
NMR (CDCl3): δ 7.95-7.82 (m, 4 H), 7.53 (d, J ) 6.9 Hz, 2
H), 7.44-7.32 (m, 7 H), 6.93-6.85 (m, 4 H), 5.25 (s, 2 H), 4.37-
4.34 (m, 4 H), 4.15 (t, J ) 4.5 Hz, 4 H), 4.01 (s, 3 H). MS (ESI):
m/z 495 [M + H]+. Anal. Calcd for C32H30O5: C, 77.71; H, 6.11.
Found: C, 77.90; H, 6.08.
Com p ou n d 27. Compound 26 was first subjected to Pd-
C-catalyzed hydrogenation in methanol and dichloromethane,
a mixture of products was obtained which were difficult to
Su p p or tin g In for m a tion Ava ila ble: The UV-vis and
fluorescent experiments of 1a -h in the CHCl3-DMSO binary
solvent system, the NOESY spectrum of complex 1f‚19 in CD3-
CN, and X-ray crystallographic data for 1c. This material is
available free of charge via the Internet at http://pubs.acs.org.
(34) Hamilton, D. G.; Davies, J . E.; Prodi, L.; Sanders, J . K. M.
Chem. Eur. J . 1998, 4, 608.
(35) Kamila, S.; Mukherjee, C.; Mondal, S. S.; De, A. Tetrahedron
2003, 59, 1339.
J O049420N
J . Org. Chem, Vol. 69, No. 19, 2004 6237