Helical twist sense bias in oligo(phenylene ethynylene)s induced by an optically active flexible tether

Article abstract of DOI:10.1021/ol9912074

(equation presented) A series of tethered phenylene ethynylene oligomers, which undergo a solvent-dependent conformational transition from a random coil to a helix, has been synthesized. The use of trimethylsilyl ether protecting groups on the (+)-tartaric acid-derived tether results in the formation of helices with a large twist sense bias. In contrast, an isopropylidene ketal protecting group or no protecting group is not only ineffective at helical discrimination but may even inhibit helix formation.

Full text of DOI:10.1021/ol9912074

ORGANIC
LETTERS
2000
Vol. 2, No. 2
135-138
Helical Twist Sense Bias in
Oligo(phenylene ethynylene)s Induced
by an Optically Active Flexible Tether
Mary S. Gin and Jeffrey S. Moore*
Departments of Chemistry and Materials Science & Engineering, 600 South Mathews
AVenue, The UniVersity of Illinois at Urbana-Champaign, Urbana, Illinois 61801
moore@scs.uiuc.edu
Received November 1, 1999
ABSTRACT
A series of tethered phenylene ethynylene oligomers, which undergo a solvent-dependent conformational transition from a random coil to a
helix, has been synthesized. The use of trimethylsilyl ether protecting groups on the (+)-tartaric acid-derived tether results in the formation
of helices with a large twist sense bias. In contrast, an isopropylidene ketal protecting group or no protecting group is not only ineffective
at helical discrimination but may even inhibit helix formation.
The design of oligomers and polymers with well-defined
secondary structures is an active area of research, aimed at
creating synthetic systems that can mimic biological poly-
mers in their ability to derive function from structure.1
Perhaps the most common secondary structural motif identi-
fied in these synthetic systems is the helix, a structure that
can exist in either a right- or left-handed twist sense.2 Several
strategies have been used to bias the twist sense of helical
conformations of chain molecules, including the use of chiral
monomers,3 additives,4 and initiators.5
Previous work in our group has demonstrated the ability
of phenylene ethynylene oligomers (3, eq 1) to undergo a
solvent-dependent conformational transition from a random
(3) (a) Yashima, E.; Maeda, Y.; Okamoto, Y. J. Am. Chem. Soc. 1998,
120, 8895. (b) Kirshenbaum, K.; Barron, A. E.; Goldsmith, R. A.; Armand,
P.; Bradley, E. K.; Truong, K. T. V.; Dill, K. A.; Cohen, F. E.; Zuckermann,
R. N. Proc. Natl. Acad. Sci. U.S.A. 1998, 95, 4303. (c) Schlitzer, D. S.;
Novak, B. M. J. Am. Chem. Soc. 1998, 120, 2196. (d) Takata, T.; Furusho,
Y.; Murakawa, K.; Endo, T.; Matsuoka, H.; Hirasa, T.; Matsuo, J.; Sisido,
M. J. Am. Chem. Soc. 1998, 120, 4530. (e) Green, M. M.; Peterson, N. C.;
Sato, T.; Teramoto, A.; Cook, R.; Lifson, S. Science 1995, 268, 1860.
(4) (a) See ref 3a and Yashima, E.; Maeda, K.; Okamoto, Y Nature 1999,
399, 449. (b) Akagi, K.; Piao, G.; Kaneko, S.; Sakamaki, K.; Shirakawa,
H.; Kyotani, M. Science 1998, 282, 1683.
(1) (a) Kirshenbaum, K.; Zuckermann, R. N.; Dill, K. A. Curr. Opin.
Struct. Biol. 1999, 9, 530. (b) Gellman, S. H. Acc. Chem. Res. 1998, 31,
173. (c) Holmes, D. L.; Smith, E. M.; Nowick, J. S. J. Am. Chem. Soc.
1997, 119, 7665. (d) Seebach, D.; Matthews, J. L. Chem. Commun. 1997,
2015. (e) Lokey, R. S.; Iverson, B. L. Nature 1995, 375, 303. (f) Smith, A.
B.; Guzman, M. C.; Sprengler, P. A.; Keenan, T. P.; Holcomb, R. C.; Wood,
J. L.; Carroll, P. J.; Hirshmann, R. J. Am. Chem. Soc. 1994, 116, 9947.
(2) (a) Bassani, D. M.; Lehn, J.-M.; Baum, G.; Fenske, D. Angew. Chem.,
Int. Ed. Engl. 1997, 36, 1845. (b) Hamuro, Y.; Geib, S. J.; Hamilton, A. D.
J. Am. Chem. Soc. 1997, 119, 10587. (c) Blake, A. J.; Cooke, P. A.; Doyle,
K. J.; Gair, S.; Simpkins, N. S. Tetrahedron Lett. 1998, 39, 9093. (d)
Williams, D. J.; Colquhoun, H. M.; O′Mahoney, C. A. J. Chem. Soc., Chem.
Commun. 1994, 1643.
(5) (a) Ito, Y.; Miyaki, T.; Hatano, S.; Shima, R.; Ohara, T.; Suginome,
M. J. Am. Chem. Soc. 1998, 120, 11880. (b) Wittung, P.; Eriksson, M.;
Lyng, R.; Nielsen, P. E.; Norden, B. J. Am. Chem. Soc. 1995, 117, 10167.
10.1021/ol9912074 CCC: $19.00 © 2000 American Chemical Society
Published on Web 12/23/1999

Herein is reported the preparation of a tartrate-derived
flexible tether that favors the formation of one helical twist
sense over the other, an effect that is highly dependent on
the nature of the tether functionality.
Three tethers, all derived from (+)-diethyl L-tartrate were
prepared for this study: one with a hydrophobic isopropyl-
idene ketal protecting group, one with trimethylsilyl ether
protecting groups, and one with no protecting groups on the
hydroxyl functionality (Scheme 1). The preparation of the
tethers commenced with the conversion of diethyl tartrate
to 410 via protection of the interior hydroxyl groups (acetone,
BF3‚OEt2) and subsequent reduction of the diester function-
ality (LiAlH4). Esterification of the resultant primary hy-
droxyl groups with 3-iodo-4-methylbenzoic acid and DCC
afforded the tethered aryl iodide 5 in 84% yield. Subsequent
Pd-catalyzed coupling with 2 equiv of hexamer 77 then
afforded 9 in modest yield. The trimethylsilyl ether-func-
tionalized tethered aryl iodide 6 was prepared from 5 (CF3-
CO2H, H2O; TMSCl, Et3N, 4-DMAP, 86%) and then coupled
to 7 in an analogous fashion to give 10 in 72% yield.
Following coupling, the trimethylsilyl ethers could be
removed to give diol 11 (Bu4NF, AcOH, 85%). Dodecamer
87 was also coupled with 6 to give 12 in modest yield.11
(1)
structure in chloroform to a helical structure in acetonitrile.6
In addition, we have demonstrated that a strong bias can be
imparted on the helical twist sense of these oligomers by
incorporating an optically active binaphthyl moiety in the
backbone (1, eq 1).7 Weaker twist sense discrimination has
been effected through the use of chiral side chains (2)8 and
by binding chiral guests in the helical cavity (3‚pinene).9
UV spectra of oligomers 9-11 in both chloroform and
acetonitrile are shown in Figure 1a. As expected, all three
Scheme 1
136
Org. Lett., Vol. 2, No. 2, 2000

signal, calling into question whether 11 even adopts a helical
conformation. When dissolved in chloroform, all three
compounds displayed very weak CD signals as anticipated
for oligomers in random conformations.12 A slight negative
signal, similar to that of diol 11 in acetonitrile, was obtained,
presumably due to the asymmetry of the tether proximal to
the interior chromophores. It should be noted that for all the
oligomers the intensities of the CD signals were linearly
dependent on concentration over a 10-fold range, thus ruling
out contributions due to aggregation.
The CD signal of tethered dodecamer 12 in acetonitrile
was more intense than that of tethered hexamer 10. Com-
parison of the CD spectra of 10 and 12 in acetonitrile to the
signals of the binaphthyl tethered oligomers (S)-1 (n ) 6,
12, eq 1) reveals that the intensities are nearly identical for
oligomers of the same length (Figure 2). It is possible that
Figure 1. (a) UV spectra of 9-11 in chloroform and acetonitrile.
(b) CD spectra of 9-11 in acetonitrile.
compounds exist in a random conformation in chloroform,
as evidenced by the comparable intensities of the absorption
bands at 313 and 295 nm. In acetonitrile the intensities of
the 313 nm bands relative to the 295 nm bands are
diminished, indicating that the oligomers reside in a helical
conformation.6 This evidence of helix formation is notewor-
thy, as the untethered hexamers are too short to form helices.
Thus, the tether is clearly enabling interaction of the two
oligomers.
With evidence of helix formation in hand, we obtained
the CD spectra to determine whether any bias in the helical
twist sense could be observed (Figure 1b). Indeed, the CD
signal of bis-trimethylsilyl ether 10 in acetonitrile was very
large, having a bisignate shape typical of what we have
previously observed for these helical oligomers.7-9 Isopro-
pylidene 9, however, had a very weak bisignate signal, a
surprising result considering the similar, hydrophobic nature
of both the isopropylidene ketal in 9 and the trimethylsilyl
ethers in 10. Furthermore, diol 11 had a weak, nonbisignate
Figure 2. CD spectra of (S)-1 (n ) 6, 12), 10, and 12 in
acetonitrile.13
the similar intensities indicate a coincidentally identical, but
incomplete, excess of one helical twist sense over the other.
A more likely explanation is that complete twist sense
selectivity has been achieved with these two dissimilar
tethers.
The use of a flexible chain to tether two oligomers
necessitates the consideration of alternative conformations
to the simple single helix (15, Scheme 2). Some possible
Scheme 2
(6) (a) Prince, R. B.; Saven, J. G.; Wolynes, P. G.; Moore, J. S. J. Am.
Chem. Soc. 1999, 121, 3114. (b) Nelson, J. C.; Saven, J. G.; Moore, J. S.;
Wolynes, P. G. Science 1997, 277, 1793.
(7) Gin, M. S.; Yokozawa, T.; Prince, R. B.; Moore, J. S. J. Am. Chem.
Soc. 1999, 121, 2643.
(8) Prince, R. B.; Brunsveld, L.; Meijer, E. W.; Moore, J. S. Angew.
Chem., Int. Ed. In press.
(9) Prince R. B.; Barnes, S. A.; Moore, J. S. Submitted for publication.
(10) Batsanov, A. S.; Begley, M. J.; Fletcher, R. J.; Murphy, J. A.;
Sherburn, M. S. J. Chem. Soc., Perkin Trans. 1 1995, 1281.
(11) Oligomers 9-12 were characterized by 1H NMR, HPLC, and
MALDI MS and were determined to be pure within our limits of detection.
Org. Lett., Vol. 2, No. 2, 2000
137

interactions of the tethered oligomers include no interaction
(13), aromatic stacking into a parallel strand (14), and
threading of two helices into a double helix (16). The
similarity of the CD signals of 10 and 12 to those of 1, which
is constrained to a single helix conformation, implies that
10 and 12 also reside in a single helix conformation. By the
same token, the absence of a bisignate shape in the CD
spectrum of 11 raises the possibility that it resides in one of
the alternative conformations.
We turned to molecular modeling in an attempt to gain
insight into the structures of 10 and 11, as well as the manner
in which the silyl ethers influence the helical conformation
(Figure 3).14 The minimum energy structure identified for
17, an analogue of 10 in which the ester side chains were
omitted, was one in which the trimethylsilyl groups were
placed in the hydrophobic interior of the helix. Such an
intramolecular templating event could conceivably give rise
to the large signals observed. In contrast, the lowest energy
structure found for the diol analogue 18 was not helical.
Rather, the oligomers appear to have stacked into a parallel
strand structure analogous to that of 14 (Scheme 2). It is
plausible that this stacking interaction leads to the significant
hypchromicity of the UV spectrum of acetonitrile solutions
of 11 (Figure 1a). More work is needed to verify these
conclusions; however, the modeling results do point to
significant differences in the conformations preferred by
oligomers 10 and 11, consistent with experimental observa-
tions.
On the basis of the preceding discussion, at least two
possibilities exist for the conformation of 9 in acetonitrile.
The weak bisignate CD signal of 9 in acetonitrile could be
a result of a nearly unbiased single helix conformation.
Alternatively, a small portion could reside in a biased, single
helix conformation, while the majority exists in unbiased
parallel strand conformations.
Figure 3. Minimized structure of an analogue of 10 in which the
ester side chains were omitted.14
but the isopropylidene-protected or unprotected diol is unable
to bias the conformation. Studies are currently underway to
determine which structures are actually present in these
systems.
In conclusion, we report the ability of an optically active
tartrate-derived tether to impart a large bias on the helical
twist sense of tethered oligomers in acetonitrile. The sensitiv-
ity of this system to substitution on the tether is remarkable,
as the bis-trimethylsilyl protected diol is extremely effective,
Acknowledgment. This research was funded by the
National Science Foundation (Grant DMR 98-08433).
(12) CD spectra in chloroform are not shown.
(13) The spectra of (R)-1 have been multiplied by (-1) for a more direct
comparison with the spectra of 10 and 12. It has been demonstrated that
the use of (S)-binaphthol in the synthesis of (S)-1 (n ) 6) affords CD spectra
identical and opposite to those of (R)-1 (n ) 6, see ref 7).
(14) Monte Carlo searches were performed using Macromodel 5.5 and
the OPLS* GB/SA force field.
Supporting Information Available: Detailed descrip-
tions of experimental procedures. This material is available
free of charge via the Internet at http://pubs.acs.org.
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