formation. Rotaxanes with functional groups in the axle centre
have been used to control molecular motion14 and thus are of
great potential use in the design of molecular machinery. In
particular, the conversion of phenols to phenolates inside a
wheel capable of hydrogen bonding may greatly affect the
mobility of the axle inside the wheel. Studies in this respect are
under way and will be reported in due course.
We thank Prof. F. Vögtle for valuable discussions and
support. P. G. is grateful to the Alexander-von-Humboldt
foundation for a postdoctoral fellowship, C. A. S. acknowledges
financial support from the Fonds der Chemischen Industrie
(Liebig fellowship) and the Deutsche Forschungsgemein-
schaft.
Fig. 1 MALDI mass spectrum of rotaxane 10.
In order to get an idea why the yields of rotaxanes are not
higher than this although the binding of a phenolate in the
wheel10 is rather strong (K = 2.200 ± 700 M21 for 8·3 in
DMSO+CH2Cl2 = 1+1), a Monte Carlo conformational search
among 1000 structures was performed with the Amber* force
field11 implemented in the MacroModel 7.1 program.12 It
resulted in a minimal energy conformation of 8·3 as shown in
Fig. 2. Clearly, the phenolate oxygen forms two intramolecular
hydrogen bonds with the amide protons of the axle centre piece.
This preorganises the centre piece allowing the two amide
carbonyls to interact via four hydrogen bonds with the wheel so
that both arms of 8 point to the same side of the wheel.
Attachment of the stoppers then leads to formation of a non-
intertwined axle-wheel complex rather than the rotaxane. This
complex can easily dissociate into the free components. If this
scenario holds true, the yields can likely be enhanced by
appropriate design of suitable, more rigid centre pieces.
Notes and references
1 Templated Organic Synthesis, ed. F. Diederich and P. J. Stang, Wiley-
VCH, Weinheim, 2000.
2 Molecular Catenanes, Rotaxanes and Knots, eds. J.-P. Sauvage and C.
Dietrich-Buchecker, Wiley-VCH, Weinheim, 1999.
3 C. O. Dietrich-Buchecker and J.-P. Sauvage, Chem. Rev., 1987, 87, 795;
J.-P. Sauvage, Acc. Chem. Res., 1990, 23, 319.
4 S. A. Nepogodiev and J. F. Stoddart, Chem. Rev., 1998, 98, 1959; F. M.
Raymo and J. F. Stoddart, Chem. Rev., 1999, 99, 1043.
5 A. G. Kolchinski, D. H. Busch and N. W. Alcock, J. Chem. Soc., Chem.
Commun., 1995, 1289; P. R. Ashton, A. N. Collins, M. C. T. Fyfe, S.
Menzer, J. F. Stoddart and D. J. Williams, Angew. Chem., 1997, 109,
760; P. R. Ashton, A. N. Collins, M. C. T. Fyfe, S. Menzer, J. F. Stoddart
and D. J. Williams, Angew. Chem., Int. Ed., 1997, 36, 735; F. G. Gatti,
D. A. Leigh, S. A. Nepogodiev, A. M. Z. Slawin, S. J. Teat and J. K. Y.
Wong, J. Am. Chem. Soc., 2001, 123, 5983.
One of the remarkable properties of these rotaxanes is the
centre piece equipped with a functionality which was expected
to permit ‘post-threading’ modifications after the preparation of
the rotaxane. Rotaxanes 10 and 12 both bear phenolic hydroxyl
groups which could be modified and equipped with additional
substituents. At least, a small reagent is expected to be able to
proceed to the core of the rotaxane axle and e.g. alkylate the
phenol oxygen atom. However, no methylation with CH3I took
place at the centre piece irrespective of the base used. This result
not only indicates that the wheel efficiently shields the centre
piece against chemical modifications,13 it also adds another
piece of evidence in favor of the rotaxane structure with the axle
centre piece deeply buried inside the wheel.
In conclusion, a novel template effect has been designed
permitting the synthesis of rotaxanes functionalised at the centre
piece. The positions mediating the template effect and the sites
for stopper attachment have been separated from each other, so
that steric problems due to the shielding of the wheel do not play
a role any more. Further research on centre piece design should
significantly improve the yields of rotaxanes and makes our
approach a candidate for an efficient synthetic route to rotaxane
6 R. Jäger and F. Vögtle, Angew. Chem., 1997, 109, 966; R. Jäger and F.
Vögtle, Angew. Chem., Int. Ed. Engl., 1997, 36, 931; D. A. Leigh, K.
Moody, J. P. Smart, K. J. Watson and A. M. Z. Slawin, Angew. Chem.,
1996, 108, 326; D. A. Leigh, K. Moody, J. P. Smart, K. J. Watson and
A. M. Z. Slawin, Angew. Chem., Int. Ed., 1996, 35, 306.
7 G. M. Hübner, J. Gläser, C. Seel and F. Vögtle, Angew. Chem., 1999,
111, 395; G. M. Hübner, J. Gläser, C. Seel and F. Vögtle, Angew. Chem.,
Int. Ed., 1999, 38, 383; C. Seel and F. Vögtle, Chem. Eur. J., 2000, 6,
21; X.-y. Li, J. Illigen, M. Nieger, S. Michel and C. A. Schalley, Chem.
Eur. J., submitted.
8 C. A. Schalley, G. Silva, C. F. Nising and P. Linnartz, Helv. Chim.. Acta,
2002, 85, 1587.
9 R. Schwesinger, C. Hasenfratz, H. Schlemper, L. Walz, E.-M. Peters, K.
Peters and H. G. von Schnering, Angew. Chem., 1993, 105, 1420; R.
Schwesinger, C. Hasenfratz, H. Schlemper, L. Walz, E.-M. Peters, K.
Peters and H. G. von Schnering, Angew. Chem., Int. Ed., 1993, 32,
1361.
10 C. Seel, A. H. Parham, O. Safarowsky, G. M. Hübner and F. Vögtle, J.
Org. Chem., 1999, 64, 7236.
11 S. J. Weiner, P. A. Kollman, D. A. Case, U. C. Singh, G. Alagona, S.
Profeta and P. Weiner, J. Am. Chem. Soc., 1984, 106, 765; R.
Schwesinger, C. Hasenfratz, H. Schlemper, L. Walz, E.-M. Peters, K.
Peters, H. G. von Schnering, S. J. Weiner, P. A. Kollman, N. T. Nguyen
and D. A. Case, J. Comput. Chem., 1987, 7, 230; R. Schwesinger, C.
Hasenfratz, H. Schlemper, L. Walz, E.-M. Peters, K. Peters, H. G. von
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12 Schrödinger, Inc. 1500 SW First Avenue, Suite 1180, Portland, OR
97201, USA; F. Mohamadi, N. G. Richards, W. C. Guida, R. Liskamp,
C. Caulfield, G. Chang, T. Hendrickson and W. C. Still, J. Comput.
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13 A. H. Parham, B. Windisch and F. Vögtle, Eur. J. Org. Chem., 1999,
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14 A. R. Pease, J. O. Jeppesen, J. F. Stoddart, Y. Luo, C. P. Collier and J.
Heath, Acc. Chem. Res., 2001, 34, 433; C. A. Schalley, K. Beizai and F.
Vögtle, Acc. Chem. Res., 2001, 34, 465; J.-P. Collin, C. Dietrich-
Buchecker, P. Gaviña, M. C. Jimenez-Molero and J.-P. Sauvage, Acc.
Chem. Res., 2001, 34, 477; also, see the other contributions to this
Special Issue on molecular motors.
Fig. 2 Lowest energy conformation of the 8·3 complex out of 1000
structures minimised in a Monte Carlo conformational search. Side view
(left) and top view (right); the wheel is shown as dotted surface, the centre
piece by space filling representation.
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