A novel synthesis of chiral rotaxanes via covalent bond formation

Article abstract of DOI:10.1039/b314744d

Chiral rotaxanes composed of the asymmetric crownophane incorporating two hydroxy groups as a rotor moiety and the asymmetric axis were effectively synthesized via covalent bond formation, i.e. tandem Claisen rearrangement, esterification, and aminolysis.

Full text of DOI:10.1039/b314744d

A novel synthesis of chiral rotaxanes via covalent bond formation†
Naohiro Kameta,a Kazuhisa Hiratani*a and Yoshinobu Nagawab
a Department of Applied Chemistry, Faculty of Engineering, Utsunomiya University, 7-1-2 Youtou,
Utsunomiya 321-8585, Japan. E-mail: hiratani@cc.utsunomiya-u.ac.jp
b Nanoarchitectonics Research Center, National Institute of Advanced Industrial Science and Technology,
Tsukuba Central 4, 1-1-1 Higashi, Tsukuba, Ibaraki 305-8562, Japan
Received 14th November 2003, Accepted 7th January 2004
First published as an Advance Article on the web 28th January 2004
Chiral rotaxanes composed of the asymmetric crownophane
incorporating two hydroxy groups as a rotor moiety and the
asymmetric axis were effectively synthesized via covalent bond
formation, i.e. tandem Claisen rearrangement, esterification,
and aminolysis.
Scheme 1 shows the synthesis of the asymmetric crownophane as
a rotor moiety. Macrocyclic polyether compound 2 was obtained by
the reaction between the aromatic compound 1, containing the
isobutenyl group synthesized through a three-step process, and
pentaethylene glycol ditosylate in the presence of base under high
dilution conditions (yield 52%). We have already found that
various macrocyclic isobutenyl bis(aryl ether) derivatives are easily
converted into compounds having two phenolic hydroxy groups via
tandem Claisen rearrangement.6 In the thermal reaction of the
macrocyclic compound 2 carried out in decalin at 160 °C for 3 h,
however, the obtained product was a macrocyclic compound 3
having only one hydroxy group (yield 71%). A second thermal
reaction at 195 °C for 6 h without solvent was performed under
vacuum conditions, and crownophane 4 having two hydroxy
groups was obtained in good isolated yield (81%). The crowno-
phane 4 is an asymmetrical structure having both benzene and
naphthalene rings. The resulting two hydroxy groups in the rotor
molecule are available for the introduction of the axis into the rotor
as detailed below.
Much attention has been paid to supramolecular systems such as
rotaxanes and catenanes from a view point of the construction of
molecular machines.1 In particular, it should be noted that
mechanically bonded molecules like rotaxanes, catenanes, and
pretzel-shaped molecules consisting of the asymmetric rotor and
the asymmetric axis can have a chirality even if both the rotor and
the axis are achiral themselves (Fig. 1). Topologically knotted
molecules also have a chirality based on the left- and right-helical
structures. Several synthetic methods for the preparation of those
chiral supramolecular systems have been reported so far. For
example, Sauvage and co-workers successfully synthesized chiral
rotaxanes, catenanes, and knots by using the metal (CuI and FeII)
template technique.2 Vögtle and co-workers developed the method
utilizing the hydrogen bond formation between the rotor and the
axis molecules, and synthesized cycloenantiomeric rotaxanes as
well as topologically chiral catenanes and pretzelanes.3 Surpris-
ingly, those corresponding racemic compounds could be separated
into each enantiomer by high performance liquid chromatography
(HPLC) equipped with a chiral column although the highly
conformational flexibility of those topological molecules leads
hardly to discriminate between the enantiomers in general.
Recently, we proposed a new synthetic strategy to make achiral
rotaxanes including the process of covalent bond formation.4 This
method through short and simple step processes gave the achiral
rotaxanes in good yield compared to the method via covalent bond
formation pioneered by Schill and Zollenkopf.5 In this work, we
tried to establish a novel synthetic methodology of chiral rotaxanes
via covalent bond formation, i.e. tandem Claisen rearrangement,
esterification, and aminolysis. Furthermore, the enantiomeric
separation of those racemates was investigated by HPLC equipped
with a chiral column and circular dichloism (CD) spectrophoto-
metry.
Scheme 2 indicates the synthetic route of rotaxane racemates via
covalent bond formation. Monoesterification of the crownophane 4
Scheme 1 Synthesis of the asymmetric rotor.
Fig. 1 Chiral rotaxane composed of the asymmetric rotor and the
asymmetric axis.
† Electronic supplementary information (ESI) available: synthesis of
rotaxanes 9 and 10, and 1H NMR, IR and ESI-MS spectral data for
crownophane 4, monoesters 6, 12, diester 11, and rotaxanes 8, 9, 10. See
http://www.rsc.org/suppdata/cc/b3/b314744d/
Scheme 2 Synthesis of rotaxane racemate via monoesterification and
aminolysis.
466
C h e m . C o m m u n . , 2 0 0 4 , 4 6 6 – 4 6 7
T h i s j o u r n a l i s © T h e R o y a l S o c i e t y o f C h e m i s t r y 2 0 0 4

with an acid chloride 5 (1.0 equiv.) having a bulky group as a
stopper was performed in THF at room temperature (yield 35%).
The obtained monoesters 6 were used in the next reaction without
isomeric separation. Aminolysis of the monoesters 6 with an amine
compound 7 having a different bulky group was carried out in a
small amount of DMF at room temperature, and the asymmetric
axis was threaded into the rotor. The rotaxane racemate 8 was
synthesized in good yield (46%) by a new strategy including the
process of covalent bond formation. Rotaxane racemates 9 and 10,
as shown in Fig. 2, were synthesized via diesterification and
aminolysis (the synthetic scheme is shown in the ESI†). That is,
intramolecular diesterification of the crownophane 4 with adipoyl
chloride in a similar way as previously reported follwed by the two
aminolysis with different amines gave rotaxane racemates 9 and 10.
By these methods descrived above, we can introduce an axis having
a variety of structures into our rotaxane system.
The enantiomeric separation of the synthesized racemates was
investigated using HPLC equipped with a Chiralcel OC as a chiral
column.7 Fig. 3 shows a typical chromatogram of the enantiomeric
separation of rotaxane 8. Two peaks on the chromatogram indicate
a clear separation with a = 1.46. CD spectra of each eluted fraction
were measured in CHCl3 (Fig. 4). Two circular dichrograms show
a completely symmetric shape having the opposite Cotton effects in
the aromatic region of each other. On the other hand, racemic
compounds of rotaxane 9 and 10 could not be separated by using the
same equipment and conditions. These results suggest that the
structure (end group and chain length) of the axis might be an
important factor affecting the separation of the chiral rotaxanes.
In conclusion, a novel synthetic method of chiral rotaxanes
composed of the asymmetric rotor and the asymmetric axis via
Fig. 4 CD (upper) and absorption (lower) spectrum of rotaxane 8 in
CHCl3.
covalent bond formation has been developed. The corresponding
racemate was completely separated into each enantiomer by HPLC
equipped with a chiral column.
K. H. would like to thank the Ministy of Education, Culture,
Sports, Science and Technology (MEXT) for being partly sup-
ported by a Grant-in-Aid for Scientific Reserch (No. 14540526).
Notes and references
1 D. B. Amabilino and J. F. Stoddart, Chem. Rev., 1995, 95, 2725; V.
Balzani, A. Credi, F. M. Raymo and J. F. Stoddart, Angew. Chem., Int.
Ed., 2000, 39, 3348; A. M. Brouwer, C. Frochot, F. G. Gatti, D. A. Leigh,
L. Mottier, F. Paolucci, S. Roffia and G. W. H. Wurpel, Science, 2001,
291, 2124; L. Raehm, J.-M. Kern and J.-P. Sauvage, Chem. Eur. J., 1999,
5, 3310.
2 D. K. Mitchell and J.-P. Sauvage, Angew. Chem., Int. Ed. Engl., 1988, 27,
930; C. O. Dietrich-Buchecker and J.-P. Sauvage, Angew. Chem., Int. Ed.
Engl., 1989, 28, 189; C. O. Dietrich-Buchecker, J. Guilhem, C. Pascard
and J.-P. Sauvage, Angew. Chem., Int. Ed. Engl., 1990, 29, 1154; Y.
Kaida, Y. Okamoto, J.-C. Chambron, D. K. Mitchell and J.-P. Sauvage,
Tetrahedron Lett., 1993, 34, 1019; J.-F. Nierengarten, C. O. Dietrich-
Buchecker and J.-P. Sauvage, J. Am. Chem. Soc., 1994, 116, 375; J.-C.
Chambron and J.-P. Sauvage, J. Am. Chem. Soc., 1997, 119, 9558; J.-C.
Chambron, C. Dietrich-Buchecker, G. Rapenne and J.-P. Sauvage,
Chirality, 1998, 10, 125; G. Rapenne, C. Dietrich-Buchecker and J.-P.
Sauvage, J. Am. Chem. Soc., 1999, 121, 994; J.-C. Chambron, J.-P.
Sauvage, K. Mislow, A. D. Cian and J. Fischer, Chem. Eur. J., 2001, 7,
4085.
Fig. 2 Synthesized rotaxane racemates 8, 9, and 10.
3 C. Yamamoto, Y. Okamoto, R. Jager and F. Vögtle, J. Am. Chem. Soc.,
1997, 119, 10 547; R. Schmieder, G. Hubner, C. Seel and F. Vögtle,
Angew. Chem., Int. Ed., 1999, 38, 3528; A. Mohry, F. Vögle, M. Nieger
and H. Hupfer, Chirality, 2000, 12, 76; C. Reuter, A. Mohry, A. Sobanski
and F. Vögtle, Chem. Eur. J., 2000, 6, 1674.
4 K. Hiratani, J. Suga, Y. Nagawa, H. Houjou, H. Tokuhisa, M. Numata
and K. Watanabe, Tetrahedron Lett., 2002, 43, 5747.
5 G. Schill and H. Zollenkopf, Liebigs Ann. Chem., 1969, 53, 721.
6 K. Hiratani, H. Uzawa, K. Kasuga and H. Kambayashi, Tetrahedron
Lett., 1997, 38, 8993; K. Hiratani, H. Uzawa, K. Kasuga and M. Goto, J.
Am. Chem. Soc., 1997, 119, 12 677; H. Uzawa, K. Hiratani, N. Minoura
and T. Takahashi, Chem. Lett., 1998, 307.
Fig. 3 Chromatogram for the enantiomeric separation of rotaxane 8.
Column: Chiralcel OC (0.46 cm i.d. 3 25 cm); mobile phase: hexane:EtOH
= 40:60; flow rate = 0.7 ml min21; detection (UV): 260 nm.
7 Equipment: column, Chiralcel OC (Daicel Chemical Industries) (cellu-
lose trisphenylcarbamate); detector and pump, Liquid chromatograph
PLC-5D (EYELA).
C h e m . C o m m u n . , 2 0 0 4 , 4 6 6 – 4 6 7
467