Constitutionally asymmetric and chiral [2]pseudorotaxanes

Article abstract of DOI:10.1021/ja970018i

The self-assembly and characterization of a range of chiral pseudorotaxanes has been explored using chiroptical methods. The syntheses of (i) constitutionally asymmetric acyclic hydroquinone-containing polyethers and (ii) optically active hydroquinone-containing acyclic polyethers, bearing pairs of methyl or isobutyl groups related to each other in a C₂-symmetric manner within the polyether backbone, are described. The combination of (i) the tetracationic cyclophane cyclobis(paraquat-p-phenylene) tetrakis(hexafluorophosphate), possessing a π-electron deficient cavity, and (ii) the linear noncentrosymmetric acyclic polyethers produces [2]pseudorotaxanes that have been characterized by ¹H NMR, UV/vis and circular dichroism (CD) spectroscopies in solution and by X-ray crystallography in the solid state. The introduction of constitutional asymmetry or chirality gives rise to a number of different geometries for the [2]pseudorotaxanes in both the solution and solid states. In particular, CD-spectroscopic measurements on the optically active [2]pseudorotaxanes have shown that-depending on the positions of the C₂ symmetrically related chiral centers in the polyether chains with respect to the hydroquinone rings - the chirality present in the π-electron rich threadlike guest can induce chirality that is associated with the supramolecular structure as a whole, resulting in a chiral charge-transfer transition involving not only the π-donors in the chiral guests but also the π-acceptors in the achiral host.

Full text of DOI:10.1021/ja970018i

920
J. Am. Chem. Soc. 1998, 120, 920-931
Constitutionally Asymmetric and Chiral [2]Pseudorotaxanes1
Masumi Asakawa,† Peter R. Ashton,† Wayne Hayes,† Henk M. Janssen,‡ E. W. Meijer,*,‡
Stephan Menzer,§ Dario Pasini,† J. Fraser Stoddart ,*,†, Andrew J. P. White,§ and
David J. Williams*,§
Contribution from The School of Chemistry, The UniVersity of Birmingham, Edgbaston, Birmingham B15
2TT, U.K., The Laboratory of Organic Chemistry, EindhoVen UniVersity of Technology, 5600 MB
EindhoVen, The Netherlands, and The Department of Chemistry, Imperial College, London SW7 2AY, U.K.
ReceiVed January 2, 1997. ReVised Manuscript ReceiVed NoVember 29, 1997
Abstract: The self-assembly and characterization of a range of chiral pseudorotaxanes has been explored using
chiroptical methods. The syntheses of (i) constitutionally asymmetric acyclic hydroquinone-containing
polyethers and (ii) optically active hydroquinone-containing acyclic polyethers, bearing pairs of methyl or
isobutyl groups related to each other in a C2-symmetric manner within the polyether backbone, are described.
The combination of (i) the tetracationic cyclophane cyclobis(paraquat-p-phenylene) tetrakis(hexafluorophos-
phate), possessing a π-electron deficient cavity, and (ii) the linear noncentrosymmetric acyclic polyethers
1
produces [2]pseudorotaxanes that have been characterized by H NMR, UV/vis and circular dichroism (CD)
spectroscopies in solution and by X-ray crystallography in the solid state. The introduction of constitutional
asymmetry or chirality gives rise to a number of different geometries for the [2]pseudorotaxanes in both the
solution and solid states. In particular, CD-spectroscopic measurements on the optically active [2]-
pseudorotaxanes have shown thatsdepending on the positions of the C2 symmetrically related chiral centers
in the polyether chains with respect to the hydroquinone ringssthe chirality present in the π-electron rich
threadlike guest can induce chirality that is associated with the supramolecular structure as a whole, resulting
in a chiral charge-transfer transition involving not only the π-donors in the chiral guests but also the π-acceptors
in the achiral host.
Introduction
ing hydrogen bonding,5 metal-ligand complexes,6 and π-π
interactions.7 Investigations of the complexation of planar
π-electron-deficient substrates [e.g., the paraquat dication] by
the crown ether8 bis(p-phenylene)-34-crown-10 (BPP34C10)
have led to the self-assembly of interwoven and mechanically
interlocked linear systems,9 such as pseudorotaxanes and
rotaxanes, respectively.
Nature employs numerous kinds of self-assembly processes2
to construct large ordered molecular assemblies and supramo-
lecular arrays. Employing the concept of self-assembly to
construct functioning synthetic systems,3 previously unattainable
using conventional chemical techniques, the nature of specific
recognition motifs is being investigated in both the solid and
solution states.4 Studies involving diVergently and conVergently
arranged recognition motifs have led to the discovery of linear
one-, two-, and three-dimensional solid-state arrays, incorporat-
Several [n]pseudorotaxanes have been reported which incor-
porate cyclobis(paraquat-p-phenylene) 14+ (Figure 1) and linear
π-electron-rich components.10 They self-assemble in solution
via a thermodynamically driven threading process to form
remarkably stable species that are stabilized by (i) π-π
interactions11 between the π-electron-deficient bipyridinium
units of the cyclophane host and the π-electron-rich aromatic
† University of Birmingham.
‡ Eindhoven University of Technology.
§ Imperial College.
Present address: Department of Chemistry and Biochemistry, Univer-
sity of California at Los Angeles, 405 Hilgard Avenue, Los Angeles, CA
90095. Phone: (310) 206-7078. FAX: (310) 206-1843. E-mail:
stoddart@chem.ucla.edu.
(1) Molecular Meccano. 21. Part 20: Ashton, P. R.; Boyd, S. E.;
Claessens, G. C.; Gillard, R. E.; Menzer, S.; Stoddart, J. F.; Tolley, M. S.;
White, A. J. P.; Williams, D. J. Chem. Eur. J. 1997, 3, 788-798.
(2) For articles on chemical and biological self-assembly processes,
see: (a) Jeffrey, G. A.; Saenger, W. Hydrogen Bonding in Biological
Structures Springer-Verlag: Berlin, 1991. (b) Lindsey, J. S. New J. Chem.
1991, 15, 153-180. (c) Philp, D.; Stoddart, J. F. Angew. Chem., Int. Ed.
Engl. 1996, 35, 1155-1196.
(3) For articles describing the potential use of self-assembly for the
construction of nanoscale devices, see: (a) Bissell, R. A.; De Silva, A. P.;
Gunaratne, H. Q. M.; Lynch, P. L. M.; Maguire, G. E. M.; Sandanayake,
K. R. A. S. Chem. Soc. ReV. 1992, 21, 187-195. (b) Go´mez-Lo´pez, M.;
Preece, J. A.; Stoddart, J. F. Nanotechnology 1996, 7, 183-192.
(4) For approaches to the design of supramolecular systems, see, for
example: (a) Lehn, J.-M. Angew. Chem., Int. Ed. Engl. 1988, 27, 89-112.
(b) Zaworotko, M. J. Chem. Soc. ReV. 1994, 23, 283-288. (c) Amabilino,
D. B.; Stoddart, J. F.; Williams, D. J. Chem. Mater. 1994, 6, 1159-1167.
(d) Desiraju, G. R. Angew. Chem., Int. Ed. Engl. 1995, 34, 2311-2327.
(5) For some recent examples of supramolecular systems assembled using
hydrogen bonding, see: (a) Ghadiri, M. R.; Kobayashi, K.; Granja, J. R.;
Chadha, R. K.; McRee, D. E. Angew. Chem., Int. Ed. Engl. 1995, 34, 93-
95. (b) Boucher, EÄ .; Simard, M.; Wuest, J. D. J. Org. Chem. 1995, 60,
1408-1412. (c) Glink, P. T.; Schiavo, C.; Stoddart, J. F. Chem. Commun.
1996, 1483-1490. (d) Zimmerman, S. C.; Zeng, F. W.; Reichert, D. E. C.;
Kolotuchin, S. V. Science 1996, 271, 1095-1098.
(6) For some recent examples of supramolecular systems assembled using
metal-ligand interactions, see: (a) Goodgame, D. M. L.; Menzer, S.; Smith,
A. M.; Williams, D. J. Angew. Chem., Int. Ed. Engl. 1995, 34, 574-575.
(b) Beissel, T.; Powers, R. E.; Raymond, K. N. Angew. Chem., Int. Ed.
Engl. 1996, 35, 1084-1086.
(7) For supramolecular systems assembled using π-π interactions, see:
(a) Ashton, P. R.; Ballardini, R.; Balzani, V.; Belohradsky, M.; Gandolfi,
M. T.; Philp, D.; Prodi, L.; Raymo, F. M.; Reddington, M. V.; Spencer,
N.; Stoddart, J. F.; Venturi, M.; Williams, D. J. J. Am. Chem. Soc. 1996,
118, 4931-4951 and references cited therein.
(8) Allwood, B. L.; Spencer, N.; Shahriari-Zavareh, H.; Stoddart, J. F.;
Williams, D. J. J. Chem. Soc., Chem. Commun. 1987, 1064-1066.
(9) Amabilino, D. B.; Stoddart, J. F. Chem. ReV. 1995, 95, 2725-2828.
S0002-7863(97)00018-8 CCC: $15.00 © 1998 American Chemical Society
Published on Web 01/27/1998

Constitutionally Asymmetric and Chiral [2]Pseudorotaxanes
J. Am. Chem. Soc., Vol. 120, No. 5, 1998 921
Scheme 1
centers within the polyether backbone of the threads. The
introduction of chirality into the linear thread component could,
in principle, lead to the formation of helical polymeric
superstructures.17 Additionally, the dissymmetry associated with
these chiral threads can be used to study the geometry of the
[2]pseudorotaxanes in solution by employing circular dichroism
(CD) spectroscopy.
Figure 1. Schematic representation of the solid-state structure of the
1:1 complexes formed between the tetracationic cyclophane 1‚4PF6 and
the π-electron-rich dicarboxylic acid components 2 and 3.
Here we describe (i) the syntheses of the thread components
featuring a range of terminal functionalities and chiralities, (ii)
the characterization of a series of [2]pseudorotaxanes incorpo-
rating constitutionally asymmetric and chiral thread components
residues of the linear guest, (ii) [CH‚‚‚O] hydrogen bonds12
between the R-bipyridinium protons on the tetracationic cyclo-
phane and polyether oxygen atoms in the linear π-electron-rich
guest, and (iii) [CH‚‚‚π] interactions13 between the aromatic
ring protons of the included π-electron-rich aromatic residues
and the π-face of the p-xylyl spacer units of the tetracationic
cyclophane. In addition, complex infinite supramolecular arrays
are evident in the solid state.
1
and 1‚4PF6 in solution by UV/vis, H NMR, and CD spectro-
scopic studies, and (iii) their characterization in the solid state
by X-ray crystallography.
Results and Discussion
Recently, we reported14 the self-assembly (Figure 1) of
pseudorotaxanes comprised of the tetracationic cyclophane 14+
and the π-electron-rich polyethers 2 and 3, possessing carboxylic
acid termini. In these superstructures, the “threads” are inserted
centrosymmetrically into the π-electron-deficient cavity of the
cyclophane, and in the solid state, they self-assemble further in
a supramolecular fashion as a result of hydrogen-bonding
interactions between the carboxylic acid termini15 to produce
pseudopolyrotaxanes.16 To verify the generality and the viability
of this noncovalent synthesis of pseudopolyrotaxanes, we have
introduced (i) constitutional asymmetry into the π-electron-rich
thread components by replacing one of the carboxylic acid
functionalities and (ii) chirality in the form of C2-related chiral
Synthesis of the Molecular Components. Compound 5 was
prepared (Scheme 1) from the methyl ester 4.18
The chiral π-electron-rich aromatic dicarboxylic acid com-
ponents were prepared by the routes shown in Schemes 2-4.
The (S)-compounds (Scheme 2) have been reported previously.19
The (R)-enantiomers were synthesized employing analogous
procedures. Using the shown synthetic route, the optical purities
of the starting compounds, leucine (S)-6, lactide (RR)-7, and
ethyl lactate (S)-9, could be preserved through to the final com-
pounds.19d
The diols (SS)-19 and (RR)-19 were prepared (Scheme 3) by
O-alkylation of 16 with the tosylates (S)-15 and (R)-15,
respectively. Coupling of the bistosylates 17 and 1820 with the
THP-protected diols 13 and 14 and subsequent deprotection of
the THP protecting groups afforded the C2-symmetric chiral
polyethers 20-23. O-Alkylation of diols 19-23 with tert-butyl
bromoacetate yielded the tert-butyl diesters 24-28 in 31-45%
(10) For reports of pseudorotaxanes incorporating π-electron-rich linear
threads and cyclobis(paraquat-p-phenylene), see: (a) Ashton, P. R.; Philp,
D.; Spencer, N.; Stoddart, J. F.; Williams, D. J. J. Chem. Soc., Chem.
Commun. 1994, 181-184. (b) Castro, R.; Berardi, M. J.; Co´rdova, E.; Ochoa
de Olza, M.; Kaifer, A. E.; Evanseck, J. D. J. Am. Chem. Soc. 1996, 118,
10257-10268. For reports of pseudorotaxanes incorporating π-electron-
deficient bipyridinium guests and BPP34C10 as the host, see: (a) Ashton,
P. R.; Philp, D.; Reddington, M. V.; Slawin, A. M. Z.; Spencer, N.; Stoddart,
J. F.; Williams, D. J. J. Chem. Soc., Chem. Commun. 1991, 1680-1683.
(b) Shen, Y. X.; Engen, P. T.; Berg, M. A. G.; Merola, J. S.; Gibson, H.
W. Macromolecules 1992, 25, 2786-2788.
(11) π-π interactions have been described in the following recent pub-
lications: (a) Diederich, F.; Philp, D.; Seiler, P. J. Chem. Soc., Chem.
Commun. 1994, 205-208. (b) Bilyk, A.; Harding, M. M.; Turner, P.;
Hambley, T. W. J. Chem. Soc., Dalton Trans. 1994, 2783-2790. (c) Otsuki,
J.; Oya, T.; Lee, S.-H.; Araki, K. J. Chem. Soc., Chem. Commun. 1995,
2193-2194.
(16) Pseudopolyrotaxanes have been defined as polymeric structures that
are comprised of a linear macromolecule which incorporates numerous
macrocycles along its length, whereas polypseudorotaxanes are defined as
a covalently linked array of pseudorotaxanes, where the macrocycles are
not confined on the polymer backbone, but rather are located on strands
emanating from the polymer backbone. See: (a) Amabilino, D. B.; Stoddart,
J. F. Pure Appl. Chem. 1993, 65, 2351-2359. (b) Marsella, M. J.; Carroll,
P. J.; Swager, T. M. J. Am. Chem. Soc. 1994, 117, 9832-9841.
(17) For articles describing an induction of chirality into polymeric
systems, see: (a) Zarges, W.; Hall, J.; Lehn, J.-M.; Bolm, C. HelV. Chim.
Acta 1991, 74, 1843-1852. (b) Gulik-Krzywicki, T.; Fouquey, C.; Lehn,
J.-M. Proc. Natl. Acad. Sci. U.S.A. 1993, 90, 163-167.
(12) For reviews describing experimental evidence and theoretical aspects
of [CH‚‚‚O] hydrogen bonding, see: (a) Desiraju, G. R. Acc. Chem. Res.
1991, 24, 290-296. (b) Steiner, T. Chem. Commun. 1997, 727-734.
(13) For a review describing [CH‚‚‚π] interactions, see: Nishio, M.;
Umezawa, Y.; Hirota, M.; Takeuchi, Y. Tetrahedron 1995, 32, 8665-8701.
(14) Asakawa, M.; Ashton, P. R.; Brown, G. R.; Hayes, W.; Menzer,
S.; Stoddart, J. F.; White, A. J. P.; Williams, D. J. AdV. Mater. 1996, 8,
37-41.
(15) For articles describing the assembly of hydrogen-bonded linear
systems featuring the carboxylic acid-carboxylic acid recognition motif,
see: (a) Hoshino, H.; Jin, J. I.; Lenz, R. W. J. Appl. Polym. Sci. 1984, 29,
547-554. (b) Zhao, Y.-L.; Fowler, F. W.; Lauher, J. W. J. Am. Chem.
Soc. 1990, 112, 6627-6634. (c) Lillya, C. P.; Baker, R. J.; Hu¨tte, S.; Winter,
H. H.; Lin, Y.-G.; Shi, J.; Dickenson, L. C.; Chien, J. C. W. Macromolecules
1992, 25, 2076-2080.
(18) Asakawa, M.; Ashton, P. R.; Menzer, S.; Raymo, F. M.; Stoddart,
J. F.; White, A. J. P.; Williams, D. J. Chem. Eur. J. 1996, 2, 877-893.
(19) (a) Perkins, M. V.; Kitching W.; Ko¨nig, W. A.; Drew, R. A. I. J.
Chem. Soc., Perkin Trans. 1 1990, 2501-2506. (b) Cowie, J. M. G.; Hunter,
H. W. Makromol. Chem. 1990, 191, 1393-1402. (c) Mori, K. Tetrahedron
1976, 32, 1101-1105. (d) Koppenhoefer, B.; Trettin, U.; Figura, R.; Lin,
B. Tetrahedron Lett. 1989, 38, 5109-5110. In a test, (R)-1,2-propanediol
was stirred overnight under basic conditions (KOH/dioxane) and checked
on a permethylated â-cyclodextrin GC column. Comparison with (S)-1,2-
propanediol showed that no racemization had taken place.
(20) Anelli, P. L.; Ashton, P. R.; Ballardini, R.; Balzani, V.; Delgado,
M.; Gandolfi, M. T.; Goodnow, T. T.; Kaifer, A. E.; Philp, D.; Pietrasz-
kiewicz, M.; Prodi, L.; Reddington, M. V.; Slawin, A. M. Z.; Spencer, N.;
Stoddart, J. F.; Vicent, C.; Williams, D. J. J. Am. Chem. Soc. 1992, 114,
193-218.

922 J. Am. Chem. Soc., Vol. 120, No. 5, 1998
Asakawa et al.
Scheme 2
Scheme 4
dimethoxy ethers (SS)-35 and (RR)-35. Similarly, the diol (SS)-
19 was converted to the ethers (SS)-36 and (SS)-37 by reaction
with EtI and the tosylate22 of 2-methoxyethanol, respectively.
1H NMR Spectroscopy. Mixing equimolar proportions of
1‚4PF6 and separately each of the π-electron-rich threads in
MeCN produced bright red solutions of the respective 1:1
complexes. The formation of these colors indicates that the
threads enter the cavity of the tetracationic cyclophane and
experience stabilizing π-π interactions. The chemical shift
changes observed (Table 1) for protons in the 1:1 complexes
2/1‚4PF6 and 3/1‚4PF6, with respect to free 1‚4PF6 and the
polyethers 2 or 3 as reference compounds, are consistent with
those found20 for similar 1:1 complexes employing 1‚4PF6 as
the host.
Scheme 3
However, the two 1:1 complexes 2/1‚4PF6 and 3/1‚4PF6 do
not exhibit the same spectroscopic behavior. There are sig-
nificant differences between the resonances of the methylene
protons adjacent to the carboxylic acid termini in the polyether
chains of these 1:1 complexes in comparison with those for the
same protons in the free polyethers 2 and 3 in CD3CN solution.
In 3/1‚4PF6, the methylene protons resonate with a significant
upfield shift (∆δ ) -0.17 ppm), implying, on a time-averaged
basis, that these protons are oriented directly over the bipyri-
dinium unit of the tetracationic cyclophane and are subsequently
shielded, whereas in 2/1‚4PF6, the methylene proton resonances
undergo a downfield shift (∆δ ) +0.12 ppm), indicating that
the termini of the polyether chains must be lying in the same
plane as the bipyridinium protons of the tetracationic cyclo-
phane.
Similar behavior was observed during the 1H NMR spectro-
scopic studies of the methyl-substituted chiral pseudorotaxanes
29/1‚4PF6, 30/1‚4PF6, 31/1‚4PF6,23 and the isobutyl-substituted
analogues 32/1‚4PF6 and 33/1‚4PF6. However, a comparison
of the spectroscopic behavior of the two 1:1 complexes 30/
(21) Hahn, B.; Percec, V. Macromolecules 1987, 20, 2961-2968.
(22) Ouchi, M.; Inoue, Y.; Liu, Y.; Nagamune, S.; Nakamura, S.; Wada,
K.; Hakushi, T. Bull. Chem. Soc. Jpn. 1990, 63, 1260-1262.
(23) The hydroquinone ring proton resonances of the included π-electron-
rich components in the 1:1 complexes 2-3/1‚4PF6 and 29-31/1‚4PF6 could
not be assigned at room temperature in CD3CN solutions, as a result of
appreciable broadening attributable to fast complexation-decomplexation
yields. Hydrolysis of these diesters afforded the dicarboxylic
acids 29-33 in quantitative yields. Remarkably, the specific
optical rotations of these acids were not reliable for determining
the enantiomeric excesses, because the [R]D values are very
sensitive to changes in temperature, concentration, and solvent.
Compound (SS)-34 was prepared (Scheme 4) by coupling of
hydroquinone 16 with the tosylate21 of (S)-2-methylbutanol. The
diols (SS)-19 and (RR)-19 were transformed with MeI into the
1
processes on the H NMR time scale. In the 1:1 complexes 2/1‚4PF6 and
3/1‚4PF6, the hydroquinone ring proton resonances were located at δ 3.74
and 3.75 by saturation transfer experiments in CD3COCD3 at 243 and 233
K, respectively, in comparison with δ 6.69 and 6.71 for free 2 and 3. The
upfield shifts for the hydroquinone ring proton resonances (∆δ -2.95 and
-2.96 ppm, respectively) are consistent with findings of variable temperature
1H NMR spectroscopic investigations of similar complexes and mechanically
interlocked systems; see ref 20.

Constitutionally Asymmetric and Chiral [2]Pseudorotaxanes
J. Am. Chem. Soc., Vol. 120, No. 5, 1998 923
1
Table 1. Chemical Shift Data [δ Values (∆δ Values)]a Obtained from the 300 MHz H NMR Spectra Recorded on 1:1 Complexes Formed
between the π-Electron-Rich Aromatic Polyethers and the Tetracationic Cyclophane 1‚4PF6and Their Components in CD3CN Solution at 298 K
charged component
â-CH C6H4
polyether component
ArH CH2CO
compound or
1:1 complex
R-CH
8.86
CH2N+
5.74
b
1‚4PF6
2
8.16
7.52
6.85
NDc
4.08
4.29
(0.12)
4.06
3.89
2/1‚4PF6
8.91
(0.05)
7.90
(-0.26)
7.74
(0.22)
5.70
(-0.04)
3
6.84
NDc
3/1‚4PF6
8.91
(0.05)
7.90
(-0.26)
7.73
(0.21)
5.72
(-0.02)
(-0.17)
4.57
5
6.84
5/1‚4PF6
8.88
(0.02)
8.02
(-0.14)
7.67
(0.15)
5.73
(-0.01)
5.28 (-1.56)
5.21 (-1.63)
6.84
4.48
(-0.09)
4.11
4.28
(0.17)
4.11
4.18
(0.07)
4.15
29
29/1‚4PF6
8.91
(0.05)
8.02
(-0.14)
7.65
(0.13)
5.73
(-0.01)
NDc
30
6.85
NDc
30/1‚4PF6
8.89
(0.03)
8.01
(-0.15)
7.66
(0.14)
5.72
(-0.02)
31
6.85
NDc
31/1‚4PF6
8.88
(0.02)
7.97
(-0.19)
7.69
(0.17)
5.72
(-0.02)
4.06
(-0.04)
32
d
32/1‚4PF6
8.86 (0.00)
8.92 (0.06)
8.16 (0.00)
7.86 (-0.30)
7.52 (0.00)
7.80 (0.28)
5.74 (0.00)
5.72 (-0.02)
6.85
(0.00)
6.84
6.84
(0.00)
6.84
4.15 (0.00)
4.30 (0.15)
4.13
4.13 (0.00)
4.10 (-0.03)
33
d
33/1‚4PF6
8.86 (0.00)
8.89 (0.03)
8.15 (-0.01)
7.86 (-0.30)
7.53 (0.01)
7.79 (0.27)
5.74 (0.00)
5.72 (-0.02)
34
34/1‚4PF6
8.87
(0.01)
8.14
(-0.02)
7.58
(0.06)
5.77
(0.03)
6.41
(-0.43)
a The ∆δ values indicated in parentheses under the respective δ values relate to the changes in chemical shift exhibited by the probe protons
upon complex formation. A negative value indicates the movement of the resonance to high field. b See ref 20. c For these complexes, the hydroquinone
ring proton resonances at 298 K in CD3CN are broad under the baseline. See refs 23. d For these complexes, exchange between the 1:1 complex
1
and free components is slow on the H NMR time scale, thus resulting in the observation of “free” and complexed cyclophane proton resonances
in these spectra at 298 K. See the text for details.
1‚4PF6 and 32/1‚4PF6 revealed important differences. In the
1H NMR spectrum (Figure 2a) of 30/1‚4PF6, there were no
pseudorotaxanes between 1‚4PF6 and 2, 3, 5, and 29-34 were
obtained (Table 2) by UV/vis spectroscopic titrations26 in MeCN
at 25 °C. Using the charge-transfer (CT) band as the probe,
stability constants (Ka) of 1900 and 1800 M-1 for 2/1‚4PF6 and
3/1‚4PF6, respectively, were obtained. They correspond to free
energies of complexation (∆G°) for 2/1‚4PF6 and 3/1‚4PF6 of
-4.5 and -4.4 kcal mol-1, respectivelysvalues that are of the
same magnitudes as those already obtained20 for similar 1:1
complexes. On the other hand, for the methyl or isobutyl-
substituted diacids 29-33, the Ka and ∆G° values for [2]-
pseudorotaxane formation are clearly reduced to values in the
1
significant differences compared with the H NMR spectrum
of 1:1 complex 2/1‚4PF6. Time-averaged signalssas a result
of fast exchange between complexed and uncomplexed
1
statesswere observed. In contrast, in the H NMR spectrum
(Figure 2b) of 32/1‚4PF6, sets of resonances could be identified
for complexed 1‚4PF6 and the complexed isobutyl-substituted
chiral thread 32, along with another set for free 1‚4PF6 and free
32.24 The same spectroscopic behavior was observed for 33/
1‚4PF6, thus confirming that the introduction of bulky isobutyl
groups into the polyether chains slows the rate of the threading-
unthreading process involving 1‚4PF6, presumably because of
steric and conformational effects in solution.25
range 170-900 M-1, i.e., from -3.0 to -4.0 kcal mol-1
,
respectively, indicating that the introduction of bulky groups
within the polyether regions of the threads lowers the relative
thermodynamic stabilities of the resulting pseudorotaxanes,
probably because of steric and conformational effects. Surpris-
ingly, the stability constant (Ka ) 1800 M-1) and free energy
(∆G° ) -4.4 kcal mol-1) of the [2]pseudorotaxane formation
for 5/1‚4PF6 are of the same magnitude as those found for
2/1‚4PF6 and 3/1‚4PF6, indicating a possible stabilizing interac-
tion between the carboxylic acid functionality and the acidic
hydrogen atoms of the tetracationic cyclophane, which in
5/1‚4PF6, are in close proximity.27 The association constant
(24 M-1) for 34/1‚4PF6 is similar to that (17 M-1) reported in
the literature20 for the 1:1 complex formed between 1,4-
dimethoxybenzene and 1‚4PF6.
Stability Constants of [2]Pseudorotaxanes. The stability
constants and derived free energies for the formation of [2]-
(24) In 32/1‚4PF6 and 33/1‚4PF6, the ratios between complexed 1‚4PF6
and free 1‚4PF6 in CD3CN at 298 K were 35:65 and 62:38, respectively, as
measured from integrations of the resonances assigned to the â-bipyridinium
1
and p-xylyl ring protons on the tetracationic cyclophane 1‚4PF6 in the H
NMR spectrum. The stability constants (Ka) of the complexes could be
obtained from the ratios of complexed and uncomplexed components.
(25) This situation is reminiscent of a synthetic approach to self-
assembling [n]rotaxanes we refer to as “slippage”. The approach relies upon
the complementarity between π-electron-deficient bipyridinium-based
dumbbell-shaped components and π-electron-rich hydroquinone-based or
dioxynaphthalene-based macrocyclic polyether components. By careful
selection of the size of the stoppers covalently attached at both ends of the
dumbbell-shaped compounds, together with the size of the macrocyclic
polyethers, the association of the complementary components to afford
rotaxanes can be achieved under the influence of thermal energy. See:
Asakawa, M.; Ashton, P. R.; Balzani, V.; Belohradsky, M.; Gandolfi, M.
T.; Kocian, O.; Prodi, L.; Raymo, F. M.; Stoddart, J. F.; Venturi, M. J.
Am. Chem. Soc. 1996, 118, 12012-12020.
X-ray Crystallography. Crystals of the monocarboxylic acid
5 contain two crystallographically independent molecules A and
B in the asymmetric unit, both having virtually identical
(26) Connors, K. A. Binding Constants; Wiley: New York, 1987.
(27) Benniston, A. C.; Harriman, A. Synlett 1993, 3, 223-226.

924 J. Am. Chem. Soc., Vol. 120, No. 5, 1998
Asakawa et al.
Figure 3. Supramolecular packing of the hydrogen-bonded macro-
cycles A and B in the solid-state structure of 5.
1
Figure 2. Partial H NMR spectra of the pseudorotaxane complexes
(a) 30/1‚4PF6, and (b) 32/1‚4PF6 in CD3CN at 298 K. The concentra-
tions of all components, 1‚4PF6, 30, and 32, was 5 mM.
Table 2. Stability Constants for [2]Pseudorotaxanes
b
[2]pseudorotaxane
λ
max (nm)a Ka (M-1
)
-∆G° (kcal mol-1
)
2/1‚4PF6
3/1‚4PF6
5/1‚4PF6
29/1‚4PF6
30/1‚4PF6
31/1‚4PF6
32/1‚4PF6
33/1‚4PF6
34/1‚4PF6
467
467
453
460
461
464
463
467
476
1900
1800
1800
320
4.5
4.4
4.4
3.4
3.4
4.0
3.0
4.0
1.9
310
Figure 4. X-ray crystal structure of the [2]pseudorotaxane 5/1‚4PF6.
860
170c
900c
24
hydroquinone ring of a B type pair via a T-type aromatic-
aromatic edge-to-face interaction ([H‚‚‚π] distance 2.69 Å,
[CH‚‚‚π] angle 145°, [H‚‚‚π] vector inclined by 76° to the ring
plane). The inter- and intramolecular [H..π] vectors subtend
an angle of 177°. Adjacent lattice-translated stacks are oriented
such that one of the phenoxymethylene CH groups of B type
pairs of molecules (that are not involved in intradimer [CH‚‚‚π]
interactions) are directed into the opposite face of the hydro-
quinone rings of A type molecules to form a [CH‚‚‚π]
interaction [B to A type] complementary to that within the A
to B type dimer pairs ([H‚‚‚π] distance 2.76 Å, [CH‚‚‚π] angle
132°, [H‚‚‚π] vector inclined by 85° to the ring plane). Here,
the inter- and intramolecular [H‚‚‚π] vectors subtend an angle
of 171°.
In 5/1‚4PF6, the thread is inserted (Figure 4) through the
center of the tetracation. In addition to π-π stacking interac-
tions, the complex is stabilized by a pair of [CH‚‚‚O] hydrogen
bonds between (a) one of the â-CH bipyridinium hydrogen
atoms and the carboxyl carbonyl oxygen atom ([C‚‚‚O] distance
3.20 Å, [H‚‚‚O] distance 2.30 Å, [CH‚‚‚O] angle 156°) and (b)
one of the R-bipyridinium hydrogen atoms and the third oxygen
atom of the polyether chain ([C‚‚‚O] distance 3.38 Å, [H‚‚‚O]
distance 2.47 Å, [OH‚‚‚O] angle 159°). There is also a [CH‚‚‚π]
a Tetrakis(hexafluorophosphate) salt in MeCN solution at 298 K.
b Calculated from values of Ka. c Calculated from the ratios of integra-
1
tions of H NMR spectra of 1:1 complexes. See ref 24.
conformations. Both A and B type molecules form head-to-
tail hydrogen-bonded macrocycles with their Ci-related coun-
terparts (Figure 3), the carboxylic hydrogen atom in one
molecule being hydrogen-bonded to the second oxygen atom
of the polyether chain of the other and vice versa.28 They are
supplemented by a further pair of weaker [CH‚‚‚π] interactions
between one of the phenoxymethylene hydrogen atoms in one
molecule and the hydroquinone ring in the other and vice
versa.29 There is a marginal overlap between the two coplanar
hydroquinone rings.30 The A and B type dimer pairs form
zigzag stacks, with one of the hydroquinone hydrogen atoms
of A type pairs being directed orthogonally into the face of the
(28) The geometries of these hydrogen-bonding interactions in type A
and type B dimer pairs are, respectively, [O‚‚‚O] distance 2.76 Å, [OH‚‚‚O]
distance 1.94 Å, and [OH‚‚‚O] angle 152° and [O‚‚‚O] distance 2.77 Å,
[OH‚‚‚O] distance 2.00 Å, and [OH‚‚‚O] angle 144°.
(29) The geometries of T-type aromatic-aromatic edge-to-face interac-
tion within type A and type B dimer pairs are, respectively, [H‚‚‚π] distance
2.81 Å, [CH‚‚‚π] angle 143°, and [H‚‚‚π] vector inclined by 85° to the
ring plane and [H‚‚‚π] distance 2.79 Å, [CH‚‚‚π] angle 145°, [H‚‚‚π] vector
inclined by 85° to the ring plane.
(30) The distances between the aromatic rings within the type A and
type B dimer pairs are, respectively, mean interplanar separations 3.56 Å
and centroid-centroid distance 4.93 and 4.92 Å.

Constitutionally Asymmetric and Chiral [2]Pseudorotaxanes
J. Am. Chem. Soc., Vol. 120, No. 5, 1998 925
Figure 6. X-ray crystal structure of the [2]pseudorotaxane (SS)-37/
1‚4PF6.
a possible explanation for the folded geometry observed for the
thread. There are no intercomplex π-π stacking or hydrogen-
bonding interactions.
Figure 5. X-ray crystal structure of the [2]pseudorotaxane (SS)-30/
1‚4PF6.
In (SS)-37/1‚4PF6, the polyether is threaded through the cavity
of the cyclophane in an approximately centrosymmetric fashion,
the exception being the methyl groups on the two chiral centers
(see Figure 6). The absolute configurations of these two
asymmetric carbon atoms have been unambiguously determined
as being both (S) by crystallographic means. The hydroquinone
ring of the polyether thread is sandwiched between the two
π-electron-deficient bipyridinium units, with the distances
separating the hydroquinone ring centroid and the centroid of
the C-C bond linking the pyridinium rings being 3.55 and 3.57
Å. The -OC6H4O- axis of the hydroquinone ring is inclined
to the mean plane of the tetracationic cyclophane (as defined
by its four methylene carbon atoms) by ca. 52°, with the
phenoxymethylene groups adopting an anti geometry. These
data contrast with the [2]pseudorotaxane (SS)-30/1‚4PF6, where
the angle is much steeper (76°). Consequently, the [H‚‚‚π]
interactions observed here between diametrically opposite
hydroquinone hydrogen atoms and the p-xylyl rings of the
cyclophane are of more usual lengths at distances of ca. 2.8 Å.
The π-π stacking interactions are supplemented by two pairs
of bifurcated [CH‚‚‚O] hydrogen bonds between the second and
the third oxygen atoms of each polyether chain and one of the
adjacent R-CH bipyridinium hydrogen atoms.32 An inspection
of the packing of the molecules reveals the presence of pairs of
relatively weak [CH‚‚‚π] interactions between one of the
methylene carbon atoms of the polyether chain of one [2]-
pseudorotaxane and a p-xylyl ring of the tetracation of a lattice-
translated [2]pseudorotaxane counterpart, forming loosely linked
chains that extend in the crystallographic c-direction.
interaction31 between one of the hydroquinone hydrogen atoms
and one of the p-xylyl rings of the tetracation ([H‚‚‚π] distance
2.70 Å, [CH‚‚‚π] angle 166°).
The packing of the 1:1 complexes shows the threads to be
linked head-to-tail via a strong [H‚‚‚O] hydrogen bond between
the hydrogen atom of the carboxylic unit of one of the threads
and the third oxygen atom of the polyether chain of the next
chain ([O‚‚‚O] distance 2.77 Å, [H‚‚‚O] distance 1.87 Å,
[OH‚‚‚O] angle 176°), thereby forming a hydrogen-bonded
pseudopolyrotaxane structure.
In the structure of the [2]pseudorotaxane (SS)-30/1‚4PF6, the
chiral thread (SS)-30 is inserted (Figure 5) through the center
of the tetracation. An unusual feature of note is the adoption
of a syn geometry by the two phenoxymethylene carbon atoms,
requiring the O-C6H4-O axis of the hydroquinone ring to be
more steeply inclined (76°) to the mean plane of the cyclophane;
cf. that observed, for example, in the previous structure (48°),
and in related systems.20 This tilt weakens the [H‚‚‚π] interac-
tions between diametrically opposite hydroquinone ring hydro-
gen atoms and the p-xylyl rings of the tetracation. These
distances are increased to ca. 3 Å; cf. values of ca. 2.8 Å in
other hydroquinone-containing related systems.20 On account
of high thermal vibration parameters, the positions of the
carboxyl hydrogen atoms could not be located, and so any
hydrogen-bonding interactions involving these groups can only
be inferred from contact distances between the oxygen centers.
These contacts reveal the possibility of [CH‚‚‚O] interactions
between the â-CH hydrogen atoms of the bipyridinium units
and one of the oxygen atoms of each of the carboxylate groups.
Indeed, the orientation of the carboxylate group directly over
the â-bipyridinium hydrogen atoms precludes, on steric grounds,
a normal “in line” geometry for the carboxylate hydrogen atoms.
However, one of the oxygen atoms of each carboxylate (that
with the longer C-O bond) lies within intramolecular hydrogen-
bonding distance of the second oxygen atom (relative to the
hydroquinone ring) of the polyether chains, thereby providing
The [2]pseudorotaxane solid-state structures of 2/1‚4PF6 and
3/1‚4PF6 reveal that all “programmed information” in the
systemscharge-transfer interactions, hydrogen bonding, and
T-type interactionssis used to construct the crystal lattice. As
evidenced by the crystal data on 5/1‚4PF6, (SS)-30/1‚4PF6, and
(SS)-37/1‚4PF6, the introduction of constitutional asymmetry or
chirality in the π-electron-rich threads (i) results in a diversity
of [2]pseudorotaxane structural features, i.e., the thread and
1‚4PF6 can be assembled in various ways, and (ii) produces a
variety of different packing motifs in the solid state. However,
(31) The [CH‚‚‚π] interaction is accompanied by a noticeable offset of
the hydroquinone ring toward the interacting p-xylyl ring relative to the
other. The hydroquinone ring, which is ca. 3.5 Å from the two bipyridinium
units, is tilted by 48° with respect to the mean plane of the tetracationic
cyclophane and shifted by ca. 0.25 Å toward one of the p-xylyl rings.
(32) The [C‚‚‚O] and [H‚‚‚O] distances and [CH‚‚‚O] angles for the four
hydrogen bonds are 3.18 and 2.34 Å, 146°; 3.32 and 2.53 Å, 139°; 3.21
and 2.40 Å, 142°; and 3.24 and 2.43 Å, 141°, respectively.

926 J. Am. Chem. Soc., Vol. 120, No. 5, 1998
Asakawa et al.
effects were -3.9 × 10-4 and 3.7 × 10-4 for the (SS)- and the
(RR)-threads, respectively.35 These results show that the chiral
centers of the threads must be close to the hydroquinone
ringscloser than the second oxygen atom of the polyether chain
relative to this ringsto give a complex with a “chiral geometry”
and thus to influence the electronic transition in the CT band.
To confirm these initial observations, additional CD measure-
ments were performed on the threads 19 and 20. In line with
the previous results, (RR)-20 did not and (RR)-19 and (SS)-19
did show induced CD effects in the CT band (see Figure 7B).
However, the nature of the observed (Figure 7B) CD effects
for the complexes (SS)-19/1‚4PF6 and (RR)-19/1‚4PF6 was
different from that observed (Figure 7A) for the pseudorotaxanes
(SS)-29/1‚4PF6 and (RR)-29/1‚4PF6.36 One explanation for
observing two maxima is an exciton coupling, implying that
two chromophoresswhich are in a chiral geometrysare in each
other’s proximity. Another explanation for the observed
phenomenon is that there are two different CT transitions in
the 19/1‚4PF6 [2]pseudorotaxane, one causing a positive and
the other a negative Cotton effect. The superposition of both
CD signals would then result in the observed CD spectrum. A
third explanation is that 19 and 1‚4PF6 self-assemble as more
than one type of 1:1 complex or as aggregates of 19 and 1‚4PF6.
These different modes of complexation would then contribute
to the observed CD effect. However, in the determination of
the association constant for the 1:1 complex of 19 and 1‚4PF6,
no indications for such diverse behavior were found. In an
additional experiment, CD effects were measured at two
concentrations of 19/1‚4PF6. For both concentrations, the same
gλ values were obtained, showing that the observed CD effect
can be attributed solely to one type of [2]pseudorotaxane formed
between 19 and 1‚4PF6.
Figure 7. (a) CD and UV spectra for pseudorotaxanes (SS)-29/1‚4PF6
(solid) and (RR)-29/1‚4PF6 (dashed) in MeCN at 24 °C. (b) CD and
UV spectra for pseudorotaxanes (SS)-19/1‚4PF6 (solid) and (RR)-19/
1‚4PF6 (dashed) in MeCN at 24 and 20 °C, respectively.
this chirality or asymmetry has not led to an asymmetric packing
in the supramolecular array; e.g., one-handed helical conforma-
tions of hydrogen-bonded chiral threads, for instance, are not
observed. Consequently, refined crystal engineering is not
readily possible with these asymmetric [2]pseudorotaxane
systems, though results14 for the symmetric analogues 2/1‚4PF6
and 3/1‚4PF6 are encouraging examples in this respect.
CD Measurements.33 Circular dichroism measurements
were performed in order to study the geometries of the
pseudorotaxanes in solution. The measurements were conducted
in the wavelength region of the CT band (400-600 nm), where
the absorbance of the pseudorotaxane can be studied separately
from the absorbance of noncomplexed material. Both CD and
UV spectra of the solutions were taken to determine the g values
of the observed CD effects.34
A series of temperature-dependent CD measurements on (SS)-
19/1‚4PF6 and (SS)-29/1‚4PF6 revealed that, over the temper-
ature range from -6 to +45 °C, the CD effects in both these
pseudorotaxanes remained of the same type, implying that the
different geometries observed for (SS)-19/1‚4PF6 and (SS)-29/
1‚4PF6 could not be interconverted by temperature changes.
These results confirm that (SS)-19/1‚4PF6 exists as one type of
[2]pseudorotaxane. The g450 value for (SS)-29/1‚4PF6 is
constant over the measured temperature domain, whereas the
g440 value of (SS)-19/1‚4PF6 decreases with increasing temper-
ature, suggesting a slight change in the geometry of this complex
as a result of heating (Figure 8).
Finally, the CD spectra of the [2]pseudorotaxanes formed
between (SS)-34-37 and 1‚4PF6 were recorded. Pseudorotax-
anes (SS)-36/1‚4PF6 and (SS)-37/1‚4PF6 show a CD effect.37
Remarkably, pseudorotaxanes (SS)-34/1‚4PF6 and (SS)-35/
1‚4PF6 do not exhibit any CD activities. In (SS)-34/1‚4PF6,
the positions of the chiral centers are the same as in the
pseudorotaxanes described previously that exhibit CD activities.
However, the second oxygen atoms in the polyether chains,
gλ ) (∆ꢀ/ꢀ)λ ) (∆A/A)λ ) ψλ/(32980Aλ)
The dicarboxylic acids 29-31 were investigated initially.
Induced chirality in the CT band could only be observed for
the enantiomers (RR)-29 and (SS)-29. The observed CD effects
are shown in Figure 7A. The g450 values of the induced CD
(35) These are low g values compared to g values of other types of
electronic transitions. For example, n-π*, π-π*, π-π* couplet, πx-πx*,
πx-πy*, and n-σ* transitions have typical g values of 30 × 10-3, 8 ×
10-3, 3 × 10-3, 2 × 10-3, and 1 × 10-3, respectively. See ref 34b, p 1014.
CD activity in charge-transfer transitions has also been observed in [2,2]-
metacyclophanes. See: Knops, P.; Windscherf, P.-M.; Vo¨gtle, F.; Roloff,
A.; Jansen, M.; Nieger, M.; Niecke, E.; Okamoto, Y. Chem. Ber. 1991,
124, 1585-1590.
(33) For books on circular dichroism, see: (a) Nakanishi, K.; Berova,
N.; Woody, R. W. Circular Dichroism, Principles and Applications; VCH
Publishers: Inc.: New York, 1994. (b) Eliel, E. L.; Wilen, S. H.
Stereochemistry of Organic Compounds; Wiley: New York, 1994. (c)
Harada, N.; Nakanishi, K. Circular Dichroic Spectroscopy, Exciton Coupling
in Organic Stereochemistry; Oxford University Press: Oxford, 1983.
(34) gλ ) (∆ꢀ/ꢀ)λ ) (∆A/A)λ ) ψλ/(32980Aλ), with gλ ) dissymmetry
factor measured at wavelength λ (in this paper mainly the values at the
maxima of the CD spectra are reported), ψλ ) measured CD effect in
millidegrees at wavelength λ, A λ ) measured absorbance at wavelength λ,
ꢀ ) specific absorbance, A ) absorbance, ∆ꢀ ) ꢀL - ꢀR ) difference in
specific absorbance between left and right circularly polarized light and
∆A ) AL - AR ) difference in absorbance between left and right circularly
polarized light.
(36) The g440 values of the effects were approximately 4 times smaller
than the g450 values observed for the 29/1‚4PF6 pseudorotaxanes (9.4 ×
10-5 and -8.3 × 10-5 for (SS)-19 and (RR)-19, respectively).
(37) For both [2]pseudorotaxanes one maximum in the CD spectrum was
observed, so a spectrum similar to that for (SS)-29/1‚4PF6 was obtained
(see Figure 8A). For (SS)-36/1‚4PF6 and (SS)-37/1‚4PF6 g values of g465
)
-2.7 × 10-4 and g460 ) -2.8 × 10-4 were measured, respectively.

Constitutionally Asymmetric and Chiral [2]Pseudorotaxanes
J. Am. Chem. Soc., Vol. 120, No. 5, 1998 927
of the π-electron rich polyether guests can be translated into a
chiral geometry that becomes associated with the whole
supramolecular structure. It is proposed that, in solution, this
chiral geometry is the result of the locking of the conformation
of the guest as a result of hydrogen bonding between the oxygen
atoms on it and the acidic R-bipyridinium protons on the
tetracationic cyclophane. Thus, in solution, a variety of [2]-
pseudorotaxanes differing in geometry are formed. Subtle
changes in the structures of the π-electron-rich guests produce
dramatic changes in the solution and solid-state structures of
the resulting [2]pseudorotaxanes.
Experimental Section
General Methods. THF was distilled from sodium before use.
Benzophenone was used as an indicator in this distillation procedure.
Pyridine was distilled from KOH and stored on dried 3 Å molecular
sieves. CH2Cl2 and TFA were both distilled from P2O5 before use.
All other solvents and materials were used as received. The tetraca-
tionic cyclophane 1‚4PF6,20 the methyl ester 4,18 and the bistosylates
17 and 1820 were prepared using previously published procedures. Thin-
layer chromatography (TLC) was performed on aluminum sheets (10
× 5 cm) coated with Merck 5735 Kieselgel 60F. Developed plates
were air-dried, scrutinized under a UV lamp, and, if necessary, then
sprayed with cerium(IV) sulfate-sulfuric acid reagent and heated to
ca. 100 °C, sprayed with an aqueous KI/I2 solution, or developed in an
iodine tank. Kieselgel 60 (0.040-0.063 mm mesh, Merck 9385) or
Merck flash silica gel 60 (particle size 0.040-0.063 mm) was used to
perform column chromatography. Melting points were determined on
an Electrothermal 9200 melting point apparatus or Bu¨chi apparatus.
Optical rotations were recorded on a JASCO DIP-370 polarimeter at a
wavelength of 589 nm (sodium D-line). CD spectra were recorded on
a JASCO J-600 spectropolarimeter. Mass spectra (MS) were obtained
from either Kratos Profile or MS80RF instruments, the latter being
equipped with a fast atom bombardment (FAB) facility (using a krypton
primary atom beam in conjunction with a 3-nitrobenzyl alcohol matrix).
FABMS were recorded in the positive-ion mode at a scan speed of 30
s per decade. Electrospray MS (ESMS) was performed on a Perkin-
Elmer Sciex API-300 LC-MS/MS. GC/MS was performed on a HP
5790 GC with an OV-1 column and a HP 5970A MSD. 1H NMR
spectra were recorded on a Bruker AC300 (300 MHz), Bruker AM400
(400 MHz), or Bruker AMX400 (400 MHz) spectrometer (using the
deuterated solvent as lock and residual solvent or tetramethylsilane as
internal reference). 13C NMR spectra were recorded on a Bruker AC300
(75 MHz), Bruker AM400 (100 MHz), or AMX 400 (100 MHz)
spectrometer using a PENDANT pulse sequence (assuming 1JCH ) 143
Hz). Infrared spectra were taken on a Perkin-Elmer 1600 series FTIR
Figure 8. (a) CD and UV spectra for the pseudorotaxane (SS)-29/
1‚4PF6 in MeCN at -6 °C (solid), 6 °C (dashed), 20 °C (dotted), 29
°C (dash-dot), and 43 °C (dash-dot-dot). The g450 -T curve is also
shown: g450 values (×10-4) are depicted. (b) CD and UV spectra for
pseudorotaxane (SS)-19/1‚4PF6 in MeCN at -6 °C (solid), 6 °C
(dashed), 15 °C (dotted), 24 °C (dash-dot), 33 °C (dash-dot-dot),
and 43 °C (short dash). The g440 -T curve is also shown: g440 values
(×10-4) are depicted.
which could form hydrogen bonds to the acidic protons on
1‚4PF6 and hence “lock” the pseudorotaxane in a chiral
geometry, are “missing”. It is difficult to explain the absence
of CD activity in the CT band of the [2]pseudorotaxane (SS)-
35/1‚4PF6. Apparently, even the subtle differences (only two
methylene groups) between (SS)-35/1‚4PF6 and (SS)-36/1‚4PF6
result in the formation of different complexes in solution.
spectrometer with wavenumbers between 4400 and 450 cm-1
. Mi-
croanalyses were performed by the University of North London
Microanalytical Service and at the Laboratory of Organic Chemistry
at Eindhoven University.
Conclusions
The introduction of constitutional asymmetry or chirality into
noncentrosymmetric π-electron-rich guests bearing carboxylic
acid termini leads to a number of geometries, both in solution
and in the solid state. In the latter, the π-electron-rich guests
are inserted into the π-electron-deficient cavity of 14+ with
conformations that are dependent on the nature and configura-
tions of the substituents present in their polyether backbones.
Often, noncovalent bonding interactions between adjacent [2]-
pseudorotaxanes bring about the formation of pseudopolyro-
taxane structures. Also in solution, distinct differences between
the [2]pseudorotaxane superstructures can be observed as
1-[2-(2-Methoxyethoxy)ethoxy]-4-(carboxymethoxy)benzene (5).
The methyl ester 418 (1.00 g, 3.5 mmol) was added to a solution of
NaOH (430 mg, 10.6 mmol) in H2O (100 mL), and the solution was
heated under reflux for 4 h. After cooling to room temperature,
acidification with dilute HCl (50 mL) gave the carboxylic acid 5 as a
white crystalline solid (710 mg, 75%): mp 84-85 °C; EIMS m/z 270
1
[M]+; H NMR (CD3CN, 300 MHz) δ 3.30 (3H, s), 3.50-3.47 (2H,
m), 3.62-3.59 (2H, m), 3.75-3.72 (2H, m), 4.06-4.03 (2H, m), 4.59
(2H, s), 6.87 (4H, s), 9.50 (1H, br s); 13C NMR (CD3CN, 75 MHz) δ
58.9, 66.2, 69.0, 70.4, 71.1, 72.6, 116.5, 116.5, 153.1, 154.7, 170.6.
Anal. Calcd for C13H18O6 (270): C, 43.81; H, 6.42. Found: C, 43.66;
H, 6.31.
4-Methyl-2(S)-[(tetrahydropyran-2-yl)oxy]pentan-1-ol [(S)-14].
Commercially available (S)-leucine [(S)-6] (ee > 97%, as measured
on a chiral Daicell CR (+) HPLC column) was transformed into (S)-
leucic acid [(S)-8] by diazotization with NaNO2 and H2SO4 in H2O.
Esterification in EtOH/PhMe containing a few drops of concentrated
HCl yielded ethyl (S)-leucate [(S)-10] (ee > 97% as determined on a
permethylated â-cyclodextrin capillary GC column; i.e., no significant
1
evidenced by H NMR and CD spectroscopies. In particular,
it was found that subtle changes in the structures of the guests
can direct the occurrence and the nature of the induced CD effect
in the CT transition of the complex, showing that different
geometries of the [2]pseudorotaxanes are possible in solution.
The [2]pseudorotaxanes which do show induced CD effects in
the CT transitions proVe that the chirality in the polyether chains

928 J. Am. Chem. Soc., Vol. 120, No. 5, 1998
Asakawa et al.
racemization had occurred during the reaction sequence). Protection
with DHP gave compound (S)-12, and subsequent reduction afforded
the protected alcohol (S)-14. All spectroscopic data of the various
compounds were in agreement with the data already reported in the
literature by Mori et al.19c
6.85 (4H, s), 4.10 (4H, m), 4.00 (2H, m), 3.85 (4H, m), 3.55 (2H, dd,
3
2
3
2J ) 9.8 Hz, J ) 3.1 Hz), 3.30 (2H, dd, J ) 9.8 Hz, J ) 8.2 Hz),
3
2.70 (2H, br s), 1.10 (6H, d, J ) 6.6 Hz); 13C NMR (CDCl3, 100
MHz) δ 152.8, 115.4, 76.8, 69.6, 67.7, 66.0, 18.4; FTIR (KBr, cm-1
)
ν ) 3483, 2970, 2907, 1513, 1454, 1371, 1328, 1279, 1232, 1135,
1043, 929, 891, 824, 751; GC/MS peak at m/z 314.05 (12.1% abundance
relative to 59.00).
2-(S)-[(Tetrahydropyran-2-yl)oxy]propan-1-ol 4-Methylbenzene-
sulfonate [(S)-15] and (R)-15. The synthesis of compound (S)-15 was
carried out starting from commercially available ethyl (S)-lactate [(S)-
9]. GC analysis with a permethylated â-cyclodextrin capillary column
In an analogous fashion, (RR)-20 was synthesized from (R)-13 and
bistosylate 17. The alcohol (RR)-20 was isolated as a white solid in
51% yield: [R]21 ) -13.4° (c ) 1.13 in MeCN). All spectroscopic
showed (S)-9 to have an ee > 99.5% ([R]24 ) -13.6° (c ) 3.25 in
D
D
data were identical with those reported for compound (SS)-20. Anal.
Calcd for C16H26O6 (314.173): C, 61.11; H, 8.34. Found: C, 61.44;
H, 8.04.
MeCN)). Reaction of (S)-9 with DHP in Et2O and a catalytic amount
of p-toluenesulfonic acid yielded (S)-11. Reduction of the ester function
yielded compound (S)-13. All spectroscopic data of the various
compounds were in agreement with the data already reported in the
literature by Perkins.19a Tosylation of (S)-13 with p-toluenesulfonyl
chloride in C5H5N afforded (S)-15 which was used in subsequent
reactions without further purification. The synthesis of compound (R)-
15 was carried out starting from (RR)-lactide (RR)-7. Transesterification
of this lactide in a refluxing mixture of EtOH, PhMe, and a few drops
of concentrated HCl and subsequent distillation afforded ethyl (R)-
lactate [(R)-9] in a 76% yield. GC analysis on a permethylated
â-cyclodextrin capillary column showed (R)-9 to have an ee > 99.9%
([R]24D ) +13.4° (c ) 3.19 in MeCN)). Ethyl (R)-lactate [(R)-9] was
converted into (R)-15 employing the same procedure as that described
for (S)-9.
1,4-Bis[2-(2-(2(S)-hydroxypropoxy)ethoxy)ethoxy]benzene [(SS)-
21] and (RR)-21. These compounds were prepared from bisotosylate
18 and alcohol (S)-13 or (R)-13, by a procedure similar to that reported
for (SS)-20 and (RR)-20. The compounds were purified by flash column
chromatography (SiO2, hexane/THF (2:3) (Rf ) 0.20)) to yield (SS)-
21 as a white solid (72%) and (RR)-21 as a clear, oily product (45%)
which slowly solidified (mp 33 °C). Spectral data (for both compounds):
1H NMR (CDCl3, 400 MHz) δ 6.80 (4H, s), 4.10 (4H, m), 3.95 (2H,
2
3
m), 3.80 (4H, m), 3.70 (8H, m), 3.50 (2H, dd, J ) 9.9 Hz, J ) 2.9
2
3
Hz), 3.25 (2H, dd, J ) 9.9 Hz, J ) 8.4 Hz), 2.80 (2H, br s), 1.10
(6H, d, J ) 6.2 Hz); 13C NMR (CDCl3, 100 MHz) δ 153.0, 115.6,
3
76.9, 70.6, 70.5, 69.8, 68.0, 66.2, 18.4; FTIR (KBr, cm-1) ν ) 3423,
2970, 2907, 1508, 1458, 1232, 1110, 935, 830. Data on (SS)-21: mp
1,4-Bis[2(S)-hydroxypropoxy]benzene [(SS)-19] and (RR)-19. A
solution of compound (S)-15 (9.4 g, 29.9 mmol) in THF (15 mL) was
added dropwise to a refluxing suspension of hydroquinone 16 (1.5 g,
13.6 mmol) and KOH (1.65 g, 29.5 mmol) in EtOH (15 mL). The
solution was maintained at reflux for 2 days. After removal of the
solvents in vacuo, a 1 M NaOH aqueous solution was added and the
mixture was extracted with CH2Cl2. The collected organic layers were
washed with a 1 M NaOH aqueous solution and dried with MgSO4.
The crude material was dissolved in MeOH, and a catalytic amount of
p-toluenesulfonic acid was added. Overnight stirring at room temper-
ature resulted in deprotection of the THP group. The reaction was
quenched by addition of NaHCO3, and the solvent was removed in
vacuo. The reaction mixture was purified by column chromatography
(SiO2, hexane/EtOAc (3:5) (Rf ) 0.25)), and crystallization from
) 32-34 °C; [R]26 ) 9.4 ° (c ) 0.87 in MeCN). Anal. Calcd for
D
C20H34O8 (402.225): C, 59.67; H, 8.52. Found: C, 59.39; H, 8.85.
Data on (RR)-21: [R]21 ) - 11.7 ° (c ) 0.84 in MeCN); GC/MS
D
peaks at m/z 401.95 and 402.92 (12.1% and 2.9% abundance relative
to 58.95).
1,4-Bis[2-(2(S)-hydroxy-4-methylpentoxy)ethoxy]benzene [(SS)-
22]. This compound was prepared from bistosylate 17 and alcohol
(S)-14 by a procedure similar to that reported for (SS)-20. The product
was purified by flash column chromatography (SiO2, hexane/EtOAc
(1:1) (Rf ) 0.27)) to yield (SS)-22 as a white solid (32%): mp 36-38
°C; [R]26D ) -3.7° (c ) 5.09 in MeCN); 1H NMR (CDCl3, 400 MHz)
δ 6.85 (4H, s), 4.05 (4H, m), 3.90 (2H, m), 3.80 (4H, m), 3.55 (2H,
2
3
2
3
dd, J ) 9.6 Hz, J ) 2.8 Hz), 3.30 (2H, dd, J ) 9.6 Hz, J ) 8.0
Hz), 2.50 (2H, br s), 1.80 (2H, m), 1.40 (2H, ddd, 2J ) 13.9 Hz, 3J )
9.0 Hz, 3J ) 5.5 Hz), 1.15 (2H, ddd, 2J ) 13.9 Hz, 3J ) 8.4 Hz, 3J )
hexane/PhMe (1:1) to give (SS)-19 as a white solid (1.0 g, 32%): mp
1
95 °C; [R]25 ) +5.8° (c ) 2.1 in MeCN); H NMR (CDCl3, 400
D
MHz) δ 6.85 (4H, s), 4.15 (2H, m), 3.9 (2H, dd, 2J ) 9.2 Hz, 3J ) 3.1
4.1 Hz), 0.93 (6H, d, J ) 6.6 Hz), 0.90 (6H, d, J ) 6.6 Hz); 13C
NMR (CDCl3, 100 MHz) δ 153.0, 115.6, 76.3, 69.9, 68.3, 68.0, 41.8,
24.4, 23.4, 22.0; FTIR (KBr, cm-1) ν ) 3442, 2955, 1510, 1455, 1367,
1286, 1231, 1128, 1064, 930, 826, 757. Anal. Calcd for C22H38O6
(398.267): C, 66.29; H, 9.62. Found: C, 66.59; H, 9.47.
3
3
2
3
Hz), 3.75 (2H, dd, J ) 9.2 Hz, J ) 7.9 Hz), 2.65 (2H, br s), 1.25
(6H, d, J ) 6.4 Hz); 13C NMR (CDCl3, 100 MHz) δ 153.0, 115.5,
3
74.0, 66.2, 18.7; FTIR (KBr, cm-1) ν ) 3328, 2976, 2917, 2868, 1514,
1459, 1383, 1290, 1245, 1111, 1053, 994, 959, 819, 788, 520. Anal.
Calcd for C12H18O4 (226.272): C, 63.70; H, 8.02. Found: C, 63.50;
H, 7.90.
1,4-Bis[2-(2-(2(S)-hydroxy-4-methylpentoxy)ethoxy)ethoxy]ben-
zene [(SS)-23]. This compound was prepared from bistosylate 18 and
alcohol (S)-14 by a procedure similar to that reported for (SS)-20. The
product was purified by flash column chromatography (SiO2, hexane/
(RR)-19 was similarly prepared from compound (R)-15 and hydro-
quinone to afford (RR)-19 as a white solid (23%): mp 96 °C; [R]23
)
D
EtOAc (2:3) (Rf ) 0.16)) to yield (SS)-23 as a clear oil (38%): [R]26
- 9.0° (c ) 1.9 in MeCN). The spectroscopic data for compound
(RR)-19 were identical with those reported for compound (SS)-19. Anal.
Calcd for C12H18O4 (226.272): C, 63.70; H, 8.02. Found: C, 63.88;
H, 8.21.
D
1
) - 2.7° (c ) 4.76 in MeCN); H NMR (CDCl3, 400 MHz) δ 6.85
(4H, s), 4.05 (4H, m), 3.90 (2H, m), 3.80 (4H, m), 3.70 (8H, m), 3.50
2
3
2
3
(2H, dd, J ) 9.9 Hz, J ) 3.0 Hz), 3.25 (2H, dd, J ) 9.9 Hz, J )
2
8.3 Hz), 2.65 (2H, br s), 1.80 (2H, m), 1.40 (2H, ddd, J ) 13.6 Hz,
1,4-Bis[2-(2(S)-hydroxypropoxy)ethoxy]benzene [(SS)-20] and
(RR)-20. 2(S)-[(Tetrahydropyran-2-yl)oxy]propan-1-ol [(S)-13] (3.3 g,
20.3 mmol, 2.3 mol equiv), the bistosylate 17 (4.4 g, 8.7 mmol), and
KOH (4.5 g, 80.4 mmol) were suspended in dry THF (50 mL). The
suspension was maintained at reflux for 60 h under an argon
atmosphere. The solvent was then removed in vacuo, H2O was added,
and the residue was extracted with CH2Cl2. The combined organic
layers were washed with H2O and concentrated in vacuo. The crude
material was dissolved in MeOH, and a catalytic amount of p-
toluenesulfonic acid was added. Stirring at room temperature for 1 h
was sufficient to deprotect the THP group. The reaction was quenched
with NaHCO3, and the solvent was then removed in vacuo, H2O was
added and the residue was extracted with CH2Cl2 to give 2.8 g of a
crude product, which was purified by flash column chromatography
(SiO2, hexane/THF (4:3) (Rf ) 0.15)), followed by crystallization from
PhMe to yield (SS)-20 as a white solid (1.35 g, 49%): mp 67-68 °C;
[R]26D ) +12.2° (c ) 0.89 in MeCN); 1H NMR (CDCl3, 400 MHz) δ
3J ) 8.8 Hz, 3J ) 5.0 Hz), 1.10 (2H, ddd, 2J ) 13.6 Hz, 3J ) 8.8 Hz,
3J ) 4.4 Hz), 0.92 (6H, d, 3J ) 6.6 Hz), 0.89 (6H, d, 3J ) 6.7 Hz); 13
C
NMR (CDCl3, 100 MHz) δ 153.0, 115.5, 76.2, 70.7, 70.5, 69.8, 68.3,
68.0, 41.8, 24.4, 23.4, 22.0; FTIR (KBr, cm-1) ν ) 3440, 2955, 1510,
1455, 1367, 1285, 1232, 1112, 1065, 950, 828. Anal. Calcd for
C26H46O8 (486.319): C, 64.16; H, 9.53. Found: C, 64.42; H, 9.69.
1,4-Bis[2(S)-(tert-butoxycarbonylmethoxy)propoxy]benzene [(SS)-
24] and (RR)-24. The diol (SS)-19 (0.31 g, 1.37 mmol) and t-BuOK
(0.34 g, 3.04 mmol, 2.2 mol equiv) were dissolved in t-BuOH (4 mL)
at 30-40 °C. After the mixture had been allowed to cool to room
temperature, tert-butyl bromoacetate (1.04 g, 5.3 mmol, 3.9 mol equiv)
was added dropwise while the solution was cooled in a water bath. A
precipitate formed immediately. The suspension was stirred overnight,
after which the reaction was quenched with an aqueous NaHCO3
solution. The solvent was removed in vacuo, and H2O was added to
the semisolid material. Subsequent extraction with CH2Cl2 and

Constitutionally Asymmetric and Chiral [2]Pseudorotaxanes
J. Am. Chem. Soc., Vol. 120, No. 5, 1998 929
3
3
concentration of the organic layers gave the crude product that was
purified by flash column chromatography (SiO2, hexane/EtOAc (85:
m), 1.25 (2H, m), 0.92 (6H, d, J ) 2.5 Hz), 0.90 (6H, d, J ) 2.6
Hz); 13C NMR (CDCl3, 100 MHz) δ 170.0, 153.0, 115.5, 81.1, 77.8,
74.9, 70.7 (2), 69.8, 68.2, 68.0, 41.0, 28.1, 24.3, 23.1, 22.4; FTIR (KBr,
cm-1) ν ) 2955, 2869, 1750, 1508, 1455, 1392, 1368, 1300, 1230,
1127, 1068, 941, 826, 751. Anal. Calcd for C38H66O12 (714.455): C,
63.82; H, 9.31. Found: C, 63.57; H, 9.30.
15) (Rf ) 0.20)) to yield (SS)-24 as a clear oil (270 mg, 45%): [R]27
D
) - 40.3° (c ) 7.96 in Me2CO); 1H NMR (CDCl3, 400 MHz) δ 6.85
2
2
(4H, s), 4.15 (2H, d, J ) 16.5 Hz), 4.10 (2H, d, J ) 16.5 Hz), 4.0
(2H, dd, 2J ) 9.2 Hz, 3J ) 5.5 Hz), 3.85 (4H, m), 1.45 (18H, s), 1.30
(6H, d, J ) 6.2 Hz); 13C NMR (CDCl3, 100 MHz) δ 169.8, 152.8,
3
1,4-Bis[2(S)-(carboxymethoxy)propoxy]benzene [(SS)-29] and
(RR)-29. The diester (SS)-24 (170 mg, 0.37 mmol) was stirred
overnight in dry CH2Cl2 (5 mL) in the presence of TFA (0.4 mL). The
solvent was removed in vacuo to afford (SS)-29 as a sticky oily product
in quantitative yield: [R]22D ) - 31.3° (c ) 4.35 in Me2CO); 1H NMR
115.2, 81.2, 74.6, 72.4, 67.4, 27.9, 17.1; FTIR (KBr, cm-1) ν ) 2977,
2932, 1748, 1508, 1456, 1368, 1228, 1127, 1045, 939, 826. Anal. Calcd
for C24H38O8 (454.56): C, 63.42; H, 8.43. Found: C, 63.68; H, 8.87.
(RR)-24 was synthesized in the same way from diol (RR)-19 and
tert-butyl bromoacetate to afford a clear oil in 46% yield: [R]27
)
2
D
(CDCl3, 400 MHz) δ 11.1 (2H, br s), 6.80 (4H, s), 4.35 (2H, d, J )
17.2 Hz), 4.20 (2H, d, 2J ) 17.2 Hz), 3.90 (6H, m), 1.25 (6H, d, 3J )
6.3 Hz); 13C NMR (CDCl3, 100 MHz) δ 174.9, 152.5, 115.3, 75.9,
72.3, 66.9, 16.7; ESMS m/z 341 [M - H]-.
+44.1° (c ) 6.97 in Me2CO). All spectroscopic data were identical
with those reported for (SS)-24. Anal. Calcd. for C24H38O8 (454.56):
C, 63.42; H, 8.43. Found: C, 63.32; H, 8.43.
1,4-Bis[2-(2(S)-(tert-butoxycarbonylmethoxy)propoxy)ethoxy]-
benzene [(SS)-25] and (RR)-25. These compounds were prepared by
procedures similar to those reported for (SS)-24 and (RR)-24. The
products were purified by flash column chromatography (SiO2, hexane/
EtOAc (5:2) (Rf ) 0.12)) to yield clear oils (46% and 36% yields for
(SS)-25 and (RR)-25, respectively). Spectral data (for both com-
(RR)-29 was prepared from (RR)-24 in a similar way. A sticky oily
product in quantitative yield was obtained: [R]21D ) +32.5° (c ) 6.80
in Me2CO). The spectroscopic data were identical with those reported
for compound (SS)-29: ESMS m/z 341 [M - H]-.
1,4-Bis[2-(2(S)-(carboxymethoxy)propoxy)ethoxy]benzene [(SS)-
30] and (RR)-30. The diester (SS)-25 (160 mg, 0.30 mmol) was stirred
in an HBr solution of dry CH2Cl2 for 1 h at 0 °C. The solvent was
removed in vacuo to yield (SS)-30 as a sticky, oily compound (130
mg, 100%). TLC and NMR spectroscopy indicated that the purity of
2
pounds): 1H NMR (CDCl3, 400 MHz) δ 6.85 (4H, s), 4.15 (2H, d, J
2
) 15.5 Hz), 4.10 (2H, d, J ) 15.5 Hz), 4.05 (4H, m), 3.80 (4H, m),
3.75 (2H, m), 3.60 (2H, dd, 2J ) 10.1 Hz, 3J ) 6.4 Hz), 3.55 (2H, dd,
3
3
2J ) 10.1 Hz, J ) 4.2 Hz),1.45 (18H, s), 1.20 (6H, d, J ) 6.7 Hz);
13C NMR (CDCl3, 100 MHz) δ 170.1, 153.1, 115.5, 81.2, 75.7, 75.2,
69.9, 68.0, 67.4, 28.0, 17.0; FTIR (KBr, cm-1) ν ) 2977, 2932, 1747,
1505, 1454, 1369, 1290, 1233, 1132, 1065, 938, 827, 751. Data on
the product was better than 95%: [R]24 ) +5.8° (c ) 3.12 MeCN/
D
1
Me2CO (2/3, v/v)); H NMR (CDCl3, 400 MHz) δ 10.7 (2H, br s),
2
2
6.85 (4H, s), 4.25 (2H, d, J ) 17.3 Hz), 4.10 (2H, d, J ) 17.3 Hz),
4.05 (4H, m), 3.85 (4H, m), 3.70 (2H, m), 3.55 (4H, m), 1.15 (6H, d,
3J ) 6.3 Hz); 13C NMR (CDCl3, 100 MHz) δ 173.3, 152.9, 115.6,
76.8, 75.0, 69.9, 67.6, 67.0, 16.3; FTIR (KBr, cm-1) ν ) 3100, 2930,
1788, 1766, 1732, 1510, 1455, 1367, 1220, 1170, 1130, 928, 827, 756;
ESMS m/z 429.0 [M - H]-.
(SS)-25: [R]29 ) -5.8° (c ) 3.28 in MeCN). Anal. Calcd for
D
C28H46O10 (542.309): C, 61.96; H, 8.55. Found: C, 62.39; H, 8.43.
Data on (RR)-25: [R]26D ) +5.9° (c ) 1.19 in MeCN). Anal. Calcd
for C28H46O10 (542.309): C, 61.96; H, 8.55. Found: C, 62.03; H, 8.57.
1,4-Bis[2-(2-(2(S)-(tert-butoxycarbonylmethoxy)propoxy)ethoxy)-
ethoxy]benzene [(SS)-26] and (RR)-26. These compounds were
prepared by procedures similar to those reported for (SS)-24 and (RR)-
24. The products were purified by flash column chromatography (SiO2,
hexane/EtOAc (3:2) (Rf ) 0.10)) to yield clear oils (38% and 44%
yields for (SS)-26 and (RR)-26, respectively). Spectral data (for both
compounds): 1H NMR (CDCl3, 400 MHz) δ 6.80 (4H, s), 4.10 (2H,
(RR)-30 was prepared from (RR)-25 in a similar deprotection
procedure to yield a sticky oil in quantitative yield. TLC and NMR
spectroscopy indicated that the purity of the product was better than
20
95%: [R]D ) -7.4° (c ) 2.54 in MeCN/Me2CO (2:3 v/v)). The
spectroscopic data were identical with those reported for compound
(SS)-30: ESMS m/z 429 [M - H]-.
2
1,4-Bis[2-(2-(2(S)-(carboxymethoxy)propoxy)ethoxy)-
ethoxy]benzene [(SS)-31] and (RR)-31. The diester (SS)-26 (155 mg,
0.25 mmol) was stirred in an HBr solution of dry CH2Cl2 for 1.5 h at
0 °C. The solvent was removed in vacuo to yield (SS)-31 as a clear
oil (130 mg, 100%). TLC and NMR spectroscopy indicated that the
purity of the product was better than 95%: [R]21D ) +16.5° (c ) 2.60
d, J ) 16.5 Hz), 4.05 (6H, m), 3.85 (4H, m), 3.75-3.60 (10H, m),
3.55 (2H, dd, 2J ) 10.3 Hz, 3J ) 6.3 Hz), 3.45 (2H, dd, 2J ) 10.3 Hz,
3
3J ) 4.0 Hz), 1.45 (18H, s), 1.20 (6H, d, J ) 6.2 Hz); 13C NMR
(CDCl3, 100 MHz) δ 170.1, 153.0, 115.5, 81.2, 75.5, 75.2, 70.8, 70.7,
69.8, 68.0, 67.4, 28.1, 17.1; FTIR (KBr, cm-1) ν ) 2975, 2931, 1748,
1510, 1455, 1368, 1290, 1230, 1125, 1065, 941, 827, 752. Data on
1
(SS)-26: [R]26 ) -4.0° (c ) 3.37 in MeCN). Anal. Calcd for
in MeCN); H NMR (CDCl3, 400 MHz) δ 10.0 (2H, br s), 6.80 (4H,
D
s), 4.25 (2H, d, 2J ) 17.3 Hz), 4.10 (6H, m), 3.85 (4H, m), 3.70 (10H,
C32H54O12 (630.361): C, 60.92; H, 8.63. Found: C, 60.48; H, 8.71.
Data on (RR)-26: [R]26D ) +3.7° (c ) 2.42 in MeCN). Anal. Calcd
for C32H54O12 (630.361): C, 60.92; H, 8.63. Found: C, 60.66; H, 8.89.
1,4-Bis[2-(2(S)-(tert-butoxycarbonylmethoxy)4-methylpentoxy)-
ethoxy]benzene [(SS)-27]. This compound was prepared by a
procedure similar to that described for (SS)-24. The product was
purified by flash column chromatography (SiO2, hexane/EtOAc (3:1)
(Rf ) 0.23)) to yield a clear oil (38%). [R]25D ) -14.6° (c ) 2.22 in
3
m), 3.50 (4H, m), 1.15 (6H, d, J ) 6.2 Hz); 13C NMR (CDCl3, 100
MHz) δ 173.0, 152.8, 115.4, 76.7, 74.7, 70.5, 70.2, 69.7, 67.8, 66.9,
16.1; FTIR (KBr, cm-1) ν ) 3200, 2920, 1766, 1760, 1505, 1455,
1355, 1230, 1120, 1065, 930, 830, 755; ESMS m/z 517.2 [M - H]-.
(RR)-31 was prepared by stirring the diester (RR)-26 in TFA for 1
h at room temperature. The solvent was removed in vacuo to yield
(RR)-31 as a brown, clear oil (100%). TLC and NMR spectroscopy
indicated that the purity of the product was better than 95%: [R]20
)
1
2
D
MeCN); H NMR (CDCl3, 400 MHz) δ 6.85 (4H, s), 4.20 (2H, d, J
2
-9.5° (c ) 3.90 in MeCN/Me2CO (2:3 v/v)). The spectroscopic data
were identical with those reported for compound (SS)-31: ESMS m/z
517.1 [M - H]-.
) 16.5 Hz), 4.10 (2H, d, J ) 16.5 Hz), 4.05 (4H, m), 3.80 (4H, m),
3.60-3.50 (6H, m), 1.80 (2H, m), 1.50 (20H, m), 1.25 (2H, m), 0.92
(6H, d, J ) 6.6 Hz), 0.90 (6H, d, J ) 6.6 Hz); 13C NMR (CDCl3,
100 MHz) δ 170.0, 153.1, 115.5, 81.1, 77.8, 75.1, 69.9, 68.3, 68.0,
40.9, 28.1, 24.3, 23.1, 22.4; FTIR (KBr, cm-1) ν ) 2956, 2870, 1748,
1509, 1455, 1392, 1368, 1301, 1231, 1128, 1047, 929, 826, 751. Anal.
Calcd for C34H58O10 (626.403): C, 65.13; H, 9.33. Found: C, 65.67;
H, 9.57.
3
3
1,4-Bis[2-(2(S)-(carboxymethoxy)-4-methylpentoxy)ethoxy]ben-
zene [(SS)-32]. The diester (SS)-27 (110 mg, 0.18 mmol) was stirred
in an HBr solution of dry CH2Cl2 for 1.5 h at 0 °C. The solvent was
removed in vacuo to yield (SS)-32 as a clear oil (90 mg, 100%). TLC
and NMR spectroscopy indicated that the purity of the product was
better than 95%: [R]21D ) +1.1° (c ) 4.4 in MeCN); 1H NMR (CDCl3,
1,4-Bis[2-(2-(2(S)-(tert-butoxycarbonylmethoxy)-4-methylpentoxy)-
ethoxy)ethoxy]benzene [(SS)-28]. This compound was prepared by
a procedure similar to that described for (SS)-24. The product was
purified by flash column chromatography (SiO2, hexane/EtOAc (2:1)
(Rf ) 0.21)) to yield a clear oil (31%): [R]25D ) - 18.6° (c ) 1.56 in
2
400 MHz) δ 10.0 (2H, br s), 6.8 (4H, s), 4.30 (2H, d, J ) 17.3 Hz),
2
4.15 (2H, d, J ) 17.3 Hz), 4.05 (4H, m), 3.85 (4H, m), 3.70-3.50
(6H, m), 1.70 (2H, m), 1.50 (2H, m), 1.25 (2H, m), 0.90 (12H, d, 3J )
6.6 Hz); 13C NMR (CDCl3, 100 MHz) δ 173.3, 152.9, 115.7, 79.5,
74.5, 70.0, 68.1, 67.6, 40.6, 24.4, 23.0, 22.4; FTIR (KBr, cm-1) ν )
3174, 2956, 1766, 1732, 1505, 1455, 1368, 1283, 1231, 1130, 928,
827, 757; ESMS m/z 512.9 [M - H]-.
1
2
MeCN); H NMR (CDCl3, 400 MHz) δ 6.85 (4H, s), 4.15 (2H, d, J
2
) 16.2 Hz), 4.10 (2H, d, J ) 16.2 Hz), 4.05 (4H, m), 3.85 (4H, m),
3.70 (4H, m), 3.65 (6H, m), 3.55 (4H, m), 1.85 (2H, m), 1.45 (20H,

930 J. Am. Chem. Soc., Vol. 120, No. 5, 1998
Asakawa et al.
Table 3. Crystal Data, Data Collection and Refinement Parametersa
data
5
5/1‚4PF6
(SS)-30/1‚4PF6
(SS)-37/1‚4PF6
formula
solvent
C13H18O6
C49H50N4O6‚4PF6
5MeCN
1576.1
orange plate
0.50 × 0.50 × 0.17
triclinic
C56H62N4O10‚4PF6
2MeCN
1613.1
red rhombs
0.83 × 0.40 × 0.40
monoclinic
P21
11.554(2)
18.325(4)
17.823(5)
C54H62N4O6‚4PF6
2.5MeCN
1545.6
red blocks
0.67 × 0.60 × 0.53
triclinic
formula weight
color, habit
crystal size / mm
lattice type
space group
cell dimensions:a/Å
b/Å
270.3
clear block
0.87 × 0.51 × 0.33
triclinic
PT
7.735(1)
11.868(3)
15.122(4)
95.72(2)
94.58(2)
95.44(2)
1369.4(5)
4b
PT
P1
13.322(4)
15.097(3)
18.748(4)
95.99(2)
105.11(2)
101.73(2)
3515(2)
11.382(1)
12.742(1)
13.863(1)
86.01(1)
75.21(1)
64.65(1)
1754.9(2)
1
1.463
793
2.04
5.0-60.0
c/Å
R/deg
â/deg
γ/deg
100.86(2)
V/Å3
Z
3706(1)
2
1.446
1652
2.00
2.5-62.1
2
Dc/(g cm-3
F(000)
µ/mm-1
)
1.311
576
0.88
3.0-62.0
1.489
1612
2.06
2.5-63.0
θ range/deg
no. of unique reflections
measured
4299
10291
6039
5413
observed, |Fo| > 4σ(|Fo|)
c
3922
344
0.054
0.153
0.081, 0.576
0.39, -0.39
8364
1012
0.071
0.184
0.104, 5.011
0.80, -0.67
4092
628
0.131
0.377
0.306, 3.939
0.87, -0.50
4918
896
0.064
0.163
0.096, 2.579
0.53, -0.45
no. of variables
R1
d
wR2
weighting factors a, be
largest difference peak, hole/eÅ-3
a Details in common: graphite-monochromated Cu KR radiation, ω scans, Siemens P4 diffractometer, 293 K, refinement based on F.2 b There
are two crystallographically independent molecules in the asymmetric unit. c R1 ) Σ||Fo| - |Fc||/Σ|Fo|. d wR2 ) {Σw(Fo2 - Fc2)2/Σw(Fo )2}1/2
.
e w-1
2
) σ2(Fo ) + (aP)2 + bP.
2
1,4-Bis[2-(2-(2(S)-(carboxymethoxy)-4-methylpentoxy)ethoxy)-
ethoxy]benzene [(SS)-33]. The diester (SS)-28 (155 mg, 0.25 mmol)
was stirred in an HBr solution of dry CH2Cl2 for 1.5 h at 0 °C. The
solvent was removed in vacuo to yield (SS)-33 as a clear oil (130 mg,
100%). TLC and NMR spectroscopy indicated that the purity of the
(1.0 g, 7.0 mmol) were added. Stirring was continued for another 2 h,
after which the solvent was removed in vacuo. H2O was added to the
residue, and the suspension was extracted with CH2Cl2. The organic
layer was dried (MgSO4), filtered, and concentrated in vacuo. The
crude product was purified by column chromatography (SiO2, hexane/
EtOAc (7:3)) to yield (SS)-35 as a yellow clear oil (345 mg, 77%):
[R]25D ) -32.0° (c ) 6.0 in Me2CO); 1H NMR (CDCl3, 400 MHz) δ
6.85 (4H, s), 3.90 (2H, dd, 2J ) 9.6 Hz, 3J ) 5.9 Hz), 3.85 (2H, dd, 2J
) 9.9 Hz, 3J ) 4.5 Hz), 3.70 (2H, m), 3.45 (6H, s), 1.25 (6H, 3J ) 6.3
Hz); 13C NMR (CDCl3, 100 MHz) δ 153.1, 115.4, 75.3, 72.0, 56.9,
16.5; FTIR (KBr, cm-1) ν ) 2975, 2929, 2823, 1507, 1455, 1449,
1375, 1231, 1154, 1104, 1069, 1040, 825; HRMS m/z calcd for
C14H22O4 254.1518, found 254.1519.
product was better than 95%: [R]25 ) +5.4° (c ) 1.17 in MeCN);
D
1H NMR (CDCl3, 400 MHz) δ 9.8 (2H, br s), 6.8 (4H, s), 4.25 (2H, d,
2J ) 17.3 Hz), 4.05 (2H, d, 2J ) 17.3 Hz), 4.00 (4H, m), 3.80 (4H, m),
3.70 (8H, m), 3.65-3.45 (6H, m), 1.70 (2H, m), 1.45 (2H, m), 1.25
2
3
3
3
(2H, ddd, J ) 14.0 Hz, J ) 7.5 Hz, J ) 5.7 Hz), 0.90 (12H, d, J
) 6.6 Hz); 13C NMR (CDCl3, 100 MHz) δ 173.0, 152.8, 115.4, 79.4,
74.1, 70.5, 70.2, 69.7, 68.0, 67.8, 40.5, 24.2, 22.9, 22.4; ESMS m/z
601.4 [M - H]-.
1,4-Bis(2(S)-methylbutoxy)benzene [(SS)-34]. Hydroquinone 16
(305 mg, 2.77 mmol), KOH (360 mg, 6.43 mmol), and a catalytic
amount of tetrabutylammonium iodide were suspended in EtOH (5 mL).
The suspension turned brown. The tosylate of 2(S)-methylbutanol21
(1.5 g, 6.20 mmol) in dry THF (10 mL) was added dropwise, after
which the suspension was brought to reflux for 48 h. The reaction
mixture was poured into a mixture of CH2Cl2 and a 1 M NaOH aqueous
solution. The aqueous layer was extracted with CH2Cl2. The combined
organic layers were dried (MgSO4), filtered, and concentrated in vacuo
to give 0.90 g of crude material, which was purified by flash column
chromatography (SiO2, hexane/CH2Cl2, (7:3)) to yield (SS)-34 as a white
(RR)-35 was prepared from the diol (RR)-19 in a similar fashion to
yield a yellow, clear oil in 70% yield. The spectroscopic data were
identical with those reported for compound (SS)-35: [R]26D ) +41.1°
(c ) 2.2 in Me2CO).
1,4-Bis(2(S)-ethoxypropoxy)benzene [(SS)-36]. The diol (SS)-19
(55 mg 0.24 mmol), KOH (95 mg 1.70 mmol), and EtI (227 mg, 1.46
mmol) were suspended in THF (2.5 mL). The mixture was stirred for
2 days at reflux, after which extra portions of KOH (35 mg, 0.63 mmol)
and EtI (80 mg, 0.51 mmol) were added. The suspension was refluxed
for another day. The solvent was removed in vacuo, H2O was added
to the residue, and the suspension was extracted with CH2Cl2. The
organic layer was dried (MgSO4), filtered, and concentrated in vacuo.
The crude product was purified by column chromatography (CH2Cl2
and then hexane/EtOAc (5:1)) to yield (SS)-36 as a yellow clear oil
solid (415 mg, 60%): mp 27-29 °C; [R]28 ) +15.1° (c ) 2.1 in
D
CHCl3); 1H NMR (CDCl3, 400 MHz) δ 6.85 (4H, s), 3.75 (2H, dd, 2J
) 8.9 Hz, 3J ) 5.8 Hz), 3.65 (2H, dd, 2J ) 8.9 Hz, 3J ) 6.6 Hz), 1.80
3
(m, 2H), 1.55 (m, 2H), 1.25 (m, 2H), 1.0 (6H, d, J ) 6.9 Hz), 0.95
(65 mg, 90%): [R]20 ) -16.6° (c ) 1.63 in Me2CO); 1H NMR
D
3
(6H, tr, J ) 7.5 Hz); 13C NMR (CDCl3, 100 MHz) δ 153.4, 115.4,
(CDCl3, 400 MHz) δ 6.80 (4H, s), 3.90 (2H, dd, 2J ) 9.2 Hz, 3J ) 5.5
Hz), 3.80 (4H, m), 3.60 (4H, m), 1.30 (6H, d, 3J ) 6.3 Hz), 1.20 (6H,
73.6, 34.8, 26.1, 16.5, 11.3; FTIR (KBr, cm-1) ν ) 2961, 2930, 2876,
1508, 1467, 1390, 1228, 1045, 823; HRMS m/z calcd for C16H26O2
250.1933, found 250.1935.
3
t, J ) 7.0 Hz); 13C NMR (CDCl3, 100 MHz) δ 153.2, 115.5, 73.6,
72.3, 64.6, 17.4, 15.6; FTIR (KBr, cm-1) ν ) 2974, 2928, 2871, 1508,
1456, 1374, 1230, 1154, 1107, 1067, 1044, 825; HRMS m/z calcd for
C16H26O4 282.1831, found 282.1818.
1,4-Bis(2(S)-methoxypropoxy)benzene [(SS)-35] and (RR)-35.
The diol (SS)-19 (400 mg, 1.77 mmol) and t-BuOK (0.435 g, 3.89
mmol) were suspended in t-BuOH (6 mL). The mixture was stirred
for 15 min at 30-40 °C, resulting in the formation of a clear yellow
solution. MeI (2.28 g, 16.1 mmol) was added dropwise, giving
immediate precipitation of KI. The suspension was stirred overnight,
after which extra portions of t-BuOK (150 mg, 1.34 mmol) and MeI
1,4-Bis[2(S)-(2-methoxyethoxy)propoxy]benzene [(SS)-37]. The
diol (SS)-19 (79 mg, 0.35 mmol), KOH (135 mg, 2.41 mmol), and the
tosylate of 2-methoxyethanol22 (480 mg, 2.09 mmol) were suspended
in THF (3 mL). The reaction mixture was stirred for 2 days at reflux,
after which extra portions of KOH (45 mg, 0.80 mmol) and tosylate

Constitutionally Asymmetric and Chiral [2]Pseudorotaxanes
J. Am. Chem. Soc., Vol. 120, No. 5, 1998 931
(160 mg, 0.70 mmol) were added. The suspension was heated under
reflux for another day. The solvent was removed in vacuo, H2O was
added to the residue, and the suspension extracted with CH2Cl2. The
organic layer was dried (MgSO4), filtered, and concentrated in vacuo.
The crude product was purified by column chromatography (CH2Cl2
and hexane/EtOAc (3:1)) to yield an oil that still was not completely
pure. Further purification by column chromatography (CH2Cl2/
components in MeCN. Table 3 provides a summary of the crystal data,
data collection, and refinement parameters for 5 and the [2]pseudoro-
taxanes 5/1‚4PF6, (SS)-30/1‚4PF6, and (SS)-37/1‚4PF6.
CD/UV Measurements. In all cases, 1‚4PF6 was dissolved in
MeCN with a few molar equivalents (between 1 and 10) of the chiral
thread. Care was taken for the optical density of the solution to be
between 0.1 and 1.5. Compounds (SS)-19, (RR)-19, (RR)-20, (SS)-29,
(RR)-29, (SS)-30, (SS)-31, (RR)-31, (SS)-34, (SS)-35, (RR)-35, (SS)-
36, and (SS)-37 (15.2, 5.9, 7.5, 7.1, 6.9, 14.5, 9.0, 8.7, 76.0, 11.0, 15.5,
8.1 and 7.0 mg, respectively) with 1‚4PF6 (10.0, 3.3, 4.2, 4.7, 4.3, 3.0,
2.9, 2.6, 15, 2.8, 3.8, 6.2, and 5.0 mg, respectively) were dissolved in
MeCN (3.25, 1.59, 2.18, 1.55, 1.69, 1.90, 1.49, 1.45, 4.1 1.65, 1.71,
1.42, and 1.59 g, respectively). These clear solutions were investigated
with UV and CD spectroscopy at room temperature. The λmax values
of the solutions were located at 474, 467, 460, 461, 464, 476, 469,
467, and 468 nm for 19, 20, 29, 30, 31, 34, 35, 36, and 37, respectively,
in the UV spectra. For the experiments shown in Figure 7 the following
solutions were prepared: (Figure 7A) 7.1 mg of (SS)-29, 4.7 mg of
1‚4PF6, 1.55 g of MeCN; 5.9 mg of (RR)-29, 4.3 mg of 1‚4PF6, 1.69
g of MeCN; (Figure 7B) 15.2 mg of (SS)-19, 10 mg of 1‚4PF6, 3.25 g
of MeCN; 5.9 mg of (RR)-19, 3.3 mg of 1‚4PF6, 1.59 g of MeCN. The
variable temperature measurements (Figure 8) were performed with
(Figure 8A) 7.1 mg of (SS)-29, 4.7 mg of 1‚4PF6, and 1.67 g of MeCN
and (Figure 8B) 15.2 mg of (SS)-19, 10 mg of 1‚4PF6, and 3.25 g of
MeCN. All solutions were measured in 1 cm sample holders.
MeCOEt (10:1)) gave pure compound (SS)-37 (64 mg, 54%): [R]20
D
1
) -11.6° (c ) 1.34 in Me2CO); H NMR (CDCl3, 400 MHz) δ 6.80
(4H, s), 4.00 (2H, dd, 2J ) 11.2 Hz, 3J ) 7.5 Hz), 3.85 (4H, m), 3.75
(4H, t, 3J ) 4.9 Hz), 3.55 (4H, m), 3.40 (6H, s), 1.30 (6H, d, 3J ) 6.2
Hz); 13C NMR (CDCl3, 100 MHz) δ 153.0, 115.4, 74.4, 72.2 (2), 68.7,
59.0, 17.3; FTIR (KBr, cm-1) ν ) 2974, 2925, 2874, 1508, 1456, 1374,
1230, 1108, 1044, 826; GC/MS peaks at m/z 342 and 343 (2.4% and
0.4% abundance relative to 59).
1H NMR Spectroscopic Studies of Complexation. Solutions with
a 1:1 molar ratio of the π-electron-rich and π-electron-deficient
components were prepared in CD3CN with concentrations of 5 × 10-3
mol dm-3. All chemical shift changes (∆δ) for the 1:1 complexes are
quoted in parts per million, and they were calculated using the equation
∆δ ) δ(observed) - δ(free).
UV Spectrophotometric Titrations. The changes in the optical
density of solutions of complexes were recorded as the relative
concentrations of thread components of the complexes were increased
with respect to the tetracationic cyclophane 1‚4PF6. All stability
constants were determined in dry MeCN solution at 298 K. In a typical
experiment, a solution of 1‚4PF6 was made up in a volumetric flask
and its optical density recorded in a 1 cm path length cuvette. A known
quantity of the guest was added to the solution. The optical density of
this solution of the complex was recorded and the procedure repeated
until no significant change in the optical density was observed when
further guest was added. Molar ratios of threads to the tetracationic
cyclophane employed were in the range 0.1:1 to 30:1 for strong 1:1
complexes and in the range 1:1 to 100:1 for weak 1:1 complexes. The
data were treated with a nonlinear curve-fitting program (UltraFit;
Biosoft: Cambridge, 1992) running on an Apple Macintosh micro-
computer.
Acknowledgment. We thank Henk Eding and Joost van
Dongen for obtaining the elemental analyses and mass spectra,
respectively. The research was supported by the CIBA-GEIGY
Foundation (Japan) for the Promotion of Science and the
Engineering and Physical Sciences Research Council in the
United Kingdom. DSM Research is gratefully acknowledged
for an unrestricted research grant to the Eindhoven Group in
The Netherlands.
Supporting Information Available: Tables listing atomic
coordinates, temperature factors, bond lengths and angles, and
torsion angles and details of the refinement of the X-ray
crystallographic data (38 pages). See any current masthead page
for ordering information and Internet access instructions.
X-ray Crystallography. Single crystals suitable for X-ray crystal-
lographic analysis of 5 were grown by vapor diffusion of i-Pr2O into
a solution of the compound 5 in CHCl3. Single crystals of the [2]-
pseudorotaxanes 5/1‚4PF6, (SS)-30/1‚4PF6, and (SS)-37/1‚4PF6 were
grown by vapor diffusion of i-Pr2O into 1:1 solutions of the appropriate
JA970018I