Diastereoselective Amplification of a Mechanically Chiral [2]Catenane

Article abstract of DOI:10.1021/jacs.1c06557

Achiral [2]catenanes composed of rings with inequivalent sides may adopt chiral co-conformations. Their stereochemistry depends on the relative orientation of the interlocked rings and can be controlled by sterics or an external stimulus (e.g., a chemical stimulus). Herein, we have exploited this stereodynamic property to amplify a mechanically chiral (P)-catenane upon binding to (R)-1,1′-binaphthyl 2,2′-disulfonate, with a diastereomeric excess of 85%. The chirality of the [2]catenane was ascertained in the solid state by single crystal X-ray diffraction and in solution by NMR and CD spectroscopies. This study establishes a robust basis for the development of a new synthetic approach to access enantioenriched mechanically chiral [2]catenanes.

Full text of DOI:10.1021/jacs.1c06557

pubs.acs.org/JACS
Communication
Diastereoselective Amplification of a Mechanically Chiral
[2]Catenane
Kenji Caprice, Dávid Pál, Céline Besnard, Bartomeu Galmés, Antonio Frontera,
and Fabien B. L. Cougnon*
Cite This: https://doi.org/10.1021/jacs.1c06557
Read Online
sı
*
Metrics & More
Article Recommendations
Supporting Information
ACCESS
ABSTRACT: Achiral [2]catenanes composed of rings with inequivalent sides may adopt chiral co-conformations. Their
stereochemistry depends on the relative orientation of the interlocked rings and can be controlled by sterics or an external stimulus
(e.g., a chemical stimulus). Herein, we have exploited this stereodynamic property to amplify a mechanically chiral (P)-catenane
upon binding to (R)-1,1′-binaphthyl 2,2′-disulfonate, with a diastereomeric excess of 85%. The chirality of the [2]catenane was
ascertained in the solid state by single crystal X-ray diffraction and in solution by NMR and CD spectroscopies. This study
establishes a robust basis for the development of a new synthetic approach to access enantioenriched mechanically chiral
[2]catenanes.
he enantioselective synthesis of chiral mechanically
T
interlocked molecules (MIMs)1−4 has made spectacular
progress in recent years, enabling the development of
sophisticated molecular machines with functional applications
in stereoselective catalysis,5 sensing,6 and chiroptical switching.7
These applications rely on the ability of MIMs to express their
chirality in different ways when the relative position of the
interlocked components changes, an unusual property that is not
accessible with traditional covalent systems. Despite major
synthetic achievements, the production of chiral MIMs generally
remains tedious and requires elaborate multistep syntheses,
involving the independent synthesis of several low symmetry
components.3,4 New strategies that can provide access to
complex chiral molecular machines in a simple, cost-effective
manner are therefore needed.
A potential way to address the above-mentioned limitations
lies in the work of Puddephatt et al.8 and Marinetti, Sauvage, and
co-workers9 who have shown that combining two rings with
inequivalent faces produces a pair of axially chiral enantiomers
(Figure 1a). These enantiomers are configurationally stable and
cannot interconvert without breaking a covalent bond. Their
stereochemistry is comparable to that of axially chiral allenes,
with one notable difference: the axial chirality of the [2]catenane
arises exclusively from the presence of the mechanical bond
connecting the rings, a phenomenon referred to as mechanically
axial chirality.10 This observation implies that chiral MIMs can
be produced by combining components that are identical,
achiral, and nondirectional. Each of these features evidently
reduces the synthetic cost of the final compound. However,
examples of such [2]catenanes are scarce. In addition, the
control of mechanically axial chirality is highly challenging and
has never been achieved: to date, only racemates have been
obtained.
Figure 1. Two situations in which mechanically axial chirality may be
encountered. (a) The stereochemistry of [2]catenanes composed of
rings with inequivalent faces (previous work) is similar to that of axially
chiral allenes. (b) The stereochemistry of [2]catenanes composed of
rings with inequivalent sides (contribution of this study) is closer to
atropisomerism.11
Received: June 24, 2021
We now present a simple alternative approach to access
enantioenriched mechanically axially chiral [2]catenanes. Figure
1b shows a [2]catenane composed of rings with inequivalent
© XXXX The Authors. Published by
American Chemical Society
https://doi.org/10.1021/jacs.1c06557
J. Am. Chem. Soc. XXXX, XXX, XXX−XXX
A

Journal of the American Chemical Society
pubs.acs.org/JACS
Communication
sides, rather than inequivalent faces. Such [2]catenanes are
commonly found in the literature.12,13 They are generally
considered to be achiral because they possess a mirror plane
when the mirror planes of the individual rings are brought to
coincide. Yet, moving the rings on either side of the mirror plane
generates axially chiral co-conformations.14,15 These co-
conformations may be either left-handed (M) or right-handed
(P), depending on the relative orientation of the rings. In
contrast with the situation presented in Figure 1a, the motion of
the rings now results in the interconversion of the enantiomeric
co-conformers.16,17 This behavior is somewhat reminiscent of
atropisomerism.11 If the motion of the rings is unconstrained,
which is typically the case in previous reports, the individual co-
conformers interconvert too rapidly to be detected and the
[2]catenane displays no sign of chirality. Here we show that the
chiral co-conformers can become observable when the motion
of the rings is hindered. More importantly, we show that the
dynamic nature of this system can be exploited to easily amplify a
single enantiomer in response to a chemical stimulus.18
Tandem mass spectrometry (Figure S4)21 rapidly confirmed
that [2]catenane 3 was composed of two identical macrocycles,
each resulting from the condensation of one dialdehyde 1 (in
gray) and one dihydrazide 2 (in green).
Attempts to obtain single crystals of 3·4CF3CO2 from
aqueous solutions were unsuccessful. Fortunately, slow vapor
diffusion of isopropyl ether in a concentrated acetonitrile
solution of the hexafluorophosphate salt 3·4PF6 (prepared by
following an anion exchange protocol described in the SI),
yielded single crystals suitable for X-ray diffraction. [2]Catenane
3 is a particularly compact structure. The optimum packing of
the aromatic units results in a decrease of solvent accessible
surface area of ca. 37% compared to that of two non-interlocked
macrocycles, explaining the high yield of the [2]catenane
assembly. The cavity of the individual rings is narrow, oblong,
and delimited by large aromatic walls. Steric demands impose
considerable constraint on the relative orientation of the rings,
which can only be interlocked if the quinoliniums stack as
depicted in Figure 2b. The [2]catenane is thus locked into a
well-expressed axially chiral state. Of all the possible co-
conformers, only the enantiomers (M)-3 and (P)-3 are present
and alternate in the three dimensions of the crystal lattice
(Figure 3).
A sterically hindered [2]catenane composed of rings with
inequivalent sides was assembled following a dynamic
combinatorial approach (Figure 2).19 In water, amphiphilic
Figure 3. Crystal packing showing the alternation between (M)-3 (in
red) and (P)-3 (in blue). Hydrogens and counterions are omitted for
clarity.
Figure 2. (a) Synthesis of [2]catenane 3 from dialdehyde 1 (in gray)
and dihydrazide 2 (in green). The HPLC chromatogram shows the
purity of the crude mixture at the end of the reaction. (b) Crystal
structure of the enantiomers (M)-3 and (P)-3. The acylhydrazone
linkages are colored in yellow. Hydrogens are omitted for clarity.
1
The H NMR spectrum of 3·4CF3CO2 in D2O (Figure 4a)
comprises sharp, well-dispersed resonances, and it does not
significantly change between 278 and 338 K (Figure S5). These
features confirm that [2]catenane 3 has little conformational
freedom. The spectrum is consistent with the C2-symmetrical
structure observed in the solid state. The two rings are
equivalent, and all the protons of an individual ring are
inequivalent.
building blocks frequently self-assemble into catenanes to
minimize the overall hydrophobic surface area in contact with
the environment.13,20 Quinolinium-based dialdehyde 1 (1 mM)
and dihydrazide 2 (1 mM) were solubilized in water at pH 5.
The solution was stirred overnight at 70 °C, allowing for the
reversible formation of acylhydrazone linkages between the
building blocks. On the following day, HPLC analysis disclosed
the near-quantitative conversion of the starting materials into
[2]catenane 3, which was isolated by semipreparative HPLC as a
trifluoroacetate salt (3·4CF3CO2) in 83% yield.
The protons of the inner quinoliniums, buried in the stack, are
substantially upfield-shifted compared to those of the outer
quinoliniums. Moreover, the methylene protons are diaster-
eotopic. In conclusion, the [2]catenane also exists as a racemic
mixture of (M)-3 and (P)-3 in solution. The spectrum shows no
evidence of any other co-conformers.
B
https://doi.org/10.1021/jacs.1c06557
J. Am. Chem. Soc. XXXX, XXX, XXX−XXX

Journal of the American Chemical Society
pubs.acs.org/JACS
Communication
1
●
Figure 4. (a) H NMR spectrum (D2O, 500 MHz, 298 K) of [2]catenane 3 highlighting the signals corresponding to the inner quinolinium ( ), outer
■
○
▲
quinolinium ( ), naphthalene ( ) and phenylene ( ) protons. Diastereotopic methylene protons are labeled with a star (∗). The cartoon
representations show that the enantiomerization results in an exchange between inequivalent quinolinium protons (
●
○
). (b) Corresponding
↔
exchange cross-peaks are observable in the NOESY spectrum (338 K, d8 = 300 ms). The full interpretation of the NMR spectra can be found in the SI.
Figure 5. Amplification of the diastereomeric complex (P)-3·(R)-4. (a) 1H NMR titration of (R)-4 to a solution of [2]catenane 3 (1.13 mM, D2O/
CD3CN 1:1, 500 MHz, 298 K). (b) Representation of the equilibria involved in the diastereoselective amplification. (c) Evolution of the
diastereomeric excess in the course of the titration.
The enantiomers (M)-3 and (P)-3 may interconvert through
either mechanism of ring pirouetting or ring circumrotation.22
In any case, the enantiomerization results in the exchange of the
inner and outer quinoliniums (Figure 4a). Their inequivalence
implies that the process is slow on the NMR time scale.
Nevertheless, the presence of exchange cross-peaks between
pairs of inequivalent quinolinium protons in the 2D NOESY
spectrum (Figure 4b) allowed for the determination of the
enantiomerization rate constants between 313 and 338 K.23 The
Eyring plot generated the enthalpy (ΔH⧧ = +61 kJ·mol−1) and
C
https://doi.org/10.1021/jacs.1c06557
J. Am. Chem. Soc. XXXX, XXX, XXX−XXX

Journal of the American Chemical Society
pubs.acs.org/JACS
Communication
entropy (ΔS⧧ = −83 J·mol−1·K−1) of activation and the energy
barrier (ΔG⧧298 K = +85 kJ·mol−1).
The barrier to interconversion is high enough to enable the
NMR resolution of the (M)- and (P)-enantiomers. Indeed,
addition of 0.07 equiv of potassium disulfonate24,25 (R)-4 to the
racemic solution of 3·4CF3CO2 (1.13 mM, D2O/CD3CN 1:1)26
resulted in the separation of each signal of the [2]catenane into
two signals at δM and δP (Figures 5a and S16).
As the quantity of disulfonate (R)-4 added increased, the
signals at δM and δP further separated and their relative intensity
noticeably changed. This phenomenon indicates that (R)-4
preferentially binds one of the two enantiomers and shifts the
equilibrium toward the formation of the most stable
diastereomeric complex. The integration of the separated signals
provided a direct measurement of the diastereomeric excess,
which increased with [(R)-4]/[3] until it reached a maximum
value, demax = 85% (Figure 5c).
DFT calculations revealed that the amplified diastereomeric
complex was (P)-3·(R)-4 (Figure 6). The [2]catenane possesses
Figure 7. (bottom) UV−visible spectra of [2]catenane 3 and (R)-4
(H2O/CH3CN 1:1). (top) ICD spectra of 3 (38 μM, H2O/CH3CN
1:1) in the presence of 0−15 equiv of (R)-4. Inset: ICD amplitude at
364 nm as a function of the number of equivalents of (R)-4.
[2]catenane 3·4CF3CO2 (38 μM) exhibited no CD signal in
H2O/CH3CN 1:1. Upon addition of disulfonate (R)-4, an
induced CD (ICD) signal appeared, consisting of a strong
negative Cotton effect at 303 nm and a weaker negative Cotton
effect at 364 nm. The intensity of the ICD increased with the
number of equivalents of (R)-4 until it reached a maximum at
[(R)-4]/[3] ≈ 10. This maximum intensity corresponds to the
diastereomeric excess demax = 85% previously measured by
NMR, as this value is independent of the range of concentration
at which the titration is performed. Taking this information into
account, the ICD intensity could be converted into a
diastereomeric excess at any stage of the titration (Figure 7,
inset). This time, fitting the titration curve successfully afforded
the association constants KP = 2.6 × 105 M−1 and KM = 2.1 × 104
M−1.
In conclusion, we have described a simple approach to access
mechanically chiral [2]catenanes in enantioenriched form. This
approach relies on the ability of [2]catenanes composed of rings
with inequivalent sides to adopt achiral and chiral co-
conformations in dynamic exchange. If the relative orientation
of the rings can be controlled by an external stimulus, it is
possible to reversibly switch the [2]catenane between achiral,
(M), and (P) states.18 Here we have exploited this property to
bias the population of co-conformers in favor of a (P)-catenane.
The stereodynamic nature of this system is its most distinctive
feature. However, we anticipate that increasing the steric bulk of
the rings will slow down the enantiomerization rate enough to
enable the isolation of the enantioenriched [2]catenane in a
Figure 6. BP86-D3/def2-TZVP optimized geometry of the diastereo-
meric complex (P)-3·(R)-4.
a binding site where (R)-4 can nest and form four short and
directional hydrogen bonds with the acylhydrazone NHs.
Disulfonate (R)-4 binds both enantiomers, but fits better in
the binding site of (P)-3 than in that of (M)-3 (Figure S24).
Since (P)-3·(R)-4 is virtually the only species observable in the
spectrum at the end of the titration, it was fully characterized by
1H and 13C NMR (Figures S17−S20).
If (M)-3 and (P)-3 bind (R)-4 with association constants KM
and KP, respectively (Figure 5b), the diastereomeric excess at
saturation is determined by the ratio κ = KP/KM, which
represents the selectivity of the anion for one of the two co-
conformational states. The value κ = 12.3 calculated from demax
indicates that KP is an order of magnitude superior to KM and
corresponds to a difference of stability ΔG°298K = 6.2 kJ·mol−1
between the two diastereomeric complexes. In principle, both
KM and KP can be obtained by fitting the plot de = f([(R)-4]/
[3]). The derivatization of the corresponding equations is
detailed in the SI. However, the early saturation of the titration
curve prevented the accurate determination of the individual
association constants. It was only possible to conclude from this
first experiment that KM and KP were greater than 104 M−1.
The diastereoselective amplification was confirmed by
circular dichroism (Figure 7). As expected, the racemic
D
https://doi.org/10.1021/jacs.1c06557
J. Am. Chem. Soc. XXXX, XXX, XXX−XXX

Journal of the American Chemical Society
pubs.acs.org/JACS
Communication
configurationally stable form. These results demonstrate a
promising route to the construction of new chiral molecular
devices for advanced applications in catalysis, molecular
recognition, and material sciences.
ABBREVIATIONS
■
NMR, nuclear magnetic resonance; CD, circular dichroism;
HPLC, high performance liquid chromatography
REFERENCES
■
ASSOCIATED CONTENT
■
(1) (a) Jamieson, E. M. G.; Modicom, F.; Goldup, S. M. Chirality in
rotaxanes and catenanes. Chem. Soc. Rev. 2018, 47, 5266−5311.
(b) Jamieson, E. M. G.; Goldup, S. M. Chirality Makes a Move. Nat.
Chem. 2019, 11, 765−767. (c) Maynard, J. R. J.; Goldup, S. M.
Strategies for the Synthesis of Enantiopure Mechanically Chiral.
Molecules. Chem. 2020, 6, 1914−1932.
sı
* Supporting Information
The Supporting Information is available free of charge at
https://pubs.acs.org/doi/10.1021/jacs.1c06557.
Experimental details, spectroscopic and X-ray crystallog-
raphy data of the [2]catenane, computational methods.
and Cartesian coordinates of the optimized diastereo-
meric complexes (PDF)
(2) Evans, N. H. Chiral Catenanes and Rotaxanes: Fundamentals and
Emerging Applications. Chem. - Eur. J. 2018, 24, 3101−3112.
(3) (a) Tian, C.; Fielden, S. D. P.; Perez-Saavedra, B.; Vitorica-
Yrezabal, I. J.; Leigh, D. A. Single-Step Enantioselective Synthesis of
Mechanically Planar Chiral [2]Rotaxanes Using a Chiral Leaving
Group Strategy. J. Am. Chem. Soc. 2020, 142, 9803−9808. (b) Jinks, M.
A.; de Juan, A.; Denis, M.; Fletcher, C. J.; Galli, M.; Jamieson, E. M. G.;
Modicom, F.; Zhang, Z.; Goldup, S. M. Stereoselective Synthesis of
Mechanically Planar Chiral Rotaxanes. Angew. Chem., Int. Ed. 2018, 57,
14806−14810. (c) Bordoli, R. J.; Goldup, S. M. An Efficient Approach
to Mechanically Planar Chiral Rotaxanes. J. Am. Chem. Soc. 2014, 136,
4817−4820. (d) Imayoshi, A.; Lakshmi, B. V.; Ueda, Y.; Yoshimura, T.;
Matayoshi, A.; Furuta, T.; Kawabata, T. Enantioselective Preparation of
Mechanically Planar Chiral Rotaxanes by Kinetic Resolution Strategy.
Nat. Commun. 2021, 12, 404. (e) Makita, Y.; Kihara, N.; Nakakoji, N.;
Takata, T.; Inagaki, S.; Yamamoto, C.; Okamoto, Y. Catalytic
Asymmetric Synthesis and Optical Resolution of Planar Chiral
Rotaxane. Chem. Lett. 2007, 36, 162−163.
Accession Codes
CCDC 2091887 contains the supplementary crystallographic
data for this paper. These data can be obtained free of charge via
www.ccdc.cam.ac.uk/data_request/cif, or by emailing data_
request@ccdc.cam.ac.uk, or by contacting The Cambridge
Crystallographic Data Centre, 12 Union Road, Cambridge
CB2 1EZ, UK; fax: +44 1223 336033.
AUTHOR INFORMATION
■
Corresponding Author
Fabien B. L. Cougnon − Department of Organic Chemistry,
University of Geneva, 1211 Geneva, Switzerland; Present
Address: School of Chemistry, National University of
Ireland, University Road, Galway, H91 TK33, Ireland;
orcid.org/0000-0003-4487-8707;
(4) Denis, M.; Lewis, J. E. M.; Modicom, F.; Goldup, S. M. An
Auxiliary Approach for the Stereoselective Synthesis of Topologically
Chiral Catenanes. Chem. 2019, 5, 1512−1520.
(5) (a) Leigh, D. A.; Marcos, V.; Wilson, M. R. Rotaxane Catalysts.
ACS Catal. 2014, 4, 4490−4497. (b) Heard, A. W.; Goldup, S. M.
Synthesis of a Mechanically Planar Chiral Rotaxane Ligand for
Enantioselective Catalysis. Chem. 2020, 6, 994−1006.
Email: fabien.cougnon@nuigalway.ie
Authors
(6) (a) Pairault, N.; Niemeyer, J. Chiral Mechanically Interlocked
Molecules − Applications of Rotaxanes, Catenanes and Molecular
Knots in Stereoselective Chemosensing and Catalysis. Synlett 2018, 29,
689−698. (b) Hirose, K.; Ukimi, M.; Ueda, S.; Onoda, C.; Kano, R.;
Tsuda, K.; Hinohara, Y.; Tobe, Y. The Asymmetry is Derived from
Mechanical Interlocking of Achiral Axle and Achiral Ring Components
− Syntheses and Properties of Optically Pure [2]Rotaxanes. Symmetry
2018, 10, 20. (c) Lim, J. Y. C.; Marques, I.; Félix, V.; Beer, P. D.
Enantioselective Anion Recognition by Chiral Halogen-Bonding
[2]Rotaxanes. J. Am. Chem. Soc. 2017, 139, 12228−12239.
Kenji Caprice − Department of Organic Chemistry, University
of Geneva, 1211 Geneva, Switzerland
Dávid Pál − Department of Organic Chemistry, University of
Geneva, 1211 Geneva, Switzerland
Céline Besnard − Laboratory of Crystallography, University of
Geneva, 1211 Geneva, Switzerland; orcid.org/0000-0001-
5699-9675
Bartomeu Galmés − Department de Química, Universitat de les
Illes Balears, 07122 Palma de Mallorca, Baleares, Spain
Antonio Frontera − Department de Química, Universitat de les
Illes Balears, 07122 Palma de Mallorca, Baleares, Spain;
orcid.org/0000-0001-7840-2139
(7) (a) David, A. H. G.; Casares, R.; Cuerva, J. M.; Campana, A. G.;
̃
Blanco, V. A [2]Rotaxane-Based Circularly Polarized Luminescence
Switch. J. Am. Chem. Soc. 2019, 141, 18064−18074. (b) Ishiwari, F.;
Nakazono, K.; Koyama, Y.; Takata, T. Induction of Single-Handed
Helicity of Polyacetylenes Using Mechanically Chiral Rotaxanes as
Chiral Sources. Angew. Chem., Int. Ed. 2017, 56, 14858−14862.
(8) McArdle, C. P.; Van, S.; Jennings, M. C.; Puddephatt, R. J. Gold(I)
Macrocycles and Topologically Chiral [2]Catenanes. J. Am. Chem. Soc.
2002, 124, 3959−3965.
Complete contact information is available at:
https://pubs.acs.org/10.1021/jacs.1c06557
Notes
The authors declare no competing financial interest.
(9) Theil, A.; Mauve, C.; Adeline, M.-T.; Marinetti, A.; Sauvage, J.-P.
Phosphorus-Containing [2]Catenanes as an Example of Interlocking
Chiral Structures. Angew. Chem., Int. Ed. 2006, 45, 2104−2107.
(10) Bruns, C. J.; Stoddart, J. F. The Nature of the Mechanical Bond:
From Molecules to Machines; Wiley, 2016.
(11) This unusual stereogenic element was formally recognized in
2018 by Goldup, who named it co-conformationally mechanically axial
chirality (see ref 1), but it has not yet received significant attention.
(12) For selected examples, see: (a) Dietrich-Buchecker, C. O.;
Sauvage, J. P.; Kern, J. M. Templated Synthesis of Interlocked
Macrocyclic Ligands: the Catenands. J. Am. Chem. Soc. 1984, 106,
3043−3045. (b) Ashton, P. R.; Ballardini, R.; Balzani, V.; Credi, A.;
Gandolfi, M. T.; Menzer, S.; Pérez-García, L.; Prodi, L.; Stoddart, J. F.;
ACKNOWLEDGMENTS
■
We are grateful to the Department of Organic Chemistry at the
University of Geneva and the MICIU/AEI of Spain (project
CTQ2017-85821-R FEDER funds) for financial support. B.G.
thanks the MICIU for a predoctoral fellowship. We warmly
thank Dr. Rosario Scopelliti and Dr. Pascal Schouwink from
EPFL (Lausanne) for letting us perform measurements with
their diffractometer. We also thank Dr. Julien Genovino, Dr.
Jasmine Viger-Gravel, and Marion Pupier for helpful comments
on the manuscript.
E
https://doi.org/10.1021/jacs.1c06557
J. Am. Chem. Soc. XXXX, XXX, XXX−XXX

Journal of the American Chemical Society
pubs.acs.org/JACS
Communication
Venturi, M.; White, A. J. P.; Williams, D. J. Molecular Meccano. 4. The
Self-Assembly of [2]Catenanes Incorporating Photoactive and Electro-
active π-Extended Systems. J. Am. Chem. Soc. 1995, 117, 11171−11197.
(c) Cao, D.; Amelia, M.; Klivansky, L. M.; Koshkakaryan, G.; Khan, S.
I.; Semeraro, M.; Silvi, S.; Venturi, M.; Credi, A.; Liu, Y. Probing Donor-
Acceptor Interactions and Co-Conformational Changes in Redox
Active Desymmetrized [2]Catenanes. J. Am. Chem. Soc. 2010, 132,
1110−1122. (d) Huang, B.; Santos, S. M.; Felix, V.; Beer, P. D. Sulfate
Anion-templated Assembly of a [2]Catenane. Chem. Commun. 2008,
4610−4612. (e) Byrne, J. P.; Blasco, S.; Aletti, A. B.; Hessman, G.;
Gunnlaugsson, T. Formation of Self-Templated 2,6-Bis(1,2,3-triazol-4-
yl)pyridine [2]Catenanes by Triazolyl Hydrogen Bonding: Selective
Anion Hosts for Phosphate. Angew. Chem., Int. Ed. 2016, 55, 8938−
8943. (f) Mitra, R.; Thiele, M.; Octa-Smolin, F.; Letzel, M. C.;
Niemeyer, J. A Bifunctional Chiral [2]Catenane Based on 1,1′-
Binaphthyl-phosphates. Chem. Commun. 2016, 52, 5977−5980.
(g) Deng, Y.; Lai, S. K.-M.; Kong, L.; Au-Yeung, H. Y. Fine-tuning of
the Optical Output in a Dual Responsive Catenane Switch. Chem.
Commun. 2021, 57, 2931−2934.
(13) (a) Wang, C.-Y.; Wu, G.; Jiao, T.; Shen, L.; Ma, G.; Pan, Y.; Li, H.
Precursor Control over the Self-assembly of [2]Catenanes via
Hydrazone Condensation in Water. Chem. Commun. 2018, 54,
5106−5109. (b) Wu, G.; Wang, C. Y.; Jiao, T.; Zhu, H.; Huang, F.;
Li, H. Controllable Self-Assembly of Macrocycles in Water for Isolating
Aromatic Hydrocarbon Isomers. J. Am. Chem. Soc. 2018, 140, 5955−
5961. (c) Caprice, K.; Pupier, M.; Kruve, A.; Schalley, C. A.; Cougnon,
F. B. L. Imine-based [2]Catenanes in Water. Chem. Sci. 2018, 9, 1317−
1322.
(20) (a) Fujita, M.; Ibukuro, F.; Hagihara, H.; Ogura, K. Quantitative
Self-assembly of a [2]Catenane from Two Preformed Molecular Rings.
Nature 1994, 367, 720−723. (b) Au-Yeung, H. Y.; Pantos,̧ G. D.;
Sanders, J. K. M. Dynamic Combinatorial Synthesis of a Catenane
Based on Donor−Acceptor Interactions in Water. Proc. Natl. Acad. Sci.
U. S. A. 2009, 106, 10466−10470. (c) Cougnon, F. B. L.; Au-Yeung, H.
Y.; Pantos,̧ G. D.; Sanders, J. K. M. Exploring the Formation Pathways
of Donor−Acceptor Catenanes in Aqueous Dynamic Combinatorial
Libraries. J. Am. Chem. Soc. 2011, 133, 3198−3207. (d) Li, H.; Zhang,
H.; Lammer, A. D.; Wang, M.; Li, X.; Lynch, V. M.; Sessler, J. L.
Quantitative Self-assembly of a Purely Organic Three-dimensional
Catenane in Water. Nat. Chem. 2015, 7, 1003−1008.
(21) (a) Schill, G. Catenanes, Rotaxanes, and Knots; Academic Press:
New York, 1971. (b) Kruve, A.; Caprice, K.; Lavendomme, R.;
Wollschläger, J. M.; Schoder, S.; Schröder, H. V.; Nitschke, J. R.;
Cougnon, F. B. L.; Schalley, C. A. Ion-Mobility Mass Spectrometry for
the Rapid Determination of the Topology of Interlocked and Knotted
Molecules. Angew. Chem., Int. Ed. 2019, 58, 11324−11328.
̌
́
(22) (a) Miljanic, O. S.; Dichtel, W. R.; Khan, S. I.; Mortezaei, S.;
Heath, J. R.; Stoddart, J. F. Structural and Co-conformational Effects of
Alkyne-Derived Subunits in Charged Donor−Acceptor [2]Catenanes.
J. Am. Chem. Soc. 2007, 129, 8236−8246. (b) Deleuze, M. S.; Leigh, D.
A.; Zerbetto, F. How Do Benzylic Amide [2]Catenane Rings Rotate? J.
Am. Chem. Soc. 1999, 121, 2364−2379. (c) Leigh, D. A.; Troisi, A.;
Zerbetto, F. A Quantum-Mechanical Description of Macrocyclic Ring
Rotation in Benzylic Amide [2]Catenanes. Chem. - Eur. J. 2001, 7,
1450−1454.
(23) (a) Perrin, C. L.; Dwyer, T. J. Application of Two-dimensional
NMR to Kinetics of Chemical Exchange. Chem. Rev. 1990, 90, 935−
967. (b) Pons, M.; Millet, O. Dynamic NMR Studies of Supramolecular
Complexes. Prog. Nucl. Magn. Reson. Spectrosc. 2001, 38, 267−324.
(24) Hatano, M.; Maki, T.; Moriyama, K.; Arinobe, M.; Ishihara, K.
Pyridinium 1,1′-Binaphthyl-2,2′-disulfonates as Highly Effective Chiral
Brønsted Acid−Base Combined Salt Catalysts for Enantioselective
Mannich-Type Reaction. J. Am. Chem. Soc. 2008, 130, 16858−16860.
(25) Sodium (1R)-(−)-10-camphorsulfonate and sodium dehydroi-
soandrosterone 3-sulfate did not elicit any clear response in NMR and
CD spectroscopies. TRISPHAT, another enantiopure anion commonly
used for chiral resolution, is not water-soluble. (a) Lacour, J.;
Ginglinger, C.; Grivet, C.; Bernardinelli, G. Synthesis and Resolution
of the Configurationally Stable Tris(tetrachlorobenzenediolato)-
phosphate(V) Ion. Angew. Chem., Int. Ed. Engl. 1997, 36, 608−610.
(b) Lacour, J.; Goujon-Ginglinger, C.; Torche-Haldimann, S.; Jodry, J.
J. Efficient Enantioselective Extraction of Tris(diimine)ruthenium(II)
Complexes by Chiral, Lipophilic TRISPHAT Anions. Angew. Chem.,
Int. Ed. 2000, 39, 3695−3697.
(14) (a) Dietrich-Buchecker, C. O.; Edel, A.; Kintzinger, J. P.;
́
̀
́
Sauvage, J. P. Synthese et Etude d’un Catenate de Cuivre Chiral
̀
Comportant Deux Anneaux Coordinant a 27 Atomes. Tetrahedron
1987, 43, 333−344. (b) Burchell, T. J.; Eisler, D. J.; Puddephatt, R. J. A
Chiral [2]Catenane Self-assembled from meso-Macrocycles of
Palladium(II). Dalton Trans. 2005, 268−272. In this latter example,
the right and left sides of the macrocycles are only differentiated by the
chirality of the 1,1′-binaphthyl group (R or S). It is important to point
out that the two sides may be inequivalent even if they are mirror
images.
(15) A related phenomenon was observed in Vignon, S. A.; Wong, J.;
Tseng, H.-R.; Stoddart, J. F. Helical Chirality in Donor-Acceptor
Catenanes. Org. Lett. 2004, 6, 1095−1098.
(16) This behavior is comparable to helicity switching: (a) Le Bailly,
B. A. F.; Clayden, J. Dynamic Foldamer Chemistry. Chem. Commun.
2016, 52, 4852−4863. (b) Miyake, H.; Tsukube, H. Coordination
Chemistry Strategies for Dynamic Helicates: Time-programmable
Chirality Switching with Labile and Inert Metal Helicates. Chem. Soc.
Rev. 2012, 41, 6977−6991.
(17) For other examples of co-conformational symmetry breaking,
see: (a) Dommaschk, M.; Echavarren, J.; Leigh, D. A.; Marcos, V.;
Singleton, T. A. Dynamic Control of Chiral Space Through Local
Symmetry Breaking in a Rotaxane Organocatalyst. Angew. Chem., Int.
Ed. 2019, 58, 14955−14958. (b) Gell, C. E.; McArdle-Ismaguilov, T.
A.; Evans, N. H. Modulating the Expression of Chirality in a
Mechanically Chiral Rotaxane. Chem. Commun. 2019, 55, 1576−
1579. (c) Mochizuki, Y.; Ikeyatsu, K.; Mutoh, Y.; Hosoya, S.; Saito, S.
Synthesis of Mechanically Planar Chiral rac-[2]Rotaxanes by
Partitioning of an Achiral [2]Rotaxane: Stereoinversion Induced by
Shuttling. Org. Lett. 2017, 19, 4347−4350.
(26) The enantiomerization rates are similar in D2O and in a mixture
D2O/CD3CN 1:1 (Figures S14 and S15).
(18) The amplification of a mechanically planar chiral [2]rotaxane was
previously realized by following a similar approach: Corra, S.; de Vet,
C.; Groppi, J.; La Rosa, M.; Silvi, S.; Baroncini, M.; Credi, A. Chemical
On/Off Switching of Mechanically Planar Chirality and Chiral Anion
Recognition in a [2]Rotaxane Molecular Shuttle. J. Am. Chem. Soc.
2019, 141, 9129−9133.
(19) (a) Jin, Y.; Yu, C.; Denman, R. J.; Zhang, W. Recent Advances in
Dynamic Covalent Chemistry. Chem. Soc. Rev. 2013, 42, 6634−6654.
(b) Corbett, P. T.; Leclaire, J.; Vial, L.; West, K. R.; Wietor, J.-L.;
Sanders, J. K. M.; Otto, S. Dynamic Combinatorial Chemistry. Chem.
Rev. 2006, 106, 3652−3711.
F
https://doi.org/10.1021/jacs.1c06557
J. Am. Chem. Soc. XXXX, XXX, XXX−XXX