Stereoselective synthesis of a topologically chiral molecule: The trefoil knot

Article abstract of DOI:10.1002/anie.200460250

Tying nice neat knots is demonstrated on a molecular level with the stereoselective synthesis of a trefoil knot. The key reaction was the completely stereoselective formation of a double-stranded helical precursor from two pinene-bipyridine threads around two Cu^I centers (the pinene moieties contain stereogenic centers). The helix was then transformed through several steps into 1; demetallation of the complex 1 yielded the configurationally predetermined free trefoil knot.

Full text of DOI:10.1002/anie.200460250

Communications
Supramolecular Chemistry
Stereoselective Synthesis of a Topologically Chiral
Molecule: The Trefoil Knot**
Laure-Emmanuelle Perret-Aebi,
Alexander von Zelewsky,* Christiane Dietrich-
Buchecker, and Jean-Pierre Sauvage
Topological chirality of a molecule is realized when any
representation of its graph is topologically distinct from its
mirror image, that is, if it cannot be converted into its mirror
image by continuous deformation in 3D space.[1] This
property implies that the graph of the molecule is nonplanar.
Molecular systems with an intrinsically nonplanar graph are
scarce. Their graphs can be contracted to Kuratowskiꢀs graphs
K5 (the complete graph on five vertices) or K3,3 (the complete
bipartite graph on two sets of three vertices each).[2–4] Many
examples of such systems are known, with the 3-rung Möbius
strip prepared more than 20 years ago by Walba et al. being a
particularly representative example.[5]
Interlocking rings (catenanes) and knots have extrinsically
nonplanar graphs. As discussed by Schill,[6] an achiral
[2]catenane can be desymmetrized by a suitable substitution
of its constitutive rings to give a topologically chiral species.
Such catenanes, which contain two oriented rings, have been
prepared in the past.[7] It has even been possible to resolve
them analytically by chiral chromatography.[8] Contrary to a
[2]catenane, a trefoil knot is unconditionally chiral; the latter
object is topologically chiral without having to orient rings.
These prototypical nonplanar systems are represented in
Figure 1.
Molecular knots were prepared some time ago using a
copper(i)-templated strategy.[9] They were resolved and crys-
tallized and their absolute configuration was thereby deter-
mined.[10] More recently, another family of molecular knots
has been elaborated by Vögtle and co-workers with their
synthesis relying on original sets of hydrogen bonds.[11] The
enantiomers of some of these knots and their derivatives were
also resolved by chiral chromatography in a collaborative
project between Vögtleꢀs and Okamotoꢀs groups.[12] Two other
examples of synthetic knots have been described,[13–16] includ-
ing an “open” knotted species constructed around an
octahedral metal center as a template.[14]
[*] L.-E. Perret-Aebi, Prof. Dr. A. von Zelewsky
Departement de Chimie, UniversitØ de Fribourg
1700 Fribourg (Switzerland)
Fax: (+41)26-300-9738
E-mail: alexander.vonzelewsky@unifr.ch
Dr. C. Dietrich-Buchecker, Dr. J.-P. Sauvage
Laboratoire de Chimie Organo-MinØrale, UMR 7513
UniversitØ Louis Pasteur, Institut Le Bel
4 rue Blaise Pascal, 67070 Strasbourg (France)
[**] We thank the Swiss National Science Foundation and the CNRS
(CERC3 project on Toplogical Chirality) for financial support.
Supporting information for this article is available on the WWW
under http://www.angewandte.org or from the author.
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DOI: 10.1002/anie.200460250
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Chemie
Figure 1. a) A [2]catenane is topologically achiral; b) through orienta-
tion of both rings, a chiral object is obtained; c) the trefoil knot is the
prototype of topologically chiral objects.
Herein, we report the stereoselective preparation of a
topologically chiral compound, a trefoil knot, from two
molecular threads that are chiral in the Euclidian sense. The
present report is concerned with the conversion of classical
(or Euclidian) chirality into topological chirality. The princi-
ple of the synthesis is depicted in Figure 2. The trefoil knot is
constructed around two copper(i) centers with the chiral
ligand 1,3-bis([5’,6’]-pinene-2,2’-bipyridin-2-yl)benzene (I),[17]
which contains stereogenic carbon centers in the pinene
moieties. In principle, two diastereomeric forms are possible
upon formation of the trefoil knot. However, our synthesis
proceeds completely stereoselectively with only one of the
two different topological enantiomers being obtained.
The strategy for the stereoselective preparation of the
knot takes advantage of the template effect of copper(i) and
of the properties of the bis(pinene-bipyridine) ligand, which
induces chirality at the metal centers (Figure 3). The molec-
ular frame for the present trefoil knot is based on the
CHIRAGEN family, which is a class of ligands developed by
some of us in recent years.[18] The molecule 1, whose synthesis
was reported recently,[17] consists of two 2,2’-bipyridine units
connected through a m-phenylene bridge. The CH2 groups in
the pinene moieties adjacent to the pyridine rings (indicated
by arrows in Figure 3) contain two diastereotopic protons.
Alkylation at these position proceeds diastereoselectively to
yield the dialkylated ligand 2.
Figure 2. The molecular thread I incorporates two bidentate chelating
units with each chelate being chiral; the red dot represents the cop-
per(i) atom. In the course of the complexation reaction, only one type
of double-stranded helix II is formed (with P or M configuration). The
appropriate connections will afford the trefoil knot enantioselectively
from I. Although I, IIM, and IIp are geometrically chiral, they are topolog-
ically achiral. By contrast, III is bothgeometrically and topologically
chiral.
Ligand 2 forms a double-stranded helix 3 around CuI ions
in a complexation reaction. As observed by UV/Vis spectros-
copy and visually from the formation of a deep red complex,
the dinuclear complex 3 is formed rapidly and quantitatively.
The ESI mass spectrum shows only one peak at m/z =
1070.53. The 1H NMR spectrum indicates a C2-symmetric
arrangement of the ligands (Figure 4a). Furthermore, there is
strong deshielding (d = 8.90–10.19 ppm) of the aromatic
proton (a) in the bridge. The presence of only one well-
defined peak for this proton indicates a very high percentage
(> 95%) of formation of the double helix 3 (Figure 4).
Figure 3. The CHIRAGEN family of ligands used for the construction
of the molecular knot (the arrow in 1 indicates the diastereotopic pro-
tons).
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Communications
Figure 6. CD spectrum (De=molar circular dichroism) of the left-
handed knotted system 4.
product can be remetallated in a rapid reaction (seconds) to
yield a product which is identical to 4. The 1H NMR spectrum
of 5 shows broad signals at room temperature, which we
believe is caused by reptation (a snakelike large-scale motion
of entangled molecular chains) within the molecule, as
observed previously for another molecular trefoil knot.[16]
The ESI mass spectrum displays a peak for the molecular
ion at m/z = 1964.22 as well as a number of fragmentation
products. As opposed to the dialkylated ligand 2, molecule 5
shows a pronounced signal in its CD spectrum in the range
280–340 nm. This arises from a relatively compact arrange-
ment of the bipyridine units which leads to through-space
coupling of the p–p* transitions, as with the metallated
species.
Unfortunately, we were not able to obtain crystals of
either 3 or 4 that were suitable for X-ray crystallographic
studies. Nevertheless, the crystal structure of a double helix
prepared from 1 and two silver(I) ions[20] was recently
obtained. The experimental evidence for the successful
synthesis of the trefoil knot 5 and its precursor CuI complex
4 is very strong. The mass and chiroptical behavior of 3 and 4
indicate very clearly the presence of the two compounds.
In conclusion, we have demonstrated the stereoselective
synthesis of a topologically chiral molecule. The reaction
sequence is based on the completely stereoselective forma-
tion of a double-stranded helical precursor from two open-
chain chelates, which incorporate the appropriate chiral
groups.[20] The transformation of the M helix 3 to the left-
handed knot 5 corresponds to the conversion of Euclidian
chirality into topological chirality.
Figure 4. 1H NMR spectra of a) complex 3 and b) the knotted system
4 before hydrogenation. Small impurity signals (intensityꢀ1%)
around d=10 ppm are from unidentified side products.
The circular dichroism (CD) spectrum, with a positive
exciton-couplet, gives the absolute configuration L at the
individual copper centers and thus induces an M configura-
tion in the double stranded helix 3, as expected from Corey–
Pauling–Koltun (CPK) molecular models.
A ring-closing metathesis (RCM)[19] reaction is then
applied for the formation of the knotted system (Figure 5).
Figure 5. The strategy for the construction of the knot; the knotted
system is obtained through a RCM reaction of 3.
Received: April 7, 2004 [Z460250]
RCM yields three isomers (from E and Z configurations at
the double bonds) in 74% total yield. Catalytic hydrogena-
tion (Pd/C (20%), H2 (3 bar), 16 h) leads to the saturated
compound 4 in quantitative yield. The ESI mass spectrum
shows one peak at m/z = 1038.50. The 1H NMR spectrum
again indicates C2 symmetry and is very similar to that of the
open form of the double-helix precursor 3, except that there
are no signals observed for the protons of the double bonds.
The CD spectrum of compound 4 is also very similar to that of
the open form of the double helix 3 (Figure 6).
Keywords: chirality · copper · helical structures · N ligands ·
template synthesis
.
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