Efficient synthesis of a molecular knot by copper(I)-induced formation of the precursor followed by ruthenium(II)-catalysed ring closing metathesis

Article abstract of DOI:10.1039/a704970f

A double-stranded helix constructed around two copper(I) centres used as templates and bearing four terminal alkenes, is converted into a trefoil knot in 74% yield by ruthenium(II)-catalysed ring closing methathesis (RCM); the cyclic alkenes can be quanti

Full text of DOI:10.1039/a704970f

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Efficient synthesis of a molecular knot by copper(i)-induced formation of the
precursor followed by ruthenium(ii)-catalysed ring closing metathesis
Christiane Dietrich-Buchecker, Gwe´nae¨l Rapenne and Jean-Pierre Sauvage*
Laboratoire de Chimie Organo-Mine´rale, URA 422 CNRS, Universite´ Louis Pasteur, Institut Le Bel, 4, rue Blaise Pascal,
F-67070 Strasbourg, France
A double-stranded helix constructed around two copper(I)
centres used as templates and bearing four terminal alkenes,
is converted into a trefoil knot in 74% yield by ruthenium(II)-
catalysed ring closing methathesis (RCM); the cyclic alkenes
can be quantitatively reduced by catalytic hydrogenation to
afford the copper(I)-complexed 82-membered knotted ring.
scribed,6 but we still looked for a more efficient and chemically
milder method. The ring-closing metathesis approach (RCM)7
which we now describe seems to be close to ideal: not only is the
yield excellent considering the complexity of the reaction but
the procedure takes place under very gentle conditions (without
any acid or base, in CH2Cl2 at room temp.).
The strategy (Fig. 1) relies on (i) quantitative formation and
high stability of the helical precursor composed of copper(i)
bisphenanthroline units with 1,3-phenylene linkers between the
phenanthroline nuclei,5c,6 and (ii) the highly efficient RCM
methodology developed by Grubbs and coworkers.7
Ligand 2 was obtained in 97% yield by reaction of 1 with
2-(2-chloroethoxy)ethanol in DMF at 80 °C, in the presence of
Cs2CO3. It could be quantitatively converted to 3 by generating
the dialcoholate with NaH and reacting it with an excess of allyl
bromide in refluxing THF. The helical precursor 42+ was
In molecular biology, knots constructed on double-stranded
DNA have been described more than twenty years ago.1
Recently, the trefoil knot, but also more complex topologies,
have been generated from single-stranded DNA.2 Some pro-
teins have also been shown to adopt knotted topologies.3 The
planned synthesis of chemical knots was first reported a few
years ago,4 but clearly the yield had to be increased both for the
synthetic challenge that this improvement represented and for
the interesting properties of this new family of compounds.5 A
more preparative procedure (30% yield) was recently de-
H
[Ru]
2
2
2
(a)
Fig. 1 Synthetic strategy. Two coordinating fragments bearing terminal
alkenes are gathered and interlaced around two copper(i) centres. RCM with
ruthenium catalyst affords the knot.
1
2
3
(b)
Z
(c)
Cu+
Cu+
Z
10
9
8
7
6
5
4
3
d
2+
2+
2+
4
5
6
Fig. 3 1H NMR spectra of (a) the helical precursor 42+ with the signals
corresponding to the four terminal alkenes (5), (b) the trefoil knot 52+ with
the signals corresponding to the two alkenes incorporated in the molecule
(2) and (c) the trefoil knot 62+ after catalytic reduction of the alkenes
Fig. 2 Chemical structure of the organic precursors and of the knots
Chem. Commun., 1997
2053

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formed quantitatively by the classical way: addition under argon
of [Cu(MeCN)4]PF6 dissolved in MeCN onto a solution of the
bis-chelate 3. The metathesis was catalysed by
[RuCl2{P(C6H11)3}2(NCHPh)] (0.05 mol. equiv.) at a substrate
concentration of 0.01 m in CH2Cl2 at room temp. The double
coupling of the terminal alkenic groups afforded the trefoil knot
52+ in 74% yield after column chromatography (Fig. 2). The
only other products were oligomers arising from intermolecular
metathesis reactions.
their specific properties possible. It can also be envisaged that
the two alkene functionalities of 52+, disposed in an antipodal
fashion, can be utilized for further functionalization.
We thank the CNRS for financial support and the French
Ministry of Research for a fellowship to G. R.
Footnote and References
* E-mail: sauvage@chimie.u-strasbg.fr
The dicopper(i) trefoil knot 52+ is thus obtained in seven steps
from commercially available 1,10-phenanthroline, with an
overall yield of 35%.
1 L. F. Liu, R. E. Depew and J. C. Wang, J. Mol. Biol., 1976, 106, 439.
2 S. M. Du, B. D. Stollar and N. C. Seeman, J. Am. Chem. Soc., 1995, 117,
1194.
3 C. Liang and K. Mislow, J. Am. Chem. Soc., 1995, 117, 4201 and
references therein.
4 C. O. Dietrich-Buchecker and J. P. Sauvage, Angew. Chem., Int. Ed.
Engl., 1989, 28, 189; C. O. Dietrich-Buchecker, J. Guilhem, C. Pascard
and J. P. Sauvage, Angew. Chem., Int. Ed. Engl., 1990, 29, 1154.
5 (a) C. O. Dietrich-Buchecker, J. P. Sauvage, J. P. Kintzinger, P. Maltese,
C. Pascard and J. Guilhem, New J. Chem., 1992, 16, 931; (b)
C. O. Dietrich-Buchecker, J. F. Nierengarten, J. P. Sauvage, N. Armaroli,
V. Balzani and L. De Cola, J. Am. Chem. Soc., 1993, 115, 11237; (c)
M. Meyer, A. M. Albrecht-Gary, C. O. Dietrich-Buchecker and
J. P. Sauvage, J. Am. Chem. Soc., 1997, 119, 4599; (d) C. O. Dietrich-
Buchecker, J. P. Sauvage, N. Armaroli, P. Ceroni and V. Balzani, Angew.
Chem., Int. Ed. Engl., 1996, 35, 1119.
The two cyclic alkenes remaining in 52+ appeared originally
as a mixture of cis and trans alkenes in a 80:20 ratio, according
1
to the H NMR spectrum. We thus obtained the cis–cis, cis–
trans and trans–trans products [compare the broad signals in
the spectrum in Fig. 3(b) to the narrow and well resolved ones
of the spectrum in Fig. 3(c)]. The alkene functionalities could be
easily and quantitatively reduced at room temp. by catalytic
hydrogenation in EtOH–CH2Cl2 (1:1) with Pd/C (5 mol% Pd).
Cyclisation and reduction could both be monitored by 1H NMR
spectroscopy in the alkenic region, the signals corresponding to
the cyclic alkenic groups in knot 52+ being sharply different
from those of the terminal alkenic groups in the precursor 42+
(see Fig. 3). Moreover, the 1H NMR spectrum of the knot after
reduction is clearly simplifed.
6 C. O. Dietrich-Buchecker, J. P. Sauvage, A. De Cian and J. Fischer,
J. Chem. Soc., Chem. Commun., 1994, 2231.
The knotted topology of 52+ could be unambiguously
established by 1H NMR spectroscopy, the signals of the
aromatic protons as well as those of the polyoxyethylenic chains
in the 3–4 ppm region being highly characteristic.8 Further
evidence was obtained from FABMS which confirmed the
absence of any starting material and displayed the expected
mass: a peak at 1965.3 corresponding to [5(PF6)]+ and a peak at
910.1 corresponding to 52+.
7 G. C. Fu and R. H. Grubbs, J. Am. Chem. Soc., 1992, 114, 5426;
A. Fu¨rstner and N. Kindler, Tetrahedron Lett., 1996, 37, 7005; B. Ko¨nig
and C. Horn, Synlett, 1996, 1013; B. Mohr, M. Weck, J. P. Sauvage and
R. H. Grubbs, Angew. Chem., Int. Ed. Engl., 1997, 36, 1308.
8 R. F. Carina, C. O. Dietrich-Buchecker and J. P. Sauvage, J. Am. Chem.
Soc., 1996, 118, 9110.
The here-described latest improvements now allow an easy
access to trefoil knots and hence render the extensive study of
Received in Basel, Switzerland, 10th July 1997; 7/04970F
2054
Chem. Commun., 1997