Copper(I)- or iron(II)-templated synthesis of molecular knots containing two tetrahedral or octahedral coordination sites

Article abstract of DOI:10.1021/ja982239+

Molecular trefoil knots have been prepared from metal-assembled precursors using the ring closing metathesis (RCM) cyclization methodology. The templating metal is either copper(I) or iron(II) and the coordinating fragments 1,10-phenanthroline or 2,2':6',2' '-terpyridine, respectively. The RCM approach, newly applied to the field of catehanes and knots, represents a spectacular synthetic improvement in terms of yield and experimental conditions (no high dilution required). The dicopper(I) trefoil knot has been synthesized in a 74% yield. A similar approach also led to the first knot constructed around two iron(II) bis(terpyridine) moieties, demonstrating that iron(II) can also be used as a highly efficient template. Moreover, for both Cu(I) and Fe(II) knots, it has been possible to quantitatively reduce the cyclic olefins formed during the macrocyclization by catalytic (Pd/C) hydrogenation. An X-ray structure of the double helix of iron(H) bis(1,2- bis(5-(5' '-methyl-2,2':6',2' '-terpyridinyl))ethane) is given which shows that the double-stranded helical precursor is well predisposed for the formation of a molecular knot.

Full text of DOI:10.1021/ja982239+

994
J. Am. Chem. Soc. 1999, 121, 994-1001
Copper(I)- or Iron(II)-Templated Synthesis of Molecular Knots
Containing Two Tetrahedral or Octahedral Coordination Sites
Gw e´ na e1 l Rapenne, Christiane Dietrich-Buchecker, and Jean-Pierre Sauvage*
Contribution from the Laboratoire de Chimie Organo-Min e´ rale, UMR 7513, CNRS,
UniVersit e´ Louis Pasteur, Institut Le Bel, 4 rue Blaise Pascal, 67070 Strasbourg, France
ReceiVed June 26, 1998
Abstract: Molecular trefoil knots have been prepared from metal-assembled precursors using the ring closing
metathesis (RCM) cyclization methodology. The templating metal is either copper(I) or iron(II) and the
coordinating fragments 1,10-phenanthroline or 2,2′:6′,2"-terpyridine, respectively. The RCM approach, newly
applied to the field of catenanes and knots, represents a spectacular synthetic improvement in terms of yield
and experimental conditions (no high dilution required). The dicopper(I) trefoil knot has been synthesized in
a 74% yield. A similar approach also led to the first knot constructed around two iron(II) bis(terpyridine)
moieties, demonstrating that iron(II) can also be used as a highly efficient template. Moreover, for both Cu(I)
and Fe(II) knots, it has been possible to quantitatively reduce the cyclic olefins formed during the
macrocyclization by catalytic (Pd/C) hydrogenation. An X-ray structure of the double helix of iron(II) bis-
(1,2-bis(5-(5"-methyl-2,2′:6′,2"-terpyridinyl))ethane) is given which shows that the double-stranded helical
precursor is well predisposed for the formation of a molecular knot.
Introduction
cedure was to use 1,3-phenylene groups as linkers between the
1
1-13
chelates. These spacers favor helical structures
and thus
Knots as molecular objects have been envisaged since the
allow quantitative formation of double-stranded helical dinuclear
complexes, used as precursors to the knots.
1
6
0’s, either in purely theoretical discussions or as real synthetic
2
targets. DNA-based knots have been identified more than two
3
4
The ring-closing metathesis of olefins (RCM), as recently
decades ago and prepared at will more recently. Knots have
1
4
also been found in proteins.5
developed by Grubbs and co-workers, represents a real
15
breakthrough in the field of large-ring synthesis. The utilization
of this methodology turned out to be surprisingly efficient as
far as the preparation of [2]-catenanes is concerned,16 leading
to almost quantitative yields of interlocking rings from open
chain diolefinic fragments. Preliminary work demonstrated that
trefoil knots could be obtained using the RCM approach.17
The use of transition metals as templates allowed us to prepare
a molecular trefoil knot a few years ago, although the pre-
parative procedure was extremely delicate and far from being
really preparative. Very recently, another strategy based on
6
aromatic acceptor-donor complexes has also produced small
quantities of a molecular trefoil knot.7
The present report deals with the use of RCM for synthesizing
molecular trefoil knots, following two markedly distinct ap-
proaches. One uses copper(I) as a template, leading to molecular
knots with two tetrahedral (or pseudotetrahedral) coordination
sites, in analogy with the previous strategies developed in our
In the course of the past few years, our original approach
has been continuously improved, by modifying various factors
of the precursors. In this way, sufficient amounts of the mole-
cules could be prepared so as to allow various physical studies
to be carried out. In particular, some of the compounds revealed
8
fascinating kinetic properties (inertness toward demetalation)
(10) Dietrich-Buchecker, C. O.; Sauvage, J. P.; Armaroli, N.; Ceroni,
and photochemical or electrochemical behavior.9 One of the
,10
P.; Balzani, V. Angew. Chem., Int. Ed. Engl. 1996, 35, 1119-1121.
(11) Williams, D. J.; Colquhoun, H. M.; O’Mahoney, C. A. J. Chem.
Soc., Chem. Commun. 1997, 2053-2054.
key factors to the dramatic improvement of the synthetic pro-
(
1) Frisch, H. L.; Wasserman, E. J. Am. Chem. Soc. 1961, 83, 3789-
795.
2) Schill, G. In Catenanes, Rotaxanes and Knots; Academic Press: New
(12) R u¨ ttimann, S.; Piguet, C.; Bernardinelli, G.; Bocquet, B.; Williams,
A. F. J. Am. Chem. Soc. 1992, 114, 4230-4237.
3
(
(13) Constable, E. C.; Hannon, M. J.; Tocher, D. A. J. Chem. Soc., Dalton
Trans. 1993, 1883-1890.
York, 1971. Schill, G.; Keller, U.; Fritz, H. Chem. Ber. 1983, 116, 3675-
3
1
1
784. Schill, G.; Doerjer, G.; Logemann, E.; Fritz, H. Chem. Ber. 1979,
12, 3603-3615. Schill, G.; Boeckmann, J. Tetrahedron 1974, 30, 1945-
957.
(14) Fu, G. C.; Grubbs, R. H. J. Am. Chem. Soc. 1992, 114, 5426-
5427. Grubbs, R. H.; Miller, S. J.; Fu, G. C. Acc. Chem. Res. 1995, 28,
446-452. Schwab, P.; Grubbs, R. H.; Ziller, J. W. J. Am. Chem. Soc. 1996,
118, 100-110.
(
(
(
3) Wang, J. C. J. Mol. Biol. 1971, 55, 523-533.
4) Seeman, N. C. Acc. Chem. Res. 1997, 30, 357-363.
5) Liang, C.; Mislow, K. J. Am. Chem. Soc. 1994, 116, 11189-11190.
(15) F u¨ rstner, A.; Kindler, N. Tetrahedron Lett. 1996, 37, 7005-7008.
K o¨ nig, B.; Horn, C. Synlett 1996, 1013-1014. Marsella, M. J.; Maynard,
H. D.; Grubbs, R. H. Angew. Chem., Int. Ed. Engl. 1997, 36, 1101-1103.
Yang, Z.; He, Y.; Vourloumis, D.; Vallberg, M.; Nicolaou, K. C. Angew.
Chem., Int. Ed. Engl. 1997, 36, 166-168. Armstrong, S. K. J. Chem. Soc.,
Perkin Trans. 1998, 371-388. Pariya, C.; Jayaprakash, K. N.; Sarkar, A.
Coord. Chem. ReV. 1998, 168, 1-48. Grubbs, R. H.; Chang, S. Tetrahedron
1998, 54, 4413-4450.
(16) Mohr, B.; Weck, M.; Sauvage, J. P.; Grubbs, R. H. Angew. Chem.,
Int. Ed. Engl. 1997, 36, 1308-1310.
(17) Dietrich-Buchecker, C. O.; Rapenne, G.; Sauvage, J. P. J. Chem.
Soc., Chem. Commun. 1997, 2053-2054.
Liang, C.; Mislow, K. J. Am. Chem. Soc. 1995, 117, 4201-4213.
(6) Dietrich-Buchecker, C. O.; Sauvage, J. P. Angew. Chem., Int. Ed.
Engl. 1989, 28, 189-192. Dietrich-Buchecker, C. O.; Guilhem, J.; Pascard,
C.; Sauvage, J. P. Angew. Chem., Int. Ed. Engl. 1990, 29, 1154-1156.
(7) Ashton, P. R.; Matthews, O. A.; Menzer, S.; Raymo, F. M.; Spencer,
N.; Stoddart, J. F.; Williams, D. J. Liebigs Ann. Chem. 1997, 2485-2494.
8) Meyer, M.; Albrecht-Gary, A. M.; Dietrich-Buchecker, C. O.;
Sauvage, J. P. J. Am. Chem. Soc. 1997, 119, 4599-4607.
9) Dietrich-Buchecker, C. O.; Sauvage, J. P.; De Cian, A.; Fischer, J.
J. Chem. Soc., Chem. Commun. 1994, 2231-2232.
(
(
1
0.1021/ja982239+ CCC: $18.00 © 1999 American Chemical Society
Published on Web 01/26/1999

Synthesis of Molecular Knots
J. Am. Chem. Soc., Vol. 121, No. 5, 1999 995
Figure 1. Synthetic strategy. Two coordinating fragments are gathered
and interlaced around two metal centers. Each stringlike molecule
incorporates two chelating subunits and bears terminal olefins. The
metal template (black dot) is either Cu(I) or Fe(II). After RCM with a
ruthenium catalyst, the desired knot is obtained which contains two
tetrahedral or two octahedral coordination sites, respectively.
group. The second approach is based on iron(II) and 2,2′:6′,2"-
terpyridine (terpy) derived ligands, Fe(terpy)22 being known
for several decades to be a very stable complex.18 The knots
obtained by following this second strategy contain two pseu-
dooctahedral coordination sites of (terpy)2 type. It should be
stressed that copper(I) has been used extensively in our group
+
1
9
and others as a template to make various interlocking and
threaded structures, but very few other metals have been
used.2 A few years ago, the synthesis of a [2]-catenane based
0,21
2+
22
on a Ru(terpy)2 core was reported, but the preparative proce-
dure was far from satisfactory, in part due to the kinetic inertness
of the ruthenium complex once incorporated in the catenane
structure, thus preventing generation of the free ligand.
Results and Discussion
1
. Strategy. The synthesis principle is indicated in Figure 1.
It uses the template effect of metal ions to form a double helix
which, after double cyclization, leads to the trefoil knot.
The cyclization step has the synthetic advantage of dividing
by two the number of reaction centers involved during the ring
6
,9
closure procedure as compared to the classical method. In
the latter, four phenolic functions of the double helix are reacting
with four electrophilic carbons of the polyoxyethylenic diiodide
chain, thus involving eight reaction centers.
Figure 2. Chemical structure of the organic precursors and of the knots
in the phenanthroline-based series.
2
. Copper(I) as Template. Synthesis of the Precursor. By
reaction of the bis(phenanthroline) thread 1 with 2-(2-chloro-
ethoxy)ethanol in DMF at 80 °C in the presence of cesium
carbonate, ligand 2 was obtained in 97% yield (Figure 2). Bis-
1
2+
The H NMR spectrum of complex 4 is typical of a double
6,9
helical structure. In particular we can see the magnetic
influence of the phenanthroline cores on the anisyl groups,
leading to significant shielding of Hm (-1.3 ppm) and Ho (-1.4
ppm) protons of these groups (Figure 3a) as compared to the
free ligand.
Cyclization. The metathesis reaction was performed in
dichloromethane at room temperature, with a copper complex
(phenanthroline) 2 was then quantitatively converted into its
olefinic derivative 3, first by generating the dialcoholate with
NaH and then reacting the latter with a large excess of allyl
bromide in refluxing THF.
2+
The helical precursor 4 was obtained quantitatively in the
9
classical way by adding Cu(MeCN)4PF6 onto a solution of the
2+
4
concentration of 0.01 M. The catalyst was ruthenium(II)
dichloride phenylmethylene bis(tricyclohexylphosphine) [RuCl2-
bischelating thread 3 under argon.
(
PCy3)2(dCHPh)].
After 16 h of reaction, purification by chromatography yielded
4% of the knotted complex 5 . H NMR spectroscopy (Figure
b) showed total disappearance of the starting material. The
(
18) IUPAC Chemical Data Series No. 17; McBryde, W. A. E., Ed.;
Pergamon: Oxford, U.K., 1978. A critical review of equilibrium data for
proton and metal complexes of 1,10-phenanthroline, 2,2′-bipyridyl, and
related compounds. Constable, E. C. AdV. Inorg. Chem. Radiochem. 1986,
2+
1
7
3
3
0, 69-121.
(19) Momenteau, M.; Loock, B.; Le Bras, F. Tetrahedron Lett. 1994,
signals of the terminal olefins (5.31 and 5.20 ppm) had vanished,
whereas those of cyclic olefins had appeared at lower field (6.38
and 6.24 ppm).
3
5, 3289-3292. Gruter, G. J. M.; De Kanter, F. J. J.; Markies, P. R.;
Nomoto, T.; Akkerman, O. S.; Bickelhaupt, F. J. Am. Chem. Soc. 1993,
15, 12179-12180.
20) Fujita, M.; Ibukuro, F.; Seki, H.; Kamo, O.; Imanari, M.; Ogura,
1
(
Mass spectroscopy also confirmed the absence of any starting
+
K. J. Am. Chem. Soc. 1996, 118, 899-900. Wu, C.; Lecavalier, P. R.; Shen,
material, the only peak observed (m/z: 1965.3, [M - PF6] )
corresponding to the expected knotted complex (Figure 4).
Y. Y.; Gibson, H. W. Chem. Mater. 1991, 3, 569-572.
(
21) Mingos, D. M. P.; Yau, J.; Menzer, S.; Williams, D. J. Angew.
1
Finally, a two-dimensional ROESY H NMR study showed
Chem., Int. Ed. Engl. 1997, 34, 1894-1895.
(22) Sauvage, J. P.; Ward, M. Inorg. Chem. 1991, 30, 3869-3874.
a spatial proximity between the protons 5 and 6 of the phenan-

996 J. Am. Chem. Soc., Vol. 121, No. 5, 1999
Rapenne et al.
or trans, the cis-cis, cis-trans, or trans-trans isomers can be
1
formed. Therefore the H NMR signals of the phenanthroline
are broad (or split into two), due to the different cycle strain in
each isomer.
The broadness of the signal enables the attribution, since we
3
know that a trans coupling ( J) between two olefinic protons is
about 16-18 Hz, whereas it is only 7-8 Hz in the case of a cis
coupling. Consequently, integration of the NMR signals leads
to the percentage of cis and trans double bonds, which was found
to be 80 and 20%, respectively.
To obtain a single species, we decided to reduce the olefins.
Hydrogenation catalyzed by palladium (5% molar in Pd) was
quantitative by saturating a 1/1 (v/v) ethanol/dichloromethane
solution of the knot with hydrogen during 16 h, at room
temperature.
1
2+
The H NMR spectrum of knot 6 does not show any olefinic
signals and the phenanthroline signals are narrow (see Figure
3c), indicating the presence of a single species. This observation
corroborates our tentative explanation of the broad signals before
reduction, due to the coexistence of three olefinic isomers.
3
. Iron(II) as Template. Design of the Ligand. The bridge
between the two terpyridines plays a crucial role. It must be
flexible enough to enable the entanglement of the ligand around
the metal-metal axis but also short enough to prevent the two
coordinating sites from folding up around a single metal and to
avoid the formation of a face-to-face dinuclear complex.23
Finally, a short connector should maintain the fragments in close
proximity thus stabilizing the double helix by stacking of the
aromatic π-systems. Relying on preceding experiments,2 we
opted for a (CH2)2 bridge.
4,28
To avoid high-spin Fe(II) complexes obtained previously24
with anisyl groups in the 6 positions, our target ligand was a
bis(terpyridine) bridged in the 5" positions by a (CH2)2 bridge
and substituted in the 5 positions by a poly(oxyethylene) chain
bearing a terminal olefin.
Preparation of a Model Iron(II) Double Helix. To test the
feasibility of the strategy and the stability of these kinds of
complexes, the bis(terpyridine) 9 was prepared to synthesize
its iron(II) complex.
Figure 3. 1H NMR (200 MHz, CDCl
) spectra of (a) the helical
3
2+
precursor 4 with the signals corresponding to the four terminal olefins
+
(
b), (b) the trefoil knot 52 with the signals corresponding to the two
2+
olefins incorporated in the molecule (O), and (c) the trefoil knot 6
after catalytic reduction of the olefins.
Following a literature method,28 the dimethylterpyridine 8 was
reacted with 1 equiv of lithium diisopropylamide (LDA) in THF
at -78 °C. The benzylic anion formed was subsequently
oxidized with 1,2-dibromoethane and the bis(terpyridine) 9 (see
Figure 5) isolated after chromatography on alumina with 28%
yield.
The metalation with iron(II) was achieved according to
2
9
literature procedures. Ligand 9 was dissolved in hot acetone,
and an aqueous iron(II) sulfate solution was added in excess
under argon and under stirring. Addition of an excess of satu-
rated aqueous potassium hexafluorophosphate and evaporation
of the acetone caused a purple solid to precipitate, yielding 104
with 94% yield.
+
Figure 4. Positive FAB-MS spectrum of the knot 52+ in a p-nitrobenzyl
alcohol matrix (display from m/z ) 800-2200). The signals at m/z
This model could be fully characterized by mass spectrometry
and NMR and its structure determined by X-ray diffraction. The
1
836.4 and 1981.3 correspond to the reduction of the product by the
(
(
(
24) Crane, J. D.; Sauvage, J. P. New J. Chem. 1992, 16, 649-650.
matrix.
25) C a´ rdenas, D. J.; Sauvage, J. P. Synlett 1996, 916-918.
26) Martin, A. E.; Bulkowski, J. E.; J. Org. Chem. 1982, 47, 415-418.
throline fragments and the olefinic protons, which constitutes
(27) Johnstone, R. A. W.; Rose, M. E. Tetrahedron 1979, 35, 2169-
2
3
2173.
28) Elliott, C. M.; Freitag, R. A.; Blaney, D. D. J. Am. Chem. Soc.
985, 107, 4647-4655. Schmehl, R. H.; Auerbach, R. A.; Wacholtz, W.
unambiguous evidence of the expected knotted structure.
Catalytic Reduction of the Cyclic Olefins. The copper(I)
(
1
2+
knot 5 is initially obtained as a mixture of three isomers. Since
F.; Elliott, C. M.; Freitag, R. A. Inorg. Chem. 1986, 25, 2440-2445. Lehn,
J. M.; Ziessel, R. HelV. Chim. Acta 1988, 71, 1511-1516. Youinou, M.
T.; Ziessel, R.; Lehn, J. M. Inorg. Chem. 1991, 30, 2144-2148.
(29) Serr, B. R.; Andersen, K. A.; Elliott, C. M.; Anderson, O. P. Inorg.
Chem. 1988, 27, 4499-4504.
each double bond formed by the metathesis reaction can be cis
(23) Dietrich-Buchecker, C. O.; Sauvage, J. P.; Kintzinger, J. P.; Malt e` se,
P.; Pascard, C.; Guilhem, J. New J. Chem. 1992, 16, 931-942.

Synthesis of Molecular Knots
J. Am. Chem. Soc., Vol. 121, No. 5, 1999 997
Figure 6. ORTEP representation of the X-ray structure of the diiron-
II) double helix 104 . The solvent molecules, PF
+
anions, and hydrogen
(
6
atoms have been omitted for clarity.
Figure 5. Terpyridine precursors leading to the double helix 104+
Table 1. X-ray Experimental Data for the Double Helix 104+
.
formula
C
C
74
H
H
64
N
12OF24
P
4
Fe
6
2
68
56
N12Fe2•4PF
•C
6
6 2
H •H O
M
r
1828.97
cryst system
space group
a (Å)
b (Å)
c (Å)
monoclinic
P121/c1
21.306(1)
11.751(1)
35.564(1)
99.86(1)
8772(1)
4
â (deg)
3
V (Å )
Figure 7. Terpyridinic precursors.
Z
color
cryst dimens (mm)
dark red
10 .. 31 85 × 0.12 × 0.10
3712
0.497
294
Synthesis of the Terpyridinic Precursors. The unexpected
-
3
ease of formation as well as the stability of model double helix
D
calc (g cm )
4
+
F
000
µ (mm-1)
10 encouraged us to undertake the synthesis of an analogous
tetraolefinic double helix, the necessary precursor in a trefoil
knot synthesis based on RCM as depicted in Figure 1.
temp (K)
wavelength (Å)
radiation
diffractometer
scan mode
0.710 73
25
The monofunctionalization of the dimethylterpyridine 8 was
Mo KR graphite monochromated
KappaCCD
æ scans
achieved by reacting 2-(2-bromoethoxy)tetrahydropyran with
the benzylic anion of dimethylterpyridine generated with 1 equiv
of lithium diisopropylamide (LDA) in THF at -78 °C. The
terpyridine 11 shown in Figure 7 was isolated in 51% yield.
The synthesis of the bromo derivative 14 was performed in
three steps from 11. After deprotection of the alcohol function
in the presence of a catalytic amount of p-toluenesulfonic acid
in refluxing ethanol, the alcohol 12 was activated via the
formation of its mesyl derivative 13 under classical conditions.26
The bromo derivative 14 was subsequently prepared by adding
a large excess of lithium bromide in refluxing acetone. The
overall yield of these three steps, each of which required
purification on alumina, was 67%.
hkl limits
0,20/0,11/-35,35
2.5/20.82
3741
θ limits (deg)
no. of data with I > 3σ(I)
weighting scheme
no. of variables
R
2
2
2) + 0.0016F 4
) + 3.0
4F
o
/(σ (F
o
o
1054
0.096
0.126
1.269
R
w
GOF
largest peak in final diff (e Å-3) 1.098
FAB-MS spectrum showed that complex 104+ was indeed of
the type two metals and two ligands, whereas its H NMR
1
spectrum corresponded to a highly symmetrical compound,
typical of a double helix.
The chain bearing a terminal olefin was prepared as explained
in the experimental part. It was then introduced in the terpyridine
subunit by generating the alcoholate of 15 with KOH in
DMSO and reacting the latter with the bromoterpyridine
derivative 14. The terpyridine 16 was obtained in a 37% yield
after purification.
The helical structure of 104 has been confirmed by X-ray
crystallographic studies (Table 1). This structure is shown in
Figure 6. Each terpyridine is gripped around the metallic centers,
as illustrated by the average angle of 103° between the two
ortho positions of the central pyridine.
+
2
7
After the homocoupling reaction described in Figure 8, the
bis(terpyridine) 17 was obtained in a 13% yield. The metalation
with iron(II) was achieved as described before, yielding the
The four terpyridine fragments are planar. The coordination
polyhedra around each iron(II) are distorted octahedra, the angles
varying between 77 and 101°.
4
+
diiron(II) double helix 18 with 91% yield.
The four terpyridines and the two bridges are chemically
equivalent, 104 having three perpendicular C2 axes.
Significant shielding of protons 6 and 6" can be noticed in
Formation of the Diiron(II) Trefoil Knot. The metathesis
reaction performed as described Figure 9 afforded, after
+
4+
chromatography on alumina, 6.5 mg of pure knot 19 from 32
4
+
4+
double helix 10 (from 8.5 ppm in ligand 9 to 7.2 for H6 and
.4 for H6"), which can be explained by their location in the
mg of 18 , corresponding to a yield of 20%.
1
6
Its H NMR (Figure 10) and mass spectra were both con-
shielding cones of the neighboring terpyridines. The situation
of the a protons is very similar; they are shielded by 0.5 ppm
sistent with the expected cyclic molecule. It is noteworthy that
the signals of the terminal olefins were replaced by signals at
lower field.
(from 2.4 to 1.9 ppm).

998 J. Am. Chem. Soc., Vol. 121, No. 5, 1999
Rapenne et al.
conditions as described previously. 204 was obtained quanti-
+
tatively.
The knotted structure of 204 was confirmed by a 2D ROESY
+
1
H NMR experiment which showed an interaction between the
central protons of the terpys (3′, 4′, and 5′) and some protons
(
d-i) of the chain. Such interaction was only expected in the
case of a knot.
These arguments, based on a detailed NMR study, brought
us to the conclusion that the only isolated product in the reaction
described was a molecular knot.
Conclusion
Figure 8. Synthetic pathway affording the bis(terpyridine) 17, precursor
of the diiron(II) double helix
By combination of the quantitative formation and the great
stability of the Cu(I) bis(phenanthroline) helix with m-phenylene
bridges and the highly efficient intramolecular metathesis
reaction developed by Grubbs and his group, the copper(I)
complex of the trefoil knot 23 could be obtained in seven steps
from commercial 1,10-phenanthroline in a 35% overall yield.
This approach also led to a knot constructed around two iron-
(
(
II) bis(terpyridine)s for the first time, demonstrating that iron-
II) can be used as highly efficient template. The latter result
may be considered as the starting point for a new generation of
knots. Due to the richness of the coordination chemistry of
terpyridines, one can imagine the tuning of their properties by
varying the transition metal used. In addition, the olefins at the
poles of knots could be used for further functionalization or
could take part in catalytic processes.
It is also interesting to note that, thanks to the high efficiency
of the metathesis reaction, the cyclization step is no longer the
yield-limiting step in the synthesis of topologically nontrivial
species.
Experimental Section
General Procedures. The following chemicals were obtained
commercially and were used without further purification: Cs
2
CO
(dCHPh)
Strem). Some materials were prepared according to literature proce-
3
6 2 3 2
(Aldrich); KCN (Janssen); KPF (Janssen); RuCl (PCy )
(
9
25
30
dures: 1; 8; Cu(MeCN)
ether.31 Dry solvents were obtained by distillation from suitable
desiccants (Et O and THF from Na with benzophenone; MeCN and
CH Cl from P ). Thin-layer chromatography (TLC) was performed
4 6
PF ;
tetrahydropyranyl 2-bromoethyl
2
2
2
2 5
O
on aluminum sheets coated with silica gel 60 F254 (Merck 5554) or
coated with neutral alumina 60 F254 (Merck 5550). After elution, the
Figure 9. Diiron(II) molecular trefoil knots obtained after the ring-
closing metathesis cyclization reaction.
plates were either scrutinized under a UV lamp or exposed to I
2
or, for
‚6H O in
O. Column chromatography was carried out on silica
gel 60 (Merck 9385, 230-400 mesh) or neutral alumina 90 (Merck
076, 0.060-0.200 mm). UV-visible spectra were recorded on a
II
terpyridine derivatives, put in a solution of (NH
0:50 MeOH/H
4
)
2
Fe (SO
4
)
2
2
5
2
1
Kontron Instruments UVIKON 860 spectrophotometer. Fast atom
bombardment mass spectra (FAB-MS) were recorded in the positive
ion mode with either a krypton primary atom beam in conjunction with
a 3-nitrobenzyl alcohol matrix and a Kratos MS80RF mass spectrometer
coupled to a DS90 system, or a xenon primary atom beam with the
1
same matrix and a ZAB-HF mass spectrometer. The H NMR spectra
were recorded on either Bruker WP200 SY (200 MHz) or WP400SY
(
400 MHz) spectrometers (using the deuterated solvent as the lock and
residual solvent as the internal reference).
Preparation of 2. A suspension of Cs CO
200 mL) was added dropwise and under argon to a degassed solution
2
3
(1.3 g, 4 mmol) in DMF
(
of m-bis(2-(p-hydroxyphenyl)-1,10-phenanthrolinyl)benzene (1) (458
mg, 0.74 mmol) in DMF (30 mL). The mixture, which immediately
turned bright orange and later red, was heated to 80 °C under vigorous
stirring. After 1 h at 80 °C, some 2-(2-chloroethoxy)ethanol (0.25 mL,
1
Figure 10. H NMR spectra (200 MHz, acetone-d
6
) of the diiron(II)
4
+
trefoil knot 19
.
2.37 mmol) was added via a syringe. The mixture progressively turned
1
According to the H NMR, the metathesis reaction yielded
cis (55%) and trans (45%) olefins. To study in more detail a
single species, the reduction of 194 was performed in the same
(
30) Kubas, G. J.; Monzyk, B.; Crumbliss, A. M. Inorg. Synth. 1990,
2
8, 68-70.
+
(31) W a¨ lchi, P. C.; Engster, R. HelV. Chim. Acta 1978, 61, 885-898.

Synthesis of Molecular Knots
J. Am. Chem. Soc., Vol. 121, No. 5, 1999 999
1
orange. The reaction was monitored by TLC (SiO
2
; eluent, CH
2
Cl
2
/
techniques. The reaction could be monitored by H NMR, the chemical
3
% MeOH), which showed that the (chloroethoxy)ethanol had disap-
shifts of the cyclic olefins being sharply different from that of the
terminal olefins. After 16 h, the solvent was evaporated and the crude
peared. This was balanced by a further addition of this reactant (0.25
mL, 2.37 mmol) after 16 h of reaction. The reaction mixture was
maintained at 80 °C under argon for a further 6 h. DMF was then
evaporated (0.1 mmHg, 50 °C), and the residue (yellow brick color)
product was chromatographed (SiO
2
; CH
2
Cl
2
/0-1% MeOH) to give
pure 52 in a 74% yield (108 mg, 51 mmol), dark red solid (mp: >280
+
+
- +
6
°C). MS (FAB ): m/z 1965.3 ([M - PF ] , calcd 1965.5; 60%),
-
- +
was dissolved in a 1:1 H
decanted, and the aqueous phase was extracted 3 times with 200 mL
portions of CH Cl2. The organic phases were combined, dried over
MgSO , and filtered. The solvent was evaporated, and the yellow brick
solid was chromatographed (SiO ; eluent, hexane/0-80% CH Cl ) to
give 2 in a 97% yield (570 mg, 0.72 mmol), beige solid (mp: 172 °C).
2
O/CH
2
Cl
2
mixture. The organic phase was
1820.4 ([M - 2PF
6
+ e ] , calcd 1820.5; 36%), 910.1 ([M -
-
2+
-1
2PF
6
]
2 2
, calcd 910.3; 58%). UV-vis (CH Cl ), [λmax (nm) ꢀ (mol ‚
-
1
2
L‚cm )]: 236 (107 300); 250 sh (104 200); 279 sh (77 700); 325
1
4
(62 400); 520 (2880). H NMR (CDCl
3
, 200 MHz): 9.67 (s, 2H, H
a
);
3
2
2
2
8.35 (d, 4H, H
7
, J ) 8.4 Hz); 7.87 (m, 12H, H4-5-6); 7.62 (d, 4H, H ,
8
3
3
J ) 8.4 Hz); 7.12 (t, 2H, H
c
, J ) 7.8 Hz); 7.03 (m, 12H, Ho-b); 6.52
, J ) 8.4 Hz); 6.38 (m, 2.8H, Hcis-olefin); 6.24 (m, 1.2H,
trans-olefin); 5.73 (m, 8H, H ); 3.20-4.50 (m, 40H, HR-â-γ-δ-ꢀ). The
latter assignment was confirmed by 2D-NMR spectroscopy (ROESY).
Anal. Calcd for C108 : C, 61.45; H, 4.39; N, 5.31.
1
3
3
H NMR (CDCl
3
, 200 MHz): 9.52 (s, 1H, H
a
); 8.43 (dd, 2H, H
b
, J )
(d, 4H, H
3
4
3
7
H
.7 Hz, J ) 1.7 Hz); 8.22 (d, 4H, H
o
, J ) 8.9 Hz); 8.19 (broad s, 4H,
H
m
3
3
3-4); 8.06 (d, 2H, H
7
, J ) 8.5 Hz); 7.85 (d, 2H, H , J ) 8.5 Hz);
3
8
3
7
)
.58 (s, 4H, H5-6); 7.56 (t, 1H, H
c
, J ) 7.7 Hz); 6.76 (d, 4H, H
m
, J
, J ) 4.3
Hz); 3.3-3.6 (m, 8H, Hγ-δ); 2.89 (t, 2H, OH, J ) 5.5 Hz). Anal.
Calcd for C50 : C, 75.55; H, 5.32; N, 7.05. Found: C, 75.22;
H, 5.37; N, 6.98.
2 12 8 12 2
H92Cu F N O P
3
3
8.9 Hz); 3.94 (t, 4H, H
R
, J ) 4.3 Hz); 3.66 (t, 4H, H
â
Found: C, 60.96; H, 4.04; N, 4.88.
Preparation of 62+. The dicopper(I) trefoil knot 52+ (95 mg, 45
3
H N O
42 4 6
mmol) was dissolved in a 1:1 mixture of CH Cl /EtOH (100 mL). The
2
2
catalyst (Pd/C, 5% mol in Pd) was then added. At room temperature
and under vigorous stirring, the solution was maintained under a
hydrogen atmosphere for 16 h. The reaction could also be monitored
Preparation of 3. A degassed solution of 2 (565 mg, 0.72 mmol)
in THF (100 mL) was added dropwise at 0 °C and under argon to a
suspension of NaH (3.6 mmol) in THF (200 mL). The mixture turned
yellow. Its temperature was allowed to rise up to room temperature
before allyl bromide (25 mL, 72 mmol) was added via a syringe. The
mixture was then heated to reflux. The reaction was monitored by TLC
1
by H NMR, since the signal of the olefin progressively disappeared.
After filtration on alumina and evaporation of the solvent, the pure
reduced knot 62 was obtained in a quantitative yield (95 mg, 45 mmol)
+
as a dark red solid (mp: >280 °C). UV-vis (CH
2
Cl
2
) [λmax (nm) ꢀ
-
1
-1
(
2 2 2
SiO ; eluent, CH Cl /5% MeOH). More allyl bromide (25 mL, 72
(mol ‚L‚cm )]: 235 (109 800); 251 sh (104 200); 280 sh (75 700);
1
mmol) was added after 40 h of reaction. The reaction mixture was
kept under reflux and under argon for 70 h. The temperature was then
brought down to 0 °C, and excess NaH was neutralized by adding small
portions (5 mL) of absolute ethanol, until there was no more gas formed.
The solvent was then evaporated, and the residue taken up in a 1:1
3
325 (63 200); 513 (3100). H NMR (CDCl , 200 MHz): 9.71 (s, 2H,
3
3
a 7
H ); 8.37 (d, 4H, H , J ) 8.4 Hz); 7.93 (AB, 8H, H5-6, J ) 8.8 Hz);
3
3
7.90 (d, 4H, H
4
, J ) 8.4 Hz); 7.62 (d, 4H, H
8
, J ) 8.4 Hz); 7.24 (t,
3
3
2H, H , J ) 7.8 Hz); 7.04 (m, 12H, Ho-b); 6.58 (d, 4H, H
Hz); 5.72 (d, 8H, H
c
3
, J ) 8.4
, J ) 8.6 Hz); 3.30-4.00 (m, 40H, HR-â-γ-δ-ꢀ).
3
m
Preparation of Free Ligand 7. To a solution of 62 (50 mg, 23
mmol) in refluxing wet acetonitrile (100 mL) was added potassium
cyanide (0.5 g, large excess). The mixture was stirred at 80 °C for 4 h,
during which the dark red color of the copper(I) complex progressively
disappeared. The solvent was evaporated, and the residue was dissolved
in dichloromethane. The crude mixture was washed 3 times with 0.1
+
H
2
O/CH
phase was extracted 3 times with 200 mL portions of CH
organic phases were combined, dried over MgSO , filtered, and
evaporated to dryness. The yellow brick solid was chromatographed
Cl
2 2
mixture. The organic phase was decanted, and the aqueous
2
Cl2. The
4
(SiO
2
; eluent, hexane/0-100% CH
2 2
Cl ) to give 3 in a 100% yield
1
(627 mg, 0.72 mmol), beige-orange solid (mp: 135 °C). H NMR
3
(
CDCl
3
, 200 MHz): 9.65 (s, 1H, H
a
); 8.66 (dd, 2H, H
b
, J ) 7.7 Hz,
4
M ammonia in water, dried over MgSO , and filtered to give 7 in a
4
3
3
1
J ) 1.5 Hz); 8.42 (d, 4H, H
Hz); 8.26 (d, 2H, H
o
, J ) 8.8 Hz); 8.34 (d, 2H, H
3
, J ) 8.5
, J ) 8.5 Hz); 7.98
, J ) 7.8 Hz); 7.67 (s, 4H,
quantitative yield (39 mg, 23 mmol). Its H NMR spectrum is very
complex and shows a mixture of conformers in reptation.
3
3
4
, J ) 8.5 Hz); 8.15 (d, 2H, H
7
3
3
(d, 2H, H
8
, J ) 8.5 Hz); 7.80 (t, 1H, H
c
Remetalation was achieved by adding a degassed solution of Cu-
(MeCN) PF (5 mg, 24 mmol) in acetonitrile (20 mL) to a solution of
3
3
H
5-6); 7.02 (d, 4H, H
m
, J ) 8.8 Hz); 5.93 (ddt, 2H, Holefin, Jtrans
)
4
6
3
3
3
1
1
7.2 Hz, Jcis ) 10.3 Hz, J ) 5.6 Hz); 5.27 (m, 2H, Holefin-trans, J )
7.2 Hz, J ) 1.3 Hz, Jgem ∼ 1 Hz); 5.17 (m, 2H, Holefin-cis, J ) 10.3
ligand 7 (39 mg, 23 mmol) in dichloromethane (20 mL), at room
temperature and under argon. The dark red solution was stirred for 1
h. The solvent was then evaporated, and the residue was washed with
4
3
4
3
Hz, J ) 1.3 Hz, Jgem ∼ 1 Hz); 4.17 (t, 4H, H
H, H
m, 4H, H
H, 5.76; N, 6.40. Found: C, 76.62; H, 6.10; N, 6.36.
R
, J ) 5.2 Hz); 4.02 (td,
3
4
3
2+
4
(
ꢀ
, J ) 5.6 Hz, J ) 1.3 Hz); 3.88 (t, 4H, H
â
, J ) 5.2 Hz); 3.74
water and dried under vacuum to give knot 6 in a quantitative yield
γ
); 3.61 (m, 4H, H ). Anal. Calcd for C56
δ
H
50
N
4
O
6
: C, 76.87;
(50 mg, 23 mmol).
Preparation of 9. A degassed solution of 8 (2 g, 7.66 mmol) in
anhydrous THF (250 mL) was cooled to -78 °C. While this temperature
was maintained, a freshly prepared LDA solution (7.7 mmol in 30 mL
THF) was added. The reaction mixture progressively turned from deep
red to purple. It was stirred for a further 2 h at -80 °C, after which the
temperature was allowed to rise to 0 °C and brought down to -78 °C
again. Dibromoethane (6.44 g, 34.3 mmol), previously filtered over
basic alumina, was then added via syringe. Once the addition was
finished, the mixture was left at -78 °C for 4 h, after which it was
allowed to heat up to room temperature. After 4 h of stirring at room
temperature, the emerald green solution was hydrolyzed by 200 mL of
water and turned orange. After evaporation of the THF and extraction
Preparation of 42+. A degassed solution of copper(I) hexafluoro-
phosphate (280 mg, 0.69 mmol) in acetonitrile (70 mL) was added at
room temperature and under argon to a solution of ligand 3 (607 mg,
0
.69 mmol) in dichloromethane. The resulting dark red mixture was
stirred for 1 h. The solvents were then evaporated and the residue
washed with water and dried under vacuum. The pure double helix
2
+
4
0
4
was obtained in a quantitative yield as a dark red solid (751 mg,
1
.69 mmol). H NMR (CDCl
H, H
3
, 200 MHz): 9.64 (s, 2H, H
a
); 8.35 (d,
3
3
7
, J ) 8.4 Hz); 7.94 (AB, 8H, H5-6, J ) 8.8 Hz); 7.87 (d, 4H,
3
3
3
H
7
4
, J ) 8.4 Hz); 7.62 (d, 4H, H
8
, J ) 8.4 Hz); 7.12 (t, 2H, H
c
, J )
3
3
.8 Hz); 7.03 (d, 8H, H
o
, J ) 8.6 Hz); 6.90 (dd, 4H, H
b
, J ) 7.8 Hz,
4
3
J ) 1.2 Hz); 6.52 (d, 4H, H
3
, J ) 8.4 Hz); 5.99 (dtd, 4H, Holefin
,
with CH
was evaporated. The crude mixture was chromatographed (Al
eluent, hexane/CH Cl 10-70%) to give pure 9 in a 28% yield (573
mg, 1.1 mmol), beige solid (mp: 187 °C). H NMR (CDCl
2 2 4
Cl , the organic layer was dried over MgSO , and the solvent
3
3
3
3
J
trans ) 17.2 Hz, Jcis ) 10.3 Hz, J ) 5.6 Hz); 5.72 (d, 8H, H
m
, J )
.6 Hz); 5.31 (m, 2H, Holefin-trans, J ) 17.2 Hz, J ) 1.3 Hz, Jgem ∼ 1
Hz); 5.20 (m, 2H, Holefin-cis, J ) 10.3 Hz, J ) 1.3 Hz, Jgem ∼ 1 Hz);
.07 (dt, 8H, H
2 3
O ;
3
4
8
2
2
3
4
1
3
, 200
MHz): 8.51 (m, 8H, H6-6′′-3′-5′); 8.39 (d, 4H, H3-3′′, J ) 7.8 Hz);
3
4
3
4
ꢀ
, J ) 5.6 Hz, J ) 1.3 Hz); 3.10-3.70 (m, 32H,
7.92 (t, 2H, H4′, 3J ) 7.9 Hz); 7.61 (AB, 4H, H4-4′′, J ) 7.8 Hz, J )
2.1 Hz); 3.07 (s, 4H, CH ); 2.40 (s, 6H, CH ). Anal. Calcd for
34 28 6
C H N : C, 78.43; H, 5.42; N, 16.14. Found: C, 79.05; H, 4.91; N,
3
4
H
R-â-γ-δ).
Preparation of the Dicopper(I) Trefoil Knot 52+. Double helix
2
3
42
+
(150 mg, 69 mmol) was dissolved in freshly distilled and degassed
dichloromethane (5 mL) at room temperature to obtain a 0.01 M
solution. The catalyst (Grubbs ruthenium(II) carbene,14 6 mg, 5% mol)
dissolved in dichloromethane (2 mL) was then added using Schlenk
15.70.
Preparation of 104+. A solution of dimethylbis(terpyridine) 9 (31
mg, 60 mmol) dissolved in hot acetone (25 mL) was added under argon,

1000 J. Am. Chem. Soc., Vol. 121, No. 5, 1999
Rapenne et al.
via cannula, at room temperature and under stirring to an aqueous
solution of FeSO (2 mmol dissolved in 5 mL). The purple mixture
was brought to 50 °C for 1 h, whereafter the acetone was evaporated.
hexane/50-100% CH
2
Cl
2
) to give 13 as a colorless powder in a 67%
1
4
yield (1.88 g, 4.91 mmol). H NMR (CDCl
3
, 200 MHz): 8.40 (m, 4H,
3
3
H3-3"-6-6"); 8.36 (d, 2H, H3′, J ) 7.7 Hz); 8.35 (d, 2H, H5′, J ) 8.0
3 3
The iron complex was subsequently precipitated by the addition of a
Hz); 7.89 (t, 1H, H4′, J ) 7.8 Hz); 7.64 (t, 1H, H
4
, J ) 7.4 Hz); 7.62
, J ) 6.2 Hz); 2.98 (s, 3H,
); 2.08 (tt,
3
3
saturated aqueous solution of KPF
6
(50 mL). The suspension was left
(t, 1H, H4", J ) 7.3 Hz); 4.24 (t, 2H, 2H
γ
3
for 2 h in the refrigerator, and the solid was filtered off, washed with
CH
2H, H
3
SO
2
); 2.80 (t, 2H, H
R
, J ) 7.2 Hz); 1.95 (s, 3H, CH
3
water, and dried under vacuum to give pure 104+ in a 94% yield (48
3
3
â
, J ) 7.2 Hz, J ) 6.2 Hz).
+
mg, 28 mmol), fuschia red solid (mp: >280 °C). MS (FAB ): m/z
Preparation of 14. Terpyridine 13 (1.88 g, 4.91 mmol) was dissolved
in acetone (100 mL, analytical grade) and reacted under argon with
anhydrous LiBr (4.26 g, 49.1 mmol). The reaction mixture was heated
to reflux for 6 h and the reaction monitored by TLC. After evaporation
of acetone, the crude mixture was dissolved in a CH Cl /H O mixture.
-
+
-
- +
1
587.2 ([M - PF
6
] , calcd 1587.2; 5%), 1442.4 ([M - 2PF
6
+ e ] ,
-
- +
calcd 1442.3; 3%), 1297.5 ([M - 3PF
152.5 ([M - 4PF
6
+ 2e ] , calcd 1297.3; 2%),
+ 3e ] , calcd 1152.4; 2%), 721.4 ([M -
-
- +
1
2
6
-
2+
-1
PF
6
]
2 2
, calcd 721.2; 18%). UV-vis (CH Cl ), [λmax (nm) ꢀ (mol ‚
2
2
2
-
1
L‚cm )]: 228 (85 700); 256 (68 600); 279 (85 100); 288 (76 400);
The organic phases were combined and dried over MgSO , and the
4
3
(
28 (100 300); 375 sh (7600); 480 sh (9800); 552 (18 700); 618 sh
solvent was evaporated to give terpyridine 14 in a 97% yield (1.75 g,
4.76 mmol). 1H NMR spectrometry showed the conversion to be
quantitative. Compound 14 was therefore used without further purifica-
1
3
4100). H NMR (acetone-d
6
, 200 MHz): 9.19 (d, 4H, H5′, J ) 8.0
3
3
Hz); 9.07 (d, 4H, H3′, J ) 8.0 Hz); 8.83 (t, 4H, H4′, J ) 8.0 Hz); 8.67
3
3
tion, colorless solid. 1H NMR (CDCl , 200 MHz): 8.45 (m, 4H,
(
H
(
d, 4H, H3′′, J ) 7.9 Hz); 8.55 (d, 4H, H
3
, J ) 8.1 Hz); 7.78 (d, 4H,
, J ) 8.1 Hz); 7.64 (d, 4H, H4′′, J ) 7.9 Hz); 7.25 (s, 4H, H ); 6.39
); 1.91 (s, 12H, CH ). The latter
assignment was confirmed by 2D-NMR spectroscopy (ROESY). Anal.
Calcd for C68 : C, 78.44; H, 5.42; N, 16.14. Found: C,
8.12; H, 5.27; N, 15.98.
Preparation of 11. A degassed solution of dimethylterpyridine 8
1.8 g, 6.89 mmol) in anhydrous THF (100 mL) was cooled to -78
C. While this temperature was maintained, a freshly prepared LDA
3
3
3
3
3
4
6
3′-5′
H3-3"-6-6"); 8.38 (d, 2H, H , J ) 8.0 Hz); 7.92 (t, 1H, H , J ) 7.9
3 3
4′
s, 4H, H6′′); 2.73 (s, 8H, CH
2
3
Hz); 7.66 (t, 1H, H , J ) 7.3 Hz); 7.64 (t, 1H, H , J ) 7.2 Hz); 3.40
3 3
4
4"
(t, 2H, 2H , J ) 6.5 Hz); 2.84 (t, 2H, H , J ) 7.1 Hz); 2.38 (s, 3H,
γ
R
3
3
H
56
F24Fe
N P
2 12 4
â
CH ); 2.19 (tt, 2H, H , J ) 7.1 Hz, J ) 6.5 Hz).
3
7
Preparation of 15. The preparation of the mono(tetrahydropyranyl)
monobromide derivative of triethylene glycol has been prepared after
mesylation26 followed by bromination of the mono(tetrahydropyranyl)
derivative according to the literature procedure. Finely crushed potas-
sium hydroxide (1.44 g, 26 mmol) was suspended in DMSO (4 mL),
and but-3-enol (0.52 mL, 432 mg, 6.4 mmol) was added. The reaction
mixture was heated to 50 °C for 1 h. The bromide derivative (1.68 g,
5 mmol), dissolved in DMSO, was then added, and the mixture was
stirred under argon for 4 h. The crude mixture was diluted with CH2-
(
°
solution (6.9 mmol in 20 mL of THF) was added. The reaction mixture
progressively turned from deep red to purple. It was stirred for a further
2
h at -80 °C, after which the temperature was allowed to rise to 0 °C
and brought down to -78 °C again. Meanwhile, a solution of
tetrahydropyrannyl 2-bromoethyl ether (1.435 g, 6.89 mmol) in
anhydrous THF (100 mL) was cooled to 0 °C and degassed. This
solution was then transferred under argon onto the anion of 8 at -78
Cl (50 mL) and washed with water (5 × 120 mL). The organic phases
2
were dried over MgSO and the solvent evaporated. The yellow oil
4
°
C, the mixture turning deep purple. Once the addition was finished,
obtained was chromatographed over alumina (eluent, hexane/50%
CH Cl ). The elimination product was very difficult to separate off,
the mixture was allowed to heat up to room temperature. After 20 h of
stirring, the deep blue solution was hydrolyzed by 200 mL of water
and turned from blue to green and finally orange. After evaporation of
2
2
because its polarity was very similar to that of the desired product.
After three chromatographies the protected 15 was isolated in a 29%
yield (530 mg, 1.84 mmol). 15 has been obtained as a pale yellow oil
after a classical deprotection reaction using catalytic p-toluenesulfonic
the THF and extraction with CH
over MgSO and the solvent evaporated. The crude mixture was
chromatographed (Al ; eluent, hexane/10-100% Et O). We obtained
2% of starting material (0.581 g, 2.22 mmol), 51% of the desired
monosubstituted product (1.367 g, 3.52 mmol), and 11% of disubstituted
2 2
Cl , the organic phases were dried
4
1
O
2 3
2
acid in refluxing ethanol. H NMR (CDCl , 200 MHz): 5.81 (m, 1H,
3
3
H ); 5.06 (m, 2H, H ); 3.3-3.8 (m, 16H, CH ); 2.62 (s, 1H, OH).
b
a
2
Preparation of 16. In a 250 mL three-necked flask were dissolved
1
product (0.382 g, 0.75 mmol), colorless solid. H NMR (CDCl
MHz): 8.58 (s, 1H, H
); 8.55 (s, 1H, H6"); 8.53 (d, 2H, H3-3", 3J ) 7.7
Hz); 8.44 (d, 2H, H3′-5′, J ) 7.9 Hz); 7.95 (t, 1H, H4′, J ) 7.9 Hz);
3
, 200
finely ground potassium hydroxide (259 mg, 4.6 mmol) and 15 (235
mg, 1.15 mmol) in DMSO (3 mL). After 3 h at 50 °C and under argon,
terpyridine 14 dissolved in DMSO (3 mL) was added to the alkoxide
solution, and the mixture was heated to 80 °C. The mixture progres-
sively turned from yellow to orange and then to dark brown. After 16
h at 80 °C, some CH Cl (100 mL) was added and the mixture was
6
3
3
3
3
7
1
0
4
.68 (t, 2H, H , J ) 7.7 Hz); 7.66 (t, 2H, H4", J ) 7.7 Hz); 4.62 (t,
3
3
H, J ) 3.5 Hz); 3.3-3.9 (m, 4H); 2.83 (t, 2H, H
R
, J ) 8.4 Hz);
.8-2 (m, 8H).
2
2
Preparation of 12. Terpyridine 11 (3.34 g, 8.6 mmol) was dissolved
thoroughly washed with water (400 mL first and 5 × 200 mL). The
in ethanol (30 mL) and heated to reflux in the presence of a catalytic
amount of p-toluenesulfonic acid (50 mg). The reaction was followed
by TLC, and the reflux was maintained during 4 h. After evaporation
crude mixture was hereafter separated from DMSO and therefore could
be chromatographed (Al
a colorless powder in a 36% yield (204 mg, 0.415 mmol). H NMR
2 3 2
O ; eluent, Et O/0-1% MeOH) to give 16 as
1
3
of the ethanol and extraction with a CH
phases were combined and dried over MgSO
evaporated. The crude mixture was chromatographed (Al
CH Cl /0-2% MeOH) to give 12 in an 86% yield (2.24 g, 7.4 mmol),
colorless solid. H NMR (CDCl
2
Cl
2
/H
2
O mixture, the organic
, and the solvent was
; eluent,
3
(CDCl , 200 MHz): 8.47 (m, 4H, H3-3"-6-6"); 8.44 (d, 2H, H3′-5′, J )
7.9 Hz); 7.95 (t, 1H, H4′, 3J ) 7.9 Hz); 7.68 (t, 1H, H
, 3J ) 7.7 Hz);
4
4
3
2
O
3
7.66 (t, 1H, H4", J ) 7.7 Hz); 5.79 (m, 1H, Holefin); 5.05 (m, 2H, Holefin);
3
2
2
3.3-3.7 (m, 18H, CH
2
polyoxo chain); 2.75 (t, 2H, H
2.37 (s, 3H, CH ); 1.95 (tt, 2H, H
R
, J ) 7.2 Hz);
1
3
3
3
, 200 MHz): 8.40 (m, 4H, H3-3"-6-6");
3
â
, J ) 7.2 Hz, J ) 6.4 Hz).
3
8
.27 (d, 2H, H3′, J ) 7.8 Hz); 8.26 (d, 2H, H5′, 3J ) 7.8 Hz); 7.82 (t,
H, H4′, J ) 7.8 Hz); 7.54 (t, 1H, H
J ) 7.0 Hz); 3.82 (s, 1H, OH); 3.58 (t, 2H, 2H
, J ) 7.3 Hz); 2.26 (s, 3H, CH
Hz, J ) 6.3 Hz).
Preparation of 13. A suspension of 12 (2.24 g, 7.36 mmol) in
anhydrous CH Cl (100 mL) was placed at -5 °C and under argon in
the presence of freshly distilled NEt (10 mL, 70 mmol). A solution of
mesyl chloride (1.42 mL, 18.4 mmol) in anhydrous CH Cl (30 mL)
was slowly added to this suspension, which progressively dissolved
-5 < T < -2 °C) to give a clear yellow solution. After 2 h of stirring,
Preparation of 17. A degassed solution of dimethylterpyridine 16
(204 mg, 0.415 mmol) in anhydrous THF (100 mL) was cooled to
-78 °C. While this temperature was maintained, a freshly prepared
solution of LDA (7.7 mmol) in THF (30 mL) was added. The reaction
mixture progressively turned from deep red to purple. After 2 h of
further stirring at -78 °C, the temperature was allowed to rise to 0 °C
and brought down to -78 °C again. Dibromoethane (previously filtered
on basic alumina) (0.18 mL, 2.08 mmol) was then added via a syringe.
After the addition was complete, the mixture was left for 4 h at -78
°C, after which the emerald green solution was allowed to heat up to
room temperature and turned yellow. After evaporation of THF and
3
3
1
4
, J ) 7.0 Hz); 7.53 (t, 1H, H4"
,
3
3
γ
, J ) 6.3 Hz); 2.66
3
3
(
t, 2H, H
R
3 â
); 1.80 (tt, 2H, H , J ) 7.3
3
2
2
3
2
2
(
TLC showed complete disappearance of the starting materials. The
reaction mixture was washed with water, the organic phases were
extraction with CH
over MgSO and the solvent was evaporated. The crude mixture was
chromatographed (Al ; eluent, CH Cl /0-2% MeOH) to give 17 in
3
a 13% yield (26 mg, 26.5 mmol), pale brown solid. H NMR (CDCl ,
2 2
Cl , the organic phases were combined and dried
4
combined and dried over MgSO
beige powder thus obtained was chromatographed (Al
4
, and the solvent was evaporated. The
; eluent,
O
2 3
2
2
1
2
O
3

Synthesis of Molecular Knots
J. Am. Chem. Soc., Vol. 121, No. 5, 1999 1001
2
7
2
00 MHz): 8.47 (m, 8H, H3-3"-6-6"); 8.34 (d, 4H, H3′-5′, 3J ) 7.9 Hz);
Preparation of 204+. The diiron(II) trefoil knot 194+ (6.4 mg, 2.4
mmol) was dissolved in a 1:1 mixture of CH Cl /EtOH (30 mL). The
2 2
.95 (t, 2H, H4′, 3J ) 7.9 Hz); 7.68 (t, 2H, H
, J ) 7.7 Hz); 7.66 (t,
3
4
3
H, H4", J ) 7.7 Hz); 5.75 (m, 2H, Holefin); 5.04 (m, 4H, Holefin); 3.3-
catalyst (Pd/C, 5% mol in Pd) was then added. At room temperature
and under vigorous stirring, the solution was maintained under a
hydrogen atmosphere for 16 h. The reaction could also be monitored
3
2 2 R
.7 (m, 36H, CH polyoxo chain); 3.03 (s, 4H, CH ); 2.73 (t, 4H, H ,
3
3
3
J ) 7.2 Hz); 1.95 (tt, 4H, H
â
, J ) 7.2 Hz, J ) 6.4 Hz).
Preparation of 184 . A solution of bis(terpyridine) 17 (26 mg, 26.5
mmol) dissolved in hot acetone (10 mL) was added via cannula, under
argon, at room temperature and under stirring to an aqueous solution
+
by H NMR, since the signal of the olefin progressively disappeared.
1
After filtration on alumina and evaporation of the solvent, the pure
reduced knot 204 was obtained in a quantitative yield (6.4 mg, 2.4
+
-
1
of FeSO
and the acetone was evaporated. The iron complex was then precipitated
by the addition of a saturated aqueous solution of KPF (20 mL). The
suspension was left for 2 h in the refrigerator, and the solid was filtered
off, washed with water, and dissolved in CH Cl . The organic phase
was washed three times with water and the solvent evaporated. The
solid wad dried under vacuum for 24 h to give pure 18 in a 91%
yield (32 mg, 12 mmol), fuschia red solid. H NMR (acetone-d
MHz): 9.21 (d, 4H, H5′, J ) 8.0 Hz); 9.09 (d, 4H, H3′, J ) 8.0 Hz);
4
(0.1 mmol). The purple mixture was left at 50 °C for 1 h,
2 2
mmol), fuschia red solid. UV-vis (CH Cl ), [λmax (nm) ꢀ (mol ‚L‚
-
1
cm )]: 231 (137 100); 259 (97 800); 278 (118 200); 283 sh (94 700);
1
6
327 (115 700); 486 sh (11 400); 551 (19 300); 620 sh (3100). H NMR
3
(acetone-d
6
, 200 MHz): 9.23 (d, 4H, H5′, J ) 8.0 Hz); 9.12 (d, 4H,
3
3
3
2
2
H3′, J ) 8.0 Hz); 8.87 (t, 4H, H4′, J ) 8.0 Hz); 8.71 (d, 4H, H3′′, J
3 3
) 7.9 Hz); 8.59 (d, 4H, H
3
, J ) 8.1 Hz); 7.82 (d, 4H, H
Hz); 7.67 (d, 4H, H4′′, J ) 7.9 Hz); 7.29 (s, 4H, H ); 6.43 (s, 4H,
6′′); 3.5-3.7 (m, 64H, CH polyoxo chain); 3.40 (m, 8H, H ); 3.17
(t, 8H, Hg, J ) 6.2 Hz); 2.72 (s, 8H, bridging CH ); 2.40 (t, 8H, H
4
, J ) 8.1
4
+
3
6
1
6
, 200
H
2
â
3
3
3
2
R
,
3
3
3
1
3
8
.85 (t, 4H, H4′, J ) 8.0 Hz); 8.68 (d, 4H, H3′′, J ) 7.9 Hz); 8.56 (d,
J ) 7.4 Hz). H NMR (CD
2
Cl
2
, 400 MHz): 8.81 (AB, 8H, H3′-5′, J
) 8.0 Hz); 8.68 (t, 4H, H4′, J ) 8.0 Hz); 8.36 (d, 4H, H
, 3J ) 8.3
, J ) 7.0 Hz);
, J ) 3.2 Hz); 6.49 (d,
polyoxo chain); 3.38
3
3
3
4
H, H
3
, J ) 8.1 Hz); 7.80 (d, 4H, H
); 6.40 (s, 4H, H6′′); 5.78 (m, 4H, Holefin);
polyoxo chain); 2.73 (s,
4
, J ) 8.1 Hz); 7.65 (d, 4H, H4′′
,
3
3
3
3
J ) 7.9 Hz); 7.27 (s, 4H, H
6
Hz); 8.32 (d, 4H, H3", J ) 8.3 Hz); 7.73 (d, 4H, H
4
3
4
5
8
.00 (m, 8H, Holefin); 3.3-3.7 (m, 80H, CH
2
7.65 (d, 4H, H4", J ) 8.0 Hz); 6.70 (d, 4H, H
6
3
4
H, bridging CH
2
); 2.48 (t, 8H, H
R
, J ) 7.1 Hz).
4H, H6′′, J ) 3.2 Hz); 3.3-3.7 (m, 64H, CH
2
4
+
4+
3
3
Preparation of 19 . Double helix 18 (32 mg, 12 mmol) and the
(m, 8H, H
Hz); 2.11 (s, 8H, bridging CH
by 2D-NMR spectroscopy (ROESY).
â
); 3.15 (t, 8H, H
γ
, J ) 5.9 Hz); 2.38 (t, 8H, H
). The latter assignment was confirmed
R
, J ) 7.5
1
4
catalyst (Grubbs ruthenium(II) carbene, 5 mg, 25% mol) were
dissolved at room temperature in freshly distilled and degassed
dichloromethane, so as to obtain a 0.01 M solution. After 100 h, the
solvent was evaporated and the crude mixture was chromatographed
2
Acknowledgment. We thank the CNRS and the EU for
financial support and the French Ministry of National Education
for a fellowship to G.R. We are also grateful to Dr. J.-P. Collin
4+
(Al
2 3 2 2
O ; eluent, CH Cl /0-5% MeOH) to give 19 in a 20% yield (6.4
mg, 2.4 mmol) as a mixture of cis (55%) and trans (45%) olefins,
fuschia red solid. MS (FAB ): m/z 2451.6 ([M - PF
+
- +
6
] , calcd 2451.8;
1
for fruitful discussions and to J.-D. Sauer for recording the H
-
- +
1
-
1
.5%), 2306.6 ([M - 2PF
6
+ e ] , calcd 2306.8; 1.9%), 2161.5 ([M
-
-
+
-
2+
NMR spectra. Special thanks are due to Nathalie Kyritsakas,
3PF
6
+ 2e ] , calcd 2161.9; 1.6%), 1153.3 ([M - 2PF ] , calcd
6
4+
-
3+
1
Andr e´ De Cian, and Jean Fischer for the X-ray structure of 10 .
153.4; 4.2%), 720.7 ([M - 3PF
6
] , calcd 720.6; 92%). H NMR
3
(
H
acetone-d , 200 MHz): 9.23 (d, 4H, H5′, J ) 8.0 Hz); 9.12 (d, 4H,
6
3
3
3
3′, J ) 8.0 Hz); 8.87 (t, 4H, H4′, J ) 8.0 Hz); 8.71 (d, 4H, H3′′, J
3 3
Supporting Information Available: Tables of X-ray data
)
7.9 Hz); 8.58 (d, 4H, H
3
, J ) 8.1 Hz); 7.82 (d, 4H, H
4
, J ) 8.1
); 6.43 (s, 4H,
4+
4+
for 10 and figures showing ROESY measurements on 20
3
Hz); 7.68 (d, 4H, H4′′, J ) 7.9 Hz); 7.29 (s, 4H, H
6
2+
and 5 (25 pages, print/PDF). See any current masthead page
H
6′′); 5.97 (m, 2.2H, Hcis-olefin); 5.82 (m, 1.8H, Htrans-olefin); 3.3-3.7
for ordering information and Web access instructions.
3
(m, 72H, CH
2
polyoxo chain); 3.40 (m, 8H, H
â
); 3.17 (t, 8H, H
γ
, J )
3
6
.2 Hz); 2.73 (s, 8H, bridging CH
2
); 2.40 (t, 8H, H
R
, J ) 7.4 Hz).
JA982239+