Molecular composite knots

Article abstract of DOI:10.1021/ja961459p

Molecular composite knots have been prepared from transition metal-assembled precursors via a Glaser acetylenic coupling reaction. The templating metal is copper(I), and the coordinating fragments incorporated into the final structure are 1,10-phenanthroline-type chelates. The compounds are composite knots as opposed to prime knots such as the classical trefoil knot. By combining two tied open-chain fragments in a cyclodimerization reaction, the simplest composite knots are obtained as a mixture of two topological diastereomers. The minimum number of crossing points used to represent the molecules in a plane is six. Due to the complexity of the entangled precursors and to the several cyclization possibilities, the formation yield of composite knots is only modest (~3%). On the other hand, the compound has been fully characterized by ES-MS (molecular weight, 4037.8) and by ¹H NMR spectroscopy, including 2D NMR (NOESY).

Full text of DOI:10.1021/ja961459p

9110
J. Am. Chem. Soc. 1996, 118, 9110-9116
Molecular Composite Knots
Riccardo F. Carina, Christiane Dietrich-Buchecker, and Jean-Pierre Sauvage*
Contribution from the Laboratoire de Chimie Organo-Mine´rale, URA 422 du CNRS,
Institut Le Bel, UniVersite´ Louis Pasteur, 4, rue Blaise Pascal, 67070 Strasbourg-Cedex, France
ReceiVed May 2, 1996X
Abstract: Molecular composite knots have been prepared from transition metal-assembled precursors via a Glaser
acetylenic coupling reaction. The templating metal is copper(I), and the coordinating fragments incorporated into
the final structure are 1,10-phenanthroline-type chelates. The compounds are composite knots as opposed to prime
knots such as the classical trefoil knot. By combining two tied open-chain fragments in a cyclodimerization reaction,
the simplest composite knots are obtained as a mixture of two topological diastereomers. The minimum number of
crossing points used to represent the molecules in a plane is six. Due to the complexity of the entangled precursors
and to the several cyclization possibilities, the formation yield of composite knots is only modest (∼3%). On the
1
other hand, the compound has been fully characterized by ES-MS (molecular weight, 4037.8) and by H NMR
spectroscopy, including 2D NMR (NOESY).
Knot theory is a very active field of mathematics within the
Chart 1
more general area of topology.1 As real objects, the emergence
of knots is mostly due to the recognition of their existence in
biology. DNA forms beautiful catenanes and knots, which have
been characterized by electron microscopy,2 the first single-
stranded DNA knot being reported in 1976 by Liu et al.3
Interestingly, knots have also been identified in proteins, by
careful screening of X-ray structures.4 In chemistry, a few
landmark papers5-10 have introduced and developed some
essential topology concepts that have been applied to hypotheti-
cal molecules, thus bringing closer two scientific fields that
appeared a priori relatively remote from one another. On the
borderline between synthetic chemistry and biology, Seeman
and co-workers have created a fascinating family of interlocking
ring systems and knots, constructed on single-stranded DNA.11
A few years ago, some of us reported the synthesis of a
molecular trefoil knot,12 i.e., the simplest nontrivial prime knot.
We now report that our synthetic approach can be extended to
the preparation of composite knots (composite, as opposed to
prime; see Chart 1) consisting of two trefoil knot units. The
strategy is represented in Figure 1.
centers. This prerequisite can be reached by careful design of
the various fragments to be incorporated in the multifunctional
linear thread D and by application of the knowledge acquired
in the course of the synthesis of various molecular trefoil
knots.13,14
Several important requirements have to be fulfilled for the
strategy of Figure 1b to be successful. In particular, the order-
creating step (iii) generating (E) will have to be favored over
the numerous other possible reactions between (D) and the metal
X Abstract published in AdVance ACS Abstracts, September 1, 1996.
(1) Adams, C. C. The Knot Book; W. H. Freeman: New York, 1994.
(2) Hudson, B.; Vinograd, J. Nature (London) 1967, 216, 647. Clayton,
D. A.; Vinograd, J. Nature (London) 1967, 216, 652. Wasserman, S. A.;
Cozzarelli, N. R. Science 1986, 232, 951. Krasnow, M. A.; Stasiak, A.;
Spengler, S. J.; Dean, F.; Koller, T.; Cozzarelli, N. R. Nature (London)
1983, 304, 559.
(3) Liu, L. F.; Depew, R. E.; Wang, J. C. J. Mol. Biol. 1976, 106, 439.
(4) Liang, C.; Mislow, K. J. Am. Chem. Soc. 1994, 116, 11189; 1995,
117, 4201.
Results and Discussion
A. Design and Synthesis. (1) Molecular String 1. The
design of the multifunctional linear thread D necessary to follow
strategy b of Figure 1 toward composite knots F and G was
achieved by taking advantage of the knowledge acquired during
all of our preceding templated syntheses. Accordingly, by a
multistep procedure depicted in Figure 2, we synthesized the
molecular string 1, which appeared suitable for our target. The
two 1,10-phenanthroline nuclei of each two-chelate coordinating
fragment (intermediate compounds 5 and 6) are separated by
1,3-phenylene spacers since this linker was revealed to be highly
efficient in the elaboration of other double-stranded helical
(5) Frisch, H. L.; Wasserman, E. J. Am. Chem. Soc. 1961, 83, 3789.
(6) Schill, G. Catenanes, Rotaxanes and Knots; Academic Press: New
York, 1971.
(7) Walba, D. M. Tetrahedron 1985, 41, 3161.
(8) Sauvage, J. P., Ed. New J. Chem. 1993, 17, (special issue).
(9) Liang, C.; Mislow, K. J. Math. Chem. 1994, 15, 35.
(10) Supramolecular Stereochemistry; Siegel, J. S., Ed.; Nato ASI Series;
Kluwer Academic Publishers: Dordrecht, The Netherlands, 1995.
(11) Seeman, N. C.; Chen, J. Nature (London) 1991, 350, 631. Seeman,
N. C.; Zhang, Y. J. Am. Chem. Soc. 1994, 116, 1661.
(12) Dietrich-Buchecker, C. O.; Sauvage, J.-P. Angew. Chem., Int. Ed.
Engl. 1989, 28, 189. Dietrich-Buchecker, C. O.; Guilhem, J.; Pascard, C.;
Sauvage, J. P. Angew. Chem., Int. Ed. Engl. 1990, 29, 1154.
(13) Dietrich-Buchecker, C. O.; Sauvage, J. P.; Kintzinger, J. P.; Malte`se,
P.; Pascard, C.; Guilhem, J. New J. Chem. 1992, 16, 931.
(14) Dietrich-Buchecker, C. O.; Sauvage, J.-P.; De Cian, A.; Fischer, J.
J. Chem. Soc., Chem. Commun. 1994, 2231.
S0002-7863(96)01459-X CCC: $12.00 © 1996 American Chemical Society

Molecular Composite Knots
J. Am. Chem. Soc., Vol. 118, No. 38, 1996 9111
Figure 1. (a) Strategy previously used for making the knot (C) by (i)
intertwining two molecular threads (A) around two transition metal
centers (black dots) to form a double-stranded helical complex (B),
followed by (ii) a double cyclization reaction leading to the knotted
structure (C). (b) In the present work, two fragments, each containing
two chelating units, are interlinked to afford the long four-coordination
site molecular thread D. In a first step (iii) (D) is preorganized by
coordination to two metal centers to afford the precursor (E). In a
cyclodimerization reaction (iv) involving chemical functions attached
to the two ends of the semiknotted thread of (E), (F) and (G) are
obtained. (F) is a chiral species, both helical components being left-
handed, whereas (G) is the meso species (left- and right-handed double
helices present in the molecule). It should be noted that, for the sake
of simplicity, in this figure and throughout this paper only one
enantiomer for a chiral species is depicted and represents this enantiomer
together with its mirror image.
Figure 2. Acyclic precursors and synthetic reactions leading to the
four-coordination site molecular thread 1.
complexes.14-16 Propargyl ethers were introduced as end-
functional groups so that the cyclization step (iv) of Figure 1
can be performed by a Glaser-Eggligton coupling reaction of
terminal acetylenes. We selected this latter reaction in the
present work because it turned out to be particularly advanta-
geous in previous cyclooligomerization reactions leading to [3]-
and [poly]catenates.17 Finally, in order to allow the system to
find its way to the desired precursor by complexation to two
metal centers (formation of (E) in Figure 1), we connected the
two rigid blocks 7 (expected to become the two strands of the
helical core) by a long and flexible linker 8 derived from
heptaethylene glycol.
The bridged bis-1,10-phenanthroline 5 was prepared in 62%
yield by reacting 1,3-dilithiobenzene18 with 2 equiv of 2-(p-
anisyl)-1,10-phenanthroline (4) in tetrahydrofuran22 at room
temperature followed by hydrolysis and oxidation by MnO2.
Diphenol 6 was obtained by the drastic pyridinium chloride
demethylation procedure described earlier13,19 and subsequently
reacted with 1 equiv of propargyl bromide, thus affording the
monoacetylenic subunit 7 in 46% yield after chromatographic
purification. Finally, the linear thread 1 was formed in 82%
yield by reacting 2 equiv of bis-chelate 7 with 1 equiv of the
chain 8, diiodo derivative of heptaethylene glycol.20
(2) Synthesis of the Helical Precursor Copper Complex.
The long flexible tetrachelating compound 1, corresponding
to the molecular thread D of Figure 1, was expected to
afford the double-helical precursor E (Figure 1) in the presence
of 2 equiv of copper(I). In fact, when 1 was reacted with
[Cu(CH3CN)4+][PF6-] in acetonitrile, we obtained a mixture
of two copper(I) complexes 22+ and 32+ depicted in Figure 3.
Both complexes appeared very stable (no detectable ligand
exchange or equilibration even after 1 h heating at 60 °C in
DMSO). Unfortunately, they could not be separated by
chromatography since they displayed identical deep red color
1
and absolutely identical polarity. Nevertheless, H NMR and
mass spectroscopy studies allowed us to determine the precise
nature as well as the respective proportions of 22+ and 32+. The
two complexes, formed in a 1/3-7/3 ratio, had both helical
structures as clearly evidenced by the highly characteristic
chemical shift of their H3; H3′ protons (see Figure 7)12,13 and
corresponded to complexes of the type one ligand/two copper-
(15) Ru¨ttiman, S.; Piguet, C.; Bernardinelli, G.; Bocquet, B.; Williams,
A. F. J. Am. Chem. Soc. 1992, 114, 4230.
(16) Constable, E. C.; Hannon, M. J.; Tocher, D. A. Angew. Chem., Int.
Ed. Engl. 1992, 31, 230. Constable, E. C.; Hannon, M. J.; Tocher, D. A.
J. Chem. Soc., Dalton Trans. 1993, 1883.
(17) Dietrich-Buchecker, C. O.; Khemiss, A. K.; Sauvage, J.-P. J. Chem.
Soc., Chem. Commun. 1986, 1376. Bitsch, F.; Dietrich-Buchecker, C. O.;
Khemiss, A. K.; Sauvage, J.-P.; Van Dorsselaer, A. J. Am. Chem. Soc. 1991,
113, 4023.
(18) Seebach, D.; Neumann, H. Chem. Ber. 1974, 107, 847.
(19) Curphey, T. J.; Hoffman, E. J.; McDonald, C. Chem. Ind. 1967,
1138.
(20) Crude heptaethylene glycol was obtained by distillation of
commercially available PEG 300. The heptaethylene glycol containing
fraction was transformed into the corresponding ditosylate, which was
purified by chromatography according to: Fenton, D. E.; Parkin, D.;
Newton, R. F. J. Chem. Soc., Perkin Trans. 1 1981, 449. Finally, the
ditosylate was reacted with NaI in refluxing acetone to afford quantitatively
the diiodo derivative 8.

9112 J. Am. Chem. Soc., Vol. 118, No. 38, 1996
Carina et al.
a)
b)
Figure 3. (a) The two helicoidal dicopper(I) precursor complexes: preknot 22+ and premacrocycle 32+. (b) Schematic representation of their
enantiomers.
Figure 4. Synthesis of the reference prime knot 92+
.
(I) as shown by ES-MS. Additional information about their
precise structures was only gained after we achieved the
independent synthesis of the corresponding prime trefoil knot
92+ depicted in Figure 4.
the acetylenic oxidative coupling reaction (cyclodimerization
step expected to afford the composite knots) was attempted on
their crude mixture following the procedure described earlier.17
A DMF solution containing (22+, 32+) was stirred for 3 days at
room temperature in the presence of large amounts of CuCl
and CuCl2. After workup and chromatographic separation (on
silica with CH2Cl2 plus small amounts of CH3OH as eluent),
three varieties of complexes were isolated and characterized as
the compounds (104+, 114+), (124+, 134+), and (144+, 154+) in
2.5, 4.8, and 1.8% yield, respectively (Figure 5).
1
Careful comparison between the H NMR and 13C NMR
spectra of the well-characterized knot 92+ and the mixture of
precursor complexes (22+, 32+) allowed us to identify the minor
component 22+ as being the expected (E) type preknot of Figure
1. 92+ and 22+ had virtually superimposable spectra both in
the aromatic region and for the signals corresponding to the
poly(oxyethylene) fragments. This evidenced the strong simi-
larity in the spatial arrangement of the organic backbone for
92+ and 22+. These preliminary conclusions were later fully
confirmed when we determined the structures of the cyclization
An ES-MS study readily showed that the complexes isolated
and depicted in Figure 5, 104+ to 154+, were all cyclic dimers.
They all displayed exactly the same mass spectra as the one
expected for the composite knots: three peaks observed at
compounds derived from 22+ and 32+
.
1873.94, 1200.85, and 864.47 corresponding to [dimer (PF6)2]2+
,
(3) Cyclodimerization Leading to the Composite Knots.
[dimer(PF6)]3+, and [dimer]4+, respectively. But since these
tetranuclear species resulted from cyclodimerization reactions
Since the precursors 22+ and 32+ could not be isolated pure,

Molecular Composite Knots
J. Am. Chem. Soc., Vol. 118, No. 38, 1996 9113
Table 1
(104+ + 114+
)
a
92+
major
minor
(124+ + 134+
)
H3/3′
H4/4′
H5/5′
H6/6′
H7/7′
H8/8′
H9/9′
Ha
Hb/b′
Hc
H0/0′
Hm/m′
HR
6.49
7.86
7.91
7.99
8.39
7.66
6.61/6.52
8.22/7.87
8.23/7.92
8.02/7.99
8.35/8.42
7.62/7.70
4.56/4.44
9.72
6.96
7.15
7.07/7.19
5.70/5.93
3.29
6.55/6.52
8.01/7.86
7.93
6.45
7.73
7.78
7.90/7.85
8.32/8.23
7.62/7.43
4.41/3.82
9.55
6.82
7.03
7.99
8.44/8.40
7.72/7.74
4.63/4.51
9.74
6.96
7.21
7.10/7.16
5.72/5.98
3.29
9.71
6.95
7.18
7.07
5.71
3.29
3.91
7.09/6.88
5.85/5.63
3.52
Hη
3.90
3.90
2.83
a Dimers 124+ and 134+ being formed in a 1/1 ratio and presenting
strong similarities in their 1H NMR spectra; the table gives only average
values for the chemical shifts of their protons. Depending on which
proton is considered, this average concerns either two identical protons
belonging to both diastereoisomers 124+ and 134+ (Hc for example) or
two nonidentical but undiscrimable protons located on the same
diastereoisomer as for example H3 and H3′.
Figure 5. Cyclization reaction leading to the three families of dimers,
K-K, M-M, and K-M. Note that 104+ (K(-)-K(-)) and 114+ (K(-)
K(+)) correspond to (F) and (G) in Figure 1, respectively.
-
Figure 6. Expected theoretical yields of the various topological
diastereoisomers when starting from a preknot (p-K) and premacrocycle
(p-M) mixture in a 1:7/3 ratio.
occurring among two types of precursors (preknot 22+ and
premacrocycle 32+), each of them being chiral, many isomers
were equally expected. The various topological stereoisomers
(enantiomers or diastereoisomers) that were assumed to be the
outcome from cyclodimerization reactions between 22+ and 32+
are schematically represented in Figure 6. Presuming that both
precursors display the same reactivity and knowing that they
were present in the initial mixture in a 1/3-7/3 ratio, we were
also able to forsee, according to statistical laws, the proportions
in which each product will be formed.
Figure 7. 1H NMR spectra at 400 MHz in CD2Cl2 of the prime knot
K (92+) and the composite knots (K-K) (dimers 104+, 114+) with
numbering scheme.
1
involved, we see nevertheless that the H NMR spectrum of
one of them is totally superposable with that of 92+. This
striking analogy observed in the aromatic region as well as in
the 3-4 ppm region (where the various signals corresponding
to the polyoxyethylenic chains appear) strongly suggested that
the dimers (104+, 114+) were the desired target composite knots
(Figure 7). Our assumption was fully confirmed by the
observation of a strong interfragment NOE between the central
protons of the flexible chains (Hη) and some of the protons
located on the phenanthroline backbones (H4′ and H5′). This
effect, also observed for 92+ and all the previous knots studied
so far13 brought precious information about the spatial arange-
ment of the OCH2(CH2OCH2)nCH2O fragments relative to the
phenanthrolines. Such spatial relative disposition was not
B. Characterization of the Composite Knots. Whereas
the dimeric nature of the copper(I) complexes belonging to one
of the three topologically different families given in Figure 6
(K-K, M-M, or K-M family) was easily established by mass
spectroscopy, discrimination between them appeared much more
difficult and could finally only be achieved after an extensive
1
1- and 2-D H NMR study. The data obtained during these
studies are collected in Table 1 (see Experimental Section) and
clearly indicate close similarities between the reference prime
trefoil knot 92+ and the complexes (104+, 114+). Although we
cannot specify which diastereoisomer of the latter family is

9114 J. Am. Chem. Soc., Vol. 118, No. 38, 1996
Carina et al.
Figure 9. 1H NMR spectra (3-4 ppm region) at 400 MHz in CD2Cl2
of the dimers, K-K, K-M, and M-M.
1
acrocycle 32+ could be identified by comparative H NMR
studies as being “mixed” complexes. The latter denomination
accredits only their special topology: according to the NMR
data, each topological diastereoisomer of the (144+, 154+) family
appeared as the summation of one preknot (p-K) and one
premacrocycle (p-M). Each of these species being chiral (left-
or right-handed), their association may lead to four topologically
distinct compounds and hence we expected a rather complicated
1H NMR spectrum.
Figure 8. 1H NMR spectra at 400 MHz in CD2Cl2 of the prime knot
K (92+) and the M-M dimer family (complexes 124+, 134+).
observed for the two other families of dimers, (124+, 134+) and
(144+, 154+).
Contrasting strongly with (104+, 114+), the family of the major
dimers isolated (124+, 134+) showed between 3 and 4 ppm a
1H NMR pattern totally different from that observed for the
prime knot 92+, its most striking feature being the chemical shift
of the Hη protons located in the central part of the polyoxyeth-
ylenic chains; their signal at 2.83 ppm (upfield chemical shift
1
The H NMR spectrum of (144+, 154+) did indeed present
an intractable aromatic region from which no structural informa-
tion could be drawn, but by contrast, the 3-4 ppm area brought
clear evidence for the “mixed” structure proposed. As shown
in Figure 9, the signals between 3 and 4 ppm (protons of the
polyoxyethylenic chains) resulted from the overlap of the two
of over 1 ppm when compared to the 3.9 value in 92+ or (104+
,
114+) indicated that they were located very close to aromatic
nuclei. On the other hand, the aromatic region of the spectrum,
although slightly different from that obtained for the prime or
patterns characterizing the composite knots K-K (104+, 114+
)
and the dimers of type M-M (124+, 134+), respectively. It is
worthwhile to mention that these K-M type dimers present only
three crossing points and therefore are, despite their complicated
appearance, simple trefoil knots.
composite knots, brought clear evidence that the dimers (124+
,
134+) contained like (104+, 114+) double helices in their central
core (see Figure 8). Finally, additional observation of a strong
interfragment NOE between Hη and Hm, Ho of the pendent
phenyl nuclei but no longer with the phenanthroline’s H4′ and
H5′, suggested that the flexible chains now stayed far away from
the phenanthroline-containing helical core, as would be the case
in a dimeric macrocycle curled up onto four copper(I) centers
(see Figure 5). Our tentative structure elucidation could later
be confirmed by a demetalation experiment. Reaction of the
dimers (124+, 134+) with a large excess of KCN afforded a
white, almost insoluble solid in quantitative yield. Its FAB mass
spectrum was the one expected for a dimer (peaks observed at
3206.8 and 1603.5 for [M‚3H]+ and [M‚3H]2+, respectively)
whereas its 1H NMR spectrum, very similar to that of the
precursor molecular string 1, corresponded fully to that expected
for a large flexible macrocycle.
Identification of the three types of dimers K-K, M-M, and
K-M being achieved, we were subsequently able to estimate
the global outcome of the coupling reaction to which a
precursors p-K and p-M mixture had been submitted. The most
striking feature was certainly the fact that target composite knot
K-K was obtained in a yield far superior to the one anticipated.
Indeed, according to statistical distribution laws, we expected
the dimers K-K/M-M/K-M in a 9/49/42 ratio, but in fact
they were obtained in the ratio 28/54/18. This diastereoselection
favoring strongly the composite knots K-K versus dimers
M-M and K-M may be related to a more suitable spatial
arrangement of the two terminal acetylenic functions in a
relatively rigid preknot p-K when compared to that in prem-
acrocycle p-M. Similar considerations may also help to explain
an other surprising observation: within each family of dimers
containing the K subunit (either K-K or K-M) the various
possible topological diastereoisomers (see Figure 6) were again
The third family of dimers obtained in the Glaser coupling
reaction performed on the mixture of preknot 22+ and prem-

Molecular Composite Knots
J. Am. Chem. Soc., Vol. 118, No. 38, 1996 9115
and was then added over 3 h to a degassed solution of 2.43 g (8.5
mmol) of 422 in 100 mL of dry THF, under argon at room temperature.
After the resulting dark red solution was stirred for a further 45 h under
argon at room temperature, it was hydrolyzed with water and then
evaporated to dryness. The crude product was dissolved in CH2Cl2
and washed with water. The organic layer was rearomatized with MnO2
(∼20 g), dried over MgSO4, filtered, and adsorbed on aluminium oxide
(activity grade II-III). Column chromatography on aluminium oxide
eluted with CHCl3/hexane (1/1), then with CHCl3, and finally with
CHCl3 + 5% MeOH afforded pure 5 (3.45 g, 5.3 mmol, 62% yield):
1H NMR (CDCl3) δ 9.75 (s, 1H, Ha), 8.72 (d, 2H, Hb, J ) 7.8 Hz),
8.55 (m, 8H, H3,4,o), 8.30 (d, 2H, H7, J ) 8 Hz), 8.11 (d, 2H, H8, J )
8 Hz), 7.82 (t, 1H, Hc, J ) 7.8 Hz), 7.80 (s, 4H, H6,5), 7.06 (d, 4H, Hm,
J ) 8 Hz); FAB-MS m/z found 647.2 [MH]+, calcd 647.7.
not formed according to the statistical distribution laws. The
1H NMR spectrum of the composite knots given in Figure 7
illustrates nicely this latter statement: instead of the 1/1 ratio
expected for the two enantiomers (K(+)-K(+); K(-)-K(-)) and
the meso diastereoisomer K(+)-K(-), we observe a 1/2 ratio.
In this case, enantioselectivity is clearly observed. Either
homochiral or heterochiral composite knots are preferred,
indicating that in the course of the cyclization reaction leading
to the product, weak forces between the two constituent preknot
fragments are significant and tend to favor interactions between
preknots of identical or different chirality respectively.
In conclusion, the present work demonstrates the power of
synthetic strategies based on the use of transition metals as
templates. Some time ago, simple catenanes were made
available on a real preparative scale,24 and the level of
complexity of the compounds prepared increased gradually with
time since the first report. In parallel, the simplest nontrivial
knot was obtained, first in very low yield and, recently, in a
much more preparative fashion.14 This improvement suggested
that more complex knots and composite knots should become
accessible, although the real making of such molecular systems
would have appeared totally unrealistic only a decade ago. The
synthesis of the composite knots 104+ and 114+ is still far from
being really preparative, but it represents a good indication that
molecular chemical topology may be extended in the future
toward more and more complex systems, in a way reminiscent
of the DNA-based approach developed by Seeman and co-
workers.11 In addition to the synthesis of the composite knots
104+ and 114+, an interesting but unexpected observation was
made, related to the selectivity of dimer formation. Remarkably,
when two preknots p-K (E of Figure 1 or 22+ of Figure 3) react
with one another to form a cyclic product (composite knot),
some kind of enantioselection clearly takes place via intermo-
lecular interactions between the two units to be coupled.
Preparation of 6. 6 was obtained following the literature procedure:
1.22 g (1.0 mmol) of 5 was added, under argon, to ∼60 mL of
22
anhydrous pyridinium hydrochloride at 130 °C. After the solution was
refluxed at 190-200 °C for 4 h, the mixture was cooled to 130 °C and
hydrolyzed. The yellow crude acidic diphenol 6 was suspended in 80
mL of hot water and the suspension neutralized to pH ∼7.3. Filtration
and drying afforded red 6 (1.02 g, 1.6 mmol, 86% yield): 1H NMR
(DMSO-d-6) δ 9.87 (s, 2H, HOH), 9.74 (s, 1H, Ha), 8.72 (d, 2H, Hb, J
) 7.8 Hz), 8.66 (m, 4H, H3,4), 8.50 (d, 2H, H7, J ) 8.4 Hz), 8.40 (d,
4H, Ho, J ) 8.4 Hz), 8.27 (d, 2H, H8, J ) 8.4 Hz), 8.00 (s, 4H, H6,5),
7.91 (t, 1H, Hc, J ) 7.8 Hz), 6.88 (d, 4H, Hm, J ) 8.4 Hz); FAB-MS
m/z found 619.1 [MH+], calcd 619.6.
Preparation of 7. According to literature,23 1 g (1.6 mmol) of 6
and 0.66 g (3.84 mmol) of K2CO3 in 50 mL of DMF were stirred under
argon at 50 °C for 1 h; a solution of 121 µL (1.6 mmol) of BrCH2CtCH
in 10 mL of DMF was then added dropwise. After a further 6 h stirring
at 50 °C, the suspension was cooled, filtered, and evaporated to dryness.
Column chromatography over aluminium oxide (eluent CHCl3 + 4%
MeOH) yielded pure 7 (0.49 g, 0.74 mmol, 46% yield): 1H NMR
(DMSO-d-6) δ 9.81 (s, 1H, HOH), 9.77 (s, 1H, Ha), 8.75-8.50 (m, 10H,
Hb,b′,o,o′,3,3′,4,4′), 8.37 (d, 2H, H7,7′, J ) 9 Hz), 8.28 (m, 2H, H8,8′), 8.03
(s, 2H, H6,5), 8.00 (s, 2H, H6′,5′), 7.90 (t, 1H, Hc, J ) 7.8 Hz), 7.02 (d,
2H, Hm, J ) 8.4 Hz), 6.82 (d, 2H, Hm′, J ) 8.4 Hz), 4.85 (d, 2H, H9,
J ) 2 Hz), 3.61 (t, 1H, H10, J ) 2 Hz); FAB-MS m/z found 657.1
[MH+], calcd 657.7.
Experimental Section
Preparation of 1. A suspension of 7 (0.78 g, 1.19 mmol) and Cs2-
CO3 (3 g, 9.2 mmol) was stirred in 12 mL of freshly distilled DMF,
under argon at 60 °C, for 1 h. Then a solution of 820 (0.31 g, 0.47
mmol) in 30 mL of DMF was added dropwise over 8 h. The solution
was stirred overnight, under argon at 60 °C, then cooled, filtered, and
evaporated to dryness. Crude 1 was dissolved in CHCl3, washed with
water, and then adsorbed onto aluminium oxide. Column chromatog-
raphy over aluminium oxide (eluent, CHCl3/EtOEt ) 1/1 and then
CHCl3) yielded pure 1 (0.612 g, 0.382 mmol, 82% yield): 1H NMR
(CDCl3) δ 9.72 (s, 2H, Ha), 8.76 (m, 4H, Hb,b′), 8.40 (m, 16H,
General Procedures. All the chemicals were of the best com-
mercially available grade and were used without further purification.
Thin-layer chromatography (TLC) was performed on aluminum sheets
coated with silica gel 60 F254 (Merck 5554), or on plastic sheets
precoated with aluminium oxide N/UV254 (Macherey Nagel 802021).
After elution, the plates were either examined under a UV lamp or
exposed to I2. Column chromatography was carried out on silica gel
60 (Merck 9385, 230-400 mesh). UV-visible spectra were recorded
on a Kontron Instruments Uvikon 860 spectrophotometer. Fast atom
bombardment mass spectrometry (FAB-MS) was performed using a
krypton primary atom beam in conjunction with a 3-nitrobenzyl alcohol
matrix on a ZAB-HF mass spectrometer. Electrospray mass spectrom-
etry was performed by dissolving the compound or complex in CH2-
Cl2 and injecting the solution into a VG BioQ triple-quadrupole
spectrometer (VG BioTech Ltd., Altrincham, UK), with a mass-to-
charge (m/z) range of 4000, using a cone voltage (Vc) of 40 V, and a
Ho,o′,3,3′,4,4′), 8.26 (d, 2H, H7, J ) 8.4 Hz), 8.24 (d, 2H, H7′, J ) 8.4
Hz), 8.07 (d, 2H, H8, J ) 8.4 Hz), 8.05 (d, 2H, H8′, J ) 8.4 Hz), 7.82
(t, 2H, Hc, J ) 8 Hz), 7.78 (s, 8H, H6′,5′,6,5), 7.12 (d, 4H, Hm′, J ) 8.8
Hz), 7.04 (d, 4H, Hm, J ) 8.4 Hz), 4.77 (d, 4H, H9, J ) 2.2 Hz), 4.19
(m, 4H, HR), 3.89 (m, 4H, Hâ), 3.65 (m, 20H, Hγfη), 2.59 (t, 2H, H10,
J ) 2.2 Hz); ES-MS m/z found 1604.3 ([MH]+) calcd 1604.7; found
802.5 ([M‚2H]2+), calcd 802.9; found 535.3 ([M‚3H]3+), calcd 535.6;
found 401.7 ([M‚4H]4+), calcd 401.9.
1
source temperature of ∼30 °C. The H NMR spectra were recorded
Preparation of 22+ and 32+. Complexes 22+ and 32+ were obtained
according to the literature22 by mixing 120 mg (0.075 mmol) of 1 and
55.8 mg (0.15 mmol) of [Cu(CH3CN)4]PF6 in CH3CN, under argon.
The solution was stirred for 1 h, and after the solvent was evaporated
to dryness 22+ and 32+ were obtained in quantitative yield as a mixture.
The two complexes exhibit the same color and Rf. Therefore, they
could not be isolated and fully characterized: 1H NMR (CD2Cl2) δ
9.68 (s, 2H, Ha), 8.42-8.35 (m, 4H, H7,7′), 8.00-7.78 (m, 12H,
with a Bruker AC 300, WP200 SY, or WP400SY spectrometer.
Preparation of 5. A 14.5 mL sample of t-BuLi (1.2 M in pentane,
17.4 mmol) was added very slowly to a degassed solution of 1.00 g
(4.2 mmol) of 1,3-dibromobenzene in 50 mL of dry THF, under argon,
at -78 °C.18 After this addition, the solution was warmed to 0 °C and
then immediately cooled to -78 °C. The solution was titrated according
to the literature21 in order to see whether all the t-BuLi had reacted
H6′,5′,6,5,44′), 7.66 (m, 4H, H8,8′), 7.16-7.06 (m, 8H, Ho,o′), 7.01 (t, 2H,
(21) Gilman, H.; Cartledge, F. K. J. J. Organomet. Chem. 1964, 2, 447.
(22) Dietrich-Buchecker, C. O.; Nierengarten, J. F.; Sauvage, J.-P.;
Armaroli, N.; Balzani, V.; De Cola, L. J. Am. Chem. Soc. 1993, 115, 11237.
(23) Dietrich-Buchecker, C. O.; Hemmert, C.; Khemiss, A. K.; Sauvage,
J. P. J. Am. Chem. Soc. 1990, 112, 8002.
(24) Dietrich-Buchecker, C. O.; Sauvage, J. P.; Kintzinger, J. P.
Tetrahedron Lett. 1983, 24, 5095. Dietrich-Buchecker, C. O.; Sauvage,
J.-P.; Kern, J.-M. J. Am. Chem. Soc. 1984, 106, 3043.
Hc, J ) 8 Hz), 6.94-6.87 (m, 4H, Hb,b′), 6.58-6.47 (m, 4H, H3,3′),
5.91-5.66 (m, 8H, Hm,m′) 4.24-4.21 (m, 4H, H9), 3.90-2.83 (m, 28H,
OCH2CH2O), 2.65 (t, 2H, H10, J ) 2.2 Hz). ES-MS m/z found 1875.8
([M(PF6)]+), calcd 1875.9; found 864.9 ([M]2+), calcd 865.4.
Preparation of 92+
reacted according to the literature14,22 in CH3CN with 234 mg (0.628
. A 388 mg (0.628 mmol) sample of 6 was

9116 J. Am. Chem. Soc., Vol. 118, No. 38, 1996
Carina et al.
mmol) of [Cu(CH3CN)4]PF6 to obtain the tetraphenolic double helix.
The 520 mg (0.314 mmol) of the tetraphenolic double helix and 360
mg (0.659 mmol) of 8 in the presence of 1.1 g (3.4 mmol) of Cs2CO3
were reacted according to the literature.14,22 Column chromatography
on silica gel (eluent, CH2Cl2 + 4% MeOH) and then on aluminium
oxide (eluent, CH2Cl2 + 2.5% MeOH) yielded 92+ (160 mg, 0.071
mmol, 22% yield): 1H NMR, see Table 1; ES-MS m/z found 2090.0
([M(PF6)]+), calcd 2090.1; found 972.5 ([M]2+), calcd 972.6.
ES-MS m/z found 1873.9 ([M(PF6)2]2+), calcd 1873.9; found 1200.8
([M(PF6)]3+), calcd 1200.9; found 864.5 ([M]4+), calcd 864.5.
Demetalation of (124+, 134+). Pure (124+, 134+) (0.040 g, 0.01
mmol) in CH2Cl2 (20 mL) was treated with a large excess of KCN
(0.440 g, 6.8 mmol) at room temperature. This demetalation reaction,
monitored by TLC and the disappearance of the characteristic dark red
color of the magnetically stirred solution, was only complete after 4
days, during which the KCN had been added in successive batches
(∼110 mg each). After decantation of the colorless CH2Cl2 layer, we
observed the formation of a white precipitate between both phases. It
was filtered on paper, washed with water, and dried affording the pure
macrocycle 16 as a colorless solid (0.030 g, quantitative yield): 1H
NMR (DMSO-d-6) δ 9.68 (s, 4H, Ha), 8.50 (d, 8H, Hb,b′, J ) 8 Hz),
8.48-8.44 (m, 8H, H3,3′), 8.40-8.35 (m, 8H, H4,4′), 8.33-8.26 (m, 24H,
Preparation of the Dimers 104+ to 154+. Under highly anhydrous
conditions, 450 mg (0.223 mmol) of the crude mixture (22+ + 32+),
3.02 g (30.5 mmol) of anhydrous CuCl, and 0.72 g (5.3 mmol) of
anhydrous CuCl2 were suspended in 32 mL of dry DMF in a simple
one-necked, round-bottomed flask. The latter was stoppered with a
drying tube filled with silica gel so that the mixture was protected
against moisture but in contact with air. The dark brown-red suspension
was magnetically stirred at room temperature over 3 days, after which
the DMF was evaporated to dryness. The almost black solid residue
was taken up in 200 mL of CH2Cl2 and 200 mL of 5% HCl-water
solution. After decantation, the acidic aqueous layer was extracted five
times with 50 mL portions of CH2Cl2. The combined organic layers
were washed twice with 100 mL portions of 5% HCl solution and once
with pure water. This wet CH2Cl2 phase was then treated (overnight,
magnetic stirring) with a large excess of KPF6 dissolved in a minimum
of water. By means of this exchange reaction the dimers were obtained
H7,7′,o,o′), 8.05 (d, 4H, H8′, J ) 8.4 Hz), 8.03 (d, 4H, H8, J ) 8.4 Hz),
7.82 (s, 8H, H5′,6′), 7.80 (s, 8H, H5,6), 7.66 (t, 4H, Hc, J ) 8 Hz), 6.80
(d, 8H, Hm′, J ) 8.9 Hz), 6.73 (d, 8H, Hm, J ) 8.9 Hz), 4.85 (s, 8H,
H9), 3.92 (m, 8H, HR), 3.63 (m, 8H, Hâ), 3.50-3.43 (m, 40H, Hγfη);
FAB-MS m/z found 3206.8 ([M‚3H]+), calcd 3206.6; found 1603.5
([M‚3H]2+), calcd 1603.3.
Acknowledgment. We thank the CNRS for financial support
and the Swiss National Science Foundation for a Postdoctoral
Fellowship to R.F.C. We also thank J.-D. Sauer, M. Mar-
tigneaux, and R. Graff for high-field NMR spectra as well as
Dr. E. Leize, Dr. A. Dupont-Gervais, and Dr. A. Van Dorsselaer
for ES-MS measurements.
-
exclusively as their PF6 salts. The resulting organic layer, washed
with water, was dried and evaporated to dryness to yield ∼102 mg of
a crude dark red mixture of dimers 104+ to 154+. Column chroma-
tography on silica gel (eluent, CH2Cl2 + 3% MeOH) afforded 23 mg
of (104+ + 114+) (2.5% yield), 40 mg of (124+ + 134+) (4.8% yield)
and 14 mg of (144+ + 154+) (1.6% yield): 1H NMR, see Table 1;
JA961459P