Synthesis of a bis-macrocycle containing two back-to-back rigidly connected 1,10-phenanthroline units as a central core and its incorporation in a handcuff-like catenane

Article abstract of DOI:10.1002/chem.200700671

A bis-macrocycle containing two back-to-back connected 1,10-phenanthroline chelates has been prepared. The synthetic strategy involves the preparation of a monocyclic precursor consisting of a 1,10-phenanthroline5,6-dione fragment incorporated in a 30-mem

Full text of DOI:10.1002/chem.200700671

FULL PAPER
DOI: 10.1002/chem.200700671
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Chem. Eur. J. 2007, 13, 7584 – 7594

FULL PAPER
Synthesis of a Bis-macrocycle Containing Two Back-to-Back Rigidly
Connected 1,10-Phenanthroline Units as a Central Core and its Incorporation
in a Handcuff-Like Catenane
Julien Frey,[a] Tomµsˇ Kraus,[b] ValØrie Heitz,*[a] and Jean-Pierre Sauvage*[a]
Abstract: A bis-macrocycle containing
two back-to-back connected 1,10-phe-
nanthroline chelates has been pre-
pared. The synthetic strategy involves
the preparation of a monocyclic precur-
sor consisting of a 1,10-phenanthroline-
5,6-dione fragment incorporated in a
30-membered ring. This important in-
termediate has been prepared via two
distinct routes, both strategies relying
on the use of a ketal as a 1,2-dione pro-
tective group. A four-component con-
densation reaction between two mole-
cules of the macrocyclic dione and two
equivalents of ammonia (used in large
excess) in the presence of a reducing
agent (Na2S2O4) leads to the desired
bis-ring in good yield. The most direct
synthetic route allows preparation of
the bis-macrocycle in seven steps from
1,10-phenanthroline in an overall yield
of 14%. Using the now well-estab-
lished “gathering and threading” effect
of copper(I), a doubly threaded species
could be obtained in quantitative yield,
in which each ring of the bis-macrocy-
cle is threaded by a “molecular string”.
These fragments bear terminal allylic
groups, which are used to prepare the
final catenane by performing a double
ring-closing metathesis reaction. This
final cyclisation reaction is high yield-
ing and affords the desired catenane
consisting of a bis-macrocycle of which
the two cyclic units are threaded by a
large ring. The compound has been
fully characterised by classical tech-
niques. Electronic spectroscopy and
electrochemical measurements suggest
that the two copper complex subunits
do not interact electronically, in spite
of the aromatic nature of the bridging
ligand between the two metal centres.
Keywords: catenanes · chelates ·
copper · macrocycles · templates
Introduction
dynamic systems, generally referred to as molecular ma-
chines, is particularly active.[2]
Catenanes and rotaxanes[1] still represent challenging syn-
thetic targets, especially when the number of constituent
units and the topological complexity of the systems is in-
creased from the simple two-component prototypes, [2]cate-
nanes or [2]rotaxanes. Besides the synthetic challenge that
the preparation of such molecules represents, the construc-
tion and study of ever more complex systems of the cate-
nane and rotaxane family also holds promise in relation to
their novel properties. In this respect, the field of controlled
Among the catenanes and rotaxanes described to date,
either as molecular machine prototypes or simply as synthet-
ic targets, there have been only a few examples containing
bis- or multi-macrocycles. One of the most remarkable ex-
amples of such compounds is the “molecular elevator”[3] re-
ported a few years ago, the cyclic component of which con-
sists of a tris-cycle, that is, three connected rings.
In the present report, we describe the synthesis of a bis-
macrocycle, the two coordinating rings of which are linked
to one another in a highly rigid fashion, and which can be
regarded as a handcuff-like compound. Such a bis-ring can
be envisaged as being particularly useful for the construction
of various relatively complex interlocking systems. In addi-
tion, as a further topic of the present report, the bis-macro-
cycle is a precursor to a catenane consisting of a large ring
threaded through both cyclic units of the bis-ring.[4] Such a
catenane can be prepared in good yield by means of a cop-
per(I)-templated strategy.
[a] J. Frey, Dr. V. Heitz, Dr. J.-P. Sauvage
Institut de Chimie, Laboratoire de
Chimie Organo-MinØrale, UniversitØ Louis Pasteur
4 rue Blaise Pascal, 67070 Strasbourg Cedex (France)
Fax : (+33)390-241-368
E-mail: heitz@chimie.u-strasbg.fr
sauvage@chimie.u-strasbg.fr
[b] Dr. T. Kraus
Institute of Organic Chemistry and Biochemistry
Flemingovo nam. 2, 16610 Prague (Czech Republic)
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J.-P. Sauvage, V. Heitz et al.
Results and Discussion
The copper(I)-assisted genera-
tion of threaded species, which
involves passing a string-like
molecular fragment through a
ring, has been used extensively
in our group to generate pre-
cursors to numerous catenanes
and rotaxanes.[5] Thus far,
monocyclic units have been
used almost exclusively as
starting compounds. The use of
a
bis-macrocycle has been
briefly described in a prelimi-
nary communication.[6] The
threading principle is indicated
in Figure 1, in a very schematic
fashion.
Figure 2. Bis-macrocycle 1 consists of two fused 30-membered rings. It was prepared by a homocondensation
reaction between two equivalents of the macrocyclic dione and two moles of ammonia.
as depicted in Schemes 1–4. The main difference between
these two routes is that, in the first, positions 2 and 9of the
phen nucleus have to be functionalised before the p-anisyl
groups are attached at these two positions, whereas in the
second, direct attachment of the p-anisyl groups can be car-
ried out without prior functionalisation.
Synthesis via 2,9-dichloro-1,10-phenanthroline and Suzuki
coupling: In executing the first route, several distinct phases
are involved: i) functionalisation of the 2- and 9-positions of
the phen nucleus, followed by ii) formation of the 5,6-dione
and its protection; iii) preparation of a 2,9-diaryl-1,10-phe-
nanthroline derivative bearing appropriate functions at the
aryl groups and the protected 5,6-dione; iv) formation of the
30-membered ring and liberation of the free a-dione;
v) condensation reaction leading to 1.
Figure 1. Principle of various threading reactions. a) The simple one-plus-
one copper(I)-induced passing of mono-chelate through
ring.[5]
a
a
b) Double threading reaction: two mono-chelate units are threaded
through the rings of a bis-macrocycle. In the present case, the coordinat-
ing units (U-shaped symbols) are connected back-to-back in a rigid fash-
ion. c) Analogous reaction as in b) but using two-chelate containing mo-
lecular threads. An example of this reaction has recently been reported.[7]
Compound 22+·2Brꢀ was obtained according to a litera-
ture account by treating 1,10-phenanthroline monohydrate
with a large excess of 1,3-dibromopropane in nitrobenzene.
The reaction could be carried out on a relatively large scale
(10 g of 1,10-phenanthroline monohydrate afforded 16.9g of
22+·2Brꢀ as ochre crystals). 22+·2Brꢀ was subsequently oxi-
dised to the neutral species 3 using [K3Fe(CN)6] in basic
aqueous solution. In spite of the mediocre yield of this reac-
tion, multi-gram batches of 3 could be prepared relatively
easily. 2,9-Dichloro-1,10-phenanthroline (4) was then pre-
pared in high yield (88%) by reacting 3 with PCl5 and
POCl3 at 1108C.
The a-dione 5 was prepared according to a literature pro-
cedure[10] by oxidising 4 with KBr and HNO3 in concentrat-
ed sulfuric acid. After work-up and column chromatography,
5 was obtained as a yellow solid. The dione function was
subsequently protected as the ketal 6 by reacting 5 with 2-
nitropropane in acetonitrile under basic conditions (chroma-
tographic purification afforded 6 in 90% yield as a bright-
yellow solid).
Design and synthesis of the bis-macrocycle: In order to
exert strict geometrical control over the system and to ad-
vantageously apply our experience in the field of 1,10-phe-
nanthroline (phen) coordination chemistry, a system com-
bining high rigidity and phenanthroline units was designed
and subsequently synthesised. The bis-macrocycle described
in the present work is depicted in Figure 2, along with its
succinct retrosynthetic analysis.
The central motif consists of two back-to-back connected
bidentate chelates, the ensemble being highly rigid. Related
compounds have been synthesised and studied in recent
years, mostly as bridging ligands between Ru and Rh cen-
tres.[8,9]
The macrocyclic dione depicted in Figure 2, precursor to
bis-macrocycle 1, could be prepared via two distinct routes,
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Synthesis of a Bis-macrocycle and Its “Threading”
FULL PAPER
The sequence of reactions leading to 6 from phen is indi-
cated in Scheme 1.
7 was subsequently reacted with 6 in toluene and aqueous
Na2CO3, with Pd(PPh3)4 as catalyst (10% per chloro sub-
A
The next step involved a Suzuki coupling reaction with
the boronic acid 7, as shown in Scheme 2. 7 was first ob-
stituent). 8 was obtained in almost quantitative yield (97%)
after column chromatography.
The following sequence of reactions is depicted in
Scheme 3: i) deprotection of the phenol groups, ii) cyclisa-
tion, and iii) deprotection of the dione. The most important
feature of this sequence is that the first deprotection reac-
tion (8!9), which provides the free diphenol 9 in very high
yield (96%), can be carried out under experimental condi-
tions (HCl in dry Et2O/methanol at room temperature) that
do not affect the ketal protective group of the a-dione. The
macrocyclic compound 11 was then prepared from 9 and the
diiodo derivative of pentaethylene glycol, I-CH2-
(CH2OCH2)4-CH2-I (10),[12] following a well-established pro-
cedure. A mixture of 9 and 10 was slowly added to a vigo-
rously stirred suspension of Cs2CO3 in DMF at 608C. An ex-
cellent yield of 59% was obtained for this ring-forming reac-
tion, without loss of the dione protective group. Compound
11 was obtained as a yellow-orange oil.
Scheme 1. Protected dione 6 obtained from 1,10-phenanthroline in five
steps in an overall yield of 17%. i) 1,3-dibromopropane, PhNO2, 1208C,
4 h (88%); ii) [K3Fe(CN)6], NaOH, 2–58C, 2 h (35%); iii) POCl3, PCl5,
1108C, 8 h (88%); iv) H2SO4, HNO3, KBr, 808C, 3 h (71%); v) 2-nitro-
propane, Na2CO3, MeCN/H2O 1:1, 558C, 5 h (90%).
Finally, the dione function was liberated from its ketal
protective group. By heating a solution of 11 in water and
F3CCOOH at 508C in the presence of air, followed by
work-up and chromatography on silica, 12 was obtained as
an orange crystalline solid.
Compound 12 is a 30-membered ring, which could be
crystallised to afford single crystals. The structure of 12 was
solved by X-ray diffraction analysis and is shown in
Figure 3. As expected, 12 can be seen to be an essentially
ꢀ
planar compound. The C5 C6 bond is clearly a single bond
(d=1.540 Š), the dione being a real, non-delocalised one,
with C=O bond lengths of 1.208 and 1.217 Š. The two
phenyl rings borne by the phen-dione nucleus form an angle
that is significantly smaller than 1208: the N1-C2-C1’ and
N10-C9-C1’’ angles are 115.2 and 113.98, respectively, which
may be ascribed to the “pinching” effect of the ring.
Scheme 2. Key intermediate obtained in good yield by a Suzuki coupling.
i) [Pd(PPh3)4], Na2CO3, PhMe/H2O 2:1, 808C, 18 h (97%).
A
Synthesis by direct arylation of a protected phen-dione
(Dietrich-Buchecker reaction): Compound 8, used in the
previous strategy (Schemes 2 and 3), can alternatively be
prepared via a more direct route. The sequence of reactions
leading to 8 without functionalisation of the 2- and 9-posi-
tions prior to the attachment of the aryl groups at these two
positions is indicated in Scheme 4.
tained from 2-(4-bromophenoxy)tetrahydro-2H-pyran under
classical conditions,[11] that is to say, reaction with nBuLi at
ꢀ788C followed by addition of triisopropyl borate, B-
A
7 was obtained.
Scheme 3. Synthesis of the macrocyclic dione 12. i) HCl in Et2O, MeOH, RT, 2 h (96%); ii) high dilution, Cs2CO3, DMF, 608C, 4 d (59%); iii) TFA/H2O,
508C, 5 h (94%).
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J.-P. Sauvage, V. Heitz et al.
the 2- and 9-positions of 14 were introduced under very sim-
ilar experimental conditions to those used previously by
Dietrich-Buchecker et al.[15] The two-step procedure (14!
15!8) was preferred to the double arylation reaction (14!
8) on the grounds that mono-arylation reactions are general-
ly high yielding. This turned out to be true in the present
case.
Compound 14 was first reacted with the in situ generated
lithium derivative obtained from nBuLi and THP-protected
4-bromophenol at ꢀ788C, after which the intermediate was
hydrolysed and rearomatised using MnO2. 15 was obtained
as a yellow crystalline powder in 84% yield. Using exactly
the same procedure as for the preparation of 15, but now
starting from this compound, nBuLi, and protected 4-bro-
mophenol, 8 was obtained as a yellow solid in 95% yield.
Samples of 8 obtained via this second route (Scheme 4)
were, of course, identical to those prepared using the first
strategy (Scheme 2). They could be used in the same way to
complete the synthesis of the cyclic compound 12
(Scheme 3).
Figure 3. Ball-and-stick representation of the crystal structure of macro-
cycle 12.
Comparison of the two routes for the synthesis of macrocy-
clic dione 12: The first route, via 2,9-dichloro-1,10-phenan-
throline (4), consists of nine steps (excluding the prepara-
tions of the boronic acid 7 and the diiodo derivative 10).
The overall yield is 8%. The strong point of this strategy is
the almost quantitative yield of the double Suzuki coupling
reaction that furnishes 8. The second route comprises only
seven steps, which is an obvious advantage over the nine-
step route discussed previously. The overall yield of 14% is
significantly higher than that of the first route. The compari-
son is thus clearly in favour of the second strategy, although
some steps are relatively delicate, such as the conversion of
14 to 8.
Synthesis of the bis-macrocycle 1: The ultimate organic
target, bis-macrocycle 1, was obtained in good yield utilising
a condensation reaction that has been used in previous work
by others[8a] in the construction of bridging acyclic ligands. It
is depicted in Scheme 5.
Scheme 4. Double nucleophilic addition/aromatisation reaction leading to
8. i) H2SO4, HNO3, KBr, 1008C, 4 h (55%); ii) 2-nitropropane, Na2CO3,
MeCN/H2O 1:1, reflux, 8 h (66%); iii) 1) 2-(4-bromophenoxy)tetrahydro-
2H-pyran, nBuLi, THF, ꢀ788C, 2 h; 2) MnO2, CH2Cl2/PhMe 1:1, RT,
12 h (84%); iv) 1) 2-(4-bromophenoxy)tetrahydro-2H-pyran, nBuLi,
THF, from ꢀ788C to RT, overnight; 2) MnO2, CH2Cl2, RT, 2 h (95%).
Compound 12 was reacted in a melt obtained by fusing
solid Na2S2O3 (0.2 equivalents) and
a large excess of
NH4OAc at 1808C under an inert atmosphere. After work-
Oxidation of 1,10-phenan-
throline to its 5,6-dione (com-
pound 13) was carried out in a
similar way as that of com-
pound
H2SO4),[13] to afford 13 in a
moderate yield (55%) as
5
(KBr,
HNO3,
a
yellow crystalline solid. Protec-
tion of the dione 13[14] using 2-
nitropropane in CH3CN/H2O
afforded 14 (66% yield) as a
brownish-yellow
amorphous
Scheme 5. Preparation of bis-macrocycle 1 from dione 12. i) NH4OAc, Na2S2O4, molten salt at 1808C, 2 h
solid. The two aryl groups at
(70%).
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Synthesis of a Bis-macrocycle and Its “Threading”
FULL PAPER
up and chromatography, a 70% yield of 1 was obtained as a
18·2PF6 and Grubbs first-generation catalyst [RuCl2
A
poorly soluble yellow solid.
ACHTREUNG
react at room temperature for a long period of time. Work-
up and chromatographic purification furnished 19·2PF6 in
good yield (80%) as a red-brown solid. Compound 192+
consists of a mixture of isomers (E/Z alkene units).
Preparation of the ancillary ligand to be used in the thread-
ing step: As shown in Scheme 6, the 1,10-phenanthroline-
based ligand 17 was prepared in moderate yield (48%) from
2,9-di(p-hydroxyphenyl)-1,10-phenanthroline and 1-bromo-
3-butenyl in DMF in the presence of K2CO3. The two termi-
nal alkene functions of 17 are suitably predisposed for use
at a later stage to prepare a macrocycle by ring-closing
olefin metathesis (Grubbs methodology[16]).
The double cyclisation reaction could be easily monitored
1
by H NMR. After about 10 days of reaction, it was com-
plete. It was noted that this reaction, as well as related cate-
nane formation reactions,[18] require a long reaction time at
room temperature, in spite of the high proportion of “cata-
lyst” (ꢁ0.25 equivalents per double bond to be formed).
1
The H NMR spectra of the catenane and its precursor
1
are depicted in Figure 4. The H NMR spectrum of 182+ is
consistent with the symmetrical structure of the compound.
In spite of the presence of three diastereomers in 192+, the
NMR spectrum of the catenane is almost identical to that of
the open form of the precursor 182+ (Figure 4), except for
the olefinic signals. The signals of protons Hd and He disap-
pear, the shape of the signal due to proton Hc is modified
(giving three sets of signals), and broadening of the aromatic
peaks is observed. The splitting of the olefinic signals and
Scheme 6. Synthesis of the ancillary ligand 17. i) 1-Bromo-3-butenyl,
K2CO3, DMF, 608C, 24 h (48%).
Synthesis of the handcuff-con-
taining catenane: By taking
advantage of the very powerful
“gathering and threading”
effect of copper(I) with appro-
priate ligands, the precursor to
the catenane was prepared
quantitatively, as depicted in
Scheme 7.
Compound
1
and [Cu-
Scheme 8. Cyclisation of the precatenane by ring-closing metathesis. i) [RuCl2
G
G
(10ꢀ3 m), RT, 10 d (80%).
ACHTREUNG
a 1:2 stoichiometry in CH2Cl2/
CH3CN under argon, affording
a yellowish suspension. The “thread” 17 was subsequently
added, causing a spectacular colour change to yield an in-
tense brown suspension, which was allowed to stand at
room temperature for some time prior to work-up. 18·2PF6
was obtained in pure form and did not require further chro-
matographic separation.
the broadening of the aromatic peaks originate from the
presence of three possible diastereoisomers, E–E, E–Z, and
Z–Z. As yet, it has not been possible to determine their rel-
ative proportions.
The interlocked nature of 192+ was supported by 2D-
1
ROESY H NMR. Indeed, correlations were observed be-
As depicted in Scheme 8, the target catenane 19·2PF6 was
prepared by subjecting 18·2PF6 in CH2Cl2 to a ring-closing
metathesis reaction analogous to those previously used for
making phenanthroline-based copper(I) catenanes.[17]
tween the H atoms belonging to the -CH2-CH2-O- fragments
of bis-macrocycle 1 (protons H-a to H-e) and the 1,10-phe-
nanthroline units of the large ring (protons H-4’,7’ and H-
5’,6’). Similarly, interactions between protons H-a/H-b and
Scheme 7. Threading reaction using the template effect of copper(I). i) [Cu
N
N
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J.-P. Sauvage, V. Heitz et al.
Figure 4. 1H NMR ([D6]acetone, 500 MHz) changes on going from precursor 182+ to catenane 192+
.
protons H-4,7/H-3,8 confirmed the threading of the large
central ring through the two cyclic components of bis-mac-
rocycle 1.
The high-resolution ES mass spectrum of 19·2PF6
(Figure 5) shows one peak at m/z 1086.3420, corresponding
to [19]2+ (calcd 1086.3433).
redox potential of E0 =0.65 V (DEp ꢁ92 mV) versus SCE in
acetonitrile, in accordance with previously reported values
for similar systems.[19] Each reversible oxidation occurs at
the same potential, confirming the absence of a strong inter-
action between the two metal centres.
Compound 192+ is a dicopper complex with 2,9-disubsti-
tuted phen-type ligands; these substituted derivatives lead
to entwined complexes in which the metals are in tetrahe-
dral environments, and thus strongly stabilise CuI. The elec-
tronic properties of the catenane are in perfect agreement
with its structure. Relatively intense MLCT bands are ob-
Conclusion
In conclusion, a novel topology has been prepared, which
consists of a bis-macrocycle (“handcuff”) and a large ring.
The large ring passes through both rings of the handcuff-like
compound. A relatively short sequence of organic reactions
led to the key organic component, namely a macrocyclic
dione, demonstrating the efficiency of the Dietrich-Bucheck-
er reaction (functionalisation of the 2- and 9-positions of the
1,10-phenanthroline backbone
served
in
the
visible
region
(lmax ꢁ411 nm,
e
ꢁ4300 Lmolꢀ1 cmꢀ1) due to the presence of two CuI com-
plexes, but no significant intervalence bands are apparent.
Cyclic voltammetry shows that the CuII/CuI couple has a
using an alkyl- or aryl-lithium,
followed by aromatisation of
the hydro- intermediate). The
“handcuff” was prepared in a
multicomponent condensation
reaction from the 1,2-dione
and ammonium ions. The
“gathering and threading”
effect of copper(I) turned out
to be particularly efficient
since the formation of the
threaded precursor was almost
quantitative in spite of its
multi-threaded nature. In the
future, such a new topology
will be incorporated into com-
Figure 5. Electrospray mass spectrum of catenane 19·2PF6.
plex molecular machines, im-
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Synthesis of a Bis-macrocycle and Its “Threading”
FULL PAPER
The brown precipitate was collected and dried under vacuum, and the
mother liquor was extracted with CH2Cl2 (2”40 mL). The resulting crude
product (4.71 g) was adsorbed on silica (30 g) and then purified by chro-
matography (220 g of silica, prepared in CH2Cl2). Elution with CH2Cl2
gave pure 4 (2.85 g, 88%). 1H NMR (300 MHz, CDCl3, 258C): d=8.22
(d, 3J=8.4 Hz, 2H; H-4,7), 7.83 (s, 2H; H-5,6), 7.65 ppm (d, 3J=8.4 Hz,
2H; H-3,8).
parting novel chemical functions to the electrochemically
driven dynamic systems already prepared.
Experimental Section
Compound 5: Solid KBr (11.25 g, 94.5 mmol, ꢁ10 equiv) was placed in a
two-necked flask equipped with a condenser. The flask was immersed in
a large ice/water bath, and then concentrated H2SO4 (98%, 16 mL) was
added dropwise with stirring (evolution of gaseous bromine), followed by
concentrated HNO3 (68%, 19mL). Compound 4 (2.36 g, 9.47 mmol) was
dissolved in concentrated H2SO4 (24 mL) and this solution was added
dropwise to the pre-cooled mixture. The resulting mixture was stirred for
20 min at room temperature and then for 3 h at 808C. It was then al-
lowed to cool to room temperature and ice (30 g) was added. After the
ice had melted, the mixture was poured over further ice (300 g) in a
larger flask and, with simultaneous cooling, was neutralised to pHꢁ6
with aqueous ammonia solution (25%, ca. 180 mL). A yellow material
precipitated. CH2Cl2 (500 mL) was layered over the suspension and the
two-phase mixture was stirred until the solid had dissolved. The organic
phase was separated, washed with water (200 mL) and brine (200 mL),
and concentrated to dryness. The crude product was adsorbed on silica
(50 g), split into two batches, and purified by flash chromatography (2”
230 g of fine silica prepared in CH2Cl2). Elution with CH2Cl2 gave 5
General: All chemicals were of the best commercially available grade
and were used without further purification (except where mentioned oth-
erwise). Dry solvents were distilled from suitable desiccants (THF from
Na/benzophenone; CH2Cl2, DMF, and MeOH from CaCl2). Thin-layer
chromatography was carried out using polymer sheets pre-coated with
silica gel (Macherey-Nagel, POLYGRAM, SIL G/UV254). Preparative
column chromatography was carried out using silica gel (Merck Kiesel-
gel, silica gel 60, 0.063–0.200 mm). Flash column chromatography was
carried out using silica gel (Merck Geduran, silica gel 60, 40–63 mm).
1H and 13C NMR spectra were recorded with a Bruker Avance 300
(300 MHz) or Avance 500 (500 MHz) spectrometer using the deuterated
solvent signal as a lock. The spectra were collected at 258C and the
chemical shifts were referenced to residual solvent proton signals as in-
ternal standards (1H: D2O 4.66 ppm, [D6]acetone 2.05 ppm, CD2Cl2
5.32 ppm, CDCl3 7.27 ppm; 13C: CDCl3 77 ppm). Attributions are dis-
played in the following manner: 1) chemical shifts (d) quoted in ppm,
and then in brackets 2) multiplicity of the signal, 3) coupling constant(s)
quoted in Hz, 4) number of protons implied, and 5) identity of proton(s)
implied. Mass spectra were obtained with a VG-BIOQ triple-quadrupole
spectrometer (ES-MS).
1
3
(3.22 g, 71%). H NMR (300 MHz, CDCl3, 258C): d=8.44 (d, J=8.2 Hz,
3
2H; H-4,7), 7.62 ppm (d, J=8.2 Hz, 2H; H-3,8).
Compound 6: Compound
5 (1.00 g, 3.58 mmol) and 2-nitropropane
The detailed procedures are presented below, some of which have been
modified with respect to previously published accounts.
(3.20 g, 34.8 mmol, ꢁ10 equiv) were dissolved in MeCN (300 mL) in a
flask fitted with a condenser. A solution of Na2CO3 (3.04 g, 2.31 mmol)
in water (300 mL) was then added. The resulting mixture was degassed
and heated to 558C for 5 h under an argon atmosphere. It was then
cooled to room temperature and the organic solvent was removed. The
remaining solution was neutralised to pHꢁ6–7 with 0.1m aqueous HCl.
CH2Cl2 (500 mL) was then added and the layers were separated. The
aqueous layer was extracted with further CH2Cl2 (200 mL). The organic
phases were combined and the solvent was evaporated to give a green
solid (1.12 g). This material was subjected to flash chromatography (240 g
of fine silica, prepared in CH2Cl2); elution with CH2Cl2 gave 6 (0.89g,
90%). 1H NMR (300 MHz, CDCl3, 258C): d=8.20 (d, 3J=8.6 Hz, 2H;
H-4,7), 7.61 (d, 3J=8.6 Hz, 2H; H-3,8), 1.87 ppm (s, 6H; Me); 13C NMR
(75 MHz, CDCl3, 258C): d=149.49, 140.74, 137.05, 131.13, 124.70, 121.85,
117.10, 26.25 ppm; ES-MS: m/z: calcd for C15H11N2O2Cl2: 321.020; found:
321.021 [M+H]+.
Compound
2·2Br:
1,10-Phenanthroline
monohydrate
(10.00 g,
50.4 mmol) was dissolved in nitrobenzene (80 mL). 1,3-Dibromopropane
(ꢁ26 mL, 253 mmol, 5 equiv) was then slowly added and the mixture
was heated to 1208C with stirring. During the reaction, a crystalline prod-
uct precipitated from the reaction mixture. After 4 h, the mixture was al-
lowed to cool to room temperature and the crystalline product was col-
lected by filtration. The mother liquor was concentrated by evaporating
the solvent under reduced pressure, producing a second crop of crystal-
line material. The products were combined, washed with small amounts
of toluene, and dried under vacuum for 24 h. The product was then dis-
solved in water (ca. 50 mL), the solution obtained was warmed to 808C,
and ethanol (ca. 300 mL) was slowly added with stirring until the precipi-
tated material no longer dissolved in the mixture upon heating and stir-
ring. The mixture was left to cool overnight and the crystals were collect-
ed to yield 2 (16.89g, 88%). 1H NMR (300 MHz, D2O, 25 8C): d=9.57
(d, 3J=5.8 Hz, 2H; H-2,9), 9.36 (d, 3J=8.5 Hz, 2H; H-4,7), 8.49(s, 2H;
H-5,6), 8.45 (dd, 3J=5.8 and 8.4 Hz, 2H; H-3,8), 5.05 (t, 3J=7.0 Hz, 4H;
Compound 13: A mixture of 1,10-phenanthroline (8.00 g, 44.4 mmol) and
potassium bromide (52.8g, 444 mmol) was cooled to 0–58C. It was slowly
dissolved in a mixture of sulfuric acid (98%, 80 mL) and nitric acid
(60%, 40 mL), maintaining a low temperature. The mixture was then
heated to 1008C with stirring. After 4 h, it was allowed to cool to room
temperature and ice (800 g) was added. The resulting solution was neu-
tralised to pHꢁ7 by the addition of 30% ammonium hydroxide solution.
A yellow solid precipitated from the reaction mixture. It was collected by
filtration and washed several times with water. This material was dis-
solved in CH2Cl2, and the solution was dried over MgSO4, filtered, and
concentrated to dryness to afford pure 13 (5.13 g, 55%). 1H NMR
(300 MHz, CDCl3, 258C): d=9.13 (dd, 3J=4.8 Hz, 4J=1.83 Hz, 2H; H-
2,9), 8.51 (dd, 3J=7.9Hz, 4J=1.83 Hz, 2H; H-4,7), 7.60 ppm (dd, 3J=4.8
and 7.9Hz, 2H; H-3,8).
3
H-a), 3.33 ppm (q, J=7.0 Hz, 2H; H-b).
Compound 3: [K3Fe(CN)6] (123.5 g, 375 mmol, ꢁ10 equiv) was dissolved
in water (200 mL) and NaOH (56.4 g, 1.41 mol, ꢁ34 equiv) was gradually
added with stirring. The flask was then placed in an ice/water bath. A so-
lution of 1 (16.0 g, 41.9mmol) in water (25 mL) was added dropwise,
maintaining the temperature in the range 2–58C. The mixture was al-
lowed to react for 2 h. It was then neutralised with 4m HCl to pHꢁ7–8
with simultaneous cooling and concentrated under reduced pressure. The
resulting brown solid was crushed and subjected to Soxhlet extraction
with refluxing CHCl3 (4”500 mL). The solvent was evaporated from the
combined organic layers to give 5.71 g of a brown crude product, which
was adsorbed on silica (40 g) and subjected to chromatography (440 g of
silica, prepared in CH2Cl2). Gradient elution from CH2Cl2 to CH2Cl2/2%
MeOH gave 3 (3.69g, 35%). 1H NMR (300 MHz, CDCl3, 258C): d=7.72
(d, 3J=9.5 Hz, 2H; H-4,7), 7.36 (s, 2H; H-5,6), 6.80 (d, 3J=9.5 Hz, 2H;
H-3,8), 4.32 (t, 3J=6.6 Hz, 4H; H-a), 2.46 ppm (q, 3J=6.6 Hz, 2H; H-b).
Compound 14: Compound 13 (2.00 g, 9.52 mmol) was suspended in a 1:1
mixture of MeCN and H2O (108 mL), and 2-nitropropane (86 mL) was
added. The mixture was degassed with argon and then a degassed aque-
ous solution of Na2CO3 (2m, 4.8 mL, 1 equiv) was added via a cannula.
The resulting mixture was refluxed for 8 h under an inert atmosphere. It
was then cooled to room temperature and the product was extracted with
CH2Cl2 (3”400 mL). The combined extracts were dried over MgSO4 and
concentrated, and the crude product was subjected to flash chromatogra-
phy (200 g of silica, prepared in CH2Cl2; gradient elution from CH2Cl2 to
CH2Cl2/0.5% MeOH) to give 14 (1.54 g, 66%). 1H NMR (300 MHz,
Compound 4: Compound 3 (3.30 g, 13.1 mmol) was suspended in POCl3
(39mL) and PCl 5 (5.44 g, 26.1 mmol, 2 equiv) was added. The mixture
was degassed and refluxed (1108C) under argon for 8 h. The excess
POCl3 was then distilled off under reduced pressure and the remaining
material was decomposed with ice. The resulting suspension was neutral-
ised with aqueous ammonia solution (30%) with simultaneous cooling.
Chem. Eur. J. 2007, 13, 7584 – 7594
ꢀ 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
7591

J.-P. Sauvage, V. Heitz et al.
3
4
CDCl3, 258C): d=9.01 (dd, J=4.4 Hz, J=1.83 Hz, 2H; H-2,9), 8.18 (dd,
3J=8.2 Hz, 4J=1.8 Hz, 2H; H-4,7), 7.54 (dd, 3J=4.4, 8.2 Hz, 2H; H-3,8),
1.79ppm (s, 6H; Me).
to warm to room temperature overnight, after which it was quenched
with water (0.2 mL). The solution was concentrated to dryness and the
residue was dried in vacuo. This material was dissolved in CH2Cl2 and
MnO2 was added portionwise. The progress of the oxidation was moni-
tored by TLC and, once complete, the solid was filtered off, the filtrate
was concentrated under reduced pressure, and the crude product was pu-
rified by chromatography (100 g of silica, prepared in toluene; isocratic
elution with toluene) to give 8 (1.61 g, 95%). 1H NMR (300 MHz,
CDCl3, 258C): d=8.41 (m, 3J=8.9Hz, 4H; H- o), 8.29(d, 3J=8.6 Hz,
2H; H-4,7), 8.10 (d, 3J=8.7 Hz, 2H; H-3,8), 6.93 (m, 3J=8.9Hz, 4H; H-
m), 5.59(t, 3J=3.0 Hz, 2H; H-a), 4.00 (m, 2H; H-b), 3.70 (m, 2H; H-b’),
2.20–1.50 ppm (m, 18H; Me + H-g + H-d + H-e); 13C NMR (75 MHz,
CDCl3, 258C): d=158.14, 158.13, 154.00, 142.16, 136.24, 133.06, 128.67,
128.60, 120.41, 119.14, 118.63, 116.60, 96.23, 96.21, 62.03, 30.32, 26.11,
25.22, 18.72 ppm; ES-MS: m/z: calcd for C37H37N2O6: 605.265; found:
605.264 [M+H]+.
Compound
7:
2-(4-Bromophenoxy)tetrahydro-2H-pyran
(2.51 g,
9.57 mmol) was dissolved in dry THF (50 mL) under an argon atmos-
phere and the solution was cooled to ꢀ788C. n-Butyllithium (8.3 mL of a
1.5m solution in hexane, 12.44 mmol, 1.3 equiv) was then added dropwise
over a period of 10 min and the mixture was allowed to react for 15 min
at ꢀ788C. Triisopropyl borate (4.5 mL, 19.11 mmol, 2 equiv) was added
in a single portion and the mixture was allowed to react for a further 1 h
at ꢀ788C. Thereafter, it was slowly warmed to room temperature, where-
upon a white precipitate formed. Water (10 mL) was slowly added to
quench the reaction, then diethyl ether (500 mL) was added, followed by
water (500 mL). The resulting mixture was slowly neutralised to pHꢁ6–7
by adding aqueous HCl (0.1m, ca. 100 mL). The layers were separated
and the aqueous layer was further extracted with diethyl ether (2”
250 mL). The organic fractions were combined, concentrated to dryness,
and the crude product (2.68 g) was purified by flash chromatography
(230 g of fine silica, prepared in toluene/acetone 8:2). Gradient elution
Compound 9: Protected diphenol 8 (1.00 g, 1.65 mmol) was dissolved in
dry methanol (ca. 150 mL) and a dry 2m ethereal solution of HCl
(2.5 mL, ꢁ3 equiv) was added. The mixture was allowed to react for 2 h
at room temperature. Freshly distilled triethylamine (1.2 mL) was then
added to quench the reaction. Evaporation of the solvents gave a deep-
orange solid (263 mg), which was adsorbed on silica (20 g) and purified
by flash chromatography (130 g of fine silica, prepared in CH2Cl2/2%
MeOH; gradient elution from CH2Cl2/2% MeOH to CH2Cl2/4%
MeOH) to give 9 (0.72 g, 96%). 1H NMR (300 MHz, CDCl3/[D6]acetone
2:1, 258C): d=8.07 (s, 2H; OH), 7.98 (m, 3J=8.7 Hz, 4H; H-o), 7.89(d,
3J=8.6 Hz, 2H; H-4,7), 7.74 (d, 3J=8.7 Hz, 2H; H-3,8), 6.67 (m, 3J=
8.7 Hz, 4H; H-m), 1.51 ppm (s, 6H; Me); 13C NMR (75 MHz, CDCl3/
[D6]acetone 2:1, 258C): d=158.44, 154.74, 141.69, 136.28, 131.08, 129.12,
129.07, 120.78, 119.84, 116.79, 115.77, 26.10 ppm; ES-MS: m/z: calcd for
C27H21N2O4: 437.150; found: 437.151 [M+H]+.
from toluene/acetone 8:2 to 8:3 gave
7
(1.68 g, 80%). 1H NMR
(300 MHz, [D6]acetone/D2O 2:1, 258C): d=7.70 (m, 3J=8.7 Hz, 2H; H-
o), 6.93 (m, 3J=8.7 Hz, 2H; H-m), 5.41 (t, 3J=3.2 Hz, 1H; H-a), 3.75
and 3.50 (2m, 2H; H-b + H-b’), 1.90–1.40 ppm (m, 6H; H-g + H-d +
H-e); ES-MS (negative polarity): m/z: calcd for C11H14BO4: 221.099;
found: 221.093 [MꢀH]ꢀ.
Compound 15: n-Butyllithium (4.95 mL, 7.92 mmol, 2 equiv) was added
dropwise over 10 min to a degassed solution of 2-(4-bromophenoxy)tetra-
hydro-2H-pyran (1.82 g, 7.92 mmol, 2 equiv) in THF (12 mL) at ꢀ788C.
The mixture was allowed to react for 15 min, and then a solution of 14
(1.00 g, 3.96 mmol) in dry THF (8 mL) was slowly introduced by means
of a cannula. The resulting mixture was stirred at ꢀ788C for 2 h. It was
then quenched with MeOH (5 mL), allowed to warm to room tempera-
ture, and concentrated to dryness. The crude product was re-aromatised
Compound 10: Commercial pentaethyleneglycol ditosylate (2.00 g, 95%)
was first purified by chromatography (100 g of silica, prepared in Et2O;
elution with Et2O/10% EtOH). After collection of the appropriate frac-
tion and evaporation of the solvents, the compound was dissolved in ace-
tone (15 mL) and NaI was added until saturation. The mixture was
heated to reflux for 2 h under a dry atmosphere (CaCl2 guard tube).
After cooling to room temperature, more NaI was added and the mixture
was stirred for a further 16 h at room temperature. The white solid was
then filtered off and washed with Et2O (3”50 mL). The solvents were re-
moved from the combined filtrate and washings under reduced pressure.
The residual orange oil was partitioned between Et2O (60 mL) and water
(60 mL); the organic layer was separated and washed with an aqueous
solution of Na2S2O3 until complete disappearance of the orange color.
After separation, the organic layer was washed with water (2”60 mL),
dried over MgSO4, filtered, and concentrated to dryness to give pure 10
(1.35 g, 96%). 1H NMR (300 MHz, [D6]acetone, 258C): d=3.76–3.72 (t,
3J=6.6 Hz, 4H; H-b), 3.65–3.59(d, 3J=8.6 Hz, 12H; H-g + H-d + H-e),
using activated MnO2 (2.58 g) in
a 1:1 mixture of CH2Cl2/toluene
(100 mL). The reaction was complete after 12 h. The mixture was filtered
through Celite, which was washed with CH2Cl2. The combined filtrate
and washings were concentrated and the product was subjected to flash
chromatography (250 g of fine silica, prepared in heptane/5% acetone).
Gradient elution from heptane/5% acetone to heptane/20% acetone
gave pure 15 (1.42 g, 84%). 1H NMR (300 MHz, CDCl3, 258C): d=9.10
(dd, 3J=4.4, 4J=1.8 Hz, 1H; H-2), 8.30–8.23 (m, 3H; H-4 + H-7 + H-
8), 8.06 (m, 3J=8.8 Hz, 2H; H-o), 7.60 (dd, 3J=4.4, 8.2 Hz, 1H; H-3),
7.21 (m, 3J=8.8 Hz, 2H; H-m), 5.53 (t, 3J=6.3 Hz, 1H; H-a), 3.94, 3.64
(2m, 2H; H-b + H-b’), 1.95–1.55 (m, 6H; H-g + H-d + H-e), 1.88 ppm
(s, 6H; Me); 13C NMR (75 MHz, CDCl3, 258C): d=158.14, 154.91,
147.86, 142.30, 136.60, 136.55, 136.00, 133.23, 128.98, 128.66, 127.94,
122.46, 120.58, 119.90, 118.63, 116.70, 116.66, 92.26, 61.99, 30.32, 26.08,
25.22, 18.71 ppm; HR ES-MS: m/z: calcd for C25H25N2O4: 429.1809;
found: 429.1811 [M+H]+.
3
3.35–3.31 ppm (t, J=6.6 Hz, 4H; H-a).
Compound 8: By Suzuki coupling: Protected phen-dione
6 (1.00 g,
Compound 11: Dry Cs2CO3 (4.42 g, 13.57 mmol) was suspended in freshly
distilled DMF (500 mL) under argon and the mixture was heated to
508C with vigorous stirring. A mixture of diphenol 9 (0.74 g, 1.70 mmol)
and pentaethyleneglycol diiodide 10 (0.82 g, 1.78 mmol, 1.05 equiv) in
DMF (100 mL) was added at a rate of one drop per minute by means of
a syringe pump. After complete addition of the reagents (approx. 72 h),
the mixture was allowed to react for a further 12 h. The solvent was then
distilled off in vacuo and the residual solid was partitioned between
water (200 mL) and CH2Cl2 (500 mL). The organic layer was separated
and concentrated to give a brown oily material (1.87 g), which was sub-
jected to flash chromatography (2”230 g of fine silica, prepared in
CH2Cl2; gradient elution from CH2Cl2 to CH2Cl2/0.1% MeOH) to yield
11 (0.64 g, 59%). 1H NMR (300 MHz, CDCl3, 258C): d=8.34 (m, 3J=
8.9Hz, 4H; H- o), 8.24 (d, 3J=8.6 Hz, 2H; H-4,7), 8.03 (d, 3J=8.6 Hz,
2H; H-3,8), 7.17 (m, 3J=8.9Hz, 4H; H- m), 4.33 (t, 3J=5.3 Hz, 4H; H-
a), 3.84 (t, 3J=5.3 Hz, 4H; H-b), 3.75–3.67 (m, 12H; H-g + H-d + H-
e), 1.87 ppm (s, 6H; Me); 13C NMR (75 MHz, CDCl3, 258C): d=159.98,
153.94, 142.03, 136.28, 132.76, 128.79, 128.74, 120.45, 119.02, 116.79,
3.11 mmol) and boronic acid 7 (1.80 g, 8.11 mmol, 2.6 equiv) were dis-
solved in toluene (70 mL) and mixed with a 2m solution of Na2CO3
(6.36 g, 60.0 mmol) in water (30 mL). The solution two-phase mixture
was degassed and then Pd(PPh3)4 (467 mg, 0.4 mmol) was rapidly added
A
under a flow of argon. The mixture was heated at 808C with vigorous
stirring for 18 h. It was then allowed to cool to room temperature and
CH2Cl2 (600 mL) was added. The organic layer was washed with water
(300 mL) and concentrated to dryness. The resulting brown solid (2.85 g)
was purified by flash chromatography (230 g of fine silica, prepared in
CH2Cl2; elution with CH2Cl2) to give the di-protected intermediate 8 as a
mixture of diastereoisomers (1.87 g, 97%).
By nucleophilic substitution: 2-(4-Bromophenoxy)tetrahydro-2H-pyran
(1.03 g, 4.68 mmol, 2 equiv) was dissolved in THF (10 mL) and the solu-
tion was cooled to ꢀ788C under an argon atmosphere. It was then treat-
ed with n-butyllithium (2.91 mL of a 1.6m solution, 4.68 mmol, 2 equiv).
The mixture was allowed to react for 15 min and then a solution of com-
pound 15 (1.00 g, 2.34 mmol) in THF (20 mL) was added by means of a
cannula at ꢀ788C. The deep-purple reaction mixture was slowly allowed
7592
www.chemeurj.org
ꢀ 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 2007, 13, 7584 – 7594

Synthesis of a Bis-macrocycle and Its “Threading”
FULL PAPER
115.63, 71.21, 70.77, 70.57, 69.54, 68.87, 26.12 ppm; ES-MS: m/z: calcd for
C37H39N2O8: 639.271; found: 639.272 [M+H]+.
Compound 18·2PF6: A solution of [Cu(MeCN)4]PF6 (20.4 mg, 5.47”
A
10ꢀ5 mol, 2.07 equiv) in dry MeCN (10 mL) was added to a degassed so-
lution of 1 (30.5 mg, 2.64”10ꢀ5 mol) in dry CH2Cl2 (10 mL) and the mix-
ture was stirred at room temperature for 12 h under an inert atmosphere.
A solution of bis-butenyl-phenanthroline 17 (24.9mg, 5.27”10 ꢀ5 mol,
2.0 equiv) in dry CH2Cl2 (10 mL) was then added; the mixture immedi-
ately turned brown, but was allowed to react for 2 days to ensure com-
plete reaction. After evaporation of the solvent, the crude product was
partitioned between CH2Cl2 (40 mL) and water (40 mL); the organic
layer was separated and worked-up to give 18·2PF6 (66 mg) in quantita-
tive yield. 1H NMR (500 MHz, [D6]acetone, COSY-ROESY, 258C): d=
Compound 12: The protected macrocycle 11 (250 mg, 0.39mmol) was
dissolved in a mixture of water (5 mL) and trifluoroacetic acid (10 mL).
The mixture was heated to 508C in the presence of oxygen. After 5 h,
the solvents were evaporated under reduced pressure and the residue
was partitioned between CH2Cl2 and a 1m aqueous solution of NaHCO3.
The organic layer was washed with water, dried over MgSO4, and con-
centrated, and the crude product was purified by flash chromatography
(30 g of fine silica, prepared in CH2Cl2; gradient elution from CH2Cl2 to
CH2Cl2/2% MeOH) to give 12 (204 mg, 87%). 1H NMR (300 MHz,
CDCl3, 258C): d=8.50 (d, 3J=8.3 Hz, 2H; H-4,7), 8.36 (m, 3J=9.0 Hz,
4H; H-o), 7.93 (d, 3J=8.3 Hz, 2H; H-3,8), 7.18 (m, 3J=9.0 Hz, 4H; H-
m), 4.35 (t, 3J=5.3 Hz, 4H; H-a), 3.87 (t, 3J=5.3 Hz, 4H; H-b), 3.85–
3.68 ppm (m, 12H; H-g + H-d + H-e); 13C NMR (75 MHz, CDCl3,
258C): d=193.46, 178.94, 162.43, 161.67, 152.96, 137.83, 130.80, 129.73,
126.22, 120.41, 115.82, 71.26, 70.83, 70.63, 69.49, 67.79 ppm; ES-MS: m/z:
calcd for C34H33N2O8: 597.224; found: 597.228 [M+H]+.
3
3
10.25 (d, J=8.4 Hz, 4H; H-4,7), 8.87 (d, J=8.4 Hz, 4H; H-4’,7’), 8.41 (s,
3
3
4H; H-5’,6’), 8.40 (d, J=8.4 Hz, 4H; H-3,8), 8.12 (d, J=8.4 Hz, 4H; H-
3’,8’), 7.74 (m, J=8.7 Hz, 8H; H-o’), 7.59(m, 3J=8.6 Hz, 8H; H-o), 6.37
3
(m, J=8.7 Hz, 8H; H-m’), 6.20 (m, 3J=8.7 Hz, 8H; H-m), 5.68–5.54 (m,
3
3J=5.0, 10.2, and 17.3 Hz, 4H; H-c), 4.93–4.78 (m, 3J=10.2 and 17.3 Hz,
8H; H-d + H-e), 3.88 (s, 8H; H-e), 3.78–3.69(m, 16H; H- d + H-a),
3.68–3.61 (m, 16H; H-b + H-g), 3.59–3.55 (m, 8H; H-a), 2.41–2.34 ppm
(m, 8H; H-b); HR ES-MS: m/z: calcd for C132H120N10O16Cu2: 1114.3746;
found: 1114.3710 [M]2+
.
Monoclinic crystals of 14 suitable for X-ray analysis were obtained by
slow diffusion of n-heptane into a solution in CH2Cl2.
Crystallographic data; space group P21/n; Z=4; 1=1.400 gcmꢀ3; cell
constants a=8.7080(2), b=21.4090(5), c=17.6640(4) Š, b=100.8200(14),
V=3234.55(13) Š3; temperature of data collection 173(2) K; 8626 unique
reflections (I>2s(I); R=0.0796; Rw=0.1494.
Compound 19·2PF6: Compound 18·2PF6 (20 mg, 2.38”10ꢀ5 mol) and
Grubbs first-generation catalyst [RuCl2(PCy3)2CHPh] (3.3 mg,
AHCTREUNG
0.50 equiv) were dissolved in freshly distilled CH2Cl2 (so as to obtain a
10ꢀ3 m solution) and kept under argon. The mixture was allowed to react
for 10 days at room temperature under vigorous stirring. The material
was then precipitated by adding a saturated aqueous solution of KPF6 to
CCDC-645664 contains the supplementary crystallographic data for this
paper. These data can be obtained free of charge from The Cambridge
Crystallographic Data Centre via www.ccdc.cam.ac.uk/data_request/cif
ꢀ
ensure the presence of PF6 as the sole counter ion. The crude product
was filtered through Celite and subjected to chromatography (150 g of
silica prepared in CH2Cl2/0.5% MeOH; gradient elution from CH2Cl2/
0.5% MeOH to CH2Cl2/1% MeOH) to give 19·2PF6 (16 mg, 80%) as a
Compound 1: Compound 12 (200 mg, 16.8”10ꢀ5 mol) and sodium di-
thionite (7.0 mg, 4.0”10ꢀ5 mol, 0.2 equiv) were mixed with dry ammoni-
um acetate. After degassing the flask, the mixture was slowly heated to
1808C and the molten salt solution was allowed to react for 2 h with
gentle stirring. The mixture was then cooled and water was added to
induce the precipitation of a brown material. The product was collected
by centrifugation, and then boiled several times in water to remove the
excess ammonium salts. After collection of the solid by centrifugation,
the poorly soluble material was boiled in pyridine (about 30 mL) and the
solution was filtered while hot; repeating this procedure three times al-
1
mixture of three diastereomers. H NMR (500 MHz, [D6]acetone, COSY-
ROESY, 258C): d=10.34–10.10 (m, 4H; H-4,7), 8.91–8.80 (m, 4H; H-
4’,7’), 8.37–8.31 (m, 4H; H-5’,6’), 8.16–8.07 (m, 4H; H-3,8), 7.75–7.66 (m,
4H; H-3’,8’), 7.99–7.76 (m, 8H; H-o’), 7.75–7.66 (m, 8H; H-o), 6.55–6.35
(m, 8H; H-m’), 6.20–6.14 (m, 8H; H-m), 5.74–5.16 (3m, 4H; H-c), 3.89
(s, 8H; H-e), 3.85–3.70 (m, 16H; H-d + H-a), 3.68–3.65 (m, 8H; H-g),
3.60–3.46 (m, 16H; H-a + H-b), 2.40, 2.30, 2.18 ppm (3m, 8H; H-b);
HR ES-MS: m/z: calcd for C128H112N10O16Cu 1086.3425; found: 1086.3420
[M]2+
.
1
lowed 1 to finally be obtained as an ochre solid (137 mg, 70%). H NMR
(300 MHz, CD2Cl2/10% F3CCO2D, 25 8C): d=10.19(d, 3J=8.4 Hz, 4H;
H-4,7), 8.72 (d, 3J=8.4 Hz, 4H; H-3,8), 8.28 (m, 3J=8.7 Hz, 8H; H-o),
7.36 (m, 3J=8.6 Hz, 8H; H-m), 4.44 (t, 3J=5.1 Hz, 8H; H-a), 4.05 (t,
8H; H-b), 3.95–3.70 ppm (m, 24H; H-g
+ H-d +
H-e); 13C NMR
Acknowledgements
(75 MHz, CD2Cl2/10% F3CCO2D, 25 8C): d=163.37, 158.78, 158.24,
139.99, 139.35, 138.81, 129.97, 126.31, 125.54, 124.63, 116.81, 112.96, 70.53,
70.33, 70.26, 69.22, 67.74 ppm; HR ES-MS: m/z: calcd for C68H65N6O12
1157.4661; found: 1157.4653 [M+H]+.
We thank the French Ministry of Education for a fellowship to J.F. and
the European Commission for financial support (Marie Curie fellowship
to T.K.). We are also grateful to Dr. Patrick Wehrung (Service Commun
de SpectromØtrie de Masse, University Louis Pasteur) for performing the
mass spectrometry experiments, to Dr. AndrØ de Cian for crystallograph-
ic structure solution, and to Dr. Lionel Allouche (Service Commun de
SpectromØtrie RMN, University Louis Pasteur) for 500 MHz NMR anal-
ysis.
Compound 17: A mixture of 2,9-di(p-hydroxyphenyl)-1,10-phenanthro-
line (200 mg, 0.55 mmol) and potassium carbonate (386 mg, 2.79mmol,
5.1 equiv) was suspended in freshly distilled DMF (60 mL) and the sus-
pension was heated to 608C under an argon atmosphere. A solution of 1-
bromo-3-butenyl (747 mg, 0.57 mmol, 10 equiv) in DMF (10 mL) was
then added over a period of 30 min. The vigorously stirred mixture was
allowed to react for a further 24 h and then concentrated to dryness. The
residue was partitioned between CH2Cl2 (200 mL) and water (150 mL)
and the organic layer was separated. The aqueous layer was further ex-
tracted with CH2Cl2 (100 mL). Evaporation of the solvent from the com-
bined organic layers gave a yellow crude product, which was purified by
flash chromatography (150 g of fine silica prepared in CH2Cl2; elution
with CH2Cl2) to give 17 (125 mg, 48%). 1H NMR (300 MHz, CDCl3,
258C): d=8.42 (m, 3J=9.0 Hz, 4H; H-o’), 8.26 (d, 3J=8.5 Hz, 2H; H-
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4’,7’), 8.08 (d, J=8.5 Hz, 2H; H-3’,8’), 7.75 (s, 2H; H-5’,6’), 7.11 (m, 3J=
8.9Hz, 4H; H- m’), 6.03–5.89(m, 3J=6.7, 10.2, and 17.0 Hz, 2H; H-c),
5.26–5.18 (m, 3J=17.1 Hz, 2H; H-d), 5.16–5.12 (m, 3J=10.2 Hz, 2H; H-
e), 4.15 (t, 3J=6.8 Hz, 4H; H-a), 2.66–2.57 ppm (m, 3J=6.7 Hz, 4H; H-
b); 13C NMR (75 MHz, CDCl3, 258C): d=160.29, 156.36, 136.86, 134.41,
132.07, 129.00, 127.54, 125.63, 119.40, 117.16, 114.84, 67.31, 33.70 ppm;
ES-MS: m/z: calcd for C32H29N2O2 473.223; found: 473.236 [M+H]+.
Chem. Eur. J. 2007, 13, 7584 – 7594
ꢀ 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
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Received: May 3, 2007
Published online: August 10, 2007
7594
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