Phosphorus-containing [2]catenanes as an example of interlocking chiral structures

Article abstract of DOI:10.1002/anie.200503625

The missing link: Chiral catenanes have been obtained by including prochiral phosphorus centers in both rings of a [2]catenane moiety. These compounds, which also contain stereogenic carbon atoms, have been prepared by the well known copper(I) template synthesis and have been isolated as enantiomerically pure, single diastereoisomers. (Figure Presented).

Full text of DOI:10.1002/anie.200503625

Communications
Template Synthesis
The synthetic approach is based on the strategy estab-
lished many years ago, which takes advantage of the
DOI: 10.1002/anie.200503625
Phosphorus-Containing [2]Catenanes
as an Example of Interlocking Chiral
Structures
Agn›s Theil, Caroline Mauve, Marie-
ThØr›se Adeline, Angela Marinetti,* and
Jean-Pierre Sauvage
In recent years, several synthetic strategies to
[2]catenanes have been designed[1] which allow
introduction of various functionalities in their
backbone or at their periphery so as to generate
targeted physical and chemical properties. For
example, suitable functionalities such as coor-
dinating sites and porphyrinic, disulfide, hy-
droxyl, and halide moieties have allowed the
generation of photoinduced electron-transfer
processes,[2] the adsorption of catenanes onto
gold surfaces,[3] the building of light-driven
machine prototypes,[4] and the development of
polymerization processes.[5] In the increasingly
active search for new structural motifs it is
surprising that phosphorus functionalities have
been neglected so far. To the best of our
knowledge, no catenanes functionalized with
phosphorus groups have been described to date.
The only reported phosphorus-containing cate-
nanes have phosphine–gold complexes as con-
stitutive elements of the catenane framework
itself,[6] and they have been mostly prepared
and characterized as solid-state species.
In the present work we envisioned that the
synthesis of [2]catenanes bearing phosphine
oxide functions would afford potential binding
sites for transition metals and, like the corre-
sponding trivalent phosphines, they would open
up new ways toward the application of cate-
nanes in coordination chemistry and organo-
metallic catalysis. Described herein is a poten-
tially general, flexible, and modular synthetic
approach for the preparation of the first [2]cat-
enanes functionalized with phosphorus groups.
Scheme 1. Synthesis of the [2]catenane 6 bearing a phosphine oxide function.
[*] A. Theil, C. Mauve, M.-T. Adeline, Dr. A. Marinetti
Institut de Chimie des Substances Naturelles—CNRS UPR 2301
1, avenue de la Terrasse, 91198 Gif-sur-Yvette (France)
Fax : (+33)1-6907-7247
temporary, three-dimensional template effect of copper(i)/
phenanthroline complexes to create the core of the inter-
locking rings.[7] The key step is a macrocyclization reaction
between the phenanthroline diphenol 2[8] and a suitable
biselectrophile. As a new application of the method, the
macrocyclization reaction has been performed here by using
the phosphorus-containing biselectrophile (S,S)-1. The indi-
vidual steps leading to catenane 6 are shown in Scheme 1.
The dichloride 1a had been designed in previous work as a
readily available starting material for building chiral macro-
E-mail: angela.marinetti@icsn.cnrs-gif.fr
Dr. J.-P. Sauvage
Laboratoire de Chimie Organo-MinØrale—CNRS UMR 7513
UniversitØ Louis Pasteur
4, rue Blaise Pascal, 67070 Strasbourg (France)
Supporting information for this article (full synthetic details and
characterization of new compounds) is available on the WWW under
http://www.angewandte.org or from the author.
2104
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Chemie
cyclic phosphines in an optically pure form.[9] It was prepared
from commercially available phenylphosphine and (S)-pro-
pylene oxide in a two-step synthesis. Unfortunately, 1a
proved to be insufficiently reactive for the purposes of the
present work (incomplete conversion in its reaction with 2)
and so it was converted into the corresponding diiodide (S,S)-
1b, whose reaction with the phenanthroline diphenol 2[8] in
DMF in the presence of cesium carbonate under high-dilution
conditions led to the expected macrocycle (S,S)-3 in 30%
yield.
Figure 1. Schematic representation of enantiomeric [2]catenanes with
stereogenic phosphorus centers. Assignment of the absolute config-
uration is made according to the oriented skew-lines convention.[12]
As mentioned above, the tetrahedral cores of catenanes
can be formed by combining CuI salts with two suitable
phenanthroline units. One of them can be part of a preformed
macrocyclic structure such as 3. Thus, addition of [Cu-
(MeCN)4]PF6 to a solution of 3 in dichloromethane, followed
by addition of one equivalent of the phenanthroline diphenol
2 afforded the precatenane 4, which was treated in situ with
As far as we know, enantiomerically pure [2]catenane
derivatives of this type have not been reported to date. In the
current study, chiral [2]catenanes bearing prochiral phospho-
rus centers have been prepared in enantiomerically pure
form.
1,14-diiodo-3,6,9,12-tetraoxatetradecane,
a usual building
block for catenanes, to form the copper catenate 5 containing
two different, interlocking macrocycles. After preliminary
purification by column chromatography, the copper was
removed by means of a ligand-exchange reaction involving
treatment of 5 with aqueous KCN under literature condi-
tions.[8]
The interlocking rings are obtained by addition of the
phosphorus-containing diodide (S,S)-1b to the precatenane
generated in situ from (S,S)-3, copper(i) hexafluorophos-
phate, and the phenanthroline diphenol 2 in the presence of
cesium carbonate (Scheme 2). After purification of the
Not only does (S,S)-6 represent the
first known catenane bearing a phos-
phine oxide function, it is a chiral,
enantiomerically pure species. The chir-
ality of 6 relies, in a most classical way,
on the incorporation of stereogenic
carbon centers in the macrocyclic struc-
ture. Another interesting case would be
that of topologically chiral catenane
frameworks. In the case of mechani-
cally interlocking macrocycles, chirality
may result from one of two different
structural arrangements: on one hand,
topological chirality is foreseen for
catenanes having oriented segments in
their macrocyclic chains. Several exam-
ples of topologically chiral [2]catenanes
of this family have been reported
during the last few years which have
generally been resolved by chromatog-
raphy on chiral stationary phases.[10] On
Scheme 2. Synthesis of the [2]catenane 8 bearing phosphine oxide functions.
the other hand, enantiomers are
expected when both macrocyclic moi-
eties contain prochiral centers, for
example, prochiral carbon atoms or phosphorus functions.[11]
In this case (Figure 1) both rings are oriented as a conse-
quence of the fact that the prochiral group makes the two
faces of the macrocycle different from one another. In other
reaction mixture by column chromatography, the cationic
catenate 7 was characterized by mass spectrometry as well as
1
by H and 31P NMR spectroscopy. The most representative
1H NMR signals come from the phenyl groups attached to the
phenantroline moiety: in analogous tetrahedral copper/
bis(phenanthroline) complexes, the meta-phenyl protons are
known to lie in the shielding field of the second phenanthro-
line moiety, which accounts for their high-field shifts at about
d = 6 ppm.[13] The corresponding signals for 7 appear at d =
6.03 (d, J = 9.0 Hz, 2H, Hm), 6.04 (d, J = 9.0 Hz, 2H, Hm’), 6.13
(d, J = 8.5 Hz, 2H, Hm), and 6.15 ppm (d, J = 9.0 Hz, 2H, Hm’).
=
words, each ring has a top face and a bottom face (the P O
À
and the P Ph faces, respectively). This arrangement is
sufficient to orient the other ring. (Note: strictly speaking,
the two objects of Figure 1 are nevertheless not topological
enantiomers since they can be interconverted by continuous
deformation of bonds at the prochiral phosphorus centers in
three-dimensional space.)
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Communications
0.33 mmol) in CH2Cl2 (16 mL) by the double-ended-needle transfer
technique. After stirring the mixture at room temperature for 0.5 h, a
solution of 2 (120 mg, 0.33 mmol) in DMF (17 mL) was added, which
resulted in the generation of a red-brown color corresponding to the
formation of 4. After stirring the mixture at room temperature for 1 h,
the solvent was partially removed in vacuo, and then a solution of
(S,S)-1b (0.35 mmol) in DMF (20 mL) was added. The mixture was
added dropwise, within 8 h, to a suspension of Cs2CO3 (0.32 g,
1 mmol) in DMF (50 mL) kept at 55–608C. After the end of the
addition, the heating was maintained for about 50 h. The DMF was
then removed under vacuum and the residue dissolved in H2O/
CH2Cl2. The organic layer was washed with brine and water,
concentrated to a volume of 20 mL, then stirred overnight with a
saturated aqueous solution of KPF6 to effect anion exchange. The
organic layer was washed with brine and water, dried with MgSO4,
and the solvent was evaporated to dryness. The crude product was
filtered through a column of silica gel using a CH2Cl2/MeOH gradient
(from 95:5 to 75:15) as the eluent. Complex 7 (150 mg, 0.07 mmol,
29% yield) was obtained as a red-brown oil as a mixture of two
diastereoisomers.
Complete characterization of 7 was prevented by the
presence of the two expected diastereoisomers.
After removal of the copper, the two diastereoisomers of
the free catenane 8 could be separated by preparative HPLC
and fully characterized. Figure 2 shows the HPLC chromato-
Demetalation of 7 (120 mg) was performed by vigorous stirring of
a solution of the copper complex in MeCN (4 mL) with an excess of
KCN (20 mg, 5 equiv) in water (1 mL) at room temperature for 3 h.
The initial reddish-brown color disappeared. The organic layer was
separated, dried over MgSO4, and the solvents evaporated to dryness.
The crude product was purified by column chromatography on silica
gel with an AcOEt/MeOH gradient (from 100:0 to 70:30) as the
eluent. Compound 8 was obtained as a mixture of two diastereoiso-
mers in 85% yield (98 mg). 31P NMR (CDCl3): d = 34.0 ppm; HRMS
(ESI): calcd for C88H95N4O14P2: 1493.6320; found: 1493.6294.
The components of a sample of 8a + 8b (60 mg) were separated
by preparative HPLC on a Waters SunFire C18 column with a
mixture of H2O/TFA/MeCN (66:0.1:34) as the eluent. The retention
times of 8a and 8b were 23 and 30 min, respectively. After
evaporation of the solvents, the residues were filtered through a
short column of silica gel by eluting successively with chloroform and
a mixture of AcOEt/MeOH (70:30) to remove the residual inorganic
salts.
Figure 2. a) HPLC chromatogram of a mixture of 8a and 8b. b) Partial
1H NMR spectra of solutions of 8a andc) 8b in CDCl3. Assignments
have been made by analogy to previously reported data (see ref. [13]).
gram as well as the 500 MHz 1H NMR spectra in the aromatic
region for the two isomers of 8. It can be noticed that, in both
isomers, the chiral environment markedly differentiates the
two halves of the phenanthroline moiety, thus giving well-
separated doublets for H3 and H8, as well as for H4 and H7.
The corresponding signals of the parent macrocycle 3 merge
into one another in the NMR spectrum despite the presence
of stereogenic carbon atoms in the molecule (d = 8.07 (d, J =
9.0 Hz, 2H, H3,8), 8.26 ppm (d, J = 8.0 Hz, 2H, H4,7)). Thus, it
seems that the presence of the interlocking rings results in a
more pronounced magnetic differentiation of the two sides of
the whole molecule, including the phenanthroline nucleus.
Phosphine oxides 8 represent an unprecedented class of
chiral phosphorus derivatives, that is, phosphorus-containing
chiral [2]catenanes, whose properties in coordination chemis-
try and catalysis will be investigated in the near future.
This exploratory study has established that catenanes
containing phosphine oxide functions can be generated by
using the template effect of copper/phenanthroline com-
plexes and suitable phosphorus-containing synthons. Stereo-
genic carbon atoms may be introduced into the above
structures so as to produce chiral derivatives. In addition,
chiral catenanes are generated as enantiomerically pure
diastereomers when both of the interlocking rings bear
phosphorus functions.
8a: 1H NMR (500 MHz, CDCl3): d = 1.08 (d, J = 5.5 Hz, 6H, Me),
1.28 (d, J = 5.5 Hz, 6H, Me), 1.91 (m, 2H, CH2P), 2.10–2.20 (m, 4H,
CH2P), 2.40 (m, 2H, CH2P), 3.27 (m, 4H), 3.38 (m, 2H), 3.51 (m, 2H),
3.60–3.70 (m, 10H), 3.82 (m, 4H), 3.90 (m, 6H), 4.20–4.30 (m, 8H),
7.10 (d, J = 8.0 Hz, 4H, Hm), 7.22 (d, J = 6.5 Hz, 4H, Hm’), 7.30 (m,
6H, PhH), 7.55 (m, 4H, PhH), 7.74 (m, 4H, H5,6), 8.10 (d, J = 8.5 Hz,
2H, H3/H8), 8.14 (d, J = 8.0 Hz, 2H, H3/H8), 8.24 (d, J = 9.0 Hz, 2H,
H4/H7), 8.27 (d, J = 7.5 Hz, 2H, H4/H7), 8.42 (brs, 4H, Ho), 8.51 ppm
(brs, 4H, Ho’).
8b: 1H NMR (500 MHz, CDCl3): d = 0.98 (d, J = 6.0 Hz, 6H,
Me), 1.27 (d, J = 5.5 Hz, 6H, Me), 1.90 (m, 2H, CH2P), 2.10–2.20 (m,
4H, CH2P), 2.35 (m, 2H, CH2P), 3.18 (m, 2H), 3.24 (m, 2H), 3.31 (m,
2H), 3.40, (m, 2H), 3.5–3.7 (m, 12H), 3.70–3.90 (m, 8H), 4.15 (m,
4H), 4.23 (m, 4H), 7.01 (d, J = 7.5 Hz, 4H, Hm), 7.10 (d, J = 7.5 Hz,
4H, Hm’), 7.20 (m, 6H, PhH), 7.45 (m, 4H, PhH), 7.64 (m, 2H, H5,6),
8.01 (d, J = 8.5 Hz, 2H, H3/H8), 8.02 (d, J = 8.5 Hz, 2H, H3/H8), 8.14
(d, J = 8.5 Hz, 2H, H4/H7), 8.18 (d, J = 8.5 Hz, 2H, H4/H7), 8.37 ppm
(brs, 8H, Ho,o’).
Received: October 13, 2005
Published online: February 27, 2006
Keywords: catenanes · chirality · copper · phosphine oxide ·
.
template synthesis
Experimental Section
8a,b: A degassed solution of [Cu(MeCN)4]PF6 (130 mg, 0.35 mmol)
in MeCN (9 mL) was transferred to a solution of (S,S)-3 (240 mg,
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