Ion-pair-mediated asymmetric synthesis of a configurationally stable mononuclear tris(diimine)-iron(II) complex.
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ABSTRACT: Three tricyclic diquats with an eight-membered ring were prepared and shown to be the first configurationally stable derivatives of their kind. Resolution was achieved by using chiral hexacoordinated phosphorus BINPHAT and TRISPHAT anions. The diquat cations were obtained in high diastereo- and enantiomeric purity (ee>96% in most cases). X-ray diffraction analysis coupled with circular dichroism (CD) measurements allowed a precise determination of the relative and absolute configuration of the salts. The barriers to racemization of these compounds were calculated by using CD time-course measurements at different temperatures, affording DeltaG(++) values above 25 kcal mol(-1). Derivatives 4a, 4b, and 4c are the first eight-membered-ring derivatives with only three ring constraints to be resolved. This manuscript also reports the first procedure to remove TRISPHAT anions after diastereomeric separation.Chemistry 03/2010; 16(9):2797-805. · 5.93 Impact Factor
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ABSTRACT: A series of ditopic ligands incorporating two 2,2′:6′,2″-terpyridine (tpy) metal-binding domains linked to a central naphthalenediyl core by ethyleneoxy chains of various lengths have been prepared and their iron(II) complexes prepared. The major thermodynamic products of complexation are ferracycles of [1 + 1], [2 + 2] or [3 + 3] stoichiometry. In the case of the [1 + 1] complexes, the linker between the two tpy domains is spatially restricted and the cations exhibit chirality associated with the conformation about the central N–Fe–N bonds. The dynamic processes by which the enantiomeric forms interconvert are investigated in the presence of chiral anions by NMR and circular dichroism spectroscopy making use of the Pfeiffer effect. We have shown that ditopic bis(2,2′:6′,2″-terpyridine) ligands give rise to conformationally restricted complexes with iron(II) centres. The absolute configuration of the cations in the diastereomeric ion pairs obtained through the Pfeiffer effect has been calculated using TDDFT methods.New Journal of Chemistry 01/2009; 33(2). · 2.97 Impact Factor
- Angewandte Chemie International Edition 02/2009; 48(33):6073-7. · 11.34 Impact Factor
Angew. Chem. Int. Ed. 2002, 41, No. 13¹ WILEY-VCH Verlag GmbH, 69451 Weinheim, Germany, 20021433-7851/02/4113-2317 $ 20.00+.50/0
Ion-Pair-Mediated Asymmetric Synthesis of a
Configurationally Stable Mononuclear
Tris(diimine)±Iron(?? ??) Complex**
David Monchaud, Jonathan J. Jodry, Didier Pomeranc,
Vale ¬rie Heitz, Jean-Claude Chambron,
Jean-Pierre Sauvage, and Je ¬ro √me Lacour*
In memory of Andre ¬ Collet
Chiral mononuclear divalent tris(diimine) complexes of
first-row transition metals–keystones of coordination chem-
istry–are notoriously known for their high chemical but low
configurational stability.The ? and ? enantiomers–right-
and left-handed propellers, respectively–can be isolated in
good enantiomeric purity by efficient resolution proced-
ures.[1d, 2]However, once dissolved, these derivatives racemize
rapidly when no other source of chiral information is present
on the ligandsor in the reaction medium.
Recently, the synthesis of a bis(1,10-phenanthroline) ligand
L that forms octahedral complexes with a well-defined axis
([PF6]2, 1.0 equiv,dmbp?4,4?-dimethyl-2,2?-bipyridine)
with L (1.0 equiv) in refluxing 1,2-dichloroethane (DCE)
afforded [Fe(dmbp)(L)][PF6]2([PF6]2) in high yield and
purity [Eq. (1); for b1 and b2, see Figure 1].Here we report
on the unusual configurational stability of 2, which can be
resolved by simple preparative thin-layer chromatography
(TLC), and on its direct asymmetric synthesis by using
TRISPHAT anions (see below) as noncovalent chiral auxil-
iaries (diastereomeric ratio, d.r.?20:1).
The ease of synthesis of 2 and the rapidity of its formation
led us to assume a high chemical stability for [PF6]2. It was
then debatable whether an improved chemical stability would
also mean an increased configurational stability, so that the ?
and ? enantiomers might be inert and separable from each
other. Previously, the synthesis and resolution of the D3-
symmetric tris(tetrachlorobenzenediolato)phosphate(?) an-
ion (3), known as TRISPHAT, was reported.In association
with mononuclear ruthenium(??) or iron(??)tris(diimine) com-
plexes, it is an efficient NMR chiral-shift, resolving, and
asymmetry-inducing agent.It was therefore foreseen that
anion 3 could behave as a NMR chiral-shift reagent for the
structurally related complex 2
and possibly lead to its resolu-
Racemic complex 2 was stud-
iedin combination with
TRISPHAT salt. In an NMR
tube, [Et4N][?-3]was added
asa solidtoa solution
spectra (a) and (b)). Efficient separation of the signals of 2
was achieved with small amounts of chiral-shift reagent (1.0±
2.5 equiv). Protons H(b1) and H(b2) [see Equation (1)] were
most easily monitored, and a rather large difference in
chemical shift (??max?0.15 ppm) was observed. A 1:1 ratio
of ? and ? enantiomers could be measured by direct
integration of the respective signals. This 1:1 ratio of the
diastereomers [?-2][?-3]2and [?-2][?-3]2indicated a possible
configurational stability of cation 2. Indeed, it was recently
shown that anions 3 act as effective asymmetry inducers on
[Fe(dmbp)3]2?(1); when associated with the labile cationic
guest, they control its configuration with high diastereoselec-
tivity (d.r.?49:1 in CDCl3in favor of [?-1][?-3]2).[7b]Two
hypotheses could then explain the lack of asymmetric
induction observed in the NMR titration experiment (Fig-
ure 1, spectrum (b)): poor chiral recognition by 3 or high
configurational stability of 2.
We thus decided to attempt an ion-pair chromatographic
resolution, as the physical separation of ion pairs [?-2][?-3]2
and [?-2][?-3]2would prove the second hypothesis to be
correct.Under previously reported conditions,[7d, e]solutions
of [cinchonidinium][?-3] (2.5 equiv) in acetone and of [rac-
2][PF6]2in CH2Cl2were prepared, mixed, and adsorbed on
silica gel plates. Development by elution with CH2Cl2showed
a much reduced affinity of salts [?-3]2for silica gel, as they
were retained to a much lesser extent than the PF6?precursor
(Rf?0).Two well-separated bands were obtained (Rf?
0.94 and 0.84 in analytical TLC), abraded from the glass
[*] Prof. J. Lacour, D. Monchaud, J. J. Jodry
De ¬partement de Chimie Organique
Universite ¬ de Gene ¡ve
quai Ernest Ansermet 30, 1211 Gene ¡ve 4 (Switzerland)
D. Pomeranc, Dr. V. Heitz, Dr. J.-C. Chambron,[?]Dr. J.-P. Sauvage
Laboratoire de Chimie Organo-Mine ¬rale
UMR CNRS n? 7513, Faculte ¬ de Chimie
Institut Le Bel, Universite ¬ Louis Pasteur
4, rue Blaise-Pascal, 67070 Strasbourg-Cedex (France)
[?] Present address:
Universite ¬ de Bourgogne
Faculte ¬ des Sciences Gabriel, LIMSAG (UMR 5633)
6, Boulevard Gabriel, 21100 Dijon (France)
[**] We are grateful for financial support of this work by the Swiss
National Science Foundation, the Federal Office for Education and
Science (COST D11), the Fondation de Famille Sandoz (JL), the EC,
the CNRS, and the MENRT (DP).
Supporting information for this article is available on the WWWunder
http://www.angewandte.org or from the author.
¹ WILEY-VCH Verlag GmbH, 69451 Weinheim, Germany, 20021433-7851/02/4113-2318 $ 20.00+.50/0
Angew. Chem. Int. Ed. 2002, 41, No. 13
surface, and stirred in CH2Cl2. The resulting suspensions were
filtered and concentrated in vacuo. The
revealed two completely different sets of signals correspond-
ing to the resolved ? and ? enantiomers of the cation 2
(Figure 1, spectra (c) and (d)). Pure separated diastereomeric
ion pairs [?-2][?-3]2/[?-2][?-3]2were thus obtained in good
chemical yields (48 and 45%, respectively). A circular
dichroism (CD) spectrum of the more strongly eluted fraction
(CH2Cl2, ca. 5¥10?6?) revealed strong exciton coupling in the
?±?* region (??270??73, ??300??101??1cm?1) and the
visible metal-to-ligand charge transfer (MLCT) transitions
also showed opposite Cotton effects (??479??16, ??553?
?18??1cm?1). The CD spectrum of the less strongly eluted
diastereomer in the 235±600 nm region is essentially the
mirror image. These spectra can be assigned to the ? and ?
configurations of the cationic complex and demonstrate that
compounds [?-2][?-3]2and [?-2][?-3]2are the more and less
strongly eluted ion pairs, respectively.We believe that the
unusual configurational stability of 2, evidenced by the
1H NMR spectra shown in Figure 1, is attributable to the
bis-bidentate nature of L. Racemization of the iron(??)
complex implies a complete rearrangement of the system
with several decoordination and recoordination steps that
result, in particular, in the inversion of the helix formed by L
within 2.[5, 12]
Asymmetric synthesis of configurationally stable mononu-
clear coordination complexes has recently been the subject of
much attention; the classical strategy is the introduction of
stereogenic elements on the ligands, which then control–by
intramolecular diastereoselective interactions–the configu-
ration around the octahedral metal center.[3, 13]Temporary
covalent interactions between a chiral medium (sugars) and
designed achiral ligands can also be used and lead to good
selectivities, as shown recently by Shinkai et al.Having
demonstrated the configurational stability of complex 2, we
1H NMR spectra
reasoned that its asymmetric synthesis could be also possible
by using TRISPHAT anions (3) as chiral auxiliaries.We
imagined that the configurational ordering induced by anions
3 on the labile [Fe(dmbp)3]2?precursor 1 could be partially or
fully transferred to complex 2 during synthesis. Treatment of a
solution of [?-3]2in refluxing CD2Cl2[d.r. 7.25:1 in favor of
the homochiral ion pair (1H NMR)] with L (0.94 equiv)
afforded the desired complex [?-3]2in quantitative yield.
Excellent diastereoselectivity (d.r.?20:1) was obtained, as a
single set of signals corresponding to those of diastereomer
[?-2][?-3]2could be observed in the1H NMR spectrum of the
crude reaction mixture (Figure 2, spectrum (c)).To our
knowledge, this is the first example of high selectivity in the
asymmetric synthesis of a stable coordination complex by
using diastereoselective interactions restricted to intermolec-
the crude reaction mixture [?-3]2?L. a) After 44 h at 20?C, d.r.?1:1;
b) after 44 h at 20?C and 14 h at reflux, d.r.?10:1; c) after 60 h at reflux,
1H NMR spectra (??6.30±5.68) in 10% [D6]DMSO/CDCl3of
Figure 1. Ion-pair chromatographic resolution of [rac-2][PF6]2with [cinchonidinium][?-3].1H NMR spectra (??8.50±5.75) in 10% [D6]DMSO/CDCl3of
a) [rac-2][PF6]2; b) [rac-2][PF6]2?2.5 equiv of [Et4N][?-3], d.r.?1:1; c) [?-2][?-3]2, d.r.?49:1; d) [?-2][?-3]2, d.r.?49:1.
Angew. Chem. Int. Ed. 2002, 41, No. 13¹ WILEY-VCH Verlag GmbH, 69451 Weinheim, Germany, 2002 1433-7851/02/4113-2319 $ 20.00+.50/0
It was then of interest to determine the origin–kinetic or
thermodynamic–of the selectivity, especially since its value
(d.r.?20:1) is higher than the asymmetric induction of anions
3 on 1 (d.r.?7.25:1). Several studies were therefore per-
formed to determine the nature of the control. First, pure
heterochiral complex [?-2][?-3]2, isolated by chromatograph-
ic resolution, was heated to reflux in CD2Cl2, and complete
transformation into the homochiral diastereomer [?-2][?-3]2
was observed after 18 h.Under similar conditions, no
change was monitored for solutions of complex [?-2][?-3]2.
These results seemed to indicate thermodynamic control, as
the high diastereoselectivity of the synthetic reaction could
result from equilibration of the diastereomers at elevated
temperature. To test this hypothesis, the asymmetric synthesis
was attempted again at room temperature (20?C) rather than
at reflux (40?C). A rather long reaction time (44 h) was
required to achieve replacement of two dmbp ligands by L,
and the resulting [?-3]2salt was obtained with essentially
no selectivity (Scheme 1; d.r.?1:1, Figure 2, spectrum (a)).
When the reaction was carried out for 44 h at 20?C and then
14 h at 40?C, a high selectivity was again observed in favor of
the homochiral complex [?-2][?-3]2 (d.r.?10:1, Figure 2,
spectrum (b)). All these experiments seem to indicate that the
reactions performed at room temperature lead to a poor
diastereoselectivity under kinetic control, and that heating is
required to induce a high degree of configurational ordering
under thermodynamic control. The selectivity of the reaction
probably results from the preferred homochiral association of
three-bladed propellers 2 and 3.
In conclusion, we have shown that the configurational
stability of a tris(diimine)±iron(??) complex can be unusually
high for a carefully designed tetradentate ligand and that its
resolution and asymmetric synthesis is feasible by using
TRISPHAT anions as noncovalent chiral auxiliaries.
Received: December 6, 2001 [Z18336]
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 A shorter reaction time (24 h) can be used, but to ensure the high
diastereoselectivity and complete ligand exchange (see below), a
prolonged reaction time (60 h) is best.
 At room temperature in CD2Cl2, no such epimerization was observed
by1H NMR spectroscopy.