"Induced fit" in chiral recognition: Epimerization upon dimerization in the hierarchical self-assembly of helicate-type titanium(IV) complexes

Article abstract of DOI:10.1002/anie.201006448

Undecided! A titanium(IV) triscatecholate bearing chiral ester groups shows different CD spectra in methanol and DMSO. The observation of different stereoisomers lies in the preferred conformation of the side groups in the monomer and dimer, which leads to different chiral induction in the different species. Copyright

Full text of DOI:10.1002/anie.201006448

Communications
DOI: 10.1002/anie.201006448
Supramolecular Metal Complexes
“Induced Fit” in Chiral Recognition: Epimerization upon
Dimerization in the Hierarchical Self-Assembly of Helicate-type
Titanium(IV) Complexes**
Markus Albrecht,* Elisabeth Isaak, Miriam Baumert, Verena Gossen, Gerhard Raabe, and
Roland Frꢀhlich
Dedicated to Professor Dieter Enders on the occasion of his 65th birthday
The processing and transfer of stereochemical information is
based on communication between two chiral units or between
a chiral and a prochiral unit. Stereoselective processes often
rely on chirality transfer from a chiral ligand to a catalytically
[
1,2]
[3]
active (metal) center.
interaction of a substrate with a receptor (which might be a
In supramolecular chemistry, the
[
4]
catalyst) follows the lock and key principle, and an “induced
fit” between the components enables optimized interaction.
[5]
Thus, stereoselection (for example, in catalysis) is often based
on supramolecular chiral recognition processes.
[6]
In helicates, the transfer of stereochemcial information
[7]
between two units has been investigated thoroughly. The
introduction of enantiomerically pure ligands can afford
[
8]
diastereomerically and enantiomerically pure helicates.
[
9]
Recently, hierarchically formed helicates with bridging
[
10]
+
lithium cations were described,
in which three Li ions
connect two mononuclear complex moieties. In this case, the
interlocking of the two propeller-type complexes, which
allows effective coordination of the lithium ions, is only
possible if the two propellers possess the same twist.
The distorted octahedral mononuclear complex exists in
solution as four fast equilibrating isomers. The ligands can
have a fac or a mer orientation (sometimes referred to as syn
and anti) and the complexes a L or D configuration
+
(
Scheme 1). A slow reversible Li -mediated dimerization
occurs only between homochiral units of the fac isomers, and
in the dimers the stereochemistry (“the helical twist”) is
locked. Racemization of the helicates proceeds by slow
dissociation, but not by direct interconversion. Although the
tetrahedrally coordinated lithium cations are extremely
labile, the cooperative binding of three cations slows down
the dissociation of the dimer.
Scheme 1. Hierarchically assembled triple lithium-bridged bistitani-
um(IV) complexes. The isomers of the monomeric unit are in fast
equilibrium with each other, while the LL and DD dimers are formed
slowly. The latter species are able to racemize by slow dissociation,
[10]
but not by direct interconversion.
[
*] Prof. Dr. M. Albrecht, E. Isaak, Dr. M. Baumert, V. Gossen,
Prof. Dr. G. Raabe
Institut fꢀr Organische Chemie, RWTH Aachen University
Landoltweg 1, 52074 Aachen (Germany)
Fax: (+49)241-809-2385
Monomers and dimers are easily distinguished by NMR
spectroscopy because of the anisotropic shift as well as the
diastereotopicity in the dimer. The monomer–dimer equi-
[10]
librium is influenced by different factors. For example, the
dimer is more stable in less-coordinating solvents such as
methanol, while the monomer is the major species in strongly
E-mail: markus.albrecht@oc.rwth-aachen.de
Dr. R. Frꢁhlich
Organisch-Chemisches Institut, WWU Mꢀnster
Corrensstrasse 40, 48149 Mꢀnster (Germany)
[10]
coordinating solvents (for example, DMSO).
In the racemic system, all the equilibria between enan-
tiomers are equivalent (Scheme 1). The introduction of chiral
information results in the formation of diastereomers, and
epimerization at the metal complex will favor one of the
diastereomeric chiral species. Therefore, the chiral esters 1-H2
[
**] This work was supported by the Fonds der Chemischen Industrie
and the DFG (International research training group SeleCa).
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/anie.201006448.
2
850
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Angew. Chem. Int. Ed. 2011, 50, 2850 –2853

and 2-H of 2,3-dihydroxybenzoic acid were prepared starting
2
[
11]
from (S)-citronellol and (S)-phenylethanol.
-H and 2-H form titanium(IV) triscatecholates on
[
12]
1
2
2
reaction (3 equiv) with [TiO(acac) ] (1 equiv) and Li CO
2
2
3
1
(
1 equiv) in methanol. H NMR spectroscopy reveals that in
the case of Li [(1) Ti], the dimer Li[Li {(1) Ti} ] is the only
2
3
3
3
2
observable species in [D ]MeOH. Both the monomer and
4
dimer are observed in [D ]DMSO, and a dimerization
6
À1
constant of Kdim = 2400m has been determined. The dimer
is identified by two multiplets of diastereotopic O-CH2
protons at d = 3.54 and 2.94 ppm, while the monomer shows
only one signal (d = 4.10 ppm). The fast isomerization at the
monomer (for example, by a Bailar twist or Ray–Dutt
rearrangement) prevents the stereoisomeric complexes (SL
and SD) from being observed separately. Thus, the g-methyl
group of the monomer appears only as one doublet at d =
Figure 1. CD spectra of Li [(2) Ti]/Li[Li {(2) Ti} ] in methanol and
DMSO.
2
3
3
3
2
0
.88 ppm, while in the dimer this methyl group splits into two
recrystallization resulted in the potassium salt of
À
doublets in a ratio of 40:60 at d = 0.77 and 0.73 ppm. This is a
measure of the stereochemical induction of the g stereocenter
on the complex units that results in 20% de. CD spectroscopic
investigations of the complex Li [(1) Ti]/Li[Li {(1) Ti} ] either
[Li {(2) Ti} ] being obtained. Figure 2 depicts one of the
3
3
2
two independent structures of the anion in the crystal, with
the interlocking of the complex units and the bridging by
three lithium cations (all L configuration). The complex has
the right-handed helical form (DD).
2
3
3
3
2
in methanol or DMSO indicate that the L configuration
dominates in the complex.
In the case of ligand 2-H , the stereocenter of the ester is
2
much closer to the metal ion and stronger stereochemical
induction occurs. In fact, only one “enantiomerically pure”
diastereoisomer is found in the NMR spectrum of the
dinuclear complex Li[Li {(2) Ti} ]. No diastereotopic NMR
3
3
2
probes are present in the case of ligand 2; however, the
dimeric titanium(IV) complex shows the characteristic high-
field shift of the a proton or of the methyl resonance. The
dimer (dCH-a = 4.47, q) is the dominant species in [D ]MeOH.
4
Only traces of the monomer (d
= 5.04, q) are observed
À
CH-a
Figure 2. Molecular structure of the anion [Li {(2) Ti} ] in the crystal
3
3
2
À1
(Kdim = 4600m ). The situation is reversed in [D ]DMSO:
6
(only one of the two inequivalent units in the lattice is shown).
C black, H white, O red, Li blue, Ti yellow.
The monomer Li [(2) Ti] (d = 5.89, q) is the major species,
2
3
CH-a
while only traces of dimer Li[Li {(2) Ti} ] (d = 4.91, q) are
CH-a
3
3
2
À1
found (Kdim = 16m ).
The CD spectra of Li [(2) Ti]/Li[Li {(2) Ti} ] in methanol
Figure 3 summarizes the rationalization of the stereo-
chemical inversion of the complex units upon dimerization.
Esters of secondary alcohols are known to adopt a conforma-
tion in which the proton at the a position is oriented in the
same direction as the carbonyl oxygen atom, which results in a
2
3
3
3
2
and DMSO are roughly mirror images (Figure 1). A positive
Cotton effect is observed around 340 nm and a negative
Cotton effect around 405 nm in methanol, while a negative
Cotton effect is found around 360 nm and a positive one at
[15]
4
20 nm in DMSO. The free ligand does not show significant
dihedral angle Ccarbonyl-O-C-H of close to 08. This orienta-
tion remains in monomeric Li [(2) Ti]. Both the carbonyl
CD signals, and so the detected transitions can be attributed
to the titanium(IV) triscatecholate. According to earlier
2
3
group as well as the a hydrogen atom point away from the
complex unit (“outwards”). This fixes the substituents at the
chiral unit relative to the coordination site. The higher steric
pressure of the phenyl compared to the methyl group controls
the tilting of the propeller-type complex, thereby resulting in
a preferred L configuration (Figure 3b, top).
[
13]
assignments
and recent computational studies (see the
Supporting Information), the configuration of the complexes
with ligand 2 depends on the solvent: D in methanol and L in
DMSO. This effect could be due to the dominating presence
of the monomer in DMSO and of the dimer in methanol.
Crystals suitable for X-ray structure analysis were
In the dimer, the carbonyl oxygen atom binds “inwards”
on coordinating to a lithium cation, and therefore rotation of
[
14]
obtained,
but an accidental cation exchange during the
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2851

Communications
The reduced steric bulk of the ester of ligand 1 and the
chiral information in the g position results in the complex
Li [(1) Ti]/Li[Li {(1) Ti} ] being present mainly as a dimer.
2
3
3
3
2
Even in DMSO, the monomer becomes only dominating at
À7
À1
concentrations as low as approximately 10 molL . The
dimer is the major species in methanol as well as in DMSO
À1
under the conditions used for the NMR (c ꢀ 0.003 molL ) as
À1
well as CD (c ꢀ 0.001 molL ) experiments. Thus, as
expected, the CD spectra are similar in both solvents.
In summary, a unique example of stereoinduction is
presented, in which the stereochemistry at a labile metal
complex unit is inverted and locked upon lithium-mediated
dimerization. The stereocontrol can be explained by different
conformations at the ester in the monomer and the dimer.
This result is impressive in the context of dynamic chiral
resolution in a supramolecular system following “induced fit”
based on stereorecognition.
Received: October 14, 2010
Revised: November 24, 2010
Published online: February 23, 2011
Keywords: CD spectroscopy · helicate · molecular recognition ·
.
NMR spectroscopy · stereochemistry
[
[
1] H. Brunner, Rechts oder links, Wiley-VCH, Weinheim, 1999.
2] a) E. L. Eliel, S. H. Wilen, Stereochemistry of Organic Com-
pounds, Wiley, 1994; b) K. Mikami, M. Lautens, New Frontiers in
Asymmetric Catalysis, Wiley, Chichester, 2007; c) H. Amouri, M.
Gruselle, Chirality in Transition Metal Chemistry, Wiley, Chi-
chester, 2008; d) for an impressive example of a chiral titani-
um(IV) complex in catalysis, see T. Katsuki, K. B. Sharpless,
J. Am. Chem. Soc. 1980, 102, 5974; e) for the mechanism, see
M. G. Finn, K. B. Sharpless, J. Am. Chem. Soc. 1991, 113, 113.
3] a) J.-M. Lehn, Supramolecular Chemistry—Concepts and Per-
spectives, VCH, Weinheim, 1995; b) J. W. Steed, J. L. Atwood,
Supramolecular Chemistry, Wiley, Chichester, 2000; c) G. M.
Whitesides, J. P. Mathias, C. T. Seto, Science 1991, 254, 1312;
d) D. Philp, J. F. Stoddart, Angew. Chem. 1996, 108, 1242; Angew.
Chem. Int. Ed. Engl. 1996, 35, 1154.
[
Figure 3. a–c) Rationalization of the preferred stereochemistry of the
monomer and dimer based on the result of the X-ray structure analysis
c; view down the Ti–Ti axis, groups of one of the chiral substituents
(
are shown in magenta (phenyl) and green (methyl)). b) The structure
of the ester group is fixed by the preferred orientation of the small
hydrogen atom towards the carbonyl oxygen atom. The formation of
the favored stereoisomers is explained on the basis of the steric
interaction in the hypothetic nontwisted “trigonal prismatic” species
[15]
[4] a) E. Fischer, Ber. Dtsch. Chem. Ges. 1894, 28, 2985 – 2993;
b) F. W. Lichtenthaler, Angew. Chem. 1994, 106, 2456; Angew.
Chem. Int. Ed. Engl. 1994, 33, 2364.
[
5] a) D. E. Koshland, Proc. Natl. Acad. Sci. USA 1958, 44, 98;
b) D. E. Koshland, Angew. Chem. 1994, 106, 2468; Angew.
Chem. Int. Ed. Engl. 1994, 33, 2375.
(
shown in parenthesis). Red arrows indicate steric interactions.
the ester groups occurs upon dimerization. Now, the steric
pressure from the large phenyl group on the trischelate of the
second complex moiety (Figure 3b, bottom) results in the
opposite twist compared to the monomer. Embedding the
chiral ester substituent in the groove of the helical complex
enforces some twisting of the dihedral angle Ccarbonyl-O-C-H to
[6] Reviews: a) C. Piguet, G. Bernardinelli, G. Hopfgartner, Chem.
Rev. 1997, 97, 2005; b) M. Albrecht, Chem. Rev. 2001, 101, 3457;
c) M. J. Hannon, L. J. Childs, Supramol. Chem. 2004, 16, 7; d) M.
Albrecht, Angew. Chem. 2005, 117, 6606; Angew. Chem. Int. Ed.
2005, 44, 6448.
[
7] For diastereoselective formation of helicates, see a) M. Albrecht,
S. Kotila, Angew. Chem. 1995, 107, 2285; Angew. Chem. Int. Ed.
Engl. 1995, 34, 2134; b) M. Albrecht, Chem. Eur. J. 2000, 6, 3485;
c) M. Albrecht, C. Riether, Chem. Ber. 1996, 129, 829 – 832.
2
0–558. This is stabilized by attractive CH–p interactions
between the secondary a proton and a neighboring catechol
unit at the second coordination site (Figure 3c). Solvent
effects on the CD spectra were observed previously, and it
was pointed out that the simple interpretation of CD spectra
[8] For pioneering work on the formation of enantiomerically pure
helicates, see a) W. Zarges, J. Hall, J.- M. Lehn, C. Bolm, Helv.
Chim. Acta 1991, 74, 1843; b) E. J. Enemark, T. D. P. Stack,
Angew. Chem. 1995, 107, 1082; Angew. Chem. Int. Ed. Engl.
[
16]
might lead to mistakes. However, in our study different
characterization techniques combined with computational
studies (see the Supporting Information) lead to a clear
picture of the situation.
1995, 34, 996.
[
9] See for comparison: a) A. K. Das, A. Rueda, L. R. Falvello, S.-
M. Peng, S. Batthacharya, Inorg. Chem. 1999, 38, 4365; b) J.
Heinicke, N. Peulecke, K. Karaghiosoff, P. Mayer, Inorg. Chem.
2
852
www.angewandte.org
ꢀ 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Angew. Chem. Int. Ed. 2011, 50, 2850 –2853

2
005, 44, 2137; c) T. Konno, K. Tokuda, T. Suzuki, K. I.
independent (Rint = 0.095) and 27748 observed reflections [I ꢂ
2
Okamoto, Bull. Chem. Soc. Jpn. 1998, 71, 1049; d) T. Konno,
K. Tokuda, K. Okamoto, Chem. Commun. 1998, 1697;
e) M. H. W. Lam, S. T. C. Cheung, K.-M. Fung, W.-T. Wong,
Inorg. Chem. 1997, 36, 4618; f) M. Albrecht, K. Witt, H. Rꢀttele,
R. Frꢀhlich, Chem. Commun. 2001, 1330.
2s(I)], 2164 refined parameters, R = 0.097, wR = 0.286, Flack
parameter 0.10(3), max. (min.) residual electron density 1.00
À3
(À0.35) eꢂ , hydrogen atoms calculated and refined as riding
atoms, hydrogen atoms at water molecules could not be located,
disordered solvents in voids could not be assigned in a chemi-
cally meaningful way. Data sets were collected with a Nonius
Kappa CCD diffractometer. Programs used: data collection
COLLECT (Nonius B.V., 1998) data reduction Denzo-SMN (Z.
Otwinowski, W. Minor, Methods Enzymol. 1997, 276, 307),
absorption correction Denzo (Z. Otwinowski, D. Borek, W.
Majewski, W. Minor, Acta Crystallogr. Sect. A 2003, 59, 228),
structure solution SHELXS-97 (G. M. Sheldrick, Acta Crystal-
logr. Sect. A 1990, 46, 467), structure refinement SHELXL-97
(G. M. Sheldrick, Acta Crystallogr. Sect. A 2008, 64, 112),
graphics SCHAKAL (E. Keller, Univ. Freiburg, 1997).
CCDC 794290 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.
[
10] a) M. Albrecht, S. Mirtschin, M. de Groot, I. Janser, J. Runsink,
G. Raabe, M. Kogej, C. A. Schalley, R. Frꢀhlich, J. Am. Chem.
Soc. 2005, 127, 10371; b) M. Albrecht, M. Baumert, J. Klanker-
mayer, M. Kogej, C. A. Schalley, R. Frꢀhlich, Dalton Trans. 2006,
4
395; c) M. Albrecht, M. Fiege, M. Baumert, M. de Groot, R.
Frꢀhlich, L. Russo, K. Rissanen, Eur. J. Inorg. Chem. 2007, 609.
11] C. J. Gramer, K. N. Raymond, Org. Lett. 2001, 3, 2827.
12] B. A. Borgias, S. R. Cooper, Y. B. Koh, K. N. Raymond, Inorg.
Chem. 1984, 23, 1009.
13] M. Albrecht, I. Janser, J. Fleischhauer, Y. Wang, G. Raabe, R.
Frꢀhlich, Mendeleev Commun. 2004, 14, 250.
14] X-ray
Li
orange crystal 0.35 ꢁ 0.20 ꢁ 0.10 mm , a = 24.1223(2), b =
[
[
[
[
crystal
structure
analysis
of
K[Li {(2) Ti} ]:
M = 1812.36,
r
3 3 2
1
3
K({C15
H
12
O
14
}
3
Ti) · =
2 2
4
C H
10O·C
2
H
6
O·2H
2
O,
3
3
2
1
8.7844(2),
c = 29.0182(5) ꢂ,
V= 20148.7(4) ꢂ ,
1calcd
=
[15] For example, K. Omata, K. Kotani, K. Kabuto, T. Fujiwara, Y.
Takeuchi, Chem. Commun. 2010, 46, 3610.
À3
À1
.195 gcm , m = 0.270 mm , empirical absorption correction
(
(
0.911 ꢁ Tꢁ 0.974), Z = 8, orthorhombic, space group P2 2 2
[16] B. Bosnich, J. M. B. Harrowfield, J. Am. Chem. Soc. 1972, 94,
989.
1
1 1
no. 19), l = 0.71073 ꢂ, T= 223(2) K, w and f scans, 136005
À1
reflections collected (Æ h, Æ k, Æ l), [(sinq)/l] = 0.59 ꢂ , 35058
Angew. Chem. Int. Ed. 2011, 50, 2850 –2853
ꢀ 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.angewandte.org
2853