A widely applicable concept for predictable induction of preferred configuration in C3-symmetric systems

Article abstract of DOI:10.1039/b502158h

Starting from a single chiral platform a widely applicable concept to introduce the preferred configuration of octahedral and tetrahedral centres in C₃-symmetric systems is described. The Royal Society of Chemistry 2005.

Full text of DOI:10.1039/b502158h

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A widely applicable concept for predictable induction of preferred
configuration in C3-symmetric systems{
Gebhard Haberhauer,* Thomas Oeser and Frank Rominger
Received (in Cambridge, UK) 11th February 2005, Accepted 8th April 2005
First published as an Advance Article on the web 22nd April 2005
DOI: 10.1039/b502158h
arms to it (E). The fixation of the arms on a centre would then
predetermine the configuration of the latter (F).
Starting from a single chiral platform a widely applicable
concept to introduce the preferred configuration of octahedral
and tetrahedral centres in C3-symmetric systems is described.
Recently, we synthesized an imidazole platform (1) to which
three arms can be attached by simple alkylation reactions.7 The
X-ray structure of a substituted platform shows that due to the
chirality of the platform the arms are oriented opposite to
the isopropyl groups of the adjacent a-C-atoms and moreover do
not point perpendicularly downward, but are arranged in a triple
helix-like structure like E in Scheme 1.7 The preorganisation of the
arms enabled us to suppose that it should be possible to realize the
above-described concept, i.e. a predictable induction of preferred
configuration in C3-symmetric systems, by using the said imidazole
platform.
In recent years, chiral systems showing C3 symmetry have created
much interest and found application in several areas, including
molecular receptors,1 dendrimers,2 organometallic ligands1k,3 and
asymmetric catalysis.1k,4 C3-symmetric tripodal ligands, which in
octahedral centres render the remaining three coordination sites
identical, have a major contribution to make to asymmetric
catalysis.1k
The formation of a C3-symmetric centre, especially one with a
predetermined configuration (C in Scheme 1), usually starts from
tripodal systems (B) assembled from an achiral platform or an
achiral centre and three chiral arms. To our knowledge, there is
only one case where a scaffold (E) assembled from a chiral
platform and three achiral arms predetermines the configuration at
a C3-symmetric centre to be formed (F in Scheme 1), namely
enterobactin, where the corresponding D-Fe(III) complex is formed
stereoselectively.5 However, the energy difference between the L-
and the D-isomer of about 2.1 kJ mol21 is low,6 which may be
explained by the high flexibility of the lactone platform. In our
opinion, it is therefore impossible to make any predictions about
the configuration when the centre and/or the arms of this system
are varied.
To verify this hypothesis, we reacted the tris(bipyridine)
platform 2a7 with ruthenium(II)8 and osmium(II)9 ions (Scheme 2).
From the hereby formed octahedral complexes 3a and 3b only one
diastereomer could be isolated. Our prediction, which was based
Nevertheless, the predictable induction of the preferred config-
uration in C3-symmetric systems by a chiral platform is of great
interest. This concept would be of a very general applicability
because starting from a single platform (D) (which carries the
complete chiral information) one would only have to attach achiral
Scheme 1
Scheme 2 Reagents and conditions: (a) C11H9N2CH2Br, K2CO3,
CH3CN, D, 65%; (b) C11H8NCH2Br, K2CO3, CH3CN, D, 77%; (c) m-
(BrH2C)C6H4(CH2Br), K2CO3, CH3CN, D, 55%; (d) Ru(DMSO)4Cl2,
EtOH, D, 55% for 3a and (NH4)2OsCl6, ethylene glycol, D, 50% for 3b; (e)
Ir(acac)3, ethylene glycol, D, 49%; (f) NH3, K2CO3, CH3CN, D, 90%.
{ Electronic supplementary information (ESI) available: experimental
preparations for 2b, 2c, and 3a–d. See http://www.rsc.org/suppdata/cc/b5/
b502158h/
*gebhard.haberhauer@urz.uni-heidelberg.de
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Chem. Commun., 2005, 2799–2801 | 2799

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on the orientation of the arms into one direction in space, was that
the L-isomers had been formed. The X-ray structure of the
isolated ruthenium complex 3a (Fig. 1) proved that the prediction
had been correct. Of particular interest is the fact that the newly-
formed ruthenium centre is more than 7 s away from the
configuration-determining a-carbon atoms of the platform.
Moreover, DFT-based calculations were carried out in order to
determine the extent of stereoselectivity by the chiral platform. The
full geometry optimization computations were performed for the
L- and the D-complexes of 3a and 3b applying the DFT-
B3LYP10,11 method and 3-21G*12 or LanL2DZ13 basis set. The
energy difference between the stereoisomers is 105.8 kJ mol21
(B3LYP/3-21G*) or 139.2 kJ mol21 (B3LYP/LanL2DZ) for 3a
and 144.7 kJ mol21 (B3LYP/LanL2DZ) for 3b, in favour of the
clearly preferred L-isomers. The very high energy difference
explains why only the L-isomers are formed. In our opinion, this
high difference is due to the strong repulsive steric interactions
between the methyl groups on the imidazole rings and the
bipyridine arms (Fig. 1).
Fig. 2 Crystal structures of 3c (left, view perpendicular to the molecular
three-fold axis) and 3d (right; view along the molecular three-fold axis). All
hydrogen atoms and some solvent molecules have been omitted for clarity.
In summary, we describe for the first time a predictable
induction of the preferred configuration by a platform, via three
arms, to a newly-formed C3-symmetric centre. The presented
concept is of a very general applicability because, starting from a
single platform (which carries the complete chiral information),
different achiral arms and centres can be used. For the future we
plan to predictably induce the configuration at a C3-symmetric
octahedral or tetrahedral catalytic centre over a wide distance, e.g.
over seven and more bonds.{
To verify the general applicability of the concept, we further
investigated whether the predictable induction of the preferred
configuration can be realized with other arms and centres. In the
first case, tolyl pyridine arms were attached to the scaffold 1 and
14
the resulting platform 2b was reacted with Ir(acac)3 to give the
octahedral iridium complex 3c (Scheme 2). In the second case, the
platform 1 was converted into the tribromide 2c, which was
subsequently treated with ammonia to give the tertiary amine 3d.
Here too, in both cases, only one diastereomer could be isolated.
The X-ray structures of these diastereomers show that both
correspond to the predicted configuration (Fig. 2). The isolated
octahedral iridium complex 3c proved to be the L-isomer, whereas
the isolated tetrahedral tertiary amine 3d forms a right-handed
rotation, as shown in Fig. 2 (right view).
We thank the Deutsche Forschungsgemeinschaft for support
and Dr. Andreea Schuster for assistance.
Gebhard Haberhauer,* Thomas Oeser and Frank Rominger
Organisch-Chemisches Institut, Universita¨t Heidelberg, Im Neuenheimer
Feld 270, D-69120 Heidelberg, Germany.
E-mail: gebhard.haberhauer@urz.uni-heidelberg.de;
Fax: +49 (0) 6221 544205
Notes and references
To investigate the extent of stereoinduction by the chiral
platform for a tetrahedral centre, the energy of the isolated amine
3d and of the isomer with inverse configuration at the nitrogen
atom was calculated by applying the DFT method. The energy
difference between the two configuration isomers is 47.2 kJ mol21
(B3LYP/3-21G*) or 21.6 kJ mol21 (B3LYP/LanL2DZ), in favour
of the isolated amine 3d.
{ Crystal data: for C63H69N15O3Ru?2PF6 (3a): M 5 1475.34, orange
crystal (irregular), dimensions 0.17 6 0.10 6 0.09 mm3, crystal system
cubic, space group P213, Z 5 4, a 5 18.999(1) s, V 5 6858.1(6) s3,
r 5 1.429 g cm23, T 5 100(2) K, hmax 5 20.79u, radiation Mo Ka,
l 5 0.71073 s, m 5 0.36 mm21, 36787 reflections measured, 2388 unique
[R(int) 5 0.097], 2311 observed [I . 2s(I)], R1(F) 5 0.044, wR(F2) 5 0.102,
residual electron density 20.32 to 0.67 e s23
.
For C63H63IrN12O3?7.8H2O (3c): M 5 1368.98, yellow crystal
(irregular), dimensions 0.16 6 0.12 6 0.04 mm3, crystal system
rhombohedral, space group R3, Z 5 3, a 5 16.214(1) s, c 5 22.071(2) s,
V 5 5024.7(7) s3, r 51.357 g cm23, T 5 100(2) K, hmax 5 28.32u,
radiation Mo Ka, l 5 0.71073 s, m 5 2.06 mm21, 17200 reflections
measured, 5546 unique [R(int) 5 0.052], 5518 observed [I . 2s(I)],
R1(F) 5 0.047, wR(F2) 5 0.111, residual electron density 20.73 to
2.72 e s23
.
For C51H60N10O3?2CH2Cl2 (3d): M 5 1030.94, colorless crystal
(polyhedron), dimensions 0.28 6 0.24 6 0.12 mm3, crystal system
monoclinic, space group P21, Z 5 2, a 5 13.0619(2) s, b 5 15.4301(3) s,
c 5 13.6751(1) s, b 5 92.0570(10)u, V 5 2754.39(7) s3, r 5 1.243 g cm23
,
T 5 200(2) K, hmax 5 21.50u, radiation Mo Ka, l 5 0.71073 s, m 5
0.26 mm21, 16688 reflections measured, 6327 unique [R(int) 5 0.097], 4978
observed [I . 2s(I)], R1(F) 5 0.060, wR(F2) 5 0.149, residual electron
density 20.58 to 0.92 e s23. CCDC 257958–257960. See http://
www.rsc.org/suppdata/cc/b5/b502158h/ for crystallographic data in CIF
or other electronic format.
Fig. 1 Crystal structure of the isolated L-isomer of 3a (left) and
calculated molecular structure of the D-isomer of 3a (right). View
perpendicular to the molecular three-fold axis; all hydrogen atoms and
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