Metal complexes of chiral Moebius aromatic [28]hexaphyrin(1.1.1.1.1.1): Enantiomeric separation, absolute stereochemistry, and asymmetric synthesis

Article abstract of DOI:10.1002/anie.201002282

Twist and sort out! Chiral separation of PdII, NiII, and PtII complexes of [28]hexaphyrin(1.1.1.1.1.1) was achieved by HPLC on a chiral stationary phase (see inset for CD trace). The absolute configuration for the PdII complex was determined by X-ray crystallography. Asymmetric metalation of hexaphyrin, achieved with a PdII binap salt, resulted in 23 □% ee. This is the first example of asymmetric synthesis of Moebius-twisted molecules.

Full text of DOI:10.1002/anie.201002282

Angewandte
Chemie
DOI: 10.1002/anie.201002282
Aromaticity
Metal Complexes of Chiral Mꢀbius Aromatic
[28]Hexaphyrin(1.1.1.1.1.1): Enantiomeric Separation, Absolute
Stereochemistry, and Asymmetric Synthesis**
Takayuki Tanaka, Tsutomu Sugita, Sumito Tokuji, Shohei Saito, and Atsuhiro Osuka*
The concept of Mꢀbius aromaticity, first proposed by
Heilbronner in 1964, predicts the aromatic characters for
[4np]annulenes with singly twisted so-called Mꢀbius top-
ology.[1] Importantly, this concept complements the estab-
lished Hꢁckel aromaticity that is based on normal planar p-
electronic network,[1,2] and therefore stimulates both theoret-
ical and experimental studies. Among these studies, the first
Mꢀbius aromatic [16]annulene was reported by Herges and
co-workers in 2003,[3] and was followed by an interesting
example of a di-p-benzi-hexaphyrin that exhibited a temper-
ature dependent structural change between Hꢁckel and
Mꢀbius conformations.[4] In the last two years, Mꢀbius
aromatic systems have been efficiently prepared starting
Figure 1. Two enantiomers of hexaphyrin metal complexes. C6F5
groups at the meso positions were omitted for simplicity.
from meso-aryl-substituted expanded porphyrins through
metal coordination,[5a,b] temperature control,[5c,d] protonatio-
n,[5e,f] and intramolecular fusion reactions.[5g,h]
Macrocycles that have a singly twisted Mꢀbius topology
are intrinsically chiral, and can be either P-twist or M-twist, as
shown in Figure 1. Control of the chirality of Mꢀbius aromatic
expanded porphyrins is important to understand their mag-
netic properties and to apply these systems to chirality sensing
and asymmetric catalysts. Although the enatiomeric separa-
tion of Mꢀbius aromatic annulenes has been accomplished by
Herges and co-workers, their absolute configurations have
not been determined.[3b] In addition, only limited examples of
the enantiomeric separations of twisted expanded porphyrins
have been reported to date.[6]
We envisioned the enantiomeric separation of Group 10
metal complexes of [28]hexaphyrin(1.1.1.1.1.1) on the basis
that hexaphyrins are considered to be rather robust, as
indicated by their almost temperature-independent 1H NMR
spectra. Herein, we report the enantiomeric separation of
these complexes by using preparative HPLC on a chiral
stationary phase, as well as the asymmetric synthesis of the
palladium(II) complex.
[28]Hexaphyrin(1.1.1.1.1.1) complexes of PdII (2), NiII (3),
and PtII (4) were prepared according to a previously reported
method that entailed the addition of PdCl2, Ni(acac)2, and
PtCl2 at reflux for 12 hours, 1 hour, and 5 days, respectively
(acac = acetylacetonate).[5a,7] In the case of complex 2, we
found a far more effective method that entailed treatment of
[26]hexaphyrin(1.1.1.1.1.1) 1 (see Scheme 1 for structure)
with [Pd2(dba)3] in the presence of sodium acetate in a
mixture of CH2Cl2/MeOH (dba = 1,5-diphenyl-1,4-pentadien-
3-one). This method produced complex 2 in 75% yield at
room temperature in 2 hours. The enantiomeric separation of
complex 2 was examined by using an analytical HPLC column
(SUMICHIRAL OA-3100; f= 10 mm), which, after exten-
sive experimentation, led to a clear separation of the
enantiomers with a mixture of CH2Cl2/n-hexane (v/v = 1:1)
as an eluent (See the Supporting Information). Based on this
finding, the preparative chiral separation of complex 2 was
performed successfully on a larger HPLC column (f=
20 mm) with a less polar eluent (CH2Cl2/n-hexane, v/v =
1:2). Under similar conditions, the enantiomeric separations
of complexes 3 and 4 were also successfully accomplished.
The spectra of the isolated enantiomers displayed oppo-
site Cotton effects (Figure 2). The CD spectrum of the
enantiomer that eluted first, 2A, shows the first Cotton effect
as a negative–positive bisignate split signal around 639 nm,
and the second signal as a positive Cotton effect at 397 nm
(Figure 2a). The enantiomers of 3 and 4 that eluted first show
practically the same CD spectra as those of 2; the bisignate
split signal and the positive signal at 639 and 387 nm for 3A
and at 619 and 383 nm for 4A, respectively (Figure 2b,c). The
large De values ( ꢀ 300mÀ1 cmÀ1) for these enantiomers,
[*] T. Tanaka, T. Sugita, S. Tokuji, Dr. S. Saito, Prof. Dr. A. Osuka
Department of Chemistry, Graduate School of Science
Kyoto University, Sakyo-ku, Kyoto 606-8502 (Japan)
Fax: (+81)75-753-3970
E-mail: osuka@kuchem.kyoto-u.ac.jp
[**] This work was supported by Grants-in-Aid (nos. 19205006 (A) and
20108001 “pi-Space”) from the MEXT. T.T. and S.S. acknowledge a
JSPS Fellowship for Young Scientists. We thank Prof. H. Sugiyama,
Kyoto University, for the CD measurement.
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/anie.201002282.
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Figure 3. X-ray crystal structure of 2A. a) ORTEP drawing of two
molecules in the unit cell. Thermal ellipsoids were scaled to 50%
probability levels. Solvent molecules were omitted for clarity. b) One
molecule representation (C6F5 substituents were omitted for clarity)
and schematic twisting model.
is a slight difference between the structures of the racemate of
2 and of 2A; the two largest values of the dihedral angles are
À41.148 and 134.138 for the former,[5a,7] and 36.55(43.28)8 and
127.67 (134.55)8 for the latter—the difference probably
arising as a consequence of crystal packing.
The [28]hexaphyrin(1.1.1.1.1.1) complex of PdII (2) is
certainly structurally robust and shows practically no spec-
troscopic change even at 1408C, as indicated by the variable-
temperature 1H NMR measurement carried out in
[D2]1,1,2,2-tetrachloroethane solution, (Figure S6 in the Sup-
porting Information). However, we found complete racemi-
zation of 2A after heating in xylene at reflux overnight. On
the basis of this finding, the racemization kinetics were
examined at temperatures of 90–1208C under a nitrogen
atmosphere by monitoring the decrease in intensity of the CD
signal. The racemization rate constants, which obeyed first-
order kinetics, were determined at different temperatures
(See the Supporting Information). From these data, the
Figure 2. CD spectra of [28]hexaphyrin(1.1.1.1.1.1) metal complexes in
CH2Cl2. a) PdII complex 2 with UV/VIS absorption spectrum directly
underneath, b) NiII complex 3, and c) PtII complex 4; where A and B
correspond to the first and second fractions collected, respectively.
following activation parameters were determined: DG°
=
373
attributed to the strong aromaticity, is interesting in view of
their potential application as chiral sensors.
127.2 kJmolÀ1, DH° = 124.1 kJmolÀ1, DS° = À8.3 JmolÀ1 KÀ1,
and DEa = 127.2 kJmolÀ1. The activation barrier DEa is higher
than that of a larger figure-of-eight octaphyrin complex of
PdII reported by Vogel and co-workers (96.5 kJmolÀ1).[6b]
Next, we examined the possibility of the asymmetric
synthesis of Mꢀbius aromatic expanded porphyrins by using
Fortunately, we obtained crystals of 2A suitable for X-ray
crystallographic analysis from an acetonitrile/H2O solution.[8]
The crystal structure is shown in Figure 3a. The asymmetric
unit contains two identical molecules, both of which have the
same P-twist configuration. Thus, the absolute configuration
of 2A has now been unambiguously determined. Notably, this
relationship between the CD spectrum and the absolute
configuration is quite analogous to the related previous
examples of [36]octaphyrin(2.1.0.1.2.1.0.1) and N-fused
[32]heptaphyrin(1.1.1.1.1.1.1), both of which have twisted
figure-of-eight structures,[6,9] which suggest the generality of
this relationship. Interestingly, this assignment was also
supported by TD-DFT calculations (Figure S5 in the Sup-
porting Information). Another interesting structural feature
chiral PdII salts.[10,11] With PdII salts containing Pd N bonds,
À
such as Pd1 and Pd2, the metalation proceeded slowly and
provided complex 2 in low yields and with poor enantiose-
lectivities (Scheme 1). However, the reaction with Pd3 gave 2
in 33% yield and with 23% ee at room temperature after
3 days. To the best of our knowledge, this is the first example
of effective chiral induction in the synthesis of Mꢀbius twisted
molecule. An increase of the reaction temperature to 408C
resulted in the isolation of 2 in 72% yield, although the
enantioselectivity decreased to 13% ee. We also found the
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Scheme 1. Asymmetric synthesis of 2 using chiral PdII salts. [a] Deter-
mined by HPLC on a chiral stationary phase. [b] Positive ee value
means 2A rich (P-twist), and negative ee value means 2B rich (M-
twist). DMSO=dimethyl sulfoxide.
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preferential precipitation of racemic crystals of 2. Thus,
simple recrystallization of 2 (+ 20% ee) gave almost racemic
crystals (+ 2% ee), thus leaving the filtrate optically more
enriched (+ 70% ee).[12]
In summary, [28]hexaphyrin(1.1.1.1.1.1) complexes of
PdII, NiII, and PtII were all resolved into their enantiomers.
The absolute configuration of an enantiomer of the PdII
complex was determined by X-ray analysis, and which, as
judged from the similarities in the elution behavior and in the
CD spectroscopic patterns, was considered to dictate the
absolute configurations for the other complexes. The activa-
tion energy for the racemization was estimated to be
127.2 kJmolÀ1 for the PdII complex. Furthermore, the asym-
metric synthesis of a Mꢀbius aromatic expanded porphyrin
was accomplished for the first time with moderate enantio-
selectivity. Current investigations are focused on applying
these chiral Mꢀbius aromatic hexaphyrins to sensing materi-
als and asymmetric catalysts.
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[8] Crystal data for 2A: C146H49F60N19Pd2 (Mr = 3421.84), mono-
clinic, space group P21 (No. 4), a = 7.4807(11), b = 30.939(4), c =
28.603(5) ꢃ, b = 91.782(7)8, V= 6616.8(17) ꢃ3, Z = 2, 1calcd
=
1.717 gcmÀ3, Flack parameter= À0.005(15) R1 = 0.0589 (I > 2s
(I)), RW = 0.1225 (all data), GOF = 1.030: CCDC 767696 con-
tains 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.
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helical cyclooctapyrrole. They used chiral 1-(1-phenyl)ethyl-
amine and accomplished 19% ee using a copper salt in CH2Cl2,
see: J. Setsune, A. Tsukajima, N. Okazaki, J. M. Lintuluoto, M.
Lintuluoto, Angew. Chem. 2009, 121, 785; Angew. Chem. Int. Ed.
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Received: April 17, 2010
Published online: July 29, 2010
Keywords: asymmetric synthesis · hexaphyrins · metalation ·
.
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[12] Racemate crystals were slightly soluble in cold n-heptane, which
is the reason why the obtained filtrate was not completely
enantiopure. Without washing with cold n-heptane, we obtained
crystals (+ 20% ee) and filtrate (+ 80% ee) from a + 40% ee
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