Chiral single-stranded metallohelix: metal-mediated folding of linear oligooxime ligand

Article abstract of DOI:10.1016/j.tetlet.2006.09.125

A linear tetraoxime ligand H₄L bearing chiral (S)-2-hydroxylpropyl groups at both ends was synthesized. Complexation between H₄L with Zn²⁺ and Mⁿ⁺ (=Ca²⁺, Y³⁺, La³⁺) afforded hel

Full text of DOI:10.1016/j.tetlet.2006.09.125

Tetrahedron Letters 47 (2006) 8419–8422
Chiral single-stranded metallohelix: metal-mediated folding
of linear oligooxime ligand
Shigehisa Akine, Takanori Taniguchi and Tatsuya Nabeshima*
Department of Chemistry, University of Tsukuba, Tsukuba, Ibaraki 305-8571, Japan
Received 4 August 2006; revised 14 September 2006; accepted 25 September 2006
Abstract—A linear tetraoxime ligand H4L bearing chiral (S)-2-hydroxylpropyl groups at both ends was synthesized. Complexation
between H4L with Zn2+ and Mn+ (=Ca2+, Y3+, La3+) afforded helical trinuclear complex [LZn2M]n+. The helical sense was the most
effectively induced when Ca2+ was used as the central metal Mn+
.
Ó 2006 Elsevier Ltd. All rights reserved.
In recent years, much interest has been focused on self-
organized abiotic oligomers and polymers, which spon-
taneously form a helical structure with the aid of weak
interactions.1 Although labile metal–ligand bonds have
been used to construct a number of self-organized dou-
ble- and triple helicates,2 there are few examples that
have metal atoms in the helical main chain.3 Such scaf-
fold with a helical array of metal ions would be useful to
make conducting nanocoils. We have been investigating
single-helical oligometallic complexes that can be
obtained from linear bis(salamo) 1a and its longer
analog.4–6 Control of the helical sense of such metal-
containing helices is important because sophisticated
functions are expected from a combination of the intrin-
sic properties of metal complex moieties with the chiral
helical structure. However, optical resolution of racemic
helices is not suitable to obtain a one-handed form,
when the helical complexes undergo reversible confor-
mational interconversion between right- and left-handed
(and non-helical) states. Instead, thermodynamic con-
trol can be used to obtain chiral helices. When the
strand is placed in a chiral environment or is functional-
ized with an appropriate chiral auxiliary, one-handed
helices can be preferentially formed.7 In such cases,
a rather small difference in thermodynamic stability
between the two forms is sufficient for a predominant
formation of one of the two forms. Thus, we designed
a linear oligooxime ligand 1b having (S)-2-hydroxy-
propyl groups as a chiral auxiliary (Chart 1). A one-
handed helical structure is preferentially formed on
complexation with zinc(II) and calcium ions.
The synthesis of ligand 1b is shown in Scheme 1. The
reaction of aldehyde 28 with tosylate 39 in the presence
of cesium carbonate in DMF afforded 4 in 76% yield.
The subsequent treatment of 4 with Pd–C/HClO4
cleaved the protecting allyl and THP groups to give chi-
ral salicylaldehyde 5 in 91% yield. The reaction of
aldehyde 5 with excess 1,2-bis(aminooxy)ethane10 in eth-
anol afforded monooxime 6. The tetraoxime ligand 1b11
was obtained in 81% yield by the reaction of dialdehyde
712 with 2 equiv of monooxime 6 in ethanol.
The complexation of 1b (=H4L) with zinc(II) acetate
afforded trinuclear complex [LZn3]2+. The formation
of 1:3 complex was clearly supported by spectroscopic
titration and mass spectrometry (Fig. 1a). The homotri-
nuclear complex [LZn3]2+ was converted to a heterotri-
nuclear complex by the site-selective transmetalation
strategy analogous to the methoxy derivative.4 When
Keywords: Oxime; Salamo ligand; Zinc complex; Helical structure;
Chirality induction.
*
Corresponding author. Tel./fax: +81 29 853 4507; e-mail:
nabesima@chem.tsukuba.ac.jp
Chart 1.
0040-4039/$ - see front matter Ó 2006 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2006.09.125

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S. Akine et al. / Tetrahedron Letters 47 (2006) 8419–8422
If the calcium complex [LZn2Ca]2+ has a helical struc-
ture similar to that of the methoxy analog,4b the com-
plex is expected to exist as a mixture of two possible
diastereomers, right- and left-handed forms (Scheme
1
2). However, the H NMR spectrum in CDCl3/CD3OD
(1:1) at 293 K (Fig. 2) showed two singlets for the oxime
protons (HD, HE), four signals for the aromatic protons
(HA, HB, HC, HF), and one singlet for the methoxy pro-
ton (not shown in Fig. 2). This result can be attributed
to the exclusive formation of one diastereomer, or the
fast interconversion between the two diastereomers.
The 1H NMR spectra at lower temperatures clearly
indicate the existence of two diastereomers, right- and
left-handed helices. At 223 K, two sets of signals for
all the protons were observed. At this temperature,
one of the two diastereomers is preferentially formed
(80:20). These two signals coalesce at higher tempera-
tures due to a fast interconversion between the two
species. The coalescence temperature was about 253 K,
which corresponds to the helix inversion barrier DG5
of 52 kJ/mol.
Scheme 1. Synthesis of chiral ligand 1b. Reagents and conditions: (a)
Cs2CO3, DMF, 60–65 °C, 76%; (b) 10% Pd/C, cat. HClO4, MeOH,
reflux, 91%; (c) EtOH, 55–60 °C, 43% and (d) EtOH, 50–55 °C, 81%.
1 equiv of calcium perchlorate was added to a solution
of [LZn3]2+, about 81% of the zinc complex was con-
verted to the heterotrinuclear complex. The addition
of 2 equiv of calcium perchlorate was required for
the complete (>97%) conversion. The formation of
the heterotrinuclear complex was confirmed by the
peaks at m/z = 417.0 for [LZn2Ca]2+ and 893.0 for
[LZn2Ca(OAc)]+ in the ESI mass spectrum (Fig. 1b).
Scheme 2. Two possible diastereomers of metallohelix [LZn2Ca]2+
.
Figure 1. ESI-mass spectra of (a) [LZn3]2+ and (b) [LZn2Ca]2+
.

S. Akine et al. / Tetrahedron Letters 47 (2006) 8419–8422
8421
Figure 2. 1H NMR spectra (600 MHz) of [LZn2Ca]2+ (1.0 mM) at
varying temperatures (223–293 K) in CDCl3/CD3OD (1:1). Signals of
the two diastereomers are indicated with open and filled circles.
Asterisk denotes the signal of chloroform. For assignment of signals,
see Chart 1.
Analogously, complexes [LZn2M]n+ (M = Y3+, La3+
)
1
were formed by the transmetalation method. H NMR
titration and ESI-mass spectra clearly indicated the
complete conversion to the heterotrinuclear complexes.
The 1H NMR spectra of [LZn2Y]3+ and [LZn2La]3+
showed sharp signals at room temperature. The fact
indicates that the interconversion of the helical com-
plexes takes place in a similar fashion. At 223 K, two
sets of signals corresponding to the right- and left-
handed helices were observable. The ratio of the two
species was 56:44 for [LZn2Y]3+ and 53:47 for
[LZn2La]3+. The result indicates that there is only a
slight difference in thermodynamic stability between
the right- and left-handed forms of [LZn2M]n+
(M = Y3+, La3+). Thus, the chirality induction was the
most effective when Ca2+ was used as the central metal
Figure 3. CD and UV–vis absorption spectra of [LZn2Ca]2+ (0.02
mM) at 293 K in chloroform/methanol (1:1).
formation of one of the two diastereomers of the helical
heterotrinuclear complex [LZn2Ca]2+. Consequently,
the terminal (S)-2-hydroxypropyl groups of the ligand
effectively affect the sense of the single-stranded helix.
In conclusion, a linear tetraoxime ligand bearing chiral
(S)-2-hydroxylpropyl groups at both ends formed heli-
cal trinuclear complexes with Zn2+ and the central metal
M (=Ca2+, Y3+, La3+). The ratio of the right- and left-
handed forms of [LZn2M]n+ depends on the central
metal Mn+; the helical sense was the most effectively
induced when Ca2+ was used as the central metal
M
n+. The conformation of [LZn2M]n+ is possibly
affected by the pendant (S)-2-hydroxypropyl group, which
may form direct coordination bonds with the metal cen-
ters or make hydrogen bonds with counter anions on the
metal centers. The Mn+ dependency of the diastereo-
meric ratio may be reflected by the non-covalent inter-
actions involving the pendant (S)-2-hydroxypropyl
group.
M
n+. The trinuclear complex with a helical p-system
would be a useful building block for molecular nanocoil
that has a helical array of metal ions. Further investigation
on the regulation of helicity of a longer-chain strand is
now in progress.
Acknowledgment
In general, chiral helicenes show the Cotton effect
around the wavelength of p–p transition bands, because
they have a helically arranged conjugated system.13
The CD spectrum of the metallohelicene [LZn2Ca]2+
recorded in a chloroform/methanol solution showed a
bisignate Cotton effect, negative at 334 nm and positive
at 286 nm (Fig. 3). The observed CD signals can be as-
signed to the helically arranged p-system of the ligand
chromophore, because the (S)-2-hydroxypropyl group
has no absorption around these wavelengths. Observa-
tion of the CD signal is consistent with the preferential
This work was supported by Grants-in-Aid for Scientific
Research from the Ministry of Education, Culture,
Sports, Science and Technology, Japan.
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