Induction of one-handed helical oligo(p-benzamide)s by domino effect based on planar-axial-helical chirality relay

Article abstract of DOI:10.1039/b818123c

One-handed helical oligo(p-benzamide)s were induced via the domino effect based on the planar-axial-helical chirality relay triggered by a planar chiral transition-metal complex at the terminal position as the single chiral source. The Royal Society of Ch

Full text of DOI:10.1039/b818123c

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Induction of one-handed helical oligo(p-benzamide)s by domino effect
based on planar-axial-helical chirality relayw
Ken Kamikawa,*a Keisuke Fukumoto,a Kohei Yoshihara,a Masaru Furusyo,b
Motokazu Uemura,c Shin Takemotoa and Hiroyuki Matsuzakaa
Received (in College Park, MD, USA) 14th October 2008, Accepted 14th January 2009
First published as an Advance Article on the web 4th February 2009
DOI: 10.1039/b818123c
One-handed helical oligo(p-benzamide)s were induced via the
domino effect based on the planar-axial-helical chirality relay
triggered by a planar chiral transition-metal complex at the
terminal position as the single chiral source.
the direction of helicity, namely, right- or left-handed. X-Ray
crystal structure analysisz indicated that ferroceneamide
1 exhibits cis conformation and has a CpFe fragment located
at the opposite side of the phenyl group, thus inducing
(S)-axial chiral amide. On the other hand, examination of
the conformation of ferroceneamide 1 in solution by variable-
temperature NMR revealed that 1 showed only one isomer
from room temperature to ꢀ60 1C. Thus, ferroceneamide 1
retains the thermodynamically stable conformation even in
solution.
Helical chirality is one of the most important and central
conformational motifs, such as found in DNA and the
secondary structure of proteins. Recent studies have focused
on the induction of one-handed helical chirality in polymers.1
One efficient and attractive method for the induction of helical
chirality in polymers and oligomers is the control of whole
helical chirality of a dynamic helix by the site-specific action of
an external stimulus upon a terminal position.2 Inai et al.
reported the outstanding domino effect on the helical screw
sense of chiral peptides possessing a terminal chiral residue
as the single chiral source.3 On the other hand, we previously
reported the stereoselective synthesis of axial chiral benzamides
or anilides induced by planar chiral transition-metal com-
plexes.4 Thus, it is expected that the fixation of terminal axial
chirality of amide in a dynamic helix composed of oligoamides
could induce chirality in the whole helix via the domino effect.
In this communication, we report the details of the induction
of a one-handed helix by the domino effect based on a
planar-axial-helical chirality relay triggered by a planar chiral
ferrocene as a single chiral source (Scheme 1).
We next examined the second stage of the one-handed
helical induction of oligobenzamides by axial chirality.
N-Alkylated poly(p-benzamide)s required three benzamides
units for one turn.5 We synthesized the trimer, the tetramer
and the hexamer of oligo N-methyl-p-benzamides and (S)-2
was attached to the terminal position of each oligobenzamides.
As shown in Fig. 2, the circular dichroism (CD) spectra of 3b,
3c and 3d indicated a negative Cotton effect at 260 nm in the
wavelength region of the benzamide unit and a positive Cotton
effect at 310 nm in CHCl3. These differences in CD patterns
from that of the monomer 3a clearly indicate that the observed
CDs of 3b, 3c and 3d are induced circular dichroisms (ICDs)
by an induced one-handed helix based on an oligoamide unit
in CHCl3.8 In addition, these observed ICD spectra were in
agreement with the reported right-handed oligobenzamides
with a chiral N-alkyl group in each monomer unit.5 Thus,
fixation of axial chirality of an amide would allow for control
of the second stage of chiral induction, i.e., the whole helical
chirality and the direction of the one-handed helix.
As the achiral and dynamic helical backbone, N-alkylated
poly(p-benzamide)s recently reported by Kobayashi and
Yokozawa were used.5 Initially, (S)-N,N-methylphenyl-2-
iodoferroceneamide 1 was synthesized and its axial chirality
corresponding to the first stage of chiral induction by the
planar chirality of 1 was studied (Fig. 1). It has been reported
that N-alkylated benzamides exhibit cis conformation in
solution and the solid phase.6,7 Thus, it is expected that
ferroceneamide 1 would also exhibit cis conformation (i.e.,
ferrocenyl and phenyl groups lie on the same side). Further-
more the axial chirality of ferroceneamide would determine
Although X-ray crystal structure analysis of 3 met with an
unsuccessful result, theoretical calculation indicates a right-
hand helical structure as the most stable conformation shown
in Fig. 3. Positive and negative CD bands that give rise to the
net electronic transition moment in oligo(p-benzamide)s
would associate with the moments that are parallel and
perpendicular to the helix axis, respectively.5 Based on these
a Department of Chemistry, Graduate School of Science, Osaka
Prefecture University Sakai, Osaka, 599-8531, Japan.
E-mail: kamikawa@c.s.osakafu-u.ac.jp; Fax: +81-72-254-9931;
Tel: +81-72-254-9721
b Analysis Technology Research Center, Sumitomo Electric Industries
Ltd., 1-1-1, Koyakita, Itami, Hyogo, 664-0016, Japan
c Kyoto Pharmaceutical University, Misasagi, Yamashina, Kyoto,
640-8412, Japan
w Electronic supplementary information (ESI) available: Details of
synthetic methods, analyses. CCDC 705176 (1). For ESI and
crystallographic data in CIF or other electronic format see
DOI: 10.1039/b818123c
Scheme 1 Chirality relay in a dynamic helix.
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Fig. 1 X-Ray crystal structure of ferroceneamide 1 with axial
chirality of amide.
Fig. 3 RHF/3-21G optimization of ferroceneamides.
On the other hand, when 3b and 3d were dissolved in
CH3CN, ‘‘clear-cut’’ ICDs were not observed in contrast with
the case where they were dissolved in CHCl3. One possibility is
that the helical conformation partially changed in CH3CN,
which might be caused by the difference in solvent polarity
(see ESIw for details). As our aim was to explore effective
chiral transfer systems, we next examined p-tris(benzamide)s
with 2-methyl- and 2-naphthyl-substituted planar chiral ferro-
cene carboxylic acids as the chiral source (Fig. 4). In the
2-methyl-substituted derivatives 4a and 4b, the negative CD
bands at B270 nm would be due to the planar chirality and no
ICD was observed.
However, as the positive CD band at 310 nm in 4b is
assigned to a newly generated CD band, we surmise that 4b
might adopt a loosely folded conformation. On the other
Fig. 2 (a) CD and (b) UV spectra of 3 in CHCl3.
aspects, a decrease of the positive CD band in 3c and 3d
compared with that in 3b would indicate a decrease in a
diastereomeric excess in the helical propensity. In connection
with the above, to discuss the limitations of a chiral trans-
mission in solution, it is necessary to introduce a marker that
acts as a diastereotopic probe at the another terminal.9 Thus,
whether the overlapping of ICDs in 3c and 3d is an indication
of the limitation of chiral transmission in our system, needs
further investigation.10
Fig. 4 (a) CD and (b) UV spectra of 4 and 5 in CHCl3.
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hand, 2-naphthyl-substituted derivative 5b did not show any
significant ICD. Thus, we could not obtain systems that are
more effective than 2-iodo-substituted ferrocene derivatives at
the present stage.
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In summary, we have succeeded in inducing one-handed
helical oligo(p-benzamide)s via the domino effect based on the
planar-axial-helical chirality relay triggered by a planar chiral
transition-metal complex as the single chiral source. Studies of
the stereocontrol of ultra-remote sites via communication of
chiral information11 through the planar-axial-helical chirality
relay are under way.
Notes and references
z Crystal data for 1: C18H16NOFeI, M = 445.08, tetragonal, P41212,
a = 11.742(3), b = 11.742(3), c = 24.521(6) A, V = 3381.0(1)3 A3,
Z = 8, Dc = 1.749 g cmꢀ3, m(Mo-Ka) = 2.718 mmꢀ1, F(000) =
1744.00, T = 296 K, 32 883 reflections collected, 3878 unique (Rint
=
0.026), R1 = 0.0308 (I 4 2s(I)), wR2 = 0.0827 (all data), S = 1.029,
Flack parameter ꢀ0.01(3). Data collection was carried out using the
RIGAKU RAXIS RAPID, and SHELXL97 programs were used for
the structure solution and refinement.
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