Designed molecular propellers based on tetraarylterephthalamide and their chiroptical properties induced by biased helicity through transmission of point chirality

Article abstract of DOI:10.1039/b808936a

The syn-atropisomers of the title bis(tertiary amide)s were designed as six-bladed molecular propellers based on the "directing effects" of amide dipoles; the helicity of the propeller is biased to prefer one handedness upon the attachment of point chiral

Full text of DOI:10.1039/b808936a

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Designed molecular propellers based on tetraarylterephthalamide
and their chiroptical properties induced by biased helicity through
transmission of point chiralityw
Ryo Katoono,*a Hidetoshi Kawai,b Kenshu Fujiwarab and Takanori Suzuki*b
Received (in Cambridge, UK) 2nd June 2008, Accepted 23rd July 2008
First published as an Advance Article on the web 10th September 2008
DOI: 10.1039/b808936a
The syn-atropisomers of the title bis(tertiary amide)s were
designed as six-bladed molecular propellers based on the ‘‘direct-
ing effects’’ of amide dipoles; the helicity of the propeller is biased
to prefer one handedness upon the attachment of point chirality to
the amide nitrogens to attain stronger circular-dichroism activity
than for the non-propeller-shaped anti-isomers.
Persubstituted benzenes have attracted much attention as
promising motifs in the design of molecular rotors, gears and
propellers.1 One of the most-studied classes of molecules is
hexaarylbenzenes,1a,2 which cannot adopt a conformation with
all aryl blades lying on the same plane as the central core due to
the steric repulsion among neighboring substituents. Instead,
Scheme 1
substituents are twisted almost perpendicularly, and slight skewing
in the former should endow the syn-isomers with a preference for
the propeller-shape by forcing conrotatory skewing of the four
aryl blades. This is the central point of our concept toward
‘‘designed molecular propellers’’, and we report here the details
of a successful demonstration. The point chirality on the amide
nitrogen is transmitted to the helicity-preference of the propellers
to attain much stronger chiroptical signals for the syn-isomers of
1/2 than for the non-propeller-shaped anti-isomers.
about the Ccentral–Caryl bond in either direction induces numerous
conformations, including several chiral ones. The propeller-shaped
conformation occurs when all blades are skewed in a conrotatory
manner, which is interesting in terms of its mobile chirality with
an easy inversion of helicity. While the parent hexaphenyl-
benzene2b,e was shown to adopt a propeller conformation in the
crystal, it is difficult to force the molecule to maintain this same
structure in solution. The control of propeller helicity is also
challenging to bias the (P)/(M)-stereoisomer.
For detailed conformational analyses, 4-methoxyphenyl (1) and
40-methoxybiphenyl-4-yl (2) groups are selected as the aryl blade
to simplify the aryl region of the NMR spectrum. The cyclohexyl-
methyl (a) or (R)-1-cyclohexylethyl (b) group is attached to each
amide nitrogen, which of the latter was anticipated to act as a
chiral handle to control the mobile helicity of the propellers.
Further substitution on nitrogens to bis(tertiary amide)s would be
necessary to suppress interconversion between syn- and anti-
atropisomers. The larger substituent on the amide may preferen-
tially occupy the ‘‘lateral’’ position (s-trans to the benzene core),
whereas the smaller one may be located at the ‘‘vertical’’ position
(s-cis to the core). The rotational freedom about the Ccentral–Caryl
bond depends on the steric bulkiness of the vertical group.
Tetraarylterephthalamides 1a,b were prepared by Suzuki–
Miyaura coupling4 of 2,3,5,6-tetrabromoterephthalamides 3a,b
and 4-methoxyphenylboronic acid followed by N-methyl-
ation of the intermediary secondary amides 4a,b. The tetrakis-
(biphenylated) derivatives 2a,b were similarly prepared by using
40-methoxybiphenyl-4-yl-boronic acid5 in the Pd-catalyzed
coupling step. The syn- and anti-atropisomers were formed as
mixtures, which were readily separated in pure form by column
chromatography since they exhibit quite different Rf (relative to
front) values. The isomers with a smaller Rf value were tentatively
assigned as syn, and this was later confirmed by X-ray analyses on
syn- and anti-1 (vide infra). The atropisomers 1/2 were
non-interconvertible even after heating at 338 K for 24 hours in
We envisaged that the rational design of persubstituted
benzenes would provide a significant preference for the propeller
geometry even in solution, and the mobile helicity could be biased
to a single handedness through the effective transmission of point
chiralities on the periphery. Based on our detailed conformational
studies on terephthalamides,3 we have designed here 2,3,5,6-
tetraarylated bis(tertiary amide)s 1/2 as promising compounds
for adopting a propeller geometry. As in the case of hexaaryl-
benzenes, all of the blades in 1/2 are twisted nearly perpendicu-
larly, which gives two atropisomers (syn and anti) in terms of the
relative direction of the two amide groups. Both isomers must
prefer the conformation with the amide dipoles reduced/canceled
to minimize the electrostatic disadvantage: a conrotatory-skewed
C2-symmetric structure for syn and a centrosymmetric structure
for anti (Scheme 1). Such ‘‘directing effects’’ by the amide groups
a School of Materials Science, Japan Advanced Institute of Science
and Technology, Nomi, Ishikawa, 923-1292, Japan.
E-mail: katoono@jaist.ac.jp; Fax: +81 (0)761 51 1645;
Tel: +81 (0)761 51 1642
b Department of Chemistry, Faculty of Science, Hokkaido University,
Sapporo, 060-0810, Japan. E-mail: tak@sci.hokudai.ac.jp;
Fax: +81 (0)11 706 2714; Tel: +81 (0)11 706 2714
w Electronic supplementary information (ESI) available: X-ray and
NMR data; preparation detail of new compounds. CCDC reference
numbers 680696 & 680697. For ESI and crystallographic data in CIF
or other electronic format see DOI: 10.1039/b808936a
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centrosymmetric structure with full cancellation of the dipole, and
thus the anti-isomer is not propeller-shaped at all (Fig. 1b). Even
with the attachment of chiral auxiliaries, the anti-isomer prefers
the pseudo-centrosymmetric geometry to minimize dipole repul-
sion, as shown by the similarity of the non-propeller structure of
(R,R)-anti-1b (Fig. S1;w P1, Z = 1) and anti-1a.
Conformational searches on achiral 1a using Macromodel
software6 indicated that the propeller conformation is the most
stable geometry for the syn-isomer among numerous conforma-
tions (Fig. 2a). This theoretical examination suggests that the
propeller-shaped geometry must also be the major contributor
in solution for the syn-isomers of 1a,b. The centrosymmetric
non-propeller-shaped structure was predicted for the anti-isomer
in accordance with the observed geometry in crystal (Fig. 2b).
The structures of syn-isomers in solution were experimentally
verified by 1H NMR spectroscopy (Fig. S2).w The chemical shifts
of their aromatic protons in CDCl3 at 298 K are summarized in
Table 1. The observed spectrum of achiral syn-1a was
C2v-symmetric, which can be accounted for by assuming a rapid
inversion of helicity between two energetically equivalent propeller
structures. Some broadening is related to rotational motion about
the Ccentral–Caryl bond (DGz = 15.3 kcal molꢁ1, coalescence
temperature = 313 K), but there is no indication of Ccentral–Camide
bond rotation. In the case of (R,R)-syn-1b with chiral auxiliaries,
the spectrum is C2-symmetric, as expected for rapidly inter-
converting diastereomeric propellers (Fig. S2).w Slight broadening
is again induced by the Ccentral–Caryl rotation. There are four sets
of resonances (HC: 7.18–6.87 ppm in CDCl3 at 298 K) that
correspond to anisyl protons close to the central benzene core.
The other four (HX: 6.77–6.48 ppm) are ortho to the methoxy
group, and are not well separated from each other. The energy
barrier for propeller inversion seems to be too low to observe the
diastereomeric propellers as two independent sets of signals, even
when the temperature is lowered to 223 K. Although the above
NMR features might be alternatively rationalized by assuming a
single geometry with all substituents twisted perpendicular to the
central core, only one of four anisyl signals (HC) showed a
correlation with the vertical methyl group in an ROE measure-
ment (Fig. S3),w which is readily accounted for by assuming a
propeller geometry. Furthermore, as shown in Fig. S4,w the
temperature-dependent shift of resonances while maintaining
the spectral symmetry in (R,R)-syn-1b shows that there are
Fig. 1 X-Ray structures of (a) (R,R)-syn-1b (P1, Z = 1) and (b) anti-1a
ꢀ
(P1, Z = 1). One of the aryl blades in (a) is almost perpendicular to the
central core. Solvated benzene molecule in the crystal in (b) is omitted for
clarity. Thermal ellipsoids are shown at 50% probability level.
CDCl3. For the bis(secondary amide)s 4a,b without vertical
methyl substituents, interconversion is much faster than the
NMR time-scale, even at room temperature, as predicted.
Single-crystal X-ray analysisz demonstrated that (R,R)-syn-1b
adopts the propeller geometry in crystal, as desired. The aryl
blades are skewed in a conrotatory manner, which must be
induced by the directing effects of amide dipoles at the
para-positions (Fig. 1a). Preliminary investigation indicates this
ꢀ
is also the case for achiral syn-1a (Fig. S1;w P1, Z = 2). In the
latter case, the enantiomeric propellers exist in pairs whereas in the
former with a chiral auxiliary on each amide nitrogen, only
propellers with (M)-helicity exist in the crystal and thus the point
chiralities are perfectly transmitted to the mobile helicity, at least
in a crystalline state of (R,R)-syn-1b.
On the other hand, the electrostatic interaction of the amide
‘‘directing effects’’ must be the major reason why anti-1a adopts a
Fig. 2 Energy-minimized structures for (a) syn-1a and (b) anti-1a
according to Monte Carlo simulations in CHCl3.
Table 1 Chemical shiftsa for the aromatic protons in 1/2b in CDCl3 at 298 K
Observed
symmetry
d/ppm
syn-1a
7.09C (4H)
7.18C (2H)
7.55C (4H)
7.59C (2Hꢂ2)
6.87C (4H)
7.02C (2H)
6.79X (4H)
6.81X (2H)
6.79X (2H)
7.07C (4H)
6.64X (4Hꢂ2)
6.93C (2H)
6.66C (4H)
6.66C (2H)
6.63C (2H)
C2v
C2
C2h
C2
(R,R)-syn-1b
anti-1a
(R,R)-anti-1b
6.87C (2H)
6.48X (4H)
6.49X (2H)
6.45X (2H)
6.74–6.49X (2Hꢂ4)
syn-2a
7.31C,X (4Hꢂ3)
C2v
—
C2h
C2
(R,R)-syn-2b
anti-2a
(R,R)-anti-2b
—
7.74C (4H)
7.80C (2Hꢂ2)
7.50X (4H)
7.53X (2H)
7.50X (2H)
7.17X (4H)
7.17X (2H)
7.11X (2H)
6.86C (4H)
6.89C (2H)
6.81C (2H)
a
Assignment is indicated by superscripts C and X. Superscript C denotes the aromatic protons close to the central benzene ring. Superscript X
denotes the aromatic protons close to X (X = MeO for 1, and 40-MeOC6H4 for 2). The aromatic protons in (R,R)-syn-2b could not be fully
b
assigned due to peak overlap and broadening. Only the protons on four phenylene rings attached on the core are shown.
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thanks to the ‘‘directing effects’’ of amide dipoles. A chiral
auxiliary on the amide nitrogen gave a preference for skewing
the direction of the propeller helicity to realize chiroptical en-
hancement. We are now studying the complexation properties of
the present amides and hydrogen-bonding guests with special
focus on guest-induced conformational changes.3b–d A prelimin-
ary examination shows that the secondary amides 4a,b prefer a
non-propeller anti-conformation, but can undergo rapid syn–anti
interconversion to attain the propeller structure upon complexa-
tion. Further details will be reported in due course.
Notes and references
Fig. 3 UV and CD spectra of (a) (R,R)-syn-1b (bold line), (R,R)-anti-
1b (thin line), and (b) (R,R)-syn-2b (bold line), (R,R)-anti-2b (thin line)
in CH2Cl2 at room temperature respectively.
z Crystal data of (R,R)-syn-1b: MF C54H64N2O6, FW 837.11, triclinic P1
(No. 1), a = 6.305(2), b = 13.323(5), c = 13.959(5) A, a = 86.986(10), b
= 81.092(9), g = 85.727(9)1, V = 1154.1(7) A3, r(Z = 1) = 1.204 g cmꢁ3
T = 153 K, 7239 independent reflections (Rint = 0.010), R = 4.3% (6810
,
energetically-nonequivalent and rapidly-interconverting (P)- and
(M)-propellers, the diastereomeric ratio of which is a function of
temperature.
data with F 4 2sF), CCDC 680696.w Crystal data of anti-1a: MF
C58H66N2O6, FW 887.17, triclinic P1 (No. 2), a = 9.668(3), b =
11.144(4), c = 11.778(4), a = 106.388(5), b = 96.224(5), g =
100.015(5)1, V = 1182.0(7) A3, r(Z = 1) = 1.246 g cmꢁ3, T = 153 K,
5029 independent reflections (Rint = 0.031), R = 7.2% (2795 data with F
4 2sF), CCDC 680697.w
ꢀ
In the case of tetrakis(biphenylated) derivatives syn-2a,b, the
NMR spectra show similar characteristics (Table 1; Fig. S2),w
suggesting that they also prefer the propeller shape. This idea was
supported by the chiroptical properties of (R,R)-syn-2b, which
resemble those of propeller-shaped (R,R)-syn-1b (vide infra). The
NMR data of anti-isomers of 1a,b/2a,b are also listed in Table 1
and Fig. S2,w and can be readily explained by assuming the
(pseudo)centrosymmetric geometries observed in crystal.
Fig. 3 shows the UV and circular dichroism (CD) spectra of
chiral (R,R)-1b/2b in CH2Cl2 at room temperature. The UV
spectra of achiral 1a/2a are quite similar to those of (R,R)-1b/
2b, respectively (Table S1).w For the atropisomers of (R,R)-1b/2b,
the amplitude of the Cotton effect in the CD spectra differs
significantly: CD signals for syn-isomers are much stronger than
those for the corresponding anti-isomers. An almost 10-fold
increase in De at the absorption shoulder (291 nm for 1b)/
maximum (286 nm for 2b) is noteworthy (Table 2). Such differ-
ences in chiroptical properties must be due to the propeller-shape
preference seen for syn-isomers.7 This is a successful demonstra-
tion of the effective transmission of chirality8 from point asym-
metry to the mobile helicity of the propeller structure.
1 (a) G. S. Kottas, L. I. Clarke, D. Horinek and J. Michl, Chem. Rev.,
2005, 105, 1281; (b) Y. Murata, M. Shiro and K. Komatsu, J. Am.
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J. Chem. Soc., Dalton Trans., 2000, 1049; (d) H. Nishide, R. Doi, K.
Oyaizu and E. Tsuchida, J. Org. Chem., 2001, 66, 1680; (e) M. P.
Thornberry, C. Slebodnick, P. A. Deck and F. R. Fronczek,
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2003, 42, 5182; (g) A. Goel, F. V. Singh, M. Dixit, D. Verma, R.
Raghunandan and P. R. Maulik, Chem.–Asian J., 2007, 2, 239.
2 (a) S. Brydges, L. E. Harrington and M. J. McGlinchey, Coord.
Chem. Rev., 2002, 233–234, 75; (b) J. C. J. Bart, Acta Crystallogr.,
Sect. B: Struct. Crystallogr. Cryst. Chem., 1968, 24, 1277; (c) D.
Gust, J. Am. Chem. Soc., 1977, 99, 6980; (d) D. Gust and A.
Patton, J. Am. Chem. Soc., 1978, 100, 8175; (e) E. M. Larson, R. B.
V. Dreele, P. Hanson and J. D. Gust, Acta Crystallogr., Sect. C:
Cryst. Struct. Commun., 1990, 46, 784; (f) H. P. Dijkstra, M. D.
Meijer, J. Patel, R. Kreiter, G. P. M. van Klink, M. Lutz, A. L.
Spek, A. J. Canty and G. van Koten, Organometallics, 2001, 20,
3159; (g) C. Lambelt, Angew. Chem., Int. Ed., 2005, 44, 7337; (h) R.
Shukla, S. V. Lindeman and R. Rathore, Org. Lett., 2007, 9, 1291.
3 (a) H. Kawai, R. Katoono, K. Nishimura, S. Matsuda, K. Fujiwara,
T. Tsuji and T. Suzuki, J. Am. Chem. Soc., 2004, 126, 5034; (b) R.
Katoono, H. Kawai, K. Fujiwara and T. Suzuki, Chem. Commun.,
2005, 5154; (c) R. Katoono, H. Kawai, K. Fujiwara and T. Suzuki,
Tetrahedron Lett., 2006, 47, 1513; (d) H. Kawai, R. Katoono, K.
Fujiwara, T. Tsuji and T. Suzuki, Chem.–Eur. J., 2005, 11, 815.
4 (a) N. Miyaura and A. Suzuki, Chem. Rev., 1995, 95, 2457; (b) K.
C. Nicolaou, P. G. Bulger and D. Sarlah, Angew. Chem., Int. Ed.,
2005, 44, 4442.
The fluorophoric properties of the tetrakis(biphenylated) deri-
vatives 2 are also interesting. Thus, (R,R)-syn-2b represents a new
entry into the less-well-developed class of chiral fluorophores.8b
The large Stokes shifts (ca. 100 nm) as well as structureless
emission are characteristic of two-dimensional p-conjugated
oligoarylenes9 (Table 2, Fig. S5).w
5 V. Percec, P. Chu and M. Kawasumi, Macromolecules, 1994, 27,
4441.
In conclusion, we have demonstrated ‘‘designed’’ six-bladed
molecular propellers based on syn-terephthalamides derivatives
6 MacroModel v6.5, Schrodinger Inc., 1998, and the GB/SA solvation
¨
model for chloroform through 5000-step Monte Carlo simulations
using the Amber* force field, and the PRCG minimization algorithm.
7 The weaker Cotton effects around 255 nm commonly observed in
both atropisomers of (R,R)-1b are also present in the tetrabromic
chiral terephthalamides (R,R)-5b derived by N-methylation of
(R,R)-3b (Table S1),w thus the shorter-wavelength region has
nothing to do with the propeller/non-propeller conformation.
8 (a) T. Suzuki, S. Tanaka, H. Kawai and K. Fujiwara, Chem.–
Asian J., 2007, 2, 171; (b) E. Ohta, T. Nehira, H. Kawai, K. Fujiwara
and T. Suzuki, Tetrahedron Lett., 2008, 49, 777, reference cited therein.
9 (a) Z. H. Li, M. S. Wonga and Y. Tao, Tetrahedron, 2005, 61, 5277;
(b) K.-H. Ahna, G. Y. Ryua, S.-W. Younb and D.-M. Shin, Mater.
Sci. Eng., C, 2004, 24, 163; (c) Q. Zeng, Z. Li, Y. Dong, C. Di, A.
Qin, Y. Hong, L. Ji, Z. Zhu, C. K. W. Jim, G. Yu, Q. Li, Z. Li, Y.
Liu, J. Qin and B. Z. Tang, Chem. Commun., 2007, 70.
Table 2 UV, CD and fluorescence spectral data of (R,R)-1b/2b in
CH2Cl2 at room temperature
syn-1b
anti-1b
syn-2b
anti-2b
l
max/nm
(log e)
max/nm
249 (sh.)
(4.54)
254, 291
259
(4.59)
261, 291
282
(5.02)
286, 312
287
(5.02)
l
256, 272,
286, 304
(ꢁ1.38, 2.11,
ꢁ1.18, 1.43)
381
(De)
(ꢁ4.06,
ꢁ7.67)
—
(ꢁ2.56,
ꢁ0.608)
—
(ꢁ10.0,
1.04)
378
lmax,ema/nm
a
Excited at each absorption maximum.
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This journal is The Royal Society of Chemistry 2008
4908 | Chem. Commun., 2008, 4906–4908