Absolute configuration of chiral [2.2]Paracyclophanes with intramolecular charge-transfer interaction. Failure of the exciton chirality method and use of the sector rule applied to the cotton effect of the CT transition

Article abstract of DOI:10.1021/ja0508323

Optically active 4,7-dicyano-12,15-dimethoxy[2.2]paracyclophanes have been separated by chiral HPLC and their absolute configurations determined by comparison of the experimental and the theoretical VCD spectra. X-ray crystallographic structures for both diastereomers are also reported. The electronic circular dichroism spectra of these enantiomeric pairs, as chiral intramolecular charge-transfer complexes, have been obtained for the first time. The exciton coupling method, usually used for determining the absolute configuration of chiral molecules, however, did not give a correct prediction for the present CT-paracyclophane system. Instead, empirical sector rules for the signs of the Cotton effects of the CT transition can be applied for the assignment of the absolute configuration. Copyright

Full text of DOI:10.1021/ja0508323

Published on Web 05/21/2005
Absolute Configuration of Chiral [2.2]Paracyclophanes with Intramolecular
Charge-Transfer Interaction. Failure of the Exciton Chirality Method and Use
of the Sector Rule Applied to the Cotton Effect of the CT Transition
Takahiro Furo,† Tadashi Mori,*,† Takehiko Wada,† and Yoshihisa Inoue*,†,‡
Department of Molecular Chemistry, Graduate School of Engineering, Osaka UniVersity, 2-1 Yamada-oka,
Suita 565-0871, Japan, and Entropy Control Project, ICORP, JST, 4-6-3 Kamishinden, Toyonaka 560-0085, Japan
Received February 8, 2005; E-mail: tmori@chem.eng.osaka-u.ac.jp
The exciton chirality method is a widely accepted and powerful
tool for determining the absolute configuration of chiral organic
and bioorganic molecules by using a small amount of optically pure
sample.1 The electronic transition moments of two chromophores
positioned at an appropriate distance and angle in a chiral
environment couple with each other, resulting in an energy level
splitting which is most clearly displayed by a bisignate coupled
circular dichroism (CD) spectrum. From the sign of the couplet,
one can immediately assign the sense of chiral arrangement of the
Figure 1. ORTEP drawings of (a) staggered 1 and (b) eclipsed 2.
relevant chromophores or the absolute configuration.
The absolute configurations of [2.2]paracyclophanes have usually
been determined by the sign of exciton coupling of the 1La and 1Lb
transitions.2 It is likely, however, that both boat-type deformation
and electronic interactions of the two facing aromatic rings in
cyclophanes will significantly affect the absorption and circular
dichroism spectra.3 Nevertheless, a variety of structurally well-
defined cyclophanes have been employed as convenient rigid
models in charge/electron-transfer studies, as well as catalysts in
asymmetric syntheses but without paying significant attention to
the above-mentioned structural and electronic features.4
In our ongoing project to elucidate the chiroptical properties of
radical cations and/or charge-transfer (CT) complexes,5 we now
Figure 2. Experimental VCD spectra of (+)- and (-)-1 (a and b) and
focus on chiral [2.2]paracyclophanes possessing CT interactions.
A large number of such compounds have already been prepared
by Staab and co-workers but have not been optically resolved.6 In
the present study, we found that the conventional exciton chirality
method fails to correctly assign the absolute configuration of chiral
paracyclophanes when intramolecular CT interactions are involved.
Alternatively, we propose an empirical sector rule for assigning
the absolute configuration of cyclophanes with CT character.
Staggered and eclipsed 4,7-dicyano-12,15-dimethoxy[2.2]para-
cyclophanes (1 and 2) were prepared as racemic mixtures7 and were
separated into enantiomers by preparative chiral HPLC (DAICEL
OD column with hexane/2-propanol as an eluent). In both cases,
the enantiomers were well separated to give enantiopure (+)-1 and
(+)-2 as the first fractions, with (-)-1 and (-)-2 as the second
(+)- and (-)-2 (d and e) in dichloromethane-d2. The levorotatory enanti-
omers (b and e) are assigned as (4Sp,12Sp)-1 and (4Rp,12Sp)-2 on the basis
of the calculated VCD spectra (c and f).
tilted in 3 and 7°, respectively. DFT-calculated structures are in
excellent agreement with these X-ray structures (vide infra).
Recent instrumental and theoretical advances in vibrational
circular dichroism (VCD) spectroscopy have enabled the elucidation
of the conformation of chiral organic and biological molecules in
solution10 and also determination of the absolute configuration of
relatively rigid chiral molecules through the combined use of DFT
calculations and a sophisticated FT-VCD instrument.11 In contrast,
calculations of the ECD spectra of such compounds that involve
the CT interactions are still arguable.3 Possessing a very rigid
skeleton and less-flexible substituents, enantiomeric [2.2]paracy-
clophanes 1 and 2 are well-suited for this VCD/DFT analysis. Thus,
the experimental VCD spectra were compared with the theoretical
DFT-calculated ones at the B3LYP/6-31G(d) level for the most
stable conformers. The global spectral profiles nicely coincide with
each other, although some peaks are only reproduced by taking
into account the minor conformers in the calculation. As shown in
Figure 2, the (-)-enantiomers of 1 and 2 are assigned without
difficulty as (4Sp,12Sp)-1 and (4Rp,12Sp)-2.
fractions ([R]20 (c 0.2, CHCl3) ) +20.5°, +89.1°, -22.8°, and
D
-90.3°, respectively). X-ray crystallographic studies were carried
out with racemic 1 and 2 (CCDC 271472 and 271473, Figure 1
and Supporting Information).8 The center-to-center distances be-
tween the two benzene rings of 1 (3.05 Å) and 2 (3.04 Å) are
slightly shorter than that of the parent (nonsubstituted) [2.2]-
paracyclophane (3.09 Å),9 likely due to intramolecular CT interac-
tions that reduce the deformation of the benzene rings to some
extent. It is also noted that the projections of two aromatic rings in
1 and 2 are not completely overlapping each other but are slightly
The electronic circular dichroism (ECD) spectra of enantiopure
1 and 2 were also measured. As can be seen from Figure 3, both
1 and 2 show complicated coupling patterns with complete mirror
images for the enantiomer pairs. The Cotton effects of the CT band
† Osaka University.
‡ ICORP, JST.
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C O M M U N I C A T I O N S
and 2, HDA being 300 and 530 cm-1, respectively. Therefore, the
CT transition can roughly be regarded as the HOMO(donor) f
LUMO(acceptor) transition.
In this first study to elucidate the chiroptical properties of
intramolecular CT complexes, we have shown that the exciton
chirality method is not always valid in the absolute configuration
assignment of CT-cyclophanes, and instead, we propose an
alternative sector rule for predicting the absolute configuration using
the sign of the CT band Cotton effect. Studies on the scope and
limitations of this empirical rule and the theoretical interpretation
of these apparently bizarre phenomena are currently in progress.16
Acknowledgment. We thank Dr. Hiroshi Izumi at AIST for
the technical advice on VCD measurements, Ms. Yumi Origane
for chiral HPLC separation, and Dr. Guy A. Hembury for assistance
in the preparation of this manuscript. Financial support from a
Grant-in-Aid for Scientific Research from the Ministry of Education,
Culture, Sports, Science, and Technology of Japan (No. 16750034,
to T.M.) is gratefully acknowledged.
Figure 3. Electronic circular dichroisms of enantiopure 1 (a and b) and 2
(c and d) in acetonitrile. Only anisotropy (g) factors are shown for clarity
(see Supporting Information for full UV-vis and ECD spectra). Solid lines
are for the (-)-enantiomer.
Supporting Information Available: Experimental details, X-ray
crystal structure analyses (CIF files), UV-vis, CD, IR, and VCD
spectra, and DFT calculations of 1 and 2 and attempted application of
the exciton chirality method to ECD. This material is available free of
charge via the Internet at http://pubs.acs.org.
References
(1) (a) Harada, N.; Nakanishi, K. Circular Dichroic Spectroscopy: Exciton
Coupling in Organic Stereochemistry; University Science Books: Mill
Valley, CA, 1983. (b) Berova, N.; Nakanishi, K. In Circular Dichroism:
Principles and Applications, 2nd ed.; Berova, N., Nakanishi, K., Woody,
R. W., Eds.; Wiley: New York, 2000; pp 337-382.
Figure 4. Sector rules applied to the CT cyclophanes 1 and 2. Quadrant
benzene sector is also shown for a comparison.
(2) (a) Weigang, O. E.; Nugent, M. J. J. Am. Chem. Soc. 1969, 91, 4555-
4558. (b) Rosini, C.; Ruzzinconi, R.; Superchi, S.; Fringuelli, F.; Piermatti,
O. Tetrahedron: Asymmetry 1998, 9, 55-62.
(3) Grimme, S.; Bahlmann, A. In Modern Cyclophane Chemistry; Gleiter,
R., Hopf, H., Eds.; Wiley-VCH: Weinheim, Germany, 2004; pp 311-
336.
1
were noticeable. Conventionally, the couplet observed for the Lb
band is used for the assignment of the absolute configuration, while
those at shorter wavelengths may not be suitable for the assignment
due to complications arising from an overlap of several transitions.
In the present case, (-)-enantiomers (traces a and c in Figure 3)
exhibit negative couplets at the 1Lb bands of 1 (280-350 nm) and
2 (300-380 nm).12 The electronic transition dipole moments of
the parent chromophores, that is, 2,5-dimethoxy-p-xylene and 2,5-
dicyano-p-xylene, were calculated by the TDDFT method at the
B3LYP/aug-cc-pVDZ level. By assuming that 1 and 2 have the
same transition moments as the component chromophores, both (-)-
enantiomers are assigned to the 4Sp configuration. This assignment
is correct for 1 but clearly erroneous for 2 (Figure S6 for details).
For benzene derivatives, the quadrant projections (Figure 4,
(4) (a) de Meijere, A.; Ko¨nig, B. Synlett 1997, 1221-1232. (b) Gibson, S.
E.; Knight, J. D. Org. Biomol. Chem. 2003, 1, 1256-1269.
(5) (a) Mori, T.; Izumi, H.; Inoue, Y. J. Phys. Chem. A 2004, 108, 9540-
9549. (b) Mori, T.; Inoue, Y. J. Phys. Chem. A 2005, 109, 2728-2740.
(c) Mori, T.; Inoue, Y. Angew. Chem., Int. Ed. 2005, 44, 2582-2585.
(6) Staab, H. A. In New Aspects of Organic Chemistry I; Yoshida, Z., Shiba,
T., Oshiro, Y., Eds.; VCH: Weinheim, Germany, 1989; pp 227-236.
(7) Staab, H. A.; Taglieber, V. Chem. Ber. 1977, 110, 3366-3376.
(8) For preliminary X-ray analysis (without 3D diagram), see ref 7.
(9) Lonsdale, K.; Milledge, H. J.; Krishna, K. V. R. Proc. R. Soc. London
1960, 225, 82-100.
(10) (a) Nafie, L. A.; Dukor, R. K.; Freedman, T. B. In Handbook of Vibrational
Spectroscopy; Chalmers, J. M., Griffiths, P. R., Eds.; John Wiley & Sons
Ltd.: Chichester, U.K., 2002; pp 731-744. (b) Monde, K.; Taniguchi,
T.; Miura, N.; Nishimura, S.-I. J. Am. Chem. Soc. 2004, 126, 9496-
9497. However, this method requires a relatively large amount (50-100
mg) of optically pure sample, compared to the ECD measurements.
(11) (a) Devlin, F. J.; Stephens, P. J.; Cheeseman, J. R.; Frisch, M. J. J. Am.
Chem. Soc. 1996, 118, 6327-6328. (b) Izumi, H.; Yamagami, S.;
Futamura, S.; Nafie, L. A.; Dukor, R. K. J. Am. Chem. Soc. 2004, 126,
194-198.
1
right), showing the sign of the Lb Cotton effect, have been used
for the empirical assignment of absolute configurations.13 Similarly,
we introduce here a sector rule for the CT cyclophane systems
(Figure 4, left). The sector boundaries are defined by the two
methoxy groups (polarization direction of the donor).14 Thus, the
sign of Cotton effect at the CT band of (Sp,Sp)-1 is predicted to be
positive since the cyano group resides in the first quadrant (although
the methylene group of the ethano bridge is in the second quadrant,
we assume CN > CH2 employing the Cahn-Ingold-Prelog priority
rule). For (Rp,Sp)-2, one of the methylene groups in the bridge sticks
out into the second quadrant, thus giving a negative Cotton effect
in the CT band region. This sector rule becomes valid because the
contribution of the “dative” resonance structure is almost negligible,
in agreement with the small electronic coupling elements15 for 1
1
(12) For an assignment of the Lb transition, see Figure S4. Note that the CT
band is significantly overlapped by the 1Lb band for 2.
(13) Smith, H. Chem. ReV. 1998, 98, 1709-1740.
(14) It is of note that the circular dichroism of the diastereomeric CT complexes
of a chiral hexahelicene with acceptors is almost dominated by that of
the chiral hexahelicene donor. See: Wynberg, H.; Lammertsma, K. J.
Am. Chem. Soc. 1973, 95, 7913-7914.
(15) (a) Hush, N. S. Trans. Faraday Soc. 1961, 57, 557-580. (b) See also:
Mulliken, R. S.; Person, W. B. Molecular Complexes; John Wiely &
Sons: New York, 1969.
(16) This sector rule was successfully applied to the analysis of other CT
cyclophanes, such as the staggered and eclipsed 4,7-bismethoxycarbonyl-
12,15-dimethoxy[2.2]paracyclophanes, for which the exciton chirality
method fails to give correct predictions for the absolute configurations;
see Figure S7 in Supporting Information.
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