Recently, researchers have reported effective probes to
determine the absolute configurations and ee of chiral
conjugates, (S)-2aꢀ(S)-8a, were prepared by the reaction
of 1 withchiral primaryaminesin the presenceof K CO in
CH CN (Scheme 1).
3
2
3
1
5ꢀ27
monoamines by CD.
Such methods previously re-
ported, however, do not fully meet the above criteria.
Elaborate derivatizations of analytes and complicated
conformational analysis are required.
Scheme 1. Coupling Reaction of 1 and Chiral Primary Amines
Exciton-coupled CD (ECCD) is a potentially sensitive
method for chiral detection. The relationship between the
sign of the CD Cotton effect and the twist of the two
electric transition moments of molecules has been estab-
1
1ꢀ14,28ꢀ30
lished in a nonempirical manner.
In connection
3
0
with a previous paper, we designed a new chiroptical
probe 1 with a m-quaterphenyl group to determine the
absolute configurations of primary amines. We expected
that (i) probe 1 would couple readily with chiral primary
amines yielding 1ꢀchiral amine conjugates with a seven-
membered ring, (ii) information on the absolute config-
urations of the amines would be transcribed into a spacial
arrangement of two biphenyl units in the m-quarter phenyl
Figure 1 shows the UV and CD spectra of the 1ꢀprimary
amine conjugates, (S)-2a, (S)-3a, (S)-6a, and (S)-7a, in
hexane. The UV spectrum of (S)-2a exhibits an intense
absorption at 257 nm due to the πꢀπ* transition arising
from polarization along the long axes in the m-quaterphenyl
group. The CD spectrum of (S)-2a exhibits significant CD
Cotton effects due to the exciton coupling between the two
3
0
group which is detected directly by the ECCD method,
and (iii) the conformers of the 1ꢀchiral amine conjugates
would be predicted by the analysis of conformational dis-
tributions using theoretical calculations. As a result, the
combination of the new chiroptical probe 1 and theoretical
calculations would permit determination of the absolute
configurations in a nonempirical manner. We here report
an effective method to determine the absolute configura-
methoxy-biphenyl chromophores; λext = 278.8 nm (Δε =
1
ꢀ9.2) and λext = 256.2 nm (Δε
= þ8.5). The amplitu =d e
(second Cotton effect), is
2
11,16ꢀ19
of ECCD (ACD value),
Δε
which is defined as ACD
3
1
tions of chiral primary amines.
The chiroptical probe 1 was synthesized from
1
(first Cotton effect) ꢀ Δε
2
ꢀ17.7. The negative exciton chirality indicates that the two
long axes in the m-quaterphenyl group constitute an Mtwist.
4
-bromobenzoic acid via six steps with an overall yield
of 20% (see the Supporting Information (SI)). 1ꢀamine
(
15) Huang, X. F.; Borhan, B.; Rickman, B. H.; Nakanishi, K.;
Berova, N. Chem.ꢀEur. J. 2000, 6, 216.
16) Borovkov, V. V.; Lintuluoto, J. M.; Inoue, Y. Org. Lett. 2000, 2,
565.
17) Kurtan, T.; Nesnas, N.; Li, Y. Q.; Huang, X. F.; Nakanishi, K.;
Berova, N. J. Am. Chem. Soc. 2001, 123, 5962.
18) Kurtan, T.; Nesnas, N.; Koehn, F. E.; Li, Y. Q.; Nakanishi, K.;
Berova, N. J. Am. Chem. Soc. 2001, 123, 5974.
19) Borovkov, V. V.; Lintuluoto, J. M.; Inoue, Y. J. Am. Chem. Soc.
001, 123, 2979.
20) Zhang, J.; Holmes, A. E.; Sharma, A.; Brooks, N. R.; Rarig,
R. S.; Zubieta, J.; Canary, J. W. Chirality 2003, 15, 180.
21) Hosoi, S.; Serata, J.; Sakushima, A.; Kiuchi, F.; Takahashi, I.;
Ohta, T. Lett. Org. Chem. 2006, 3, 58.
22) Nieto, S.; Dragna, J. M.; Anslyn, E. V. Chem.ꢀEur. J. 2010, 16,
27.
(
1
(
(
(
2
(
(
(
2
(
(
(
(
23) Iwaniuk, D. P.; Wolf, C. J. Am. Chem. Soc. 2011, 133, 2414.
24) Iwaniuk, D. P.; Wolf, C. Org. Lett. 2011, 13, 2602.
25) Ghosn, M. W.; Wolf, C. Tetrahedron 2011, 67, 6799.
26) Fujiwara, T.; Taniguchi, Y.; Katsumoto, Y.; Tanaka, T.; Node,
M.; Ozeki, M.; Yamashita, M.; Hosoi, S. Tetrahedron: Asymmetry 2012,
3, 981.
27) Dragna, J. M.; Pescitelli, G.; Tran, L.; Lynch, V. M.; Anslyn,
E. V.; Di Bari, L. J. Am. Chem. Soc. 2012, 134, 4398.
28) Fujita, T.; Kuwahara, S.; Watanabe, M.; Harada, N. Enantio-
mer 2002, 7, 219.
29) Ohmori, K.; Mori, K.; Ishikawa, Y.; Tsuruta, H.; Kuwahara, S.;
Harada, N.; Suzuki, K. Angew. Chem., Int. Ed. 2004, 43, 3167.
30) Kuwahara, S.; Chamura, R.; Tsuchiya, S.; Ikeda, M.; Habata,
Y. Chem. Commun. 2013, 49, 2186.
31) Dutot et al. reported a biphenyl probe to detect the chirality of
R- and β-amino esters. Although the probe shows an induced CD (ICD)
at A band, the relationship between the sign of ICD and the absolute
configurations of R- and β-amino esters was not fully rationalized.
Dutot, L.; Wright, K.; Wakselman, M.; Mazaleyrat, J.-P.; Peggion,
C.; De Zotti, M.; Formaggio, F.; Toniolo, C. Tetrahedron Lett. 2008, 49,
2
(
(
Figure 1. CD (a) and UV (b) spectra of (S)-2a, (S)-3a, (S)-6a,
and (S)-7a (2.0 ꢁ 10 M in hexane, 293 K).
(
ꢀ
4
(
(
On the other hand, (R)-2a exhibited the mirror image
of the CD spectrum of (S)-2a (Figure S29 in the SI). Also
varying the solvents for (S)-2a from EtOH to CH CN to
3
1,2-dichloroethane resulted in almost no change in the CD
amplitude and shape (Figure S30 in the SI).
3475.
Org. Lett., Vol. 15, No. 22, 2013
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