J . Org. Chem. 2000, 65, 5069-5071
5069
Sch em e 1. P r ep a r a tion of Com p ou n d 1
A New Ca se of Ch ir a l Recogn ition betw een
Isotop om er s. P r ep a r a tion a n d Stu d y of (R)
a n d (S) P er d eu ter io
2,2,2-Tr iflu or o-1-(1-p yr en yl)eth a n ol
Anna Mun˜oz,† Marta Sa´nchez,† Thomas J unk,‡ and
Albert Virgili*,†
Unitat de Quı´mica Orga`nica, Departament de Quı´mica,
Universitat Auto`noma de Barcelona, 08193 Bellaterra,
Barcelona, Spain, and Department of Chemistry, University
of Lousiana at Monroe, Monroe, Louisiana 71209-0530
albert.virgili@uab.es
Received March 23, 2000
In tr od u ction
The analysis of enantiomers using a chiral solvating
agent1 (CSA) is becoming a very common methodology
in the observation and determination of the enantiomer
composition of a compound. Recently we reported2 the
preparation and use of the perdeuterio 2,2,2-trifluoro-1-
(9-anthryl)ethanol (3), which is the result of replacing
proton atoms by the deuterium atoms in the Pirkle
alcohol, the most common of the CSA’s. Compound 3 is
the first compound of this type that does not present
signals in the NMR spectra (1H and 13C), affording the
advantage that we can see the NMR spectrum of each
enantiomer alone, without interfering signals. We have
also demonstrated2 that this compound (3), besides being
a very useful CSA, can distinguish two enantiomers of
Pirkle alcohol (4). This is the first time that this
phenomenon has been described.
In the present paper we describe a second case of this
particular enantio-differentiation, that demonstrates, at
least in the area of used compounds, the generalization
of this “chiral self-discrimination:3 the chiral recognition
of a compound by the same perdeuterated enantiopure
compound. A more extensive overview would require the
study of several molecules where the association would
be governed by other binding forces.
The absolute configuration was established by com-
parison of the optical activity with that described6 for the
perprotio compound. The first enantiomer eluted was
S(+) ([R]25D ) +20°, c ) 0.5, CH2Cl2) and the second was
R(-) ([R]25 ) -20°, c ) 0.5, CH2Cl2).
D
The perprotio compound4 (2) was obtained in the same
way and used as racemic compound.
Proton NMR spectra of 2 (5 mg, 0.017 mmol, 4.2 × 10-2
M) containing varying amounts of perdeuterated enan-
tiomers 1S or 1R were recorded at 400 MHz in CDCl3,
under saturation of the exchanging hydroxyl signal
(Figure 1). The two enantiomers of 2 were distinguished
by the presence of the enantiomer 1S. This is observed
by the protons H9, H10, and H11, and it increases with
the ratio [1S]/[2]. As the concentration of 1S increases,
the doublets corresponding to H9 and H10 split into two
doublets and the H11 quartet split into two quartets. No
more signals other than those corresponding to 2 are
observed. Therefore, the spectra obtained correspond to
the each enantiomer. Similar results were achieved when
1R is used. When we used known nonracemic mixtures
of 2 we assigned the signals of each enantiomer as
indicated in Figure 1.
Lowering of the temperature resulted in a considerable
increase in chemical shift differences. Figure 2 shows the
1H NMR spectra of racemic 2 at four temperatures in the
presence of 3 equiv of perdeuterated 1S, and values are
plotted in Figure 3. At low temperature the protons H5
and H7 are also enantio-differentiated, and even at 270
K the H2 is duplicated. The arrangement of Figure 4, a
hypothetical dimer in a head-to-tail, face-to-face π-π
stacking association, could explains the shifts observed
in the protons, as happens in Pirkle alcohol.2 As in this
case of isotopomeric chiral recognition2 of Pirkle alcohol,
when 1S is used, protons of enantiomer 2S are shifted
to higher field than enantiomer 2R. This means that the
associated complex 1S2S could be more stable than the
associated 1S2R. In the same way, using 1R, the complex
1R2R is more shielded (more stable too) than 1R2S.
For comparison, if the two compounds were the same
isotopomer, the SS or RR association between two identi-
Resu lts a n d Discu ssion
Scheme 1 affords the preparation (74% yield) of race-
mic compound 1.4 The deuteration of pyrene was carried
out by supercritical deuterium exchange5 (SDE) using
NaOD /D2O as deuterium source. The intermediate
ketone was isolated, purified, and reduced to racemic
alcohol. The chiral HPLC allowed us to obtain the
separated enantiomers.
† Universitat Auto`noma de Barcelona.
‡ University of Lousiana at Monroe.
(1) (a) Pirkle, W. H.; Hoover, D. J . Top. Stereochem. 1982, 13, 263-
331 (b) Weisman, G. R. Asymmetric Synthesis; Academic Press: New
York, 1983; Vol. 1, Chapter 8. (c) Parker, D. Chem. Rev. 1991, 91,
1441-1457.
(2) Gil, J .; Virgili, A. J . Org. Chem. 1999, 64, 7277-7280.
(3) (a) Luchinat, C.; Roelens, S. J . Am. Chem. Soc. 1986, 108, 4873
and citations therein. (b) Dobashi, A.; Saito, N.; Yuuichi, M.; Hara, S.
J . Am. Chem. Soc. 1986, 108, 307 (c) Giordano, C.; Restelli A.; Vila,
M. J . Org. Chem. 1991, 56, 2270 and citations therein.
(4) Kiselyov, A. S.; Hervey, R. G. Tetrahedron Lett. 1995, 36, 4005.
(5) J unk, T.; Catallo, W. J . Chem. Soc. Rev. 1997, 26, 401-406.
(6) Kato, K.; Katayama, M.; Fujii, S.; Kimoto, H. Biosci. Biotech.
Biochem. 1997, 61, 194.
10.1021/jo0004411 CCC: $19.00 © 2000 American Chemical Society
Published on Web 07/20/2000
Munoz, Anna
