Synthesis and structural study of the enantiomers of α, α′-bis(trifluoromethyl)-10,10′-(9,9′-bianthryl) dimethanol as a chiral solvating agent

Article abstract of DOI:10.1016/S0957-4166(03)00625-6

We describe the synthesis, the structure, and the behavior as a chiral solvating agent of the enantiomers of α,α′- bis(trifluoromethyl)-10,10′-(9,9′-biantryl)dimethanol. The thermodynamics of several associations are presented. We conclude that the association needs the approximation of the aromatic systems and that the geometry of complexation is the main factor that defines the enantiodiscrimination.

Full text of DOI:10.1016/S0957-4166(03)00625-6

TETRAHEDRON:
ASYMMETRY
Pergamon
Tetrahedron: Asymmetry 14 (2003) 3129–3135
Synthesis and structural study of the enantiomers of
a,a%-bis(trifluoromethyl)-10,10%-(9,9%-bianthryl)dimethanol as a
chiral solvating agent
Marta S a´ nchez-Aris, Carla Estivill and Albert Virgili*
Departament de Qu ´ı mica Universitat Aut o` noma de Barcelona, 08193 Bellaterra, Barcelona, Spain
Received 2 June 2003; accepted 24 July 2003
Abstract—We describe the synthesis, the structure, and the behavior as a chiral solvating agent of the enantiomers of
a,a%-bis(trifluoromethyl)-10,10%-(9,9%-biantryl)dimethanol. The thermodynamics of several associations are presented. We conclude
that the association needs the approximation of the aromatic systems and that the geometry of complexation is the main factor
that defines the enantiodiscrimination.
©
2003 Elsevier Ltd. All rights reserved.
1. Introduction
2. Results and discussion
1
Recently, we described the preparation and structural
As the bianthracenyl 4 is a well-known system, we start
the synthesis (Scheme 1) by preparing this compound
by reductive coupling of the anthraquinone using Zn in
study of the enantiomers of a,a%-bis(trifluoromethyl)-
,10-anthracenedimethanol 1 and their perdeuterated
isotopomers, which are compounds with an excellent
capacity to behave as chiral solvating agents (CSA).
2
9
6
acidic medium . Dibromination of 4 in the 10 and 10%
7
positions has also been described and we obtained the
1
0,10%-dibromo-9,9%-bianthracenyl 5 in a 60% yield. By
1
Appropriately substituted biaryl compounds have been
used as chiral auxiliaries in the study of several enan-
extension of the previously applied methodology, the
generation of the di-lithium derivative by using
3
tioselective reactions and also in the study of structural
chirality. BINOL and derivatives have been shown to
be very important reagents in several reactions when
4
enantioselectivity has been sought.
Target compound 2 presents the same substituted aro-
5
matic ring as Pirkle’s alcohol 3, and the arrangement
between two aromatic rings is similar to the binaphthol.
Moreover, as we show with compound 1, the double
functionality increases the capacity of enantiodifferenti-
ation.
The
a,a%-bis(trifluoromethyl)-10,10%-(9,9-
bianthryl)-dimethanol 2 is also a doubly functionalized
compound that will be capable to associate, in a biden-
tate way, with compounds that present a complemen-
tary structure. The distance between these chemical
functions will mean that the choice of the substrates
should be crucial in the behavior of this chiral auxil-
iary. The present work analyzes the behavior of 2 as a
CSA in front of several simple and small racemic
compounds.
*
0
Corresponding author. E-mail: albert.virgili@uab.es
Scheme 1. Synthesis of compound 2.
957-4166/$ - see front matter © 2003 Elsevier Ltd. All rights reserved.
doi:10.1016/S0957-4166(03)00625-6

3
130
M. S a´ nchez-Aris et al. / Tetrahedron: Asymmetry 14 (2003) 3129–3135
butylithium and the subsequent reaction with trifluo-
racetic anhydride yields 10,10%-bis(trifluoroacetyl)-9,9-
bianthracenyl 6. This intermediate product was isolated
and characterized by NMR. Reduction of the diketone
6
with LiAlH give us the mixture of the isomers of
a,a%-bis(trifluoromethyl)-10,10%-(9,9%-
4
biantryl)dimethanol 2.
A more direct way to obtain 2 uses a double Friedel–
Crafts reaction with trifluoroacetaldehyde. Although
this compound is in the gas phase under normal condi-
tions, we substitute it with the more easily manipulated
8
trifluoroacetaldehyde ethyl hemiacetal whose use as an
electrophilic reactant in front of aromatic compounds
9
has only been described a few times. We therefore first
tested this reaction using the anthracene as substrate.
When the anthracene ring was treated with trifluoroac-
etaldehyde ethyl hemiacetal in the presence of a Lewis
1
Figure 1. H NMR spectra of meso-2 at several temperatures.
acid as a catalyst (BF ), we obtained, in high yield
3
(
90%), 1-(9-anthryl)-2,2,2-trifluorethanol. Although the
conditions of the reaction were adapted to the double
reaction, the di-reaction product was not detected. Pos-
sibly the presence of the first group decreases the reac-
tivity of the anthracene towards a second electrophilic
attack. In the case of bianthracenyl 4, when it was
treated with trifluoroacetaldehyde ethyl hemiacetal
under the conditions for the double reaction, we
obtained a,a%-bis(trifluoromethyl)-10,10%-(9,9%-biantryl)-
dimethanol 2 in a 81% yield. The disconnection of the
aromatic rings was demonstrated.
Compound 7, the diacetate derivative of 2, was pre-
pared quantitatively by treatment with acetyl chloride
and was used to isolate pure enantiomers by HPLC on
a semi-preparative Whelk-O1 (and preparative Whelk-
O2) column using hexane/isopropyl alcohol (95/5) as
the elution solvent (2 ml/min). The first eluted com-
pound was assigned to (−)-(R,R)-7, the second to the
meso-7, and the third to the (+)-(S,S)-7. These assigna-
tions were made with the help of (i) the analysis of the
integration of the peaks (ii) the comparison with the
elution order in the same conditions of the Pirkle’s
1
Figure 2. H NMR spectra of (R,R)-2 at several tempera-
tures.
(
those that are near the OH) become broad doublets.
The rest of signals are only partially resolved.
To explain this behavior we must look to the corre-
sponding conformational equilibrium. The more stable
conformation corresponds to the perpendicular position
of the CF groups to the anthracene rings. Figure 3
shows the two stabilized conformations of meso-2 com-
ing from the rotation of 180° of the C ꢀC bond.
1
0
alcohol acetate and of the a,a%-bis(trifluoromethyl)-
1
9
,10-anthracenedimethanol diacetate and (iii) the coin-
11
3
cidence of the chromophores with the cited acetates or
with the alcohols suggesting a similar sign of the optical
activity. Treatment of each isolated ester with K CO (1
10
11
2
3
M) gave the stereoisomers (−)-(R,R)-2, meso-2 and
Neither structure has a symmetry element that converts
one anthracene ring into the other anthracene ring,
each proton being anisochronous to each prima proton.
Thus, there is a slight difference between analogous
protons of two anthracene rings broadening the corre-
sponding absorption. The presence of two stereogenic
centers and the rigidity of the bond between the
anthracenes afford two distributions of the substituents
(
+)-(S,S)-2, respectively. The parallelism of the experi-
ments of enantiodiscrimination using 2 or the other
chiral solvating agents 1 and 3, giving a similar sense of
the change of chemical shift in the same nucleus, rein-
forces the above assignation and configuration of the
three isomers.
1
At room temperature, the H NMR spectrum of each
of C11 and C , a Minus and a Plus. These two con-
11%
isomer of 2 shows broad resonances for several protons
formers (S,M,R and S,P,R) are enantiomers, and con-
sequently, their hydrogen atoms are isochronous.
by the slow rotation of each C ꢀC bond. Figures 1
1
0
11
1
and 2 show the H NMR spectra of meso-2 and (R,R)-
at several temperatures. At low temperatures, the
2
For the other diastereoisomer [for example the enan-
tiomer (R,R)-2] we find a different behavior but a
similar result.
internal rotation is frozen and the peaks of the pairs of
protons H , H (those that are near H ) and H , H
5%
4
4%
11
5

M. S a´ nchez-Aris et al. / Tetrahedron: Asymmetry 14 (2003) 3129–3135
3131
Figure 3. Frontal and vertical views of the conformational
equilibrium of meso-2.
Figure 4. Frontal and vertical views of the conformational
equilibrium of (R,R)-2.
Figure 4 shows the two stabilized conformations of
(
R,R)-2 resulting from the rotation of 180° of the
C ꢀC bond. Each structure has C symmetry that
10
11
2
converts one anthracene ring into the other anthracene
ring. Each proton is isochronous of the corresponding
prima proton. The two components of the conforma-
tional equilibrium (R,P,R)-2 and (R,M,R)-2 are
diastereoisomers and each rotamer shows 10 different
protons, each slightly different from the other. This
also results in a lack of the resolution for the NMR
spectrum.
Scheme 2. Chiral substrates analyzed in the tests of the
behavior of 2 as CSA.
3
. Enantiorecognition activity
The behavior of 2 as a chiral solvating agent was tested
with the compounds described in Scheme 2. The follow-
ing racemic substrates were used: 1-phenylethylamine 8,
Enantiodifferentiation of 8 is observed for H , appear-
7
ing as two quartets, one for each enantiomer [(R)-8 at
lower frequency]. Figure 5 shows the chemical shift
variation of H-7 in 8 when several portions of (S,S)-2
or (S)-3 were added. Figure 6 shows the graphic differ-
ence between the enantiomers. As can be seen, compar-
ing the results of both CSA’s, the use of 2 affords lower
shifting of signals for each enantiomer if alcohol 3 is
used. However, a similar distinction exists between the
signals of the two enantiomers using both chiral agents
1-(1-pyrenyl)ethylamine 9, cis-1-amino-2-indanol 10
and fluoxetine 11. In all cases, the presence of a basic
point and an aromatic ring allows the formation of an
intermolecular hydrogen bond and a p/p stacking stabi-
lization interaction.
Although both enantiomers of 2 are used, as the behav-
iors are symmetrical against the same racemic mixture,
the results are always referred to those obtained when
the (S,S)-2 enantiomer is used. Given its structural
relation, parallel experiments were obtained using
2
and 3. Moreover, while the effect of 3 seems to reach
a plateau, the addition of 2 further increases the differ-
ence after the addition of 2.4 equiv. For similar equi-
librium constants, it means that the two
diastereoisomeric complexes of association show
greater differences in the case of the use of the new
compound 2.
5
Pirkle’s alcohol 3 that is a very useful CSA. The
experiments were carried out in CDCl , adding portions
3
of the CSA to a solution (0.04–0.05M) of racemic
substrate until a maximum differentiation of the corre-
sponding enantiomer’s signals was obtained. The iden-
tification of signals of each enantiomer was reached
using mixtures enriched in one of the enantiomers with
a known composition. The integration of the separated
signals affords the enantiomeric identity.
The distinction of enantiomers of 1-(1-pyrenyl)-
ethylamine 9 was principally produced in the aromatic
protons H , H , H , H , in H and in the methyl
2
7
9
10
11
group. As most of the aromatic part of the spectrum

3
132
M. S a´ nchez-Aris et al. / Tetrahedron: Asymmetry 14 (2003) 3129–3135
Figure 7. Evolution of the enantiodifferentiation of H and
3
Figure 5. Evolution of the chemical shift of H7 of enan-
tiomers of 1-phenylethylamine 8 when portions of a,a%-
bis(trifluoromethyl)-10,10%-(9,9%-bianthryl)dimethanol [(S,S)-2]
or Pirkle’s alcohol (S)-3 were added.
H3% of fluoxetine 11 when (S,S)-2, (S)-3 or (S,S)-1 were
added.
1
Figure 8. Aliphatic part of H NMR spectrum of the enan-
tiodiscrimination process of a mixture 3/1 of (1R,2S)- and
(
1S,2R)-cis-1-amino-2-indanol 10 by the addition of portions
of 0.5 equiv. of (S,S)-a,a%-bis(trifluoromethyl)-10,10%-(9,9%-
bianthryl)dimethanol 2.
Figure 6. Evolution of the difference of the chemical shift of
H [lH (R)−lH (S)] of enantiomers of 1-phenylethylamine 8
7
7
7
when portions of (S,S)-a,a%-bis(trifluoromethyl)-10,10%-(9,9%-
bianthryl)dimethanol (S,S)-2 or Pirkle’s alcohol (S)-3 were
added.
Although most of the fluoxetine protons 11 are differ-
entiated, only H , H and the methyl group could be
3
3%
measured. Figure 7 shows the ability of compound 2 to
becomes a complex broad signal, only the evolution of
last three signals could be quantified. The maximum
separation obtained was observed after the addition of
separate by NMR the H and H of enantiomers of
3
3%
fluoxetine 11 and is compared with the always
improved separation using bis(trifluoromethyl)-9,10-
anthracenedimethanol 1. The use of Pirkle’s alcohol 3
allows a better separation of H and the action on H
2
equiv. of 2 and was 0.023 ppm for H , 0.009 ppm for
1
0
CH and 0.016 ppm for H . The differentiation of the
3
11
3
3%
bencilic protons of two enantiomers is much greater in
the case of 1-phenylethylamine 8. Possibly, the perpen-
dicular disposition of two anthracene groups of a,a%-
bis(trifluoromethyl)-10,10%-(9,9%-bianthryl)dimethanol 2,
avoids the approximation of the extended and rigid
coplanar distribution of four aromatic rings of the
pyrenyl group of subtract 9. That is, if an hydrogen
bond is formed between the hydroxy and the amine
groups of 2 and 9, respectively, the second anthracene
group (perpendicular to the first one) keeps shuns the
parallelism of aromatic parts eluding the p,p-stacking
interaction.
is similar. The methyl group is not moved by 3 while,
after the addition of two equivalents of 2, the methyl
group signals of each enantiomer could be easily inte-
grated since are separated 0.01 ppm.
1
Figure 8 shows the aliphatic part of the H NMR
spectra of a mixture of the enantiomers of cis-1-amino-
2
-indanol 10 in a molar relation (1R,2S)/(1S,2R) of 3/1
when portions of entitled compound 2 were added. We
can observe the doubling of all signals with a good
resolution that also would allow a good integration

M. S a´ nchez-Aris et al. / Tetrahedron: Asymmetry 14 (2003) 3129–3135
3133
Table 1. Values of the enantiodiscrimination observed on
several protons of cis-1-amino-2-indanol 10 when parts of
.5 equiv. of (S)-3 or (S,S)-2 were added
0
Proton
CSA (subtract) (S)-3 D(Dl)
ppm)
(S,S)-2 D(Dl)
(ppm)
(
H3%
0.5
1
0.015
0.027
0.037
0.042
0.006
0.013
0.013
0.013
0
0.016
0.027
0.037
0.042
0.005
0.010
0.013
0.015
0.07
1
2
.5
H3
H1
0.5
1
1
2
.5
0.5
1
0.010
0.015
0.018
0.014
0.020
0.026
1
2
.5
Figure 9. Measurement of the binding constant of the associ-
ation of (R)- and (S)-1-phenylethylamine 8 with (S,S)-a,a%-
bis(trifluoromethyl)-10,10%-(9,9%-bianthryl)dimethanol 2 by the
equimolar method at three temperatures.
The comparison with the results obtained using Pirkle’s
alcohol are shown in Table 1 where the difference
obtained after the addition of portions of 0.5 equiva-
lents is reproduced for the two chiral agents (S,S)-2 and
Table 2. Binding constant (and the standard error) of the
complex formation between each enantiomer of 1-phenyl-
ethylamine 8 and (S,S)-a,a%-bis(trifluoromethyl)-10,10%-
(
S)-3. In his case the behavior of both agents is very
similar.
(
9,9%-bianthryl)dimethanol 2
The stoichiometry of the complex was measured using
1
2
Job methodology obtaining in all cases a molar rela-
tion 1:1.
T (K) (R)-8+(S,S)-2
(S)-8+(S,S)-2
K (M−1)
DG°
(kJ/mol)
K (M−1
)
DG°
(kJ/mol)
13
NMR is one of the most widely used techniques for
measuring Ka in the chemistry of associated com-
298
283
268
39.2±20.8
61.8±6.9
95.1±12.85
−9.1±1.4
−9.7±0.3
−10.1±0.3
28.6±12.0
45.9±6.0
66.3±15.2
−8.4±1.1
−9.0±0.3
−9.3±0.5
14
pounds. In our case, the equimolar method was
applied to measure the binding constant of the
1
5
association of the CSA 2 with compounds 8 and 10.
1
6
In all cases, the degree of association was kept at
between 40 and 70% and, to avoid the presence of
competitive processes, the pure enantiomers were used.
Several solutions of identical concentration of substrate
and solvating agent were analyzed at several tempera-
complexes is enough different to distinguish the two
enantiomers. Only when the temperature decreases the
difference between binding constants increase. A signifi-
cant difference in the proportions of the complex could
be responsible for the increment in the value of the
enantiodiscrimination.
1
tures. Plotting (Fig. 9) the variation of the H NMR
chemical shift (Dl) of H of 8 in front of the square
7
root of the relation between the changes of chemical
0.5
shift versus concentration ((Dl/S) ), yielded straight
In the case of the aminoindanol 10, we obtained the
constants measuring the chemical shifts on protons H1,
H and H obtaining (the mean value) lower values and
lines. These lines converge and intercept the abscissa
where we obtained the chemical shift of the H in the
7
3
3%
complex (4.335 and 4.225 for H (R) and H (S), respec-
7
7
quite similar for two isomers: KRS=6.9 and KSR=4.4.
Considering that the enantiodiscrimination is so good,
newly, the different geometry of the approximation of
the two components is the responsible for the enan-
tiodistinction phenomenon.
tively, from 4.100 of free molecule). From the scope we
found the equilibrium constant value at several
temperatures.
Table 2 shows the equilibrium constants (and the stan-
dard error) obtained for the association of the (R)- and
We can conclude that compound 2 is an active chiral
solvating agent, with a similar behavior to the Pirkle’s
alcohol 3. Possibly, the distance between the two
stereogenic and active centers of association is too high
for a common action. Moreover, in some cases, the
relative position of two anthracene rings obstructs a
correct approximation of two components of complex.
Possibly, the use of compound 2 will improve the
separation of enantiomers with a complementary three-
dimensional structure.
(
S)-1-phenylethylamine 8 with (S,S)-a,a%-bis(trifluoro-
methyl)-10,10%-(9,9%-bianthryl)dimethanol at three
temperatures. It is obtained by measuring the variation
2
of chemical shift of H protons of each enantiomer. The
7
similarity of the measured constants implies a very near
thermodynamic behavior. This could be interpreted as
the occurrence of the enantiodifferentiation thanks to
the differential magnetic properties of each associate
species. Therefore, the geometry of two diastereomeric

3
134
M. S a´ nchez-Aris et al. / Tetrahedron: Asymmetry 14 (2003) 3129–3135
4
. Experimental
30%) of
a
yellow 10,10%-bis(trifluoroacetyl)-9,9%-
bianthracenyl 6. Mp: decompose. EM m/z (%): 546 (M,
NMR spectra were recorded at 400.13 and 500.13 MHz
for H. The temperature was controlled to 0.1°C.
27), 477 (100), 450 (17), 380 (52), 350 (43),204 (33), 175
1
1
(52). H NMR (CDCl3, 400 MHz) l (ppm): 7.86 (d,
Chemical shifts are reported in parts per million relative
to internal TMS. The complete identification of the
NMR signals was carried out with the aid of several 1D
J4,5/3,6=8.52 Hz, 4H, H , H , H and H ), 7.57 (m, 4H,
4
4%
5
5%
H , H , H and H ), 7.24 (m, 4H, H , H , H and H ),
3
3%
6
6%
2
2%
7
7%
7.10 (d, J1,8/2,7=8.80 Hz, 4H, H , H , H and H )
1
1%
8
8%
(NOE) and 2D (COSY, HMQC and HMBC) spectra.
4
.3. a,a%-Bis(trifluoromethyl)-10,10%-(9,9%-bianthracenyl)-
The NMR titration method was carried out with 0.4–
dimethanol 2
0
1
.5 ml of a solution 0.03–0.05 M of the compound 8 to
1. After addition (at constant volume) of several por-
4
1
1
.3.1. Method A. A diethyl ether solution (20 ml) of
0,10%-bis(trifluoroacetyl)-9,9%-bianthracenyl 6 (0.60 g,
.10 mmol) was slowly added to a diethyl ether slurry
tions of 0.2–0.5 equiv. of CSA 2, NMR spectra were
measured and the variations of the chemicals shifts
calculated for each addition. The measures were contin-
ued until a maximum enantiodiscrimination (1.5–2.5
equiv.). The comparative experiments were carried out
in identical conditions.
(
10 ml) of LiAlH (60 mg, 1.65 mmol) and kept under
4
N with continuous stirring at rt. After 2 h, reduction
2
was completed. The reaction was quenched with water
and the organic layer was separated, dried, and concen-
trated. The solid residue was purified by column chro-
matography on silica gel (hexane/dichloromethane 1/1
v/v) to give a white product 2 (0.42 g, 69% yield).
Binding constants were determined (equimolar method)
by measuring chemical shifts of an equimolar solution
in CDCl of each compound 8 or 10 and the corre-
3
sponding chiral solvating agent 2. From 0.5 ml of an
initial concentration of 0.06 M of each and after four
additions of 0.1 ml of solvent we obtained four values
of chemical shift correlated to the corresponding con-
centration. In the case of compound 8, the measures
were carried out at three temperatures after each dilu-
tion. Chiral semipreparative HPLC was carried out
using a (R,R)-Whelk-O1 (250 mm×10 mm) column and
a preparative HPLC using a (R,R)-Whelk-O2 (250
mm×25 mm) column.
4.3.2. Method B. At rt and under inert conditions 1.43
ml (11.28 mmol) of BF ·Et O was slowly added to a
3
2
solution of 9,9%-bianthracenyl 4 (0.208 g, 0.59 mmol) in
15 ml of CH Cl containing 0.26 ml (2.26 mmol) of
2
2
trifluoroacetaldehyde ethyl hemiacetal. After 72 h, the
reaction was quenched with ice/HCl, treated with
CH Cl and the organic phase was dried and evapo-
2
2
rated. The yellow crude was purified by column chro-
matography on silica-gel (hexane/CH Cl 1:1) yielding
2
2
0
.262 g (0.47 mmol, 81%) of 2. Mp: decompose. IR
−1
4.1. 1-(9-Anthryl)-2,2,2-trifluoroethanol
(KBr) cm : 3370 (OꢀH, broad), 1447 (m), 1262 (s),
165 (s), 1127 (s), 1097 (s), 1036 (m), 877 (w), 768 (s).
UV umax (nm) (CH Cl ): 240, 340, 358. EM m/z (%):
1
To a solution of anthracene (1.50 g, 8.4 mmol) in
anhydrous CH Cl (75 ml) and in a stream of N2,
2
2
550 (M,100), 481 (78), 463 (38), 435 (22), 354 (36), 206
2
2
1
BF ·Et O (5.0 ml, 40 mmol) and trifluoroacetaldehyde
(82), 175 (46). H NMR (CDCl T=300 K, 400 MHz)
3
2
3,
ethyl hemiacetal (3.0 ml, 26 mmol) were added. The
mixture was stirred at rt for 3.5 h. The mixture was
treated with ice cold water and diluted sulfuric acid and
extracted with CH Cl The organic layer was washed
l (ppm): 9.31 (broad, 2H, H and H ), 8.58 (broad, 2H,
5
5%
H and H ), 7.52 (broad, 4H, H , H , H and H ), 7.20
4
4%
3
3%
6
6%
(broad, 4H, H , H , H , H ), 7.05 (q, J11/F=7.92 Hz,
2
2%
7
7%
2H, H , H ), 7.00 (broad, 4H, H H1%, H and H ),
2
2
11
11%
1,
8
8%
1
with water and dried with anhydrous Na SO . After
6.60 (d, JOH/H11=4.72 Hz, 2H, OH and OH%). H NMR
(CD COCD , T=270 K, 400 MHz) l (ppm): 9.33 (d,
2
4
evaporation of the solvent under vacuum, the residue
3
3
was purified by column chromatography (SiO , hexane/
J5/6=J5%/6%=9.08 Hz, 2H, H and H ), 8.61 (d, J4/3=J4%/,3%
=9.40 Hz, 2H, H and H ), 7.60 (m, 2H, H and H )
4 4% 3 3%
2
5 5%
CH Cl 8/2) giving 1-(9-anthryl)-2,2,2-trifluoroethanol
2
2
(
2.10 g, 90%).
7,52 (m, 2H, H and H ), 7.21 (m, 4H, H , H , H and
6 6% 2 2% 7
H ), 7.08 (q, J11/F=8.20 Hz, 2H, H11 and H ), 7.00
7%
11%
4
.2. 10,10%-Bis(trifluoroacetyl)-9,9%-bianthracenyl 6
(m, 2H, H and H ), 6.93 (m, 2H, H and H ), 6.88 (d,
1 1% 8 8%
13
JOH/H11=5.88 Hz, 2H, OH and OH%). C NMR
(CD COCD , T=270 K, 100 MHz) l (ppm): 70.44 (C
11
10,10%-Dibromo-9,9%-bianthracenyl (0.38 g, 0.75
5
3
3
mmol) was dissolved in dried diethyl ether (20 ml)
under inert conditions. At rt, butyllithium (1.26 ml, 1.6
M in hexane) was slowly added. At −78°C The mixture
was stirred for 1.5 h and a solution of trifluoroacetic
anhydride (0.85 ml, 7.50 mmol in 10 ml of diethyl
ether) was added. After 2 h, the reaction was quenched
and the resultant brown liquid was washed with a
and C ), 125.23 (C and C ), 126.47, 129.29 (C and
11% 4 4% 9
C ), 126.69, 126.75 (C and C ), 127.02, 127.38 (C and
9%
6
6%
2
C ), 127.18 and 127.22 (C and C ), 128.03, 128.09 (C
2%
7
7%
8
and C ), 128.41, 128.48 (C and C ), 128.71, 128.77 (C
8%
3
3%
1
and C ), 130.11 (C and C ), 132.02, 132.06, 132.11,
1%
5
5%
132.15 (C , C , C and C10a%), 132.27, 132.32 (C9a
4a
4a%
10a
and C ), 132.99, 133.04 (C and C ), 137.53 (C and
9a%
8a
8a%
10
saturated solution of NH Cl (2×50 ml), a solution of
C ).
10%
4
1
0% NaOH (2×50 ml), and finally water (2×50 ml).
1
13
After dried and evaporated, the solid residue was
purified by column chromatography on silica gel (hex-
ane/dichloromethane 90/10) giving 0.14 g (0.26 mmol,
Since the signals of the H and C NMR spectra are
broad the spectrum corresponding to each isomer
appears indistinguishable from those of the mixture.

M. S a´ nchez-Aris et al. / Tetrahedron: Asymmetry 14 (2003) 3129–3135
3135
The pure enantiomers are obtained after hydrolysis of the
isolated acetate derivatives 7
Acknowledgements
2
5
(
S,S)-2: [h] =+7.3 (c 2.2, CH Cl )
25
D
2
2
(
R,R)-2: [h] =−7.3 (c 2.2, CH Cl )
Financial support from CICYT (project PPQ3000-369)
is gratefully acknowledged.
D
2
2
2
5
meso-2: [h] =0.0 (c 2.2, CH Cl )
D
2
2
4
.4. a,a%-Bis(trifluoromethyl)-10,10%-(9,9%-bianthracenyl)-
dimethyl diacetate 7
References
To a solution of 2 (0.59 g, 1.13 mmol) in dichloromethane
(
(
60 ml) was added 0.055 g of (dimethylamino)pyridine
DMAP) (0.45 mmol), 2.19 ml of triethylamine (15.83
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h, the reaction was finished and the mixture was washed
2
with water (2×50 ml), HCl 1 M (2×50 ml), and a solution
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dichloromethane 1/1 v/v) to give a pale yellow product
(
71% yield). Mp: 311–314°C. Anal. calcd for C H F O :
36 24 6 4
C, 68.14%; H, 3.81%. Found: C, 68.10%; H, 3.98%. IR
−
1
(KBr) cm : 2958 (w), 1758 (s), 1448 (w), 1370 (w), 1272
(
(
m), 1217 (s), 1176 (s), 1133 (s), 1077 (m), 1040 (m), 943
1
w), 765 (s). H NMR (CDCl 400 MHz) l (ppm): 8.88
3
,
(
2
d, J5/6=8.80 Hz, 2H, H and H ), 8.50 (d, J4/3=8.80 Hz,
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5
5%
H, H and H ), 8.01 (q, J11/F=7.92 Hz, 2H, H11 and
4 4%
H ), 7.59 (broad, 2H, H and H ), 7.52 (broad, 2H, H
and H ), 7.15 (broad, 4H, H , H , H and H ), 7.05 (m,
1
1%
3
3%
6
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6
%
2
2%
7
7%
4
H, H , H , H and H ), 2.30 (s, 6H, CH and CH ).
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1 1% 8, 8% 3 3%
1
3
C NMR (CDCl , 100 MHz) l (ppm): 169.01 (CꢁO),
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3
1
(
37.38 (C and C ), 131.53, 131.16, 130.54 and 130.94
9
9%
C , C , C , C , C , C , C and C10a%), 127.99 (C3
4a 4a% 8a 8a% 9a 9a% 10a
and C ), 127.64 (C , C , C and C ), 126.64 (C and C )
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3
%
1
1%
8
8%
5
5% ,
1
26.29 (C and C ), 125.67 (C , C , C and C ), 122.84
6 6% 2 2% 7 7%
(
C10 and C ), 122.28 (C and C ), 69.08 (C and C11%),
10% 4 4% 11
2
0.76 (CH and CH%).
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3
3
13. Fielding, L. Tetrahedron 2000, 56, 6151–6170.
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u=290 nm, flow 2.8 ml/min. KRR=2.10, Kmeso=3,05 and
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K =4.80
SS
2
5
(
R,R)-5: [h] =−50.5 (c 1.9, CH Cl )
S,S)-5: [h] =+50.5 (c 1.9, CH Cl )
D
2
2
25
(
16. Deranleau, D. A. J. Am. Chem. Soc. 1969, 91, 4044–4049.
D
2
2