Assembly of chiral monodentate ligands to chelates by donor-acceptor interactions

Article abstract of DOI:10.1016/j.tetasy.2008.04.008

The first examples of assembling monodentate oxazoline donor and acceptor ligands by charge transfer interactions are described to mimic bidentate ligands in asymmetric catalysis. The corresponding copper(II) complexes were used in an enantioselective Die

Full text of DOI:10.1016/j.tetasy.2008.04.008

Available online at www.sciencedirect.com
Tetrahedron: Asymmetry 19 (2008) 1010–1019
Assembly of chiral monodentate ligands to chelates
by donor–acceptor interactions
Olivier Chuzel, Caroline Magnier-Bouvier and Emmanuelle Schulz*
ˆ
Equipe de Catalyse Mole´culaire, ICMMO, UMR 8182, Universite´ Paris-Sud 11, Bat 420, 91405 Orsay cedex, France
Received 29 February 2008; accepted 7 April 2008
Abstract—The first examples of assembling monodentate oxazoline donor and acceptor ligands by charge transfer interactions are
described to mimic bidentate ligands in asymmetric catalysis. The corresponding copper(II) complexes were used in an enantioselective
Diels–Alder reaction and showed very high efficiency, but only moderate stereoselectivity. These complexes were successfully recovered
and reused after precipitation in pentane.
Ó 2008 Elsevier Ltd. All rights reserved.
1. Introduction
tate ligands, probably favoured by weak interactions, such
as van der Waals, p-stacking or dipole–dipole interactions.
This was simultaneously reported by Reetz et al.3 and
Feringa and Minnaard.4 Stronger interactions, such as
hydrogen bonding, were also studied by Breit et al. who
modified monodentate ligands by structural complemen-
tary motifs to mimic the adenine–thymine base pair in
DNA5 or prepared various chelates by interactions based
on the 2-pyridone/hydroxypyridine tautomeric system.6
The urea motif, and its complementary hydrogen bonds,
was exploited by Reek et al. for the supramolecular
assembly of Binol-based phosphite ligands.7 Coordinative
interactions were also studied for the assembly of
monodentate ligands in a heterodimeric way; Reek et al.
studied the ability of zinc(II) porphyrins to form stable
complexes with pyridine derivatives as nitrogen donors.
They thus prepared various phosphite zinc(II) porphyrins
and monodentate phosphorous ligands bearing a nitrogen
donor group.8 Metal-directed self-assembly based on the
rapid formation of bis(oxazoline) Zn complex has also
been reported by Takacs et al. in which other coordinating
groups are suitably disposed to bind a second metal, useful
for the catalysis.9 Recently, Ishihara et al. synthesized
and characterized self-assembled macrocyclic Pd(II) and
Cu(II) complexes through trans-chelation with new
P,N- or bis(oxazoline) ligands.10 Most of these chelates
associated by non-covalent interactions involved phospho-
rous-containing ligands. They were mainly tested in the
presence of rhodium pre-catalysts for the efficient asym-
metric hydrogenation of various substrates or with palla-
dium complexes for successful nucleophilic allylic
substitutions.
Asymmetric catalysis is nowadays a subject of great con-
cern for the preparation of enantioenriched valuable syn-
thons in an economic and environmentally friendly way.
The efficient transfer of the chirality from an optically ac-
tive catalyst to the reaction product is a transformation
that perfectly meets the concept of atom economy, one of
the fundaments of the twelve principles of green chemis-
try.1 Highly valuable catalysts, in terms of activity and
enantioselectivity, are often designed from bidentate li-
gands and numerous efforts have thus been devoted to-
wards the fine tuning of synthetic methodologies for their
easy preparation. Although combinatorial procedures have
been developed, the facile access to numerous, structurally
different bidentate ligands is not obvious. An alternative
strategy consists of the preparation of targeted monoden-
tate ligands that can then be assembled around the metal
to form chelates, thanks to additional non-covalent inter-
actions. According to the reversibility of this additional
link, a great diversity of new two-point coordinating
ligands is available for the search of efficient chiral catalysts
active in various asymmetric transformations. Some
research has already been performed to prove the success
of this strategy for homogeneous catalysis and has recently
been reviewed.2 For example, they involve the preferential
formation of heterodimeric catalysts from two monoden-
*
Corresponding author. Fax: +33 (0) 1 69 15 46 80; e-mail: emmaschulz@
icmo.u-psud.fr
0957-4166/$ - see front matter Ó 2008 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetasy.2008.04.008

O. Chuzel et al. / Tetrahedron: Asymmetry 19 (2008) 1010–1019
1011
We have recently described the efficient recovery of chiral
2. Results and discussion
copper–bis(oxazoline) complexes by the formation of
reversible non-covalent donor–acceptor interactions, be-
tween anthracene-modified ligands and additional trinitro-
fluorenone.11 We herein report as preliminary results, the
first example, to the best of our knowledge, concerning
the possibility of assembling monodentate oxazoline
ligands by charge transfer interactions to mimic bidentate
ligands for asymmetric catalysis. A schematic representa-
tion for this concept is given below (Fig. 1).
2.1. Synthesis
Both types of substituted mono(oxazolines) were synthe-
sized following the same strategy, that is, the formation
of the oxazoline moiety from a carboxylic acid functional
group via the synthesis of various amides according to
the targeted amino alcohols. The final step involved the
ring closure to the heterocycle by diethylaminosulfur tri-
fluoride-induced activation.13 We were successful in pre-
paring derivatives from (S)-valinol, (R)-phenyglycinol
and (S)-tert-leucinol; however all attempts to cyclize
(1R,2S)-1-amino-2-indanol compounds with this procedure
failed. The modification of the coordinating oxazoline
group by either a donor or an acceptor motif was consid-
ered from commercially or easily available substituted
anthracene or nitrofluorenone derivatives. In both cases,
flexible link with a similar length was installed between
the functional groups suitable for either the formation of
the active chiral organometallic species or the preparation
of the charge transfer complex for the reversible self-assem-
bly. The synthesis of the donor derivatives is depicted in
Scheme 1.
D
A
L1*
L2*
D
A
L1*
L2*
D
A
L1*
L2*
"M"
+
M
D: electron-rich compound, A: electron-deficient compound,
L1* and L2*: chiral monodentate ligands, M: metal for the catalysis
covalent link
Figure 1. Formation of asymmetric catalysts from chelates assembled by
reversible charge transfer interactions.
The synthesis of various mono(oxazolines) possessing
either an electron-rich motif (an anthracene group) or an
electron-deficient substituent (based on the 2,4,7-trinitro-
fluoren-9-one backbone) is described; these new ligands
are fully characterized. In the presence of copper(II) triflate
as precatalyst, different ligand combinations were tested in
the asymmetric Diels–Alder reaction between cyclopenta-
diene and 3-but-2-enoyl-oxazolidin-2-one. Using this pro-
cedure, non-symmetric bis-(oxazolines) type ligands were
easily generated and afforded various new chiral environ-
ments around the coordinating metal, by assembling differ-
ent monodentate oxazoline ligands. The direct synthesis of
non-symmetrical bis(oxazolines) is not straightforward
with only few examples reported in the literature.12 More-
over, these new assembled copper complexes were easily
recovered by precipitation in pentane and directly recycled
in a new catalytic transformation.
The amidation reaction of 4-(9-anthrylmethoxy)-4-oxo-
butanoic acid 114 was performed in the presence of three
different aminoalcohols. The coupling was activated with
N-(3-dimethylaminopropyl)-N0-ethylcarbodiimide (EDC)15
and 1-hydroxybenzotriazole hydrate (HOBt) providing
the targeted amide derivatives in moderate to good yields
that were not further optimized. The final cyclization into
the oxazoline ligands 3a–c was realized with fluoride
activation and allowed the isolation of three donor ligands
that were fully characterized.
A similar procedure (see Scheme 2) was followed for the
synthesis of the corresponding acceptor ligands starting
from 2,5,7-trinitro-9-oxo-9H-fluorene-4-carboxylic acid
4.16 The spacer was settled via the reaction with 1,4-butane-
diol to provide alcohol 5 in good yield. Subsequent oxida-
O
R
*
O
COOH
O
OH
N
H
O
O
EDC, HOBt
CH2Cl2
2a 86%
2b
2c
88%
31%
R
OH
1
H2N
*
DAST, K2CO3
CH2Cl2, -78°C
a R = CH(CH3)2, (S)-Valinol
R
*
b
R = C6H5, (R)-Phenylglycinol
c R = C(CH3)3, (S)-tert-Leucinol
N
O
O
O
3a
80%
3b
20%
3c 98%
Scheme 1. Synthesis of anthracene-modified mono(oxazolines).

1012
O. Chuzel et al. / Tetrahedron: Asymmetry 19 (2008) 1010–1019
O N
O
OH
O
O
2
O2N
OH
(COCl)2, DMF
O2N
O2N
1,4-butanediol
pyridine
NO2
NO2
77 %
O
4
O
5
CrO3
H2SO4
H2O
R
83 %
OH
H2N
*
O
a R = CH(CH3)2, (S)-Valinol
O
R
O
O
b R = C6H5, (R)-Phenylglycinol
O2N
O
O
O
O2N
O
OH
c R = C(CH3)3, (S)-t er -Leucinol
N
H
*
O2N
O2N
OH
ED C, HOBt, CH2Cl2
NO2
7 a 85%
7 b 14%
7 c 67%
NO2
6
O
*
N
O
O
R
O2N
O
DAST, K2CO3
CH2Cl2, -78°C
O2N
8a 90%
8b 28%
8c 88%
NO2
Scheme 2. Synthesis of trinitrofluorenone-modified mono(oxazolines).
tion of the hydroxyl group by the Jones procedure fur-
nished the carboxylic acid 6 in 83% yield. The synthesis
of the acceptor ligands was identical to that described in
Scheme 1 for the preparation of the donor counterparts,
and the targeted compounds 8a–c were thus isolated in
moderate to high unoptimized yields.
isomer (endo/exo = 96/4) with a high enantioselectivity
(97% ee). This transformation was thus chosen as a test
reaction to confirm our concept. Ligands arising from
(S)-valinol 3a and 8a were first selected for the preparation
of a copper complex.
The experimental procedure involves mixing the ligands in
dichloromethane before their addition to Cu(OTf)2 (each
compound in an equimolar quantity). The resulting solu-
tion is stirred for at least 3 h before the addition of the reac-
tants. The formation of the complex is accompanied with
the appearance of a red colour (which is characteristic of
the charge transfer) although the reaction mixture remains
homogeneous. Results obtained with the valinol ligands are
reported in Table 1. The first catalytic test was attempted at
ꢀ15 °C, and after 15 h reaction time, the expected mixture
of endo/exo products could be isolated albeit in a quite low
yield (entry 1). These results nevertheless confirm that an
active species for the Diels–Alder reaction can be obtained
from monodentate ligands and copper(II) triflate. The
enantiomeric excesses could be determined for each diaste-
reoisomer by chiral HPLC analysis indicating, however, a
2.2. Catalytic tests
Chiral bis(oxazoline) ligands are valuable chelates for
asymmetric catalysis involving a large variety of metals,
for the use of the corresponding complexes in numerous
enantioselective transformations.17 We have decided to test
our charge-transfer assembled chelates in the bis(oxazo-
line)–copper catalyzed Diels–Alder reaction developed by
Evans et al.18 This transformation uses the catalytic system
derived from 2,20-isopropylidenebis[(4S)-4-tert-butyl-2-
oxazoline] and copper (II) and allows the simultaneous
formation of two new carbon–carbon bonds in a highly
diastereo- and enantioselective fashion (see Scheme 3).19
Under optimized conditions (in dichloromethane at
ꢀ15 °C), the endo compound was prepared as the major
O
2 TfO-
*
O
Donor
R
N
O
Cu2+
R'
N
*
O
O
O
O
O
Acceptor
O
O
O
+
+
O
N
O
N
N
O
O
(endo)
(exo)
Scheme 3. Diels–Alder reaction for the evaluation of the new chiral copper complexes.

O. Chuzel et al. / Tetrahedron: Asymmetry 19 (2008) 1010–1019
Table 1. Catalytic tests with valinol-type ligands
1013
Entrya
Ligand
T (°C)
Convb (%)
Yieldc (%)
endo/exod
endo eee (%) (config)
exo eee (%) (config)
1 1st run
2 2nd run
3a/8a
3a/8a
ꢀ15
25
50
20
35
76/24
77/23
8 (2S)
<5
15 (2S)
5 (2S)
25
a Conditions: Cu(OTf)2 12 mol % (0.036 mmol), each ligand 10 mol % (0.033 mmol) in 500 lL anhydrous CH2Cl2, oxazolidinone (0.33 mmol) in 250 lL
anhydrous CH2Cl2, cyclopentadiene (2.4 mmol, 200 lL), 15 h.
b Determined by 1H NMR spectroscopy.
c Isolated yield.
d Diastereoselectivity was determined by 1H NMR spectroscopy.
e Enantioselectivity was determined by chiral HPLC analysis, absolute configuration was assigned by comparison (see Ref. 21 and Section 4).
low enantioselectivity for both compounds. Interestingly,
the catalytic species could be recovered by the addition of
pentane that led to the precipitation of a red powder. Sub-
sequent washing with pentane and the addition of new re-
agents (Table 1, entry 2) allowed the reuse of the catalyst at
room temperature, as an attempt to improve the yield,
affording the products in a moderate yield but with dimin-
ished enantioselectivities. In our hands, the more usual 2,20-
isopropylidenebis[(4S)-4-isopropyl-2-oxazoline] associated
to copper(II) triflate promoted the reaction between 3-
(but-2-enoyl)oxazolidin-2-one and cyclopentadiene at
0 °C in dichloromethane, and the expected endo major
product was obtained with an enantioselectivity of
40%.11b,20 The targeted self-assembled bidentate ligand
arising from CTC interactions between 3a and 8a thus
afforded a moderately active catalytic species in the pres-
ence of copper, a precatalyst for the Diels–Alder reaction,
but a significant loss in enantioselectivity was unfortu-
nately observed compared to the parent methylene-bridge
bis(oxazoline).
was thus run in the presence of 3b as a unique ligand and
copper triflate in excess, leading to the formation of a
homodimeric complex (Table 2, entry 1). The resulting cat-
alyst proved to be much more efficient than that derived
from the valinol ligands since an almost complete conver-
sion of the substrates was obtained in 15 h at ꢀ15 °C lead-
ing to the isolated products in 85% yield. The endo product
was obtained as the major compound with 66% de and 28%
ee in favour of the major (2R) enantiomer. The exo com-
pound was isolated with 22% ee. Accordingly, trinitrofluor-
enone-substituted monooxazoline ligand 8b was tested as
ligand under the same conditions (Table 2, entries 2–4).
This new homodimeric catalyst was again efficient for the
formation of the endo product with 62% de albeit in a
nearly racemic form. The enantioselectivity of the minor
exo product was interestingly enhanced up to 39%. This
catalyst was successfully reused twice more without show-
ing any loss in activity (even at ꢀ40 °C) but a slight de-
crease in enantioselectivity at each recycling. The 1:1
mixture of compounds 3b and 8b in the presence of cop-
per(II) triflate also led to an efficient Diels–Alder catalyst
that could be very efficiently recycled three times (Table
2, entries 5–8). This ligand mixture may lead to the forma-
tion of two homodimeric copper complexes (with two do-
nor or two acceptor ligands) and one heterodimeric
complex, resulting from the charge transfer complex. The
results in terms of diastereoselectivity are analogous to
those obtained in the presence of the homodimeric com-
plexes from either 8b or 3b, but the exo product showed
only 20% ee. While the endo product was obtained in all
cases with a low enantioselectivity, it is worthwhile men-
tioning that a reversal in the major enantiomer is observed
Similar experiments were performed in the presence of
ligands 3b and 8b arising from (R)-phenylglycinol (see
Table 2). Some preliminary tests showed that an active
species was only obtained if the complex was prepared in
the presence of an excess of copper(II) triflate compared
to the oxazoline ligands. Even if this phenomenon
remained unclear, we propose that undesired complexation
of copper to the anthracene/trinitrofluorenone link may
occur, leading to less active complexes in the subsequent
catalysis experiments.22 It was verified that no reaction
occurred in the absence of any ligand. A catalytic test
Table 2. Catalytic tests with phenylglycinol-type ligands
Entrya
Ligand
T (°C)
Convb (%)
Yieldc (%)
endo/exod
endo eee(%) (config)
exo eee (config)
1 1st run
2 1st run
3 2nd run
4 3rd run
5 1st run
6 2nd run
7 3rd run
8 4th run
3b
8b
ꢀ15
ꢀ15
ꢀ15
ꢀ40
ꢀ15
ꢀ15
ꢀ15
ꢀ40
96
85
90
90
90
85
90
90
55
83/17
81/19
83/17
87/13
83/17
83/17
85/15
86/14
28 (2R)
7 (2S)
7 (2S)
6 (2S)
8 (2R)
8 (2R)
7 (2R)
<5
22 (2R)
39 (2R)
29 (2R)
21 (2R)
20 (2R)
20 (2R)
19 (2R)
16 (2R)
100
100
100
100
100
100
60
8b
8b
3b/8bf
3b/8bf
3b/8bf
3b/8bf
a Conditions: Cu(OTf)2 10 mol % (0.033 mmol), ligand 6 mol % (0.020 mmol) in 500 lL anhydrous CH2Cl2, oxazolidinone (0.33 mmol) in 250 lL
anhydrous CH2Cl2, cyclopentadiene (2.4 mmol, 200 lL), 15 h.
b Determined by 1H NMR spectroscopy.
c Isolated yield.
d Diastereoselectivity determined by 1H NMR spectroscopy.
e Enantioselectivity determined by chiral HPLC analysis, absolute configuration was assigned by comparison (see Ref. 21 and Section 4).
f 6 mol % of each ligand.

1014
O. Chuzel et al. / Tetrahedron: Asymmetry 19 (2008) 1010–1019
using only ligand 3b or the corresponding acceptor 8b. The
major (2R)-endo-compound is also obtained in the presence
of the mixture of both ligands, suggesting that different cat-
alytic species are involved in those experiments.
two donor ligands (of the 3 series) are reacting with copper
triflate, the resulting solution becomes brown-yellow but
turns to dark purple when two electron-deficient compounds
(series 8) are involved. Mixing both types of ligands led to a
typically different brown-red solution. One can thus not ex-
clude that in this case, the heterodimeric complex exists
thanks to the donor–acceptor interactions. The resulting cat-
alyst seems, however, less selective.
Further experiments could be conducted with the tert-
leucinol derived ligands. The parent bridge bis(oxazoline)
ligand is indeed the most efficient chelate for copper to
promote this transformation.18 In this case again, the
formation of the organometallic species proved to be more
challenging and reproducible results could only be
obtained by working with a higher catalyst loading in the
presence of molecular sieves. The donor ligand 3c allowed
the formation of an active and diastereoselective catalyst
that led to the formation of the major endo-compound in
42% ee (Table 3, entry 1). This catalyst, however, was
demonstrated to be less stable than the other previously de-
scribed since its recycling (albeit run at ꢀ65 °C) was
accompanied with an important loss of activity and enanti-
oselectivity. The corresponding acceptor ligand 8c was also
engaged alone in the catalytic transformation and led inter-
estingly to the isolation of both compounds with a similar
diastereoisomeric ratio but the endo product was nearly
racemic, whereas the minor exo compound was prepared
with high enantiomeric excess (up to 73%), the highest va-
lue obtained in this study (Table 3, entries 3 and 4).
Finally, some catalytic tests were attempted in the presence
of a mixture of ligands, as donor–acceptor chelates possess-
ing non-symmetric oxazoline moieties. A first experiment
implied the use of the donor ligand with the tert-leucinol
oxazoline 3c and the acceptor one substituted by a valin-
ol-type derivative 8a. In the presence of equimolar quanti-
ties of copper, the resulting catalyst proved to be poorly
active (Table 4, entry 1) and led mainly to the endo product
with an (S)-configuration and 16% ee. The reuse of this cat-
alytic species was preceded with the addition of 10 mol %
more Cu(OTf)2 thus leading in the second run to a more
active complex that also afforded the minor exo product
with 16% ee (Table 4, entry 2).
Mixing ligand 3b and acceptor 8c also afforded an active
catalyst that led to the formation of the endo product with
13% ee in the (2R)-configuration, and the exo product was
prepared with 38% ee. From all these results, it seems that,
albeit they probably possess different structures, all the pre-
pared complexes are active catalysts for the preparation of
the expected products at various temperatures with very
similar diastereoselectivities. The enantiofacial differentia-
tion is, however, much more sensitive to these structural
variations since the homodimeric complexes arising from
the acceptor series markedly favour the enantioselectivity
of the minor exo isomer (see Table 2, entries 2–4 and Table
3, entries 3 and 4). Contrarily, the homodimeric complexes
prepared with the donor ligands 3b and 3c (Table 2 entry 1
and Table 3, entries 1 and 2) afforded the major endo com-
pound with a higher enantioselectivity. From Table 4—en-
try 3, it is interesting to note that the configuration of the
major enantiomer of the endo product (2R) is probably dri-
ven by ligand 3b, while the enantioselectivity of the exo
counterpart by ligand 8c (2S), is in complete accordance
with the above-mentioned observations.
Mixing both ligands in the presence of 25 mol % copper tri-
flate also led to the preparation of an active catalyst that
could be successfully reused. The results in terms of enantio-
selectivity indicated that probably several species were pres-
ent in solution since both compounds were recovered with
different enantiomeric excesses: the endo product with 19%
ee and the exo compound with 46% ee. The lowering of the
temperature (Table 3, entry 7) improved the enantiomeric ex-
cess of the endo diastereoisomer (up to 36%) but had no influ-
ence on the exo product. It can be concluded that the
homodimeric complexes formed from the donor or the
acceptor ligands gave the best enantioselectivities, either on
the endo or on the exo compound, respectively. When both
ligands are present, it is difficult to conclude on the structure
of the active species. From a descriptive point of view, it
should be noted that the colour of the reaction mixture varies
markedly depending on the species present in solution. When
Table 3. Catalytic tests with tert-leucinol-type ligands
Entrya
Ligand
T (°C)
Convb (%)
Yieldc (%)
endo/exod
endo eee (%) (config)
exo eee (%) (config)
1 1st run
2 2nd run
3 1st run
4 2nd run
5 1st run
6 2nd run
7 1st run
3c
3c
ꢀ15
ꢀ65
ꢀ15
ꢀ65
ꢀ15
ꢀ15
ꢀ65
100
24
68
90
20
60
40
90
90
55
84/16
88/12
86/24
79/21
81/19
83/17
87/13
42 (2S)
28 (2S)
<5
<5
<5
8c
70 (2S)
73 (2S)
46 (2S)
46 (2S)
47 (2S)
8c
48
<5
3c/8cf
3c/8cf
3c/8cf
100
100
60
19 (2S)
19 (2S)
36 (2S)
a Conditions: Cu(OTf)2 25 mol % (0.082 mmol), ligand 22 mol % (0.072 mmol) in 500 lL anhydrous CH2Cl2, oxazolidinone (0.33 mmol) in 250 lL
anhydrous CH2Cl2, cyclopentadiene (2.4 mmol, 200 lL), 15 h, molecular sieves.
b Determined by 1H NMR spectroscopy.
c Isolated yield.
d Diastereoselectivity determined by 1H NMR spectroscopy.
e Enantioselectivity determined by chiral HPLC analysis, absolute configuration was assigned by comparison (see Ref. 21 and Section 4).
f 11 mol % of each ligand.

O. Chuzel et al. / Tetrahedron: Asymmetry 19 (2008) 1010–1019
1015
Table 4. Catalytic tests with mixed ligands
Entrya
Ligand
T (°C)
Convb (%)
Yieldc (%)
endo/exod
endo eee (%) (config)
exo eee (%) (config)
1 1st run
2 2nd run
3 1st run
3c/8a
3c/8af
3b/8c
ꢀ15
ꢀ15
ꢀ15
40
100
100
35
90
90
83/17
80/20
80/20
16 (2S)
16 (2S)
13 (2R)
<5
16 (2S)
38 (2S)
a Conditions: Cu(OTf)2 25 mol % (0.082 mmol), each ligand 11 mol % (0.036 mmol) in 500 lL anhydrous CH2Cl2, oxazolidinone (0.33 mmol) in 250 lL
anhydrous CH2Cl2, cyclopentadiene (2.4 mmol, 200 lL), 15 h, molecular sieves.
b Determined by 1H NMR spectroscopy.
c Isolated yield.
d Diastereoselectivity determined by 1H NMR spectroscopy.
e Enantioselectivity determined by chiral HPLC analysis, absolute configuration was assigned by comparison (see Ref. 21 and Section 4).
f 10 mol % Cu(OTf)2 are added.
3. Conclusion
4. Experimental
In conclusion, we have reported the synthesis of new
mono(oxazoline) ligands from three different amino alco-
hols and bearing either an electron-rich anthracene group
or an electron-poor trinitrofluorenone substituent. In the
presence of copper triflate as a pre-catalyst, all ligand com-
binations that were tested proved to lead to active and
enantioselective catalysts in the Diels–Alder reaction be-
tween cyclopentadiene and 3-but-2-enoyl-oxazolidin-2-
one. When using only one mono(oxazoline) ligand in the
catalysis,23 the best results were obtained in terms of
enantioselectivity for either the endo or the exo product,
according to the presence of the anthracene or trinitroflu-
orenone group. In those cases, it can be proposed that
the interactions of type p-stacking are involved for favour-
ing the formation of bidentate homodimeric complexes as
efficient catalysts in asymmetric catalysis. Mixing one elec-
tron-deficient and one electron-rich ligand also afforded ac-
tive Diels–Alder catalysts as the first examples of bidentate
ligands assembled by charge-transfer interactions. As a
weak assembling is, however, involved, the formation of
the heterodimeric complex is probably not largely favoured
and a mixture of different species, as equilibria in solution,
is present leading to lower enantioselectivities for the ex-
pected products. For favouring the privileged formation
of the heterodimeric complex, the structure of the targeted
ligands will be modified towards a more rigid and/or short-
er link between the donor–acceptor centre and the catalytic
site. These assemblies by charge-transfer interactions fur-
thermore allow the easy preparation of new catalysts bear-
ing oxazoline groups that are not symmetrical. The
synthesis of corresponding bis(oxazolines) from different
amino-alcohols is indeed not straightforward,12 but some
of them were already particularly active in targeted
transformations. Guiry et al. reported the efficient use of
non-symmetric bis(oxazoline) ligands in the asymmetric
methallylation of various aldehydes.12d We aim to test
our new catalytic systems in such a type of transforma-
tions. Finally, we have shown that our catalysts can be eas-
ily recovered by precipitation through pentane addition
and could be reused several times with no loss in their effi-
ciency. Work is currently in progress in our laboratory to
improve the ligand structures and to optimize the charge
transfer interactions for favouring the formation of hetero-
dimer combinations with both enhanced activities and
enantioselectivities.
4.1. General
All reactions were carried out under argon in oven-dried
glassware with magnetic stirring. Solvents were distilled be-
fore use from calcium hydride. Cyclopentadiene was dis-
tilled by cracking dicyclopentadiene over calcium
1
hydride. H NMR spectra were recorded on a BRUKER
AM 250 (250 MHz), AM 300 (300 MHz) or AM 360
(360 MHz) as CDCl3 solutions, and data are reported in
ppm relative to the solvent (7.27 ppm). 13C NMR spectra
were recorded on a BRUKER AM 250 (62.5 MHz) as
CDCl3 solutions and data are reported in ppm relative to
the solvent (77.0 ppm). Optical rotations were measured
as solutions in 10 cm cells using a PERKIN ELMER 241
polarimeter. Melting points were measured with a Reichert
instrument. Mass spectra were recorded on a Finnigan
MAT 95 S spectrometer. HPLC analyses were carried out
on a PERKIN–ELMER chromatograph equipped with a
diode array UV detector using an IA or a WHELK col-
umn. IR spectra were recorded as KBr disks using a PER-
KIN–ELMER spectrometer. Elemental analyses were
performed by the C.N.R.S. Service of Microanalyses in
Gif-sur-Yvette (France). 4-(9-Anthrylmethoxy)-4-oxobuta-
noic acid 1 was prepared according to Ref. 14. 2,5,7-trini-
tro-9-oxo-9H-fluorene-4-carboxylic acid 4 was synthesized
from 9-oxo-9H-fluorene-4-carboxylic acid24 following the
procedure described in Ref. 16. (E)-3-but-2-enoyloxazoli-
din-2-one was prepared according to the procedure de-
scribed in Ref. 11.
4.1.1. 2,5,7-Trinitro-9-oxo-9H-fluorene-4-carboxylic acid 4-
hydroxy-butyl ester 5. In an oven-dried flask and under
an argon atmosphere, 2,5,7-trinitro-9-oxo-9H-fluorene-4-
carboxylic acid (5.00 g, 13.9 mmol, 1.0 equiv) was dissolved
in 30 mL CH2Cl2. Oxalyl chloride (3.6 mL, 41.7 mmol,
3.0 equiv) was added at room temperature followed by 3
drops of DMF. The mixture was stirred for 1 h at room
temperature until effervescence stopped, and then oxalyl
chloride in excess was removed under reduced pressure.
In a 50 mL flask under argon, butane-1,4-diol (11.6 mL,
130.9 mmol, 10.0 equiv), pyridine (2.4 mL, 29.4 mmol,
2.1 equiv) were dissolved in anhydrous dichloromethane
(5 mL). This solution was transferred under argon to the
freshly prepared acylchloride and further stirred overnight
at room temperature. The solution was hydrolyzed with an

1016
O. Chuzel et al. / Tetrahedron: Asymmetry 19 (2008) 1010–1019
aqueous solution of HCl 1 N (20 mL). The aqueous layer
was extracted with CH2Cl2 (2 ꢁ 20 mL), and the combined
organic layers were dried over MgSO4, filtered and concen-
trated in vacuum. The residue was purified by chromato-
graphy on silica gel (CH2Cl2/AcOEt, 90/10) to afford
product 5 as a yellow solid (4.6 g, 77% yield).
4.1.4. (Anthracen-10-yl)methyl 3-((S)-1-hydroxy-3-methyl-
butan-2-ylcarbamoyl)propanoate 2a. C24H27NO4 (393.48).
86% yield. Beige powder. Mp = 179–180 °C. Rf (in AcOEt/
cyclohexane, 70/30) = 0.09. 1H NMR (300 MHz in
CDCl3): d 0.88 (3H, d, 3J = 6.8 Hz); 0.91 (3H, d,
3J = 6.8 Hz); 1.70–1.90 (1H, m); 2.40–2.75 (4H, m); 3.50–
3.65 (3H, m); 5.74 (1H, d, 3J = 7.2 Hz); 6.14 and 6.20
(2H, 2d, 3J = 12,5 Hz); 7.50–8.02 (4H, m); 8.03 (2H, d,
C18H13N3O10 (431.31). Yellow powder. Mp = 173–175 °C.
1
3
Rf (in CH2Cl2/MeOH, 98/2) = 0.80. H NMR (300 MHz,
3J = 8.3 Hz); 8.32 (2H, d, J = 8.3 Hz); 8.50 (1H, s). 13C
in CDCl3): d 1.67 (1H, s); 1.68–1.77 (2H, m); 1.92–1.97
(2H, m); 3.76 (2H, t, 3J = 6.4 Hz); 4.44 (2H, t,
3J = 6.4 Hz); 8.76–8.95 (4H, m). 13C NMR (62.5 MHz in
CDCl3): d 25.6; 28.3; 61.9; 64.3; 113.9; 123.0; 125.9;
126.9; 127.8; 129.6; 133.1; 134.1; 134.2; 134.8; 135.6;
147.0; 169.1; 182.1. MS (ESIꢀ) m/z: 431.0 [Mꢀ1] (100%).
Anal. Calcd for C18H13N3O10 C, 50.12; H, 3.04; N, 9.74,
O 37.09. Found: C, 50.17; H, 2.98; N, 9.47. IR (KBr): m
1050; 1089; 1159; 1232; 1342; 1466; 1542; 1594; 1617;
1738; 2874; 3091; 3300.
NMR (62.5 MHz in CDCl3): d 18.7; 19.3; 28.9; 29.7;
31.2; 57.1; 59.2; 63.5; 123.8; 125.1; 125.9; 126.7; 129.0;
129.2; 130.9; 131.3; 172.3; 173.3. MS (ESI+) m/z: 416
[M+Na+] (100%). HRMS (ESI+) m/z calcd for
C24H27NO4Na: 416.1832, found: 416.1846. IR (KBr): m
1063; 1169; 1385; 1434; 1559; 1639; 1725; 2870; 2929;
3087; 3293.
4.1.5.
3-((S)-1-Hydroxy-3-methylbutan-2-ylcarbamoyl)-
propyl 2,5,7-trinitro-9-oxo-9H-fluorene-4-carboxylate 7a.
C23H22N4O11 (530.44). 85% yield. Brown powder.
Mp = 83 °C. Rf (in AcOEt/cyclohexane, 70/30) = 0.81.
4.1.2. 2,5,7-Trinitro-9-oxo-9H-fluorene-4-carboxylic acid 3-
carboxy-propyl ester 6. A solution of sulfuric acid
(0.8 mL, 14.0 mmol, 1.5 equiv), CrO3 (1.86 g, 18.6 mmol,
2.0 equiv) and water (2.7 mL, 149.0 mmol, 16.0 equiv)
was added slowly to a solution of 5 (4.02 g, 9.3 mmol,
1.0 equiv) in acetone (16 mL). The black mixture was stir-
red for 40 min at room temperature, and then diluted with
Et2O (20 mL) and water (20 mL). The aqueous layer was
extracted with CH2Cl2 (2 ꢁ 20 mL), and the combined or-
ganic layers were dried over MgSO4, filtered and concen-
trated in vacuum. The residue was precipitated in a
Et2O/CH2Cl2 (9/1) mixture, filtered, washed with Et2O,
and dried in vacuum to afford a yellow powder (3.44 g,
83% yield).
1H NMR (250 MHz in CDCl3):
d 0.94 (3H, d,
3J = 4.7 Hz); 0.97 (3H, d, 3J = 4.7 Hz); 1.85–1.93 (1H,
m); 2.17–2.25 (2H, m); 2.46 (2H, t, 3J = 7.0 Hz); 3.60–
3.80 (3H, m); 4.40–4.50 (2H, m); 5.78 (1H, d, 3J =
7.3 Hz); 8.77 (1H, d, 4J = 2.2 Hz); 8.84 (1H, d,
4J = 1.9 Hz); 8.87 (1H, d, 4J = 2.4 Hz); 8.95 (1H, d,
4J = 1.9 Hz). 13C NMR (62.5 MHz in CDCl3): d 18.9;
19.5; 24.7; 29.0; 32.8; 57.2; 63.9; 66.8; 121.9; 122.6; 125.3;
130.6; 132.2; 137.8; 138.9; 139.8; 143.6; 146.6; 149.4;
149.7; 164.5; 172.6; 184.9. MS (ESI+) m/z = 553.3
[M+Na+] (100%). HRMS (ESI+) m/z calcd for
C23H22N4O11Na: 553.1177, found: 553.1173. IR (KBr): m
1088; 1180; 1233; 1346; 1451; 1538; 1593; 1614; 1713;
1742; 3090.
C18H11N3O11 (445.29). Yellow powder. Mp = 176 °C. Rf
1
(in CH2Cl2/AcOEt, 90/10) = 0.80. H NMR (300 MHz in
4.1.6. (Anthracen-10-yl)methyl 3-((R)-2-hydroxy-1-phenyl-
ethylcarbamoyl)propanoate 2b. C27H25NO4 (427.49). 88%
yield. Yellow powder. Mp = 160 °C. Rf (in AcOEt/cyclo-
CDCl3): d 2.13–2.23 (2H, m); 2.58 (2H, t; 3J = 7.0 Hz);
4.30–4.60 (2H, m); 8.75–8.84 (4H, m). 13C NMR
(62.5 MHz in CDCl3): 26.4; 30.9; 64.6; 114.1; 123.0;
126.1; 126.9; 127.8; 129.6; 133.1; 134.1; 134.4; 134.8;
135.6; 147.0; 169.1; 179.7; 182.1. MS (ESIꢀ) m/z: 370.0
(100%); 444.0 [Mꢀ1] (46%). HRMS (ESIꢀ) m/z calcd for
C18H10N3O11: 444.031, found: 444.031. IR (KBr): m 1088;
1180; 1233; 1315; 1345; 1451; 1537; 1593; 1614; 1713;
1742; 2880; 3090; 3567; 3819.
1
hexane, 40/60 + 1% Et3N) = 0.48. H NMR (250 MHz in
CDCl3): d 2.50–2.60 (2H, m); 2.70–2.80 (2H, m); 3.81
(2H, br s); 4.90–5.10 (1H, m); 6.18 (2H, s); 6.42 (1H, br
s); 7.40–7.50 (5H, m); 7.50–7.61 (4H, m); 8.04 (2H, d,
3
3J = 9.8 Hz); 8.33 (2H, d, J = 10.6 Hz); 8.50 (1H, s). 13C
NMR (62.5 MHz in CDCl3): d 29.4; 30.8; 55.7; 59.0;
66.2; 123.7; 123.9; 125.1; 125.6; 126.7; 127.9; 128.8; 129.1;
129.3; 131.0; 131.3; 138.8; 171.8; 173.2. MS (ESI+)
m/z = 450.1 [M+Na+] (100%). HRMS (ESI+) m/z calcd
for C27H25NO4Na: 450.1676, found : 450.1682. IR (KBr):
m 1060; 1158; 1321; 1375; 1425; 1644; 1718; 2925; 3058;
3081; 3300.
4.1.3. b-Hydroxy-amides: general procedure. In a 100 mL
flask under argon, acid 1 or 6 (7.7 mmol, 1.0 equiv), and
HOBt (1.20 g, 8.5 mmol, 1.1 equiv) were dissolved in
CH2Cl2 (70 mL). Next, EDC (1.5 mL, 8.5 mmol, 1.1 equiv)
dissolved in CH2Cl2 (10 mL) was added at 0 °C and the
mixture was stirred for 1 h. The amino alcohol (9.2 mmol,
1.2 equiv) in CH2Cl2 (15 mL) was added dropwise, and the
solution was stirred overnight at room temperature. The
solution was quenched with an aqueous HCl 3 M solution
(20 mL). The aqueous layer was extracted with CH2Cl2
(2 ꢁ 20 mL), and the combined organic layers were dried
over MgSO4, filtered and concentrated in vacuum. The res-
idue was purified by chromatography on silica gel
(CH2Cl2/AcOEt, 20/80, 1% Et3N, then AcOEt 100%, 1%
Et3N) to afford the desired product.
4.1.7.
3-((R)-2-Hydroxy-1-phenylethylcarbamoyl)propyl
2,5,7-trinitro-9-oxo-9H-fluorene-4-carboxylate 7b. C26H20-
N4O11 (564.46). 14% yield. Purple powder. Mp = 223 °C.
1
Rf (in AcOEt/cyclohexane, 40/60 + 1% Et3N) = 0.57. H
NMR (300 MHz in CDCl3): d 2.05–2.20 (2H, m); 2.36–
2.48 (2H, m); 3.27 (1H, br s); 3.66–3.82 (2H, m); 4.48
(2H, t, 3J = 6.0 Hz); 5.10–5.15 (1H, m); 6.75 (1H, d,
3J = 7.3 Hz); 7.08–7.32 (5H, m); 8.63 (1H, s); 8.79 (2H, s);
8.88 (1H, s). 13C NMR (62.5 MHz in CDCl3): d 24.3;
32.6; 55.5; 66.0; 66.7; 121.7; 122.4; 125.2; 126.5; 127.5;

O. Chuzel et al. / Tetrahedron: Asymmetry 19 (2008) 1010–1019
1017
128.5; 130.5; 131.9; 137.6; 138.7; 139.0; 139.5; 143.3; 146.3;
149.2; 149.4; 164.4; 172.3; 184.9. MS (ESI+) m/z = 304.2
(100%); 587.0 [M+Na+] (46%). HRMS (ESI+) m/z calcd
for C26H20N4O11Na: 587.1026, found: 587.1016. IR
(KBr): m 1742; 1088; 1180; 1233; 1346; 1451; 1538; 1593;
1614; 1615; 1713; 3090.
m); 6.15 (2H, s); 7.44–7.58 (4H, m); 7.98 (2H, d,
3
3J = 7.6 Hz); 8.33 (2H, d, J = 8.2 Hz); 8.44 (1H, s). 13C
NMR (62.5 MHz in CDCl3): d 17.9; 18.5; 23.1; 30.5;
32.3; 58.8; 69.9; 71.8; 123.8; 124.9; 126.0; 126.4; 128.9;
129.0; 130.9; 131.2; 165.5; 172.3. MS (ESI+) m/z = 398.1
[M+Na+] (100%). HRMS (ESI+) m/z calcd for
C24H25NO3Na: 398.1727, found: 398.1729. IR (CaF2 in
CHCl3): m 1159; 1211; 1384; 1447; 1499; 1527; 1625; 1672;
4.1.8. (Anthracen-10-yl)methyl 3-((S)-1-hydroxy-3,3-dimethyl-
butan-2-ylcarbamoyl)propanoate 2c. C25H29NO4 (407.50).
31% yield. Yellow oil. Rf (in AcOEt/cyclohexane, 40/
25
25
1735; 2905; 3031. ½aꢂ589 ¼ ꢀ28; ½aꢂ436 ¼ ꢀ56 (c 0.5, CHCl3).
1
60 + 1% Et3N) = 0.56. H NMR (250 MHz in CDCl3): d
4.1.12. 3-((S)-4,5-Dihydro-4-isopropyloxazol-2-yl)propyl
0.88 (9H, s); 2.40–2.55 (2H, m); 2.60–2.75 (2H, m); 3.35–
3.60 (1H, m); 3.70–3.90 (2H, m); 6.02 and 6.10 (2H, 2d,
3J = 12.3 Hz); 6.26 (1H, d, 3J = 9.8 Hz); 7.40–7.55 (4H,
2,5,7-trinitro-9-oxo-9H-fluorene-4-carboxylate 8a. C23H20-
N4O10 (512.43). 90% yield. Brown powder. Mp = 137–
140 °C. Rf (in AcOEt/cyclohexane, 40/60 + 1% Et3N) =
0.30. 1H NMR (360 MHz in CDCl3): d 0.88 (3H, d,
3
3
m); 7.91 (2H, d, J = 8.2 Hz); 8.25 (2H, d, J = 8.9 Hz);
8.36 (1H, s). 13C NMR (62.5 MHz in CDCl3): d 26.6;
29.6; 31.0; 33.3; 59.0; 59.3; 62.1; 123.7; 124.9; 125.7; 126.4;
128.8; 129.0; 130.7; 131.1; 172.5; 173.3. MS (ESI+) m/z =
430.1 [M+Na+] (100%). HRMS (ESI+) m/z calcd for
C25H29NO4Na: 430.1989, found: 430.1996. IR (CaF2 in
CHCl3): m 1048; 1250; 1390; 1450; 1602; 1720; 2976; 3443.
3
3J = 6.8 Hz); 0.95 (3H, d, J = 6.6 Hz); 1.71–1.77 (1H, m);
2.10–2.25 (2H, m); 2.45–2.55 (2H, m); 3.85–4.10 (2H, m);
4.23 (1H, dd, 2J = 7.9 Hz, 3J = 9.2 Hz); 4.46 (2H, t,
3J = 6.6 Hz); 8.75–8.94 (4H, m). 13C NMR (62.5 MHz in
CDCl3): d 18.1; 18.7; 24.4; 25.0; 32.6; 66.6; 70.1; 72.1;
121.8; 122.5; 125.3; 130.5; 132.4; 137.8; 138.8; 139.7;
143.5; 146.7; 149.4; 149.6; 164.4; 166.0; 185.0. MS (ESI+)
m/z = 513.1 [M+1] (100%); 535.1 [M+Na+] (72%). HRMS
(ESI+) m/z calcd for C23H21N4O10: 513.1252, found:
513.1255. IR (CaF2 in CHCl3): m 1088; 1175; 1234; 1341;
1459; 1508; 1536; 1542; 1615; 1649; 1718; 1738; 2905;
4.1.9. 3-((S)-1-Hydroxy-3,3-dimethylbutan-2-ylcarbamoyl)-
propyl 2,5,7-trinitro-9-oxo-9H-fluorene-4-carboxylate 7c.
C24H24N4O11 (544.47). 67% yield. Purple powder.
Mp = 163–164 °C. Rf (in AcOEt/cyclohexane, 40/60 + 1%
1
25
25
Et3N) = 0.61. H NMR (360 MHz in CDCl3): d 0.94 (9H,
3010. ½aꢂ589 ¼ ꢀ35; ½aꢂ436 ¼ ꢀ102 (c 0.3, CHCl3).
3
s); 2.15–2.30 (2H, m); 2.50 (2H, t, J = 7.2 Hz); 3.45–3.65
(1H, m); 3.80–3.90 (2H, m); 4.40–4.55 (2H, m); 5.83 (1H,
d, 3J = 9.2 Hz); 8.74 (1H, d, 4J = 2.2 Hz); 8.80 (1H, d,
4J = 1.9 Hz); 8.86 (1H, d, 4J = 2.2 Hz); 8.92 (1H, d,
4J = 2.2 Hz). 13C NMR (62.5 MHz in CDCl3): d 24.8;
26.9; 33.0; 33.4; 59.6; 63.1; 66.9; 121.9; 122.6; 125.3;
130.7; 132.2; 137.8; 138.9; 139.1; 143.2; 146.7; 149.4;
149.6; 164.6; 173.0; 185.1. MS (ESI+) m/z = 567.1
[M+Na+] (100%). HRMS (ESI+) m/z calcd for
C24H24N4O11Na: 567.1334, found: 567.1337. IR (CaF2 in
CHCl3): m 1047; 1265; 1364; 1390; 1450; 1543; 1601; 1710;
1739; 2895; 2976.
4.1.13. (Anthracen-10-yl)methyl 3-((R)-4,5-dihydro-4-phen-
yloxazol-2-yl)propanoate 3b. C27H23NO3 (409.48). 20%
yield. Yellow oil. Rf (in AcOEt/cyclohexane, 40/60 + 1%
Et3N) = 0.61. 1H NMR (300 MHz in CDCl3): d 2.40–
2
2.70 (4H, m); 3.85 (1H, dd, J = 3J = 8.3 Hz); 4.92 (1H,
dd, 2J = 3J = 8.5 Hz); 4.92 (1H, dd, 3J = 3J = 8.5 Hz);
6.02 (2H, s); 6.90–7.30 (9H, m); 7.84 (2H, dd,
3
3
4J = 1.7 Hz, J = 7.2 Hz); 8.18 (2H, d, J = 8.7 Hz); 8.30
(1H, s). 13C NMR (62.5 MHz in CDCl3): d 24.6; 32.7;
65.2; 66.8; 73.6; 121.8; 122.5; 124.4; 125.3; 125.3; 127.2;
128.3; 130.6; 132.2; 137.7; 138.8; 139.9; 140.4. MS (ESI+)
m/z = 432.1 [M+Na+] (100%). HRMS (ESI+) m/z calcd
for C27H23NO3Na: 432.1576, found: 432.1561. IR (CaF2
in CHCl3): m 1156; 1210; 1383; 1448; 1494; 1527; 1603;
4.1.10. Oxazolines: General cyclization procedure. In an
oven-dried schlenck under an argon atmosphere, DAST
(0.29 mL, 2.2 mmol, 1.1 equiv) was added dropwise to a
cold (ꢀ78 °C) solution of b-hydroxamide (2.0 mmol,
1.0 equiv) in anhydrous CH2Cl2 (12 mL). After stirring
for half an hour at ꢀ78 °C, anhydrous K2CO3 (0.4 g,
3.0 mmol, 1.5 equiv) was added in one portion and the mix-
ture was allowed to warm to ambient temperature. The
reaction was poured into saturated aqueous NaHCO3
and the biphasic mixture was extracted with CH2Cl2. The
combined organic extracts were dried over MgSO4, filtered
and concentrated in vacuum. Purification of the residue by
chromatography on silica gel (AcOEt/cyclohexane, 20:80,
Et3N 1 mol %) led to the desired oxazoline.
25
25
1668; 1732; 2925; 3030; 3059. ½aꢂ589 ¼ þ12; ½aꢂ436 ¼ þ24 (c
0.6, CHCl3).
4.1.14.
3-((R)-4,5-Dihydro-4-phenyloxazol-2-yl)propyl
2,5,7-trinitro-9-oxo-9H-fluorene-4-carboxylate 8b. C26H18-
N4O10 (546.44). 28% yield. Purple powder. Mp = 85 °C.
Rf (in AcOEt/cyclohexane, 40/60 + 1% Et3N) = 0.75.
1
NMR H (360 MHz in CDCl3): d 2.24–2.28 (2H, m); 2.59
(2H, t, 3J = 6.9 Hz); 4.09–4.13 (1H, m); 4.52 (2H, t,
3
3J = 6.4 Hz); 4.60–4.70 (1H, m); 5.19 (1H, t, J = 8.5 Hz);
3
7.22–7.35 (5H, m); 8.74 (1H, d, J = 2.2 Hz); 8.81 (1H, d,
3J = 2.2 Hz); 8.85 (1H, d, 3J = 2.2 Hz); 8.94 (1H, d,
3J = 2.2 Hz). NMR 13C (62.5 MHz in CDCl3): d 24.4;
24.9; 66.6; 69.6; 74.7; 121.8; 122.4; 125.2; 126.5; 127.5;
128.7; 130.5; 132.3; 137.7; 138.8; 139.7; 142.1; 143.5;
146.6; 149.3; 149.6; 164.5; 167.5; 185.0. MS (ESI+) m/z =
547.1 [M+1] (100%); 569.0 [M+Na+] (66%). HRMS
(ESI+) m/z calcd for C26H19N4O10: 547.1096, found:
547.1106. IR (CaF2 in CHCl3): m 1041; 1089; 1174; 1345;
4.1.11. (Anthracen-10-yl)methyl 3-((S)-4,5-dihydro-4-iso-
propyloxazol-2-yl)propanoate 3a. C24H25NO3 (375.46).
80% yield. Yellow powder. Mp = 57–58 °C. Rf (in
1
AcOEt/cyclohexane, 40/60 + 1% Et3N) = 0.44. H NMR
(250 MHz in CDCl3): d 0.80 (3H, d, 3J = 7.9 Hz); 0.88
(3H, d, 3J = 7.9 Hz); 1.57–1.65 (1H, m), 2.58–2.61 (2H,
m); 2.67–2.73 (2H, m); 3.71–3.83 (2H, m); 4.05–4.12 (1H,

1018
O. Chuzel et al. / Tetrahedron: Asymmetry 19 (2008) 1010–1019
1480; 1538; 1595; 1615; 1663; 1720; 1738; 2895; 3010.
½aꢂ589 ¼ þ33 (c 0.4, CHCl3).
s); 3.25 (1H, br s); 3.49–3.55 (1H, m); 3.87–4.08 (2H, m);
4.39 (2H, dd, 3J = 8.1 Hz, 3J = 8.1 Hz); 5.78 (1H, dd,
3J = 5.6 Hz, 3J = 2.9 Hz, endo); 6.15 (1H, dd, 3J =
5.7 Hz, 3J = 3.0 Hz, exo); 6.31 (1H, dd, 3J = 5.7 Hz,
25
4.1.15. (Anthracen-10-yl)methyl 3-((S)-4-tert-butyl-4,5-dihy-
drooxazol-2-yl)propanoate 3c. C25H27NO3 (389.49). 98%
yield. Yellow oil. Rf (in AcOEt/cyclohexane, 40/60 + 1%
3
3
3J = 3.1 Hz, exo); 6.43 (1H, dd, J = 5.7 Hz, J = 2.9 Hz,
endo).
1
Et3N) = 0.50. H NMR (300 MHz in CDCl3): d 0.79 (9H,
s); 2.40–2.75 (4H, m); 3.55–3.70 (1H, m); 3.85–4.05 (2H,
m); 6.07 (2H, s); 7.30–7.55 (4H, m); 7.88 (2H, d,
3J = 8.3 Hz); 8.20–8.35 (3H, m). 13C NMR (90 MHz in
CDCl3): d 22.9; 25.3; 30.3; 33.1; 58.5; 68.2; 75.2; 123.6;
124.7; 125.9; 126.2; 128.7; 128.8; 130.7; 131.0; 165.3;
172.0. MS (ESI+) m/z = 389.2 (32%). HRMS (EI) m/z
calcd for C25H27NO3: 389.1985, found: 389.1984. IR
(CaF2 in CHCl3): m 1156; 1210; 1383; 1448; 1494; 1527;
HPLC (Whelk 01, hexane/EtOH (99/1), flow:
0.8 mL minꢀ1
, k = 215 nm): tr = 36.4 min (exo (2R)),
tr = 38.2 min (exo (2S)), tr = 41.2 min (endo (2S)),
tr = 44.7 min (endo (2R)). The configurations were as-
signed by injections on an IA column (and comparison
with the literature).21
25
25
1603; 1668; 1732; 2925; 3030; 3059. ½aꢂ589 ¼ ꢀ2; ½aꢂ436
¼
Acknowledgements
ꢀ6 (c 0.4; CHCl3).
We thank CNRS and MENESR for their financial sup-
port. Emilie Kolodziej is gratefully acknowledged for tech-
nical assistance.
4.1.16.
3-((S)-4-tert-Butyl-4,5-dihydrooxazol-2-yl)propyl
2,5,7-trinitro-9-oxo-9H-fluorene-4-carboxylate 8c. C24H22-
N4O10 (526.45). 88% yield. Purple powder. Mp = 135–
140 °C. Rf (in AcOEt/cyclohexane, 40/60 + 1% Et3N) =
1
0.61. H NMR (250 MHz in CDCl3): d 0.87 (9H, s); 2.05–
References
2.20 (2H, m); 2.40–2.55 (2H, m); 3.70–3.85 (1H, m); 4.03
(1H, dd, 2J = 3J = 8.5 Hz); 4.16 (1H, dd, 3J = 8.5 Hz;
2J = 10.1 Hz); 4.43 (2H, t, 3J = 6.6 Hz); 8.72 (1H, d,
4J = 2.2 Hz); 8.78 (1H, d, 4J = 1.9 Hz); 8.80 (1H, d,
4J = 2.2 Hz); 8.90 (1H, d, 4J = 2.2 Hz). 13C NMR
(62.5 MHz in CDCl3): d 24.2; 24.9; 25.6; 33.4; 66.4; 68.5;
75.5; 121.6; 122.3; 125.2; 130.4; 132.1; 137.6; 138.7; 139.6;
143.4; 146.5; 149.2; 149.4; 164.2; 165.8. 184.9. MS (ESI+)
m/z = 527.1 [M+1] (100%); 549.1 [M+Na+] (42%). HRMS
(ESI) m/z calcd for C24H23N4O10: 527.1409, found:
1. Anastas, P. T.; Warner, J. C. Green Chemistry: Theory and
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4212; (d) Duursma, A.; Pena, D.; Minnaard, A. J.; Feringa,
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W. N. M.; Reek, J. N. H. J. Am. Chem. Soc. 2004, 126, 4056–
4057; (b) Reek, J. N. H.; Ro¨der, M.; Goudriaan, P. E.;
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527.1418. IR (KBr): m 1089; 1161; 1231; 1341; 1458; 1541;
25
1595; 1616; 1672; 1723; 1744; 2961; 3030. ½aꢂ589 ¼ ꢀ29;
25
½aꢂ436 ¼ ꢀ74 (c 0.5; CHCl3).
4.2. Catalytic tests
A schlenk tube was charged with Cu(OTf)2 (see the
quantities specified in each table) under argon. The com-
bined ligands (see tables) dissolved in CH2Cl2 (500 lL) were
added dropwise, and the complex was stirred for 3 h at room
temperature, and then cooled at the desired temperature. 3-
But-2-enoyl-oxazolidin-2-one (51 mg, 0.33 mmol, 1.0 equiv)
dissolved in CH2Cl2 (250 lL) was added via syringe, fol-
lowed by freshly cracked cyclopentadiene (200 lL,
2.4 mmol, 7.2 equiv). When the reaction was finished, pen-
tane (10 mL) was added to precipitate the complex. The
product solution was removed from the reaction vessel,
and the precipitate was washed twice more with pentane
before its reuse. The product solution is hydrolyzed with a
sat. NH4Cl solution (2 mL) and extracted with CH2Cl2.
The combined organic layers are dried over MgSO4 and
the products are purified on preparative TLC (toluene/ethyl
acetate 80/20).
4.2.1.
3-[[3-Methylbicyclo[2.2.1]hept-5-en-2-yl]carbonyl]-
oxazolidin-2-one (endo/exo mixture). 1H NMR (360
MHz in CDCl3): d 0.87 (3H, d, 3J = 7.0 Hz, exo); 1.13
(3 H, d, 3J = 7.0 Hz, endo); 1.48 (1H, d, 3J = 8.4 Hz);
3
1.66 (1H, d, J = 8.6 Hz); 2.02–2.15 (1H, m); 2.53 (1H, br

O. Chuzel et al. / Tetrahedron: Asymmetry 19 (2008) 1010–1019
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´
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monodentate ligands for asymmetric catalysis, see: Bonini, B.
ˇ
´
´
ˇ
´
ˇ
ˇ
`
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