Reusable chiral bis(oxazoline)-copper complexes immobilized by donor-acceptor interactions on insoluble organic supports

Article abstract of DOI:10.1016/j.catcom.2009.10.029

Heterogeneous asymmetric Diels-Alder reactions between cyclopentadiene and 3-but-2-enoyl-oxazolidin-2-one were efficiently promoted by reusable chiral bis(oxazoline)-copper catalysts, immobilized through charge transfer interactions with trinitrofluorenon

Full text of DOI:10.1016/j.catcom.2009.10.029

Catalysis Communications 11 (2010) 351–355
Contents lists available at ScienceDirect
Catalysis Communications
journal homepage: www.elsevier.com/locate/catcom
Reusable chiral bis(oxazoline)–copper complexes immobilized by donor–acceptor
interactions on insoluble organic supports
*
Guillaume Chollet, Dorian Didier, Emmanuelle Schulz
Equipe de Catalyse Moléculaire, ICMMO, UMR 8182, Université Paris-Sud XI, 91405 Orsay, France
a r t i c l e i n f o
a b s t r a c t
Article history:
Heterogeneous asymmetric Diels–Alder reactions between cyclopentadiene and 3-but-2-enoyl-oxazo-
lidin-2-one were efficiently promoted by reusable chiral bis(oxazoline)–copper catalysts, immobilized
through charge transfer interactions with trinitrofluorenone, that was covalently grafted on Merrifield
resins. The modified support was also used for the synthesis of both enantiomers of the target product,
thanks to the non-covalent anchoring of the catalyst that allowed its easy removal and exchange.
Ó 2009 Elsevier B.V. All rights reserved.
Received 23 September 2009
Received in revised form 23 October 2009
Accepted 29 October 2009
Available online 31 October 2009
Keywords:
Asymmetric catalysis
Heterogeneous catalysis
Charge-transfer complexes
Bis(oxazolines)
Diels–Alder reaction
1. Introduction
ligand’s structure concern non-covalent electrostatic interactions
of the charged complexes with ionic supports [9].
Extensive work has been devoted to the catalyzed synthesis of
enantio-enriched valuable synthons by chiral bis(oxazoline) com-
plexes [1]. Associated to various metals, these ligands were partic-
ularly efficient for the enantioselective formation of carbon–carbon
bonds, although these transformations generally suffered from a
high catalyst loading. The costs of both precious metal and opti-
cally pure ligand that are required to achieve satisfactory yields
of the expected products are dissuasive for an economical develop-
ment of these processes. To overcome these constraints, several
methods have been proposed towards an easy recovery and reuse
of the chiral catalysts [2]. These procedures are mainly based on
the heterogenization of the complex by a structural modification
of the bis(oxazoline) ligand. Its subsequent grafting on an insoluble
(organic [3] or inorganic [4]) support allows the catalytic reaction
to be performed under heterogeneous conditions and the catalyst,
recovered by simple filtration, is further reused. Some examples
have also been reported in which the structure of the ligand is
modified so that it can be polymerized, creating an insoluble cata-
lyst with the chirality present in the pendant groups or in the main
chain of the polymer [5]. Bis(oxazolines) have also been covalently
grafted onto soluble polymers [6], or used in non-conventional sol-
vents such as ionic liquids [7] or fluorous phases [8]. Other meth-
odologies that generally do not imply a drastic modification of the
We have reported the efficient reuse of chiral bis(oxazoline)–
copper catalysts in Diels–Alder reactions by their precipitation as
charge-transfer complexes (CTC) [10]. Several bis(oxazoline) li-
gands were substituted via a short methylene linker by an anthra-
cene moiety. The corresponding copper complexes were prepared
and charge-transfer complexes were synthesized by the addition
of trinitrofluorenone (TNF) as electron deficient moiety (Fig. 1).
At the end of the catalytic transformation promoted by these com-
plexes, pentane was added to the reaction mixture leading to the
precipitation of the catalysts. Removal of the products solution
for analysis was then followed by addition of new substrates to
the catalysts in the same reaction vessel for convenience. The effi-
ciency of this procedure was demonstrated in a Diels–Alder reac-
tion [11] between cyclopentadiene and 3-acryloyl-oxazolidin-2-
one to reach the expected endo product as major isomer (up to
97% de and 94% ee): the catalyst was used 12 times without loss
of either activity or selectivity.
The efficient use and recycling of these modified bis(oxazoline)
complexes is satisfying but the method should be improved to
avoid the addition of pentane for the precipitation of the complex
in a batch procedure. The ultimate goal of our work is to develop a
fixed-bed reactor for a continuous flow process, as the best way to-
wards an economic and environmentally friendly production of
enantio-enriched valuable products [12]. We thus report here our
preliminary results for the immobilization of bis(oxazoline)
complexes through charge-transfer interactions with trinitrofluo-
renone covalently grafted on solid supports and their use in
* Corresponding author. Tel.: +33 (0) 169157356; fax: +33 (0) 169154680.
E-mail address: emmaschulz@icmo.u-psud.fr (E. Schulz).
1566-7367/$ - see front matter Ó 2009 Elsevier B.V. All rights reserved.
doi:10.1016/j.catcom.2009.10.029

352
G. Chollet et al. / Catalysis Communications 11 (2010) 351–355
loading in chlorine of 1.89 mmol Cl/g. 10 eq. of hydrazine monohy-
drate (1.90 mL, caution toxic compound) was slowly added to 2 g
of this Merrifield resin (1.89 mmol Cl/g) in 12 mL of ethanol at
ambient temperature. At the end of the addition, the mixture
was mechanically stirred for 24 h at 60 °C. The resin was then fil-
tered, washed with water then with ethanol.
PS-B: A Merrifield polymer resin commercially available from
Acros Organics was used (2% crosslinked with DVB, 2.0–2.2
mmol Cl/g, 200–400 mesh) for the synthesis of TNF-PS-B. 10 eq.
of hydrazine monohydrate (1.95 mL, caution toxic compound)
was slowly added to 2 g of Merrifield resin (2.00 mmol Cl/g) in
12 mL of ethanol at ambient temperature. At the end of the addi-
tion, the mixture was mechanically stirred for 24 h at 60 °C. The re-
sin was then filtered, washed with water then with ethanol.
+
2
O
Cu
N
N
O
O
O2N
-
+ 2 OTf
O2N
NO2
2.3. TNF-PS-A
O
1.35 g of trinitrofluorenone (4.3 mmol) was dissolved in 57 mL
of toluene and 5.7 mL of acetic acid, then 2 g of hydrazine resin
(PS-A) was added. The mixture was mechanically stirred for 3 days
at room temperature. The resin was washed for 3 days with tolu-
ene in a soxhlet, then with pentane and was dried. Anal. Found:
C 79.48; H 7.25; N 3.53. The loading capacity was based on the
TNF mass balance and nitrogen elemental analysis and was found
to be 0.5 mmol/g.
Fig. 1. Charge-transfer complex structure for bis(oxazoline)–copper catalyst’s
recycling.
heterogeneous asymmetric catalysis. Our methodology involving
both a solid support, for a direct filtration without the need of an
additional precipitation procedure, and non-covalent donor–
acceptor interactions, for a reversible anchoring of targeted asym-
metric complexes, should allow the implementation of various
processes for a wide range of applications. Usually, indeed, the
same batch of heterogenized material, often prepared through long
and fastidious procedures, is only useful for one reaction type. To
overcome this difficulty, we propose to test a new immobilization
strategy based on non-covalent reversible interactions of type
charge transfer, between the support and the chiral organometallic
complex. This methodology should allow the facile exchange of
various catalysts on the support for a broad use in numerous enan-
tioselective transformations.
2.4. TNF-PS-B
1.29 g of trinitrofluorenone (4 mmol) was dissolved in 46 mL of
toluene and 4.6 mL of acetic acid, and then 2 g of hydrazine resin
(PS-B) was added. The mixture was mechanically stirred for 3 days
at room temperature. The resin was washed for 3 days with tolu-
ene in a soxhlet, then with pentane and was dried. Anal. Found:
C 77.51; H 6.53; N 5.76. The loading capacity was based on the
TNF mass balance and nitrogen elemental analysis and was found
to be 0.8 mmol/g.
2. Experimental section
2.5. Bis(oxazoline)-ent-3 (according to Ref. [10a])
2.1. General methods and materials
A 50 mL flask was charged with diethyl-malonimidate dihydro-
chloride (185 mg, 0.80 mmol), (1S,2R)-1-amino-2-indanol (250 mg,
1.67 mmol), and dry CH2Cl2 (18 mL). The mixture was heated un-
der reflux overnight. The resulting suspension was cooled to room
temperature, washed with water and extracted with CH2Cl2
(3 ꢀ 20 mL). The combined organic phases were dried over MgSO4,
and the solvent was removed under reduced pressure. The residue
was purified by recrystallization in propan-2-ol, giving the corre-
sponding bis(oxazoline) as a white solid (235 mg, 0.71 mmol, 89%
yield). 1H NMR (250 MHz, CDCl3) d 7.48–7.46 (m, 2H), 7.30–7.28
(m, 6H), 5.58 (d, 2H, J = 8.2 Hz), 5.39–5.34 (m, 2H), 3.40 (dd, 2H,
J = 7.0 Hz, J = 17.7 Hz), 3.29 (s, 2H), 3.18 (dd, 2H, J = 17.7 Hz,
J = 1.7 Hz). HRMS (ESI): calcd for C21H18O2N2Na (M + Na+):
353.1260, found: 353.1269.
All reactions were carried out under argon in oven-dried glass-
ware with magnetic or mechanic stirring. Solvents were distilled
before use: toluene and CH2Cl2 from calcium hydride, THF from so-
dium metal/benzophenone ketyl. Cyclopentadiene was distilled by
cracking dicyclopentadiene over calcium hydride. Bis(oxazoline) 3
was prepared as described in Ref. [10a].
1H NMR spectra were recorded on a Bruker AM 200 (200 MHz)
or AM 250 (250 MHz) as CDCl3 solutions and data are reported in
ppm relative to the solvent (7.27 ppm). 13C NMR spectra were re-
corded 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 at the sodium
D line, using a PERKIN ELMER 241 polarimeter. 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 a WHELK column. Elemental
analyses were performed by the CNRS. Service of Microanalyses in
Gif-sur-Yvette (France) for C, H, N.
A Schlenk tube was charged with dry THF (2 mL), TMEDA
(161
(445
l
L, 1.07 mmol) and iPr2NH (120
lL, 0.85 mmol). n-BuLi
lL, 1.6 M in hexanes) was added at ꢁ20 °C, and the mixture
was stirred at this temperature for 1 h. The above synthesized
bis(oxazoline) (235 mg, 0.71 mmol) was dissolved in THF (2 mL)
and LDA, prepared ex situ, was added at ꢁ20 °C to this solution.
The mixture was stirred for 3 h, then methanesulfonic acid 3-
(anthracen-9-ylmethoxy)-propyl ester (see Ref. [1]) (245 mg,
0.71 mmol) in THF (10 mL) was added at ꢁ20 °C. The mixture
was heated at 60 °C during 24 h. The solution was cooled, washed
with NH4Clsat and extracted with AcOEt (3 ꢀ 30 mL). The combined
organic phases were dried over MgSO4, and the solvent was
removed under reduced pressure. The residue was purified by flash
2.2. Hydrazine resin (see Ref. [13])
PS-A: The Merrifield resin leading to TNF-PS-A was synthesized
in the Laboratoire de Catalyse et Synthèse Organique (ICBMS, UMR
5246, Lyon) that is gratefully acknowledged for a gift. It is prepared
from Amberlite XAD1180 (Rohm & Haas Company) leading to a

G. Chollet et al. / Catalysis Communications 11 (2010) 351–355
353
chromatography (cyclohexane/AcOEt: 1/2, then AcOEt 100%), giv-
ing the expected anthracene-substituted bis(oxazoline) as a white
solid (52 mg, 0.09 mmol, 13% yield). 1H NMR (250 MHz, CDCl3) d
8.43 (s, 1H), 8.28 (d, 2H, J = 9.3 Hz), 7.98 (d, 2H, J = 9.3 Hz), 7.48–
7.43 (m, 6H), 7.26–7.18 (m, 6H), 5.51 (d, 2H, J = 7.8 Hz), 5.28–
5.23 (m, 4H), 3.52 (t, 2H, J = 6.3 Hz), 3.50–3.25 (m, 3H), 2.99 (d,
2H, J = 19.1 Hz), 1.97–1.91 (m, 2H), 1.51–1.46 (m, 2H). HRMS
(ESI): calcd for C39H34O3N2Na (M + Na+): 601.2462, found:
601.2486.
1H), 2.55 (bs, 1H), 2.13–2.09 (m, 1H), 1.73–1.70 (m, 1H), 1.48–
1.45 (m, 1H), 1.16 (d, 3H, J = 6.3 Hz). 13C NMR (62.5 MHz, CDCl3)
d 175.3, 154.0, 138.7, 132.2, 62.6, 50.8, 47.0, 43.8, 43.5, 43.4, 30.1.
3. Results and discussion
Trinitrofluorenone-modified polystyrene resins (TNF-PS) were
synthesized according to a procedure described by Lemaire’s group
[13]. The Merrifield resin was first treated with hydrazine monohy-
drate in ethanol and trinitrofluorenone was then introduced as a
toluene/acetic acid solution (Scheme 1). The resin was finally
washed with toluene by soxhlet extraction to yield the expected
TNF-PS. A thorough washing of the resin is of major importance
for the complete removal of hydrazine, as it can reduce Cu(II) to
Cu(I), [14] an unreactive catalyst in the Diels–Alder reaction. Two
modified supports were prepared arising from different sources
of polystyrene beads (see Section 2.2.). A first batch of resin
A Schlenk tube was charged with dry THF (2 mL), TMEDA
(23.5
(97
lL, 0.16 mmol) and iPr2NH (11 lL, 0.08 mmol). n-BuLi
L, 1.6 M in hexanes) was added at ꢁ20 °C, the mixture was
l
stirred at -20 °C for 1 h and was added at ꢁ20 °C to a solution of
the anthracene-substituted bis(oxazoline) (45 mg, 0.08 mmol) in
THF (2 mL). The mixture was stirred for 3 h. Then, MeI (15 lL,
0.24 mmol) was added at ꢁ20 °C. The mixture was heated at
60 °C during 24 h. The solution was cooled, washed with NH4Clsat
and extracted with AcOEt (3 ꢀ 10 mL). The combined organic
phases were dried over MgSO4, and the solvent was removed under
reduced pressure. The residue was purified by flash chromatogra-
phy (cyclohexane/AcOEt: 1/2), giving 46 mg of compound ent-3
(0.08 mmol, 96% yield). 1H NMR (250 MHz, CDCl3) d 8.43 (s, 1H),
8.31 (d, 2H, J = 9.3 Hz), 7.99 (d, 2H, J = 9.3 Hz), 7.48–7.46 (m, 6H),
7.26–7.12 (m, 6H), 5.51–5.47 (m, 2H), 5.29 (s, 2H), 5.27–5.16 (m,
2H), 3.53–3.50 (m, 2H), 3.27–3.18 (m, 2H), 2.94–2.78 (m, 2H),
2.01–1.88 (m, 2H), 1.45–1.41 (m, 2H), 1.39 (s, 3H). 13C NMR
(62.5 MHz, CDCl3) d 169.0, 141.9, 139.6, 139.5, 131.7, 131.2,
128.9, 128.5, 127.6, 126.4, 125.8, 125.5, 125.1, 124.9, 124.5, 83.4,
(TNF-PS-A) was synthesized possessing
a loading in TNF of
0.5 mmol/g and a particle size lower than 50 mesh, and another
batch was prepared (TNF-PS-B) with a higher loading in TNF
(0.8 mmol/g) and smaller particles (200–400 mesh).
To check our new immobilization procedure, we have tested the
anthracene-modified bis(oxazoline) ligand 3 derived from enantio-
merically pure (1R,2S)-1-amino-2-indanol associated to copper tri-
flate. The test reaction under homogeneous conditions implied the
cycloaddition between 3-but-2-enoyl-oxazolidin-2-one
2 and
cyclopentadiene 1 at room temperature in dichloromethane and
the chiral copper complex provided the desired endo product 4
with both a high diastereoselectivity (80%) and enantioselectivity
(78%, Scheme 2) [10a]. These values are in good accordance with
those reported in the literature with similar ligands. This transfor-
mation was indeed run under analogous operating conditions with
the ligand (3aS,3a0S,8aR,8a0R)-2,20-(cyclopropane-1,1-diyl)bis(8,8a-
dihydro-3aH-indeno[1,2-d]oxazole), developed by Sibi and his
group [15]. They obtained at room temperature the expected major
endo product with 83% ee and 78% de. By comparing these results
with ours, we assume that the introduction of the anthracene
group is not detrimental to the progress of the catalytic
transformation.
76.6, 70.8, 64.6, 39.9, 32.7, 24.5, 20.9. [
a
]
D
ꢁ122 (c = 1, CHCl3).
2.6. Diels–Alder reaction between cyclopentadiene and 3-(but-2-
enoyl)-oxazolidin-2-one
A Schlenk tube was charged with Cu(OTf)2 (0.033 mmol) and
the ligand (3 or ent-3) (0.036 mmol), dissolved in CH2Cl2
(650 lL), was added dropwise. The solution was stirred for 1 h.
Then, the newly formed complex was added to the resin TNF-PS
(0.144 mmol) and the mixture was stirred for 4 h. Then, 3-but-2-
enoyl-oxazolidin-2-one (0.33 mmol, 51 mg) was added as a solu-
tion in CH2Cl2 (650
lL) via syringe. Immediately thereafter, cyclo-
The chiral copper-3 complex was then tested as catalyst to per-
form the same transformation in the presence of the TNF-PS resins.
According to the TNF loading, the resins were used in a four-molar
excess compared to the copper catalyst (10 mol%). The evaluation
of the global loading in TNF is based on the TNF mass balance
and elemental analysis. As the exact amount of accessible TNF on
this resin is not easily measurable, we chose to use our recoverable
support in excess compared to the stoichiometry required for the
CTC formation.
The organometallic copper-3 complex was prepared ex situ from
ligand 3 and Cu(OTf)2 in dichloromethane as a green solution be-
fore its addition on the resin. Stirring was then pursued for 4 h
and both the acyloxazolidinone 2 and freshly distilled cyclopenta-
diene 1 were added in DCM. After completion of the reaction, the
pentadiene, freshly cracked, (200
l
L, 2.4 mmol) was added via
syringe. The resulting mixture was stirred at room temperature
for the specified amount of time. When the reaction was finished,
the products solution was removed by syringe from the Schlenk,
washed with NH4Clsat and extracted with CH2Cl2 (2 ꢀ 10 mL). The
combined organic phases were dried over MgSO4 and the solvent
was removed under reduced pressure. The residue was purified
by flash chromatography (toluene/ethylacetate: 80/20) and ana-
lyzed by HPLC for the determination of the de and ee (see below).
The resin in the Schlenk was washed twice with pentane and dried
under reduced pressure. New substrates were then added in
dichloromethane for a new run of the catalytic asymmetric
Diels–Alder reaction. For removing the organometallic complex
immobilized on the resin, the resin is additionally washed three
times with toluene (15 mL) prior to the introduction of a new
catalyst.
O2N
2.7. General procedure for HPLC analyses
NO2
i
ii
Cl
N
H
NH2
The ee for the major endo isomer was determined by HPLC anal-
ysis using a WHELK column (flow rate = 0.8 mL/min; 99% hexane,
1% ethanol, k = 215 nm), which resolves the two diastereoisomers
(exo1 tr = 35.4 min, exo2 tr = 36.8 min, endo1 tr = 40.3 min, endo2
N
H
N
O2N
tr = 42.8 min). 1H NMR (250 MHz, CDCl3)
d 6.38 (dd, 1H,
J = 5.8 Hz, J = 3.4 Hz), 5.82 (dd, 1H, J = 5.8 Hz, J = 3.4 Hz), 4.40 (t,
2H, J = 7.8 Hz), 4.03–3.87 (m, 2H), 3.55–3.47 (m, 1H), 3.29 (bs,
Scheme 1. Synthesis of the TNF-PS resins. Reagents and conditions: (i) NH2–NH2,
EtOH, 60 °C, 24 h; (ii) TNF, CH3COOH, toluene, RT, 3 days.

354
G. Chollet et al. / Catalysis Communications 11 (2010) 351–355
O
N
11 mol%
N
O
O
3
O
O
10 mol% Cu(OTf)2
N
1
+
O
+
RT, CH2Cl2, 3h
O
N
)
4
O
N
O
O
R
de 80 %
ee 78 % (2
O
2
O
Scheme 2. Diels–Alder reaction between cyclopentadiene and 3-but-2-enoyl-oxazolidin-2-one in the presence of copper-3 under homogeneous conditions.
solution was removed for products analysis and the resin was
washed twice with pentane. New substrates were then added in
DCM on the resin for the next run. The results obtained for the
catalysis in the presence of TNF-PS-A are collected in Table 1.
The first use of the immobilized copper-3 complex allowed the
synthesis of the expected endo product as major compound with
an excellent isolated yield (91%) and enantioselectivity (76%) in
18 h reaction time. The recorded activity and enantioselectivity
values are comparable to those obtained under homogeneous con-
ditions. Part of the catalytic transformation probably occurred in
solution for this first run since 46 h were further necessary to ob-
tain a high conversion in the second run. Yet, product 4 was again
obtained with the expected high selectivity. The third run was also
carried out with a high efficiency as a proof of concept for this new
immobilization strategy of bis(oxazoline)-based catalysts. The chi-
ral copper-complex associated to the resin by donor–acceptor
interactions was used again for three successive runs. Nevertheless
its reuses proceeded every time with a loss of activity indicating a
partial leaching of the catalyst. The selectivity values also de-
creased, probably due to a competitive racemic, non-catalyzed,
transformation of the substrates.
Some blank tests were performed to evaluate the exact role of
the CTC formation for the reuse of the chiral organometallic com-
plex. The catalysis was for example run under exactly similar con-
ditions, but in the presence of a Merrifield resin that was not
modified with an electrodeficient compound. The first run of the
reaction led, as expected to the desired product with an efficiency
similar to that obtained under homogeneous conditions (>95% con-
version, 78% ee). The same recycling procedure was performed and
the Merrifield support was subjected again to the introduction of
new substrates. After 20 h reaction time, only 50% of 3-but-2-en-
oyl-oxazolidin-2-one was transformed and the desired product
was isolated with 65% ee, indicating thus a slight adsorption of
the catalyst on the resin. A third run allowed only the formation
of 4 as traces. By comparison with results reported in Table 1,
and the steady formation of the enantio-enriched endo product 4
at the 6th run, the contribution of the CTC complex to maintain
the chiral copper-complex at a close proximity of the surface is
here verified.
However, the undeniable partial leaching of the catalyst via
these reversible CTC interactions could also be verified as follows.
A dichloromethane solution of ligand 3 with an equimolar amount
of added Cu(OTf)2 was stirred at room temperature for 4 h with
TNF-PS-B. The solution was then separated from the beads and
both substrates 1 and 2 were added to this filtrate. After 20 h reac-
tion time, product 4 was isolated with 78% ee, albeit with only 28%
yield. Thus, under our conditions, leaching of the catalyst from the
beads is obvious and the CTC interaction has still to be improved.
Another set of experiments was conducted by using TNF-PS-B
resin and immobilizing firstly copper-ent-3 complex, prepared
from (1S,2R)-1-amino-2-indanol, by charge-transfer interactions
(see Table 2). Product 4 possessing the expected (2S) configuration
was isolated in the two first runs with high yield and enantioselec-
tivity. The subsequent reuse of the catalyst in the next 3rd and 4th
run was accompanied with a significant loss of efficiency. To illus-
trate the possible use of the TNF-modified support with different
chiral catalysts thanks to the reversible grafting on the solid, cop-
per-ent-3 catalyst was removed after the 4th run by simple wash-
ing of the resin with toluene, a competitive solvent for the
formation of CTC with electrodeficient molecules. The same TNF-
PS-B batch reacted then with copper-3 complex. After addition of
the substrates in a 5th reaction run, product 4 possessing the oppo-
site configuration (2R) was isolated with the same enantiomeric
excess value than in the first catalytic run. The recycling of the
new catalyst followed then the same trend than its enantiomer
analogue. These experiments proved the validity of this new con-
cept for the successive non-covalent immobilization of different
Table 2
Heterogeneous Diels–Alder reaction between 1 and 2 with copper-3 and copper-ent-3
complexes in the presence of TNF-PS-B.
Run
t (h)
Conv (%)a
Yield (%)
de (%)b
ee 4 endo (%)b
Table 1
Heterogeneous Diels–Alder reaction between
immobilized by CTC interactions on TNF-PS-A.
1 and 2 with copper-3 complex
Copper-ent-3 catalyst
1st
46
46
72
72
100
100
79
82
81
62
32
76
76
73
67
73 (2S)
74 (2S)
62 (2S)
30 (2S)
2nd
3rd
4th
Run
t (h)
Conv (%)a
Yield (%)
de (%)b
ee 4 endo (%)b
1st
18
46
45
46
45
45
100
82
100
81
33
47
91
80
82
67
22
28
74
73
74
70
69
68
76 (2R)
71 (2R)
73 (2R)
63 (2R)
37 (2R)
39 (2R)
59
2nd
3rd
4th
5th
6th
Copper-3 catalyst
5th
6th
7th
8th
46
46
72
72
84
95
96
92
72
86
79
72
78
76
73
73
73 (2R)
72 (2R)
61 (2R)
52 (2R)
a
a
Determined by 1H NMR analysis.
Determined by HPLC chromatography (Whelk column, hexane/ethanol).
Determined by 1H NMR analysis.
Determined by HPLC chromatography (Whelk column, hexane/ethanol).
b
b

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Lett. 4 (2002) 3927–3930;
chiral catalysts on the same modified support. As far as we know,
such reuse of a support for performing another catalytic reaction,
here affording the opposite enantiomer, has never been described.
Our procedure could be interestingly evaluated as a new system to
perform asymmetric catalysis in a fixed-bed reactor, suitable for
different transformations. However and as very often observed
by using reversible interactions, some leaching of the catalyst
could not be avoided after several runs.
(b) E. Díez-Barra, J.M. Fraile, J.I. García, E. García-Verdugo, C.I. Herrerías, S.V.
Luis, J.A. Mayoral, P. Sánchez-Verdú, J. Tolosa, Tetrahedron: Asymmetry 14
(2003) 773–778;
4. Conclusion
(c) A. Mandoli, S. Orlandi, D. Pini, P. Salvadori, Chem. Commun. (2003) 2466–
2467;
(d) J.M. Fraile, J.I. García, C.I. Herrerías, J.A. Mayoral, Chem. Commun. (2005)
4669–4671.
We have described a new procedure for the recovery of chiral
bis(oxazoline)-based catalysts, involving the formation of charge-
transfer complexes with insoluble organic supports. Some valuable
preliminary results have been obtained for the promotion of the
Diels–Alder reaction. Work is still in progress to improve the resin
structure and optimize the charge-transfer interaction for a better
recycling of the system after several batches. For instance, new (or-
ganic and inorganic) supports are being prepared in which the
acceptor moiety is placed far away from the solid to favour its
accessibility. Furthermore, the inversion of the CTC interactions is
currently under progress, namely the introduction of the electron
poor moiety covalently on the active chiral organometallic site
and the use of an electron rich support, to study the catalyst leach-
ing under those conditions.
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Pitillo, J. Org. Chem. 66 (2001) 3160–3166;
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M. Vaultier, Green Chem. 6 (2004) 93–98;
(b) S. Doherty, P. Goodrich, C. Hardacre, J.G. Knight, M.T. Nguyen, V.I.
Pârvulescu, C. Paun, Adv. Synth. Catal. 349 (2007) 951–963.
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Eur. J. Org. Chem. (2003) 1191–1197;
(b) J. Bayardon, O. Holczknecht, G. Pozzi, D. Sinou, Tetrahedron: Asymmetry 17
(2006) 1568–1572.
[9] (a) Non-covalent interactions: J.M. Fraile, J.I. García, J.A. Mayoral, T. Tarnai,
Tetrahedron: Asymmetry 8 (1997) 2089–2092;
(b) Y. Wan, P. McMorn, F.E. Hancock, G.J. Hutchings, Catal. Lett. 91 (2003) 145–
148;
(c) P. O’leary, N.P. Krosveld, K.P. De Jong, G. van Koten, R.J.M. Klein Gebbink,
Tetrahedron Lett. 45 (2004) 3177–3180;
(d) H. Wang, X. Liu, H. Xia, P. Liu, J. Gao, P. Ying, J. Xiao, C. Li, Tetrahedron 62
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(e) J.M. Fraile, J.I. García, J.A. Mayoral, M. Roldán, Org. Lett. 9 (2007) 731–733;
(f) J.M. Fraile, J.I. García, J.A. Mayoral, Chem. Rev. 109 (2009) 360–417;
(g) J.M. Fraile, J.I. García, C.I. Herrerías, J.A. Mayoral, E. Pires, Chem. Soc. Rev. 38
(2009) 695–706.
To the best of our knowledge, this study is the first report of a
procedure involving the preparation of immobilized chiral cata-
lysts via reversible linkage for which the same batch of support
is suitable for the synthesis of different enantio-enriched
compounds.
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(b) G. Chollet, M.-G. Guillerez, E. Schulz, Chem. Eur. J. 13 (2007) 992–1000;
(c) O. Chuzel, C. Magnier-Bouvier, E. Schulz, Tetrahedron: Asymmetry 19
(2008) 1010–1019.
[11] (a) D.A. Evans, S.J. Miller, T. Lectka, P. von Matt, J. Am. Chem. Soc. 121 (1999)
7559–7573;
Acknowledgements
The CNRS and the MENESR are kindly acknowledged for finan-
cial support of this work.
(b) A.K. Ghosh, H. Cho, J. Cappiello, Tetrahedron: Asymmetry 9 (1998) 3687–
3691;
(c) I.W. Davies, C.H. Senanayake, R.D. Larsen, T.R. Verhoeven, P.J. Reider,
Tetrahedron Lett. 37 (1996) 1725–1726.
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