A new method for recycling asymmetric catalysts via formation of charge transfer complexes

Article abstract of DOI:10.1021/ol053036a

A new concept for recycling asymmetric bis(oxazoline)-type catalysts is reported. The formation of charge-transfer complexes between the chiral ligand and trinitrofluorenone and their subsequent precipitation and reuse by addition of new substrate solutions is described. The efficiency of this procedure is demonstrated in a Diels-Alder reaction to reach the expected endo product as major isomer (up to 97% de and 94% ee): the catalyst was used up to 12 times without loss of either activity or selectivity.

Full text of DOI:10.1021/ol053036a

ORGANIC
LETTERS
2006
Vol. 8, No. 3
539-542
A New Method for Recycling
Asymmetric Catalysts via Formation of
Charge Transfer Complexes
Guillaume Chollet, Fernand Rodriguez, and Emmanuelle Schulz*
Laboratoire de Catalyse Mole´culaire, Institut de Chimie Mole´culaire et des Mate´riaux
d’Orsay, UniVersite´ Paris Sud, Baˆt 420, 91405 Orsay, France
emmaschulz@icmo.u-psud.fr
Received December 14, 2005
ABSTRACT
A new concept for recycling asymmetric bis(oxazoline)-type catalysts is reported. The formation of charge-transfer complexes between the
chiral ligand and trinitrofluorenone and their subsequent precipitation and reuse by addition of new substrate solutions is described. The
efficiency of this procedure is demonstrated in a Diels−Alder reaction to reach the expected endo product as major isomer (up to 97% de and
94% ee): the catalyst was used up to 12 times without loss of either activity or selectivity.
A new concept for the recovery and recycling of asymmetric
bis(oxazoline)-type catalysts is reported: charge-transfer
complexes are formed between the chiral ligand and a
targeted electron-poor compound for their precipitation,
before their reuse in an asymmetric catalytic transformation.
Investigation of the formation of carbon-carbon bonds
by asymmetric catalysis is challenging particularly for the
improvement of enantioselectivity and for the increase of
the substrate-to-catalyst ratio. Among the enormous variety
of ligands tested for these transformations, bis(oxazolines)
led to highly active and enantioselective catalysts. Indeed,
associated with different metals, these ligands allowed
numerous C-C bonds to be formed very efficiently. How-
ever, a major drawback is the large quantity of catalyst
required for a total conversion in a reasonable time. To get
around this problem, numerous attempts for an efficient
recycling of the asymmetric catalysts have been published.
These results are presented in a recent exhaustive review.1
Most of the reported articles deal with the covalent im-
mobilization of various bis(oxazolines) on insoluble supports,
either on organic polymers (by grafting on commercially
available resins2 and via solid-phase synthesis)3 or on
inorganic materials.4 Although promising results have been
obtained, some decrease in yield and enantioselectivity is
(1) Rechavi, D.; Lemaire, M. Chem. ReV. 2002, 102, 3467.
(2) (a) Hallman, K.; Moberg, C. Tetrahedron: Asymmetry 2001, 12, 1475.
(b) Hocke, H.; Uozumi, Y. Synlett 2002, 2049. (c) Lundgren, S.; Lutsenko,
S.; Jo¨nsson, C.; Moberg, C. Org. Lett. 2003, 5, 3663. (d) Knight, J. G.;
Belcher, P. E. Tetrahedron: Asymmetry 2005, 16, 1415.
(3) (a) Weissberg, A.; Portnoy, M. Chem. Commun. 2003, 1538. (b)
Weissberg, A.; Halak, B.; Portnoy, M. J. Org. Chem. 2005, 70, 4556.
10.1021/ol053036a CCC: $33.50
© 2006 American Chemical Society
Published on Web 01/10/2006

Scheme 1. Synthesis of the New Bis(oxazoline)-Based Ligand 8
however observed due to a negative influence of the support
are reported here. Indeed, we aimed to recycle bis(oxazo-
line)-copper complexes by the formation of charge-transfer
complexes. Our procedure is based on a short synthesis of a
suitable enantiomerically pure ligand functionalized with an
electron-rich molecule (see Scheme 1). The formation of the
corresponding organometallic complex upon addition of
copper(II)-triflate is followed by the addition of an electron-
deficient molecule for the formation of a reversible charge-
transfer complex 9 (see Figure 1).
and/or partial leaching of the catalyst during the recyclings.5
The immobilization of bis(oxazoline) complexes has also
been performed on soluble organic polymers (i.e., poly-
(ethylene glycol)) to allow the catalytic transformation to
be run in an homogeneous phase before precipitation of the
catalyst for its reuse.6 To best preserve the local environment
around the catalytic site, insoluble systems have been
prepared by polymerization of properly functionalized bis-
(oxazolines) either by radical copolymerization7 or by
formation of a polyurethane chain polymer.8 To limit the
synthetic work required for the modification of the ligand
structure, immobilization methods involving noncovalent
interactions with the support have been developed. Mayoral’s
group has successfully supported bis(oxazoline)-copper
complexes by cation exchange in inorganic solids (laponite)
or organic polymers (Nafion-like solids).9 However, the
results obtained through these strategies are very dependent
on the catalyst structure, the solvent, and the substrate.
Alternatively, ionic liquids as “green solvents” have been
used to immobilize and recycle stable bis(oxazoline)-copper
complexes.10
Promising preliminary results on the development of a new
method for the efficient recycling of asymmetric complexes
(4) (a) Rechavi, D.; Lemaire M. Org. Lett. 2001, 3, 2493. (b) Burguete,
M. I.; Fraile, J. M.; Garcia, J. I.; Garcia-Verdugo, E.; Herrerias, C. I.; Luis,
S. V.; Mayoral, J. A. J. Org. Chem. 2001, 66, 8893.
Figure 1. Structure of the charge-transfer complex.
(5) Burguete, M. I.; Fraile, J. M.; Garc´ıa-Verdugo, E.; Luis, S.; V.;
Mart´ınez-Merino, V.; Mayoral, J. A. Ind. Eng. Chem. Res. 2005, 44, 8580.
(6) (a) Annunziata, R.; Benaglia, M.; Cinquini, M.; Cozzi, F.; Pitillo,
M. J. Org. Chem. 2001, 66, 3160. (b) Gissibl, A.; Finn, M. G.; Reiser, O.
Org. Lett. 2005, 7, 2325.
(7) (a) D´ıez-Barra, E.; Fraile, J. M.; Garc´ıa, J. I.; Garc´ıa-Verdugo, E.;
Herrer´ıas, C. I.; Luis, S. V.; Mayoral, J. A.; Sa´nchez-Verdu´, P.; Tolosa, J.
Tetrahedron: Asymmetry 2003, 14, 773 and references therein. (b) Mandoli,
A.; Orlandi, S.; Pini, D.; Salvadori, P. Chem. Commun. 2003, 2466.
(8) Rechavi, D.; Lemaire, M. J. Mol. Catal. A: Chem. 2002, 182-183,
239.
We have tested this methodology in the bis(oxazoline)-
copper-catalyzed Diels-Alder reaction developed by Evans.11
This transformation uses the catalytic system derived from
2,2′-isopropylidenebis[(4S)-4-tert-butyl-2-oxazoline] and cop-
per(II) and allows indeed the simultaneous formation of two
new carbon-carbon bonds in a highly diastereo- and
enantioselective fashion. However, a large amount of cata-
(9) Fraile, J. M.; Garc´ıa, J. I.; Herrer´ıas, C. I.; Mayoral, J. A.; Harmer,
M. A. J. Catal. 2004, 221, 532.
(10) Fraile, J. M.; Garc´ıa, J. I.; Herrer´ıas, C. I.; Mayoral, J. A.; Gmough,
S.; Vaultier, M. Green Chem. 2004, 6, 93.
(11) Evans, D. A.; Miller, S. J.; Lectka, T.; von Matt, P. J. Am. Chem.
Soc. 1999, 121, 7559
540
Org. Lett., Vol. 8, No. 3, 2006

lysts has to be used to get these good results and an efficient
recycling of the catalyst to allow a development of this
process is still lacking.
1). Complex 9 was then tested under similar conditions and
reused numerous times to optimize the procedure. The first
Complex 9 was thus tested in the aforementioned trans-
formation and then precipitated in the mixture after comple-
tion of the reaction. The product was removed from the
reaction vessel, and new solutions of reactants were added
to check the possibility of recycling catalyst 9.
Bis(oxazoline) 1 derived from indane was proved12 to be
an excellent copper ligand for the Diels-Alder reaction
between cyclopentadiene and 3-acryloyl-oxazolidin-2-one.
The modification of this structure by an anthracene func-
tionality was performed in a five-step synthesis. Com-
mercially available 9-chloromethyl-anthracene 2 was trans-
formed in a mesylated analogue 3. The indabox skeleton was
prepared by condensation of the imidate salt 4 with (1R,2S)-
(+)-cis-1-amino-2-indanol 5.13 Alkylation of 6 with 3
occurred after deprotonation with LDA in THF and methy-
lation afforded the targeted anthracene-modified new bis-
(oxazoline) 8.
Table 1. Copper-Catalyzed Diels-Alder Reaction between
Cyclopentadiene and 3-Acryloyl-oxazolidin-2-one 11
catalyst reuse time (h) T (°C) conv (%)b de (%) ee 12 (%)c
Cu-1a
20
20
44
44
44
20
20
7
3
1
1
0.5
-50 100
-50 100
-50 100
-50 100
92
95
93
95
93
93
96
91
94
92
88
92
91
97
88 (2R)
87 (2R)
84 (2R)
87 (2R)
87 (2R)
86 (2R)
91 (2R)
86 (2R)
87 (2R)
87 (2R)
90 (2R)
87 (2R)
87 (2R)
94 (2R)
Cu-8a
9a
9
9
9
9
9
9
9
9
9
9
9
1st
2nd
3rd
4th
5th
6th
7th
8th
9th
10th
11th
-50 100
-50 100 (91)
-65 100 (87)
-50 100 (85)
-50 100 (84)
-50 100 (86)
-65 90 (65)
-50 100 (92)
-50 100 (66)
-75 100 (95)
0.5
2
Complex 9 was prepared from a mixture of ligand 8 and
copper(II) triflate in dry dichloromethane followed by the
addition of trinitrofluorenone. The formation of the new
electron donor-acceptor complex was easily visible by the
immediate change of color (from green to red) corresponding
to a new absorption band (λmax 538 nm) in UV-visible
detection.14
We first examined the ability of the new bis(oxazoline)
ligand 8 associated to Cu(OTf)2 (Cu-8) to catalyze the
enantioselective Diels-Alder reaction between cyclopenta-
diene and 3-acryloyl-oxazolidin-2-one 11 depicted in Scheme
2. All of our catalytic tests were performed with 10 mol %
a 3-Acryloyl-oxazolidin-2-one (0.33 mmol), cyclopentadiene (2.40 mmol),
chiral catalyst (0.03 mmol), CH2Cl2 (1.3 mL). b Isolated yields are indicated
in brackets. c The product configuration was determined by comparison with
literature data.12
test was performed with a long reaction time (44 h) to ensure
a total conversion that was indeed obtained together with
excellent results in terms of diastereomeric and enantiomeric
excesses. Pentane was added at the end of the transformation,
leading to the precipitation of 9. The product solution was
removed for analysis, the complex was washed with pentane
and dried under vacuum, and substrates and solvent were
added to the same reaction vessel for the catalyst recycling.
Activity and enantioselectivity were maintained during
several recycling steps, and the reaction time was optimized.
Complete conversion could be achieved within less than 30
min (Table 1). Lowering the temperature (4th, 8th, and 11th
reuse) led to an increase in the enantiomeric excess (up to
94%) albeit with a slight decrease in the activity since 2 h
of reaction time was necessary to obtain a total conversion
at -75 °C. Reaction products were isolated in high yield
after each recycling procedure. This precipitation was also
performed to attempt to recover Cu-8, free of the charge
transfer complex. Under analogous conditions, this catalyst
could indeed be recovered but maintained its activity and
selectivity for only three reuses: the 4th recycling afforded
product 12 with 50% conversion and 73% enantiomeric
excess. The presence of the charge-transfer complex seems
necessary for an efficient recycling procedure.
Scheme 2. Diels-Alder Reaction between Cyclopentadiene
and 3-Acryloyl-oxazolidin-2-one 11 or
3-But-2-enoyl-oxazolidin-2-one 13
catalyst, as usually reported for this transformation. Cu-8
proved as efficient in activity and selectivity as Cu-1,
demonstrating that the presence of the anthracene group is
not detrimental to the enantiofacial discrimination (see Table
To confirm the reproducibility of the procedure, a separate
series of reactions was carried out under optimized condi-
tions, i.e., by reacting cyclopentadiene and 3-acryloyl-
oxazolidin-2-one 11 in the presence of 10 mol % complex 9
at -50 °C for a reaction time of 0.5 h. The results are
gathered in Table 2 with five efficient recyclings under those
conditions.
(12) Davies, I. W.; Senanayake, C. H.; Larsen, R. D.; Verhoeven, T. R.;
Reider, P. J. Tetrahedron Lett. 1996, 37, 1725.
(13) Hall, J.; Lehn, J. M.; DeCian, A.; Fischer, J. HelV. Chim. Acta 1991,
74, 1.
(14) Gil, R.; Fiaud, J.-C.; Poulin, J.-C.; Schulz, E. Chem. Commun. 2003,
2234.
To widen the scope of this procedure, the same catalyst
batch was also used in the presence of 3-but-2-enoyl-
(15) Ghosh, A. K.; Mathivanan, P.; Cappiello, J. Tetrahedron Lett. 1996,
37, 3815.
Org. Lett., Vol. 8, No. 3, 2006
541

lysts by precipitation of the corresponding charge-transfer
complexes. This original procedure improved the practicality
of the catalytic transformation by simple removal of the
product from the reaction vessel, subsequent washing of the
remaining catalyst, and addition of new solutions of reactants.
Complex 9 was thus used 12 times, leading to the expected
Diels-Alder endo products with high yield and enantiose-
lectivity.
Table 2. Diels-Alder Reaction between Cyclopentadiene and
11 or 13 in the Presence of Complex 9
substrate reuse time (h) T (°C) conv (%)b ee 12 (%)c ee 14 (%)d
11a
11
11
11
11
11
13
13
13
13
13
0.5
0.5
0.5
0.5
0.5
1
2.5
3
3
-50 83 (82)
-50 100 (91)
-50 100 (88)
-50 100 (95)
-50 79 (61)
-50 93 (92)
20 83
20 90 (90)
20 90 (87)
20 84 (72)
20 87 (85)
83 (2R)
84 (2R)
84 (2R)
85 (2R)
80 (2R)
84 (2R)
1st
2nd
3rd
4th
5th
6th
7th
8th
9th
10th
The diastereomeric and enantiomeric excesses afforded by
this procedure are identical to the results obtained by the
corresponding homogeneous system. No loss of catalytic
activity or enantioselectivity could be detected during numer-
ous recyclings, which demonstrates the high stability of the
complex.
nde
77 (2R)
78 (2R)
77 (2R)
77 (2R)
3
3
The formation of charge-transfer complexes to recover
chiral catalysts was thus proved to be a very efficient method
for an overall enormous saving of both precious chiral ligand
and metal.
a 11 or 13 (0.33 mmol), cyclopentadiene (2.40 mmol), chiral catalyst
(0.03 mmol), CH2Cl2 (1.3 mL). b Isolated yields are indicated in brackets.
c The product configuration was determined by comparison with literature
data.12 d The product configuration was determined by comparison with
literature data.15 e Not determined
Work is in progress to develop this new recycling concept
using other catalytic reactions. We also aim to use im-
mobilized trinitrofluorenone on insoluble supports toward
heterogeneous asymmetric catalysis in a continuous flow
reactor.
oxazolidin-2-one 13 as another dienophile. The reaction was
carried out at 20 °C, and the 6th recycling of the catalyst
led to the formation of the expected endo adduct 14. This
product was obtained together with traces of 12, probably
arising from coordination to the copper center of the
precipitated catalyst during the previous reuse. Further
recyclings were successfully performed with substrate 13,
and the corresponding product 14 was isolated in its pure
form in high yield and high enantioselectivity for five
additional reuses. Cu-8 affords 14 under analogous conditions
with 93% conversion (84% isolated yield) and 78% ee.
As a conclusion, we have developed an efficient im-
mobilization strategy for bis(oxazoline)-based copper cata-
Acknowledgment. The CNRS and the MENESR are
kindly acknowledged for financial support.
Supporting Information Available: Details of experi-
mental procedures and characterization data for all new
compounds. This material is available free of charge via the
Internet at http://pubs.acs.org.
OL053036A
542
Org. Lett., Vol. 8, No. 3, 2006