Bis(oxazoline)copper complexes covalently bonded to insoluble support as catalysts in cyclopropanation reactions

Article abstract of DOI:10.1021/jo0159338

Chiral bis(oxazolines) are readily dialkylated in the methylene bridge, opening the way to immobilization at that position, keeping the C₂ symmetry of the chiral ligand. Bis(oxazolines) functionalized with two allyl or vinylbenzyl groups are easily grafted onto mercaptopropylsilica. Another approach to immobilization is the polymerization of the ligands bearing vinylbenzyl groups to yield insoluble polymers. The Cu(OTf)₂ complexes of the immobilized ligands promote the enantioselective cyclopropanation reaction between styrene and ethyl diazoacetate. The results depend on the nature of the support and the method of immobilization. With regard to the type of solid, the best results, which are similar to or even better than those obtained with the corresponding dibenzylated homogeneous catalysts, are obtained with homopolymers. With regard to the bis(oxazoline), that bearing indan groups leads to good results both onto silica and polymers, whereas with the ligand bearing tert-butyl groups good enantioselectivities are only obtained with homopolymeric catalysts. Some of the heterogeneous catalysts can be easily recovered and reused, as much as five times, with the same yield and stereoselectivities.

Full text of DOI:10.1021/jo0159338

J . Org. Chem. 2001, 66, 8893-8901
8893
Bis(oxa zolin e)cop p er Com p lexes Cova len tly Bon d ed to In solu ble
Su p p or t a s Ca ta lysts in Cyclop r op a n a tion Rea ction s
M. Isabel Burguete,† J ose´ M. Fraile,‡ J ose´ I. Garc´ıa,‡ Eduardo Garc´ıa-Verdugo,†
Clara I. Herrer´ıas,‡ Santiago V. Luis,*,† and J ose´ A. Mayoral*,‡
Departamento de Quı´mica Inorga´nica y Orga´nica, ESTCE, Universidad J aume I, E-12080 Castello´n,
Spain, and Departamento de Quı´mica Orga´nica, Instituto de Ciencia de Materiales de Arago´n, Facultad
de Ciencias, Universidad de Zaragoza-CSIC, E-50009 Zaragoza, Spain
mayoral@posta.unizar.es
Received J uly 17, 2001
Chiral bis(oxazolines) are readily dialkylated in the methylene bridge, opening the way to
immobilization at that position, keeping the C2 symmetry of the chiral ligand. Bis(oxazolines)
functionalized with two allyl or vinylbenzyl groups are easily grafted onto mercaptopropylsilica.
Another approach to immobilization is the polymerization of the ligands bearing vinylbenzyl groups
to yield insoluble polymers. The Cu(OTf)2 complexes of the immobilized ligands promote the
enantioselective cyclopropanation reaction between styrene and ethyl diazoacetate. The results
depend on the nature of the support and the method of immobilization. With regard to the type of
solid, the best results, which are similar to or even better than those obtained with the corresponding
dibenzylated homogeneous catalysts, are obtained with homopolymers. With regard to the bis-
(oxazoline), that bearing indan groups leads to good results both onto silica and polymers, whereas
with the ligand bearing tert-butyl groups good enantioselectivities are only obtained with
homopolymeric catalysts. Some of the heterogeneous catalysts can be easily recovered and reused,
as much as five times, with the same yield and stereoselectivities.
In tr od u ction
in a large number of enantioselective reactions.5 Recently,
we showed that cationic complexes bearing bis(oxazoline)
ligands can be immobilized onto anionic supports and we
studied the scope and limitations of these solids as
catalysts in enantioselective cyclopropanation6 and Di-
els-Alder reactions.7 Bis(oxazoline)copper complexes
have also been noncovalently immobilized onto Y zeolite
and used as catalysts for aziridination reactions.8 In a
preliminary paper, we reported that bis(oxazolines) can
be immobilized onto organic supports through a co-
polymerization process9 and that the copper complexes
The study of enantioselective reactions promoted by
chiral catalysts constitutes a research area of great
interest.1 In this regard, the development of new hetero-
geneous catalysts to promote enantioselective reactions
is important in connection with the application of het-
erogeneous catalysis in the industrial synthesis of fine
chemicals and specialities.2 There are several strategies
available to obtain chiral heterogeneous catalysts, but
the grafting of a chiral complex onto an insoluble support
is the most widely used. It is known that both the method
used to immobilize the complex and the nature of the
support have a decisive influence on the catalytic activity
and the enantioselectivity of a given system.3,4 However,
very few studies have been undertaken to compare the
immobilization of the same complex on different supports
and through different strategies.
(3) (a) Sung, D. W. L.; Hodge, P.; Stratford, P. W. J . Chem. Soc.,
Perkin Trans. 1 1999, 1463-1472. (b) Altava, B.; Burguete, M. I.;
Garc´ıa-Verdugo, E.; Luis, S. V.; Pozo, O.; Salvador, R. V. Eur. J . Org.
Chem. 1999, 2263-2267. (c) Fraile, J . M.; Mayoral, J . A.; Royo, A. J .;
Salvador, R. V.; Altava, B.; Luis, S. V.; Burguete, M. I. Tetrahedron
1996, 52, 9853-9862. (d) Altava, B.; Burguete, M. I.; Fraile, J . M.;
Garc´ıa, J . I.; Luis, S. V.; Mayoral, J . A.; Vicent, M. J . Angew. Chem.,
Int. Ed. Engl. 2000, 39, 1503-1506. (e) Breysse, E.; Pinel, C.; Lemaire,
M. Tetrahedron: Asymmetry 1998, 9, 897-900.
(4) Altava, B.; Burguete, M. I.; Garc´ıa-Verdugo, E.; Luis, S. V.;
Salvador, R. V.; Vincent, M. J . Tetrahedron 1999, 55, 12897-12906.
(5) (a) Gosh, A. K.; Mathivanan, P.; Capiello, J . Tetrahedron:
Asymmetry 1998, 9, 1-45. (b) J ørgensen, K. A.; J ohannsen, M.; Yao,
S. L.; Audrain, H.; Thorhauge, J . Acc. Chem. Res. 1999, 32, 605-613.
(c) Pfaltz, A. Synlett 1999, 835-842. (d) Pfaltz, A. J . Heterocycl. Chem.
1999, 36, 1437-1451. (e) J ohnson, J . S.; Evans, D. A. Acc. Chem. Res.
2000, 32, 325-335. (f) Fache, F.; Schulz, E.; Tommasino, M. L.;
Lemaire, M. Chem. Rev. 2000, 100, 2159-2231.
To undertake such a study, we selected bis(oxazolines),
a well-known family of chiral ligands that has been used
* To whom correspondence should be addressed. E-mail: (S.V.L.)
luiss@mail.uji.es.
† Universidad J aume I.
‡ Universidad de Zaragoza-CSIC.
(1) (a) Comprehensive Asymmetric Catalysis; J acobsen, E. N., Pfaltz,
A., Yamamoto, H., Eds.; Springer-Verlag: Berlin-Heidelberg, 1999. (b)
Noyori, R. Asymmetric Catalysis in Organic Synthesis; Wiley: New
York, 1994.
(6) (a) Fraile, J . M.; Garc´ıa, J . I.; Mayoral, J . A.; Tarnai, T.
Tetrahedron: Asymmetry 1997, 8, 2089-2092. (b) Fraile, J . M.; Garc´ıa,
J . I.; Mayoral, J . A.; Tarnai, T. Tetrahedron: Asymmetry 1998, 9, 3997-
4008. (c) Fraile, J . M.; Garc´ıa, J . I.; Mayoral, J . A.; Tarnai, T.; Harmer,
M. A. J . Catal. 1999, 186, 214-221. (d) Alonso, P. J .; Fraile, J . M.;
Garc´ıa, J .; Garc´ıa, J . I.; Mart´ınez, J . I.; Mayoral, J . A.; Sa´nchez, M. C.
Langmuir 2000, 16, 5607-5612. (e) Ferna´ndez, A. I.; Fraile, J . M.;
Garc´ıa, J . I.; Herrer´ıas, C. I.; Mayoral, J . A.; Salvatella, L. Catal.
Commun. 2001, 2, 165-170.
(2) (a) Chiral Catalyst Immobilization and Recycling; De Vos, D.
E., Vankelecom, I. F. J ., J acobs, P. A., Eds.; Wiley-VCH: Weinheim,
2000. (b) Blaser, H.-U.; Pugin, B. In Chiral Reactions in Heterogeneous
Catalysis; J annes, G., Dubois, V., Eds.; Plenum Press: New York, 1995;
pp 33-57. (c) Sherrington, D. C.; Hodge, P. Synthesis and Separations
using Functional Polymers; Wiley: New York, 1988. (d) Ford, W. T.
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Mayoral, J . A. J . Mol. Catal. A 2001, 165, 211-218.
10.1021/jo0159338 CCC: $20.00 © 2001 American Chemical Society
Published on Web 12/04/2001

8894 J . Org. Chem., Vol. 66, No. 26, 2001
Burguete et al.
of these immobilized ligands are efficient catalysts in
cyclopropanation reactions. Members of a related family
of chiral ligands, azabis(oxazolines), have been attached
to soluble organic polymers and used in enantioselective
reactions.10 Very recently, the grafting of bis(oxazolines)
onto soluble polymers11 and the immobilization by co-
polymerization12 have been also described. However, no
precedents exist concerning covalent immobilization of
these kinds of chiral ligands onto inorganic supports.13
In this paper we compare the immobilization of bis-
(oxazoline) ligands by different methods: grafting onto
silica using two different spacers, and immobilization
onto organic supports by both grafting and copolymeri-
zation. The corresponding copper-complexes are tested
in the benchmark cyclopropanation reaction of styrene
with ethyl diazoacetate, one of the reactions in which
these ligands form excellent soluble catalysts.14
situation of the ligand in nonaccessible sites, as shown
by the drastic decrease in surface area from 475 m2 g-1
in the original silica to 200-225 m2 g-1 in solids 4 and 6.
In an attempt to overcome this limitation we tried to
immobilize the copper complex itself (Scheme 1, route B).
On using this approach a higher functionalization in
copper, at nearly 50%, was achieved (Table 1).
The catalytic performances of the solids 6, prepared
by both strategies, were compared in the benchmark
cyclopropanation reaction between styrene and ethyl
diazoacetate (Scheme 2) with the corresponding analo-
gous homogeneous catalysts (Table 2, entries 1-8). The
reaction conditions were not optimized and equimolecular
amounts of both reagents were used only for comparison
purposes. In all cases, total conversion of ethyl diazoac-
etate was observed, with formation of diethyl fumarate
and maleate as main side products. With regard to
catalytic activity, the solids obtained by route B (Table
2, entries 6-8) gave similar yields to those obtained with
the homogeneous catalysts (Table 2, entries 1-3). How-
ever, the yields are lower with the catalysts obtained by
route A (Table 2, entries 4 and 5), which may be due to
the diffusion limitations mentioned above. All of these
catalysts led to similar trans/cis selectivity, but the
immobilization gives rise to a noticeably decrease in the
enantioselectivity (Table 2, entries 1-3 vs 4-8). Surpris-
ingly, the asymmetric induction also depends on the
immobilization method, with the solids prepared by route
A (Table 2, entries 4 and 5) being more enantioselective
than those prepared by route B (Table 2, entries 6 and
7). This different behavior could be associated with
differences in the structure of the catalytic site.
Resu lts a n d Discu ssion
Im m obiliza tion of Bis(oxa zolin es) by Gr a ftin g
on to Silica . Methylenebis(oxazolines) 1 are easily modi-
fied by alkylation of the central methylene bridge in the
presence of strong bases. Thus, the reactions of bis-
(oxazolines) with allyl bromide in the presence of meth-
yllithium lead to bis(oxazolines) 2, which contain two allyl
substituents. In this way the C2 symmetry of the original
ligand is maintained. These bis(oxazolines) were im-
mobilized by reaction with mercaptopropylsilica (3) in the
presence of azoisobutyronitrile (AIBN)15 following two
different strategies (Scheme 1). In the first strategy (route
A), the chiral ligand was immobilized and the complex
with Cu(OTf)2 was then formed. In the second approach
(route B), the complex was formed in solution prior to
the immobilization process. Table 1 gathers the results
obtained from the analysis of the different immobilized
chiral ligands and catalysts.
Surprisingly, the results obtained with the immobilized
catalysts strongly depend on the method of grafting used.
On using route A, although the immobilization of the bis-
(oxazoline) ligand takes place with moderate to high yield
(Table 1, solids 4), the complexation with copper leads
to solids 6 with very low degree of functionalization. This
effect may be due to diffusion limitations imposed by the
To shed some light on this area, we carried out a
comparative study of the IR spectra of the homogeneous
and the immobilized systems. As can be seen in Figure
1, the bis(oxazoline) ligand 2b and the homogeneous
complex 5b show a CdN band near 1650 cm-1 and a
series of weaker bands in the region 1400-1525 cm-1
.
These bands are also observed in the ligand immobilized
by route A (4b). Complexation of 4b with copper does not
modify the spectrum (not shown), a fact that is not
unexpected given the very low degree of copper function-
alization. However, the catalyst immobilized by route B
(6b) shows a marked reduction of the CdN band, indicat-
ing the partial loss of the oxazoline structure. Complex-
ation with Cu(OTf)2, a Lewis acid, increases the electro-
philic character of the CdN bond and favors its reaction
with different nucleophiles present on the solid surface,
such as thiol and silanol groups or residual water.
In an attempt to improve the results, we tried to
increase the size of the spacer between the bis(oxazoline)
and the support. This was achieved by using p-vinylben-
zyl instead of allyl group (Scheme 1). In view of the
results discussed above it was decided to test only route
A. As can be seen from the results in Table 1, the chiral
ligands 7 are grafted with good yields (solids 8) but once
again the complexation with copper (solids 9) leads to
very low degrees of functionalization. The solids 9 were
tested in the same cyclopropanation reaction and the
results were compared with the corresponding homoge-
neous systems (Table 2, entries 9-14). The nature of the
substituents in the methylene bridge has a noticeable
influence on the results obtained with homogeneous
catalysts. This fact can be seen by comparing the results
for ligands 2 and 10. The presence of a benzyl instead of
an allyl group leads to a reduction in enantioselectivity
(8) (a) Hutchings, G. J .; Langham, C.; Piaggio, P.; Taylor, S.;
McMorn, P.; Willock, D. J .; Bethell, D.; Bulman-Page, P. C.; Sly, C.;
Hancock, F. E.; King, F. Stud. Surf. Sci. Catal. 2000, 130, 521-526.
(b) Langham, C.; Taylor, S.; Bethell, D.; McMorn, P.; Bulman-Page,
P. C.; Willock, D. J .; Sly, C.; Hancock, F. E.; King, F.; Hutchings, G. J .
J . Chem. Soc., Perkin Trans. 2 1999, 1043-1049.
(9) Burguete, M. I.; Fraile, J . M.; Garc´ıa, J . I.; Garc´ıa-Verdugo, E.;
Luis, S. V.; Mayoral, J . A. Org. Lett. 2000, 2, 3905-3908.
(10) Glos, M.; Reiser, O. Org. Lett. 2000, 2, 2045-2048.
(11) Annunziata, R.; Benaglia, M.; Cinquini, M.; Cozzi, F.; Pitillo,
M. J . Org. Chem. 2001, 66, 3160-3166.
(12) Orlandi, S.; Mandoli, A.; Pini, D.; Salvadori, P. Angew. Chem.
2001, 113, 2587-2589.
(13) During the revision of this manuscript, the immobilization of
the bis(oxazoline) derived from indan onto silica and its application to
Diels-Alder reactions has been described: Rechavi, D.; Lemaire, M.
Org. Lett. 2001, 3, 2493-2496.
(14) (a) Lowenthal, R. E.; Abiko, A.; Masamune, S. Tetrahedron Lett.
1990, 31, 6005-6008. (b) Lowenthal, R. E.; Masamune, S. Tetrahedron
Lett. 1991, 32, 7373-7376. (c) Evans, D. A.; Woerpel, K. A.; Hinman,
M. M.; Faul, M. M. J . Am. Chem. Soc. 1991, 113, 726-728. (d) Bedekar,
A. V.; Andersson, P. G. Tetrahedron Lett. 1996, 37, 4073-4076. (e)
Bedekar, A. V.; Koroleva, E. B.; Andersson, P. G. J . Org. Chem. 1997,
62, 2518-2526. (f) End, N.; Pfaltz, A. Chem. Commun. 1998, 589-
590. (g) Boulch, R.; Scheurer, A.; Mosset, P.; Saalfrank, R. W.
Tetrahedron Lett. 2000, 41, 1023-1026.
(15) Fraile, J . M.; Garc´ıa, J . I.; Mayoral, J . A.; Royo, A. J . Tetrahe-
dron: Asymmetry 1996, 7, 2263-2276.

Covalent Support of Bis(oxazoline)-Cu Complexes
J . Org. Chem., Vol. 66, No. 26, 2001 8895
Sch em e 1. Im m obiliza tion of Bis(oxa zolin e)cop p er Com p lexes on to Silica
with bis(phenyloxazoline) (2b and 10b), despite the use
of a larger amount of catalyst 10b-Cu(OTf)2. On using
bis(tert-butyloxazoline) (2c and 10c), the normal trans
preference of the cyclopropanation is reversed to a cis
preference. The enantioselectivities are also modified,
with a slight decrease and increase in trans and cis
isomers, respectively. As far as the heterogeneous cata-
lysts are concerned, the use of a longer spacer does not
significantly influence the cyclopropanation results (Table
2, entries 5 and 12). The best results are obtained with
9d , which arises from the grafting of 7d , in agreement
with the results obtained in homogeneous phase with
ligands 10. Compound 9c, on the other hand, leads to
disappointingly low enantioselectivities. After the results
described by Rechavi and Lemaire,13 the immobilized
ligand 8c was treated with N-trimethylsilylimidazole and
then with Cu(OTf)2. This catalyst showed the same
results than the nonsililated material, excluding in this
way the role of the free silanol groups of the silica support
in the poor results of this ligand.
The IR spectra of the different solids 8 do not show
noticeable differences, and so analysis of the solids was
carried out by Raman spectroscopy, a useful method for
the study of organic molecules immobilized on different
supports.4 The Raman spectra (Figure 2) show bands
corresponding to the bis(oxazoline), in particular the Cd
N band near 1600 cm-1. However, solid 8c also shows a
band at 1631 cm-1, which can be assigned to a CdC
deformation and it is present in the Raman spectrum of
7. This band is not present in the spectra of the rest of

8896 J . Org. Chem., Vol. 66, No. 26, 2001
Burguete et al.
Ta ble 1. An a lysis of th e Liga n d s a n d Ca ta lysts
Im m obilized on to Silica a
solid route Sb (mmol/g) Nb (mmol/g) Cuc (mmol/g) % DFd
3
1.09
0.97
0.91
0.88
0.83
0.92
0.93
0.92
0.89
0.91
0.90
0.88
0.89
0.87
4a
4b
6a
6b
6a
6b
6c
8b
8c
8d
9b
9c
9d
A
A
A
A
B
B
B
A
A
A
A
A
A
0.58
0.84
0.52
0.75
0.44
0.48
0.47
0.72
0.68
0.66
0.70
0.67
0.64
60
92
18
24
49
48
48
82
75
74
5
0.08
0.10
0.23
0.22
0.22
0.04
0.07
0.04
8
5
a
Silica has a surface area of 475 m2 g-1, which decreases upon
grafting of the complexes. All the silicas obtained have surface
b
areas in the range 200-225 m2 g-1
.
Determined by elemental
analysis. c Determined by plasma emission spectroscopy. Degree
of functionalization in ligand or copper referred to the thiol
functionalization.
d
Sch em e 2. Cyclop r op a n a tion Rea ction betw een
Styr en e a n d Eth yl Dia zoa ceta te
F igu r e 1. Infrared spectra of ligand 2b, complex 5b, and
solids 4b and 6b (method B).
Ta ble 2. Resu lts Obta in ed fr om th e Cyclop r op a n a tion
Rea ction betw een Styr en e a n d Eth yl Dia zoa ceta te
Ca ta lyzed by Silica -Ba sed Ca ta lystsa
eec (%)
(%) trans/cisb transd cise
yieldb
entry
catalyst
diazo/Cu
1
2
3
4
5
6
7
8
9
10
11
12
13
14
2a -Cu(OTf)2
2b-Cu(OTf)2
2c-Cu(OTf)2
6a (route A)
6b (route A)
6a (route B)
6b (route B)
6c (route B)
10b-Cu(OTf)2
10c-Cu(OTf)2
10d -Cu(OTf)2
9b
100
100
100
100
100
100
100
100
10
40
36
58
29
28
36
37
47
32
46
49
24
19
35
62:38
68:32
67:33
62:38
64:36
63:37
66:34
68:32
70:30
33:67
58:42
62:38
60:40
47:53
29
60
80
15
29
9
33
50
72
18
31
14
10
27
40
79
86g
32
12
65g
10
26
50
70
83f
33
6
50
F igu r e 2. Raman spectra of solids 8b-d .
125
1720
983
1720
9c
9d
organic support was carried out using the same general
strategy as described above, namely alkylation in the
methylene bridge. However, in this case a chloromethy-
lated polystyrene-divinylbenzene resin (1% cross-linking,
1 mmol Cl g-1) was used as the alkylating agent (Scheme
3). The IR spectrum of the resulting solid (13b) shows
the absence of the C-Cl band at 1265 cm-1 and the
presence of the CdN band at 1655 cm-1. The amount of
ligand, 0.54 mmol g-1 determined by nitrogen analysis,
is consistent with double alkylation of most of the bis-
(oxazoline) ligand. In contrast with silica-supported bis-
(oxazolines), ligand 13b is able to complex the expected
amount of copper (Table 3). However, this immobilized
complex is less active and less enantioselective (Table 4,
entry 3) than the corresponding homogeneous system. It
is also important to note that the polymer-grafted
catalyst 13b-Cu(OTf)2 leads to lower enantioselectivity
than the analogous catalyst grafted on silica (9b) (Table
2, entry 11).
52f
a
Using equimolecular amounts of styrene and ethyl diazoac-
b
etate at room temperature. Determined by GC. Total conversion
of ethyl diazoacetate. c Determined by GC with a Cyclodex-B
column. 11R is the major isomer. e 12R is the major isomer. f 11S
d
g
is the major isomer. 12S is the major isomer.
the silica-immobilized ligands. The presence of this band
indicates that the bis(oxazoline) is bound to the support,
at least in part, by only one benzyl arm. This change in
the structure of the immobilized ligand may account for
the difference observed in copper functionalization and
enantioselectivity.
In view of the limitations found in grafting onto silica,
we turned our attention toward the use of organic
supports.
Im m obiliza tion of Bis(oxa zolin es) on to Or ga n ic
P olym er s. The grafting of the bis(oxazoline) 1b onto an

Covalent Support of Bis(oxazoline)-Cu Complexes
J . Org. Chem., Vol. 66, No. 26, 2001 8897
Ta ble 3. Solid s Obta in ed by Gr a ftin g on to
Ch lor om eth yla ted P olystyr en e-Divin ylben zen e (13) or
P olym er iza tion w ith th e Ch ir a l Mon om er s 7b-d a n d 22c
(Sch em es 3 a n d 4)a
Sch em e 3. P r ep a r a tion of P olym er ic
Bis(oxa zolin e) Liga n d s by Gr a ftin g a n d
P olym er iza tion
composition of the
mixture
chiral
Cu
polymer monomer styrene cross-linkerb (mmol g-1
)
% DFc
13b
14b
15b
16b
17b
18b
19b
20b
21b
21c
21d
23c
24c
25c
(grafted)
10 (7b) 70
0.44
0.19
0.18
0.04
0.16
0.09
0.11
0.39
0.14
0.08
0.03
0.08
0.08
0.07
98
36
51
9
15
9
14
64
13
7
20 (X)
20 (Y)
20 (Z)
0
0
0
0
0
10 (7b) 70
10 (7b) 70
80 (7b) 20
50 (7b) 50
20 (7b) 80
10 (7b) 90
100 (7b)
100 (7c)
100 (7d )
10 (22c)
0
0
0
0
0
0
3
90 (X)
50 (X)
20 (X)
16
15
13
10 (22c) 40
10 (22c) 70
a
At 80 °C using 60% (w/w) of a mixture toluene/dodecanol (1/5
w/w) as a porogen and 1% AIBN. Quantitative yields of the
b
polymers were obtained in all cases. In parentheses the cross-
linker used: X ) divinylbenzene; Y ) di(vinylbenzyl)polyethyl-
eneglicol; Z ) O,O′-di(vinylbenzyl)resorcinol. c Degree of function-
alization in copper referred to the ligand content.
Ta ble 4. Resu lts Obta in ed fr om th e Cyclop r op a n a tion
Rea ction betw een Styr en e a n d Eth yl Dia zoa ceta te
Ca ta lyzed by P olym er ic Ca ta lystsa
eec (%)
entry ligand diazo/Cu run yieldb (%) trans/cisb transd cise
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
10b
10c
10d
13b
14b
15b
16b
17b
18b
19b
20b
10
50
125
122
176
95
428
208
371
304
86
1
1
1
1f
1f
1f
1
1
1
1
1
2
1
3
1
3
1
2
1
1
1
1
32
46
49
18
11
32
12
26
18
20
28
24
40
19
36
33
35
22
11
15
21
16
70:30
33:67
58:42
66:34
71:29
67:33
58:42
57:43
57:43
60:40
60:40
60:40
52:48
53:47
37:63
36:64
44:56
44:56
58:42
56:44
57:43
60:40
50
70
83g
26
18
8
40
79
86h
21
18
8
50
56
57
46
46
43
57
47
78
75
69g
69g
28
45
29
23
46
51
51
42
42
41
53
49
72
72
75h
75h
33
44
34
22
21b
21c
21d
510
796
2630
23c
24c
25c
26c
417
417
477
550
a
Using equimolecular amounts of styrene and ethyl diazoac-
etate. Reaction carried out at room temperature unless otherwise
indicated in the table. The catalysts were prepared by treatment
b
of the ligand with Cu(OTf)2. Determined by GC. Total conversion
of ethyl diazoacetate. c Determined by GC with a Cyclodex-B
d
column. 11R is the major isomer. e 12R is the major isomer. f At
g
h
60 °C. 11S is the major isomer. 12S is the major isomer.
cases, better results than grafting,4,16 so we decided to
use bis(oxazolines) 7 to prepare copolymers.17 Monomers
were copolymerized with styrene and different cross-
linking agents by following the protocol for the prepara-
tion of monolithic resins developed by Frechet.18 To
In the preparation of polymer-supported enantioselec-
tive catalysts, polymerization has provided, in some
(16) (a) Itsuno, S.; Sakurai, Y.; Ito, K.; Maruyama, T.; Nakahama,
S.; Fre´chet, J . M. J . J . Org. Chem. 1990, 55, 304-310. (b) Kamahori,
K.; Tada, S.; Ito, K.; Itsuno, S. Tetrahedron: Asymmetry 1995, 6, 2547-
2555.
(17) Copolymerization could not be carried out with allylic monomers
2 because they have a polymerization rate very slow in comparison
with that of styrene.

8898 J . Org. Chem., Vol. 66, No. 26, 2001
Burguete et al.
Sch em e 4. P r ep a r a tion of P olym er s w ith Bis(oxa zolin e) Liga n d s in th e Ma in Ch a in
compare different polymerization conditions, initial ex-
periments were carried out with bis(oxazoline) 7b. Table
3 shows the conditions used for the synthesis of each
polymer. Catalysts were obtained by treatment of the
polymeric ligand with Cu(OTf)2 and the data for copper
incorporation are also given in Table 3.
cross-linking by its own chiral monomer, is the only
catalyst with high copper content in both absolute (0.39
mmol g-1) and relative terms. Higher accessibility and
greater flexibility could account for the higher copper
content in this case.
All the immobilized catalysts were tested in the cyclo-
propanation reaction between styrene and ethyl diazoac-
etate. The results in Table 4 show that, in the case of
polymers containing a nonchiral cross-linker, both the
activity and enantioselectivity strongly depend on the
nature of the cross-linker. The use of a longer cross-linker
seems to lead to a more enantioselective catalyst, as
deduced from the comparison between 14b and 16b
(Table 4, entries 4 and 6). However, polymer 15b leads
to low values of enantiomeric excess (Table 4, entry 5).
In this case, the presence of a poly(ethylene glycol) chain,
which is able to form nonchiral complexes with copper,
accounts for this result. This hypothesis is also consistent
with the unexpectedly high relative copper content in this
polymer. This result is in strong contrast with the high
enantioselectivities obtained when bis(oxazolines)11 or
azabis(oxazolines)10 are bonded to soluble PEG.
It is important to note that all the polymers are cross-
linked because the bifunctionalization of the chiral
monomer makes it act as a cross-linker. In general the
incorporation of copper is low, probably as a consequence
of the high degree of cross-linking. Typical values for the
copper content are in the range 0.04-0.16 mmol g-1
,
corresponding to 7-15% of the maximum copper func-
tionalization. This situation occurs even with polymer
19b, which contains only 20% of chiral monomer as a
cross-linking agent. There are two possible explanations
for this low degree of copper incorporation. One possibil-
ity would be the result of a high reactivity of the chiral
monomer, which could then be incorporated in the inner
part of the polymer particles and lead to low accessibility.
The other possibility involves a distorted disposition of
the majority of the chiral ligand due to the double
bonding to the polymer. Such a situation could prevent
the formation of a chelate complex, with the copper being
washed out in the catalyst preparation process. Excep-
tions to this trend include polymers 14b and 15b, which
contain other cross-linking agents. In these cases, the
copper content is not markedly higher, but it represents
a higher proportion in comparison with the maximum
functionalization. Finally, polymer 20b, with only 10%
The polymers prepared with the chiral bis(oxazoline)
as the only cross-linker (17b-20b) are more active and
give rise to enantioselectivities (Table 4, entries 8-11)
that are similar to those obtained with the analogous
homogeneous catalyst (Table 4, entry 1). The catalysts
can be recovered and reused, as demonstrated with
polymer 20b (Table 4, entries 11 and 12). A particularly
interesting result concerns the enantioselectivities. These
values increase as the amount of bis(oxazoline) in the
polymer increases. In view of this fact, we decided to
explore the use of homopolymers, obtained using bis-
(oxazolines) 7 as the sole monomers. Despite the low
copper content, polymers 21b, 21c, and 21d efficiently
(18) (a) Svec, F.; Fre´chet, J . M. J . Chem. Mater. 1995, 7, 707-715.
(b) Svec, F.; Fre´chet, J . M. J . Science 1996, 273, 205-211. (c) Xie, S.;
Svec, F.; Fre´chet, J . M. J . Chem. Mater. 1998, 10, 4072-4078. (d) Svec,
F.; Fre´chet, J . M. J . Ind. Eng. Chem. Res. 1999, 38, 34-48. (e) Hird,
N.; Hughes, I.; Hunter, D.; Morrison, M. G. J . T.; Sherrington, D. C.;
Stevenson, L. Tetrahedron 1999, 55, 9575-9584.

Covalent Support of Bis(oxazoline)-Cu Complexes
J . Org. Chem., Vol. 66, No. 26, 2001 8899
promote the cyclopropanation reaction and lead to enan-
tioselectivities that are similar to, or even better than,
their homogeneous counterparts (Table 4, entries 1 and
2 vs 13 and 15). Moreover the catalysts are recyclable,
particularly catalyst 21c, which does not show any loss
of activity or selectivity. In the conditions of equimolecu-
lar amounts of reagents, the catalysts show a decline in
activity after the third run because of the coordination
of byproducts detected by IR. The life of the catalysts can
be enlarged by using a 5-fold excess of styrene in the
cyclopropanation reaction, leading to higher yields, in the
range of 55-75%, and stability during five runs. It is
important to note the reversal of the trans/cis selectivity
with the homogeneous system with 10c and the related
polymeric catalyst from 21c. This behavior was not
observed with the silica-immobilized catalyst 9c (Table
2, entry 13) and it is difficult to find a simple explanation.
The trans/cis selectivity is also reduced with the diben-
zylated bis(oxazoline) 10d derived from indan and a
reversal is observed with the polymer 21d . Polymeric
catalysts derived from 7b gave rise to a similar trend and
a reduction in the trans preference was observed. How-
ever, reversal of the trans/cis selectivity is not seen in
this case. These results show the importance of the
bulkiness of the substituents in the methylene bridge and
in the oxazoline rings for the stereoselectivity of the
cyclopropanation reaction.
Despite the good results obtained, the polymeric cata-
lysts suffer from the drawback of low copper content. This
fact must be related to the situation of the chiral ligand
in places that are difficult to access, i.e., corresponding
to cross-linking points, despite of the fact that a porogen
is used. To overcome these problems, we tried to obtain
polymers in which the chiral ligand is situated in the
main chain by using monofunctionalized bis(oxazolines)
(Scheme 4). This strategy was applied to the chiral ligand
that led to the best enantioselectivity. However, this
methodology was not found to improve the incorporation
of copper into polymers 23-25, as can be seen from the
results in Table 3. The results obtained in the cyclopro-
panation reaction depend on the composition of the
polymerization mixture. A higher yield was obtained with
the less cross-linked polymer (25c), but it is difficult to
find a clear relationship between composition and enan-
tioselectivity. Polymer 25c was treated with methyl-
lithium and methyl iodide in order to obtain a polymer
26c with bis(oxazoline) moieties with two substituents
in the central methylene bridge placed in the main chain
of the polymer. However, the results obtained in the
cyclopropanation reaction (entry 22 in Table 4) are even
slightly worse than those obtained with 25c.
lectivity and recoverability were observed for homopoly-
mers 21b, 21c and 21d . With these polymers enantiose-
lectivites up to 78% e.e. were obtained with a catalyst
that can be reused five times with the same results.
Although some chiral ligands must be situated in inac-
cessible sites, the use of doubly functionalized bis-
(oxazolines) is advantageous, probably due to the con-
servation of the C2 symmetry in the immobilized catalyst.
Exp er im en ta l Section
Gen er a l Meth od s. 1H and 13C NMR spectra (CDCl3, δ
(ppm), J (Hz)) were obtained at 300 and 75 MHz, respectively,
in a Varian Unity 300 and a Bruker ARX 300 apparatus.
Specific rotations were measured with a Perkin-Elmer 241MC
polarimeter. Quantitative elemental analyses were performed
in duplicate on a Carlo Erba EA1108 CHNS-O instrument.
Copper analyses were carried out by plasma emission spec-
troscopy on a Perkin-Elmer Plasma 40 emission spectrometer.
Transmission FTIR spectra of self-supported wafers of silica-
based solids evacuated (<10-4 Torr) at 50 °C were obtained
with a Mattson Genesis series FTIR spectrometer. FTIR
spectra of KBr pellets of the polymers were recorded on a
Perkin-Elmer 2000 FTIR spectrometer. Surface area was
measured by BET method19 on a Micromeritics Flowsorb 2300
apparatus. Raman spectra of polymers and silicas were
obtained on the Raman accessory FT-Raman Perkin-Elmer Na:
YAG Laser PSU for the same instrument. Gas chromatography
was carried out on two Hewlett-Packard 5890 chromatographs,
equipped with FID detector and cross-linked methyl silicone
(25 m × 0.2 mm × 0.33 µm) and Cyclodex B (30 m × 0.25 mm
× 0.25 µm) columns.
P r ep a r a tion of th e Mod ified Ch ir a l Liga n d s. 2,2′-(1-
Allylbu t-3-en ylid en e)bis[(4S)-4-ben zyl-4,5-d ih yd r o-2-ox-
a zole] (2a ). Methyllithium (2.2 mmol) was added to a solution
of 2,2′-methylenebis[(4S)-4-benzyl-4,5-dihydro-2-oxazole] (1a )
(1 mmol) in anhydrous THF at -55 °C under argon atmo-
sphere, and the resulting solution was stirred for 1 h. Allyl
bromide (2.2 mmol) was then added dropwise, and the reaction
was stirred at -10 °C for 3 h. The mixture was washed with
a saturated NH4Cl solution, the organic layer was dried over
MgSO4, and the solvent was evaporated under reduced pres-
sure. The product was purified by column chromatography
using an end-capped silica20 and n-hexane/diethyl ether (9:1)
as an eluent. Yield: 87%. 1H NMR: 7.4-7.2 (m, 10H), 5.63
(m, 2H), 5.11 (m, 4H), 4.40 (m, 2H), 4.15 (dd, 2H, J 1 ) 7.5, J 2
) 7.5), 3.98 (dd, 2H, J 1 ) 7.5, J 2 ) 7.4), 3.13 (dd, 2H, J 1
)
12.0, J 2 ) 3.8), 2.71 (d, 4H, J ) 7.3), 2.59 (dd, 2H, J 1 ) 12.0,
J 2 ) 3.8). 13C NMR: 167.6, 138.5, 133.5, 130.0, 129.2, 127.1,
119.3, 72.5, 67.9, 42.3, 38.1, 31.6. Anal. Calcd for C27H30N2O2:
C, 78.2; H, 7.3; N, 6.8. Found: C, 78.4; H, 7.2; N, 7.0. [R]D
-95.1 (c 1.045, CHCl3).
)
2,2′-(1-Allylbu t-3-en ylid en e)bis[(4S)-4-p h en yl-4,5-d ih y-
d r o-2-oxa zole] (2b). Using the same procedure from 2,2′-
methylenebis[(4S)-4-phenyl-4,5-dihydro-2-oxazole]
Yield: 85%. 1H NMR: 7.3-7.2 (m, 10H), 5.82 (m, 2H), 5.22
(dd, 2H, J 1 ) 10.1, J 2 ) 7.7), 5.13 (m, 4H), 4.64 (dd, 2H, J 1
(1b ).
)
10.1, J 2 ) 8.4), 4.09 (dd, 2H, J 1 ) 8.4, J 2 ) 7.7), 2.87 (d, 4H,
J ) 7.9). 13C NMR: 168.0, 142.2, 132.9, 128.7, 127.6, 126.8,
118.9, 75.2, 69.7, 46.1, 37.7. Anal. Calcd for C25H26N2O2: C,
Con clu sion s
77.7; H, 6.8; N, 7.2. Found: C, 77.9; H, 7.0; N, 7.1. [R]D
)
Bis(oxazolines) can be readily immobilized on silica and
organic polymers by means of appropriate functionaliza-
tion of the methylene bridge. Copper complexes of the
immobilized chiral bis(oxazolines) can act as catalysts of
the cyclopropanation reactions. The results obtained with
the catalysts grafted onto mercaptopropylsilica depend
on both the spacer used (allylic or benzylic) and the
immobilization method. With regard to organic polymers,
monolithic polymerized catalysts are better than those
grafted onto flexible polymers. The composition of the
mixture of monomers has an enormous influence on the
results. The best results in terms of activity, enantiose-
-107.0 (c 1.06, CHCl3).
2,2′-(1-Allylbu t-3-en ylid en e)bis[(4S)-4-ter t-bu tyl-4,5-d i-
h yd r o-2-oxa zole] (2c). Using the same procedure from 2,2′-
methylenebis[(4S)-4-tert-butyl-4,5-dihydro-2-oxazole]
(1c).
Yield: 79%. 1H NMR: 5.71 (m, 2H), 5.08 (m, 4H), 4.12 (dd,
2H, J 1 ) 9.9, J 2 ) 8.4), 3.99 (dd, 2H, J 1 ) 8.4, J 2 ) 7.8), 3.82
(dd, 2H, J 1 ) 9.9, J 2 ) 7.8), 2.76 (dd, 2H, J 1 ) 12.3, J 2 ) 8.0),
2.65 (dd, 2H, J 1 ) 12.3, J 2 ) 8.0), 0.82 (s, 18H). 13C NMR:
(19) (a) Pure Appl. Chem. 1985, 57, 603-619. (b) Brunauer, S.;
Emmett, P. H.; Teller, E. J . Am. Chem. Soc. 1938, 60, 309-319.
(20) Fraile, J . M.; Garc´ıa, J . I.; Gracia, D.; Mayoral, J . A.; Pires, E.
J . Org. Chem. 1996, 61, 9479-9482.

8900 J . Org. Chem., Vol. 66, No. 26, 2001
Burguete et al.
166.2, 133.2, 118.5, 75.5, 68.6, 45.7, 37.4, 33.8, 25.8. Anal.
Calcd for C21H34N2O2: C, 72.8; H, 9.9; N, 8.1. Found: C, 72.6;
H, 10.0; N, 7.9. [R]D ) -101.5 (c 0.4, CHCl3).
(d, 2H, J ) 18.7), 3.29 (d, 2H, J ) 15.2). 13C NMR: 167.4, 141.7,
140.0, 136.8, 135.9, 135.7, 130.5, 128.6, 127.7, 126.0, 125.7,
125.4, 113.2, 83.8, 76.7, 47.9, 39.6, 38.9. Anal. Calcd for
2,2′-(1-Ben zyl-2-p h en ylet h ylid en e)b is[(4S)-4-p h en yl-
4,5-d ih yd r o-2-oxa zole] (10b). Methyllithium (2.2 mmol) was
added to a solution of 2,2′-methylenebis[(4S)-4-phenyl-4,5-
dihydro-2-oxazole] (1b) (1 mmol) in anhydrous THF at -55
°C under argon atmosphere, and the resulting solution was
stirred for 1 h. Benzyl chloride (2.2 mmol) was then added
dropwise, and the reaction was heated under reflux for 4 h.
The mixture was washed with a saturated NH4Cl solution, the
organic layer was dried over MgSO4, and the solvent was
evaporated under reduced pressure. The product was purified
by column chromatography using an end-capped silica17 and
n-hexane/ethyl acetate (10:1) as an eluent. Yield: 88%. 1H
NMR: 7.25 (m, 20H), 5.04 (t, 2H, J ) 9.4), 4.50 (t, 2H, J )
8.7), 3.88 (t, 2H, J ) 8.7), 3.40 (m, 4H). 13C NMR: 167.4, 136.3,
136.2, 136.0, 130.6, 128.3, 127.2, 126.6, 125.9, 74.9, 69.4, 48.7,
38.8. Anal. Calcd for C33H30N2O2: C, 81.5; H, 6.2; N, 5.8.
Found: C, 81.6; H, 6.3; N, 5.7.
C
39H34N2O2: C, 89.2; H, 6.1; N, 5.0. Found: C, 89.5; H, 6.0; N,
5.0.
2,2′-[2-(4-Vin ylp h en yl)eth ylid en e]bis[(4S)-4-ter t-bu tyl-
4,5-d ih yd r o-2-oxa zole] (22c). Using the same procedure
described for 7c but only 1.1 mmol of methyllithium and
4-vinylbenzyl chloride were used. The product is easily poly-
merizable and only a small amount was purified for analytical
1
identification. H NMR: 7.32 (d, 2H, J ) 8.9), 7.23 (d, 2H, J
) 8.9), 6.62 (dd, 1H, J 1 ) 18.5, J 2 ) 11.7), 5.65 (d, 1H, J )
18.5), 5.16 (d, 1H, J ) 11.7), 4.09 (dd, 4H, J 1 ) 29?, J 2 ) 21?),
3.99 (t, 1H, J ) 9.0), 3.82 (dd, 2H, J 1 ) 20?, J 2 ) 10?), 3,21 (t,
2H, J ) 9.0), 0.82 (s, 9H), 0.81 (s, 9H). 13C NMR: 163.8, 163.4,
137.7, 136.4, 135.7, 129.0, 125.9, 113.1, 75.4, 68.4, 41.2, 35.5,
33.5, 25.7. Anal. Calcd for C24H34N2O2: C, 75.3; H, 8.9; N, 7.3.
Found: C, 75.2; H, 8.9; N, 7.4.
Im m obiliza tion on Silica Gel. Syn th esis of Mer ca p to-
p r op ylsilica (3). To a suspension of 4 g of silica gel (Merck
60, 63-200 nm, dried at 140 °C under vacuum) in anhydrous
toluene (25 mL) under argon atmosphere were added dropwise
dry pyridine (6 mL) and 3-mercaptopropyltrimethoxysilane
(2.75 g, 14 mmol). The suspension was heated under reflux
for 40 h, and the solid was separated by filtration and washed
with toluene, THF, and n-hexane. After drying, the content of
sulfur (1.09 mmol g-1) was determined by elemental analysis.
Im m obiliza tion of F u n ction a lized Bis(oxa zolin es) by
Rou te A (4a ,b, 8b-d ). To a suspension of mercaptopropyl-
silica (3) (1 g, 1.09 mmol) in chloroform (15 mL) under argon
atmosphere were added 1.09 mmol of the corresponding bis-
(oxazoline) (2a ,b, 7b-d ) and 0.08 mmol of azoisobutyronitrile.
The suspension was heated under reflux for 40 h, and the solid
was separated by filtration and washed with dichloromethane
and toluene. The method was repeated once. After drying, the
content of chiral ligand (Table 1) was determined by elemental
analysis.
P r ep a r a tion of Im m obilized Cop p er Com p lexes (6 a n d
9). To a suspension of the immobilized bis(oxazoline) (4 or 8)
a solution of Cu(OTf)2 (stoichiometric amount) in anhydrous
methanol (approximately 1 M) was slowly added. The mixture
was stirred at room temperature for 24 h. The solid was
separated by filtration, washed with methanol, and dried
under vacuum at 50 °C. The copper content (Table 1) was
determined by plasma emission spectroscopy.
2,2′-(1-Ben zyl-2-p h en yleth ylid en e)bis[(4S)-4-ter t-bu tyl-
4,5-d ih yd r o-2-oxa zole] (10c). Using the same procedure from
2,2′-methylenebis[(4S)-4-tert-butyl-4,5-dihydro-2-oxazole] (1c).
1
Yield: 76%. H NMR: 7.25 (m, 10H), 4.06 (dd, 2H, J 1 ) 9.9,
J 2 ) 8.4), 3.97 (dd, 2H, J 1 ) 8.4, J 2 ) 7.5), 3.78 (dd, 2H, J 1
)
9.9, J 2 ) 7.5), 3.44 (d, 2H, J ) 14.1), 3,15 (d, 2H, J ) 14.1),
0.82 (s, 18H). 13C NMR: 166.2, 137.1, 130.5, 127.9, 126.5, 75.6,
68.3, 53.4, 39.3, 33.9, 25.8. Anal. Calcd for C29H38N2O2: C, 80.0;
H, 8.6; N, 6.3. Found: C, 79.8; H, 8.5; N, 6.2.
[3a R-[2(3′a R*,8′a S*),3′a r,8′a r]]-2,2′-(1-Ben zyl-2-p h en -
yle t h ylid e n e )b is[3a ,8a -d ih yd r o-8H -in d e n o[1,2-d ]ox-
a zole] (10d ). Using the same procedure from [3aR-
[2(3′aR*,8′aS*),3′aR,8′aR]]-2,2′-methylenebis[3a,8a-dihydro-
1
8H-indeno[1,2-d]oxazole] (1c). Yield: 86%. H NMR: 7.5-6.9
(m, 18H), 5.59 (d, 2H, J ) 8.0), 5.28 (dd, 2H, J 1)8.0, J 2)6.7),
3.32 (dd, 2H, J 1)18.5, J 2)6.7), 3.23 (d, 2H, J ) 14.4), 3,06 (d,
2H, J ) 14.4), 3.05 (d, 2H, J ) 18.5). 13C NMR: 167.1, 141.5,
139.8, 136.0, 130.2, 128.4, 127.7, 127.5, 126.3,125.9, 125.1,
83.4, 76.4, 47.5, 39.3, 38.0. Anal. Calcd for C35H30N2O2: C, 82.3;
H, 5.9; N, 5.5. Found: C, 82.6; H, 6.1; N, 5.4.
2,2′-[2-(4-Vin ylp h en yl)-1-(4-vin ylben zyl)eth yliden e]bis-
[(4S)-4-p h en yl-4,5-d ih yd r o-2-oxa zole] (7b). Using the same
procedure described for 10b with 4-vinylbenzyl chloride as the
alkylating agent. The product is easily polymerizable and only
1
a small amount was purified for analytical identification. H
NMR: 7.3-7.1 (m, 14H), 6.84 (m, 4H), 6.61 (dd, 2H, J 1 ) 17.7,
J 2 ) 10.6), 5.70 (d, 2H, J ) 17.7), 5.15 (d, 2H, J ) 10.6), 5.07
(t, 2H, J ) 9.4), 4.52 (t, 2H, J ) 8.7), 3.89 (t, 2H, J ) 8.7),
3.41 (m, 4H). 13C NMR: 167.4, 141.5, 136.3, 136.2, 130.6, 130.4,
128.3, 127.2, 126.6, 125.9, 113.5, 74.9, 69.5, 48.7, 38.9. Anal.
Calcd for C37H34N2O2: C, 82.5; H, 6.4; N, 5.2. Found: C, 83.0;
H, 6.5; N, 5.0.
2,2′-[2-(4-Vin ylp h en yl)-1-(4-vin ylben zyl)eth ylid en e]bis-
[(4S)-4-ter t-bu tyl-4,5-d ih yd r o-2-oxa zole] (7c). Using the
same procedure described for 10c with 4-vinylbenzyl chloride
as the alkylating agent. The product is easily polymerizable
and only a small amount was purified for analytical identifica-
tion. 1H NMR: 7.33 (d, 4H, J ) 8.0), 7.25 (d, 4H, J ) 8.0),
6.71 (dd, 2H, J 1)17.8, J 2)10.9), 5.74 (d, 2H, J ) 17.8), 5.22
(d, 2H, J ) 10.9), 4.10 (dd, 2H, J 1)9.9, J 2)8.8), 3.99 (dd, 2H,
J 1)8.8, J 2)7.8), 3.85 (dd, 2H, J 1)9.9, J 2)7.8), 3.48 (d, 2H, J
) 14.1), 3,19 (d, 2H, J ) 14.1), 0.87 (s, 18H). 13C NMR: 165.6,
136.5, 135.6, 130.4, 125.9, 125.6, 113.0, 75.5, 68.3, 48.2, 39.1,
33.9, 25.8. Anal. Calcd for C33H42N2O2: C, 79.5; H, 8.5; N, 5.6.
Found: C, 79.9; H, 8.5; N, 5.4.
[3a R-[2(3′a R*,8′a S*),3′a r,8′a r]]-2,2′-[2-(4-Vin ylp h en yl)-
1-(4-vin ylben zyl)eth yliden e]bis[3a,8a-dih ydr o-8H-in den o-
[1,2-d ]oxa zole] (7d ). Using the same procedure described for
10c, from 1d with 4-vinylbenzyl chloride as the alkylating
agent. The product is easily polymerizable and only a small
amount was purified for analytical identification. 1H NMR:
7.7-7.5 (m, 8H), 7.12 (d, 4H, J ) 10.9), 6.93 (d, 4H, J ) 10.9),
6.78 (dd, 2H, J 1 ) 17.8, J 2 ) 10.7), 5.86 (d, 2H, 7.3), 5.85 (d,
2H, J ) 17.8), 5.54 (t, 2H, J ) 7.2), 5.41 (d, 2H, J ) 10.7),
3.59 (dd, 2H, J 1 ) 18.7, J 2 ) 7.1), 3.52 (d, 2H, J ) 15.2), 3.32
Im m obiliza tion of Bis(oxa zolin e)cop p er Com p lexes by
Rou te B. A mixture of bis(oxazoline) (2) (1.09 mmol) and Cu-
(OTf)2 (1.09 mmol) in anhydrous chloroform (5 mL) was stirred
at room temperature under argon atmosphere until complete
solution. This solution was added to a suspension of mercap-
topropylsilica (3) (1 g, 1.09 mmol) in chloroform (10 mL), and
finally 0.08 mmol of azoisobutyronitrile was also added. The
suspension was heated under reflux for 40 h, and the solid
was separated by filtration and washed with dichloromethane.
After drying, the content of chiral ligand was determined by
elemental analysis and copper content by plasma emission
spectroscopy (Table 1).
P r ep a r a tion of P olym er ic Ca ta lysts. P r ep a r a tion of
P olym er -Gr a fted Bis(oxa zolin e) (13b). The method de-
scribed for the synthesis of 10b was followed but using 0.3 g
of a chloromethylated resin (polystyrene-divinylbenzene, 1%
cross-linking, 1.04 mequiv g-1) as the alkylating agent. The
mixture was heated under reflux for 40 h, and the solid was
separated by filtration and thoroughly washed with THF,
dichloromethane, and methanol and dried under vacuum at
50 °C. The content of chiral ligand was determined by
elemental analysis (Table 3).
Im m obiliza tion of Bis(oxa zolin es) by P olym er iza tion
(14-25). A mixture of monomers (composition in Table 3),
toluene, and 1-dodecanol (ratio 40:10:50 w/w) was placed in a
glass mold and purged with nitrogen in the presence of
azoisobutyronitrile (1% w/w). The mold was closed and heated
at 80 °C for 24 h. The mold was broken, and the polymer was
extracted with THF in a Soxhlet apparatus. The content of
chiral ligand was determined by elemental analysis (Table 3).

Covalent Support of Bis(oxazoline)-Cu Complexes
J . Org. Chem., Vol. 66, No. 26, 2001 8901
P r ep a r a tion of P olym er ic Ca ta lysts. To a suspension of
the polymer (14 to 25) in methanol was added a solution of
Cu(OTf)2 (stoichiometric amount) in the same solvent. The
mixture was stirred at room temperature for 24 h. The solid
was separated by filtration, washed with methanol, and dried
under vacuum at 50 °C. The copper content (Table 3) was
determined by plasma emission spectroscopy.
consumption of the diazoacetate, a second portion of this
reagent was added in the same way (the diazoacetate/Cu ratio
is given in Tables 2 and 4). After the reaction was finished,
the catalyst was separated by filtration, washed with dichlo-
romethane, and air-dried. Some catalysts were reused under
the same conditions. The results were determined by gas
chromatography as described elsewhere.6,9
Cyclop r op a n a tion Rea ction s. To a suspension of the
corresponding catalyst in a solution of styrene (358 mg, 3.44
mmol) and n-decane (150 mg, internal standard) in dichlo-
romethane (3.5 mL) at room temperature under argon atmo-
sphere was added ethyl diazoacetate (196 mg, 1.72 mmol) in
the same solvent (0.5 mL) during 2 h using a syringe pump.
Reactions at 60 °C were carried out in 1,2-dichloroethane. The
reaction was monitored by gas chromatography, and after
Ack n ow led gm en t. This work was made possible
through the generous financial support of the CICYT
(Project No. MAT99-1176) and the Generalitat Valen-
ciana (Project No. GV99-64-1-02). C.I.H. is indebted to
the MCYT for a grant.
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