Immobilization of Pybox ligand on modified starch

Article abstract of DOI:10.1246/cl.2006.44

Starch, one of the most abundant natural polymer was used as support for chiral pyridine-bis(oxazoline) ligand. The corresponding ruthenium complex was used as catalyst in cyclopropanation reaction of styrene with ethyl diazoacetate. Yield, diastereoisome

Full text of DOI:10.1246/cl.2006.44

44
Chemistry Letters Vol.35, No.1 (2006)
Immobilization of Pybox Ligand on Modified Starch
Alfonso Cornejo,2 Victor Martinez-Merino,Ã2 Maria J. Gil,2 Christine Valerio,1 and Catherine PinelÃ1
1Institut de Recherches sur la Catalyse, UPR 5401-CNRS, 2 avenue Albert Einstein, 69626 Villeurbanne, France
2Dep. Quimica Aplicada, Universidad Publica de Navarra, 31006 Pamplona, Spain
(Received October 12, 2005; CL-051298; E-mail: pinel@catalyse.cnrs.tr)
Starch, one of the most abundant natural polymer was used
preliminary results in asymmetric cyclopropanation reaction.
Treatment of starch in i-PrOH/NaOH 0.1 M with butadiene
at 50 ꢀC overnight, in the presence of catalytic amount of
Pd(OAc)2/TPPTS (trisodium tris(m-sulfonatophenyl)phos-
phine) yielded telomerized starch. The degree of substitution,
determined as the average number of ether groups per glycosidic
moiety, was significantly affected by the experimental condi-
tions. In order to avoid undefined interactions between two adja-
cent ligands, we prepared modified starch with moderate degree
of substitution (DS). The reaction was performed in the presence
of 0.25 mol % catalyst per glycosidic unit, for 21 h at 50 ꢀC.
After workup, the DS was determined by 1H NMR analysis
and was equal to 0.62. In a second step, the telomerized starch
1 was effectively peracetylated in pyridine in 85% yield.11 This
as support for chiral pyridine–bis(oxazoline) ligand. The corre-
sponding ruthenium complex was used as catalyst in cyclopropa-
nation reaction of styrene with ethyl diazoacetate. Yield, diaster-
eoisomeric excess and enantiomeric excess kept constant after 3
runs.
The preparation of tethered organometallic complexes to
perform enantioselective synthesis has been reported over sever-
al types of supports. Most commonly chiral catalysts were
immobilized over solid support through covalent bondings.1
Ligands have been covalently grafted to inorganic materials such
as amorphous silica or mesoporous structured inorganic solid.
They can also be introduced in organic polymers either by mod-
ification of Merrifield type resin or by copolymerisation. On the
other hand, natural polymers such as polysaccharides are largely
available on great scale and can be applied as support of molecu-
lar catalysts. In this sense, the starch is a particularly attractive
molecule: its swelling is strongly affected by the nature of the
solvent. Moreover, it is very cheap and not toxic. Few reports
are dealing with the use of polysaccharides as support for
organometallic species. Allylic substitution was performed with
Pd/TPPTS complex entrapped in different polysaccharides.2
Silica-supported starch–polysulfosiloxane–Pt complexes were
used for asymmetric hydrogenation of 4-methyl-2-pentanone
to 4-methyl-2-pentanol with 94% ee.3 In that approach, the in-
trinsic chirality of the starch was responsible of the enantioselec-
tivity. Recently, organometallic complexes were grafted to func-
tionalized cellulose for potential application in nonlinear optic.4
Chiral pyridine–bis(oxazoline) (Pybox) ligands complexed
to ruthenium are very efficient in cyclopropanation reaction of
alkenes with diazoesters.5 Pybox ligands have been supported
onto silica6 and polymers7 via grafting or copolymerized with
styrene and divinylbenzene.8 These studies showed that the
nature of the support played a significant role on the activity
of the supported catalyst as well as on the enantioselectivity of
the reaction.9 To our knowledge, carbohydrate type solids have
not been developed as supports for chiral catalysts, and this
could be of interest because the additional chirality of the
support. Thus, the aim of this work was the covalent grafting
of Pybox ligands to starch and their test in the asymmetric cyclo-
propanation benchmark reaction (ACP). In order to get high
flexibility of the catalyst over the support, it is necessary to insert
a long chain as a linker between the starch and the ligand. We
previously reported palladium-catalyzed telomerization of
starch with butadiene.10 This transformation allowed the intro-
duction of a 8-carbons chain in starch. Owing to the presence
of unsaturated double bonds in the lateral chain, subsequent
functionalization is conceivable. In this paper, we reported the
grafting of a Pybox ligand to a telomerized starch and the
1
protection did not affect the ether group and H NMR analysis
confirmed the DS (0.65).
HO
O
HO
HO
O
O
O
HO
OH
O
1
O
N
N
1) Ac2O, Pyridine
2) AIBN, CHCl3, reflux, HS
N
AcO
O
AcO
O
AcO
3
O
O
O
O
AcO
N
N
OAc
O
5
N
S
4
O
Figure 1. Synthesis of immobilized Pybox ligand.
The radical coupling of 4-sulfanylpybox7 (3) and modified
starch was studied (Figure 1). With starch containing free OH
groups 1, in the presence of catalytic amount of AIBN, very
low amounts of grafted ligand were detected by 1H NMR analy-
sis. This was attributed to the radical scavenger properties of
hydroxyl groups. On the other way, reaction with peracetylated
telomerized starch 2 was slow but successful. Owing to the
low reactivity of the system, the 4-sulfanylpybox was added
portion wise over a two-days period. After extensive washing,
1
the resulting solid was analyzed by H NMR analysis. Specific
Copyright Ó 2006 The Chemical Society of Japan

Chemistry Letters Vol.35, No.1 (2006)
45
of chiral ligand on polymer.8 So, the Pybox starch–Ru–ethylene
1:1:1 complex 5a was tested. This complex 5a exhibited lower
activity and selectivity toward the cyclopropanation reaction
than homogeneous complex 5b pointing out the dramatic influ-
ence of the support. However, ruthenium catalyst supported on
starch 5a showed better performance on ACP than silica immo-
bilized catalysts,9 although with worse asymmetric induction
than copolymers (specially on the trans/cis ratio and cis enantio-
selectivity).8 After removing of the liquid solution and washing
of the solid with degassed ethanol, the performance of the cata-
lyst was established again. Over 3 runs, the trans/cis selectivity
as well as the enantioselectivity keep constant. However, the
yield increases between runs 1 and 2. This was attributed to
the presence in the first run of residual free ruthenium complex
which is not active in cyclopropanation reaction but decomposes
the ethyl diazoacetate. In terms of recycling, starch immobilized
catalyst 5a allowed more runs without decreasing of perform-
ance than reported copolymers.8
R
S
O
O
N
Cl
N
N
Ru
L
Cl
R = Starch; L: CH2=CH2 5a
R = H
5b
CO2Et
CO2Et
Ph
+
N2
CO2Et
Ph
Figure 2. Asymmetric catalyzed cyclopropanation.
signals of the Pybox moiety were observed at 8.18 and 8.06 ppm
as result of the different environment of the pyridine rings in 4
(i.e. by a non-homogeneous distribution of the C8 linker on
starch). Moreover, the presence of nitrogen was detected by
elemental analysis of 4 that corresponded to 0.1 mmol of ligand
per g of support.
Treatment of the ligand 4 with [RuCl2(p-Cymene)]2 in di-
chloromethane under an ethylene atmosphere yielded the corre-
sponding red wine-colored Pybox–Ru–ethylene 1:1:1 complex
5a (Figure 2) as previously reported by Nishiyama.12 Metal anal-
ysis showed that 80% of the Pybox ligands reacted with the
ruthenium dichloride dimer to form the complex 5a. This means
that most of the ligand grafted on the starch was easily accessible
to the ruthenium salt. In parallel, the homogeneous complexes
5b synthesized from 4-sulfanylpybox 3 was prepared in situ
(ligand:Ru = 4:1).
Catalytic performances of these complexes were tested
in asymmetric cyclopropanation reaction between styrene and
ethyl diazoacetate in dichloromethane at room temperature.
(Table 1)
The homogeneous 4-sulfanylpybox–Ru catalyst 5b was effi-
cient for the cyclopropanation reaction and significant 89/11
trans/cis ratio was achieved. The enantiomeric excess of the
trans and cis isomers reach 77 and 63% respectively. As
expected, these values are some lower than those achieved using
4H-Pybox–Ru catalysts (88 and 70% respectively8) owing to the
presence of a slightly electron-donating group on the pyridine
moiety of the ligand in 5.12
In conclusion, we have shown the possibility of immobiliz-
ing chiral pybox system on modified starch. This fact, make us
consider that other polysaccharides can be developed as new
types of supports for organometallic species. Further works are
under progress to graft Pybox moieties using different linkers
and biopolymer.
A.C. thanks European Commission for a Marie Curie Host
Fellowship grant, and PPQ2002-04012 project for a financial
support. C.V. thanks ADEME (Agrice program) for a financial
support.
References
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8
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Table 1. Enantioselective catalyzed cyclopropanationa
Ligand/
Ru
Catalyst/%
Yield/% trans/cis eetrans/% eecis/%
5b/3
4:1
1:1
67
28
45
44
89/11
74/26
75/25
76/24
77
49
50
46
63
18
16
16
´
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5a run 3
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aReaction conditions: 5 mmol of styrene, 0.5 mmol of ethyl diazo-
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Published on the web (Advance View) December 3, 2005; DOI 10.1246/cl.2006.44