Remarkable efficiency improvement in the preparation of insoluble polymer-bound (IPB) enantioselective catalytic systems by the use of silicone chemistry

Article abstract of DOI:10.1002/adsc.200700359

The use of platinum-catalyzed hydrosilylation chemistry of silicones greatly simplifies the preparation of bis-oxazoline (box) ligands covalently bound to an insoluble polymeric support. The use of such immobilized chiral ligands in different copper-catalyzed asymmetric transformations (carbonyl-ene, Mukaiyama aldol and olefin cyclopropanation reactions) allows the attainment of high levels of enantioselectivity (91-99% ee).

Full text of DOI:10.1002/adsc.200700359

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DOI: 10.1002/adsc.200700359
Remarkable Efficiency Improvement in the Preparation of Insolu-
ble Polymer-Bound (IPB) Enantioselective Catalytic Systems by
the Use of Silicone Chemistry
Alessandro Mandoli,a Marco Lessi,a Dario Pini,a,* Claudio Evangelisti,a
and Piero Salvadoria
a
Dipartimento di Chimica e Chimica Industriale, Università di Pisa, and C.N.R. – I.C.C.O.M. (Section of Pisa),
Via Risorgimento 35, 56126, Pisa, Italy
Fax : (+39)-050-221-9260; e-mail: pinida@dcci.unipi.it
Received: July 23, 2007; Published online: February 6, 2008
Supporting information for this article is available on the WWW under http://asc.wiley-vch.de/home/.
Abstract: The use of platinum-catalyzed hydrosily-
lation chemistry of silicones greatly simplifies the
preparation of bis-oxazoline (box) ligands covalent-
ly bound to an insoluble polymeric support. The
use of such immobilized chiral ligands in different
copper-catalyzed asymmetric transformations (car-
bonyl-ene, Mukaiyama aldol and olefin cyclopropa-
nation reactions) allows the attainment of high
levels of enantioselectivity (91–99% ee).
inside the polymer network, which are virtually un-
available for catalysis.
In an effort to solve these problems, we recently
undertook an investigation of cross-linked poly(di-
methylsiloxane) (PDMS) as a new support type.[3,4]
The underlying idea of this approach was that the
robust Pt-catalyzed hydrosilylation technology[5] could
significantly improve the covalent heterogenization
efficiency, yet still providing insoluble materials with
a proper microenvironment for asymmetric transfor-
mations. Given the current interest in the develop-
ment of recoverable bis-oxazolines (box) and the
array of techniques explored for this purpose,[6,7] the
anchoring of box ligands was chosen as a convenient
arena for testing this hypothesis.
À
Keywords: asymmetric catalysis; bis-oxazoline; C
C bond formation; silicones; supported catalysts
With this aim in mind, a route was designed
The development of easily recoverable variants of (Scheme 1) which involves the use of a simple modi-
chiral catalysts has been pursued for over three de- fied box, provided with a terminal olefin group. By
cades as a means to improve homogeneous enantiose- following the same procedures described for the
lective systems,[1] but the actual exploitation of this parent ligands 1a, b,[8] the derivatives 2a, b were
concept in a real scenario seems to be still awaiting a therefore easily prepared from the corresponding
convincing proof.[2] Arguably, this is a consequence of chiral amino alcohols and subjected to immobilization
the inherent limitations of the approaches disclosed into an insoluble PDMS matrix by a two-step proce-
so far, including the additional synthetic efforts for dure. Accordingly, 2a or 2b was initially reacted
the preparation of recoverable derivatives and the under Pt catalysis with linear poly(dimethylsiloxane-
frequent reduction in the catalytic performances with co-methylhydrosiloxane) (PMHS, 3), to afford the
respect to the parent (unmodified) catalyst. In this soluble silicones 4a, b, and then made insoluble by
regard, the covalent binding of a chiral ligand to an cross-linking with a suitable diene compound (5–7).
insoluble polymer (IPB approach) has been often This choice allowed the monitoring of the first stage
1
considered a least attractive option, because of the by H and 13C NMR, which confirmed the consump-
difficulties in the handling of sensitive (e.g., styrene- tion of the olefinic double bond of 2a, b and ruled out
type) monomer derivatives or the poor overall yield any significant isomerization of the alkene moiety or
of the heterogenization procedure.[2] Depending upon degradation of the box core (Supporting Informa-
the strategy adopted, additional shortcomings are also tion). Initial attempts to cross-link 4a, b with divinyl-
frequently encountered, such as the adverse effect of benzene (5) in bulk, afforded the materials 8 and 9 as
the support structure on stereoselectivity and the oc- insoluble powders, but the yields were fair at most. In
currence of a significant fraction of chiral units buried order to improve both the anchoring efficiency and
Adv. Synth. Catal. 2008, 350, 375 – 379
ꢀ 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
375

Alessandro Mandoli et al.
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Scheme 1. Preparation of silicones-type IPB-box materials 8–11
the handling of the final IPB-box, the preparation of
In order to evaluate the accessibility of the anch-
polymeric films was therefore explored.[4,5b] For this ored chiral units in the materials 8–11, their Cu(II)
purpose, a solution of 4b was transferred to a Teflon- ion uptake (U) from a THF solution of Cu(OTf)2 was
A
lined vessel, a diene was added and the resulting mix- also determined (Table 1 and Supporting Informa-
ture was gently cured under air, followed by end-cap- tion). From these data the available box fraction (A)
À
ping of residual Si H with 1-hexadecene. Under these could be calculated, as the U/L ratio, which was
conditions the use of 5 as the cross-linker resulted in found to be strongly dependent upon the support
extremely fragile materials, but its replacement with a composition and curing procedure. Indeed, while in 8
combination of low and high molecular weight vinyl- and 9 only 40–65% of the ligand content proved to
terminated PDMS (6 and 7) was sufficient for obtain- be readily involved in the metal complexation, in the
ing the IPB-box 10 and 11 as robust films. After re- case of 10 and 11 the U and L values appeared to
moval of any soluble component by continuous ex- match each other, within the experimental accuracy.
traction, nitrogen elemental analysis of 8–11 allowed As a result, a complete accessibility of the chiral sites
us to calculate the ligand loading (L) and the yield of in the latter materials seems therefore possible, high-
supported chiral units with respect to starting 2a or lighting a significant improvement attained with the
2b (Ya, see Table 1). These data confirmed a dramatic support architecture of 10 and 11.
improvement in the anchoring efficiency by the film
The performances of 8–11 were initially tested in
technique with siliconic cross-linkers. In fact, thanks some of the enantioselective transformations devel-
to the nearly quantitative incorporation of 2b into the oped by Evans and co-workers,[9] where a [box-Cu-
insoluble network (Table 1, entries 3 and 4), the over-
all yield of IPB-box 10 and 11 from the common (S)- cordingly, the Ph-substituted material 8 was loaded
tert-leucinol precursor (77–80%) appears comparable with Cu(OTf)2 and employed to promote the bench-
(OTf)2] complex behaves as a chiral Lewis acid. Ac-
AHCTREUNG
to that of the corresponding soluble ligand 1b mark addition of a-methylstyrene to ethyl glyoxyla-
(87%).[8b]
te.[9a] In comparison to the use of the soluble ligand
1a and a previously reported polystyrene IPB-box,[6d]
some reduction in activity was evident under these
conditions, but we were pleased to find that [8·Cu-
Table 1. Characterization of the IPB-box ligands 8–11.
Entry IPB-
box
R
L
Ya
U
A
(OTf)2] smoothly promoted the formation of the ene
[mmolg]À1[a] [%][b] [mmolg]À1[c] [%][d]
product 12 (Table 2, entry 1),[10] with an ee value
slightly exceeding that provided by the soluble cata-
lyst from 1a.[9a] As already demonstrated for a similar
IPB-box system,[6d] the supported complex could be
recovered by filtration and directly used in two fur-
ther runs, without any major loss of catalytic efficien-
cy (Table 2, entries 2 and 3).
1
2
3
4
8
9
10
11
Ph
0.20
35
67
92
96
0.13
0.14
0.23
0.18
65
40
>95
>95
t-Bu 0.35
t-Bu 0.22
t-Bu 0.17
[a]
[b]
The box loading, determibned by Nanalysis.
Yield of the anchoring step, based on the amount of 2a
or 2b.
Moving to the t-Bu-substituted materials, the Mu-
kaiyama aldol reaction was selected as competent
Cu(II)-catalyzed processes.[9b] When the addition was
[c]
[d]
Cu
A
U/L ratio.
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Preparation of Insoluble Polymer-Bound (IPB) Enantioselective Catalytic Systems
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Table 2. Asymmetric ene and Mukaiyama reactions with the IPB-box ligands 8, 10 or 11.[a]
Entry
Eq.
Ligand
Cycle
T [8C]
t [h]
Product
Yield [%][b]
ee [%][c]
1
2
3
4
5
6
7
8
9
(1)
(1)
(1)
(2)
(2)
(2)
(2)
(2)
(2)
8
8
8
10
10
10
11
11
11
0
1
2
0
0
0
0
0
0
0
0
-78
0
22
22
22
2
2
2
2
22
2
12
12
12
13
13
13
13
13
13
83
70
72
83
84
82
98
91
95
91 (89)
91
91
94 (94)
92
92
93
99 (99)
93
1
2[d]
0
1
2[d]
[a]
Reagents and conditions: for Eq. (1) a-methylstyrene (0.18 mmol), ethyl glyoxylate (4 equivs.); for Eq. (2) methyl pyru-
vate (0.25 mmol), 1-(tert-butylthio)-1-(trimethylsiloxy)ethene (1.2 equivs.).
Isolated yield. For runs 4–9, GLC yield with methyl 1-naphthoate as internal standard; 82% yield after purification of
the pooled crude products
[b]
[c]
[d]
By HPLC. In parentheses ee values with 1a or 1b.[9a,b]
After recharging with Cu(OTf)2 and adding 3Š MS.
G
carried out at 08C, in the presence of the materials 10 light, this proved sufficient to cause a large improve-
and 11 charged with Cu(OTf)2, the product 13 was ment of the enantioselectivity, eventually leading to
AHCTREUNG
isolated in high yield and ee values (Table 2, entries 4 the cyclopropanes 14 with ee values within 1% of
and 7), which again appear to match those provided those provided by 1b under comparable conditions
by the soluble counterpart [1b·Cu
(OTf)2].[9b] Recy- (Table 3, entries 1–3).[11] With this simple modifica-
U
cling of the supported catalysts proved also readily tion, the supported catalysts were also found to be ef-
feasible (Table 2, entries 5, 6, 8, and 9). In this regard, fective at low loadings and in the course of several re-
the film shape of 10 and 11 greatly aided the recovery cycle runs (Table 3, entries 1 and 4–8, respectively),
of the material, allowing the separation from the reac- outperforming in this case also analogous polystyr-
tion mixture by siphoning instead of filtration. In ad- ene-supported systems.[6c,e,f] More in general, the ma-
dition to this practical improvement, another remark- terials 8 and 10–11 provided the highest ee values re-
able advantage of the siliconic architecture became ported to date for any Evansꢁ type IPB-box ligand
evident by running the reaction at low temperature. (either on organic[6b–f] or inorganic supports),[6g] in the
Indeed, at variance with polystyrene materials which aforementioned reactions. For the sake of comparison
perform poorly under these conditions,[6b] [11·Cu- it is worth noting that catalyst loadings and ee values
ACHTREUNG
For testing the t-Bu-substituted ligands 9–11 in a tion of styrene with a structurally related aza-box on
process involving box-Cu(I) species,[9c] olefin cyclo- a Merrifield resin;[12] this class of ligands, however,
propanation was explored next. With this aim, the appears to have a somewhat different reaction and
supported complex obtained by phenylhydrazine re- substrate scope than carbon-based box ligands.[12]
duction of [9·Cu
C
In conclusion, a new strategy has been described
Adv. Synth. Catal. 2008, 350, 375 – 379
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377

Alessandro Mandoli et al.
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Table 3. Asymmetric cyclopropanation of olefins with IPB-box ligands 10 and 11.[a]
Entry
Product R1, R2
Ligand[b]
Cycle
T [8C]
t [h][c]
Yield [%][d]
ee [%][e]
1
2
3
4
5
6
7
8
Me, Me
Ph, Ph
H, Ph
Me, Me
Me, Me
Me, Me
Me, Me
Me, Me
10 (0.2)
10 (1)
10 (1)
11 (0.5)
11 (0.5)
11 (0.5)
11 (0.5)
11 (0.5)
0
1
2
0
0
22
22
22
4
4
4
90
96
95
95
97
95
96
91
91
25
25
0
0
0
96
96[f]
91[g]
[g]
1
-
-
[g]
2
3[h]
4
0
0
4
4
-
[g]
[g]
-
[a]
Reagents and conditions: ethyl diazoacetate (1 mmol), olefin (2–7 equivs.), PhNHNH2 (2 equivs. vs. Cu).
Amount of supported complex in parentheses [mol%].
Addition time of ethyl diazoacetate.
By GLC with dodecane as internal standard.
By HPLC or GLC; ee values with 1b in parentheses.
[b]
[c]
[d]
[e]
[f]
trans:cis=78:22 (cis 90% ee).
With 5 mmol of ethyl diazoacetate per run; 75% isolated yield after distillation of the pooled crude product.
[g]
[h]
Material recharged with Cu(OTf)2 and reduced before use.
A
The solution was placed under air into a flat PTFE-lined
vessel (40 cm2 bottom area), together with a solution of 6
and 7 in toluene (2 mL). The vessel was covered with a glass
plate and heated overnight at 508C. The resulting film was
swollen with a solution of 1-hexadecene (0.56 mL) in tolu-
ene (1 mL) and the solvent was evaporated again, by gently
heating for 2 h at 508C. The polymer film was moistened
with a little n-hexane, transferred to a metal-net thimble,
and countinuously extracted in a Soxhlet device, for 2–3
days, with dry CH2Cl2 and THF; the UV spectra of the final
washings were flat in the 240–350 nm region (A<0.005,
1 cm cell). The almost colorless and nearly transparent films
10 and 11 (approx. 0.2–0.4 mm thick) were dried under re-
duced pressure and characterized by IR, elemental analysis
and copper uptake measurements.
grade chemicals. As demonstrated herein for the box
case, this may allow an unprecedented simple prepa-
ration of the IPB system. Moreover, thanks to the
specific properties of the PDMS network a virtually
complete access to the supported chiral units and the
attainment of an adequate microenvironment for a
range of mechanistically different asymmetric trans-
formations seems possible: In fact, besides closely
mimicking the corresponding soluble ligands in each
case, the optimized materials obtained in this work
appear to rank as the most effective Evansꢁ type IPB-
box systems reported so far.
The application of the present strategy to other
supported enantioselective catalysts is currently un-
derway.
Acknowledgements
Experimental Section
Work supported by the University of Pisa, MIUR (Project
“Sintesi e Stereocontrollo di Molecole Organiche per lo Svi-
luppo di Metodologie Innovative di Interesse Applicativo”)
and ICCOM-C.N.R.
Detailed procedures for the synthesis of monomers 2a and
b, shown in Scheme 1, are given in the Supporting Informa-
tion. Mesitylene-solvated Pt catalyst (1 mg Pt/mL) was pre-
pared by metal vapor synthesis (MVS) as described
before.[13]
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Adv. Synth. Catal. 2008, 350, 375 – 379

Preparation of Insoluble Polymer-Bound (IPB) Enantioselective Catalytic Systems
COMMUNICATIONS
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Adv. Synth. Catal. 2008, 350, 375 – 379
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