Ruthenium-catalysed cross metathesis binding of functionalized olefins to polystyrene resin via a novel allylsilyl linker suitable for electrophilic cleavage

Article abstract of DOI:10.1039/a701122i

1% Divinylbenzene-crosslinked allyldimethylsilyl polystyrene 1 undergoes highly efficient ruthenium-catalysed cross-metathesis with functionalized terminal olefins and allows electrophilic cleavage of the resulting functionalized allylsilane.

Full text of DOI:10.1039/a701122i

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Ruthenium-catalysed cross metathesis binding of functionalized olefins to
polystyrene resin via a novel allylsilyl linker suitable for electrophilic cleavage
Matthias Schuster, Norbert Lucas and S. Blechert*†
Institut fu¨r Organische Chemie, Sekr. C3, Technische Universita¨t Berlin, Straße des 17. Juni 135, D-10623, Germany
1% Divinylbenzene-crosslinked allyldimethylsilyl polysty-
rene 1 undergoes highly efficient ruthenium-catalysed cross-
metathesis with functionalized terminal olefins and allows
electrophilic cleavage of the resulting functionalized allyl-
silane.
of 1.3 mmol g21. Cross metathesis was performed in refluxing
dichloromethane using 0.05 mmol of Ru and 1.0–2.0 mmol of
terminal olefin per gram of resin.§ Loadings of cross metathesis
Table 1 Results of the electrophilic cleavage of metathetically obtained
polystyrene-supported allylsilanes 2
During the last decade, olefin metathesis has emerged as a
powerful synthetic tool for the formation of CNC double bonds.1
Most recently, it has been demonstrated that highly selective
cross-coupling2 between functionalized terminal olefins can be
performed under catalysis of well defined metathesis catalysts.3
In the advent of combinatorial chemistry there is an increasing
demand for innovative chemistry on solid supports including
novel linker concepts. Cross metathesis involving polymer-
supported olefins should enable the binding of target molecules
via the highly stable CNC double bond in a catalytic manner. In
an initial report4 we described the catalytic immobilisation of
several small nonpolar molecules to a modified trityl poly-
styrene resin using Grubbs’ ruthenium initiator3 Cl2(PCy3)2-
RuNCHPh Ru (Cy = cyclohexyl). Cross metathesis products
were characterized after cleavage from the acid-labile trityl
linker.
Here we present allyldimethylsilyl polystyrene 1, which upon
ruthenium-catalysed cross metathesis with terminal olefins
yields immobilized products 2 (Scheme 1). Products 2 can be
subject to electrophilic attack5 resulting in C–Si cleavage and,
thus, the formation of soluble products 3. Cleavage can be
performed either as protodesilylation or in combination with an
additional synthetic step, when electrophiles other than H+ are
employed.
Metathesis product 2
Cleavage product 32
R =
Ph
Ph
2ab
3ad (0.5 mmol g–1
)
MeO
MeO
O
2
2bb
O
2
3bd (0.43 mmol g–1
)
AcO
AcO
AcO
AcO
O
O
O
AcO
O
AcO
OAc
OAc
2cc
3cd (0.34 mmol g–1
)
AcO
AcO
AcO
AcO
O
O
AcO
O
O
AcO
OH
OAc
2dc
OAc
3dd (0.41 mmol g–1
)
OH
ZHN
Z HN
Polystyrene 1 closely resembles soluble allyltrimethylsilane,
which was found to be an excellent cross metathesis partner by
us and others.2 The synthesis of 1 by treatment of polystyrene
(1% DVB-crosslinked) (DVB = divinylbenzene) with BuLi–
TMEDA and subsequently with allyldimethylsilyl chloride is
based on the observation6 that under these conditions metal-
lation occurs in the para-position of the phenyl ring, ex-
clusively.‡ The silicon content of 1 was determined by
Inductive Coupled Plasma-Optical Emission Spectroscopy
(ICP-OES) of sodium tertaborate melt samples. We found that
removal of excess BuLi–TMEDA by repeated washing of the
lithiated polymer ensures high loading capacities and sig-
nificantly decreases the amount of the electrophile required.
The resin employed throughout this study had a silicon content
O
2ec
O
3ed (0.59 mmol g–1
)
O
O
BocHN
O
BocHN
OH
N
H
N
H
Bn
O
Bn
O
2fc
3fe (0.38 mmol g–1
)
FmocHN
FmocHN
OAc
3gd (<0.1 mmol g–1
OAc
2gc
2ab
)
O
i, BuLi–TMEDA
Me
ii, wash (3x)
Bn
3hf (0.50 mmol g–1
Si
iii, Me2ClSiCH2CH=CH
)
Me
Polystyrene
(1% DVB)
1
a
Isolated yield of cleavage product 3 per gram of 2 given in parentheses.
b Methathesis conditions: 300 mg 1; 0.6 mmol terminal olefin; 0.015 mmol
Ru; 5 ml CH2Cl2 (reflux); 18 h. Metathesis conditions: 300 mg 1; 0.3
R
c
Me
Si
R
E+
mmol terminal olefin; 0.015 mmol Ru; 5 ml CH2Cl2 (reflux); 18 h.
1
cleavage product 3
d
e
Cleavage conditions: 3% TFA in CH2Cl2, 18 h. Cleavage conditions:
Ru
1.5% TFA in CH2Cl2, 24 h. f To 500 mg of 2a in 20 ml CH2Cl2 was added
1.3 mmol 1,1-diethoxypropane and 1.3 mmol TiCl4 at 278 °C. After 22 h
aqueous work-up (NaHCO3) and flash chromatography of the CH2Cl2
phase gave the product.
Me
2
Scheme 1 Synthesis of, Ru-catalysed cross-metathesis with, and electro-
philic cleavage from polystyrene-supported allylsilane 1
Chem. Commun., 1997
823

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Nu–
Me
Si
employing intramolecular electrophilic attack is currently being
developed.
OR
H+
+ ROH
Footnotes
Me
† E-mail: sibl@wap0105.chem.tu-berlin.de
Scheme 2 Proposed mechanism for the protodesilylation of allysilanes 2
‡ Synthesis of 1: 8 g of polystyrene (1% DVB) was suspended in 12 ml of
cyclohexane, 12 ml (80 mmol) TMEDA and 48 ml (1.6 m in hexane, 77
mmol) BuLi were added and the suspension was gently shaken for 3 d at
ambient temperature under exclusion of moisture and air. The supernatant
was removed through a septum and replaced by 30 ml cyclohexane. This
procedure was repeated twice, before 12 ml (80 mmol) allyldimethylsilyl
chloride was added under shaking. After 1 h the reaction was quenched with
40 ml methanol, the resin was quickly filtered off, washed repeatedly with
methanol, dichloromethane and MeOBut and dried under vacuum.
§ Synthesis of 2b: to 300 mg of 1 in 5 ml absolute dichloromethane was
added 120 mg (0.6 mmol) of 2a and 12 mg (0.015 mmol) of Ru. The
resulting suspension was refluxed under argon atmosphere (glove box) for
18 h. The resin was filtered off and washed with 20 volumes each of DMF,
chloromethane, methanol and diethyl ether. Residual diethyl ether was
removed under high vacuum.
with oxygen in the allyl position
immobilisation products 2 were calculated from the amount of
soluble cleavage products 3, liberated from 2 by protodesilyla-
tion with TFA (3% in CH2Cl2).
As shown in Table 1, protodesilylation of 2a furnished the
homologized product 3a;¶ 0.5 mmol was released per gram of
2a. This modification level indicates a highly effective
metathesis reaction. A diester function does not affect the
immobilisation reaction as demonstrated by the synthesis of 2b
with 0.43 mmol g21. Protodesilylation yields the expected
product 3b. A major goal of this study was to demonstrate that
polyfunctional molecules of biological interest such as glyco-
sides and amino acid derivatives can also be effectively coupled
¶ After acidic cleavage homoallyldimethylsilanol was isolated as a minor
byproduct. Its formation can be rationalized by the following reaction
sequence:
to 1. Indeed 2c was formed with a capacity of 0.34 mmol g21
.
Protodesilylation to 3c proceeded with complete retention of the
acetal, thus underlining the exceptionally mild cleavage condi-
tions. However, cleavage of 2d under identical conditions
furnished tetra-O-acetyl glucose 3d instead of the expected
homoallyl glycoside. Possibly, deglycosylation of 2b proceeds
through a modified protodesilylation mechanism as shown in
Scheme 2.
Me
HO Si
Me
Me
Ar Si
Me
Me
Ar Si
Me
Me
Me
Ar Si
Me
H+
H+
Ru
Si Ar
Me
1
References
The same cleavage pattern should be obsered when allyl
esters are used in the metathesis reaction. Indeed, cleavage of 2e
and 2f furnished the respective free carboxylic acids 3e and 3f.
This special type of allyl ester is even more acid sensitive than
the Boc group, which remains intact when the cleavage reaction
is performed using 1.5% TFA for 24 h. The scope of this
unexpected cleavage reaction remains to be investigated. In
contrast to isoleucin allyl ester derivatives the metathetical
immobilisation of the protected C-allylglycinol was less
successful, as demonstrated by the amount of 3g that could be
released from 2g. Eventually, we wished to demonstrate the
utility of solid phase-bound allylsilanes 2 as starting materials
for C–C bond formation. To give a first example of the addition
of a carbon electrophile to a polymer-supported allylsilane, a
mixture of 2a and 1,1-diethoxyethane was treated with TiCl4.
The yield of product 3h proved comparable to the yield of the
corresponding protodesilylation product 3a.
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In conclusion, we have presented a novel polystyrene resin
containing an allylsilyl linker moiety. The linker enables both
binding of functionalized olefins by catalytic cross metathesis
and cleavage under exceptionally mild acidic conditions. The
linker allows the cleavage to be performed under formation of
an additional C–C bond. A cyclisation–cleavage strategy
5 For
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Received in Cambridge, UK, 18th February 1997; Com.
7/01122I
824
Chem. Commun., 1997