Catalytic atom-transfer radical cyclization by copper/bipyridine species encapsulated in polysiloxane gel

Article abstract of DOI:10.1039/b923213c

Novel polysiloxane gel, in which CuCl/bipyridine species are immobilized, is prepared by treatment of polymethylhydrosiloxane with 4,4′-bis[(2- propenyl)oxy]-2,2′-bipyridine and 1,5-hexadine in the presence of Karstedt′s catalyst followed by addition of CuCl. This polysiloxane gel acts as a reusable catalyst in the atom-transfer radical cyclization of α-halogenated acetamide derivatives in high turnover numbers without allowing leakage of the metal species.

Full text of DOI:10.1039/b923213c

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Catalytic atom-transfer radical cyclization by copper/bipyridine species
encapsulated in polysiloxane gelw
Yukihiro Motoyama,ab Kazuyuki Kamo,b Akihiro Yuasaa and Hideo Nagashima*ab
Received (in Cambridge, UK) 5th November 2009, Accepted 15th December 2009
First published as an Advance Article on the web 21st January 2010
DOI: 10.1039/b923213c
Novel polysiloxane gel, in which CuCl/bipyridine species are
immobilized, is prepared by treatment of polymethylhydrosiloxane
with 4,40-bis[(2-propenyl)oxy]-2,20-bipyridine and 1,5-hexadine
in the presence of Karstedt0s catalyst followed by addition of
CuCl. This polysiloxane gel acts as a reusable catalyst in the
atom-transfer radical cyclization of a-halogenated acetamide
derivatives in high turnover numbers without allowing leakage of
the metal species.
species active towards catalytic reactions is somehow
stabilized in the gel. These actually provided us an idea:
if a functional group that can ligate to the metal is introduced
to the bridge for cross-linking, the gel would soak up a
metal salt and produce a metal complex in the gel active
towards the homogeneous catalysis. The resulting active
species in the gel would be barely leachable, and more stable
than those in solution, contributing to reusability of the gel
catalyst.
To examine this idea, we prepared CuCl(bipy) species in a
polysiloxane gel, which is useful for catalytic atom-transfer
radical cyclization of N-allyl-a-halogenated acetamides.4,5
It is known that the copper-catalyzed cyclization of these
acetamides rapidly takes place in dichloromethane but that
the catalytic species is sensitive to air and easily deactivated.5c,6
If the polysiloxane network contributes to stabilization of the
active species and the gel catalyst is reusable, the catalytic
efficiency would be improved. The facile separation of the gel
catalyst from the product makes us skip the removal of the
copper residue from the product. Questions were how to
synthesize the polysiloxane gel containing bipyridine, and
how to absorb CuCl, which is hardly soluble in CH2Cl2, into
the gel.
The utility of molecular catalysts immobilized on solid
supports is well recognized from environmental and economical
points of view because metal catalysts are easily separated
from the product and reusable.1 Cross-linked polydimethyl-
siloxanes (PDMS) prepared by curing them with tetrakis-
(dimethylsiloxy)silane reportedly act as efficient carrier
materials for entrapment of transition metal complexes.2 Since
leaching of the occluded metal species does not occur in
solvents in which solubility of the metal complex is low, the
metal-containing PDMS gels behave as a reusable catalyst in
limited solvents, usually in aqueous or alcoholic media.2
We have recently developed novel access to metal-containing
cross-linked polysiloxanes by using polymethylhydrosiloxane
(PMHS) as a silicone source.3 The Si–H group of PMHS is
easily activated by transition metals, reacting with carboxamides,
diols, and a,o-alkadienes to make oxygen-, alkylenedioxy-,
and alkylene-bridges, respectively, between the polysiloxane
chains. Several late transition metal compounds such as
(m3,Z2,Z3,Z5-acenaphthylene)Ru3(CO)7, H2PtCl6, Karstedt’s
catalyst, and Vaska’s complex are active towards the
crosslinking, and metals are self-encapsulating to the polysi-
loxane gels during the reaction. The formed metal-containing
polysiloxane gels behave as good catalysts for alkene
isomerization3c and hydrogenation of nitroarenes,3d which
are reusable several times without leaching the metal species
even in common organic solvents. During the study, we were
aware of three important properties of metal-containing
polysiloxane gels. First, rapid transfer of organic molecules
occurs inside and outside of the swelled gel in organic solvents.
Second, a metallic species once entrapped in the polymer
network very little leaches outside of the gel. Third, a metallic
The polysiloxane gel encapsulating CuCl(bipy) species
([Cu/bipy]@Si) was synthesized as shown in Scheme 1. In
tetrahydropyran 4,40-bis[(3-propenyloxy)methyl]-2,20-bipyridine
(DABipy was prepared in three-step sequences from
2,20-bipyridine-4,40-dicarboxylic acid, see ESIw) (DABipy;
0.05 mmol) and PMHS [Si–H = 2 mmol] were treated with
Karstedt’s catalyst ([Pt] = 0.01 mmol) at room temperature
for 30 min. Subsequent addition of 1,5-hexadiene (1.5 mmol)
at 40 1C for 2 h resulted in cross-linking of PMHS to gave a
yellow solid. All of the DAbipy and a part of 1,5-hexadiene
a Institute for Materials Chemistry and Engineering,
Kyushu University, Kasuga, Fukuoka 816-8580, Japan.
E-mail: nagasima@cm.kyushu-u.ac.jp; Fax: +81-92-583-7819;
Tel: +81-92-583-7819
b Graduate School of Engineering Sciences, Kyushu University,
Kasuga, Fukuoka 816-8580, Japan
w Electronic supplementary information (ESI) available: Detailed
experimental procedures and results, and characterization data and
NMR spectra of both the substrates and the products. See DOI:
10.1039/b923213c
Scheme 1 Preparation of [Cu/bipy]@Si.
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charged were linked to the siloxane chain. Solid-state 29Si and
13C NMR suggested that Si–H groups [1.04 mmol (52%)] in
the PMHS used were converted to the Si–C moieties, and
ca. 14% of alkenyl moieties remained unreacted. The cross-
linking density of the formed gel was calculated to be 38%.
The unreacted Si–H groups (0.96 mmol, 48% in PMHS used)
in the gel were completely end-capped by the subsequent
reaction with ethylene.w The resulting gel containing
bipyridine and a small amount of Pt ([bipy]@Si) was treated
with CuCl (0.02 mmol) in dichloromethane at room tempera-
ture under an argon atmosphere. Although CuCl is hardly
soluble in CH2Cl2, the solid CuCl quickly disappeared and the
color of the gel turned from yellow to reddish brown. After
1 h, the gel was washed with dichloromethane and dried under
vacuum to afford [Cu/bipy]@Si. ICP-MS analysis revealed
that the dichloromethane solution contained 102 mg of copper;
which meant that 92% of the charged CuCl was entrapped in
the gel.w
Table 1 ATRC of 1a with homogeneous CuCl/bipyridine and
[Cu/bipy]@Si catalystsa
Entry Catalyst
S/Cb Time/h Yield (%) TONc
1
2
3
4
5
6
CuCl/bipyridine
10
o0.5
1
1
4
15
60
>99
66d
10
66
73
220
220
110
CuCl/bipyridine
[Cu/bipy]@Si
[Cu/bipy]@Si
[Cu/bipy]@Si (2nd) 220
[Cu/bipy]@Si (3rd) 220
100
220
220
33d
>99
>99
50d
a
All reactions were carried out with 1a and CuCl/bipyridine
(0.02 mmol) or of [Cu/bipy]@Si (0.018 mmol Cu) catalyst in CH2Cl2
b
at room temperature. Substrate/catalyst mole ratio. Product/
d
catalyst mole ratio. Determined by H NMR analysis.
c
1
It is known that a 1 : 1 mixture of CuCl and bipyridine forms
a brown solution of CuCl(bipy), which is extremely sensitive
towards oxygen and is instantly turned into a blue Cu(II)
species by exposure to air.5c The CuCl(bipy) in the gel is more
stable than that in solution, and can be stored under nitrogen
atmosphere for over a month; its handling can be done under
aerobic conditions as long as the contact time with air is short.
Treatment of [Cu/bipy]@Si with N,N-diallyl-a,a,a-trichloro-
acetamide (1a) results in cyclization to the lactam 2a as shown
in Table 1.z The reaction with [Cu/bipy]@Si (S/C = 220)
proceeded without loss of the catalytic activity and the
substrate was completely consumed after 4 h (entries 2 vs.
3 and 4).y Separation of 2a from [Cu/bipy]@Si can be done by
filtration. The [Cu/bipy]@Si recovered from the experiment
shown in Table 1, entry 4 was still active and reusable for a
further catalytic run, though the catalytic activity gradually
decreased. The total turnover number (TON) of these
recycling experiments reached 550 [mol (2a)/mol (Cu)]
(entries 4–6). ICP-MS analysis of the product obtained in
each cycle has shown that metallic species (both Cu and Pt)
leached from the gel were lower than the detection limit
(o0.3 ppm). This is in sharp contrast to the fact that
the CuCl(bipy) species generated in situ in solution catalyzed
the quick conversion of 1a to 2a. However, the catalyst
upon decrease in the number of halogens on the a-carbon
and/or the ratio of syn-rotamer (both a-carbon and olefinic
moiety are syn-orientation favorable for the cyclization) to the
anti-rotamer.7,8 This explains the slower reactions of 1d, 1g,
and 1h.4–7 Interesting solvent effects were seen in the
[Cu/bipy]@Si-catalyzed cyclization of 1d, the reaction
occurred at lower temperatures in CH2Cl2 than that in ethyl
acetate (entries 4–6). The cyclization of N-allyl-N-tosyldichloro-
acetamide (1g) gave the product 2g as a trans/cis mixture
(4 : 1) (entry 8).7a The reaction of N-benzyl-N-(2-methyl-1-
propenyl)-a,a,a-trichloroacetamide (1h) afforded the b-lactam
2h in quantitative yield (entry 10). The present system
was adaptable to a gram-scale production of lactams. For
example, the reaction of 1c (1.065 g; S/C = 167) in ethyl
acetate at room temperature for 8 h afforded 1.040 g of 2c
(98% yield). In all cases listed in Table 2, the product was
separated from the gel catalyst simply by filtration. Removal
of the solvent in vacuo afforded the product in almost quanti-
tative yields. High purity of the product was demonstrated by
NMR showing no contamination of either by-product or
solvent, and also showing a melting point within a narrow
temperature range.w
was deactivated after
1
h
when TON reached 66
In summary, our siloxane gel, [bipy]@Si, in which a
bipyridine is embedded, is facilely prepared from PMHS
and DAbipy by the platinum-catalyzed hydrosilylation
of alkenes. The [bipy]@Si quickly soaks up CuCl species to
form [Cu/bipy]@Si. The CuCl(bipy) species in the gel is
more stable than that in solution, showing high catalytic
efficiency towards ATRC of N-allyl or N-vinyl-a-halogenated
acetamides. The product without contamination by metallic
species and organic impurities is obtained by simple filtration,
whereas the recovered [Cu/bipy]@Si is reusable. We believe
that this facile access to ‘‘polysiloxane gel catalysts’’ will open
the way to preparation of easily separable and reusable
catalysts and thus take part in progress of immobilized
catalysts.
[mol (2a)/mol (Cu)] (entries 1 and 2); at this time, an insoluble
copper species was formed.5c The separation of the
insoluble species by filtration enabled removal of the
copper species, however, 6% of the charged Cu species was
detected in the crude product in the experiment shown
in entry 1.
Conventional copper-catalyzed cyclization proceeds in
halogenated solvents such as dichloromethane or dichloro-
ethane due to the poor solubility of the copper catalyst. In
contrast, various solvents such as diethyl ether, dimethoxy-
ethane, tetrahydrofuran, tetrahydropyran, toluene, acetnitrile,
and ethyl acetate, were applicable to the reaction with
[Cu/bipy]@Si.w In fact, cyclization of several N-allyl-a-halo-
acetamides proceeded smoothly by catalysis of [Cu/bipy]@Si
in ethyl acetate at room temperature (Table 2).z It is well
known that reactivity of olefinic a-haloacetoamides lowers
This work was supported by a Grant-in-Aid for Scientific
Research from the Ministry of Education, Culture, Sports,
Science and Technology, Japan.
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Table 2 ATRC of various a-halogenated acetamides 1a–ha
Entry
Substrate
Conditions
Product
Yield (%)
1
1a: Z = allyl
1b: Z = Bn
1c: Z = Ts
1d: Z = Ph
1d: Z = Ph
1d: Z = Ph
rt, 1 h
2a: Z = allyl
2b: Z = Bn
2c: Z = Ts
2d: Z = Ph
2d: Z = Ph
2d: Z = Ph
>99
99
>99
58
99
2
3
4
rt, 1.5 h
rt, 1.5 h
rt, 12 h
60 1C, 6 h
rt, 1 h
5
6b
99
7
1e
rt, 12 h
2e
97
8
9
1f
rt, 16 h
2f
99
98
1g
80 1C, 2 h
2g
(trans/cis = 4 : 1)c
10
1h
80 1C, 2 h
2h
99
a
b
All reactions were carried out with 1 (0.2 mmol) and [Cu/bipy]@Si (S/C = 11) in ethyl acetate (1.5 mL). In CH2Cl2. The trans/cis ratio was
c
1
determined to be 4 : 1 by H NMR analysis. The diastereomer ratio is similar to that obtained by CuCl(bipy) in CH2Cl2, see ref. 7.
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M. A. Schiavon, I. V. P. Yoshida, K. J. Ciuffi and M. D. Assis,
Appl. Catal., A, 2005, 296, 120.
prepared from PMHS with 1,5-hexadiene (ref. 3d). One may have
considered that the Pt species remaining in [Cu/bipy]@Si might
contribute to catalytic ATRC. This possibility is excluded, however,
by the experiment in which no cyclization took place in the reaction of
1a with [bipy]@Si which contains ca. 2 mg (0.01 mol%) of Pt species.
y The CuCl content in the gel affected both the yield of the product
and the amount of the metal leached. Preliminary experiments showed
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detected. In increasing the ratio of CuCl to bipy = 5 : 5, the catalytic
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(S/C = 11), and AcOEt (1.5 mL). After the reaction completed, the
insoluble [Cu/bipy]@Si catalyst was removed by filtration with
membrane filters (Teflon; 0.45 mm), and the residual gel was washed
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1
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ꢀc
This journal is The Royal Society of Chemistry 2010
2258 | Chem. Commun., 2010, 46, 2256–2258