Recyclable polyisobutylene-supported pyridyl N-oxide allylation catalysts

Article abstract of DOI:10.1016/j.tetlet.2008.07.047

Polyisobutylene (PIB) is a useful soluble polymer support that facilitates catalyst recovery and recycling in liquid-liquid biphasic systems because the long polyisobutylene chain confers high phase selective solubility in the nonpolar phase of polar-nonpolar liquid-liquid biphasic systems on groups attached to the polymer's terminus. This work shows that PIB-supports that are effective with metal catalysts can also facilitate synthesis and use of organocatalysts. This is demonstrated by the use of a PIB-supported pyridyl N-oxide to promote the allylation of several aromatic aldehydes with allyltrichlorosilane. These studies show that a PIB-supported pyridyl N-oxide is a very active recyclable catalyst that promotes the allylation of aromatic aldehydes in yields of up to 99% yield. These PIB-supported pyridyl N-oxide catalysts were recovered in the hexane phase of a hexane/90% EtOH-H₂O solvent system and were successfully recycled through 5 cycles with little effect on catalyst efficiency.

Full text of DOI:10.1016/j.tetlet.2008.07.047

Tetrahedron Letters 49 (2008) 5608–5610
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Tetrahedron Letters
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Recyclable polyisobutylene-supported pyridyl N-oxide allylation catalysts
*
David E. Bergbreiter , Denisse Ortiz-Acosta
Department of Chemistry, Texas A&M University, PO Box 30012, College Station, TX 77842-3012, USA
a r t i c l e i n f o
a b s t r a c t
Article history:
Polyisobutylene (PIB) is a useful soluble polymer support that facilitates catalyst recovery and recycling
in liquid–liquid biphasic systems because the long polyisobutylene chain confers high phase selective
solubility in the nonpolar phase of polar–nonpolar liquid–liquid biphasic systems on groups attached
to the polymer’s terminus. This work shows that PIB-supports that are effective with metal catalysts
can also facilitate synthesis and use of organocatalysts. This is demonstrated by the use of a PIB-sup-
ported pyridyl N-oxide to promote the allylation of several aromatic aldehydes with allyltrichlorosilane.
These studies show that a PIB-supported pyridyl N-oxide is a very active recyclable catalyst that
promotes the allylation of aromatic aldehydes in yields of up to 99% yield. These PIB-supported pyridyl
N-oxide catalysts were recovered in the hexane phase of a hexane/90% EtOH–H2O solvent system and
were successfully recycled through 5 cycles with little effect on catalyst efficiency.
Received 17 May 2008
Revised 1 July 2008
Accepted 7 July 2008
Available online 11 July 2008
Ó 2008 Elsevier Ltd. All rights reserved.
1. Introduction
nate to the carbonyl group activating the carbonyl toward nucleo-
philic attack.9 More recently Denmark described schemes that
Organocatalysts are currently of intense interest as metal-free
alternatives to commonly used organometallic catalysts.1 While
organocatalysts avoid the use of transition metals, recycling of
these potentially environmentally friendly catalysts remains an
important objective in green chemistry as recycling can reduce
costs involved in these catalysts’ synthesis and use. Recycling of
organocatalysts on soluble and insoluble polymer supports has
been described by various authors using liquid/solid separa-
tions.2–6 However, few examples use liquid/liquid separation to
recover and reuse organocatalysts on nonpolar soluble polymers.7,8
This Letter describes the use of hydrocarbon-soluble, terminally
functionalized, polyisobutylene (PIB) to support an amine N-oxide
catalyst. The studies described below show that this support facil-
itates the synthesis, separation, and reuse of this organocatalyst.
This catalyst is efficiently recovered and separated from products
using a gravity separation of a biphasic liquid/liquid mixture after
a homogeneous catalytic allylation of a variety of aromatic alde-
hydes by allyltrichlorosilane.
use a Lewis basic catalyst that acts as an electron-pair donor
and strong nucleophile toward silicon forming a reactive hyperva-
lent silicate intermediate.10 His group described phospho-
ramides,7 but others have noted that other bases including
formamides, imines, and amine N-oxides are also useful Lewis
base catalysts for allylation reactions.12–18 Kobayashi has also
described insoluble-supported catalysts for similar reactions.19
Here we show that a hydrocarbon polymer, polyisobutylene, can
effectively be used as a phase anchor for these Lewis basic cata-
lysts, and that this polymer facilitates separation, recovery, and
reuse of pyridine N-oxide catalysts in allyltrichlorosilane allyla-
tions of aromatic aldehydes.
2. Results and discussion
As we noted above, others have previously shown amine N-oxi-
des are effective catalysts for allylation reactions.11–14 Based on
that work, we sought to design a PIB-supported amine N-oxide
and to use it to show that nonpolar soluble supports could be use-
ful for organocatalysis. To do this, low molecular weight analogs of
possible PIB-supported pyridyl N-oxides were first synthesized and
tested to determine which mode of attachment to the polymer
would provide the most active basic pyridine N-oxide catalyst for
catalytic formation of homoallylic alcohols from aryl aldehydes.
To this end, pyridyl N-oxides 3 and 6 were synthesized (Eqs. 1
and 2). Then allylation reactions were carried out in 5 mL of CH2Cl2
at 40 °C for 24 h or 48 h using 10 mol % of 3 or 6 as catalyst (Eq. 3).
Catalyst 3 did not show much activity in allylation of either
Allylation of aldehydes is a useful carbon–carbon bond forming
reaction. The product homoallylic alcohols prepared in such reac-
tions can be easily converted into a variety of other products. Ally-
lation reactions with chiral catalysts can introduce chirality into
products with high ee. Historically, these reactions have been cat-
alyzed by electrophilic Lewis acidic metal catalysts. Common
examples of such catalysts include transition metals that coordi-
* Corresponding author. Tel.: +1 979 845 3437; fax: +1 979 845 4719.
E-mail address: bergbreiter@tamu.edu (D. E. Bergbreiter).
0040-4039/$ - see front matter Ó 2008 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2008.07.047

D. E. Bergbreiter, D. Ortiz-Acosta / Tetrahedron Letters 49 (2008) 5608–5610
5609
benzaldehyde or tolualdehyde (63% conversion after 48 h). In con-
1. MsCl, Et3N
CH2Cl2
1. BH3-SMe2
2. H2O2, NaOH
100%
trast, catalyst 6 was effective under these same conditions (P99%
conversion of benzaldehyde, p-tolualdehyde, p-fluoro-benzalde-
hyde, or p-nitrobenzaldehyde).
H
OH
H
2. LiBr, 80 °C
17
17
8
heptane-acetone
O
7
NH2NH2
K-phthalimide
heptane-DMF
H
N
heptane-EtOH
80 °C, 100%
17
C5H11
O
90 °C, 94%
C5H11COCl
K2CO3
MCPBA
CH2Cl2
K2CO3, 87%
C5H11
O
10
O
N
ð1Þ
ð2Þ
EDC, HOBT
N+
O-
N
H
N
N
H
heptane-DMF
2
1
NH2
3
6
H
N
H
NH2
H
CO2H
N+
O-
17
C8H17
NH
HOBT, DMAP
C8H17NH2
105 °C
81%
17
11
H2O2, NaOH
CH3OH, 74%
N+
12
O
OH
O-
N
N+
O-
N+
O-
CH2Cl2, 92%
O
O
4
CO2H
5
Scheme 1. Synthesis of PIB-supported pyridyl N-oxide 12.
O
OH
10 mol% catalyst
(3, 6, or 12)
R
+
H
(Fig. 1).14,15,20 On the basis of these results, a PIB–pyridyl N-oxide
similar to picolinic acid amide N-oxide 6 was synthesized follow-
ing the procedure shown in Scheme 1.
ð3Þ
SiCl3
CH2Cl2, 40 °C
R
R = -H, -CH3, -F, -NO2
The synthesis of the PIB-supported pyridyl N-oxide 12 started
with hydroboration–oxidation of a vinyl-terminated PIB 721 to
form the alcohol 8. A primary bromide 9 was then prepared in a
two-step, one-pot reaction and 9 was in turn converted into
a PIB–phthalimide 10 by reaction with potassium–phthalimide in
a 1:1 v/v mixture of heptane/DMF at 90 °C. Hydrazinolysis in a
heptane–ethanol mixture at 80 °C converted 10 into the primary
amine 11. Finally, the PIB–amine 11 was coupled with picolinic
acid N-oxide to form 12 using EDC and HOBT in a mixture of
heptane–DMF (1:1 v/v). These syntheses were facilitated by the
preferential solubility of the PIB products in an alkane phase and
the polar by-products in a polar phase. All the intermediates could
be fully characterized by solution-state NMR spectroscopy.
Catalytic allylation reactions of benzaldehyde, p-tolualdehyde,
p-fluorobenzaldehyde, or p-nitrobenzaldehyde using 12 were car-
ried out on a 1 mmol scale. These reactions used 10 mol % 12 and
the corresponding aldehyde in 5 mL of CH2Cl2. Then, 2 equiv of
allyltrichlorosilane was added, and the reaction mixture was stir-
red for 48 h at 40 °C. The reactions were quenched with 7 mL of
saturated aqueous NaHCO3. The organic phase was isolated and
the CH2Cl2 was removed under reduced pressure. Catalyst/product
The results obtained from the studies of catalysts 3 and 6
suggest that the six-membered cyclic transition state between
the allylsilane and the oxygen atoms of the pyridine N-oxide
catalyst is important in these allylations. Only catalyst 6 can form
this six-membered ring between the allylsilane and the catalyst
H
NH
N
N+
O
R
N+
O
R
O
O
Si
Si
Cl
Cl
O Cl
Cl
O
Ar
Ar
Figure 1. Possible seven- and six-membered transition states (a and b, respec-
tively) for the allylation reaction of benzaldehyde with allyltrichlorosilane using
catalysts 3 and 6.
Table 1
Allylation reactions catalyzed by PIB-supported pyridyl N-oxide 12a
Substrate
Product
Cycle 1b,c (%)
Cycle 2b,c (%)
84 (100)
Cycle 3b,c (%)
99 (100)
Cycle 4b,c (%)
95 (100)
Cycle 5b,c (%)
47 (77)
O
OH
74 (100)
H
O
OH
H
86 (98)
67 (91)
89 (100)
P99 (97)
84 (90)
99 (98)
84 (90)
99 (100)
99 (95)
84 (90)
99 (100)
99 (90)
66 (80)
95 (100)
H3C
H3C
O
OH
H
O
F
F
OH
92 (100)
H
O2N
O2N
a
In a typical reaction, 10 mol % of the PIB-supported pyridyl N-oxide was used. The reactions were carried out in 5 mL of CH2Cl2 with 1 mmol of the aldehyde and a 2-fold
excess of allyltrichlorosilane at 40 °C. After each cycle, the reaction was quenched with 7 mL of saturated aqueous NaHCO3. After workup, the product and catalyst were
partitioned between hexane and 90% aqueous EtOH. The PIB-supported catalyst was recycled from the hexane phase.
b
Isolated yield of 1H NMR-characterized product.
Conversion (%) based on starting aldehydes using GC analysis of the ethanolic phase using decanol as an internal standard.
c

5610
D. E. Bergbreiter, D. Ortiz-Acosta / Tetrahedron Letters 49 (2008) 5608–5610
separation was then effected by dissolving the residues in 10 mL of
hexane and 10 mL of 90% EtOH–H2O. The phases were separated by
a liquid–liquid extraction. The catalyst-containing hexane phase
was concentrated under reduced pressure, and the residue catalyst
was reused with fresh substrate and solvent. Catalysts could be
used in this way for 5 cycles. Conversions were analyzed by gas
chromatography. Isolated yields of products characterized by 1H
NMR spectroscopy were based on the product obtained after
removing solvent from the ethanol phase. Solvent removal pre-
sumably led to some loss in product so conversions and isolated
yields are not usually equal. A control reaction using benzaldehyde
under the same reaction conditions but without 12 showed that
allylation of benzaldehyde did not occur in the absence of the
catalyst.
Acknowledgments
Support of this work by the National Science Foundation (CHE-
0446107) and the Robert A. Welch Foundation (A-0639) is grate-
fully acknowledged.
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catalyst for the allylation of aromatic aldehydes. As shown in the
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pyridyl N-oxide 12 was effective in promoting the allylation of
benzaldehyde, p-tolualdehyde, p-fluorobenzaldehyde, and p-nitro-
benzaldehyde with isolated yields of pure products based on 1H
NMR spectroscopy from the ethanol phase that generally ranged
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21. The PIB was a gift of BASF and is sold under the tradename Glissopal.