Soluble polyisobutylene-supported reusable catalysts for olefin cyclopropanation

Article abstract of DOI:10.1016/j.tetlet.2007.04.147

Polyisobutylene oligomers (PIB) have been used as soluble supports for the immobilization of cyclopropanation catalysts. In addition to simple carboxylate ligands, chiral bisoxazolines have been successfully attached to these heptane-soluble polymers. The

Full text of DOI:10.1016/j.tetlet.2007.04.147

Tetrahedron Letters 48 (2007) 4499–4503
Soluble polyisobutylene-supported reusable catalysts for olefin
cyclopropanation
David E. Bergbreiter* and Jianhua Tian
Department of Chemistry, Texas A&M University, PO Box 30012, College Station, TX 77842-3012, USA
Received 10 March 2007; revised 27 April 2007; accepted 30 April 2007
Available online 5 May 2007
Abstract—Polyisobutylene oligomers (PIB) have been used as soluble supports for the immobilization of cyclopropanation catalysts.
In addition to simple carboxylate ligands, chiral bisoxazolines have been successfully attached to these heptane-soluble polymers.
Their use and recovery has been investigated using cyclopropanation of styrene as an example. An achiral PIB-bound Rh(II) cat-
alyst showed good activity and could be easily recycled nine times using a liquid–liquid biphasic separation technique. PIB-sup-
ported bisoxazoline ligands for Cu(I) catalysts were also prepared. These chiral catalysts showed good catalytic activity and
stereoselectivity. A chiral ligand prepared from phenylglycine provided the most effective stereocontrol and gave the trans- and
cis-cyclopropanation products in 94% ee and 68% ee, respectively. All three PIB-bound chiral bisoxazoline-Cu(I) catalysts prepared
could be reused five to six times.
Ó 2007 Elsevier Ltd. All rights reserved.
1. Introduction
appended to the polymer for asymmetric catalysis.8 An
alternative approach developed by our group in the last
few years that has parallels in the strategy used in fluor-
ous biphasic catalysis is to use phase selectively soluble
hydrocarbon-soluble polymers as supports. Such poly-
mers can be used as homogeneous catalysts in a single
phase with the substrate and then separated using
either thermomorphic or latent liquid–liquid biphasic
approaches.9,10 Either approach can be a convenient and
efficient way to effect the separation of a soluble poly-
mer-supported homogeneous catalyst from a product
if the polymer selectively dissolves in a phase different
than that of the product. Such separations are most
practical if the polymer can be isolated as a hydrocarbon
(e.g., heptane) solution, where the polymer has a phase
selective solubility of 200:1, or more because most
organic products of interest are more soluble in polar
phases.11 Here, we describe an example of this sort of
approach and its application with a low temperature,
heptane-soluble polyisobutylene oligomer (PIB), that
can be used to support achiral or chiral transition metal
cyclopropanation catalysts.
The use of polymers as supports to facilitate the recov-
ery and recycling of both transition metal catalysts
and ligands for transition metal catalysts continues to
be a current topic of great interest. During the past sev-
eral decades, most of the research in this area has been
focused on the immobilization of ligands and catalysts
on insoluble polymeric supports.1 Soluble supports,
however, can be used too.2,3 A solid/liquid separation
like that typically effected with a cross-linked polymer
can be carried out with soluble polymers using either
solvent precipitation or the upper critical solution tem-
perature for specific polymers. However, the higher tem-
peratures, limited solvent choices or the need for excess
solvent in a precipitation have hindered the widespread
use of such strategies. For example, while most recent
work on polymer-bound cyclopropanation catalysts
has focused on using insoluble polymer supports,4–6
we earlier described polyethylene (PE)-bound cyclo-
propanation catalysts that separate as solids on simple
cooling.7 These supports are effective but require ele-
vated temperature—a problem when chiral ligands were
2. Results and discussion
Keywords: Cyclopropanation; Bisoxazoline; Polyisobutylene; Polymer
supports.
*
The dimer of rhodium(II) acetate is an established cata-
lyst for cyclopropanation of alkenes by diazoalkanes. In
Corresponding author. Tel.: +1 979 845 3437; fax: +1 979 845
4719; e-mail: bergbreiter@tamu.edu
0040-4039/$ - see front matter Ó 2007 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2007.04.147

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D. E. Bergbreiter, J. Tian / Tetrahedron Letters 48 (2007) 4499–4503
a previous study, a polyethylene (PE) supported rho-
dium carboxylate dimer was prepared and successfully
used in catalytic alkene cyclopropanation reactions.7
This PE-bound rhodium catalyst was successfully reused
10 times in cyclopropanation of 2,5-dimethyl-2,4-buta-
diene. Analysis of the product phase showed that less
than 1% of the charged metal leached into product
phase. However, because polyethylene and polyethylene
oligomers are insoluble in all organic solvents at room
temperature, the reaction had to be conducted in toluene
under reflux. This proved to be a limitation when a sim-
ilar PE support was used in asymmetric catalysis.8 Since
our earlier work has shown that polyisobutylene (PIB)
derivatives are soluble in a wide range of organic sol-
vents, even at À78 °C,11 we have prepared a carboxyl-
ated PIB support and used it to prepare a rhodium
carboxylate, that was in turn used as a catalyst for cyclo-
propanation reactions.
for olefin cyclopropanation. As shown in Table 1, cyclo-
propanations using 1 mol % 2 as catalyst at 25 °C in
heptane are comparable to those using the [(PE-
CO2)2Rh]2 catalyst at 110 °C. The catalyst 2 was
successfully reused through 9 cycles without an obvious
decrease in activity. In all cases the reactions were car-
ried out as a single phase in heptane. The catalyst sepa-
ration/recycling process was carried out in one of the
two ways. Specifically, the products were extracted from
a heptane solution of the catalyst after the reaction was
complete using either acetonitrile or ethyleneglycol
diacetate (EGDA). While either solvent was effective,
acetonitrile was generally preferred because the cyclo-
propanation product could be more easily isolated using
this lower boiling point solvent. Analysis of the polar
phase for rhodium showed that about 2% (1.8% and
2.3%, respectively) of the charged rhodium had leached
into the EGDA and acetonitrile phases, respectively, in
each cycle. The higher leaching in the case of acetonitrile
might reflect the better coordination ability of aceto-
nitrile to the metal ion. Indeed, there was evidence for
complexation between acetonitrile and the rhodium of
the PIB-bound rhodium carboxylate dimer, since once
acetonitrile was added to a solution of 2 in the heptane,
the color of the solution changed from green to pink
immediately. However, while there is acetonitrile present
in the heptane solution of recycled catalyst, this aceto-
nitrile had no discernable negative influence on the
catalysis observed in the reactions listed in Table 1.
The carboxylated PIB support PIB-CH2CO2H 1 was
prepared according to a reported procedure.12 Subse-
quent ligand exchange with [(CH3CO2)2Rh]2 in refluxing
toluene yielded the PIB-supported Rh(II) carboxylate 2
as a blue-green viscous oil with a metal loading of
0.36 mmol of Rh/g as determined by ICP-MS of a di-
gested sample (Scheme 1).
The PIB-bound Rh catalyst 2 prepared as shown above
was first compared to the soluble [(PE-CO2)2Rh]2
catalysts we described earlier, as a recyclable catalyst
We also looked at 1-octene as a substrate with the cata-
lyst 2. As expected, 1-octene was a suitable substrate for
this reaction. When the reaction was carried out in hep-
tane under the same condition as that used for styrene
except addition of EGDA, an overall 68% yield was
obtained after 4 cycles. However, the yields with 1-
octene after biphasic separations were lower. Together
these experiments show that catalyst 2 is comparably
active to the prior polyethylene-bound Rh(II)cyclopro-
panation catalysts with the important distinction that
the catalysis can be carried out at 25 °C.
[Rh(OAc)2]2
toluene
O
O
O
O
PIBCH2
CH2PIB
Rh
PIB
PIB
CO2H
H
O
O
O
reflux, 24 h
1
Rh
PIBCH2
=
CH2PIB
O
n
2
PIB1000, n = ca. 18
Scheme 1. Synthesis of a PIB-supported Rh(II) carboxylate dimer.
Table 1. PE and PIB1000 supported rhodium carboxylate catalyzed cyclopropanation reactions
Catalysts
Substrate
Work up
Temperature
Cycle
Yield (%)
Trans/cis (average)e
71/29
[(PE-CO2)2Rh]2
2,5-Dimethyl-2,
4-hexadiene
Styrene
Cooling and filtration
110 °C in toluene
1
10
54
59
96
Cooling and filtration
110 °C in toluene
25 °C in heptane
64/36
59/41
a
[(PIB-CH2CO2)2Rh]2
Styrene
Liquid–liquid extraction
with EGDAb
1
2
3–9
1
2
44
66
76d
53
Liquid–liquid extraction
with acetonitrilec
25 °C in heptane
59/41
75
77d
3–9
a In a typical cyclopropanation reaction, 1 mol % PIB-bound catalyst was used and the reaction was carried out in heptane or cyclohexane with 5- to
10-fold excess of substrate at room temperature. The solution of ethyl diazoacetate in the same non-polar solvent was added to the reaction mixture
via a syringe pump over 5–8 h period. After each cycle, the non-polar phase was extracted with ethyleneglycol diacetate (EGDA) or acetonitrile to
separate the cyclopropanation product from the PIB-bound catalyst. After that, a portion of the non-polar solvent was evaporated and the
substrate was added for the next cycle. The EGDA phase was analyzed by GC using an internal standard to determine the yield.
b This reaction used 0.5 mmol of ethyl diazoacetate.
c This reaction used 1 mmol of ethyl diazoacetate.
d Average yield over seven cycles. In the case of using EGDA, for example, the yields for the 3rd and 9th cycles are 79% and 75%, respectively.
e Determined by GC.

D. E. Bergbreiter, J. Tian / Tetrahedron Letters 48 (2007) 4499–4503
4501
Over recent years, chiral bisoxazoline ligands have been
R
i)
-78 ºC, THF
ii)
reflux, 16 h
n
-BuLi
O
PIB
recognized as a broadly useful class of chiral ligands and
they have been used in a large number of asymmetric
transformations.13 Usually the catalysis is conducted
at room temperature or below, with 1–10 mol % of bis-
oxazoline-ligated transition metal catalyst. Given the
cost of the chiral bisoxazoline ligands, the accepted
desirability of recovering transition metal catalysts,
and the utility of the PIB-bound catalysts at room tem-
perature, we extended our work with 2 to include the
synthesis of chiral bisoxazoline-ligated catalysts.
O
*
O
*
R
N
O
*
O
*
N
N
8
Cu(OTf)2
N
R'
R'
CH2Cl2, r.t.
4
R'
R'
9
O
PIB
R
N
a: R = benzyl; R' = i-Pr (S,S), PIB1000
b: R = Me; R' = Ph (R,R), PIB2300
c: R = benzyl; R' = Et (R,R), PIB1000
O
O
*
N
*
Cu
R'
R'
OTf
TfO
10
Scheme 4. Preparation of PIB-supported bisoxazoline ligands and
catalysts.
Bisoxazolines 4a–c were synthesized as shown in Scheme
2. The dihydroxy malonodiamides 3a–c were readily
prepared from diethyl methyl-, or benzylmalonate and
corresponding chiral amino alcohols in good to excellent
yields. The cyclization was accomplished by a one pot
literature method involving activation of the terminal
hydroxyl groups with p-toluenesulfonyl chloride, fol-
lowed by a DMAP promoted ring closure.14
The PIB-mesylate 5 was prepared as a racemic com-
pound. To eliminate the possible interference from the
racemic center of PIB on the catalysis, we added a linker
between the polymer chain and bisoxazolines 4. The
synthesis of the PIB derivative is shown in Scheme 3.
PIB-mesylate 5 was converted to the PIB-bound n-pro-
pyl benzoate 6 by an SN2 substitution. The ester group
on 6 was then reduced by LiAlH4. The resulting alcohol
7 was treated with SOCl2 to afford the desired PIB-benz-
ylchloride 8.
Figure 1. 1H NMR spectrum of PIB-supported bisoxazoline ligand 9b.
These syntheses were facilitated by the heptane solubil-
ity of the PIB derivatives which reduced purification to
a simple heptane extraction step. Reaction of 9 with
Cu(OTf)2 in dichloromethane at room temperature led
to the complexes 10a–c with metal loadings of 0.50,
0.21 and 0.44 mmol of Cu/g, respectively. The resulting
copper complexes were studied as asymmetric catalysts
for the cyclopropanation of styrene with ethyl diazoace-
tate. The results of these cyclopropanation reactions are
collected in Table 2.
With PIB-benzylchloride 8 and bisoxazoline 4 in hand,
PIB supported ligands 9a–c were prepared by alkylation
of 4a–c with 8 (Scheme 4). All of these reactions of PIB
had the attractive feature, that they could be analyzed
1
by solution state H NMR spectroscopy which verified
that the conversion of 8 to 9 was quantitative. Figure
1
1 shows a portion of the H NMR spectrum of 9, illus-
trating that the solution state resolution is attainable in
analyses of terminally-functionalized PIB oligomers.
R'
*
O
O
R'
*
O
O
amino alcohol
p-TsCl, TEA
Table 2. PIB-supported bisoxazoline-Cu(I) complex catalysed cyclo-
propanation of styrene
N
N
EtO
OEt
110 ºC, 48 h
DMAP, CH2Cl2
OH
24 h, r.t.
H
H
OH
R
R
Catalystsa
Cycle
Yieldb
(%)
Trans/cisb
69/31
Trans
ee%c
Cis
ee%c
R
3
O
O
*
a: R = benzyl; R' = i-Pr (S,S), 73%, 91%
b: R = Me; R' = Ph (R,R), 90%, 95%
c: R = benzyl; R' = Et (R,R), 77%, 81%
10a
1
2–5
68
58
37
70
*
N
N
R'
R'
4
10b
10c
1–6
1–6
48
54
81/19
66/34
92
68
68
40
Scheme 2. Synthesis of bisoxazoline ligands.
a The procedure for cyclopropanation reactions using catalysts 10 is
same as that used in Table 1 except that the active copper(I)species
was generated in situ by reducing copper(II) with phenylhydrazine
(5% in DCNM, v/v) After each cycle, EGDA was used to extract
cyclopropanation products from the heptane phase. Reaction of 10a
and 10c used ca.1.9 mol % catalyst. Reactions with 10b used 1 mol %.
The yield and stereoselectivity values are reported as average values
over several cycles instead of as individual values for each cycle. In
the case of using 10b, for example, the yields for the 1st and 6th cycle
were 32% and 56%.
OPr
O
O
K2CO3
PIB-OMs
+
PIB
O
toluene/DMF
100 ºC, 48 h
OPr
5
6
OH
PIB
7, X = OH
8, X = Cl
LiAlH4
SOCl2
O
THF, reflux
X
b Determined by GC.
Scheme 3. Synthesis of benzylchloride-terminated PIB oligomer.
c Determined by GC using a chiral cyclodextrin-b-CD column.

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D. E. Bergbreiter, J. Tian / Tetrahedron Letters 48 (2007) 4499–4503
All three PIB-supported bisoxazoline ligands showed
moderate catalytic activity and modest to very good ste-
reoselectivity. Of these catalysts, 10b demonstrated a
higher diastereoselectivity (trans/cis 81/19) and good
enantioselectivity in both cis- and trans-cyclopropana-
tion (68% ee, and 92% ee, respectively). Cyclopropana-
tion of styrene with ethyl diazoacetate using catalyst
10a afforded the cis- product in 70% ee while a similar
reaction with catalyst 10c yielded the trans-product in
68% ee. These results are encouraging as they suggest
that the soluble PIB support and its use in heptane-rich
solution is compatible with an asymmetric catalytic
reaction at room temperature.
the lower phase selectivity of the PIB-bound catalyst is
the origin of the catalyst leaching problem. This suggests
that a higher molecular weight PIB will afford a more
recyclable catalyst.
3. Conclusions
In summary, both PIB-bound rhodium carboxylate and
bisoxazoline-copper triflate complexes have been syn-
thesized and used in the olefin cyclopropanation reac-
tions. Catalyst reusability was demonstrated in both
heptane/EGDA and heptane/acetonitrile solvent sys-
tems. Oligomeric PIB-carboxylate ligands can be used
to prepare rhodium(II) cyclopropanation catalysts that
work at room temperature and that can be recycled
and reused in both heptane/EGDA and heptane/aceto-
nitrile solvent systems with liquid/liquid catalyst recov-
ery and separation. Up to 9 cycles with ca. 2% metal
leaching were seen in a typical cyclopropanation. PIB-
supported bisoxazoline-Cu(I) complexes were prepared
and were shown to have moderate to good activity
and enantioselectivity at room temperature. Catalyst
10b was the most effective of these catalysts yielding
68% ee and 92% ee for the cis- and trans-cyclopropana-
tion product, respectively. However, catalyst leaching
for PIB-bound copper catalysts is more problematic
due to the higher mass percent loading of polar groups
in these oligomeric catalysts. Recyclability can be
improved by increasing the length of PIB chain but
metal leaching is still a problem with PIB groups having
a degree of polymerization of 40–50.
Both catalysts 10b and 10c could be reused up to six
times without a decrease in the enantio- and diastereo-
selectivity. The PIB2300-supported copper catalyst
showed slightly lower catalytic activity compared to
the PIB1000 version. In the case of using 10c, 33%,
16% and 5% of metal leaching was observed in the
EGDA phases for the 1st, 2nd and 5th cycles, respec-
tively, by ICP-MS analysis. We believe this reflects mass
transfer of a portion of the PIB-bound copper catalyst
10c to the polar phase because the polar part of these
ligands is relatively large in comparison to the size of
the non-polar PIB group. This makes the catalysts less
phase selectively soluble. The decrease in leaching
through several cycles is presumed to reflect a greater
loss of less phase selectively soluble lower molecular
weight fractions of the polydisperse PIB-bound catalyst
in the initial biphasic separations. The loss of PIB-
bound copper species into the polar phase is thus both
greater than that seen for 2 and decreases as the number
of cycles increases.
We also analyzed EGDA phases in another recycling
experiment using the higher molecular weight PIB-
bound catalyst 10b. This catalyst too was reusable
through multiple cycles. Metal leaching for the 1st,
2nd, 3rd, 4th and 6th cycles was 13%, 7%, 6% 7% and
7% of the charged catalyst, respectively. These leaching
rates are larger than we wished. Nonetheless, they show
that the recyclability of PIB2300 supported Cu(I) cata-
lysts is better than that seen for PIB1000 supported cata-
lysts, a result which we ascribe to the larger non-polar
PIB chain in 10b.
Acknowledgements
The support of this work by the National Science Foun-
dation (CHE-0446107) and the Robert A. Welch Foun-
dation (A-639) is gratefully acknowledged. We also
thank Professor Gyula Vigh for his help in GC analysis
of cyclopropanation products. Mr. Ye Zhu is acknowl-
edged for his help in performing GC analysis.
References and notes
Separate experiments examined the phase selective solu-
bility of 10b in a heptane/EGDA biphasic extraction in
the absence of a catalytic reaction to confirm that the
observed leaching reflects the inherent phase selective
solubility of these oligomeric PIB-bound bisoxazoline
catalysts in liquid/liquid biphasic separations. EGDA
was added to a heptane solution of 10b and the concen-
tration of 10b in both the heptane and EGDA phases
was analyzed by UV–visible spectroscopy using the
absorbance of 10b at 720 nm. Assuming that the extinc-
tion coefficient of 10b in the heptane and EGDA phases
is the same, we estimate the phase selective solubility of
10b in the first two cycles in this experiment where the
condition that no reaction occurs is ca. 14% and 7%,
respectively. These UV–visible spectroscopy results
match our ICP-MS results and support the notion that
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