Using soluble polymers to enforce catalyst-phase-selective solubility and as antileaching agents to facilitate homogeneous catalysis

Article abstract of DOI:10.1002/anie.201402805

The enforced phase-selective solubility of polyisobutylene (PIB)-bound Rh^II catalysts in biphasic heptane/acetonitrile mixtures can be used not only to recycle these catalysts but also to minimize bimolecular reactions with ethyl diazoacetate. When cyclopropanation and O - H insertion reactions are carried out with PIB-bound Rh^II catalysts either with or without addition of an unfunctionalized hydrocarbon polymer cosolvent, dimer by-product formation is suppressed even without slow syringe pump addition of the ethyl diazoacetate. This suppression of by-product formation is shown to be due to increased phase segregation of the soluble polymer-bound catalyst and the ethyl diazoacetate reactant. These studies also reveal that added hydrocarbon polymer cosolvents can function as antileaching agents, decreasing the already small amount of a soluble polymer-bound species that leaches into a polar phase in a biphasic mixture during a liquid/liquid separation step.

Full text of DOI:10.1002/anie.201402805

Angewandte
Chemie
DOI: 10.1002/anie.201402805
Polymers as Antileaching Agents
Using Soluble Polymers to Enforce Catalyst-Phase-Selective Solubility
and as Antileaching Agents to Facilitate Homogeneous Catalysis**
Yannan Liang, Mary L. Harrell, and David E. Bergbreiter*
II
Abstract: The enforced phase-selective solubility of polyiso-
butylene (PIB)-bound Rh catalysts in biphasic heptane/
polymerꢀs phase-selective solubility segregates the Rh cata-
lyst and diazo reactant in nonpolar and polar phases of
II
acetonitrile mixtures can be used not only to recycle these
catalysts but also to minimize bimolecular reactions with ethyl
diazoacetate. When cyclopropanation and OÀH insertion
a biphasic heptane/CH CN mixture enabling both catalyst
3
recycling and suppression of dimer formation without syringe
pump addition of the N CHCO Et. This is possible because
2
2
II
reactions are carried out with PIB-bound Rh catalysts either
the low solubility of the diazo reactant in the heptane-
catalyst-containing phase lowers the bimolecular rate of
dimer formation more than the rate of cyclopropanation or
OÀH insertion. We further show that adding an unfunction-
with or without addition of an unfunctionalized hydrocarbon
polymer cosolvent, dimer by-product formation is suppressed
even without slow syringe pump addition of the ethyl
diazoacetate. This suppression of by-product formation is
shown to be due to increased phase segregation of the soluble
polymer-bound catalyst and the ethyl diazoacetate reactant.
These studies also reveal that added hydrocarbon polymer
cosolvents can function as antileaching agents, decreasing the
already small amount of a soluble polymer-bound species that
leaches into a polar phase in a biphasic mixture during a liquid/
liquid separation step.
alized hydrocarbon polymer to the heptane phase of a hep-
tane/polar solvent biphasic mixture further limits both dimer
formation and leaching of PIB-bound species into the polar
phase of a heptane/polar solvent biphasic mixture. These
results suggest new roles for soluble polymers or oligomers as
supports or as cosolvents in catalysis where soluble polymer
[
6]
supports recycle catalysts, suppress undesired side reactions,
and reduce leaching of heptane-soluble polymer-bound
species.
II
S
oluble polymer supports are useful tools in homogeneous
A PIB-supported heptane-soluble Rh catalyst was pre-
[1]
catalysis. This work shows that the enforced phase-selective
solubility of polyisobutylene (PIB)-supported catalysts can be
used to both recycle catalysts and to suppress by-product
formation involving the bimolecular reac-
tion of a polar-phase-soluble reactant.
Such effects are enhanced using added
hydrocarbon polymer cosolvents that can
serve as antileaching agents.
pared as shown in Scheme 1. This route to a [(PIB2300
-
CO ) Rh] catalyst was more convenient for multigram
2
2
2
[
3c]
syntheses than a previous one. Using PIB2300 as the starting
Rhodium(II) carboxylates have been
used as catalysts in cyclopropanation, CÀH
insertion, XÀH (X = O, N, S) insertion, and
aromatic cycloaddition reactions of diazo
[
2]
compounds. Both soluble supported cat-
alysts we developed and insoluble sup-
ported catalysts others have used are
[
3,4]
recyclable in these processes.
However,
all these catalysts require slow addition of
the diazo substrate with a syringe pump
II
because of the facile and exothermic Rh -
Scheme 1. Synthesis of a PIB2300-bound carboxylic acid and its use in the formation of
a PIB2300-bound Rh catalyst.
catalyzed dimerization of the diazo reac-
II
[
5]
tant. Here we describe how a soluble
[
7]
material, the ester 4 was prepared and hydrolyzed to form 5
which was used to form the Rh catalyst 6 by ligand exchange
with [Rh(OAc) ] in toluene at 808C. The product 6 was
[
*] Y. Liang, M. L. Harrell, Dr. D. E. Bergbreiter
Department of Chemistry, Texas A&M University
P.O. Box 30012, College Station, TX (USA)
E-mail: bergbreiter@tamu.edu
2
2
a viscous oil which was characterized by UV/Vis spectroscopy.
À1
A Rh loading of 0.167 mmol g in 6 was determined based on
[
**] Support of this research by the Robert A. Welch Foundation (Grant
A-0639) and the National Science Foundation (CHE-0952134) is
gratefully acknowledged.
the absorbance at 588 nm (lmax) of a known amount of 6 in
EtOH/toluene and the e of [Rh(OAc) ] in this same solvent
2
2
À1
À1
mixture (e = 260m cm , l = 587 nm). These spectral data
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/anie.201402805.
max
are comparable to the reported data for [Rh(OAc)2]2 in
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Angewandte
Communications
À1
À1 [8]
octanol (l = 585 nm, e = 298m cm ). The green PIB2300
-
three cycles (as a 61/39 Z/E mixture). The catalyst 6 was
recycled by separating the heptane phase containing 6 from
max
II
bound Rh carboxylate complex was visually insoluble in
CH CN.
the CH CN product phase and reusing the heptane solution in
3
3
The studies in this paper make use of the phase-selective
another cycle. The average yield of the isolated cyclopropa-
nation product was 65%/cycle. These results show that phase
solubility of 6 and the fact that N CHCO Et is relatively
2
2
II
insoluble in heptane versus CH CN to facilitate cyclopropa-
isolation of a PIB-bound Rh catalyst from N CHCO Et
3
2
2
nation and OÀH insertion catalytic reactions of 6 (Scheme 2).
suppresses the dimerization of diazo substrates while still
affording typical products in a reasonable time frame.
We attribute the low amount of dimer formation under
biphasic conditions to two factors: the enforced phase-
selective solubility of 6 in the heptane phase of the heptane/
CH CN biphasic mixture and the relatively low concentration
3
of N CHCO Et in the catalyst-rich heptane phase. The low
2
2
concentration of catalyst in the CH CN phase, in which there
3
is a high concentration of N CHCO Et, slows dimer forma-
2
2
Scheme 2. N CHCO Et reactions catalyzed by the PIB-bound Rh car-
2
2
tion in CH CN whereas the low concentration of N CHCO Et
3
2
2
boxylate catalyst 6 in a biphasic heptane/CH CN solvent mixture at
3
in heptane slows what would otherwise be a fast bimolecular
dimer reaction in the catalyst-rich heptane phase. This control
of an unwanted bimolecular reaction in a liquid/liquid
biphasic system has been reported in isolated instances in
other chemistry. For example, Collins et al. have shown that
pseudobiphasic conditions facilitate macrocyclization under
conditions, in which a bimolecular oligomerization is sup-
2
58C.
We first confirmed that the PIB-bound Rh complex 6 was
effective in cyclopropanation of styrene in CH Cl2 using
syringe pump addition of N CHCO Et to minimize the
maleate/fumarate dimer formation (Table 1). This reaction
produced a 71% yield of the 2-phenyl-1-cyclopropylcarbox-
ylic acid ester as a 67/33 trans/cis mixture with 2.3% of the
carbene dimer. These results are comparable to previous
results with soluble polymer-bound Rh catalysts that used
syringe pump addition of the N CHCO Et to suppress
carbene dimer formation.
a recyclable catalyst for cyclopropanation of styrene with
N CHCO Et under biphasic conditions without the use of
a syringe pump. The reaction was carried out in a heptane/
CH CN biphasic system at room temperature using 0.5 mol%
2
2
2
[9]
pressed.
In addition to cyclopropanation, rhodium carbenoids
generated from diazo compounds are also used to insert
a carbene equivalent in XÀH bonds. This reaction can also be
II
effected by phase-segregated catalyst 6 in a heptane/CH CN
2
2
3
[
3a,c]
Next, we examined 6 as
biphasic mixture without the need for syringe pump addition
of N CHCO Et to suppress maleate/fumarate dimer forma-
2
2
tion. As shown in Table 2, 6 was successfully recovered and
reused through three cycles of an OÀH insertion into
2
2
isopropyl alcohol affording the product in a 63% average
yield/cycle. The average yield of dimers was 6.6%, a result
similar to that obtained using syringe pump addition with 6 as
a catalyst in monophasic CH Cl .
3
of 6. In this case, most of the N CHCO Et was in the CH CN
2
2
3
phase. Under these conditions, 6 was successfully reused
affording the cyclopropanation product in 66, 67, and 74%
yield (as a ca. 67/33 trans/cis mixture) in cycles 1–3. The yield
of dimer by-product was 7.7, 7.1, and 6.7% for these same
2
2
Our hypothesis is that the small amount of dimer formed
results either from minimal catalyst 6 leaching into the
N CHCO Et-rich CH CN phase, from a lowered N CHCO Et
2
2
3
2
2
concentration in the heptane phase, or from a combination of
these scenarios. Thus we could further reduce by-product
Table 1: Results for the styrene cyclopropanation reaction catalyzed by 6
using biphasic conditions to effect the N CHCO Et dimerization
suppression.
formation either by reducing the leaching of 6 into CH CN or
3
2
2
[
a]
[
b]
Polyolefin Cosolvent
Cycle
Yield [%]
Dimer
Table 2: Results of O
ÀH insertion of isopropyl alcohol catalyzed by 6
[
b,c]
Yield [%]
using biphasic conditions to effect the N CHCO Et dimerization
2
2
[
d]
[e]
[a]
CH Cl as solvent
none
–
1
2
3
1
2
3
71
2.3
7.7
7.1
6.7
3.8
4.5
5.4
suppression.
2
2
66
67
74
61
58
[b]
[c]
Cycle
Yield [%]
Dimer Yield [%]
none
none
PIB2300
PIB2300
PIB2300
1
2
3
72
66
51
65
66
6.4
6.8
6.6
4.1
2.6
[
f]
f]
f]
[
[
[g]
[d]
64
–
[
e]
–
[
a] 2 mmol scale reactions with 0.5 mol% of 6 and 20 mmol of styrene at
2
58C using a 5 mL/15 mL mixture of heptane/CH CN. [b] Yields are
[a] 2 mmol scale reactions with 0.5 mol% of 6 and 20 mmol of styrene at
3
1
based on H NMR spectroscopy. [c] A mixture of maleate/fumarate
products. [d] Syringe pump addition was used to suppress N CHCO Et
258C using a 5 mL/15 mL mixture of heptane/CH CN. [b] Average
3
1
H NMR spectroscopy yields of product from two independent runs.
2
2
dimerization in this CH Cl monophasic reaction. [e] Yield of isolated
[c] NMR yield of the by-product (a ca. 60/40 Z/E mixture). [d] An OÀH
2
2
product. [f] PIB2300 was added as a cosolvent. [g] Combining the products
of three cycles in which PIB was present afforded 0.67 g of the
cyclopropanation product.
insertion reaction carried out in the presence of added unfunctionalized
PIB. [e] An OÀH insertion carried out in CH Cl adding N CHCO Et with
2
2
2
2
a syringe pump.
2
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1
by further reducing the concentration of N CHCO Et in the
H NMR spectroscopy experiments (see the Supporting
2
2
heptane phase.
Information) determined the amount of leaching of the added
copolymer into the polar phase. Based on a quantitative
The first scheme we explored was to add unfunctionalized
PIB cosolvent to the heptane phase. The premise was that
addition of unfunctionalized PIB would competitively satu-
1
3
analysis using the C satellite peaks of the CH OH or DMF
3
[13]
and the methyl peaks of the added hydrocarbon cosolvent,
À4
rate the CH CN phase, thereby reducing the amount of 6 in
this leaching corresponds to less than 7.5 ꢁ 10 m copolymer
in the polar phase.
3
that phase. Since there was no visually apparent leaching of 6
into CH CN, we tested this idea by examining how added
hydrocarbon polymer cosolvents reduced the leaching of two
chromogenic PIB derivatives 7 and 8 that had visible leaching.
The results of experiments in which PIB was added as
a cosolvent to reduce by-product formation in cyclopropana-
tion and OÀH insertion are listed in Tables 1 and 2. In
3
cyclopropanation, average dimer yields through three cycles
of a catalytic reaction decreased from 7.4% without any
addition of PIB to 4.6% with PIB2300 as the cosolvent. Similar
results for dimer formation were obtained with PIB2300 as the
cosolvent in OÀH insertions (Table 2). The reduction of dimer
formation linearly correlated with the amount of added PIB.
PIB1000 was comparable in effect to PIB2300 (see Figure 1S in
the Supporting Information). A small decrease in the cyclo-
propanation product yield was also noted.
The addition of PIB cosolvent could reduce by-product
formation either by lowering the leaching of 6 into CH CN or
3
by reducing the concentration of N CHCO Et in the heptane
2
2
The first study of the antileaching effect of added hydro-
phase. The decrease in yield for the cyclopropanation product
suggested the latter explanation. This was confirmed by
analyses showing that the N CHCO Et concentration in
[
10]
carbon cosolvents used the PIB2300 bound azo dye 7. In
a thermomorphic mixture containing 3 g of heptane and 3 g of
CH OH, 7 has a small but detectable solubility in CH OH at
2
2
À3
À3
heptane decreased from 5.0 ꢁ 10 to 3.2 ꢁ 10 to 2.5 ꢁ
3
3
À3
2
58C with an absorbance of 0.36 at 492 nm. Replacing 1 g of
10 m as the amount of added PIB in heptane increased
[
11]
the heptane with 1 g of a polypropylene polymer decreased
from 0 to 0.07 to 0.22m.
the leaching of 7 by ca. 30% (the dye absorbance in CH OH
was 0.25). Using 3 g of this same polypropylene polymer and
Suppression of dimer formation due to a lowered con-
centration of 6 in the N CHCO Et-rich CH CN phase is an
3
2
2
3
3
g of CH OH as the solvent mixture, the concentration of 7 in
alternative explanation for decreased dimer by-product in
experiments where PIB is added as a cosolvent. However,
studies of the dimerization of N CHCO Et by [Rh(OAc) ] or
3
the CH OH phase dropped by over 50% (the absorbance of 7
in CH OH was 0.16) (Figures 2S and 3S in the Supporting
3
3
2
2
2 2
Information). Studies with a chromogenic PIB-bound Ru
6 under monophasic and biphasic conditions showed that
bipyridine complex 8 used previously as a photoredox
a lowered concentration of 6 in the CH CN phase was less
3
[
12]
catalyst
showed that the antileaching effect of added
important than a decrease in the N CHCO Et concentration
2
2
hydrocarbon copolymers on soluble PIB-bound dyes also
affects PIB-bound metal complex leaching. Dissolving 8 in
a thermomorphic heptane/ethanol/DMF (4/2/3 vol/vol/vol)
system forms a monophasic solution at 908C that becomes
biphasic on cooling to 258C. Reheating and adding 0.4 g of
PIB2300 to the hot monophasic mixture and cooling this
solvent mixture to reform a biphasic mixture at 258C
drastically decreased the leaching of 8 into the polar phase
in heptane in accounting for the effect of added PIB.
N CHCO Et in CH Cl2 quantitatively dimerizes with
2
2
2
0.5 mol% of either [Rh(OAc) ] or 6 at 258C within 10 min.
2
2
Other experiments showed that reaction of N CHCO Et
2
2
with [Rh(OAc) ] in CH CN only proceeds to 16% after 10 h
2
2
3
at 258C. Thus, even if 6 were to leach into the CH CN phase, it
3
would not produce much dimer. While added PIB cosolvent
could decrease leaching of 6 into CH CN, the antileaching
3
(
Figure 1).
effect of PIB is not the primary reason for the lower dimer by-
product formation upon PIB cosolvent addition.
In summary, this report describes new roles for soluble
polymer-bound catalysts and soluble polymers in homoge-
II
neous catalysis. Using a recyclable Rh cyclopropanation/
OÀH insertion catalyst as an example, we show how the
phase-enforced solubility of a polymer support can suppress
the undesired bimolecular dimerization reaction of ethyl
diazoacetate in a heptane/CH CN biphasic reaction mixture
3
without recourse to the use of syringe pump addition to
maintain a low ethyl diazoacetate concentration. We show
that adding a hydrocarbon polymer as a cosolvent further
suppresses the formation of by-products from ethyl diazo-
acetate dimerization. These experiments also show that added
hydrocarbon polymers in biphasic nonpolar/polar liquid/
Figure 1. Antileaching effect of PIB2300 for the Ru bipyridine complex 8
in a heptane/ethanol/DMF solvent system; no PIB (left) or 0.45 g of
added PIB2300 in 4 mL of a heptane phase containing 80 mg of 8
(
right).
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Communications
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inexpensive way to minimize the leaching of precious
catalysts or ligands during liquid/liquid biphasic separations.
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Angew. Chem. Int. Ed. 2014, 53, 1 – 5
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Angewandte
Chemie
Communications
Polymers as Antileaching Agents
Y. Liang, M. L. Harrell,
Suppression of by-product: In biphasic
heptane/CH CN mixtures, heptane-solu-
3
II
ble polyisobutylene (PIB)-bound Rh
D. E. Bergbreiter*
&&&& — &&&&
cyclopropanation and OÀH insertion
catalysts form only modest amounts of
the undesired carbene dimer. It was
shown that the phase isolation of these
catalysts is enhanced by the addition of
a polyolefin oligomer cosolvent, which
acts as antileaching agent and minimizes
the leaching of the PIB-bound species
into the polar phase in liquid/liquid
separations.
Using Soluble Polymers to Enforce
Catalyst-Phase-Selective Solubility and as
Antileaching Agents to Facilitate
Homogeneous Catalysis
Angew. Chem. Int. Ed. 2014, 53, 1 – 5
ꢀ 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.angewandte.org
5
These are not the final page numbers!