Redox-switchable phase tags for recycling of homogeneous catalysts

Article abstract of DOI:10.1002/anie.200502182

(Chemical Equation Presented) A homogeneous catalytic complex is tagged with two ferrocenyl groups to control its solubility properties by reversible switching between its neutral and dicationic states (see scheme). This approach is carried out on an olefin-metathesis catalyst and is shown to effectively switch its catalytic activity on and off; furthermore, efficient separation of the catalyst from the reaction products and subsequent recycling of the catalyst is possible.

Full text of DOI:10.1002/anie.200502182

Angewandte
Chemie
Homogeneous Catalysis
To avoid these problems, we propose herein a strategy for
the separation of homogeneous catalysts from the products of
the reaction based on a new class of solubility-determining
groups, which we term redox-switchable phase tags. In
contrast to other phase tags, the solubility properties of
redox-switchable phase tags can be altered through the
employment of tag-centered reactions, thus resulting in
drastic changes in the polarity of the respective solubility-
determining group. In this manner, it should be possible to
exert perfect control over the solubility behavior of cata-
lysts by using a single solvent. We decided to utilize tag-
centered redox reactions which mutate neutral (lipophilic)
tags into charged (lipophobic) tags and back. One significant
advantage of such an approach is that drastic changes in the
solubility behavior can be effected with only very small
amounts of switching reagent, which is stoichiometric with
respect to the catalytic amounts of catalyst complex present in
a reaction mixture.
DOI: 10.1002/anie.200502182
Redox-Switchable Phase Tags for Recycling of
Homogeneous Catalysts**
Marcus Süßner and Herbert Plenio*
Dedicated to Professor H. W. Roesky
on the occasion of his 70th birthday
[
25]
A fundamental problem of homogeneous catalysis is the
difficulties associated with the recovery of the molecular
catalyst after product formation, thus leading to loss of the
catalyst and contamination of the reaction products with
[
1,2]
heavy-metal impurities.
This problem is aggravated by the
fact that increasingly sophisticated complexes with tailor-
made ligands result in high-value catalysts. Consequently,
numerous concepts have been tested to overcome the
To illustrate this principle, we chose a ruthenium-based
catalyst of the Grubbs–Hoveyda type for olefin metathesis as
numerous recycling concepts have been tested on these high-
[
3,4]
[26–32]
imminent problem of catalyst/product separation,
soluble polymeric catalysts, biphasic solvent systems which
involve various solvent combinations (namely, organic/
such as
value catalysts because of their effectiveness.
Prior to the
[
5,6]
synthesis of a modified olefin-metathesis catalyst of the
Grubbs–Hoveyda type with redox-switchable tags, a suitable
redox-active group needed to be found. We chose a ferrocene
(Fc) unit because such metallocenes are well-behaved outer-
sphere redox reagents that display a high degree of reversi-
bility. Furthermore, the redox potential of the ferrocene unit
can be varied readily over a large potential range through the
[
7]
[8]
organic,
fluorous/organic,
ionic liquids/supercritical
[
9]
[10,11]
[12,13]
fluids, aqueous/organic
ated nanoparticles,
), nanofiltration,
incarcer-
supported
[
14,15]
[16]
interphase catalysts,
[
17]
liquid films, and immobilization of molecular catalysts on
[
18]
[19]
organic or inorganic supports.
Clearly, these approaches rely on manipulation of the
attachment of different substituents on the cyclopentadienyl
[
20]
[33]
solubility properties; most often, distinct solubility proper-
ties are imposed by so-called phase tags, such as sulfonate
groups (in triphenyl phosphorothionates), fluorous pony-
rings,
which is clearly a very important property as the
redox potential of the redox tag must be fine-tuned to avoid
electron-transfer reactions that involve the catalytically active
[
21]
[
8]
[22,23]
II
III
tails, or polar and nonpolar soluble polymers.
metal center. The Fe /Fe redox couple of the ferrocene unit
should differ by between 236 mV (ratio of Fe/Ru oxidation =
100:1) and 354 mV (1000:1) from that of the olefin-metathesis
Such solubility-determining groups are referred to as
phase tags and are an important tool in separation strat-
[
24]
II
III
egies.
Despite the success of this approach, certain dis-
catalyst to be useful. Thus, the Ru /Ru redox potential of
the Grubbs–Hoveyda catalyst was first established by cyclic
advantages of this concept are apparent. Clearly, two solvents
are required in biphasic systems, one to hold the product and
the other for the tagged catalyst complex. Both solvents need
to be compatible with the catalytic reaction, their mutual
solubility should be low, the leaching of the catalyst into the
product-containing solvent has to be minimized, and the
partition coefficient of the reactants/products needs to be in a
suitable range. Alternatively, the tagged catalyst can be
precipitated from the reaction solvent by addition of another
solvent after the catalytic transformation. However, very
large amounts of this second solvent are typically needed to
effect the quantitative precipitation of the tagged catalyst.
voltammetry (CV). The CV waves are well behaved, that is,
they are fully reversible and the redox potential was + 0.85 V
in CH Cl (Figure 1). As the redox potential of ferrocene
[
*] Dipl.-Ing. M. Süßner, Prof. Dr. H. Plenio
Anorganische Chemie im Zintl-Institut des FB Chemie
TU Darmstadt, Petersenstrasse 18
2
2
itself is + 0.46 V under the same conditions, we conclude that
any ferrocene compound with electron-donating substituents
64287 Darmstadt (Germany)
II
III
can undergo independent Fe /Fe redox reactions that do not
Fax: (+49)6151-16-6040
E-mail: plenio@tu-darmstadt.de
II
interfere with the catalytically active Ru center.
The synthesis of a ferrocenyl-tagged olefin-metathesis
catalyst is shown in Scheme 1. We chose a monoalkylated
ferrocene as the redox tag, as its redox potential fulfils the
[
**] This work was supported by the TU Darmstadt and the DFG. We
thank Dr. A. Köllhofer for assistance with the electrochemical
experiments.
Angew. Chem. Int. Ed. 2005, 44, 6885 –6888
ꢀ 2005 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
6885

Communications
functionalities of this salt underwent Sonogashira coupling to
ferrocenyl acetylene, thus giving the coupled product in 85%
yield. It should be noted that the reaction conditions for the
Sonogashira coupling are critical: First, the imidazolinium
chloride displays solubility only in a few polar solvents, and
second, the number of suitable bases is rather limited because
the competing deprotonation of the imidazolinium ring must
be suppressed as the corresponding N-heterocyclic carbene
appears to inhibit the Pd catalyst.
Next, the acetylene linker was reduced with H over Pd/C
2
to the ꢀC H ꢀ bridge in almost quantitative yield. The reason
2
4
for this transformation is threefold: 1) an alkyl substituent
attached to the ferrocene unit is electron donating rather than
electron withdrawing, which consequently leads to an
increase in the difference in the redox potential between
the Fe /Fe and Ru /Ru redox couple; 2) the hydrogena-
tion of the acetylene linker electronically decouples the
redox-active ferrocene group from the
catalytically active center to avoid any
undesired influence of the ferrocene
cation on the catalytically active center
after oxidation; 3) the absence of a triple
bond avoids potential problems in olefin
metathesis.
Figure 1. Cyclic voltammogram of the diferrocenyl-tagged Grubbs–
II
III
Hoveyda-type catalyst 1. DE (Fe /Fe )=+0.410 V (70 mV), DE
1
/2
1/2
II
III
II
III
II
III
(
Ru /Ru )=+0.847 V (60 mV) referenced versus FcMe (ꢀ0.010 V) in
8
CH Cl .
2
2
Finally, the imidazolinium cation is
deprotonated with KOtBu and treated
with the Grubbs I catalyst; subsequently,
the remaining PCy3 ligand and the
benzylidene in the resulting complex
are substituted with 2-isopropoxystyr-
ene to yield the desired redox-tagged
Grubbs–Hoveyda-type catalyst 1.
The catalytic properties of 1 are
demonstrated in the ring-closing meta-
thesis (RCM) reaction of N-tosyldiallyl-
amide (Figure 2). The unperturbed reac-
tion (*) proceeds to completion exactly
as expected for such catalysts. In a
second run (
alents of
[FcCOCH ][CF SO ] as a 10% solution
&
), a solution of two equiv-
oxidation reagent
(
3
3
3
in 0.1 mL of CH Cl (DE = + 0.73 V))
2
2
with respect to the catalyst was added
after exactly 60 minutes. The two ferro-
cenyl tags were oxidized virtually instan-
2
+
taneously, and the resulting dication 1
precipitates from the solution of toluene
within a few seconds. The precipitated
catalyst does not display significant
catalytic activity, as can be seen in the
plot of conversion versus time (Figure 2,
Scheme 1. Synthesis of the ferrocenyl-tagged olefin-metathesis catalyst 1 of the Grubbs–Hoveyda type:
a) NEt , EtOH, HCOOH, 24 h; b) 1. LiAlH , THF; 2. HCl; c) HC(OEt) , 1308C, 24 h; d) FcCCH, Na PdCl ,
3
4
3
2
4
CuI, Ad PBn·HBr, DMSO, HNiPr 808C, 24 h; e) Pd/C 5 bar H , 5 h, RT; f) KOtBu, Grubbs I catalyst,
2
2,
2
toluene, THF; g) 2-isopropoxystyrene, CuCl, CH Cl , 408C, 1 h. Cy=cyclohexyl, Ad=adamantyl, DMSO=
2
2
dimethyl sulfoxide.
&
). The product of the catalytic reaction
can be readily separated from the pre-
cipitated catalyst by filtration, which is preferably done after
completion of the reaction. The catalyst can be reactivated
(namely, redissolved) at any time by addition of two
equivalents of a reducing agent (1,1’,2,2’,3,3’,4,4’-octamethyl-
criteria defined above. 4-Bromo-2,6-dimethylaniline was
treated with glyoxal to give the respective 1,2-diimine in
7
5% yield, which was reduced to the corresponding 1,2-
diamine in 80% yield using LiAlH . Ring-closure with
4
HC(OEt) yielded the respective imidazolinium salt in 75%
ferrocene (FcMe )), which was carried out after 135 minutes
3
8
yield. For the introduction of the redox tag, the aryl bromide
in our experiment. It can be seen that the catalytic activity is
6
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Angewandte
Chemie
monitoring the UV/Vis spectrum of the reaction mixture;
catalyst 1 is characterized by a strong Ru-centered absorption
band at 375 nm, the intensity of which reflects the concen-
tration of the catalyst in solution.
As an alternative to chemical redox switching, which
requires stoichiometric amounts of redox reagent (only with
respect to the catalyst), electrochemical triggering of the tag
switching only requires an applied current. Ideally, the
catalyst is electrodeposited on the surface of an electrode
on oxidation and is redissolved on application of a reductive
potential. In this manner, the transfer of the loaded electrode
from a solution containing the product into a solution
containing fresh reactants allows efficient reuse of the
catalyst. For the coulometric deposition of a redox-tagged
catalyst, solvents are needed that display a reasonable
conductivity after addition of supporting electrolytes. Con-
sequently, electrolysis in toluene is not possible as the currents
observed are far too small to effect electrolysis within a
reasonable time frame, and so slightly more polar solvents are
required. We tested a number of solvents of intermediate
polarity and were able to quantitatively oxidize 1 electro-
chemically. However, the minute concentrations of catalyti-
cally active dication used for the RCM reactions are soluble in
solvents of intermediate polarity (e.g., CH Cl ). Therefore,
Figure 2. Switching of the olefin-metathesis catalyst 1 in toluene,
monitored by GC: unperturbed RCM (*), off/on switched RCM (
&
).
Ox. and red. denote the respective oxidation and reduction of the
redox tag with [FcCOCH ][CF SO ] and FcMe . Ts=p-toluenesulfonyl.
[
35]
3
3
3
8
immediately restored to its initial value and the reaction
[
34]
proceeds to completion (not shown in Figures 2 and 3).
Following this procedure, the catalyst can also be switched
[
36,37]
off and on
several times after completion of the RCM
reaction, thus allowing multiple recycling of the catalyst. We
tested redox-switching of the phase tag for three consecutive
reaction cycles composed of 1) olefin metathesis, 2) oxidation
with an acetyl ferrocene cation, 3) precipitation and separa-
tion, and 4) reduction and redissolution of the catalyst, and
we observed quantitative yields for all the reaction steps. We
probed the identity of the recycled catalyst after a single
2
2
the synthesis of new catalysts with multiple redox tags is
[
38]
required to solve these problems.
2
+
oxidation/reduction sequence 1!1 !1 and identified the
In conclusion, we have demonstrated that redox-switch-
able phase tags, whose solubility properties are controlled by
redox reagents or electrochemical redox processes, can be
used to effectively switch the catalytic activity of an olefin-
metathesis catalyst of the Grubbs–Hoveyda type on and off.
More importantly, this approach allows the efficient separa-
tion of such catalysts from the products of a catalytic reaction
at any time during the reaction and after its completion. We
expect the principle of redox-switchable phase tags to become
a general concept for control over solubility properties and,
consequently, the recyclability of a wide variety of homoge-
neous catalysts. We are currently working towards the
application of this principle several to other types of
homogeneous catalytic processes, such as enantioselective
hydrogenation and various Pd-mediated cross-coupling reac-
tions.
1
initial Grubbs–Hoveyda-type catalyst 1 by H NMR spec-
troscopy.
Furthermore, it is also possible to adjust the rate of the
catalytic transformation as desired by reversible precipitation
of a limited amount of the catalyst after addition of
substoichiometric amounts of the oxidation reagent.
Although the curve denoted by
&
in Figure 3 displays a
single off/on switching event, the double-switched RCM
reaction in the curve denoted by * shows an off/on switching
event during the first 30 minutes and a partial-off event after
5
7
0 minutes, with a full restoration of catalytic activity after
5 minutes.
Instead of monitoring the switching events by gas-
chromatographic or NMR spectroscopic analysis, the removal
of the catalyst from the solution can be followed readily by
Received: June 22, 2005
Publication delayed at authorꢀs request.
Keywords: carbenes · cyclic voltammetry ·
.
homogeneous catalysis · olefin metathesis · phase tags
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Angew. Chem. Int. Ed. 2005, 44, 6885 –6888
ꢀ 2005 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.angewandte.org 6887

Communications
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34] Dynamic phase-tag switching of 1: Diallyltosylamide (25 mg,
0.1 mmol) was added to a solution of 1 (0.8 mg, 1 mol%) in
toluene (10 mL), and the reaction mixture was warmed to 358C.
After 3 h, the solution was cooled to room temperature with
subsequent addition of [FcCOCH ][BF ] (2 equiv) in CH Cl
3
4
2
2
ꢀ1
2+
(
200 mL; c = 0.01 molL ) to oxidize/precipitate 1 . The solu-
tion was filtered over cotton wool, and the volatiles were
evaporated to obtain the crude product. The cotton wool was
2
+
rinsed with CH Cl2 (0.5 mL) to dissolve 1 , which was sub-
2
sequently treated with a solution of FcMe (2.1 equiv) in toluene
8
ꢀ3
ꢀ1
(
300 mL; c = 7.0·10 molL ) to regenerate 1. After addition of
fresh toluene (10 mL) and diallyltosylamide (25 mg, 0.1 mmol),
a new reaction cycle was started. The whole procedure was
repeated three times, and quantitative product formation was
observed after each cycle. The switching on/off of catalyst 1
during the reaction was carried out by addition of solutions of
2
+
2+
[
FcCOCH ][BF ] (1!1 = off) and FcMe8 (1 !1 = on) as
3
4
oxidizing and reducing agents, respectively. Spectroscopic data
of 1: H NMR (500 MHz, C D ): d = 1.37 (d, 6H, J = 6.0 Hz,
1
6
6
(
CH ) CHOAr), 2.61 (bs, 12H, ortho-CH ), 2.73 (m, 4H, CH ),
3
2
3
2
2.86 (m, 4H, CH ), 3.47 (s, 4H, NCH CH N), 4.03 (“t”, 4H, J =
2 2 2
1.8 Hz, FcH), 4.09 (s, 10H, FcH), 4.12 (“t”, 4H, J = 1.8 Hz, FcH),
6
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Angew. Chem. Int. Ed. 2005, 44, 6885 –6888