Ferrocene redox controlled reversible immobilization of ruthenium carbene in ionic liquid: A versatile catalyst for ring-closing metathesis

Article abstract of DOI:10.1002/adsc.200800713

A ferrocene-tagged ruthenium carbene 15 that can be reversibly immobilized in an ionic liquid (IL) via the controlled oxidation and reduction of a ferrocene tag was prepared. This offers a new strategy which uses redox chemistry to control immobilization and to recycle both the catalyst and the IL. In this experiment, 11 recycles were performed for the ring-closing metathesis (RCM) of a substrate using 16 as the catalyst in an ionic liquid (IL). More importantly, after the reaction was completed, the ruthenium catalyst was easily separated from the supporting IL by just adding decamethylferrocene (DMFc) to reduce the cationic ferrocene and then extracting it with benzene. Thus, this recycle system offers an easy way to recycle both the ruthenium catalyst and the IL.

Full text of DOI:10.1002/adsc.200800713

FULL PAPERS
DOI: 10.1002/adsc.200800713
Ferrocene Redox Controlled Reversible Immobilization of
Ruthenium Carbene in Ionic Liquid: AVersatile Catalyst for
Ring-Closing Metathesis
Guiyan Liu,a Haiyan He,a and Jianhui Wanga,*
a
Department of Chemistry, College of Science, Tianjin University Tianjin 300072, Peopleꢀs Republic of China
Fax : (+86)-022-2740-3475; e-mail: wjh@tju.edu.cn
Received: November 18, 2008; Revised: May 5, 2009; Published online: June 30, 2009
Supporting information for this article is available on the WWW under
http://dx.doi.org/10.1002/adsc.200800713.
Abstract: A ferrocene-tagged ruthenium carbene 15 um catalyst was easily separated from the supporting
that can be reversibly immobilized in an ionic liquid IL by just adding decamethylferrocene (DMFc) to
(IL) via the controlled oxidation and reduction of a reduce the cationic ferrocene and then extracting it
ferrocene tag was prepared. This offers a new strat- with benzene. Thus, this recycle system offers an
egy which uses redox chemistry to control immobili- easy way to recycle both the ruthenium catalyst and
zation and to recycle both the catalyst and the IL. In the IL.
this experiment, 11 recycles were performed for the
ring-closing metathesis (RCM) of a substrate using
16 as the catalyst in an ionic liquid (IL). More impor- Keywords: ferrocene ligands; homogeneous catalysis;
tantly, after the reaction was completed, the rutheni- ring-closing metathesis; ruthenium
Introduction
carbon bond formation.[2] However, like many other
homogeneous catalysts, these ruthenium carbene
Since the discovery of well-defined modern rutheni- complexes are difficult to recycle and are usually de-
um catalysts 1–4, and 5–11,[1] olefin metathesis has stroyed after a single use. Another serious problem is
become one of the most important tools for carbon- the removal of Ru residuals from the products. To
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overcome these disadvantages of ruthenium carbene Results and Discussion
catalysts, various strategies have been employed to re-
cycle and to reuse them.[3]
Scheme 1 illustrates the reaction of (E)-[4-isopro-
Traditionally, Ru carbene complexes can be recy- poxy-3-(prop-1-enyl)phenyl]methanol 12 with 4-ferro-
cled and reused via immobilization on a solid or poly- cenylbutanoic acid 13 to give the ferrocene-tagged
mer surface through covalent or non-covalent ligand 14 in good yield. The treatment of 14 with 2 in
bonds.[4] More recently, utilization of a tag has been the presence of CuCl in CH2Cl2 at 408C, as described
extensively employed for the immobilization of transi- by Hoveyda and co-workers[4m] resulted in the ex-
tion metal catalysts.[5] For example, a catalyst may change of the styrene group to give the ferrocene-
become suitable for use in ionic liquid (IL) by intro- tagged ruthenium complex 15 in good yield (68%) as
ducing a cation- or anion-appended ligand to the a greenish crystalline solid.
ruthenium metal center.[6] Another method that has
Complex 15 was subjected to cyclic voltammetry
been adapted for recycle and reuse is to introduce a (CV) in order to select a suitable oxidant. The well
fluorous tag to Hoveydaꢀs boomerang ligand which behaved CV peaks of the ferrocene tag indicate that
makes the catalyst suitable for use in fluorous sol- the reaction is reversible and the redox potential is
vents.[7] The key factors in this tagging strategy are +0.534 V (see Figure 1). Redox peaks for the Ru(II)
the polarity and solubility of the catalyst which are center are also observed at higher potentials. The E1/2
largely determined by the connecting tag. If an Ru for this reaction is +1.016 V. The separation between
catalyst is connected to a redox switchable phase tag,
dramatic polarity changes occur in the catalyst when
the tag is switched. The catalyst will then shift from
one solvent phase to another that has a different po-
larity, thus offering a better chance to separate and
recycle both the catalyst and the supporting material.
A previous report demonstrated that a redox-switcha-
ble phase-tagged Ru carbene catalyst could be recy-
cled in a single solvent, presenting a new way to
employ switchable phase tags for the recycling of ho-
mogeneous catalysts.[8] This current study shows that
the recyclability of an Ru catalyst with a redox-
switchable phase tag can be significantly enhanced in
a biphasic solvent system containing an ionic liquid
and a non-polar solvent.
Figure 1. Cyclic voltammogram of the ferrocene-tagged 15.
E1/2 (FeII/FeIII)=+0.534 V (DEp =90 mV), E1/2 (RuII/RuIII)=
+1.016 V (DEp =136 mV) versus SCE.
Scheme 1. Synthesis of redox-switchable ferrocene-tagged Ru carbene catalyst 15.
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Figure 2. The UV/Vis spectra of ruthenium carbene complexes of 15 and 16.
the ferrocence and the Ru redox events is more than ferrocene-tagged 16 are air- and heat-stable com-
sufficient for selective oxidation of the ferrocene. plexes which are comparable to their parent com-
Several oxidants with redox potentials between pound 4.
+0.699 V and +0.806 V, including AgBF4 (E1/2 As expected, 15 and 16 have very different solubili-
=
+0.75 V), AgPF6 (E1/2 =+0.75 V), benzoquinone ties due to the different properties of the ferrocene
(E1/2 =+0.699 V), and I2 (+0.806 V in CH2Cl2) were tag. Compound 15 exhibits very good solubility in
tested as oxidizers for the ferrocene tag in CH2Cl2. non-polar solvents, such as benzene, toluene, and hex-
The reaction of 15 with AgBF4, or AgPF6 resulted in anes. On the other hand, 16 is very soluble in polar
a very unstable yellow complex which showed no ac- solvents, such as alcohols, acetone, and acetyl acetate.
tivity in ring-closing metathesis (RCM) reactions. The More importantly, the solubility of these complexes
ferrocene tag could be oxidized by benzoquinone in can be adjusted by varying the ferrocene tag through
the presence of an HPF6-water solution, resulting in redox reactions. An experiment to demonstrate this
an air-sensitive green complex. This complex was very concept was conducted in a biphasic system contain-
active for RCM reactions under inert gas, but it de- ing benzene and an IL (see Figure 3).
composed immediately in the presence of air. When
With its neutral ferrocene tag, 15 showed very good
I2 was employed as an oxidant, the reaction proceed- solubility in the benzene solvent (upper layer), where-
ed smoothly to give cationic ferrocene-tagged rutheni- as only a trace amount of 15 was found in the IL
um complexes, identified as 16, in nearly quantitative (lower layer). When I2 was added, the ferrocene tag
yield (>98%). The oxidation of 15 in situ with I2 was was immediately oxidized to the cationic ferrocene to
1
1
confirmed by H NMR and ESI-MS. In the H NMR give 16 which was very soluble in the IL. A further
spectra the benzylidene proton shifted from study showed that the cationic ferrocene could be re-
16.523 ppm to 15.494 ppm. The MS of catalyst 15 has duced to neutral ferrocene by adding one equivalent
a dominant peak at m/z=910.2 [M]+ (calcd.: 910.19). decamethylferrocene (DMFc) (E1/2 =À0.59 V) to give
The spectrum of catalyst 16 has a peak at m/z= 15 which then shifted back to the benzene layer. This
1059.6 [M+Na]+ (calcd.: 1060.08) and a fragment procedure was completely reversible, and at least 4
peak at m/z=911.4. This difference corresponds to cycles were repeated. Figure 3 shows the result.
the loss of one IÀ unit. In order to verify that iodide
does not exchange with the Ru Cl to give Ru I, an- diene to investigate the catalytic activity of 15 and 16
other ESI-MS for catalyst 16 was obtained under dif- for RCM. The relative conversion rates for RCM by
Diethyl diallymalonate 17 was chosen as a test
À
À
ferent
conditions.
A
dominant
peak
for 15 and 16 under similar conditions are shown in
[C46H54Cl2N2O3RuFe]+ appears at m/z=910.12 Figure 4. At 308C, the catalytic activities of 15 and 16
(calcd.: 910.19) in the +c ESI full MS. A dominant are slightly lower than that of the parent compound 4.
peak for IÀ is also found at m/z=127.16 (calcd.: This can be explained by the alkyl substitution at the
126.90) in the Àc ESI full MS. This indicates that Cl is para-position which enhances the electron donor be-
not displaced by I and the anion is IÀ.
haviour of the isopropoxy group to the Ru center.
Further evidence that 15 has been oxidized to 16 is The ferrocene-tagged 15 exhibits a slightly better per-
seen in their UV/Vis spectra (Figure 2). The UV/Vis formance than the cationic ferrocene-tagged 16.
spectra of the oxidation product 16 showed a new
Nevertheless, both 15 and 16 are active RCM cata-
peak at 290 nm. Further study shows that the ferro- lysts. For both catalysts, high conversions (> 94%)
cene-tagged ruthenium carbene 15 and the cationic were achieved after 30 min for the RCM of 17 at
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Figure 3. Redox controlled ferrocene-tagged 15 and 16 exhibiting different solubility in ionic liquid (ILs) and benzene (Bz).
(Switching on and off of the ferrocene tag detected by UV/Vis at l=381 nm.)
308C, which is comparable with 4 under similar reac-
tion conditions.[9] Compared with other reported Ru
carbene catalysts[1a–h], both 15 and 16 are moderately
active RCM catalysts.
Further studies showed that 15 and 16 are also
active for ring closures of the N-protected substrates
19, 23, 31, 33 and a sulfur-containing substrate 21.
These reactions resulted in the formation of either
five-, or six-membered rings with di- or trisubstituted
double bonds. The products were obtained in high
conversions with low catalyst loading (0.1–1.0 mol%)
(see Table 1).
For the bulky-substituted dienes 37 and 39, both 15
and 16 gave low conversions at room temperature in
CH2Cl2. However RCM was achieved in good conver-
sions for both catalysts at elevated temperatures
(458C in CH2Cl2 or 808C in toluene) with a longer re-
action time (24 h). The conversion of oxygen-contain-
ing dienes, 25, 27, and 35 was consistently lower for
16 than for 15. These substrates form seven-mem-
bered rings with a di- or trisubstituted double bond.
Nevertheless, both 15 and 16 are highly active cata-
lysts for a large scope of RCM reactions, and are tol-
Figure 4. Relative conversion rates of 15 and 16 using
1 mol% catalyst in CH2Cl2 at 308C.
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Table 1. Application of catalysts 15 and 16 to different substrates.[a]
[a]
[b]
Reactions were conducted in CH2Cl2 and relative conversion rates of substrates
were obtained by 1H NMR spectroscopy.
Reaction in toluene.
erant to many functional groups which is similar to
ACHTUNGTRENNUNG
the behaviour of their parent compound 4.
To test the recyclability, the ferrocene-tagged cata- of catalyst loading (0.1–2.5 mol%), the cationic ferro-
lyst 16 was evaluated for RCM in 1-butyl-3-methyl- cene-tagged catalyst 16 can be recycled and reused 2
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Table 2. Recycling and reuse of 16 in BMI.PF6.
[a]
1
Relative conversion rates of substrates were obtained by H NMR spectroscopy.
times with 0.1 mol% loading, 3 times with 0.5 mol%, tained. Even for cross-metathesis, catalyst 16 could be
6 times with 1.0 mol%, and 11 times with 2.5 mol% recycled and reused 3 times with 2.5 mol% loading
for substrate 19. For the oxygen-containing diene 27 and 2 times with 1.0 mol%. This is comparable to the
and N-protected substrates 33 and 41, catalyst 16 is results for other cation-[6a,c,d,e,f] or anion-appended[6b]
also very recyclable and high conversions were ob- ruthenium carbene catalysts. The total TON of cata-
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Table 3. Recycling and reuse of 16 in BMI.PF6 for different substrates.
[a]
[b]
16 (2.5 mol%) relative to the substrate.
Relative conversion rates of substrates were obtained by H NMR spectroscopy.
1
lyst 16 for substrates is reduced with increased cata- mass spectrometry (ICP-MS) analysis of product 20
lyst loading. This can be attributed to decomposition after the first recycle using catalyst 16 (2.5 mol% Ru)
of the catalyst, which was accelerated in the presence indicates only 26.1 ppm Ru contamination in the
of ruthenium residues and other decomposition prod- crude products. This value is substantially lower than
ucts. Nevertheless, 16 is a recyclable catalyst in IL for that obtained for homogeneous monomeric catalysts 2
many different diene substrates.
or 4, where all of the catalyst remains in the product
In addition, the utilization of ferrocene-tagged cata- mixture (1.0%, by mass) and this is similar to previ-
lysts is a far superior strategy to decrease the Ru con- ously reported methods,[6e,10] although further purifica-
taminations in the products. Catalyst 16 dissolves in tion was still needed to obtain products pure enough
the ionic liquid via electrostatic interactions of the for medical uses.
cationic ferrocene tag. At the same time, the use of
Having established the recyclability and reusability
an ionic liquid should make most of the Ru residue of catalyst 16, we next focused on its performance for
stay within the ionic liquid, which decreases the Ru RCM in a variety of other tri- and tetrasubstituted
residues in the products. Inductively coupled plasma- dienes as well as for cross-metathesis. As shown in
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(5.91 mmol, 1 equiv.) was added slowly via a syringe. The re-
sulting solution was stirred for 1 h at this temperature. The
mixture was then concentrated under vacuum to obtain a
thick oily residue. A 20 mL portion of dichloromethane was
added to this residue. After being washed four times with
water, the organic layer was dried over magnesium sulfate.
Removal of the solvent from the filtration gave an oily resi-
due. The residue was then dissolved in 15 mL methanol, and
then 0.48 g NaBH4 (12.7 mmol, 2.5 equiv.) were added. The
mixture was stirred for 5 h at room temperature, and was
then concentrated under vacuum to give a colourless resi-
due. Next, 20 mL of water and 100 mL of dichloromethane
were added to the residue. The organic layer was separated
and washed four times with water, dried over magnesium
sulfate, filtered and concentrated. The residue was purified
by silica gel chromatography using dichloromethane as the
eluant. The desired (E)-[4-isopropoxy-3-(prop-1-enyl)phe-
nyl]methanol (12) was obtained as a colourless oil; yield:
0.86 g (4.20 mmol, 71%); analytical data: found (calcd) for
Table 3, use of 2.5 mol% of the catalyst relative to the
substrate led to high conversions even for the tetra-
substituted dienes. As expected, extended reaction
times and higher temperatures were necessary to
achieve high conversions for the tetrasubstituted
dienes. The recycled catalyst and ionic liquid from the
reaction of 37 were used for the metathesis of the
next substrate. The catalyst remained highly active for
27 even after being recovered 7 times. It should be
noted that the crude product from 27 consisted of
only the cyclic product 28 and was devoid of any de-
tectable amount of the product from the previous re-
actions. This demonstrates the advantage of the se-
quential use of a recyclable and reusable catalyst.
This recycle system offers an easy way to recycle
both the Ru catalyst and the IL and it is significantly
different from traditionally redox-tagged systems.
After the reaction was finished, the Ru catalyst could
be easily separated from the supporting IL by just
adding DMFc to reduce the cationic ferrocene and
then extracting it with benzene. The recycled Ru cata-
lyst and the IL could then be used for other purposes
without any further purification. More than 81% Ru
carbene 15 was recovered from a reaction system
after one RCM reaction cycle. The remaining IL
could be used in further reactions after simply treat-
ing it with a reducing reagent, and extracting it with
benzene to remove the ferrocenes. This new strategy
using redox chemistry to control the immobilization
and to recycle both the catalyst and the IL offers a
new step toward the ideal catalyst.
C13H18O2:
C 75.60 (75.69), H
8.70 (8.80); 1H NMR
(400 MHz, CDCl3): d=1.35 (d, 3JH,H =6.0 Hz, 6H, CH3),
1.90 (dd, 3JH,H =1.6, 3JH,H =6.8 Hz, 3H, CH3), 2.84 (s, 1H,
3
OH), 4.47 (m, JH,H =6.0 Hz, 1H, CH), 4.53 (s, 2H, CH2),
6.208 (m, 1H, 3JH,H =6.8 Hz, =CH), 6.71 (dd, 3JH,H =1.6,
3
3JH,H =16 Hz, CHar), 6.81 (d, 1H, JH,H =8.4 Hz, =CH), 7.08
3
3
3
(dd, JH,H =2.0 Hz, JH,H =8.4 Hz, 1H, CHar), 7.38 (d, JH,H
=
2 Hz, 1H, CHar); 13C NMR (125 MHz, CDCl3): d=19.2,
22.4, 65.0, 71.3, 114.7, 125.7, 126.1, 126.3, 126.8, 128.5, 133.5,
154.3; IR (CH2Cl2): v=3395, 3035, 2977, 2932, 2728, 2650,
1651, 1608, 1492, 1448, 1378, 1245, 1120, 1020, 967, 816, 623,
631, 519, 469 cmÀ1.
Preparation of 4-Ferrocenebutyric Acid (13)
A solution of ferrocene (4.4 g, 23.4 mmol) and succinic an-
hydride (2.34 g, 23.4 mmol) in dry CH2Cl2 (40 mL) was
added drop wise to a mixture of AlCl3 (8.5 g, 64.4 mmol)
and dry CH2Cl2 (40 mL) at 08C under N2. After being
Conclusions
A ferrocene-tagged Ru carbene, which can be reversi-
bly dissolved in an IL by varying the ferrocene tag via stirred for 2 h at 08C, the reaction mixture was poured into
ice and extracted with CH2Cl2 to remove the unreacted fer-
rocene. The aqueous layer was acidified with hydrochloric
acid to give an orange crystalline precipitation of 4-ferrocen-
yl-4-oxobutyric acid; yield: 4.5 g (73.5%).
redox reactions, has been developed. Given the grow-
ing interest in the development of recyclable catalytic
systems for different tasks in organic synthesis, the
ferrocene tagging strategy described here could be ap-
plied to the design of other transition-metal-based
catalysts.
Within 15 min, Zn-amalgam (30.1 g, containing 5% Zn)
was added in small portions to a solution of 4-ferrocenyl-4-
oxobutyric acid (4.0 g, 11.6 mmol) in cold AcOH (80 mL).
The reaction mixture was stirred at 90–1008C for 1.5 h, and
then the liquid part of the reaction mixture was poured into
water, and extracted with ethyl ether. The obtained organic
layer was washed with a saturated solution of NaCl, and
dried with anhydrous MgSO4. Orange crystals of 4-ferroce-
nebutyric acid 13 were obtained after evaporation of the sol-
vent; yield: 1.41 g (5.18 mmol, 37%); analytical data found
(calcd.) for: C14H16O2Fe: C 61.91 (61.79), H 5.94 (5.93);
Experimental Section
Synthesis of (E)-[4-Isopropoxy-3-(prop-1-enyl)-
phenyl]methanol (12)
A flask was charged with 1.50 g (5.91 mmol) (E)-4-bromo-1-
isopropoxy-2-(prop-1-enyl)-benzene (precursor for 12) and
5 mL anhydrous diethyl ether. The solution was cooled to
À788C, and 4.27 mL n-BuLi (1.66M in hexanes, 7.08 mmol,
1.2 equiv.) was slowly added via a syringe. The reaction mix-
ture was then allowed to warm to room temperature slowly.
After being stirred for 1 h at room temperature, the reaction
mixture was cooled to À788C. To this mixture, 0.43 g DMF
3
1H NMR (500 MHz, CDCl3): d=1.85 (t, JH,H =9.0 Hz, 2H,
3
CH2), 2.39 (t, 3JH,H =9.0 Hz, 4H, CH2), 4.07 (d, JH,H
=
4.0 Hz, 4H, FcH), 4.12 (s, 5H, FcH); 13C NMR (125 MHz,
CDCl3): d=26.2, 29.1, 34.0, 67.6, 68.4, 68.8, 88.2, 180.6: IR
(KBr): v=3095, 2949, 2917, 2855, 1713, 1455, 1433, 1410,
1329, 1276, 1220, 1185, 1103, 1036, 1001, 911, 818, 702, 485,
415 cmÀ1.
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Guiyan Liu et al.
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ence electrode with a BAS Epsilon voltammetric analyzer
(scan rate 50 mV/s). Before each experiment the electrodes
were washed in ultrapure water containing a protein remov-
er for 5 min and then sonicated in ultrapure water and ace-
tone for 5 min. The CV spectra were obtained by a linear
scan from À0.3 to 1.5 V vs. SCE in a solution of catalyst 15
(10À3 M) in 0.1M electrolyte (Bu4NClO4-CH2Cl2). The re-
sults are shown in Figure 1.
Preparation of the Ferrocene-Tagged Ligand 14
To a solution of (E)-[4-isopropoxy-3-(prop-1-enyl)phenyl]-
methanol (0.15 g, 0.73 mmol) and 1-ferrocenebutyric acid
(0.24 g, 0.73 mmol) in anhydrous CH2Cl2, DCC (0.15 g,
0.73 mmol) and DMAP (0.178 g, 1.46 mmol) were added at
08C. After being stirred for 1 h at 08C, the mixture was
stirred for 12 h at room temperature. Then, the insoluble
materials were filtered out to obtain a clear filtrate. Remov-
al of the solvent from the filtrate under vacuum gave a
crude product of 14. Pure 14 was obtained as yellow oil
after flash column chromatography purification of the crude
product on silica using pentanes/CH2Cl2 (1:1) as the eluant;
yield: 0.26 g (0.51 mmol, 70%); analytical data found
(calcd.) for C27H32O3Fe: C 70.57 (70.44), H 7.02 (7.01).
Preparation of the Cationic Ferrocene-Tagged
Ruthenium Complex (16)
A solution of catalyst 15 (0.30 g, 0.33 mmol) in dry dichloro-
methane (10 mL) was added to a flask under N2. A solution
of I2 (43.2 mg, 0.17 mmol, 0.5 equiv.) in dry dichloromethane
(5 mL) was added slowly to the reaction mixture via a sy-
ringe at room temperature. The resulting mixture was then
stirred for 10 min. Removal of the solvent from the reaction
mixture under vacuum gave a green solid. The ruthenium
complex 16 was obtained by chromatographic purification
of the residue using CH2Cl2/ethyl acetate (2:1) as the eluant;
yield: 0.31 g (0.30 mmol, 90%); analytical data found
(calcd.) for C46H54Cl2N2O3FeRuI: C 53.28 (53.24), H 5.24
(5.25), N 2.69 (2.70); 1H NMR (500 MHz, CDCl3: d=
À6.64~-4.55 (FcH), 0.77 (6H, 2CH3), 0.86 (2H, CH2), 1.26
(6H, 2CH3), 1.44 (2H, CH2), 2.06 (12H, 4CH3), 2.27 (2H,
CH2), 3.91 (4H, CH2), 4.56 (2H, CH2), 6.10 (1H, CHar),
7.23 (1H, CHar), 7.34 (1H, CHar), 15.49 (1H, Ru-H);
13C NMR (125 MHz, CDCl3): d=64.8, 74.5, 112.4, 121.3,
129.6, 129.9, 142.7, 150.2, 171.0, 171.0, 208.3; ESI-MS: m/z=
1059.6 [M+Na]+ (calcd.: 1060.08); +c ESI-MS: m/z=910.12
3
1H NMR (500 MHz, CDCl3): d=1.34 (d, JH,H =7.5 Hz, 6H,
CH3), 1.84 (d, 3JH,H =8.5 Hz, 3H, CH3), 1.89 (d, JH,H
=
3
3
7.5 Hz, 2H, CH2), 2.34 (m, JH,H =5.0 Hz, 4H, CH2), 4.04 (s,
4H, FcH), 4.04 (s, 5H, FcH), 4.53 (m, 3JH,H =7.5 Hz, 1H,
3
CH), 5.04 (s, 2H, CH2), 6.22 (m, JH,H =8.5 Hz, 1H, =CH),
3
6.68 (d, JH,H =20 Hz, 1H, =CH), 6.81 (d, JH,H =10.5 Hz, 1H,
CHar), 7.13 (d, 3JH,H =10.5 Hz, 1H, CHar), 7.41 (s, 1H,
CHar); 13C NMR (125 MHz, CDCl3): d=19.2, 22.5, 26.5,
29.2, 34.2, 66.4, 67.6, 68.5, 68.9, 71.057, 88.5, 114.2, 125.9,
126.6, 127.3, 128.2, 128.3, 128.5, 154.9, 173.7; IR (CH2Cl2):
n=3088, 2975, 2932, 1733, 1609, 1498, 1447, 1378, 1245, 967,
817, 683, 497, 463, 436, 410 cmÀ1.
Preparation of the Ferrocene-Tagged Catalyst 15
To
a flask charged with Grubbsꢀ catalyst 2 (0.42 g,
+
0.50 mmol) and CuCl (0.05 g, 0.50 mmol), a solution of 14
(0.30 g, 0.6 mmol) in 25 mL dry dichloromethane was added
at room temperature under N2. The resulting mixture was
then refluxed for 20 min. After being cooled down to room
temperature, the reaction mixture was filtered to collect a
clear filtrate. The solvent from the filtrate was evaporated
under vacuum to give a residue. The residue was purified by
flash column chromatography on silica using CH2Cl2 as the
elutant to give the desired product 15 as a green crystalline
solid; yield: 0.32 g (0.34 mmol, 68%); analytical data found
(calcd.) for C46H54Cl2N2O3FeRu: C 60.81 (60.66), H 5.98
[C46H54Cl2N2O3RuFe] (calcd.: 910.19); Àc ESI-MS: m/z=
127.16 (calcd.: 126.90).
Reduction Study of the Ruthenium Carbene Complex
16
To a solution of catalyst 16 (0.10 g, 0.1 mmol) in dry di-
chloromethane (5 mL), bis(pentamethylcyclopentadienyl)-
AHCTUNGTREGiNNUN ron (65.2 mg, 0.2 mmol, 2 equiv.) was added at room tem-
perature under N2. The resulting mixture was then stirred
for 10 min. Removal of solvent from the reaction mixture
under vacuum gave a dark green solid. Ruthenium complex
15 was obtained by chromatographic purification of the resi-
1
(5.98), N 3.09 (3.08); H NMR (500 MHz, CDCl3): d=1.26
(d, 3JH,H =6.5 Hz, 6H, 2CH3), 1.82 (d, 3JH,H =7.5 Hz, 2H,
3
CH2), 2.34 (m, JH,H =7.5 Hz, 4H, CH2), 2.41 (s, 6H, CH3),
due using CH2Cl2 as the eluant; yield: 0.082 g (0.09 mmol,
3
90%); 1H NMR (400 MHz, CDCl3): d=1.25 (d, JH,H
=
2.47(s, 12H, CH3), 4.07 (s, 4H, FcH), 4.12 (s, 5H, FcH), 4.18
3
3
(s, 4H, CH2), 5.07 (s, 2H, CH2), 4.87 (m, JH,H =6.5 Hz, H,
6.0 Hz, 6H, 2CH3), 1.77 (d, JH,H =1.6 Hz, 2H, CH2), 2.34
(m, JH,H =7.2 Hz, 4H, CH2), 2.41 (s, 6H, CH3), 2.47 (s, 12H,
3
CH), 6.76 (d, JH,H =8.5 Hz, H, CHar), 6.91 (s, 1H, CHar),
7.07 (s, 4H, CHar), 7.50 (dd, 3JH,H =2.0 Hz, 3JH,H =8.5 Hz,
1H, CHar), 16.52 (s, 1H, Ru-H); 13C NMR (125 MHz,
CDCl3): d=21.3, 21.4, 26.3, 29.2, 29.9, 34.2, 51.7, 51.8, 51.8,
65.4, 68.1, 69.0, 69.5, 75.6, 89.3, 13.1, 123.2, 129.6, 129.9,
130.0, 130.3, 135.7, 139.1, 145.4, 152.4, 173.5, 211.0, 296.1; IR
(KBr): n=3091, 2924, 2864, 2738, 1891, 1734, 1670, 1595,
1486, 1446, 1425, 1384, 1262, 1133, 1105, 1032, 930, 855, 819,
757, 579, 544, 497, 442 cmÀ1.
CH3), 4.18 (s, 4H, FcH), 4.20 (s, 5H, FcH), 4.24 (s, 4H,
3
CH2), 4.88 (m, JH,H =5.6 Hz, 1H, CH), 5.07 (s, 2H, CH2),
6.76 (d, JH,H =8.4 Hz, 1H, CHar), 6.90 (s, 1H, CHar), 7.07
(s, 4H, CHar), 7.50 (dd, 3JH,H =1.2 Hz, 3JH,H =8.2 Hz, 1H,
CHar), 16.51 (s, 1H, Ru-H); ESI-MS: m/z=910.2 [M]+
(calcd. for [C46H54Cl2N2O3FeRu]+: 910.19).
Shuttling of 15 between the IL and Organic Phase by
Switching On and Off the Ferrocene Tag Monitored
with UV/Vis Spectroscopy
Cyclic Voltammogram of the Ferrocene-Tagged
Catalyst 15
Under N2 gas, a glass vial with a screw-cap top was charged
with 3.0 mg (0.0033 mmol) 15, 0.50 mL CH2Cl2/benzene
(1:10), and 0.20 mL BMIPF6. The resulting mixture was
shaken at room temperature. After 15 min, 10.0 mL aliquots
Cyclic voltammetry (CV) was carried out in a standard one-
compartment cell under a nitrogen atmosphere at 258C
using a platinum-wire counter electrode and an SCE refer-
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Adv. Synth. Catal. 2009, 351, 1610 – 1620

Ferrocene Redox Controlled Reversible Immobilization of Ruthenium Carbene
FULL PAPERS
were taken from the upper organic layer using a microsyr-
inge and were diluted to 10.0 mL with CH2Cl2. The resulting
solutions were subjected to UV detection. The concentra-
tion of 15 in the organic layer was obtained by comparing
the absorption value with a standard solution of 15. I2
(0.42 mg, 0.0017 mmol, 0.5 equiv.) was then added to the
mixture and the resulted mixture was shaken at room tem-
perature for 10 min. Aliquots (10 mL) were taken from the
upper organic layer, and subjected to UV detection. Next,
1.1 mg (0.0033 mmol, 1 equiv.) bis(pentamethylcyclopenta-
dienyl)iron was introduced into the vial and the resulting
mixture was shaken at room temperature for a few minutes.
Aliquots (10 mL) were again taken from the upper organic
layer to detect the concentration of 15. The operation was
repeated 4 times and the concentration changes of 15 in the
upper organic layer are shown in Figure 2.
taining 16). The ionic layer (containing 16) was then subject-
ed to another cycle. Solvent from the organic solution was
evaporated to afford the crude cyclized product. After pu-
rification by short column chromatography to remove trace
amounts of Ru residue, the sample was subjected for
1H NMR. Conversions were obtained by comparing the
ratios of the integrals of starting materials with those of
products. The recycle data for 16 are shown in Table 2.
Sequential Use of Catalyst 16 in the RCM of
Different Substrates
3.4 mg (0.0033 mmol) 16, and 0.04 mL BMI.PF6 in dry
CH2Cl2 (0.5 mL) were mixed in a reaction flask under N2.
After the solution had been stirred for 5 min, substrate
(0.13 mmol) was introduced into this solution via a syringe.
The reaction mixture was stirred at different temperature
until the reaction was completed (monitored by TLC).
Then, CH2Cl2 from the solution was removed under vacuum
and petroleum ether was added. The mixture was subjected
to centrifugation to separate the ionic layer (containing 16).
The ionic layer (containing 16) was then subjected to anoth-
er cycle. Solvent from the organic solution was evaporated
to afford the crude cyclized product. After purification by
short column chromatography to remove trace amounts of
Kinetics Study of 15 and 16
A Schlenk flask was charged with catalyst (0.012 mmol,
1.0 mol%) and CH2Cl2 (12.0 mL). The sample was equili-
brated at 308C before 17 (289.5 mL, 288 mg, 1.2 mmol,
0.1M) was added via a syringe. Aliquots were taken from
the reaction mixture at appropriate times using a syringe
and were quenched immediately with 0.1 mol/L PEI in
CH2Cl2. The resulting solution was then subjected to short
column chromatography to remove the Ru metal residue
using CH2Cl2 as the eluant. Solvent from the collected solu-
tion was evaporated under vacuum. The conversion to 17
was determined by comparing the ratio of the integrals of
the methylene proton peaks in the starting material, d=2.63
(dt), with those in the product, d=3.01 (s). The result is
shown in Figure 3.
1
Ru residue, the sample was subjected to H NMR analysis.
Conversions were obtained by comparing the ratios of the
integrals of starting materials with those of products. The re-
cycle data for 16 are shown in Table 3.
Recovery of the Ru Catalyst 15 and the IL
The general procedure for metathesis reactions with 16 in
IL is as described above. When the conversion of the sub-
strate was completed, the product was removed as described
above. To the separated ionic layer (containing 16), a solu-
tion of DMFc (one equiv.) in dry dichloromethane (0.5 mL)
was added at room temperature under N2. The resulting
mixture was then stirred for 30 min. After the CH2Cl2 from
the mixture had been removed under vacuum, the residue
was repeatedly washed with benzene (1 mL/each). The re-
moval of solvent from the combined benzene layers gave
the ruthenium complex 15; yield: 2.4 mg (0.0030 mmol,
81%).
Catalytic Study of the Ruthenium Carbenes 15 and 16
The general procedure for metathesis reactions with the
ruthenium carbene 15 and 16 is performed as follows: a cer-
tain amount of ruthenium carbene catalyst 15 (or 16) and a
solution of substrate in dry CH2Cl2 or toluene was mixed in
a reaction flask under nitrogen. The reaction mixture was
stirred for 0.5–24 h. At the end of the reaction (monitored
by TLC), the catalysts were separated by silica gel chroma-
tography using CH2Cl2 as the eluant to remove trace
amounts of Ru residues. Conversions were estimated by
ꢂH NMR spectroscopy and obtained by comparing the ratios
of the integrals of the starting materials with those of prod-
ucts. The catalytic activities of ruthenium carbene 15 and 16
for a variety of substrates are shown in Table 1.
Acknowledgements
The authors would like to acknowledge that this work was
supported by NSFC 20872108 and Tianjin University.
Recycle Study of the Ruthenium Carbene 16 in IL
The general procedure for metathesis reactions with 16 in
IL was performed as follows: catalyst 16 (2.5 mol%, References
1.0 mol%, 0.5 mol%, or 0.1 mol% Ru), and 0.04 mL BMI
PF6 in dry CH2Cl2 (0.5 mL) were mixed in a reaction flask
under N2. After the complete transfer of 16 from the organ-
ic phase to the ionic phase, substrate (0.13 mmol) was intro-
duced to the solution of 16. The reaction mixture was stirred
at 358C until the conversion of substrate was completed
(monitored by TLC). Then the solvent was removed under
vacuum and petroleum ether was added. The mixture was
subjected to centrifugation to separate the ionic layer (con-
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Adv. Synth. Catal. 2009, 351, 1610 – 1620