Synthesis of stable ruthenium olefin metathesis catalysts with mixed anionic ligands

Article abstract of DOI:10.1002/ejic.201101048

A series of ruthenium carboxylate complexes that contain two different anionic ligands was prepared. The complexes that bear iodide ligands exhibit remarkable chemical stability. Such complexes have a diminished tendency to undergo anionic ligand exchange

Full text of DOI:10.1002/ejic.201101048

FULL PAPER
DOI: 10.1002/ejic.201101048
Synthesis of Stable Ruthenium Olefin Metathesis Catalysts with Mixed
Anionic Ligands
Rafał Gawin[a] and Karol Grela*[a]
Keywords: Ruthenium / Metathesis / Chiral ligands / Anionic ligands / Carbene ligands
A series of ruthenium carboxylate complexes that contain
two different anionic ligands was prepared. The complexes
that bear iodide ligands exhibit remarkable chemical sta-
bility. Such complexes have a diminished tendency to un-
dergo anionic ligand exchange and can be activated by
various acids to form catalysts, which are active in olefin
metathesis reactions.
nium carboxylate can be cleaved by a broad selection of
organic and inorganic acids[7b] to give highly active catalysts
(e.g. 4a and 4b, Scheme 1).
Introduction
Olefin metathesis has become a standard tool in organic
synthesis.[1a,1b] Since ruthenium complex 1a was developed
by Grubbs, modifications of the parent core have improved
its catalytic activity.[1c] The real breakthrough came with
the introduction of N-heterocyclic carbene ligands[1d] and
discovery of Hoveyda-type catalysts 2, which possess better
stability and activity profiles (Figure 1).[1e]
Scheme 1. Complex 3 and catalytically active 4a and 4b.[7a]
The method to introduce an acid to the ruthenium coor-
dination sphere is straightforward and does not require the
use of silver or thallium salts.[2] We used this method to
obtain a surfactant-decorated catalyst for metathesis in
water emulsions,[8] whereas Lee and coworkers used 3 for
metathesis in an ionic liquid.[9] Although 3 was used in
some interesting applications, we observed that carboxylate
complexes that bear two different anionic ligands (e.g. 4b)
undergo disproportionation to give a mixture of complexes.
Our present work is focused on the inhibition of this pro-
cess.
Figure 1. Ruthenium olefin-metathesis catalysts.
One of the platforms for the modification of catalyst
properties are anionic ligands. A lot of research has been
devoted to replace the parent chloride ligands with other
halides, carboxylic, sulfonic, phosphonic, and nitric acids,
etc.[2] Some of these modifications have been used to immo-
bilize catalysts,[3] whereas others changed their reactivity
and selectivity in olefin metathesis reactions.[4] Although ex-
amples of catalysts with two different anionic ligands have
been reported,[4,5] halides and pseudohalides are generally
labile, and the synthesis of catalysts with mixed anionic li-
gands seems to be problematic.[6] We have previously devel-
oped 3 with a chelating carboxylate ligand (Scheme 1).[7a]
Although 3 is inactive in olefin metathesis, the cyclic ruthe-
Results and Discussion
We have reported that different acids can be used to acti-
vate 3 to form active catalysts, which include complexes
with mixed anionic ligands (e.g. 4b).[7a] We observed that
these complexes undergo disproportionation through an-
ionic ligand exchange.[6] For example, when 1 equiv. of per-
fluorononanoic acid was added to a solution of 3 in CDCl3,
4b was formed immediately, however, 1H NMR spectro-
scopic inspection of the reaction mixture has shown the
presence of minor amounts of 5 and 4a (Scheme 2).[10]
[a] Institute of Organic Chemistry, Polish Academy of Sciences,
Kasprzaka 44/52, 01-224 Warsaw, Poland
Fax: +48-22-632-66-81
E-mail: klgrela@gmail.com
http://www.karolgrela.eu/
Supporting information for this article is available on the
WWW under http://dx.doi.org/10.1002/ejic.201101048.
Eur. J. Inorg. Chem. 2012, 1477–1484
© 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
1477

R. Gawin, K. Grela
FULL PAPER
of this reaction was 10, which underwent spontaneous cycli-
zation to 9 during silica gel chromatography. Isolated 9 can
be transformed back to the active 10 by the addition of
1 equiv. of HCl in diethyl ether, and 10 can be cyclized
again to 9 using silica gel or a base.
Scheme 2. Formation and disproportionation of 4b.
Scheme 4. Synthesis of 9 and 10.
Although the desired complex 4b was the major com-
pound in this equilibrium (74%), the dichloride complex 4a
(13%) is much more active in metathesis and the overall
reactivity of such a mixture is not well defined. This dispro-
portionation may be irrelevant in many applications,[8,9] but
could be a problem in some cases, such as immobilization.
Moreover, the isolation of complexes with mixed anionic
ligands in pure forms can be problematic due to the equilib-
rium mentioned. In one of our projects related to nanofil-
tration,[11] we became interested in well-defined complexes
that show no tendency for anionic ligand exchange. We pre-
sumed that changing the chloride in 3 to another ligand
may affect the equilibrium of the anionic ligand exchange.
As the lability of anionic ligands in monoiodide ruthenium
catalysts has not been investigated and the introduction of
iodide is straightforward, we decided to prepare an iodide
analogue of 3. It is well known that changing a chloride
ligand to iodide in ruthenium complexes can cause a serious
decrease in the catalytic activity.[2r,12] To minimize this ef-
fect, we focused on the optimization of the parent structure
of 3. Our assumption was that the replacement of the
methyl substituent in 3 with a bulkier isopropyl group
would increase the activity of the resulting complex, which
would compensate for the expected decrease in activity
caused by the introduction of iodide.
During the cyclization of 10 to 9, a new stereogenic cen-
ter was created at the ruthenium centre. Because 8 also has
a stereogenic center, one can expect the formation of a mix-
ture of diastereoisomers. However, a careful inspection of
1
the H NMR spectrum of 9 shows that this product was
formed as a single diastereoisomer.[13] Therefore, we think
that the cyclization of carboxylate is stereospecific (the
same is true for 3). The activity of 10 was compared to the
activity of 4a and commercially available Hoveyda second
generation catalyst 2 in the model ring closing metathesis
(RCM) reaction of diethyl diallylmalonate (DEDAM, Fig-
ure 2).
Starting from commercially available 2-propenylphenol 6
and methyl 2-bromo-3-methylbutanoate, ester 7 was ob-
tained. Mild hydrolysis afforded the carboxylic acid ligand
precursor 8 in good yield (Scheme 3).
Figure 2. Comparison of the activity of 4a (᭢), 10 (᭜), and 2 (᭣)
in the RCM of DEDAM. Conditions: catalyst loading 5 mol-%, T
= 24 °C, c = 0.1 m, CD2Cl2. Conversion measured by 1H NMR
spectroscopy.
As expected, changing the methyl group in 4a (obtained
by acid activation of 3) to a bulkier isopropyl group in 10
(obtained from 9) greatly enhanced the catalytic activity in
olefin metathesis. Interestingly, 10 was found to be slightly
more active than 2 (Figure 2).
Scheme 3. Synthesis of 8.
With the optimized structure of 9 in hand, we attempted
Precursor 8 was treated with Grubbs’ second generation to replace the chloride ligand to obtain the iodide analogue.
catalyst 1b in the presence of CuCl as a phosphane scaven- A solution of 9 in acetone was treated with an excess of
ger to give 9 in good yield (Scheme 4). The initial product potassium iodide followed by filtration of the inorganic
1478
www.eurjic.org
© 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Inorg. Chem. 2012, 1477–1484

Ru Olefin Metathesis Catalysts with Mixed Anionic Ligands
salts. After triple repetition of this procedure, 11 was ob-
tained in almost quantitative yield and high purity
(Scheme 5).
Scheme 5. Synthesis of 11.
Figure 3. Comparison of activity of 10 (᭿), 12a (♦), and 12b (᭢)
in the RCM of DEDAM. Conditions: catalyst loading 5 mol-%, T
= 24 °C, c = 0.1 m, CD2Cl2. Conversion measured by 1H NMR
spectroscopy.
Although chloride complexes 3 and 9 were found to be
very stable (no decomposition in solution for days), to our
surprise the iodide complex 11 was even more stable and
could be stored as a stock solution for months, even in non-
degassed solvents. Similar to 3 and 9, 11 is not active in
olefin metathesis and requires activation by acids. To test
its susceptibility to anionic ligand exchange, we used HCl
and trifluoroacetic acid to form mixed ligand complexes
12a–b (Scheme 6).
tion times it was possible to reach higher conversions (15%
after 8 h, 50% after 24 h, and 70% after 48 h) even at room
temperature. Next, we examined 12b under different reac-
tion conditions (Figure 4).
Scheme 6. Activation of 11.
Figure 4. Activity of 12b in the RCM of DEDAM. Conditions:
catalyst loading 5 mol-%, c = 0.1 m; CH2Cl2, 40 °C (᭿); THF,
60 °C (᭢); DCE, 60 °C (᭡); toluene, 60 °C (♦). Conversion mea-
When 1 equiv. of HCl in diethyl ether was added to a
solution of 11 in CDCl3 (0.02 m), the “opened” complex
12a was formed immediately. We noted that the equilibra-
tion is significantly slower than for 4b. Dichloride 10 and
diiodide complexes were observed only in small amounts
1
sured by H NMR spectroscopy.
We noted that simply changing the reaction temperature
(Ͻ 5%).[14] Similarly, when 1 equiv. of trifluoroacetic acid from 24 to 40 °C gave better activity in CH2Cl2 (᭿). We
was added to a solution of 11 in CDCl3 (0.02 m), 12b was decided to increase the temperature to 60 °C and test tetra-
obtained as the sole product without equilibration (cf. hydrofuran (THF), 1,2-dichloroethane (DCE), and toluene
Scheme 2).[15] Moreover, after 2 h at 60 °C in [D8]toluene or as possible solvents. The reaction in THF at 60 °C (᭢) was
CDCl3, no equilibration was observed. Complex 12b was slower than that in CH2Cl2 at 40 °C. Although switching to
stable in solution for days without any sign of decomposi- DCE (᭡) gave much better results, toluene (♦) was the best
tion.
solvent (Figure 4).
These results show that iodide-bearing 12a and especially
Using 5 mol-% of catalyst in the RCM of a straightfor-
12b have a greatly reduced tendency to disproportionation ward substrate such as DEDAM is far from the current
compared with 4b. Careful analysis of the 1H NMR spectra state of the art of olefin metathesis. We decided to check
of 12a and 12b suggests that cleavage of the carboxylate is the lower limit of catalyst loading in this reaction. We de-
diastereoselective.[16]
creased the loading of 12b to 0.1 mol-% and carried out the
Next, we compared 10, 12a, and 12b in the RCM of RCM of DEDAM in toluene at 80 and 100 °C (Table 1).
DEDAM at room temperature (Figure 3). Taking advantage of the excellent thermal stability of the
As expected, 10 was the most active. Complex 12a with iodide complex, the best results were obtained in toluene at
mixed chloride–iodide ligands was only slightly less active, 100 °C (Table 1, Entry 2). Thus, we decided to decrease the
and 12b with mixed iodide–trifluoroacetate ligands was far loading of 12b to 0.05 mol-% and switch to boiling xylene
less active at room temperature. However, because of the as the solvent (Entry 3). It is surprising that even at 142 °C
excellent stability of 12b in solution, after prolonged reac- 12b is stable for 2 h, and quite high conversion can be
Eur. J. Inorg. Chem. 2012, 1477–1484
© 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjic.org
1479

R. Gawin, K. Grela
FULL PAPER
Table 1. Low loading and high temperature application of 12b.
Entry Conditions
Loading of 12b
2 h
24 h 48 h 72 h
1
2
3
toluene, 80 °C
toluene, 100 °C
xylene, 142 °C
0.1 mol-%
0.1 mol-%
0.05 mol-%
3% 55% 75% 84%
32% 88% 93% 95%
61% 70% 71% 71%
achieved for RCM under these conditions. At such a tem-
perature, many commercially available catalysts decompose
rapidly, even in the absence of a substrate.
In summary, the test reactions show that the introduction
of iodide and trifluoroacetate ligands instead of chloride
deactivates the complex, as the activity of 12b at 60 °C is
comparable to that of 12a at 24 °C. However, the observed
Scheme 7. Concept of chirality transfer from benzylidene to Ru.
activity and thermal stability is high enough to make 12b could observe asymmetric induction in a model enantiose-
useful for a number of applications at higher tempera- lective olefin metathesis reaction promoted by acid-acti-
tures.[17]
vated, optically active 11*.
Encouraged by our observation that the self-cyclization
To synthesize an optically pure version of 11, we started
of 10 to 9 is diastereospecific, we decided to check if the from methyl (S)-2-hydroxy-3-methylbutanoate and 2-iodo-
chiral information that originated from the optically pure phenol 13 (Scheme 8). Compound 14 was prepared by a
benzylidene ligand and transferred to the metal center in 9 Mitsunobu reaction according to the described pro-
can be utilized in practical manner. We presumed that due cedure.[19] To introduce a vinyl group, a Suzuki reaction was
to the stabilization of the anionic ligand sphere by iodide, used to obtain styrene 15. Mild hydrolysis afforded pec-
the chiral information will be preserved at ruthenium, ursor 16 without the loss of optical purity.
which would enable the use of chiral-at-metal iodide com-
Precursor 16 was used to obtain optically pure 9*. Next,
plexes, such as 12b*, in enantioselective metathesis we introduced the iodide ligand to obtain 11*. The optical
(Scheme 7).
purity of 9* and 11* was determined by HPLC (Figure 5).
In an analogous procedure to the formation of 12a and
Isolated attempts to use optically active benzylidene li-
gands to obtain chiral ruthenium catalysts for enantioselec- 12b, optically active 12a* and 12b* were obtained from 11*.
tive olefin metathesis have been reported without success.[18] Analysis of their H NMR spectra showed the presence of
1
The proposed explanation of the observed lack of asymmet- only one diastereoisomer, which suggests no epimerization
ric induction with these catalysts is that the optically active of the Ru center. Unfortunately, due to the reversible cycli-
benzylidene ligand dissociates during the first catalytic cycle zation of 12a* and 12b* back to 11*, the activated com-
to leave achiral propagating species.[18a]
plexes were not suitable for chiral HPLC measurements.
However, the reduced lability of the anionic ligands in Complexes 12a* and 12b* were tested in the model desym-
12a and 12b would, at least in theory, lead to stable chiral metrization of triene 17 under conditions previously de-
propagating species. Therefore, we decided to check if we scribed in literature (Scheme 9).[20]
Scheme 8. Preparation of 9*, 11*, and 12b*.
1480
www.eurjic.org
© 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Inorg. Chem. 2012, 1477–1484

Ru Olefin Metathesis Catalysts with Mixed Anionic Ligands
remarkable stability and can be stored as a stock solution
for months with no sign of decomposition. Upon activation
of 11 by HCl and trifluoroacetic acid, 12a and 12b were
obtained and their activity was investigated in the model
RCM reaction of DEDAM.
We also found that the replacement of the methyl group
with a more sterically demanding isopropyl group led to a
significant increase of activity of the corresponding dichlo-
ride complex 10. Finally, optically pure 9* and 11* were
obtained and their purity was proven by HPLC. Despite the
inhibition of anionic ligand exchange by the introduction of
iodide, no asymmetric induction was observed when 12a*
and 12b* were used in a model triene desymmetrization re-
action.
It is important to note that 12a and 12b have a dimin-
ished tendency to undergo anionic ligand exchange. This
property can be used to tag or immobilize a metathesis cat-
alyst on various supports. Research in this direction is now
underway in our laboratories.[22]
Experimental Section
General: The preparation of 9, 10, 12a, and 12b was carried out
under Ar in predried glassware using Schlenk techniques. The prep-
aration of 7 and 8 was carried out in air. CH2Cl2 (Aldrich) and
DCE (Aldrich), were dried by distillation with CaH2 under argon
and were stored under argon. THF, toluene, and xylene were dried
by distillation with Na/K alloy. The preparation of 11 was carried
out in air in reagent-grade acetone. Column chromatography was
performed using Merck silica gel 60 (230–400 mesh). NMR spectra
were recorded in CDCl3 or CD2Cl2 with Varian Gemini 200 MHz,
Varian Mercury 400 MHz, Varian VNMRS 500 MHz, and Varian
VNMRS 600 MHz spectrometers. MS (FD/FAB) were recorded
with a GCT Premier spectrometer from Waters. MS (EI) spectra
were recorded with a AMD 604 Intectra GmbH spectrometer.
HPLC analysis was performed with a Daicel Chiralpak® AD-H
column (254 nm). Optical rotations were measured with a Jasco P-
2000 polarimeter, and the concentration (c) is given as g/100 mL.
Compounds 1b and 14 were prepared according to published pro-
cedures.[19] All other commercially available chemicals were used as
received.
Figure 5. HPLC of 11* (solid line) and racemic 11 (dashed line).
Scheme 9. Model desymmetrization of 17.
Unfortunately, despite many trials, which included varia-
tion of solvents, concentration, temperature, etc., no traces
of asymmetric induction were observed with 12a* and 12b*.
This result can be explained by the fast racemization of the
chiral 14-electron X–Ru*–I center after dissociation of the
benzylidene ligand (Scheme 10).[21]
Methyl 3-Methyl-2-(2-propenylphenoxy)butanoate (7): Cs2CO3
(3.26 g, 10 mmol) was added to a solution of an E/Z mixture of 2-
propenylphenol (671 mg, 5 mmol) in N,N-dimethylformamide
(DMF, 20 mL). After stirring for 30 min at room temperature,
methyl 2-bromo-3-methylbutanoate (1.07 g, 5.5 mmol) was added,
and the reaction mixture was stirred for 24 h at 40 °C. The reaction
mixture was poured onto water (100 mL) and extracted with diethyl
ether (3ϫ25 mL). The combined extracts were washed with brine
and water and dried (Na2SO4). The solvent was evaporated to give
the crude product as a yellow oil. Purification by silica gel
chromatography (AcOEt/c-hexane, 97:3, v/v) afforded 7 as a color-
less oil (615 mg, 50%). Mixture of isomers: E/Z = 4.5:1. IR
Scheme 10. Racemization of chiral propagating species: possible
reason for the observed lack of asymmetric induction.
(CH Cl ): ν = 2966, 1757, 1486, 1235, 749 cm–1. C H O (248.32):
˜
2
2
15 20
3
calcd. C 72.55, H 8.12; found C 72.45, H 8.14. 1H NMR (500 MHz,
CDCl3): δ = 7.43 (dd, J = 7.6, 1.5 Hz, 0.8ϫ1 H), 7.30–7.27 (m,
0.2ϫ1 H), 7.17–7.12 (m, 0.2ϫ1 H), 7.12–7.07 (m, 0.8ϫ1 H), 6.96–
6.88 (m, 1 H), 6.84–6.78 (m, 0.8ϫ1 H), 6.69 (br. d, 0.2ϫ1 H),
6.68–6.61 (m, 0.8ϫ1 H + 0.2ϫ1 H), 6.23 (dq, J = 15.9, 6.7 Hz,
Conclusions
We have reported the preparation of stable ruthenium
carboxylate complexes that contain different anionic li-
gands. Complex 11, which bears an iodide ligand, exhibits 0.8ϫ1 H), 5.82 (dq, J = 11.6, 7.1 Hz, 0.2ϫ1 H), 4.41 (d, J =
Eur. J. Inorg. Chem. 2012, 1477–1484
© 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjic.org
1481

R. Gawin, K. Grela
5.3 Hz, 1 H), 3.73 (s, 3 H), 2.37–2.26 (m, 1 H) 1.91 (dd, J = 6.7, line solid (68 mg, quant.). IR (CH Cl ): ν = 3015, 2967, 1758, 1481,
FULL PAPER
˜
2
2
1.8 Hz, 0.8ϫ3 H), 1.84 (dd, J = 7.1, 2.0 Hz, 0.2ϫ3 H) 1.12 (d, J 1267, 1015, 749 cm–1. C33H40Cl2N2O3Ru (684.67): calcd. C 57.89,
= 6.8 Hz, 0.8ϫ3 H), 1.08 (d, J = 6.8 Hz, 0.8ϫ3 H + 0.2ϫ3 H),
1.06 (d, J = 6.8 Hz, 0.2ϫ3 H) ppm. 13C NMR (125 MHz, CDCl3):
δ = 171.9, 155.6 (Z), 154.6 (E), 130.4, 127.7, 127.6, 126.4, 125.4
(E), 125.1 (Z), 121.4 (E), 120.7 (Z), 112.2 (E), 112.1 (Z), 81.8 (E),
H 5.89, Cl 10.36, N 4.09; found C 57.74, H 5.79, Cl 10.56, N 3.86.
1H NMR (600 MHz, CDCl3): δ = 16.83 (s, 1 H), 10.62 (br., 1 H),
7.58–7.53 (m, 1 H), 7.16–7.04 (m, 4 H), 7.03–6.98 (m, 1 H), 6.96–
6.92 (m, 1 H), 6.87–6.83 (m, 1 H), 4.67 (d, J = 5.3 Hz, 1 H), 4.18
81.7 (Z), 51.9 (E), 51.9 (Z), 31.8, 18.9 (E), 18.8 (E), 18.7 (Z), 17.9 (s, 4 H), 2.64–2.22 (m, 19 H), 1.06 (d, J = 6.8 Hz, 3 H), 0.78 (d, J
(E), 17.8 (Z), 14.7 (Z) ppm. HRMS (EI): calcd. for C15H20O3 [M] = 6.9 Hz, 3 H) ppm. 13C NMR (150 MHz, CDCl3): δ = 300.2,
+
248.1412; found 248.1419.
207.4, 168.4, 151.6, 143.8, 139.2, 131.0, 129.7, 124.5, 123.4, 112.9,
86.9, 29.6, 21.1, 21.0, 17.9 ppm.
3-Methyl-2-(2-propenylphenoxy)butanoic Acid (8): LiOH (479 mg,
20 mmol) was added to a solution of 7 (1241 mg, 5 mmol) in THF/
H2O (20 mL; 9:1 v/v). The mixture was heated to reflux with stir-
ring for 24 h, cooled to room temperature, and acidified with di-
luted HCl. THF was removed in vacuo, and the residue was ex-
tracted with AcOEt (3ϫ25 mL). The combined extracts were
washed with brine and water and dried (Na2SO4). The solvent was
evaporated to give the crude product as a yellow oil. Purification
by silica gel chromatography (AcOEt/c-hexane = 2:1 v/v) afforded
8 as a white crystalline solid (1050 mg, 90%). Mixture of isomers:
Synthesis of 11: Complex 9·MeOH (136 mg; 0.2 mmol) was dis-
solved in reagent-grade acetone (10 mL) in air, and KI was added
(1.66 g; 10 mmol). The mixture was stirred for 30 min and then
filtered. The addition of KI and stirring for 30 min was repeated
twice more. The mixture was filtered, and the solvent was evapo-
rated in vacuo. The residue was redissolved in CH2Cl2 (2 mL),
passed through a pad of silica, and washed with AcOEt (10 mL).
The solvents were evaporated in vacuo, and the residue was dis-
solved in CH2Cl2 (1 mL). MeOH was added (3 mL), and CH2Cl2
was slowly removed under vacuum. The precipitated product was
collected by filtration, washed with MeOH (1 mL), and dried in
vacuo to afford 11·MeOH as a dark green microcrystalline solid
E/Z = 4.5:1. IR (CH Cl ): ν = 3036, 2935, 1723, 1486, 1234, 749
˜
2
2
cm–1. C14H18O3 (234.30): calcd. C 71.77, H 7.74; found C 71.87, H
1
7.65. H NMR (500 MHz, CDCl3): δ = 9.74 (br. s, 1 H), 7.42 (dd,
(150 mg, 97%). IR (CH Cl ): ν = 2960, 1661, 1480, 1266, 752 cm–1.
˜
J = 7.7, 1.5 Hz, 0.8ϫ1 H), 7.30–7.27 (m, 0.2ϫ1 H), 7.19–7.14 (m,
0.2ϫ1 H), 7.14–7.09 (m, 0.8ϫ1 H), 6.99–6.90 (m, 1 H), 6.82–6.76
(m, 0.8ϫ1 H), 6.75 (bd, 0.2ϫ1 H), 6.70 (bd, 0.8ϫ1 H), 6.64–6.58
(m, 0.2ϫ1 H), 6.23 (dq, J = 15.9, 6.7 Hz, 0.8ϫ1 H), 5.82 (dq, J
= 11.6, 7.1 Hz, 0.2ϫ1 H), 4.47 (d, J = 4.8 Hz, 1 H), 2.42–2.30 (m,
1 H) 1.90 (dd, J = 6.7, 1.7 Hz, 0.8ϫ3 H), 1.83 (dd, J = 7.0, 1.9 Hz,
0.2ϫ3 H) 1.15 (d, J = 6.8 Hz, 0.8ϫ3 H), 1.12 (d, J = 6.8 Hz, 0.8*3
H + 0.2ϫ3 H), 1.10 (m, 0.2ϫ3 H) ppm. 13C NMR (125 MHz,
CDCl3): δ = 176.8 (E), 176.5 (Z), 155.2 (Z), 154.3 (E), 130.5, 127.9,
127.7, 126.7, 125.3 (E), 125.0 (Z), 121.7 (E), 121.2 (Z), 112.4 (Z),
112.3 (E), 81.3 (Z), 81.1 (E), 31.7, 19.0 (E), 18.9 (E), 18.8 (Z), 17.6
(E), 17.5 (Z), 14.7 (Z) ppm. HRMS (EI): calcd. for C14H18O3 [M]
2
2
C33H39IN2O3Ru·CH4O (739.66 + 32.04): calcd. C 52.92, H 5.62, I
1
16.44, N 3.63; found C 52.27, H 5.66, I 16.58, N 3.59. H NMR
(600 MHz, CD2Cl2): δ = 15.80 (s, 1 H), 7.62–7.57 (m, 1 H), 7.12–
7.03 (m, 5 H), 7.03–7.00 (m, 1 H), 7.00–6.97 (m, 1 H), 4.29 (d, J
= 5.5 Hz, 1 H), 4.25–4.05 (br., 4 H), 2.75–2.10 (br., 18 H), 1.84 (m,
1 H), 1.05 (d, J = 6.8 Hz, 3 H), 0.71 (d, J = 6.8 Hz, 3 H) ppm. 13C
NMR (150 MHz, CD2Cl2): δ = 290.1, 211.3, 179.8, 155.1, 146.6,
139.1, 130.2, 129.6, 126.4, 122.1, 118.6, 93.1, 31.3, 20.8, 19.1, 18.9,
17.4 ppm.
Synthesis of 12a: HCl (2 m in Et2O, 50 μL, 0.1 mmol) was added to
a solution of 11·MeOH (77 mg, 0.1 mmol) in CHCl3 (0.5 mL). The
product was precipitated by the addition of n-pentane (3 mL), col-
lected by filtration, and dried in vacuo to give a green microcrystal-
+
234.1256; found 234.1252.
Synthesis of 9: Compound 1b (849 mg, 1 mmol) was dissolved in
CH2Cl2 (10 mL), and 8 (234 mg, 1 mmol) was added under an ar-
gon atmosphere. The mixture was stirred for 5 min, CuCl (148 mg,
1.5 mmol) was added, and the mixture was heated to reflux for
30 min. The reaction mixture was allowed to cool to room tempera-
ture and concentrated in vacuo. From this point, all manipulations
were carried out in air with reagent-grade solvents. The product
was purified by silica gel chromatography (AcOEt/c-hexane = 1:3
v/v). The solvent was evaporated under vacuum, and the residue
was dissolved in CH2Cl2 (2 mL). MeOH (5 mL) was added and
CH2Cl2 was slowly removed under vacuum. The precipitated prod-
uct was collected by filtration, washed with MeOH (5 mL), and
dried in vacuo to afford 9·MeOH as a green microcrystalline solid
line solid (77 mg, quant.). IR (CH Cl ): ν = 3008, 2965, 1759, 1479,
˜
2
2
1265, 749 cm–1. C33H40ClIN2O3Ru (776.13): calcd. C 51.07, H 5.19,
1
I 16.35, N 3.61; found C 50.93, H 5.18, I 16.23, N 3.38. H NMR
(500 MHz, CDCl3): δ = 16.34 (s, 1 H), 10.75 (br., 1 H), 7.61–7.56
(m, 1 H), 7.17–7.11 (br., 1 H), 7.11–7.01 (br. m, 4 H), 4.77 (d, J =
4.5 Hz, 1 H), 2.69–2.60 (m, 1 H). 1.07 (d, J = 7.0 Hz, 3 H), 0.73
(d, J = 6.9 Hz, 3 H) ppm. 13C NMR (125 MHz, CDCl3): δ = 301.0,
208.6, 168.3, 151.9, 143.5, 131.5, 129.8, 124.4, 123.7, 113.10, 86.8,
29.7, 21.2, 17.7 ppm.
Synthesis of 12b: Trifluoroacetic acid (8 μL, 0.1 mmol) was added
to a solution of 11·MeOH (77 mg, 0.1 mmol) in CHCl3 (0.5 mL).
The product was precipitated by the addition of n-pentane (3 mL),
collected by filtration, and dried in vacuo to give a green microcrys-
(471 mg, 69%). IR (CH Cl ): ν = 2960, 1661, 1481, 1267 cm–1.
˜
2
2
C33H39ClN2O3Ru·CH4O (648.21 + 32.04): calcd. C 60.03, H 6.37,
talline solid (85 mg, quant.). IR (CH Cl ): ν = 3397, 2963, 2917,
˜
2
2
1
1776, 1657, 1482, 1267, 1173, 578 cm–1. C35H40F3IN2O5Ru
(853.69): calcd. C 49.24, H 4.72, F 6.68, I 14.87, N 3.28; found C
48.95, H 4.73, F 6.66, I 14.76, N 3.06. 1H NMR (500 MHz,
CDCl3): δ = 16.06 (s, 1 H), 8.45 (br., 1 H), 7.64–7.59 (m, 1 H),
7.12–7.02 (m, 4 H), 7.01–6.95 (m, 2 H), 4.48 (d, J = 5.4 Hz, 1 H),
4.35–4.00 (br., 4 H), 2.90–2.55 (br., 3 H), 2.55–2.00 (br., 15 H),
1.90–1.76 (m, 1 H), 1.06 (d, J = 6.8 Hz, 3 H), 0.73 (d, J = 6.8 Hz,
3 H) ppm. 13C NMR (125 MHz, CDCl3): δ = 295.6, 210.5, 184.4,
158.6 (q, J = 40 Hz), 154.7, 146.6, 131.0, 129.8, 126.9, 122.5, 118.7,
92.7, 31.4, 21.1, 19.2, 17.4 ppm.
Cl 5.21, N 4.12; found C 60.12, H 6.38, Cl 5.33, N 4.02. H NMR
(600 MHz, CDCl3): δ = 16.47 (s, 1 H), 7.52–7.47 (m, 1 H), 7.11–
7.06 (m, 4 H), 7.06–7.02 (m, 1 H), 6.94–6.89 (m, 2 H), 4.26 (d, J
= 4.8 Hz, 1 H), 4.17 (br. s, 4 H), 2.6–2.3 (m, 18 H), 1.93–1.84 (m,
1 H), 1.07 (d, J = 6.8 Hz, 3 H), 0.70 (d, J = 6.8 Hz, 3 H) ppm. 13C
NMR (150 MHz, CDCl3): δ = 291.8, 210.0, 180.9, 155.3, 146.6,
139.1, 129.9, 129.7, 129.5, 126.5, 122.1, 118.7, 93.1, 31.3, 21.1, 19.5,
18.5, 16.9 ppm.
Synthesis of 10: HCl (2 m in Et2O, 50 μL, 0.1 mmol) was added to
a solution of 9·MeOH (68 mg, 0.1 mmol) in CH2Cl2 (0.5 mL). The
product was precipitated by the addition of n-pentane (3 mL), col-
lected by filtration, and dried in vacuo to give a green microcrystal-
Methyl (R)-3-Methyl-2-(2-vinylphenoxy)butanoate (15): Methyl (R)-
2-(2-iodophenoxy)-3-methylbutanoate (14, 334 mg, 1 mmol) was
1482
www.eurjic.org
© 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Inorg. Chem. 2012, 1477–1484

Ru Olefin Metathesis Catalysts with Mixed Anionic Ligands
dissolved in DME (7 mL). Tetrakis(triphenylphosphane)palla-
dium(0) (23 mg, 0.02 mmol) was added, and the mixture was stirred
under an argon atmosphere for 30 min. Potassium carbonate
(138 mg, 1 mmol), water (3 mL), and 2,4,6-trivinylcyclotriboroxane
pyridine complex (241 mg, 1 mmol) were added, and the reaction
mixture was heated to reflux under argon for 2 h. The reaction
mixture was cooled to room temperature, diluted with water
(50 mL), and extracted with diethyl ether (3ϫ10 mL). The com-
bined extracts were dried (Na2SO4), and the solvent was evapo-
rated. The residue was dissolved in hexane (50 mL) and passed
through a short aluminum oxide column. The solvent was evapo-
rated to give the crude product as a yellow oil. Purification by silica
gel chromatography (AcOEt/c-hexane = 2:98 v/v) afforded 15 as a
colorless oil (194 mg, 83%). [α]rDt = +3.06 (CHCl3, c = 0.97). IR
Acknowledgments
R. G. thanks the Foundation for Polish Science (“Ventures” Pro-
gram) for financial support. The project “Ventures/2009-4/1” was
executed within the “Ventures” program of the Foundation for Pol-
ish Science, cofinanced by the European Union Regional Develop-
ment Fund.
[1] a) Handbook of Metathesis (Ed.: R. H. Grubbs), Wiley-VCH,
Weinheim, Germany, 2003; b) M. Michalak, Ł. Gułajski, K.
Grela, “Alkene Metathesis” in Science of Synthesis: Houben–
Weyl Methods of Molecular Transformations, vol. 47a (Alkenes)
(Ed.: A. de Meijere), Thieme, Stuttgart, Germany, 2010, pp.
327–438; c) P. Schwab, M. B. France, J. W. Ziller, R. H. Grubbs,
Angew. Chem. 1995, 107, 2179; Angew. Chem. Int. Ed. Engl.
1995, 34, 2039–2041; d) M. Scholl, S. Ding, C. W. Lee, R. H.
Grubbs, Org. Lett. 1999, 1, 953–956; e) S. B. Garber, J. S.
Kingsbury, B. L. Gray, A. H. Hoveyda, J. Am. Chem. Soc.
2000, 122, 8168–8179.
(CH Cl ): ν = 2967, 1756, 1485, 1235, 749 cm–1. C H O (234.30):
˜
2
2
14 18
3
calcd. C 71.77, H 7.74; found C 71.61, H 7.50. 1H NMR (400 MHz,
CDCl3): δ = 7.52 (dd, J = 7.7, 1.7 Hz, 1 H), 7.23–7.13 (m, 2 H),
6.99–6.91 (m, 1 H), 6.71–6.65 (m, 1 H), 5.75 (dd, J = 17.8, 1.5 Hz,
1 H), 5.28 (dd, J = 11.1, 1.4 Hz, 1 H), 4.44 (d, J = 5.2 Hz, 1 H),
3.73 (s, 3 H), 2.42–2.27 (m, 1 H), 1.12 (d, J = 6.8 Hz, 3 H), 1.09
(d, J = 6.9 Hz, 3 H) ppm. 13C NMR (100 MHz, CDCl3): δ = 172.0,
155.3, 131.6, 129.0, 127.6, 126.7, 121.6, 114.6, 112.4, 81.9, 52.3,
32.0, 19.0, 18.1 ppm. HRMS (EI): calcd. for C14H18O3 [M]+
234.1256; founcded 234.1248.
[2] For selected contributions, see: a) J. C. Conrad, D. Amoroso,
P. Czechura, G. P. A. Yap, D. E. Fogg, Organometallics 2003,
22, 3634–3636; b) S. Monfette, D. E. Fogg, Organometallics
2006, 25, 1940–1944; c) J. C. Conrad, H. H. Parnas, J. L. Snel-
grove, D. E. Fogg, J. Am. Chem. Soc. 2005, 127, 11882–11883;
d) S. Monfette, D. E. Fogg, Organometallics 2006, 25, 1940–
1944; e) J. O. Krause, O. Nuyken, K. Wurst, M. R. Buchmeiser,
Chem. Eur. J. 2004, 10, 777–784; f) T. S. Halbach, S. Mix, D.
Fischer, S. Maechling, J. O. Krause, C. Sievers, S. Blechert, O.
Nuyken, M. R. Buchmeiser, J. Org. Chem. 2005, 70, 4687–
4694; g) M. Mayr, D. Wang, R. Kröll, N. Schuler, S. Prhs, A.
Fürstner, M. R. Buchmeiser, Adv. Synth. Catal. 2005, 347, 484–
492; h) J. O. Krause, S. H. Lubbad, O. Nuyken, M. R. Buch-
meiser, Macromol. Rapid Commun. 2003, 24, 875–878; i) J. O.
Krause, S. Lubbad, O. Nuyken, M. R. Buchmeiser, Adv. Synth.
Catal. 2003, 345, 996–1004; j) J. O. Krause, M. T. Zarka, U.
Anders, R. Weberskirch, O. Nuyken, M. R. Buchmeiser, An-
gew. Chem. 2003, 115, 6147; Angew. Chem. Int. Ed. 2003, 42,
5965–5969; k) J. O. Krause, O. Nuyken, M. R. Buchmeiser,
Chem. Eur. J. 2004, 10, 2029–2035; l) L. Yang, M. Mayr, K.
Wurst, M. R. Buchmeiser, Chem. Eur. J. 2004, 10, 5761–5770;
m) J. J. Van Veldhuizen, D. G. Gillingham, S. B. Garber, O. Ka-
taoka, A. H. Hoveyda, J. Am. Chem. Soc. 2003, 125, 12502–
12508; n) J. J. Van Veldhuizen, J. E. Campbell, R. E. Giudici,
A. H. Hoveyda, J. Am. Chem. Soc. 2005, 127, 6877–6882; o)
PTC Patent Application WO 2004/089974 A1 (2004, Boehr-
inger Ingelheim International); p) W. Buchowicz, F. Ingold,
J. C. Mol, M. Lutz, A. L. Spek, Chem. Eur. J. 2001, 7, 2842–
2847; q) S. Rogalski, C. Pietraszuk, B. Marciniec, J. Organomet.
Chem. 2009, 694, 3918–3922; r) J. Wappel, C. A. Urbina-
Blanco, M. Abbas, J. H. Albering, R. Saf, S. P. Nolan, C. Slu-
govc, Beilstein J. Org. Chem. 2010, 6, 1091–1098; s) J. M. Blac-
quiere, R. McDonald, D. E. Fogg, Angew. Chem. Int. Ed. 2010,
49, 3807–3810; t) M. Jovic, S. Torker, P. Chen, Organometallics
2011, 30, 3971–3980.
[3] a) M. R. Buchmeiser, Chem. Rev. 2009, 109, 303–321; b) H.
Clavier, K. Grela, A. Kirschning, M. Mauduit, S. P. Nolan,
Angew. Chem. 2007, 119, 6906; Angew. Chem. Int. Ed. 2007,
46, 6786–6801.
[4] P. Teo, R. H. Grubbs, Organometallics 2010, 29, 6045–6050.
[5] a) X. Miao, A. Blokhin, A. Pasynskii, S. Nefedov, S. N. Osipov,
T. Roisnel, C. Bruneau, P. H. Dixneuf, Organometallics 2010,
29, 5257–5262; b) K. Vehlow, S. Maechling, K. Köhler, S. Ble-
chert, Tetrahedron Lett. 2006, 47, 8617–8620.
[6] K. Tanaka, V. P. W. Böhm, D. Chadwick, M. Roeper, D. C.
Braddock, Organometallics 2006, 25, 5696–5698.
[7] a) R. Gawin, A. Makal, K. Woz´niak, M. Mauduit, K. Grela,
Angew. Chem. 2007, 119, 7344; Angew. Chem. Int. Ed. 2007,
46, 7206–7209; b) The unique property of 3 that allows it to
be opened by various acids encouraged us to attempt the for-
(R)-3-Methyl-2-(2-vinylphenoxy)butanoic Acid (16): LiOH (96 mg,
4 mmol) was added to a solution of 15 (234 mg, 1 mmol) in THF/
H2O (10 mL, 9:1 v/v). The mixture was stirred at room temperature
for 3 d and acidified with diluted HCl. THF was removed in vacuo,
and the residue was extracted with AcOEt (3ϫ25 mL). The com-
bined extracts were washed with brine and water and dried
(Na2SO4). The solvent was evaporated to give the crude product as
a yellow oil. Purification by silica gel chromatography (AcOEt/c-
hexane = 2:1 v/v) afforded 16 as a colorless oil (198 mg, 90%).
[α]rDt = +1.52 (CHCl , c = 1.11). IR (CH Cl ): ν = 3068, 2968, 1722,
˜
3
2
2
1485, 1234, 748 cm–1. C13H16O3 (220.27): calcd. C 70.89, H 7.32;
found C 70.23, H 7.15. 1H NMR (400 MHz, CDCl3): δ = 10.02
(br., 1 H), 7.55–7.49 (m, 1 H), 7.23–7.11 (m, 2 H), 7.01–6.93 (m, 1
H), 6.75–6.69 (m, 1 H), 5.80–5.70 (m, 1 H), 5.32–5.25 (m, 1 H),
4.49 (d, J = 4.7 Hz, 1 H), 2.37 (m, 1 H), 1.18–1.09 (m, 6 H) ppm.
13C NMR (100 MHz, CDCl3): δ = 176.9, 155.1, 131.5, 129.0, 127.6,
126.8, 121.7, 114.8, 112.4, 81.2, 31.9, 19.1, 17.7 ppm. HRMS (EI):
calcd. for C13H16O3 [M]+ 220.1099; found 220.1092.
Synthesis of 9*: Complex 9* was prepared from 1b and 16 in a
procedure analogous to the formation of 9. Optical purity was con-
firmed by HPLC with a Daicel Chiralpak® AD-H column. 254 nm;
n-hexane/2-propanol 9:1 v/v. 1 mL/min; ee = 96%.
Synthesis of 11*: Complex 11* was prepared from 9* in a procedure
analogous to the formation of 11. Optical purity was confirmed by
HPLC with a Daicel Chiralpak® AD-H column. 254 nm; n-hexane/
2-propanol 9:1 v/v. 1 mL/min; ee = 96%.
Synthesis of 12a* and 12b*: Complexes 12a* and 12b* were pre-
pared in a procedure analogous to the formation of 12a and 12b.
Due to their self-cyclization to 11*, HPLC analysis was not pos-
sible.
NMR spectroscopic data for 9*, 11*, 12a*, and 12b* were identical
to those recorded for racemic complexes. Due to the intense color
of the catalyst solutions, we were unable to measure optical rota-
tions for these compounds.
Supporting Information (see footnote on the first page of this arti-
cle): 1H and 13C NMR spectra of complexes 9, 10, 11, 12a and 12b.
Eur. J. Inorg. Chem. 2012, 1477–1484
© 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjic.org
1483

R. Gawin, K. Grela
FULL PAPER
Characteristic shifts of benzylidene proton in the 1H NMR
spectrum (CDCl3): major 12a (Ͼ 90%) at 16.34 ppm, minor 10
(Ͻ 5%) at 16.83 ppm, and diiodide complex (Ͻ 5%) at
15.84 ppm.
mation of a mixed ruthenium fluoride complex. In typical ex-
periment, a solution of 3 in CD2Cl2 was mixed with small
amount of aqueous HF or HF·py complex. A new benzylidene
signal was observed in the 1H NMR spectra, which was fol-
lowed in seconds by complete decomposition of the newly
formed complex.
[14]
Only one benzylidene proton was observed in the 1H NMR
spectra at 16.01 (CDCl3), 15.98 (CD2Cl2), and 16.00 ppm
([D8]toluene).
[15]
[16]
[17]
[18]
1
In the H NMR spectra of 12a and 12b, only one signal from
the benzylidene proton and one group of signals from the iso-
propyl group were observed.
For a related discussion on thermal activation, see: M. Bieniek,
A. Michrowska, D. Usanov, K. Grela, Chem. Eur. J. 2008, 14,
806–818.
a) H. Wakamtsu, S. Blechert, Angew. Chem. 2002, 114, 832;
Angew. Chem. Int. Ed. 2002, 41, 794–796; b) A. Hryniewicka,
J. W. Morzycki, L. Siergiejczyk, S. Witkowski, J. Wójcik, A.
Gryff-Keller, Aust. J. Chem. 2009, 62, 1363–1370.
[8] R. Gawin, P. Czarnecka, K. Grela, Tetrahedron 2010, 66, 1051–
1056.
[9] J. H. Kim, B. Y. Park, S. Chen, S. Lee, Eur. J. Org. Chem. 2009,
[19] M. Fujita, Y. Yoshida, K. Miyata, A. Wakisaka, T. Sugimura,
Angew. Chem. Int. Ed. 2010, 49, 7068–7071.
[20] T. W. Funk, J. M. Berlin, R. H. Grubbs, J. Am. Chem. Soc.
2006, 128, 1840–1846.
[21] For a discussion on initiation and propagation mechanisms in
Hoveyda systems, see: a) T. Vorfalt, K. Wannowius, H. Plenio,
Angew. Chem. Int. Ed. 2010, 49, 5533–5536; b) T. Vorfalt, K.
Wannowius, T. Thiel, H. Plenio, Chem. Eur. J. 2010, 16, 12312–
12315.
14, 2239–2242.
[10] The reaction was monitored by the characteristic shifts of the
1
benzylidene proton in the H NMR spectra (CDCl3): 3 16.52,
4a 16.73, 4b 16.61 ppm, 5 17.01 ppm.
[11] J. Czaban, R. Gawin, K. Grela, unpublished results.
[12] E. L. Dias, S. T. Nguyen, R. H. Grubbs, J. Am. Chem. Soc.
1997, 119, 3887–3897.
1
[13] In the H NMR spectrum (CDCl3), only one signal from the
benzylidene proton (16.47 ppm) and one group of signals from
the isopropyl group (doublets at 4.26 CH, 1.07 CH3, and
0.70 ppm CH3) were observed.
[22] D. Bek, R. Gawin, H. Balcar, K. Grela, unpublished results.
Received: October 1, 2011
Published Online: January 31, 2012
1484
www.eurjic.org
© 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Inorg. Chem. 2012, 1477–1484