Catalytic and structural studies of hoveyda-grubbs type pre-catalysts bearing modified ether ligands

Article abstract of DOI:10.1002/adsc.201200385

Catalytic and crystallographic studies of Hoveyda-Grubbs type pre-catalysts M51TM and M52TM were performed. These two new instruments in the olefin metathesis catalyst toolbox were shown to be active at ambient temperature and at low loading, leading to c

Full text of DOI:10.1002/adsc.201200385

FULL PAPERS
DOI: 10.1002/adsc.201200385
Catalytic and Structural Studies of Hoveyda–Grubbs Type Pre-
Catalysts Bearing Modified Ether Ligands
a
a
b
Stefano Guidone, Enguerrand Blondiaux, Cezary Samojłowicz,
c
c
c
c
Łukasz Gułajski, Mariusz K e˛ dziorek, Maura Mali n´ ska, Aleksandra Pazio,
Krzysztof Wo z´ niak, Karol Grela, * Angelino Doppiu,
and Catherine S. J. Cazin *
EaStCHEM School of Chemistry, University of St Andrews, St Andrews, KY16 9ST, U.K.
Fax : (+44)-1334-463-808; e-mail: cc111@st-andrews.ac.uk
Institute of Organic Chemistry, Polish Academy of Sciences, Kasprzaka 44/52, 01-224 Warsaw, Poland
E-mail: klgrela@gmail.com
Department of Chemistry, Warsaw University, Pasteura 1, 02-093 Warszawa, Poland
Umicore AG & Co. KG, Rodenbacher Chaussee 4, 63457 Hanau-Wolfgang, Germany
c
b,c,
d
a,
a
b
c
d
Received: May 3, 2012; Published online: October 4, 2012
Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/adsc.201200385.
Abstract: Catalytic and crystallographic studies of ing, leading to clean formation of ring-closing, ring-
TM
Hoveyda–Grubbs type pre-catalysts M51
and closing enyne and cross metathesis products.
TM
M52 were performed. These two new instruments
in the olefin metathesis catalyst toolbox were shown Keywords: N-heterocyclic carbenes; olefin metathe-
to be active at ambient temperature and at low load- sis; ring-closing metathesis; ruthenium
Introduction
order to further improve the activity/stability of such
pre-catalysts, various modifications have been imple-
[
4]
Olefin metathesis is a powerful tool for carbon- mented by several research groups.
carbon double bond formation with important appli-
The first example of a phosphine-free (NHC bear-
cations in synthetic organic and pharmaceutical ing) complex Hov-II (known as Hoveyda–Grubbs
[1]
chemistry. Numerous pre-catalyst types have been type pre-catalyst) was reported independently by
[
2]
[5]
developed in the last 20 years. Ruthenium-based Hoveyda and Blechert (Figure 2). The isopropoxy
pre-catalysts have gained popularity because of their moiety on the benzylidene ring which acts as a fifth
[
2c]
stability and tolerance to various functional groups.
Well-known 1 and 2 generation benzylidene (G-I ture of this class of complexes. The coordination of
ligand in the metal coordination sphere is a key fea-
st
nd
and G-II) and indenylidene (Ind-I and Ind-II) com- the oxygen atom is believed to be influenced by the
[
6b]
plexes have been extensively studied showcasing the electronic density in the aromatic ring. Attempts to
[
3]
enormous potential of these systems (Figure 1). In tune the steric and electronic properties of the car-
Figure 1. Ruthenium pre-catalysts for olefin metathesis reactions.
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Catalytic and Structural Studies of Hoveyda–Grubbs Type Pre-Catalysts
Results and Discussion
Catalytic Performance
In order to compare the catalytic activity of M51 and
M52 with Hov-II and Ind-II, the room temperature
ring-closing metathesis (RCM) of diethyl diallylmalo-
nate using 1 mol% of catalyst was first monitored.
Figure 2. Hoveyda–Grubbs type pre-catalysts examined in While M51 and M52 display a similar kinetic profile,
this study.
the reaction is slightly to drastically slower with Hov-
II and Ind-II (Figure 3).
The effect of the solvent and temperature on this
bene moiety were carried out by Blechert and Grela reaction using M51 and M52 was next examined
[6]
(
Figure 1). Grelaꢁs complex with an electron-with- (Table 1). In order to obtain reliable data, all reac-
drawing group in the para position relative to the iso- tions were carried out at 308C. At this temperature,
propoxy moiety is one of the most active pre-catalysts in dichloromethane, M51 is more active than M52
[6b]
of this class. All such complexes are highly active in (97% and 77% conversion obtained using 0.05 mol%
catalysis and their potential recyclability is claimed in Ru). Reactions carried out in toluene led to slightly
[7]
the literature. The reactivity of these complexes has lower catalyst performance for both M51 and M52
been clarified with kinetic studies reported by the (Table 1, entries 11 and 16). At very low catalyst load-
[8]
Plenio group.
ing (100 ppm), increasing the temperature led to an
Recently, further functionalized Hoveyda–Grubbs essentially similar catalyst activity as that obtained at
type pre-catalysts have been reported by Grela and 308C (Table 1, entries 4, 5, 12 and 13).
[9]
co-workers. Several complexes with both higher
The scope of the RCM reaction leading to other
thermal stability and catalytic activity than Hov-II five-membered ring compounds was next investigated
were obtained by adding electron-withdrawing groups (Table 2). Pre-catalysts M51 and M52 afforded di-
at the isopropoxy moiety. Some of these complexes and trisubstituted five-membered ring products at low
adopt an octahedral geometry due to coordination of catalyst loading at 308C (Table 2, entries 1–4 and 10–
a carbonyl moiety positioned at the functionalized 23). Poor conversions were observed when using
isopropoxy unit.
more challenging substrates such as tetrasubstituted
TM
TM
In this context, complexes M51 and M52 are dienes (Table 2, entries 5–9, 24 and 25). Complex M51
now gaining attention as efficient Hoveyda–Grubbs shows similar (Table 2, entries 1, 2, 10–14 and 18–21)
[
10]
type pre-catalysts.
tailed study on their catalytic activity in olefin meta- tries 3, 4, 15-17, 22 and 23).
thesis reactions (Figure 2). Further reactions with more challenging substrates
Herein we report the first de- to higher catalytic activity than M52 (Table 2, en-
were carried out with pre-catalyst M51 only (Table 3)
because of its higher activity compared to M52. Di-
Figure 3. Reaction profiles of RCM of diethyl diallylmalonate promoted by Ind-II (~), Hov-II (
&
), M51 (^) and M52 (*) de-
1
termined by H NMR in CD Cl (at 238C).
2
2
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Table 1. Ring-closing metathesis reactions of diethyl diallyl- cult due to the eventual homo-cross metathesis be-
[
a]
malonate with pre-catalysts M51 and M52.
tween two substrate molecules (Table 3, entries 4, 5
and 8, 9). Ring-closing enyne metathesis of 29 was
performed at very low catalyst loading (0.05 mol%)
and produced a high yield of product 30 (Table 3,
entry 10). Pre-catalyst M51 catalyzes cross metathesis
reactions between methyl acrylate and different func-
tionalized olefins (Table 3, entries 12 and 13). The
benzoate derivative 35 gave lower conversion than
the tert-butyldimethylsilyl ether 33, and both of these
show the same E/Z ratio (20/1) as determined by
Entry Solvent Pre-catalyst
mol%)
Temperature Conversion
[b]
(
[8C]
[%]
1
2
3
4
5
6
7
8
9
1
1
1
1
1
1
1
CH Cl2 M51 (1)
30
30
30
30
50
30
30
30
30
30
30
30
80
30
30
30
>99
98 (94)
97
4
5
>99
92 (88)
77
>99
96
90
10
10
>99
88
2
CH Cl2 M51 (0.1)
2
CH Cl2 M51 (0.05)
1
2
H NMR spectroscopy.
CH Cl2 M51 (0.01)
2
Furthermore, catalytic reactions focusing on the use
of pre-catalysts M51 and M52 in the formation of two
selected bio-active compounds were performed
(Scheme 1). First, a rather straightforward RCM of
sclareol (fragrant compound naturally occurring in
Salvia sclarea) derivative 37 was performed with
CH Cl2 M51 (0.01)
2
CH Cl2 M52 (1)
2
CH Cl2 M52 (0.1)
2
CH Cl2 M52 (0.05)
2
toluene M51 (1)
0
1
2
3
4
5
6
toluene M51 (0.1)
toluene M51 (0.05)
toluene M51 (0.01)
toluene M51 (0.01)
toluene M52 (1)
toluene M52 (0.1)
toluene M52 (0.05)
1
mol% of M51 leading to five-membered product 38
in good isolated yield (87%). Interestingly, the same
reaction catalyzed by M52 under identical conditions
gave almost the same isolated yield (85%) of 38.
These results show that both M51 and M52 can be
successfully used in easily ring-closed substrates.
In order to provide additional examples of the cata-
lytic performance of M51 and M52 in more challeng-
ing transformations involving biologically active com-
pounds, the cross metathesis (CM) reaction of estrone
derivative 39 was examined. Reaction of 39 with
67
[
a]
Reaction conditions: substrate (0.25 mmol), pre-catalyst
0.01 to 1 mol%), solvent (0.5 mL), 18 h.
Conversion determined by GC; isolated yield in paren-
theses.
(
[
b]
and trisubstituted six-membered rings were obtained equivalents of tert-butyl acrylate initiated by 1 mol%
in high yields (Table 3, entries 1–3, 6 and 7). Reac- of M51 led to the desired product 40 in excellent iso-
tions forming seven-membered rings are more diffi- lated yield (95%). However, pre-catalyst M52 was
Scheme 1. RCM and CM reactions with bioactive compounds.
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Catalytic and Structural Studies of Hoveyda–Grubbs Type Pre-Catalysts
[a]
Table 2. Scope of the reaction affording five-membered rings.
[b]
Entry
Substrate
Product
Solvent
CH Cl
Pre-catalyst (mol%)
Conversion [%]
1
2
3
4
5
6
7
8
9
M51 (0.1)
M51 (0.1)
M52 (0.1)
M52 (0.1)
M51 (0.5)
M51 (0.5)
M51 (2)
96 (95)
2
2
toluene
CH Cl
74
79
56
5
8
8
2
2
toluene
CH Cl
2
2
toluene
CH Cl
2
2
toluene
toluene
CH Cl
M51 (2)
M51 (5)
12[
c]
21
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
M51 (0.1)
M51 (0.1)
M51 (0.01)
M51 (0.01)
M51 (0.01)
M52 (0.01)
M52 (0.01)
M52 (0.01)
M51 (0.1)
M51 (0.1)
M51 (0.05)
M51 (0.05)
M52 (0.1)
M52 (0.1)
M51 (0.5)
M51 (2)
97
96
84
94 (88)
86
84
93
79
97 (92)
96
94
92
95
85
28
36
2
2
toluene
CH Cl
2
2
toluene
MTBE
CH Cl
2
2
toluene
MTBE
CH Cl
2
2
toluene
CH Cl
2
2
toluene
CH Cl
2
2
toluene
CH Cl
2
2
2
CH Cl
2
[
[
[
a]
Reaction conditions: substrate (0.25 mmol), pre-catalyst, solvent (0.5 mL), 308C, 18 h. MTBE is methyl tert-butyl ether.
Conversion determined by GC, isolated yields in parentheses.
At 708C for 20 h.
b]
c]
shown to be less active in the same transformation,
In the case of M51A, the geometry of the molecule
leading to lower yield (52%) of 40, despite the use of in the crystal lattice revealed a five-coordinated
higher catalyst loadings.
ruthenium atom and disorder in the isopropoxy
Crystallographic Analysis
In order to understand the varied behaviour of the
pre-catalysts, X-ray structural studies were conducted
for both complexes. Pre-catalyst M51 was crystallized
from three different mixtures of solvents resulting in
three types of solvates and, as a consequence, three
different crystal structures have been obtained for
[11]
this compound. For example, M51 crystallized from
benzene/n-pentane and benzene/n-hexane mixtures in
the triclinic P-1 space group (Figure 4, M51A) with
two molecules of the catalyst and two molecules of
benzene in the asymmetric part of the unit cell. How-
ever, when this compound was crystallized from a mix-
ture of dichloromethane (CH Cl /pentane), the crystal
2
2
lattice accommodates one independent molecule of
CH Cl2 (see M51B). For more polar mixtures
2
Figure 4. Molecular structure of M51A crystallized from
benzene/n-pentane and benzene/n-hexane (solvent mole-
cules and hydrogen atoms are omitted for clarity). Thermal
ellipsoids are shown at the 50% probability level.
(
CH Cl /MeOH), the solvent molecules are absent
2 2
from the crystal lattice.
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[a]
Table 3. Scope of RCM reactions affording larger rings, ring-closing enyne and cross metathesis products.
[b]
Entry
Substrate
Product
Catalyst (mol%)
Conversion [%]
1
2
M51 (0.1)
M52 (0.1)
96 (95)
93 (86)
3
4
M51 (1)
M51 (1)
98 (98)
70 (54)
5
M51 (1)
82 (85)
6
7
8
M51 (0.1)
M51 (0.5)
M51 (1)
>99 (98)
97 (97)
80 (67)
9
M51 (1)
75 (60)
1
0
1
M51 (0.05)
>99 (97)
[c]
1
M51 (5)
(89)
[
[
d]
d]
1
1
2
3
M51 (1)
M51 (2)
85 (82)
76 (75)
[
[
[
[
a]
Reaction conditions: substrate (0.25 mmol), pre-catalyst, dichloromethane (0.5 mL), 308C, 18 h.
Conversion determined by GC; isolated yields in parentheses.
In toluene at 708C for 20 h.
b]
c]
d]
1
Methyl acrylate (2 equiv.) as coupling partner, E/Z ratio 20/1 determined by H NMR.
moiety with two positions occupied close to 50% (the acting with the oxygen atom from the carbonyl group
open conformer). as the sixth ligand. The geometry of the ruthenium
Single crystals of M51 grown from a CH Cl /n-pen- catalyst with six ligands surrounding the ruthenium
2
2
tane mixture adopt the monoclinic C2/c space group atom is almost unchanged compared to the ruthenium
symmetry. There are two conformers present in this complex with five ligands. The geometry of the rest of
crystal: the open conformer and the closed one (see the molecule with the exception of the extra RuÀO
Figure 5, M51B). The conformers are found with 70% bond is practically the same as the other conformed
and 30% occupancies, respectively. The open form is (for a more detailed description of crystals packing,
similar to M51A, whereas the closed conformer con- see the Supporting Information).
tains a six-coordinated ruthenium atom directly inter-
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Catalytic and Structural Studies of Hoveyda–Grubbs Type Pre-Catalysts
Figure 7. Molecular structure of M52 crystallized from
CH Cl /n-pentane mixture. All solvent molecules and hydro-
gen atoms are omitted for clarity. Thermal ellipsoids are
shown at the 50% probability level.
Figure 5. Molecular structure of M51B crystallized from
CH Cl /n-pentane mixture. All solvent molecules and hydro-
gen atoms are omitted for clarity. Thermal ellipsoids are
shown at the 50% probability level. The closed form is
shown with gray bonds and the open form with dotted
bonds.
2
2
2
2
space group with one disordered molecule of CH Cl2
2
(
Figure 7). The M52 molecule forms the closed con-
Pre-catalyst M51 crystallized from a solution of former in the crystal structure with the O(2) oxygen
CH Cl and MeOH forms a triclinic P-1 structure atom as the sixth ligand. The crystal packing reveals
2
2
with two molecules of the pre-catalyst in the asym- the layered arrangement of molecules with one layer
metric unit (M51C, Figure 6). Both of these are in the consisting of the NHC ligands and the second of the
open form, with a five-ligand coordination around the rest of the molecules (see the Supporting Informa-
ruthenium center. The pre-catalyst molecules form tion).
dimers connected by weak p-p interactions between
The most striking differences between crystal forms
two carbon atoms in the NHC ligands [the length of of the M51 pre-catalyst are the molecular geometry
the C(56)ÀC(58) [1Àx, 1Ày, 1Àz] contact is and molecular packing in the crystal lattices. As we
3.782(7) ꢂ, see the Supporting Information).
have already mentioned, M51 can form either the six-
The structure of M52 which has already been or the five-coordinated structures. In the crystal latti-
[9b]
report
A
C
H
T
U
N
G
T
R
E
N
N
U
N
G
ed,
was measured again at low temperature ces of M51A and M51C, only the open form of the
to permit comparison with the other structures exam- complexes occurs, whereas in the case of M51B both
[11]
ined in this study. M52 crystallizes in the P-1 triclinic forms are present.
For M52, the closed form is found with the rutheni-
um atom coordinated by six ligands. A comparison of
all structures reveals that the formation of the closed
form leads to an elongation of bonds between the
Ru(1) and C(1), C(22), Cl(1) and Cl(2) atoms. The
bond distances Ru(1)ÀC(1), Ru(1)ÀC(22) are
1
1
.978(2) ꢂ and 1.819(3) ꢂ for M51A and 1.959(5) ꢂ,
.815(5) ꢂ for M51C, while in M51B and M52 respec-
tive values are 1.985(3), 1.827(3) ꢂ and 1.983(3) ꢂ,
.836(2) ꢂ. A similar relationship is present for the
1
bond lengths between the ruthenium and the chloride
atoms. However, the opposite trend occurs for the
Ru(1)ÀO(1) bond length where values of 2.271(2) ꢂ
for M51A, 2.243(3) ꢂ for M51C are found but for
M51B is measured as 2.200(2) and 2.225(2) ꢂ for
M52. For the Ru(1)ÀO(2) bond, lengths of 2.458(3) ꢂ
and 2.511(2) ꢂ for M51B and M52 are measured, re-
spectively. Moreover, the six-coordinated ruthenium
complexes have wider angles between the chloride li-
Figure 6. Molecular structure of M51C crystallized from
CH Cl /MeOH mixture. Hydrogen atoms are omitted for
2
2
clarity. Thermal ellipsoids are shown at the 50% probability gands: 166.25(3)8 for M52, 164.25(3)8 for M51B and
level.
158.63(3)8 for M51A, 161.51(4)8 for M51C. However,
Adv. Synth. Catal. 2012, 354, 2734 – 2742
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Stefano Guidone et al.
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Figure 8. Left: Overlay of molecules from the M51A structure (dark) and the Hov-II (light) one; RMS=0.026. Right: Over-
lay of molecules from the M52 structure (dark) and Hov-II (light); RMS=0.087.
the most significant differences are found in torsion of the initial catalyst remained), although complete
angles. The M52 molecule forms a non-planar five- decomposition was not observed even after 10 days
membered ring based on the Ru(1), C(22), C(23), (10% of M52 was still present after 240 h). This lower
C(28) and O(1) atoms. The torsion angle C(22)À stability of M52 must have an important impact on its
Ru(1)ÀO(1)ÀC(28) is 16.2(3)8 for M52 while the cor- overall catalytic performance, especially in reactions
responding values for M51A, M51B, M51C are requiring longer time and higher temperatures. In
2
.8(2)8, À8.0(2)8 and 7.4(3)8.
such cases better results are obtained with M51 (see
The root mean square (RMS) analysis, taking into CM in Scheme 1).
account the following six atoms: Ru(1), C(1), C(22),
O(1), Cl(1) and Cl(2), reveals similarities with the re-
[
12]
ported structure of pre-catalyst Hov-II. The RMS Conclusions
values are 0.026, 0.067, 0.078 and 0.087 for M51A,
M51B, M51C and M52, respectively, see Figure 8. The efficiency in olefin metathesis reactions of the
M51A has the most closely related molecular geome- modified Hoveyda–Grubbs type pre-catalysts M51
try to that of Hov-II and the small values of the RMS and M52 has been described. Both pre-catalysts can
indicate a possible presence of several molecular con- be used with di- and trisubstituted dienes in ring-clos-
formers.
ing metathesis achieving high yields at room tempera-
The molecular structure of M51 varies in different ture. Nevertheless, these complexes are not thermally
crystalline environments. This means that the mole- stable enough to perform efficiently ring-closing
cule is flexible and can adjust its geometry. This sug- metathesis leading to products with a tetrasubstituted
gests that the flexibility of the pre-catalyst is strongly double bond. M52 does not exhibit high solution
dependent on polarity and size of the solvent mole- phase stability. Enyne cyclization and cross metathesis
cules used for crystallization and weak interactions reactions can be performed and products are obtained
within the crystal lattice. It may also help explain in good yields. In the case of easily ring-closed sub-
some catalytic behaviour.
strates, M51 and M52 provide similar results. Howev-
er, in more challenging transformations, M51 exhibits
higher catalytic activity than M52. This is a result of
poorer solution phase stability of M52 when com-
pared to M51. M51 exhibits the typical Hoveyda–
Stability of Pre-Catalysts in Solution
Catalytic performance of any given pre-catalyst is Grubbs type configuration (five-coordinated rutheni-
always affected by its stability in solution. In order to um) while M52 possesses six-coordination and octahe-
highlight this factor, we performed a comparative sta- dral geometry. While the crucial bond lengths are
bility study of M51 and M52 in dry CD Cl solution rather similar in both complexes, the torsion of the
2
2
under argon at 228C in sealed NMR tubes. Pre-cata- five membered ruthenacycle [C(22)ÀRu(1)ÀO(1)À
lyst M51 shows progressive decomposition, however C(28)] is much more significant in M52 than in M51.
after 10 days still a large amount of catalyst was pres- Although geometries obtained in the solid state can
ent (54% of the initial amount, according to hardly provide information about existing solution
1
H NMR, using durene as internal standard). Its ana- conformations, the X-ray studies show that the geom-
logue, M52, in contrast, underwent visibly faster de- etry of M51 is strongly dependent on solvent of crys-
composition during the first day (after 20 h, only 30% tallization polarity and size. We propose that the
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Catalytic and Structural Studies of Hoveyda–Grubbs Type Pre-Catalysts
higher activity of M51 with more difficult substrates is temperature for 3 h. The solvent was removed under
vacuum and the crude product purified by column chroma-
related to its higher stability.
tography (SiO , EtOAc:cyclohexane 1:4) and recrystallized
2
from cold n-hexane. 40 was obtained as a colorless solid;
yield: 172 mg (95%); mp 134–1368C. IR (film): n=2932,
Experimental Section
1
1
5
757, 1739, 1712, 1653, 1494, 1454, 1368, 1291, 1223, 1151,
140, 1084, 1007, 978, 849, 820 cm ; H NMR (CDCl3,
00 MHz): d=7.29 (d, J=8.1 Hz, 1H), 6.90 (dt, J=15.6 Hz,
À1
1
All reactions were carried out under an inert atmosphere of
argon.
J=6.7 Hz, 1H), 6.85 (dd, J=8.4 Hz, J=2.5 Hz, 1H), 6.80 (d,
J=2.5 Hz, 1H), 5.85 (dt, J=15.7 Hz, J=1.6, 1H), 2.93–2.88
(m, 2H), 2.71 (dt, J=7.9 Hz, J=1.3 Hz, 2H), 2.64–2.58 (m,
RCM of Diethyl Diallylmalonate (Figure 3)
2
1
1
1
1
1
1
H), 2.55–2.47 (m, 1H), 2.44–2.37 (m, 1H), 2.28 (dt, J=
0.7 Hz, J=4.0 Hz, 1H), 2.15 (dt, J=19.1 Hz, J=8.9 Hz,
H), 2.09–1.93 (m, 3H), 1.68–1.52 (m, 5H), 1.48 (s, 9H),
An NMR tube was charged with 1 (0.16 mmol, 38.6 mg) dis-
solved in CD Cl (0.7 mL) and a stock solution (100 mL) of
2
2
the catalyst (0.016 mmol dissolved in 1 mL) in CD Cl . The
13
1
2
2
.47–1.42 (m, 1H), 0.91 (s, 3H); C-{ H} NMR (CDCl ,
1
3
reaction was followed by H NMR spectroscopy (Varian
00 MHz) at 296 K.
25 MHz): d=220.7 (C), 171.1 (C), 165.6 (C), 148.4 (C),
44.7 (CH), 138.0 (C), 137.5 (C), 126.4 (CH), 124.3 (CH),
21.5 (CH), 118.6 (CH), 80.3 (C), 50.4 (CH), 47.9 (C), 44.1
2
General Procedure for Olefin Metathesis Reactions
Table 1, Table 2, Table 3)
(CH), 37.9 (CH), 35.8 (CH ), 32.6 (CH ), 31.5 (CH ), 29.3
2
2
2
(
(CH
), 28.1 (CH
2
3
), 27.1 (CH ), 26.3 (CH ), 25.7 (CH ), 21.5
2 2 2
(
CH ), 13.8 (CH ); HR-MS (ESI) m/z=475.2445, calcd. for
2 3
A 5-mL screw-cap vial fitted with a septum and equipped
with a magnetic stirring bar was charged with the substrate
C H O Na: 475.2455; elem. anal. calcd. for C H O : C
2
8
36
5
28 36
5
7
4.31, H 8.02; found: C 74.28, H 8.19.
(
0
0.25 mmol), methyl acrylate if appropriate (45 mL,
.5 mmol), the appropriate solvent (0.5 mL) and a stock so-
lution of the pre-catalyst. The reaction mixture was stirred
at the indicated temperature for 18 h. The crude product
was analyzed by GC and purified by column chromatogra-
phy (SiO , Et O/pentane, see the Supporting Information
Acknowledgements
The authors gratefully acknowledge the Royal Society (Uni-
versity Research Fellowship to CSJC), the EC (CP-FP
2
2
for details).
2
11468-2 EUMET) and the Polish Ministry of Science and
Higher Education (grant number NN204404940) for funding.
Additionally, CS acknowledges personal fellowship from the
RCM Reaction Leading to 38 (Figure 4)
“
START-2012” grant for young researchers, which was given
In a Schlenk tube, substrate 37 (140 mg, 0.4 mmol) was dis-
solved in CH Cl (2 mL) under an argon atmosphere, M51
by The Foundation for Polish Science.
2
2
(
3 mg, 1 mol%) was added in one portion as a solid. The re-
action mixture was heated to reflux temperature for 3 h.
The solvent was removed under vacuum and the crude References
product was purified by column chromatography (SiO2,
EtOAc:cyclohexane 1:9). Product 38 was obtained as a vis-
cous oil; yield: 111 mg (87%); mp 67–698C. IR (film): n=
[1] a) R. H. Grubbs, in: Handbook of Olefin Metathesis,
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3
1
5
2
3
3
1
447, 2925, 1459, 1387, 1366, 1347, 1191, 1110, 1084, 1041,
À1
1
014, 938, 805, 712 cm ; H NMR (CDCl , 500 MHz): d=
3
.80 (dt, J=6.0 Hz, J=1.4 Hz, 1H), 5.80 (dt, J=6.0 Hz, J=
.4 Hz, 1H), 4.67–4.59 (m, 2H), 1.85 (dt, J=12.2 Hz, J=
.2 Hz, 1H), 1.75–1.61 (m, 6H), 1.56 (tt, J=13.5 Hz, J=
.4 Hz, 1H), 1.46–1.29 (m, 6H), 1.27 (s, 3H), 1.13 (s, 3H),
.06 (t, J=4.1 Hz, 1H), 0.96–0.89 (m, 2H), 0.86 (s, 3H), 0.78
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2
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[
3] On the
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2
2
in one portion and the reaction mixture was heated to reflux
Adv. Synth. Catal. 2012, 354, 2734 – 2742
ꢀ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
asc.wiley-vch.de
2741

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