Fast olefin metathesis at low catalyst loading

Article abstract of DOI:10.1002/chem.201201010

Reactions of the Grubbs 3rd generation complexes [RuCl₂(NHC) (Ind)(Py)] (N-heterocyclic carbene (NHC)=1,3-bis(2,4,6- trimethylphenylimidazolin)-2-ylidene (SIMes), 1,3-bis(2,6- diisopropylphenylimidazolin)-2-ylidene (SIPr), or 1,3-bis(2,6- diisopropylphenylimidazol)-2-ylidene (IPr); Ind=3-phenylindenylid-1-ene, Py=pyridine) with 2-ethenyl-N-alkylaniline (alkyl=Me, Et) result in the formation of the new N-Grubbs-Hoveyda-type complexes 5 (NHC=SIMes, alkyl=Me), 6 (SIMes, Et), 7 (IPr, Me), 8 (SIPr, Me), and 9 (SIPr, Et) with N-chelating benzylidene ligands in yields of 50-75 %. Compared to their respective, conventional, O-Grubbs-Hoveyda complexes, the new complexes are characterized by fast catalyst activation, which translates into fast and efficient ring-closing metathesis (RCM) reactivity. Catalyst loadings of 15-150 ppm (0.0015-0.015 mol %) are sufficient for the conversion of a wide range of diolefinic substrates into the respective RCM products after 15 min at 50 °C in toluene; compounds 8 and 9 are the most catalytically active complexes. The use of complex 8 in RCM reactions enables the formation of N-protected 2,5-dihydropyrroles with turnover numbers (TONs) of up to 58 000 and turnover frequencies (TOFs) of up to 232 000 h^-1; the use of the N-protected 1,2,3,6-tetrahydropyridines proceeds with TONs of up to 37 000 and TOFs of up to 147 000 h^-1; and the use of the N-protected 2,3,6,7-tetrahydroazepines proceeds with TONs of up to 19 000 and TOFs of up to 76 000 h^-1, with yields for these reactions ranging from 83-92 %. The tortoise and the hare: The use of diphenylalkylamino-based instead of phenyldialkylamino-based styrenes (see figure) leads to rapidly initiating precatalysts that enable very fast ring-closing metathesis reactions with turnover numbers of up to 58 000 and turnover frequencies of up to 232 000 h^-1. Copyright

Full text of DOI:10.1002/chem.201201010

FULL PAPER
DOI: 10.1002/chem.201201010
Fast Olefin Metathesis at Low Catalyst Loading
Lars H. Peeck, Roman D. Savka, and Herbert Plenio*[a]
Abstract: Reactions of the Grubbs 3rd
generation complexes [RuCl2A(NHC)-
ACHTUNGTRENNUNG(Ind)(Py)] (N-heterocyclic carbene
(NHC)=1,3-bis(2,4,6-trimethylphenyli-
midazolin)-2-ylidene (SIMes), 1,3-
bis(2,6-diisopropylphenylimidazolin)-2-
ylidene (SIPr), or 1,3-bis(2,6-diisopro-
tive, conventional, O-Grubbs–Hoveyda
complexes, the new complexes are
characterized by fast catalyst activa-
tion, which translates into fast and effi-
cient ring-closing metathesis (RCM)
reactivity. Catalyst loadings of 15–
150 ppm (0.0015–0.015 mol%) are suf-
ficient for the conversion of a wide
range of diolefinic substrates into the
respective RCM products after 15 min
at 508C in toluene; compounds 8 and 9
are the most catalytically active com-
plexes. The use of complex 8 in RCM
G
reactions enables the formation of N-
protected 2,5-dihydropyrroles with
turnover numbers (TONs) of up to
58000 and turnover frequencies
(TOFs) of up to 232000 hÀ1; the use of
the N-protected 1,2,3,6-tetrahydropyri-
dines proceeds with TONs of up to
pylphenylimidazol)-2-ylidene
(IPr);
Ind=3-phenylindenylid-1-ene,
Py=
37000 and TOFs of up to 147000 hÀ1
and the use of the N-protected 2,3,6,7-
tetrahydroazepines proceeds with
;
pyridine) with 2-ethenyl-N-alkylaniline
(alkyl=Me, Et) result in the formation
of the new N-Grubbs–Hoveyda-type
TONs of up to 19000 and TOFs of up
to 76000 hÀ1, with yields for these reac-
tions ranging from 83–92%.
complexes
5 (NHC=SIMes, alkyl=
Me), 6 (SIMes, Et), 7 (IPr, Me), 8
(SIPr, Me), and 9 (SIPr, Et) with N-
chelating benzylidene ligands in yields
of 50–75%. Compared to their respec-
Keywords: alkenes · metathesis ·
precatalyst activation · ring-closing
reactions · ruthenium
Introduction
The rate at which precatalysts[1] for olefin metathesis reac-
tions are activated[2] has a strong influence on the rate of
substrate conversion.[3] Slowly initiating precatalysts (latent
complexes)[4] lead to slow reactions or require high tempera-
tures, and appear to be useful for ring-closing metathesis
(RCM) reactions of sterically hindered substrates.[5] More
rapidly initiating complexes provide good substrate conver-
sion within a short time or at low temperatures.[6] Extremely
fast precatalysts, such as the Grubbs 3rd generation (1-Br in
Scheme 1)[7] or Piers-type (3 in Scheme 1) complexes, are
also known.[8] These complexes are indispensable tools for
the synthesis of low-dispersity polymers by ring-opening
metathesis polymerization (ROMP), which requires a faster
rate of initiation than the rate of chain growth.[9] On the
other hand, the Grubbs 3rd generation complexes have
Scheme 1. Grubbs 3rd generation complexes (1), O-Grubbs–Hoveyda
complexes (2a, 2b, 2c), N-Grubbs–Hoveyda complex (2d), and Piers
complex with a SIMes-type NHC ligand (3).
[a] Dr. L. H. Peeck,+ R. D. Savka,+ Prof. H. Plenio
Organometallic Chemistry, Technische Universitꢀt Darmstadt
Petersenstrasse 18, 64287, Darmstadt (Germany)
E-mail: plenio@tu-darmstadt.de
rarely been employed in reactions other than ROMP[10]
,
probably due to their low stability under the reaction condi-
tions.[11] Complexes that are closely related to 1 (for exam-
ple, those containing an indenylidene instead of a benzyli-
dene ligand) also display a modest performance in RCM
and enyne metathesis.[12] From a synthetic point of view,
there should be an optimum rate of precatalyst activation
[+] These authors contributed equally to this work.
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/chem.201201010. It includes the syn-
thesis of starting materials, reaction and screening procedures, copies
1
of H and 13C NMR spectra, gas chromatograms, UV/Vis spectra, and
mass spectra.
Chem. Eur. J. 2012, 00, 0 – 0
ꢁ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
&
1
&
ÞÞ
These are not the final page numbers!

that lies somewhere between the extremes of latent and ex-
tremely fast precatalysts. Slowly initiating precatalysts can
lead to impractical, slow, initiation-rate-limited metathesis
conversions, whereas very quickly initiating complexes tend
to be labile and may also generate the active species too
rapidly. Compared with 1, the initiation rates of the stable
Grubbs–Hoveyda-type complexes[13] are much slower, but
can be somewhat improved by replacing a hydrogen (2a in
Scheme 1) with a 5-NO2 (complex 2b)[6] or a 3-phenyl
group.[13a,14] Even-faster initiating complexes are obtained
when the isopropoxy group is replaced by a smaller methoxy
group (2c in Scheme 1).[2e] Closely related complexes that
have an amine ligand (2d in Scheme 1) instead of the ether
oxygen donor were first reported by Slugovc et al.[15] and the
Grela group.[3b,16] These precatalysts are characterized by
very slowly initiating reactions and are employed as latent
catalysts for ROMP reactions.[4b,15,17]
Scheme 2. a) nBuLi, N,N,N’,N’-tetramethylethylenediamine (TMEDA),
cyclohexane, 608C; b) DMF, THF, À788C to RT, then NH4Cl, H2O;
c) MePPh3I, KOtBu, THF, À108C to RT.
AHCTUNGTRENNUNG
AHCTUNGTRENNUNG
the desired complexes was not observed and only the stil-
benes resulting from the cross-metathesis reaction of the
styrenes were isolated. The desired N-Grubbs–Hoveyda-
type complexes 5, 6, 7, 8, and 9 (Scheme 3) were formed in
modest yields of 10–36% when using substoichiometric
amounts of the styrenes at elevated temperatures.
A structural peculiarity of these complexes (and of relat-
ed complexes that contain thioether[18] and sulfoxide donor
atoms) is the formation of cis-dichloro complexes during
synthesis under kinetic control;[3b] however, the cis arrange-
ment appears to be thermodynamically preferred by the
thio
ACHTUNGTRENNUNGences appear to be based on the stronger s-donor capacity
ACHTUNGTRENNUNG
ether complexes.[19] The geometric cis or trans prefer-
of sulfur and nitrogen compared with that of an ether oxy-
gen,[19a] as well as on solvent polarity and steric effects.[20]
Relative to PhNMe2, the basicity of the nitrogen atom is
reduced by more than four orders of magnitude when a
single methyl substituent is replaced by a phenyl group in
Ph2NMe.[21] We anticipated that such a marked change at
the donor atom in the benzylidene amine of a Grubbs–Hov-
eyda-type complex should lead to a pronounced weakening
À
of the Ru N interaction, and consequently to a significant
increase in the initiation rate of the precatalyst. This may be
useful for sterically unhindered olefin metathesis reactions,
and we were hoping that more-rapidly initiating precatalysts
should lead to faster olefin metathesis reactions, as long as
the respective precatalysts are sufficiently stable. This does
not appear to be the case for complex 1, thus it was our aim
to synthesize ruthenium complexes with a Ph2NACTHUNRTGNE(GNU alkyl)-de-
rived styrene ligand and to study their behavior in olefin
metathesis reactions.
Scheme 3. Synthesis of ruthenium complexes 5 (yield 30%, with acidic
resin 70%), 6 (yield 10%, with acid resin 50%), 7 (yield 34%, with
acidic resin 68%), 8 (yield 36%, with acidic resin 75%), and 9 (yield
27%, with acidic resin 60%).
The reason for the modest yields could be the reluctant
substitution of pyridine by the weak nitrogen donor (alkyl-
diarylamine). To facilitate the formation of the desired com-
plexes, we decided to efficiently remove the pyridine by in
situ protonation with a protic ion-exchange resin (Amber-
lyst). Due to the pronounced difference in their Brønsted
basicities, the protonation of pyridine is preferred to the
protonation of the respective alkyldiarylamines. A related
approach was first used by Verpoort et al. in the synthesis of
various O-Grubbs–Hoveyda type complexes in excellent
yields, by removing PCy3 with a protic resin as the respec-
tive phosphonium salt.[23] When the synthesis of the new
ruthenium complexes was carried out in the presence of
Amberlyst resin in CH2Cl2 at 408C by using stoichiometric
Results and Discussion
Synthesis of ligands and ruthenium complexes: The ortho-
vinyl-substituted alkyldiphenylamines were prepared by di-
rected ortho-metalation[22] of RNPh2 (R=Me, Et) with
nBuLi. The reaction of the respective lithium salts with di-
methylformamide gave the respective aldehydes, which were
then converted into the 2-vinyl-substituted amines by em-
ploying the Wittig reagent (Scheme 2).
The vinylated alkyldiarylamines were treated with the re-
spective Grubbs 3rd generation complexes [RuCl
(Ind)(Py)] (N-heterocyclic carbene (NHC)=1,3-bis(2,4,6-tri-
methylphenylimidazolin)-2-ylidene (SIMes), 1,3-bis(2,6-di-
2ACHTUNGTNER(NUNG NHC)-
ACHTUNGTRENNUNG
&
2
&
www.chemeurj.org
ꢁ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 0000, 00, 0 – 0
ÝÝ
These are not the final page numbers!

Fast Olefin Metathesis at Low Catalyst Loading
FULL PAPER
amounts of the alkyldiarylamines, the desired complexes
were obtained in much better yields (see Scheme 3). All
complexes (except for 6) are stable in the solid state and sol-
utions of each could be exposed to an ambient atmosphere
for 24 h without appreciable decomposition.
By employing the optimized reaction conditions, the syn-
thesis of complexes 5, 6, 7, 8, and 9 was straightforward.
However, in the absence of a protic resin when using tol-
uene as the solvent, the reaction of 2-ethenyl-N-methyl-N-
gands coordinated to this metal.[2e,5b,25] Consequently, the
redox potentials in CH2Cl2 of the complexes reported herein
were determined (5: E=0.806 V, Ea–Ec =74 mV; 7: E=
0.757 V, Ea–Ec =76 mV; 8: E=0.827 V, Ea–Ec =79 mV; and
9: E=0.813 V, Ea–Ec =90 mV). The redox potentials for the
complexes with a saturated NHC backbone (5, 8, and 9) are
comparable to and only slightly less anodic than those of
the respective O-Grubbs–Hoveyda complexes (2a: E=
0.84 V).[2e] This underlines the modest donor capacity of the
diarylamino nitrogen atom. The redox potentials for the
three complexes with saturated NHC ligands (5, 8, and 9)
are fairly similar, whereas complex 7, with an unsaturated
IPr backbone, can be oxidized more easily. This is unexpect-
ed, as normally the donor abilities of saturated and unsatu-
rated NHC ligands are fairly similar.[26]
phenylaniline with [RuCl2ACTHNUTRGENNUG(SIMes)ACHUTNGTRENN(UNG Ind)(Py)] can result in
the formation of two isomeric species. When the reaction
was carried out at a low reaction temperature (below 758C
in toluene) a mixture of two isomers was formed. The char-
acteristic resonance of the benzylidene proton of the trans
complex is located at d=17.00 ppm (see below for the X-
ray crystal structure of complex 5). The other isomer could
not be isolated from trans-5, but is characterized by a
1H NMR resonance at d=17.23 ppm. Based on literature
X-ray crystal structure of complex 5: With a view to the
rapid initiation reactions of complex 5, the most interesting
1
À
precedent and the H NMR shift of the benzylidene proton,
structural parameter appeared to be the Ru N separation.
this is most likely to be the cis-isomer of 5.[19b] This cis/trans
ratio critically depends on the reaction temperature and at
lower temperatures the cis isomer is primarily formed, for
example, at 658C the cis/trans ratio is 1.7, and at 608C the
cis/trans ratio is 4.0.
Single crystals of 5 were obtained by evaporating a solution
in cyclohexane in an open beaker, which also provided con-
vincing evidence for the excellent stability of
5 (see
À
Figure 2). However, at 234.7(4) pm the Ru N separation is
Preliminary tests revealed that the catalytic activity of
pure trans-5 is excellent (Figure 1), and at a 0.1 mol% load-
ing of complex trans-5, the room temperature reaction of di-
Figure 2. ORTEP diagram for the crystal structure of complex 5. Impor-
tant bond lengths [pm] and angles [o]: Ru–N 234.7(4), Ru CHAr
À
À
À
182.6(5), Ru C
N
162.58(6), N-Ru-CACTHNGUTRNE(NUG NHC) 175.53(15).
Figure 1. Conversion–time curves for the room temperature (293 K)
RCM reaction of DEDAM (0.1 molLÀ1) with [Ru] (0.1 mol%) in toluene
unspectacular. In closely related complexes in which the
&
*
:
by using trans-5 and mixtures of trans-5 and cis-5. : trans/cis=0.25;
À
phenyl group in 5 is replaced by an alkyl group, the Ru N
~
trans/cis=0.59; : trans-5.
separation averages 232 pm (based on three complexes with
232.1, 232.0, 231.9 pm).[3b] Such small structural changes can
hardly account for the massive difference in the initiation
rates of the diarylalkylamino complex 5 compared with the
aryldialkylamino complexes. On the other hand, these sepa-
ethyl diallyl malonate (DEDAM) leads to the quantitative
formation of the desired cyclic product within about 10 min.
A mixture of isomers, when primarily composed of cis-5, is
less active. We therefore concluded that either cis-5 is less
active, or the time needed for cis-5 to convert into trans-5 is
limiting the catalytic turnover. Based on literature prece-
dent, the latter explanation is more likely.[24] Consequently,
in the later catalytic and initiation studies pure trans-5 is em-
ployed (which will be denoted as 5).
À
rations are much longer than the Ru O bond length in com-
plex 2a (226.1 pm).[13b] The nitrogen coordinated to the
ruthenium atom is nearly tetrahedral (the sum of the three
C-N-C angles is 3348, which is not much smaller than the
328.48 for a tetrahedron).
Evaluation of the catalytic activity of complexes 2a, 2b, 4a,
5, 6, 7, 8, and 9: To gauge the performance of the new com-
plexes 5, 7, 8, and 9, and the benchmark precatalysts 2a and
2b, were tested in the RCM reaction of diallyl-N-tosylamide
Redox potentials: We have previously shown that the redox
potentials of ruthenium in Grubbs-type complexes are an
excellent indicator to evaluate the donor capacity of the li-
Chem. Eur. J. 2012, 00, 0 – 0
ꢁ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
&
3
&
ÞÞ
These are not the final page numbers!

H. Plenio et al.
at 08C in toluene (Figures 3 and 4). Excellent substrate con-
version is observed for all of the new complexes, which cata-
lyze RCM reactions faster than the benchmark catalysts; be-
Figure 5. RCM reaction of DEDAM (0.1 molLÀ1) at 208C in toluene
&
*
with the complexes 2a, 2b, and 5 (1000 ppm). : Complex 2b; : com-
~
plex 5; : complex 2a.
tained within 15 min by using only 25 ppm of complex 5
(Table 1). This pronounced difference in RCM reactivity in-
dicates that the rate of the catalytic transformation increases
more rapidly with temperature than does the decomposition
rate of the active species.
Figure 3. RCM of diallyl-N-tosylamide (0.1 molLÀ1) at 08C in toluene
&
with the trans complexes 2b, 5, and 7–9 (0.1 mol%; 1000 ppm). : Com-
~
!
*
plex 8; : complex 5; : complex 7; : Complex 9; 3: complex 3; ":
complex 2.
To optimize the performance of the different ruthenium
complexes, the temperature for the RCM reaction of diallyl-
N-tosylamide and complex 5 in toluene was systematically
varied between 08C and 608C. An increase in the reaction
temperature to 508C led to an increase in the catalytic effi-
ciency. Next, complexes 5, 6, 7, 8, and 9 were systematically
tested in a number of ring-closing metathesis reactions at
this temperature. The results of the extensive screening
studies are summarized in Table 1. Complex 7 is less effi-
cient than the other complexes and was therefore only stud-
ied in a few transformations. For many reactions, the bench-
mark complexes 2a and 2b and the Grubbs 3rd generation
type complex 4a were employed under the same reaction
conditions. Complex 4a was tested in four RCM reactions
(Table 1, entries 1, 7, 9, and 13) and turned out to be less
active than the newly synthesized complexes. The data in
Table 1 also show that precatalysts 2a and 2b perform quite
well under our optimized reaction conditions. For several
substrates (Table 1, entries 1, 3, 4, 6, and 7), the catalytic
performance is close to that of complex 5, and for other sub-
strates (Table 1, entries 2, 5, and 8–12), complex 5 is clearly
more effective than both 2a and 2b. For most metathesis
transformations (Table 1, entries 1, 3–5, 7–10, and 14), the
SIPr complexes 8 and 9 are even more efficient than com-
plex 5.
Apart from the very modest catalyst loading, the short re-
actions times required for this transformation are notable;
all of the reactions that involve the new complexes studied
herein are complete in less than 15 min. Dorta et al.[27] also
demonstrated very fast RCM reactions at low catalyst load-
ings by performing the reactions in the neat substrate, or in
highly concentrated solutions, and by employing a Grubbs–
Hoveyda-type complex with a specialized NHC ligand. The
latter approach is extremely useful but may be limited to
liquid or highly soluble substrates, the RCM reactions of
which lead to five or six-membered rings. The much lower
effective molarities with other substrates that result in the
Figure 4. RCM of diallyl-N-tosylamide (0.1 molLÀ1) at 08C in toluene
&
with the trans complexes 2a, 5, and 9 (0.025 mol%; 250 ppm). : Com-
~
*
plex 2a; : complex 9; : complex 5.
tween 75 (complex 5) and 96% (complex 9) of the substrate
is converted to product within 40 min and at 1000 ppm [Ru].
In the series of reactions involving SIMes-based complexes
2a and 2b, faster initiation rates appears to translate into
faster catalysis at low temperatures. However, the nature of
the active species is also important: the SIPr based com-
plexes 8 and 9 show higher activities than the SIMes com-
plexes. The ability of complex 5 to rapidly catalyze RCM re-
actions is also apparent for DEDAM reactions (Figure 5).
With the use of this precatalyst, full substrate conversion is
achieved within about 10 min, whereas precatalysts 2a and
2b need a much longer reaction time to achieve full conver-
sion.
These initial experiments demonstrate that one advantage
of the newly synthesized complexes is the short time re-
quired for the RCM transformations. Furthermore, we note
a strong influence of temperature on the catalyst perform-
ance. To obtain a yield of about 84% in the RCM of diallyl-
N-tosylamide at 08C requires 1000 ppm of complex 5 and a
reaction time of 120 min. At 508C, the same yield is ob-
&
4
&
www.chemeurj.org
ꢁ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 0000, 00, 0 – 0
ÝÝ
These are not the final page numbers!

Fast Olefin Metathesis at Low Catalyst Loading
FULL PAPER
Table 1. Screening of different catalysts for the ring closing metathesis
reactions.
In conclusion, the formation of N-protected 2,5-dihydro-
pyrroles by using complex 8 (Table 1, entry 1) proceeds with
a TON of 58000 (yield 87%) and a TOF of 232000 hÀ1. The
formation of N-protected 1,2,3,6-tetrahydropyridines by
using complex 8 (Table 1, entry 8) proceeds with a TON of
37000 (92% yield) and a TOF of 147000 hÀ1. The respective
N-protected 2,3,6,7-tetrahydroazepines (Table 1, entry 5) re-
quire a catalyst loading of 50 ppm (0.005 mol%), resulting
Substrate[a]
[Ru][b]
Conversion[c] [%]
A
5
6
7
8
9
1
50
25
15
150
50
–
–
–
98 (94)
–
–
–
–
70 61 60 84
–
–
71 55 98 97
–
–
in a TON of 19000 (95% yield) and a TOF of 76000 hÀ1
.
–
–
–
–
–
–
–
–
87 76
–
This is a very significant improvement with respect to the
literature data.[29] For the various DEDAM type substrates
(Table 1, entries 10–12), the catalyst loadings and yields re-
ported herein are comparable to those reported by Nolan,
Slugovc et al., although the time required for such transfor-
mations by using complex 5 is much shorter.
2
3
99 (95)
93
–
39 83
45 40 81 72
200
150
–
–
–
–
96 (94)
90
–
–
–
–
–
–
76 80
96 98
4
200
100
50
100
50
–
–
–
–
–
–
–
93 (89)
82
–
95 (91)
91
–
–
–
–
–
–
–
–
–
67 76
–
–
71 93
The reactions described herein were carried out by using
standard Schlenk techniques. However, the use of purified
toluene and of purified reactants is very important in order
to minimize the decomposition of the sensitive, catalytically
active species. To learn more about the nature of potential
impurities, we tested the effect of water on the substrate
conversion. A small amount of water was deliberately added
to the toluene solvent prior to the RCM conversion to es-
tablish a water content of about 100 ppm.[32] The RCM of
the diallyl-N-tosylamide was performed in this “wet” tol-
uene with a 25 ppm loading of 5, and the product was ob-
tained in 71% yield (instead of 84%, see Table 1, entry 1).
We therefore concluded that the water concentration only
has a weak influence on the RCM reaction. It is likely that
the limiting factor for RCM reactions is the presence of
other trace impurities in the solvent (sulfur-containing com-
pounds, such as methyl thiophene, are potential candi-
dates[33]) or in the RCM substrates.
–
–
–
–
–
83 82
–
92 95
5
6
–
28 55
100
50
–
–
–
–
97 (93)
89
–
–
–
–
75 51
44 45 77 81
7
8
50
25
15
100
50
25
–
–
–
98 (95)
–
–
–
–
77 68 37 87
–
–
60 67
–
66 65 91 93
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
78 83
–
99
92 87
98
99(93)
79
–
–
–
–
9
10
11
12
13
300
150
53 61 34 85
–
–
–
–
–
51 85 86
200
100
29 65
–
–
–
84
58
67 72 97 91
–
–
–
68 74
86
79 77
200
100
84 82
62 65
–
–
–
–
–
–
–
–
–
100
50
–
–
–
–
95 (91)
58
–
–
–
–
–
54
–
–
36 15
100
50
–
–
–
8
98
59
–
–
–
–
–
–
–
–
Precatalyst activation: The new ruthenium complexes dis-
play a strong absorbance at around 370 nm, which probably
results from a ligand–metal charge transfer (LMCT),[34] and
provides an excellent UV/Vis spectroscopic handle for ki-
netic studies. The reactions of the ruthenium complexes
with butyl vinyl ether (BuVE) could serve as a reasonable
model for the initiation reactions with RCM substrates.
After the addition of BuVE to a solution of complex 5 in
toluene, the time dependent UV/Vis spectra at 308C were
recorded and the respective absorbance–time curves at
around 370 nm were fitted with an exponential function ac-
cording to the method reported previously.[2e,5a] Complex 5
26 35
[a] [substrate]=0.5m. [b] 100 ppm [Ru] corresponds to 0.01 mol% cata-
lyst loading. [c] Conversions determined by GC, averaged over two runs;
yields of isolated products are reported in parentheses.
formation of seven-membered rings could easily lead to the
undesired formation of acyclic diene metathesis (ADMET)
polymers.[28] Other examples of olefin metathesis reactions
with a low catalyst-loading that involve the use of robotic
equipment in a glove box have been reported by Nolan, Slu-
govc et al.[29] and Grubbs et al.[30] Pederson, Grubbs et al.
have recently evaluated several ruthenium complexes in the
synthesis of five-, six-, and seven-membered N-heterocycles.
In their work, 500 ppm of the Ru complex was used for the
full conversion of substrates (Table 1, entries 7–9) during a
reaction time of 8 h;[31] for entry 7, this leads to a TON of
2000 and a TOF of 310 hÀ1. We are reporting here that the
synthesis of the respective heterocycles in less than 15 min
requires only 15–150 ppm of the newly synthesized N-
Grubbs–Hoveyda complexes.
is characterized by very fast precatalyst activation (kobs
=
0.2 sÀ1 at [BuVE]=0.1 molLÀ1). This step is about 30 times
faster than the reaction that uses reference complex 2a
(kobs =0.006 sÀ1), and is about 15 times faster than the reac-
tion that uses 2b (kobs =0.013 sÀ1).[35] Complex 6 is even
faster; it is in fact too fast to obtain accurate data by using
conventional cuvette-based UV/Vis spectroscopy at 308C.
Even at [BuVE]=0.1 molLÀ1 the initiation reaction is fin-
ished in less than 10 s. This fast reaction time may explain
the faster RCM reactions observed with 5 compared with
complexes 2a and 2b. This also confirms that the diarylami-
Chem. Eur. J. 2012, 00, 0 – 0
ꢁ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
&
5
&
ÞÞ
These are not the final page numbers!

H. Plenio et al.
no-based ligands in the N-Grubbs–Hoveyda complexes pre-
sented herein lead to a pronounced acceleration of precata-
lyst activation.
The new alkylidene ligand 2-(N,N-methyphenyl)amino-
benzylidene (L) will be useful in a large number of [RuCl2-
AHCTUNGTREG(NNUN NHC)(L)] complexes with different NHC ligands and
The rates of the BuVE (0.1 molLÀ1) reactions when using
the more bulky complexes 8 and 9 were also determined
under the same reaction conditions. Based on the evaluation
of the 370 nm absorbance peak, the SIPr ruthenium com-
plexes show a much slower precatalyst activation; the initia-
tion rates for complexes 7, 8, and 9 are kobs =0.0080, 0.0025,
and 0.0072 sÀ1, respectively. The slower initiation rate for
the SIPr-based complexes compared with the SIMes com-
should lead to a new family of rapidly initiating, but stable,
ruthenium precatalysts. As already demonstrated by numer-
ous research groups for the O-Grubbs–Hoveyda complex
2a, additional modifications at the N substituents of the new
N-Grubbs–Hoveyda complexes can enable fine-tuning of
the catalytic activity to obtain tailored catalysts for specific
olefin metathesis transformations.
plex
5 was unexpected. Therefore the SIPr-based O-
Grubbs–Hoveyda complex 10 (same as complex 2a, but
with an SIPr ligand instead of the SIMes ligand in complex
2a) was also investigated.[36] Activation of this complex is
even slower, and at [BuVE]=0.1 molLÀ1 a kobs =0.00044 sÀ1
was determined; complex 10 initiates the reaction almost six
times more slowly than complex 8, and almost sixteen times
more slowly than complex 9. The slow rates determined for
the SIPr-based complexes (compared with SIMes com-
plexes) appear to be in contrast to the fast and efficient
olefin metathesis reactivity observed for complex 10. The
rapid substrate conversion of complex 10 was also confirmed
for several ADMET polymerization reactions of a,w-dienes,
as the initial polymerization rate was found to be higher
than that of complex 2a.[36] Considering the very fast rate of
catalyst initiation for the SIMes complexes 5 and 6 reported
herein, it is also possible to consider a second initiation step
that becomes rate limiting when the first initiation step is
very fast.[37]
Experimental Section
General experimental: All chemicals were purchased as reagent grade
from commercial suppliers and used without further purification, unless
otherwise noted. All reactions involving ruthenium complexes were per-
formed under an atmosphere of argon. CH2Cl2 (99.5%) and pentane
(99%) were obtained from Grꢂssing GmbH, toluene from Sigma–Al-
drich (lab. reagent grade, 99.3%, Lot.: STBB5057). These solvents were
dried and degassed by using a column purification system described by
Grubbs et al.[38] In this system, the solvents are sparged and pressurized
with argon (0.1–1 bar), successive passed through one column filled with
activated alumina and then a second column, either filled with a support-
ed copper catalyst (toluene, pentane) or, again, activated alumina
(CH2Cl2). Toluene was additionally dried over CaH2 and distilled onto
molecular sieves (4 ꢃ). RCM substrates were purified by column chro-
matography using distilled mixtures of pentane and diethyl ether. Diethyl
diallyl malonate was purified by distillation. Cyclohexane, n-hexane, pyri-
dine, and dimethylformamide were heated at reflux over calcium hydride
and distilled under an argon atmosphere. Tetrahydrofuran was dried
under sodium and distilled under an argon atmosphere. All solvents were
stored over molecular sieves (4 ꢃ). 1H and 13C NMR spectra were re-
corded on a Bruker DRX300 spectrometer. The chemical shifts are given
in parts per million (ppm) on the delta scale (d) and are referenced to
tetramethylsilane (1H, 13C NMR=0.0 ppm) or the residual peak of
CHCl3 (1H NMR=7.26, 13C NMR=77.16 ppm).[39] Abbreviations for
NMR data: s=singlet, d=doublet, t=triplet, q=quartet, sep=septet,
m=multiplet, br=broad signal, Ar=aromatic protons. UV/Vis spectro-
photometric data were acquired on an Analytik Jena SPECORD S 600
UV/Vis spectrophotometer. Thin layer chromatography (TLC) was per-
formed by using silica 60 F 254 (0.2 mm) on aluminum plates. Preparative
chromatography was done on Merck silica 60 (0.063–0.02 mesh), but
complexes 6–9 were purified by column chromatography on granular
silica (60 ꢃ pore size, 40–63 mm, 230–400 mesh) from Roth AG. GC ex-
periments were run on a Clarus 500 GC with an autosampler and FID
Conclusion
The reactions of the Grubbs 3rd generation type complexes
[RuCl2ACHTUNGTRENNUNG(NHC)ACHTUNGTRENNUNG(Ind)(py)] (NHC=SIMes, SIPr, or IPr) with
2-ethenyl-N-alkyl-N-phenylaniline (alkyl=Me, Et) result in
the efficient formation of new N-Grubbs–Hoveyda-type
complexes 5–9 in yields of 50–75%. These complexes com-
bine a fast precatalyst initiation and high stability with ex-
cellent activity in various ring-closing metathesis reactions.
Low precatalyst loadings of 15–300 ppm are sufficient for
the conversion of a range of RCM substrates into the re-
spective cyclic olefins in reaction times of less than 15 min.
For most reactions, the SIPr complexes 8 and 9 are the most
efficient precatalysts, especially for the synthesis of N-het-
erocycles: 15–25 ppm (0.0015–0.0025 mol%) of complex 8
are sufficient for the formation of N-protected 2,5-dihydro-
pyrroles (TOF of up to 232000 hÀ1) and N-protected 1,2,3,6-
tetrahydropyridines (TOF of up to 147000 hÀ1) in yields of
around 90%; the synthesis of the respective N-protected
2,3,6,7-tetrahydroazepines with 8 requires a catalyst loading
of 50 ppm (0.005 mol%, 95% yield, TOF of up to
76000 hÀ1).
detector [column: Varian CP-Sil
8 CB (l=15 m, di =0.25 mm, dF =
1.0 Lm), N2 (flow: 17 cmsÀ1; split 1:50); injector temperature: 2708C, de-
tector temperature: 3508C]. Cyclic voltammograms were recorded in dry
CH2Cl2 under an argon atmosphere at ambient temperature. A three-
electrode configuration was employed. The working electrode was a Pt
disk (diameter 1 mm) sealed in soft glass with a Pt wire as a counter elec-
trode. The pseudoreference electrode was a Ag wire. Potentials were cali-
1
brated internally against the formal potential of ferrocene (E = = +0.46 V
2
(CH2Cl2)). NBu4PF6 (0.1 molLÀ1) was used as a supporting electrolyte.
Preparation of catalyst stock solution: c=0.75 mmolLÀ1: The ruthenium
complex (4.0ꢄ10À6 mol) was weighed into a Schlenk tube (10 mL). The
tube was evacuated, backfilled with nitrogen, and then dried toluene
(5.34 mL) was added under a stream of argon. The Schlenk tube was
kept in an ultrasonic bath for 1 min for complete dissolution of the preca-
talyst.
Catalyst Screening: All reactions were carried out in sealed Schlenk
tubes (10 mL) under an atmosphere of argon at 0, 20, or 508C. In a
Schlenk tube (10 mL), the substrate (0.2–0.6 mmol) was dissolved in dry
toluene under an atmosphere of argon. This solution was either cooled to
08C or heated to 20 or 508C, and the catalyst (0.0015–0.1 mol%; 15–
The initiation rates of the SIPr based complexes 8 and 9
are much slower than those of the related SIMes-based com-
plexes 5 and 6.
&
6
&
www.chemeurj.org
ꢁ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 0000, 00, 0 – 0
ÝÝ
These are not the final page numbers!

Fast Olefin Metathesis at Low Catalyst Loading
FULL PAPER
1000 ppm) from a stock solution in toluene (0.75 mmolLÀ1) was added
(for screenings carried out at 08C, the stock solution was precooled to
08C). The substrate concentration was defined as C(S)=n(S)/(V(S)+V-
1.8 Hz, 1H), 7.29–7.25 (m, 1H), 7.21–7.13 (m, 3H), 6.79 (dd, J=17.7,
11.0 Hz, 1H), 6.73 (tt, J=7.3, 1.0 Hz, 1H), 6.62–6.58 (m, 2H), 5.74 (dd,
J=17.7, 1.3 Hz, 1H), 5.22 (dd, J=11.0, 1.3 Hz, 1H), 3.21 ppm (s, 3H;
NCH3); 13C NMR (75 MHz, CDCl3): d=149.57, 146.41, 136.35, 133.23,
129.48, 129.05, 128.64, 126.66, 126.54, 117.38, 115.26, 113.58, 39.82 ppm;
HRMS (EI): m/z calcd for C15H15N: 209.1205 [M]+; found: 209.1177.
ACHTUNGTRENNUNG(toluene)+V(stock sol.)). For the determination of substrate conversion,
samples (50 mL, substrate conc. 0.1m or 10 mL, substrate conc. 0.5m) were
taken after the specified times under a stream of argon and injected into
GC vials containing a 25% (v/v) ethyl vinyl ether solution in toluene
(250 mL). The conversions were determined by GC. The products were
isolated by column chromatography (silica) using mixtures of pentane/di-
ethyl ether as the eluent.
2-Ethenyl-N-ethyl-N-phenylaniline:
2-Ethenyl-N-ethyl-N-phenylaniline
was obtained as a colorless liquid (197 mg, 81%). 1H NMR (300 MHz,
CDCl3): d=7.71–7.65 (m, 1H), 7.36–7.24 (m, 2H), 7.19–7.11 (m, 3H),
6.78 (dd, J=17.7, 11.0 Hz, 1H), 6.68 (tt, J=7.4, 1.0 Hz, 1H), 6.58–6.52
(m, 2H), 5.72 (dd, J=17.7, 1.3 Hz, 1H), 5.20 (dd, J=11.0, 1.3 Hz, 1H),
3.64 (q, J=7.1 Hz, 2H; NCH2CH3), 1.20 ppm (t, J=7.1 Hz, 3H;
NCH2CH3); 13C NMR (75 MHz, CDCl3): d=148.69, 144.42, 137.08,
133.40, 130.29, 129.36, 129.15, 126.83, 126.56, 116.90, 115.20, 113.32, 46.19,
12.60 ppm; HRMS (EI): m/z calcd for C16H17N: 223.1361 [M]+; found:
223.1341.
Synthesis of 2-[methyl
(phenyl)amino]benzaldehyde: {2-[Methyl
and {2-[ethyl(phenyl)amino]phenyl}lithium were generated in situ accord-
ACHTUNGTRENNUNG
A
ACHTUNGTRENNUNG
ACHTUNGTRENNUNG
ing to a modified procedure reported for [2-(NMe2)phenyl]lithium.[40]
Ph2NMe or Ph2NEt (5.46 mmol), TMEDA (122 mL, 0.82 mmol), and an-
hydrous cyclohexane (2.8 mL) were added to a dry Schlenk tube under a
nitrogen atmosphere to reach a 2m concentration of the respective ani-
lines. Next, a solution of nBuLi in n-hexane (2.5m, 2.18 mL, 5.46 mmol)
was added by syringe to the vigorously stirred mixture at RT. The solu-
tion was warmed to 608C and stirring was continued for 90 min (for N-
methyl-N-phenylaniline) or for 5 h (for N-ethyl-N-phenylaniline). Then
the mixture was allowed to cool to room temperature and the volatile
compounds were removed in vacuo. Dry tetrahydrofuran (5 mL) was
added under an atmosphere of nitrogen and the resulting orange solution
was cooled to À788C. Next, dry dimethylformamide (844 mL, 10.9 mmol)
was added dropwise with vigorous stirring. The now colorless solution
was allowed to warm to room temperature, stirred for 60 min, and then
poured into a half-saturated solution of ammonium chloride (200 mL).
The product was extracted with diethyl ether (3ꢄ100 mL). The organic
phases were combined, washed with brine, and dried over magnesium
sulfate. The solvent was removed in vacuo and the residue was purified
by column chromatography (cyclohexane/diethyl ether, 10:1 v/v).
Synthesis of [RuCl2ACHTNUGTRENN(UG IPr)AHCUTGNTRENN(NUG PCy3)ACHUTGTNRENNGU(Ind)]: [RuCl2AHTCNUGTREN(NUGN IPr)AHCTUGNTREN(NNUG PCy3)ACHUTNGTREN(NNUG Ind)] is a
known compound,[42] but was prepared according to a modified proce-
dure: A Schlenk flask containing 1,3-bis(2,6-diisopropylphenyl)-1H-imi-
dazol-3-ium chloride (485 mg, 1.14 mmol) was evacuated and back-filled
with argon three times. n-Hexane (40 mL) and a solution of sodium ta-
mylate in tetrahydrofuran ( 2.5m, 456 mL, 1.14 mmol) were added to the
flask under an atmosphere of argon. The mixture was allowed to stir at
RT for 90 min, then [RuCl2ACTHNUTRGNEN(UG PCy3)2ACHTUNGTERN(NUGN Ind)] (523 mg, 0.566 mmol) was
added as a solid. The mixture was stirred overnight at 508C. Next, the
volatiles were removed in vacuo and the residue was passed through a
short column of silica (cyclohexane/diethyl ether, 10:1 v/v). After evapo-
ration of the volatile compounds, n-hexane (5 mL) was added to the re-
maining solid, and the mixture was sonicated and kept in the fridge at
À358C for 2 h. After filtration, washing with cold methanol (5 mL), and
drying in vacuo, the product was obtained as
a bright-red powder
1
(362 mg, 62% yield). H NMR (300 MHz, CDCl3): d=8.85 (d, J=6.9 Hz,
1H), 7.67–7.59 (m, 2H), 7.56–7.38 (m, 4H), 7.34 (t, J=7.5 Hz, 2H), 7.25–
7.05 (m, 3H), 7.01 (s, 1H), 6.98–6.87 (m, 3H), 6.73 (d, J=7.3 Hz, 1H),
2-[Methyl
ACHTUNGTRENNUNG
(phenyl)amino]benzaldehyde:
2-[MethylACTHNGUTERNNU(G phenyl)amino]benz-
aldehyde[41] was obtained as a yellow oil (461 mg, 40% yield). 1H NMR
(300 MHz, CDCl3): d=10.16 (d, J=0.8 Hz, 1H; CHO), 7.96 (dd, J=7.8,
1.7 Hz, 1H), 7.65 (ddd, J=8.0, 7.3, 1.7 Hz, 1H), 7.36 (tt, J=7.5, 1.0 Hz,
1H), 7.30–7.18 (m, 3H), 6.84 (tt, J=7.5, 1.0 Hz; 1H), 6.78–6.72 (m, 2H),
3.38 ppm (s, 3H; NCH3); 13C NMR (75 MHz, CDCl3): d=191.35, 152.10,
150.19, 135.89, 132.89, 129.37, 129.05, 127.82, 126.11, 119.27, 115.30, 41.63,
29.82 ppm.
6.62 (d, J=7.6 Hz, 1H), 3.77 (sep, J=6.6 Hz, 1H; CH
J=6.6 Hz, 1H; CH(CH3)2), 3.06 (sep, J=6.6 Hz, 1H; CH
(sep, J=6.6 Hz, 1H; CH(CH3)2), 2.06 (q, J=11.1 Hz, 3H), 1.78–1.64 (m,
3H), 1.63–0.89 (m, 45H), 0.75 (d, J=6.7 Hz, 3H; CH(CH3)2), 0.61 ppm
(CH3)2); 31P NMR (202 MHz, CDCl3): d=
ACHTUNGTRENNUNG
G
ACHTUNGTRENNUNG
AHCTUNGTRENNUNG
AHCTUNGTRENNUNG
(d, J=6.6 Hz, 3H; CHACHTUNGTRENNUNG
24.46 ppm.
2-[Ethyl
N
2-[EthylACHTNGUTERNNU(G phenyl)amino]benz-
A
2ACHTUNGETNR(NUNG IPr)(py)CAHUTNGTREN(NGU Ind)]: A Schlenk tube containing [RuCl2ACHTUNGERTN(GNUN IPr)ACHTUNGTRENNUNG(PCy3)-
ACHTUNGTRENNUNGaldehyde was obtained as a yellow oil that crystallized upon cooling
AHCTUNGTRENNUNG
(357 mg, 29% yield). 1H NMR (500 MHz, CDCl3): d=10.14 (d, J=
0.8 Hz, 1H; CHO), 7.96 (dd, J=7.8, 1.7 Hz, 1H), 7.65 (ddd, J=8.0, 7.4,
1.7 Hz, 1H), 7.36 (tt, J=7.5, 1.0 Hz, 1H), 7.27 (dd, J=8.1, 0.9 Hz, 1H),
7.21–7.16 (m, 2H), 6.79 (tt, J=7.4, 1.0 Hz, 1H), 6.71–6.67 (m, 2H), 3.81
(q, J=7.1 Hz, 2H; NCH2CH3), 1.26 ppm (t, J=7.1 Hz, 3H; NCH2CH3);
13C NMR (126 MHz, CDCl3): d=191.63, 150.57, 149.39, 135.85, 133.74,
129.47, 129.26, 129.04, 126.34, 118.84, 115.28, 47.93, 12.83 ppm; HRMS
(EI): m/z calcd for C15H15NO: 225.1154 [M]+; found: 225.1144.
three times. Pyridine (2 mL) was added by syringe under an atmosphere
of argon. The resulting solution was stirred at room temperature for 1 h
and concentrated to half of its volume. Next, pentane (20 mL) was added
and the reaction was left stirring for 15 min. The resulting suspension was
then cooled to À408C. The precipitate was filtered off, washed with cold
pentane, and dried in vacuo to give the desired complex as a brownish
solid (251 mg, 88% yield). 1H NMR (500 MHz, CDCl3): d=7.98 (d, J=
7.0 Hz, 1H), 7.91 (dd, J=6.4, 1.3 Hz, 2H), 7.65 (dd, J=8.2, 1.0 Hz, 2H),
7.61–7.52 (m, 2H), 7.52–7.38 (m, 3H), 7.34 (t, J=7.7 Hz, 2H), 7.31 (br,
1H), 7.20 (td, J=7.5, 1.0 Hz, 1H), 7.08 (d, J=7.1 Hz, 1H), 6.99–6.83 (m,
5H), 6.74 (d, J=6.5 Hz, 1H), 6.67 (t, J=7.5 Hz, 1H), 5.95 (s, 1H; NCH),
Synthesis of 2-ethenyl-N-methyl-N-phenylaniline and 2-ethenyl-N-ethyl-
N-phenylaniline: A Schlenk flask containing methyltriphenylphosphoni-
um iodide (525 mg, 1.30 mmol) was evacuated and back-filled with argon
three times. Tetrahydrofuran (10 mL) was added by syringe and the
formed suspension was cooled to À108C. KOtBu (140 mg, 1.25 mmol)
was added in portions to the stirred mixture under a stream of argon,
and stirring was continued at À108C for 20 min. Next, a solution of 2-
4.24–4.10 (m, 1H; CH
(m, 1H; CH(CH3)2), 1.53 (br, 6H; CH
CH(CH3)2), 1.24–1.13 (m, 9H; CH(CH3)2), 0.68 (d, J=5.4 Hz, 3H; CH-
(CH3)2), 0.50 ppm (d, J=5.0 Hz, 3H; CH
(CH3)2); 13C NMR (126 MHz,
A
ACHTUGNTRENN(UNG CH3)2), 2.62–2.46
A
ACHTUNGTRENNUNG
A
ACHTUNGTRENNUNG
A
ACHTUNGTRENNUNG
CDCl3): d=300.85, 181.29, 152.91, 149.17, 148.99, 146.83, 146.69, 141.82,
141.29, 140.58, 139.61, 136.92, 136.54, 135.91, 135.05, 131.12, 130.57,
129.39, 129.27, 128.60, 127.92, 127.36, 126.64, 126.24, 125.79, 123.97,
123.71, 123.41, 117.18, 30.14, 29.28, 28.53, 27.59, 27.27, 27.16, 26.59, 25.78,
23.50, 23.02, 22.57, 20.84 ppm; MS (ESI): m/z calcd for C42H46N2Ru:
679.5 [MÀHÀ2ClÀPy]+; found: 679.3.
[methyl
ACHTUNGTRENNUNG(phenyl)amino]benzaldehyde (230 mg, 1.09 mmol) or 2-[ethyl-
ACHTUNGTRENNUNG(phenyl)amino]benzaldehyde (246 mg, 1.09 mmol) in tetrahydrofuran
(2 mL) was added. The mixture was allowed to warm to room tempera-
ture, stirred overnight, and was poured into water (200 mL). The product
was extracted with diethyl ether (3ꢄ100 mL). The organic phases were
combined, washed with brine, and dried over magnesium sulfate. The sol-
vent was removed in vacuo and the residue was purified by column chro-
matography (cyclohexane/0.5% NEt3).
General procedure for the synthesis of complexes 5–9: A flame-dried
Schlenk tube containing [RuCl2ACTHNUTRGENNU(G NHC)ACHTUNGTNER(NUGN Ind)(py)] (0.13 mmol) was evacu-
2-Ethenyl-N-methyl-N-phenylaniline: 2-Ethenyl-N-methyl-N-phenylani-
line was obtained as
(500 MHz, CDCl3): d=7.67 (dd, J=7.7, 1.7 Hz, 1H), 7.31 (td, J=7.5,
ated and back-filled with argon three times. Methylene chloride (2 mL),
2-ethenyl-N-methylaniline (32.0 mL, 0.16 mmol) or 2-ethenyl-N-ethylani-
line (36.2 mL, 0.16 mmol) and Amberlyst resin (dry form, 137 mg,
a
colorless liquid (184 mg, 80%). 1H NMR
Chem. Eur. J. 2012, 00, 0 – 0
ꢁ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
&
7
&
ÞÞ
These are not the final page numbers!

H. Plenio et al.
4.70 mmol H+ gÀ1) were added under an atmosphere of argon. The mix-
ture was stirred at 408C for 30 min (for NHC=SIMes) or 60 min (for
NHC=IPr, SIPr) and then filtered to separate the resin. The filtrate was
evaporated in vacuo and the remaining solid was purified as follows:
mixture was stirred for 120 min at 758C (at lower temperatures a mixture
of cis-5 and trans-5 was obtained). The mixture was concentrated in
vacuo and purified by column chromatography (cyclohexane/acetone, 7:1
v/v+0.5% NEt3). The obtained product was recrystallized from cyclo-
hexane to yield the desired complex as a green, microcrystalline solid
(52 mg, 30%). Rf =0.15 (cyclohexane/acetone, 7:1 v/v+0.5% NEt3).
Complex 5: The solid was dissolved in a minimal amount of methylene
chloride, then pentane (15 mL) was added under vigorous stirring and
the resulting suspension was cooled to À358C. The precipitated product
was collected by filtration, washed with cold pentane, and dried in vacuo
(61.5 mg, 70% yield). 1H NMR (300 MHz, CDCl3): d=17.00 (s, 1H;
RuCH), 7.59 (td, J=8.0, 1.5 Hz, 1H), 7.30 (d, J=8.0 Hz, 1H; o-ArH),
7.19 (td, J=7.5 Hz, 1.0 Hz, 1H; m-ArH), 7.13–6.88 (m, 8H; ArH), 6.80–
6.70 (m, 2H; ArH), 4.07 (s, 4H; NCH2CH2N), 2.91 (s, 3H; NCH3), 2.79–
1.70 ppm (m, 18H; o-ArCH3); 13C NMR (75 MHz, CDCl3): d=299.2,
210.3, 208.5, 155.8, 151.4, 146.5, 139.2, 138.9, 138.6, 129.5, 129.4, 129.3,
127.9, 127.4, 126.9, 123.5, 122.0, 121.1, 53.8, 51.7, 21.3, 19.5 ppm; elemen-
tal analysis calcd (%) for C35H39Cl2N3Ru: C 62.40, H 5.84, N 6.24; found:
C 62.53, H 5.95, N 5.96.
X-ray crystal structure analysis of complex trans-5: The crystal structure
was solved and refined by using the SHELX package.[43] A brief summary
of crystal data and structure refinement, and bond lengths, angles, and
coordinates can be found in the Supporting Information. CCDC-872791
(5) contains the supplementary crystallographic data for this paper.
These data can be obtained free of charge from The Cambridge Crystal-
lographic Data Centre via www.ccdc.cam.ac.uk/data_request/cif.
Acknowledgements
Complexes 6, 7, 8, and 9: The solid was purified by column chromatogra-
phy (ethyl acetate/cyclohexane, 1:5 v/v for 6; cyclohexane/acetone, 5:1
v/v for 7; ethyl acetate/cyclohexane, 1:4 v/v for 8; and pentane/diethyl
ether, 8:1 v/v for 9). The complexes were treated with pentane (5 mL)
and the resulting suspension was cooled to À358C. The products were
collected by filtration, washed with cold pentane, and dried in vacuo:
complex 6 (45 mg, 50% yield), complex 7 (67 mg, 68% yield), complex 8
(74 mg, 75% yield), and complex 9 (60 mg, 60% yield).
This work was supported by the DFG through DFG 178/13–1. We wish
to thank Vasco Thiel and Pavlo Kos for help with the determination of
initiation rates. The Umicore AG & Co. KG is thanked for a generous
donation of ruthenium complexes. Sabine Foro kindly solved and refined
the crystal structure of 5.
Complex 6: 1H NMR (300 MHz, CDCl3): d=16.93 (s, 1H; RuCH), 7.53
(t, J=7.4 Hz, 1H), 7.33 (d, J=7.9 Hz, 1H), 7.17 (t, J=7.3 Hz, 1H), 7.12–
7.01 (m, 5H), 7.01–6.88 (m, 5H), 4.05 (s, 4H; NCH2CH2N), 3.69–3.49 (m,
1H; NCHaHbCH3), 2.95–2.75 (m, 1H; NCHaHbCH3), 2.68–2.09 (m, 18H;
ArCH3), 0.55 ppm (t, J=6.8 Hz, 3H; NCH2CH3); 13C NMR (75 MHz,
CDCl3): d=300.60, 300.47, 210.53, 196.57, 157.83, 148.00, 143.93, 139.14
(br), 138.68 (br), 138.52, 129.56, 129.30, 128.68, 127.60, 127.02, 123.24,
121.31, 121.01, 56.77, 51.66, 21.31, 19.55 (br), 11.24 ppm; HRMS (EI):
m/z calcd for C36H40N3ClRu: 651.1950 [MÀHCl]+; found: 651.1909.
[1] a) G. C. Vougioukalakis, R. H. Grubbs, Chem. Rev. 2010, 110, 1746–
1787; b) C. Samojłowicz, M. Bieniek, K. Grela, Chem. Rev. 2009,
109, 3708–3742.
[2] a) E. F. van der Eide, W. E. Piers, Nat. Chem. 2010, 2, 571–576;
b) M. S. Sanford, J. A. Love, R. H. Grubbs, J. Am. Chem. Soc. 2001,
123, 6543–6554; c) T. Vorfalt, K.-J. Wannowius, V. Thiel, H. Plenio,
Chem. Eur. J. 2010, 16, 12312–12315; d) J. A. Love, M. S. Sanford,
M. W. Day, R. H. Grubbs, J. Am. Chem. Soc. 2003, 125, 10103–
10109; e) V. Thiel, M. Hendann, K. J. Wannowius, H. Plenio, J. Am.
Chem. Soc. 2012, 134, 1104–1114.
Complex 7: 1H NMR (500 MHz, CDCl3): d=16.86 (s, 1H; RuCH), 7.58
(t, J=7.7 Hz, 2H), 7.51 (td, J=7.9, 1.5 Hz, 1H), 7.38 (dd, J=7.8, 1.3 Hz,
2H), 7.34 (d, J=7.7 Hz, 2H), 7.23 (d, J=8.0 Hz, 1H), 7.15 (td, J=7.6,
1.0 Hz, 1H), 7.09–7.04 (m, 4H), 6.96–6.91 (m, 2H), 6.87–6.83 (m, 2H),
[3] a) M. Zaja, S. J. Connon, A. M. Dunne, M. Rivard, N. Buschmann, J.
Jiricek, S. Blechert, Tetrahedron 2003, 59, 6545–6558; b) E. Tzur, A.
´
Szadkowska, A. Ben-Asuly, A. Makal, I. Goldberg, K. Wozniak, K.
Grela, N. Lemcoff, Chem. Eur. J. 2010, 16, 8726–8737; c) M. Bien-
iek, A. Michrowska, D. L. Usanov, K. Grela, Chem. Eur. J. 2008, 14,
806–818; d) Ł. Gułajski, A. Michrowska, R. Bujok, K. Grela, J.
Mol. Catal. A 2006, 254, 118–123.
3.12–3.00 (m, 4H; CH
6H; CH(CH3)2), 1.11 (d, J=6.9 Hz, 6H; CH
6H; CH(CH3)2), 1.04 ppm (d, J=6.7 Hz, 6H; CHACTHUNGTRENNUNG
ACHTUNGTRENNUNG
A
ACHTUNGTRENNUNG
T
(126 MHz, CDCl3): d=288.97. 288.93, 177.81, 155.43, 150.81, 148.39,
148.24, 148.00, 136.41, 130.31, 128.84, 127.40, 126.19, 125.80, 124.01,
123.88, 123.44, 121.20, 120.77, 53.15, 28.87, 28.77, 26.67, 26.41, 23.17,
23.00 ppm; HRMS (EI): m/z calcd for C41H49N3Cl2Ru: 755.2338 [M]+;
found: 755.2291.
[4] a) S. Monsaert, A. L. Vila, R. Drozdzak, P. V. D. Voort, F. Verpoort,
Chem. Soc. Rev. 2009, 38, 3360–3372; b) C. E. Diesendruck, O. Ilia-
shevsky, A. Ben-Asuly, I. Goldberg, N. G. Lemcoff, Macromol.
Symp. 2010, 293, 33–38.
[5] a) T. Vorfalt, S. Leuthꢀußer, H. Plenio, Angew. Chem. 2009, 121,
5293–5296; Angew. Chem. Int. Ed. 2009, 48, 5191–5194; b) V.
Sashuk, L. H. Peeck, H. Plenio, Chem. Eur. J. 2010, 16, 3983–3993;
c) L. H. Peeck, H. Plenio, Organometallics 2010, 29, 2761–2768.
[6] A. Michrowska, R. Bujok, S. Harutyunyan, V. Sashuk, G. Dolgonos,
K. Grela, J. Am. Chem. Soc. 2004, 126, 9318–9325.
1
Complex 8: H NMR (300 MHz, CDCl3): d=16.74 (s, 1H; RuCH), 7.58–
7.46 (m, 3H), 7.40–7.28 (m, 4H), 7.22–7.03 (m, 4H), 6.98–6.77 (m, 4H),
4.18–4.00 (m, 4H; NCH2CH2N), 3.69–3.51 (m, 4H; CH
3H; NCH3), 1.23 (d, J=6.7 Hz, 18H; CH(CH3)2), 1.05 ppm (d, J=
6.2 Hz, 6H; CH
(CH3)2); 13C NMR (126 MHz, CDCl3): d=291.20, 212.03,
154.85, 150.86, 149.29, 148.85, 148.62, 129.56, 128.61, 128.04, 127.30,
125.97, 124.59, 124.31 (br), 123.31, 121.27, 121.17, 54.59, 52.53, 28.70,
26.62, 23.95 ppm; HRMS (EI): m/z calcd for C41H51N3Cl2Ru: 757.2495
[M]+; found: 757.2537.
ACHTUGNTREN(UNNG CH3)2), 2.94 (s,
AHCTUNGTRENNUNG
ACHTUNGTRENNUNG
[7] T.-L. Choi, R. H. Grubbs, Angew. Chem. 2003, 115, 1785–1788;
Angew. Chem. Int. Ed. 2003, 42, 1743–1746.
[8] a) P. E. Romero, W. E. Piers, R. McDonald, Angew. Chem. 2004,
116, 6287–6291; Angew. Chem. Int. Ed. 2004, 43, 6161–6165;
b) P. E. Romero, W. E. Piers, J. Am. Chem. Soc. 2007, 129, 1698–
1704; c) E. M. Leitao, E. F. van der Eide, P. E. Romero, E. P.
Warren, R. McDonald, J. Am. Chem. Soc. 2010, 132, 2784–2794.
[9] a) A. Leitgeb, J. Wappel, C. Slugovc, Polymer 2010, 51, 2927–2946;
b) C. W. Bielawski, R. H. Grubbs, Angew. Chem. 2000, 112, 3025–
3028; Angew. Chem. Int. Ed. 2000, 39, 2903–2906; c) C. W. Bielaw-
ski, R. H. Grubbs, Prog. Polym. Sci. 2007, 32, 1–29.
[10] a) J. A. Love, J. P. Morgan, T. M. Trnka, R. H. Grubbs, Angew.
Chem. 2002, 114, 4207–4209; Angew. Chem. Int. Ed. 2002, 41, 4035–
4037; b) T. Ritter, A. Hejl, A. G. Wenzel, T. W. Funk, R. H. Grubbs,
Organometallics 2006, 25, 5740–5745.
1
Complex 9: H NMR (300 MHz, CDCl3): d=16.69 (s, 1H; RuCH), 7.62–
7.28 (m, 6H), 7.25 (d, J=7.7 Hz, 2H), 7.14–7.00 (m, 5H), 6.96–6.88 (m,
1H), 6.83 (dd, J=7.6, 1.3 Hz, 1H), 4.27–3.14 (br, 4H; NCH2CH2N+dq,
J=13.8, 6.9 Hz, 1H; NCHaHbCH3 +m, 4H; CH
ACHTUNGTRENNUNG
13.8, 6.9 Hz, 1H; NCHaHbCH3), 1.93–0.56 (br, 24H; CHAHCTUNGTRENNUNG
0.43 ppm (t, J=7.0 Hz, 3H; NCHaHbCH3); 13C NMR (75 MHz, CDCl3):
d=293.24, 293.15, 212.14, 156.93, 148.95 (br), 147.52, 144.76, 129.54,
127.99, 127.65, 127.58, 126.81, 124.62 (br), 123.20, 121.51, 120.79, 56.24,
54.48 (br), 28.72, 26.82 (br), 23.74 (br), 10.97, 8.41 ppm; HRMS (EI): m/z
calcd for C42H53N3Cl2Ru: 771.2651 [M]+; found: 771.2588.
Synthesis of complex 5 in the absence of protic resin: [RuCl
(Ind)(Py)] (200 mg, 0.27 mmol) was added to a solution of 2-(N-methyl-
N-phenyl)aminostyrene (70 mg, 0.32 mmol) in toluene (2.5 mL) and the
2ACHTUNGTRNE(NUNG SIMes)-
G
[11] S. H. Hong, A. G. Wenzel, T. T. Salguero, M. W. Day, R. H. Grubbs,
J. Am. Chem. Soc. 2007, 129, 7961–7968.
&
8
&
www.chemeurj.org
ꢁ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 0000, 00, 0 – 0
ÝÝ
These are not the final page numbers!

Fast Olefin Metathesis at Low Catalyst Loading
FULL PAPER
[12] a) C. A. Urbina-Blanco, S. Manzini, J. P. Gomes, A. Doppiu, S. P.
Nolan, Chem. Commun. 2011, 47, 5022–5024; b) J. Broggi, C.
Urbina-Blanco, H. Clavier, A. Leitgeb, C. Slugovc, A. Slawin, S.
Nolan, Chem. Eur. J. 2010, 16, 9215–9225.
[26] S. Leuthꢀußer, V. Schmidts, C. M. Thiele, H. Plenio, Chem. Eur. J.
2008, 14, 5465–5481.
[27] M. Gatti, L. Vieille-Petit, X. Luan, R. Mariz, E. Drinkel, A. Linden,
R. Dorta, J. Am. Chem. Soc. 2009, 131, 9498–9499.
[13] a) C. E. Diesendruck, E. Tzur, N. G. Lemcoff, Eur. J. Inorg. Chem.
2009, 4185–4203; b) S. B. Garber, J. S. Kingsbury, B. L. Gray, A. H.
Hoveyda, J. Am. Chem. Soc. 2000, 122, 8168–8179.
[14] S. Randl, S. Gessler, H. Wakamatsu, S. Blechert, Synlett 2001, 430–
432.
[28] S. Monfette, D. E. Fogg, Chem. Rev. 2009, 109, 3783–3816.
[29] C. A. Urbina-Blanco, A. Leitgeb, C. Slugovc, X. Bantreil, H. Cla-
vier, A. M. Slawin, S. P. Nolan, Chem. Eur. J. 2011, 17, 5045–5053.
[30] K. M. Kuhn, J.-B. Bourg, C. K. Chung, S. C. Virgil, R. H. Grubbs, J.
Am. Chem. Soc. 2009, 131, 5313–5320.
[15] C. Slugovc, D. Burtscher, F. Stelzer, K. Mereiter, Organometallics
2005, 24, 2255–2258.
[31] K. M. Kuhn, T. M. Champagne, S. H. Hong, W.-H. Wei, A. Nickel,
C. W. Lee, S. C. Virgil, R. H. Grubbs, R. L. Pederson, Org. Lett.
2010, 12, 984–987.
[32] 100 ppm is the lower limit of water content; in fact, 100 ppm of
water were added to carefully dried toluene.
[16] a) M. Barbasiewicz, A. Szadkowska, R. Bujok, K. Grela, Organome-
˙
tallics 2006, 25, 3599–3604; b) K. Zukowska, A. Szadkowska, A. E.
´
Pazio, K. Wozniak, K. Grela, Organometallics 2012, 31, 462–469.
[17] a) A. Szadkowska, X. Gstrein, D. Burtscher, K. Jarzembska, K.
[33] K. M. Kadish, X. Mu, J. E. Anderson, Pure Appl. Chem. 1989, 61,
1823–1828.
´
Wozniak, C. Slugovc, K. Grela, Organometallics 2010, 29, 117–124;
b) X. Gstrein, D. Burtscher, A. Szadkowska, M. Barbasiewicz, F.
Stelzer, K. Grela, C. Slugovc, J. Polym. Sci. Part A 2007, 45, 3494–
3500; c) Y. Vidavsky, N. G. Lemcoff, Beilstein J. Org. Chem. 2010, 6,
1106–1119.
[34] S. M. Hansen, F. Rominger, M. Metz, P. Hofmann, Chem. Eur. J.
1999, 5, 557–566.
[35] Determined under identical reaction conditions with [BuVE]=0.1m.
[36] F. C. Courchay, J. C. Sworen, K. B. Wagener, Macromolecules 2003,
36, 8231–8239.
[37] T. Vorfalt, K. J. Wannowius, H. Plenio, Angew. Chem. 2010, 122,
5665–5668; Angew. Chem. Int. Ed. 2010, 49, 5533–5536.
[38] A. B. Pangborn, M. A. Giardello, R. H. Grubbs, R. K. Rosen, F. J.
Timmers, Organometallics 1996, 15, 1518–1520.
[39] G. R. Fulmer, A. J. M. Miller, N. H. Sherden, H. E. Gottlieb, A. Nu-
delman, B. M. Stoltz, J. E. Bercaw, K. I. Goldberg, Organometallics
2010, 29, 2176–2179.
[18] A. Ben-Asuly, E. Tzur, C. E. Diesendruck, M. Sigalov, I. Goldberg,
N. G. Lemcoff, Organometallics 2008, 27, 811–813.
[19] a) C. E. Diesendruck, E. Tzur, A. Ben-Asuly, I. Goldberg, B. F.
Straub, N. G. Lemcoff, Inorg. Chem. 2009, 48, 10819–10825; b) A.
Poater, F. Ragone, A. Correa, A. Szadkowska, M. Barbasiewicz, K.
Grela, L. Cavallo, Chem. Eur. J. 2010, 16, 14354–14364.
[20] D. Benitez, W. A. Goddard, J. Am. Chem. Soc. 2005, 127, 12218–
12219.
[21] A. J. Hoefnagel, M. A. Hoefnagel, B. M. Wepster, J. Org. Chem.
1981, 46, 4209–4211.
[40] D. W. Slocum, T. L. Reece, R. D. Sandlin, T. K. Reinscheld, P. E.
Whitley, Tetrahedron Lett. 2009, 50, 1593–1595.
[22] V. Snieckus, Chem. Rev. 1990, 90, 879–933.
[41] W. Lin, I. Sapountzis, P. Knochel, Angew. Chem. 2005, 117, 4330–
4333; Angew. Chem. Int. Ed. 2005, 44, 4258–4261.
[42] L. Jafarpour, H.-J. Schanz, E. D. Stevens, S. P. Nolan, Organometal-
lics 1999, 18, 5416–5419.
[23] S. F. Monsaert, F. W. C. Verpoort, WO/2011/091980, 2011.
[24] a) T. E. Schmid, X. Bantreil, C. A. Citadelle, A. M. Slawin, C. S.
Cazin, Chem. Commun. 2011, 47, 7060–7062; b) A. Ben-Asuly, A.
Aharoni, C. E. Diesendruck, Y. Vidavsky, I. Goldberg, B. F. Straub,
N. G. Lemcoff, Organometallics 2009, 28, 4652–4655.
[43] G. M. Sheldrick, Acta Crystallogr. Sect. A 2008, 64, 112–122.
[25] a) M. Sꢂßner, H. Plenio, Chem. Commun. 2005, 5417–5419; b) M.
Sꢂßner, H. Plenio, Angew. Chem. 2005, 117, 7045–7048; Angew.
Chem. Int. Ed. 2005, 44, 6885–6888.
Received: March 24, 2012
Revised: June 22, 2012
Published online: && &&, 0000
Chem. Eur. J. 2012, 00, 0 – 0
ꢁ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
&
9
&
ÞÞ
These are not the final page numbers!

H. Plenio et al.
Metathesis
L. H. Peeck, R. D. Savka,
H. Plenio* ..................... &&&& — &&&&
Fast Olefin Metathesis at Low Catalyst
Loading
The tortoise and the hare: The use of
diphenylalkylamino-based instead of
phenyldialkylamino-based styrenes
(see figure) leads to rapidly initiating
precatalysts that enable very fast ring-
closing metathesis reactions with turn-
over numbers of up to 58000 and turn-
over frequencies of up to 232000 hÀ1.
&
10
&
www.chemeurj.org
ꢁ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 0000, 00, 0 – 0
ÝÝ
These are not the final page numbers!