Isotopic probes for ruthenium-catalyzed olefin metathesis

Article abstract of DOI:10.1039/c4cy01118j

Routes are described to previously unreported first- and second-generation Grubbs metathesis catalysts bearing a ¹³C label at the key benzylidene or methylidene site. Improved syntheses of the ²H-labelled isotopologues are also presented. Labelling at the alkylidene position is important because it provides unique, direct information about changes at the active site of the catalyst, and the fate of the [Ru]CHR ligand during catalyst deactivation. A case study demonstrates the power of ¹³C-labelling in tracking the methylidene moiety in amine-induced decomposition of the second-generation complex RuCl₂(PCy₃)(H₂IMes)(¹³CH₂). Also reported is the solubility of ethylene in C₆D₆ and CD₂Cl₂, measured at 296 ± 1.5 K and 101.0 ± 0.8 kPa. This journal is

Full text of DOI:10.1039/c4cy01118j

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Isotopic Probes for Ruthenium-Catalyzed Olefin
Metathesis
Cite this: DOI: 10.1039/x0xx00000x
Justin A. M. Lummiss, Adrian G. G. Botti, Deryn E. Fogg*
Received 00th January 2012,
Accepted 00th January 2012
Routes are described to previously unreported first- and second-generation Grubbs metathesis
1
3
catalysts bearing a C label at the key benzylidene or methylidene site. Improved syntheses of
2
DOI: 10.1039/x0xx00000x
the H-labelled isotopologues are also presented. Labelling at the alkylidene position is important
because it provides unique, direct information about changes at the active site of the catalyst,
and the fate of the [Ru]=CHR ligand during catalyst deactivation. A case study demonstrates the
www.rsc.org/
1
3
power of C-labelling in tracking the methylidene moiety in amine-induced decomposition of the
1
3
2 3 2 2
second-generation complex RuCl (PCy )(H IMes)(= CH ). Also reported is the solubility of
ethylene in C
6
D
6
and CD
2
Cl
2
, measured at 296 ±1.5K and 101.0 ±0.8kPa.
Introduction
promiscuous metals such as ruthenium). Also significant are the
higher receptivity and slower T2 relaxation relative to
deuterium, which significantly improve resolution, while
drastically reducing acquisition time.
1
ꢀ4
Olefin metathesis is now a core tool in organic synthesis.
20
With industrial applications of molecular metathesis catalysts
now emerging, improved understanding of their deactivation
1
pathways is becoming increasingly urgent, particularly for the
dominant ruthenium catalysts. Isotopic labelling has long been
an important tool in organometallic chemistry, enabling direct
insight into the rates and fates of bondꢀforming and bondꢀ
breaking reactions via NMR and mass spectrometric (MS)
5
ꢀ7
analysis. Within the context of olefin metathesis, experiments
with labelled olefins afforded key evidence for the Chauvin
8
ꢀ10
mechanism,
for the chainꢀcarrying role of metal alkylidene
1
3
1
1
Figure 1. Isotopically labelled targets synthesized in this work. (a) C-tagged (*)
2
and (b) H-tagged (D) first- and second-generation Grubbs catalysts, and their
intermediates, and for the relative competence of ringꢀ
1
2,13
14,15
closing
or crossꢀmetathesis
relative to degenerate methylidene resting states. (H IMes = N,N’-bis(mesityl)imidazolin-2-ylidene).
2
exchange. Deuteriumꢀlabelled
ligands have also been used
N
ꢀheterocyclic carbene (NHC)
1
6,17
13
to probe CꢀH activation during
Marciniec and coꢀworkers recently reported successful Cꢀ
catalyst deactivation and to track the release and return of solidꢀ labelling of the Hoveyda catalyst at the benzylidene carbon, and
1
8
supported metathesis catalysts.
use of the labelled complex to confirm catalyst anchoring on
2
1
The present work was motivated by the potential offered by silica supports. In subsequent studies, this compound was
isotopic labelling for insight into the operation and decay of invaluable in affording unequivocal evidence for reꢀuptake of
the Grubbs catalysts, which remain among the most important the styrenyl ether ligand during metathesis. Similarly labelled
catalyst systems used in olefin metathesis.
particularly interested in accessing derivatives bearing a C tag the [Ru]= CHOCH Ph unit into a ruthenium hydridocarbonyl
at the key Ru=CHR site (Figure 1a). Labelling at the alkylidene moiety. To date, however, Grubbs catalysts bearing an
1
9
2
2
1,2
We were Fischer carbene complexes earlier revealed transformation of
1
3
13
2
2
3
position is of keen interest because this reports directly on isotopic label at the alkylidene site are limited to deuterated
1
3
24ꢀ27
13
changes at the active site. The diagnostic potency of the
C
derivatives.
Here we report routes to the Cꢀlabelled
2
isotope, relative to the more routinely incorporated isotope H, analogues, for both firstꢀ and secondꢀgeneration Grubbs
is a function of its orderꢀofꢀmagnitude expansion of the NMR catalysts (Figure 1a). In the course of optimizing these
2
chemical shift window, as well as elimination of potential syntheses with less costly Hꢀlabelled reagents, we improved
scrambling pathways (a particular issue for catalytically
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2
4ꢀ26
D
D
routes to the known
deuterated isotopologues GI
,
GIm
,
off in the glovebox, and the styrene was extracted with acetone.
D
and GIIm, and developed the first route to the deuterated This treatment gave clean, straightforward access to the
secondꢀgeneration Grubbs catalyst, GII (Figure 1b).
D
13
previously unreported Cꢀlabelled *GI in 85% yield, with an
isotopic purity of 97%.
Results and discussion
First-generation catalysts via labelled styrenes
Crossꢀmetathesis of GI with isotopicallyꢀlabelled styrenes
offers a convenient means of installing a labelled benzylidene
moiety on the firstꢀgeneration Grubbs catalyst, as demonstrated
2
5
D
by Dinger and Mol in synthesis of GI. A challenge,
however, lies in the selectivity for the labelled benzylidene
complex – that is, the kinetic product – relative to the unwanted
thermodynamic product, methylidene GIm (Scheme 1). Clean
interception of labelled GI is especially important because the
similar solubilities of these species hampers their separation.
Ph
Ph
Figure 2. Formation and stability of *GI via the method of Scheme 1 (first pass).
1
Inset: Benzylidene region of the H NMR spectrum for isolated *GI (300 MHz,
5
*
Cl
PCy3
Cl
Ph
Cl
PCy
Cl
3
Ru
Ru
C
commercial starting GI. Upper trace: *GI with 2.2% residual GI
6
D
6
), illustrating the ease with which crossover can be measured. Lower trace:
.
Cy3P
Cy
3
P
GI
*GI
D
RT, C H , 45 min
2 cycles; acetone wash
6
6
Essentially identical yields and enrichment were obtained in
the corresponding synthesis of GI via crossꢀmetathesis of GI
5
D
85% isolated yield
Ph
with styreneꢀαꢀD (400 mg scale). Dinger and Mol previously
prepared this complex in 62% yield and 95% isotopic
D
Ph
Cl
Cy3P
PCy3
Cl
Cl
PCy3
Cl
enrichment, via a similar sequence involving reaction with 2 x
Ru
Ru
Cy3P
25,29
DGI
10 equiv styrene in CH Cl .
2
2
A key contributor to the nearly
GIm
(
unwanted)
25% increase in isolated yield in the present work (despite the
lower proportion of the styrene reagent) is the improved
workup procedure. Use of acetone to extract residual styrene,
Scheme 1. Kinetic vs. thermodynamic selectivity in synthesis of labelled GI
.
We find that the timescale for degenerate exchange is much rather than pentane, takes advantage of the sparing solubility of
1
3
2
30
more readily established for Cꢀlabelled *GI than Hꢀlabelled GI in acetone. The level of enrichment attainable for these
D
1
GI. The doublet multiplicity of the H NMR signal for the benzylidene targets is limited by (1) the isotopic purity of the
benzylidene proton in *GI (Figure 2: δH 20.61 ppm; JCH
1
=
styrene reagent; (2) the stoichiometry of the reaction: that is,
1
46.6 Hz) provides
a
unique, convenient means of the equilibrium ratio of unlabelled vs. labelled styrene; and (3)
simultaneously quantifying both formation of *GI, and the number of reaction cycles, coupled with the efficiency with
conversion of GI. This is especially useful in conjunction with which the nonꢀlabelled styrene can be extracted.
use of an internal standard to detect net loss of [Ru]=C
species (i.e. decomposition to nonꢀalkylidene products). In the
HR
Labelled second-generation catalysts via ligand exchange
corresponding reactions with H C=CDPh, in contrast, the In sharp contrast, synthesis of the labelled secondꢀgeneration
2
starting material and product cannot be simultaneously benzylidenes via crossꢀmetathesis of GII is unsatisfactory in
observed, and exchange is thus difficult to distinguish from both yield and purity. The nonꢀlability of the phosphine ligand
decomposition.
To favour interception of the kinetic benzylidene product, accelerate reaction by heating result in coꢀformation of GIIm
we carried out the exchange reaction at RT (glovebox; ca. 27 As with the firstꢀgeneration complexes, the benzylidene and
C). We chose benzene in preference to dichloromethane as the methylidene complexes exhibit very similar solubilities, and are
reaction medium, given the accelerating effect of aromatic not readily separated.
in GII renders exchange very slow (days) at RT, but efforts to
.
°
2
8
solvents on metathesis. On NMR scale, equilibration of GI
More attractive as an entry point is therefore ligand
1
3
with a fiveꢀfold excess of styreneꢀ
α-
C was complete within exchange of labelled GI with free H IMes (Scheme 2). We
2
4
5 min at RT. Neither GIm nor decomposition was evident previously described the efficiency of this route to GII
,
over 3 h (Figure 2), and the proportion of *GI present at especially where combined with use of an ionꢀexchange resin to
3
1
equilibrium was 83%, as expected from the 1:5 stoichiometry remove the phosphine coꢀproduct and excess NHC.
D
of unlabelled vs. labelled styrene. Reactions on preparative Accordingly, treating *GI and GI with free H IMes for 1 h in
2
scale (200 mg GI) involved two 45ꢀminute cycles of reaction THF at RT, then stirring with Amberlyst resin, enabled access
1
3
D
with styreneꢀα- C. After each pass, the solvent was stripped to clean *GII and GII in nearly 90% isolated yield (97%
2
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D
isotopic purity for *GII; 96% for GII). It should be noted, saturating the solution in ethylene by five sequential freezeꢀ
however, that the THF must be scrupulously dry to prevent pumpꢀthaw cycles. An equilibrium concentration of 89 mM
hydrolysis of the free H IMes, which adversely affects the was found in C D , nearly double that in CD Cl (54 mM), for
2
6
6
2
2
reaction stoichiometry, compromising product yields and/or experiments in triplicate, using independentlyꢀprepared stock
3
6
purity.
solutions.
1
Figure 3. Measuring the solubility of ethylene in organic solvents by H NMR
Scheme 2. Successful ligand-exchange route to labelled second-generation
benzylidene complexes.
analysis (300.1 MHz). Left: representative spectrum. Signal labelled (*) is due to
2 4 6 5
C H , (×) denotes TMB; C HD signal not labelled. Right: tabulated data.
Conditions: 296 ±1.5 K, 101.0 ±0.8 kPa, 5 x freeze-pump-thaw cycles prior to
equilibrating under ethylene; experiments in triplicate.
Methylidene complexes: Additional challenges
Synthesis of the labelled methylidene complexes is much more
Notably, we also find that the highly sensitive methylidene
demanding, owing to the instability of these species. A halfꢀlife complex GIm is much longerꢀlived in benzene. These
3
2
of 6 h has been reported for GIIm at 55 °C in C D , and this experiments were likewise carried out by integrating the signal
6
6
3
3
figure drops to just 40 min for GIm
.
(For added data of interest (in this case, the methylidene singlet) against that for
concerning the lifetimes of these species, see below). The firstꢀ TMB. The halfꢀlife in CD
Cl
or CDCl
D (Figure 4). Unexpectedly, THF is
6
was ca. 2.4 h at 35 °C,
2
2
3
generation methylidene complex GIm is nevertheless as compared to 6.6 h in C
6
accessible in high yields and high purity via ethenolysis at even more deleterious, with the halfꢀlife in this solvent
3
4,35
RT.
RuH (N ) (PCy ) with CH Cl2 or CD Cl2 is attractive for product stability, therefore, benzene is preferred for the
An alternative route utilizing reaction of dropping to ca. 1 h. On the basis of both ethylene solubility and
2
2 2
3 2
2
2
2
6
circumventing the need for a gaseous labelled reagent. In situ synthesis of GIm
yields of GIm or GIm were limited to ca. 65%, however, and
.
D
the product was contaminated with a RuHCl(H )(PCy ) byꢀ
2
3 2
8
0
6
.6 a
product. Also examined in the present study was a potential
route involving crossꢀmetathesis with ꢀlabelled styrenes. As
β
this also proved less satisfactory (resulting in <60% *GIIm, as
a mixture with GII), it is briefly described in a closing section.
Our principal focus in this section is on adapting the
successful ethenolysis route to permit efficient use of labelled
ethylene gas. Sparging to maintain high ethylene concentrations
is economically prohibitive, given the high prices of these
2.5
2.3
1.1
C6D6
CD Cl2 CDCl3 THF-d8
2
reagents ($550 or $1400 CAD, respectively, for 1 L of C D or Figure 4. Impact of solvent on the lifetime of GIm (18 mM) at 35 °C. Assessed by
2
4
1
3
1
a
H NMR analysis; integration against TMB as internal standard. Cf. reported
C H gas; SigmaꢀAldrich). Instead, we carried out reactions in
sealed vessels, and optimized procedures with deuterated
ethylene, before proceeding to the more expensive Cꢀlabelled
gas. As a first step, however, we measured the solubility of
dissolved ethylene (a critical parameter in these sealedꢀtube Following these probe experiments, synthesis of GIm was
experiments) in the proposed reaction solvents, using nonꢀ undertaken on preparative scale (400 mg GI). For details of
2
4
3
3
6 6
half-life at 55 °C in C D : 40 min.
1
3
First-generation methylidenes via labelled ethylene
D
labelled ethylene.
practical measures aimed at maximizing the efficiency of gas
delivery from the lecture bottles, readers are referred to the
supporting information. Crossꢀmetathesis with C D in benzene
2 4
Impact of solvent on ethylene solubility and methylidene lifetime
The published data for the solubility of ethylene vary widely. was conducted in two 45ꢀminute cycles; Scheme 3. After each
The IUPACꢀNIST Solubility Database cites no study as pass, the solvent was stripped off on the Schlenk line, and the
authoritative, although it excludes several values on the basis of styrene byproduct was extracted with pentane. (Pentane was
3
6
unreliability. Given the scatter in the data reported, we used in preference to acetone because GIm – unlike GI – is
measured the solubility of ethylene in CD Cl and C D , at 23 very sparingly soluble in pentane: this is convenient as pentane
2
2
6
1
6
±
1.5 °C. In these experiments, we integrated the H NMR residues are more readily removed under vacuum). The first
D
singlet for dissolved C H against that for
a
known cycle of treatment afforded GIm in 85% isolated yield, with
2
4
concentration of trimethoxybenzene (TMB; Figure 3), after 5% GI remaining. A second treatment enabled isolation of
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GIm in 75% total yield (>99% enrichment; no GI detected).
1
3
The corresponding reaction with C H afforded *GIm in 71%
2
4
yield (99.5% enrichment). These isolated yields are well below
the 85% level that we were able to attain for nonꢀlabelled
3
4
GIm
. The difference is due in part to the smaller scale for the
labelling reactions (400 mg, vs. 1 g). Parallel experiments with
C H in sealed systems, however, also indicate consistently
2
4
lower yields relative to the continuouslyꢀsparged reactions.
D
Scheme 4. Synthesis of *GIIm and GIIm by ligand exchange.
Ph
*
Limitations in ethylene-free access to labelled methylidenes
Cl
PCy3
Cl
5 *
*
Cl
PCy
Cl
3
Ru
Ru
Cy3P
Cy P
3
Given the cost and technical demands involved in handling the
labelled gases, we also explored the potential accessibility of
GI
*GIm
D
D
D
D
RT, C H , 45 min
6
6
+
*
the labelled methylidenes by crossꢀmetathesis with styreneꢀβꢀ
2
cycles; pentane wash
ca. 75% isolated yield
Ph
5
1
3
D
C (Scheme 5). Here we hoped to exploit the thermodynamic
preference for the methylidene species in metathesis of terminal
olefins; see above. This approach failed for the synthesis of
GIm, however. Exchange of GI with 5 equiv of styrene at RT
was far too slow: NMRꢀscale reactions proceeded to only 13%
GIm after 7 days, with 27% net loss of alkylidene (as judged
by integration against internal standard). Increasing the
temperature to 40 °C caused catalyst degradation to dominate
over the desired metathesis exchange: after 28 h at 40°C, just
D
Cl
Cy3P
PCy3
D
D
Ru
+
Cl
DGIm
Ph
D
Scheme 3. Synthesis of *GIm and GIm by ethenolysis.
Second-generation methylidenes via ligand exchange
Ethenolysis is impractical as a route to the secondꢀgeneration 4% GIm was observed, accompanied by 43% decomposition.
1
3
methylidene complexes. Competing decomposition has been The corresponding reaction of GII with
β
ꢀ C labelled styrene
*GIIm after 24 h.
More efficient is the “freeꢀcarbene” Longer reaction increased conversion of GII, but at the cost of
shown to limit isolated yields to 27ꢀ36% for GIIm or its Dꢀ at 40 °C resulted in a 60:40 mixture of GII
:
2
4,37
labelled isotopologue.
3
4
route developed by our group, in which GIm is treated with competing decomposition of *GIIm
.
H IMes at 60 °C (cf. the corresponding synthesis of the
2
benzylidene complex GII described above). The challenge in
using this methodology to prepare the methylidene complexes
lies in their thermal instability (see Figure 4 and discussion
D
above). Nevertheless, GIIm could be obtained by heating
D
GIm with free H IMes for 45 min (Scheme 4). Traces of the
2
decomposition byproduct [MePCy ]Cl were extracted with
degassed water (a technique used successfully to refine workup
for the nonꢀlabelled target, which was obtained in 80% yield for
3
1
3
Scheme 5. Potential installation of C-labelled methylidenes by cross-metathesis
1
3
with β- C-labelled styrene.
reactions on 700 mg scale; see SI). Free PCy and decomposed
Ru were removed by successive extraction with acetone and
cold pentane. The partial solubility of the product in these wash
3
Case study: Amine-induced deactivation of GIIm
The ease with which these isotopically labelled complexes
solvents limited isolated yields to 60% for reactions on ca. 200 enable tracking of the methylidene moiety during catalyst
mg scale: the >99% enrichment of the precursor was deactivation was tested in a study of the amineꢀinduced
maintained. Purification with Amberlyst in THF was not decomposition of GIIm. Amines have long been regarded as
3
8
feasible for these methylidene complexes, in contrast to the detrimental to ruthenium metathesis catalysts, and have been
1
a
benzylidene analogues discussed above, owing to extensive flagged as problematic in reports from pharma. We recently
decomposition.
demonstrated that during catalysis, sterically accessible primary
Use of the same procedure, but omitting the acetone wash, and secondary amines decompose GII via
enabled isolation of *GIIm in 68% yield (160 mg scale), mechanism, involving (1) replacement of the PCy
without any deleterious effect on purity.
a
twoꢀstep
ligand by
3
amine, and (2) abstraction of the methylidene ligand by the
3
9
released PCy3. Given the extreme vulnerability exhibited by
GIIm during catalysis, however, our original study focused on
equimolar proportions of amine relative to catalyst.
Here we wished to examine the susceptibility of the
methylidene ligand to direct attack by amine. We therefore
n
selected H N Bu, as the least bulky (i.e. most aggressive) of the
2
4
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1
amines originally tested, and added it in tenfold excess relative identified by H NMR analysis of the nonꢀlabelled GIIm
1
to *GIIm. While H NMR analysis of nonꢀlabelled GIIm reaction, as their methyl resonances are obscured by
suffices to reveal loss of the methylidene signal, which is overlapping signals (see inverted spectrum).
1
3
complete within 10 min at RT, the C label in *GIIm proved
These results indicate a surprising bias toward nucleophilic
invaluable in tracking the fate of the methylidene moiety. Thus, attack by phosphine, relative to amine, even where amine is
1
3
1
C{ H} NMR analysis at 10 min revealed two dominant present in tenfold excess. While the origin of this effect is under
species in a ca. 70:30 ratio. These are [*MePCy ]Cl, which further study, the data above illustrate the power of these
3
1
13
appears as a doublet at 1.5 ppm ( JCP = 47.9 Hz), and isotopically labelled complexes, and particularly Cꢀlabelling
NH Bu*Me, a singlet at 36.8 ppm (Figure 5, top).
n
at the [Ru]=CHR center, in enabling rapid, quantitative insight
The ratio of these two species, which reports on the into transformations that involve the active site.
propensity for nucleophilic attack by phosphine, vs. amine, is
difficult to ascertain by any other method (including GC Conclusions
analysis, which is hampered by the involatility of the salt). In
1
3
1
The foregoing describes the first synthesis of Grubbs metathesis
the absence of the label, C{ H} NMR analysis is of limited
use: see inverted spectrum. The signal for the methyl carbon of
1
3
catalysts bearing a C label at the key alkylidene site, as well
2
as improved routes to their Hꢀlabelled isotopologues. Both
[MePCy ]Cl (1.52 ppm) is lost in the baseline, and that for
3
NH BuMe is obscured by H N Bu present in excess. The longer
acquisition time should also be noted: 5.5 h, vs. 20 min.
n
n
firstꢀ and secondꢀgeneration Grubbs catalysts (that is, the
benzylidene precatalysts) were prepared, as were their restingꢀ
state methylidene complexes. A case study was presented that
demonstrates the ease with which the methylidene label can be
2
1
3
tracked via the C label. This study revealed an unexpected,
profound bias for abstraction of the methylidene moiety by
phosphine, relative to amine. While the basis for this
phenomenon is the subject of ongoing study, the data above
illustrate the power of these isotopically labelled complexes for
insight into catalyst activation and deactivation, and their
potential to expand understanding of the behaviour of the
important Grubbs metathesis catalysts.
Experimental
General procedures
Reactions were carried out under N using standard Schlenk and
2
glovebox techniques. Dry, oxygenꢀfree C H and CH Cl were
6
6
2
2
obtained using a Glass Contour solvent purification system.
Pentane was distilled over sodium benzophenone, acetone over
calcium sulphate. All solvents were stored under N over Linde
2
4
Å molecular sieves. C D and CD Cl (Cambridge Isotopes)
6 6 2 2
were degassed by five successive freeze/pump/thaw cycles and
stored over 4Å molecular sieves under N for at least 6 h prior
2
to use. Ethylene (BOC UltraꢀHigh Purity Grade 3.0; 99.9%)
was used as received from Linde. The firstꢀgeneration Grubbs
1
3
13
catalyst (GI, 97% purity), styreneꢀ
enrichment, 4ꢀtertꢀbutylcatechol as a stabilizer), styreneꢀα-d
1
α- C (98% purity, 99% Cꢀ
2
1
3
(98% purity, 98% Hꢀenrichment, hydroquinone as stabilizer),
Figure 5. Spectra showing the superior rapidity and clarity with which C-
1
3
13
labelling enables tracking of the methylidene moiety during decomposition. Top: styreneꢀ
β
ꢀ C (99% Cꢀenrichment, 4ꢀtertꢀbutylcatechol as
Cꢀenrichment), and 1,3,5ꢀ
trimethoxybenzene (TMB, >99%) were obtained from Sigmaꢀ
Aldrich, C D (99.8% Hꢀenrichment) from C/D/N Isotopes.
Free H IMes was prepared by the literature method.
13
1
C{ H} NMR spectra; 20 min acquisition for *GIIm and (inverted) 5.5 h
2
acquisition for non-enriched GIIm. Bottom: H spectrum for GIIm and (inverted)
13
13
stabilizer),
C H
2 4
(99%
D
1
H NMR spectrum for GIIm (2 h and 5 min acquisition, respectively).
2
2
4
4
0
D
The corresponding experiment with GIIm supported the
2
NMR spectra were recorded on a Bruker Avance 300 NMR
at 296 1.5 K, and referenced to the residual proton/deuteron or
carbon signals of the solvent ( H, H, C). Signals are reported
inference from the *GIIm experiment, but was less diagnostic.
n
±
While the methyl signals for [MePCy ]Cl and HN BuMe can
3
1
2
13
be observed at 2.8 and 2.2 ppm, respectively, assignment is
1
13
31
2
in ppm, relative to TMS ( H, C) or 85% H PO ( P) at 0 ppm.
hampered by the poor resolution of the JDP signal, and the
3
4
The number of intervening bonds for JPC coupling constants is
narrow chemical shift window (Figure 5, bottom). It should be
n
noted that neither [MePCy ]Cl nor HN BuMe can be readily
3
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Journal Name
1
3
1
omitted for cyclohexyl carbons, for which specific assignments mg (87%, 97% Cꢀenriched). H NMR analysis indicated the
were not attempted.
presence of ca. 2% of the H IMes hydrolysis product N,N’
ꢀ
2
3
1
dimesitylꢀ
Nꢀformylethylenediamine.
This impurity was
Synthesis of Labelled Ru Complexes.
removed from an 18 mg portion of the product by washing with
cold pentane (3 x 1 mL): catalyst purity increased to >98%,
1
3
13
RuCl (PCy ) (= CHPh), *GI. In the glovebox, styreneꢀ
α-
C
2
3 2
(
144
ꢀ
L, 1.26 mmol, 5.0 equiv) was added to a purple solution albeit to the detriment of the isolated yield (13 mg; 72%). NMR
4
1
of GI (208 mg, 0.253 mmol) in C H (20 mL) in a 100 mL chemical data agree well with the values reported for nonꢀ
Schlenk tube. The reaction was stirred at RT for 45 min. The labelled GII, with the addition of C splitting. P{ H} NMR
solvent was removed under vacuum to yield a purple solid, (C D ): δ 30.2 (d, JPC = 8.3 Hz, PCy ). H NMR (300.1 MHz,
3
which was washed with acetone (3 x 2 mL) to remove excess C D ): δ 19.64 (d, JHC = 147.9 Hz, 1H, Ru=C
styrene. The crude product (196 mg, 83% Cꢀenriched) was 1H, Ph
then reꢀsubjected to styreneꢀ
equiv) as before. Workꢀup afforded *GI as a dark purple H IMes). C{ H} NMR (C D , 75.5 MHz): δ 294.8 (d, JCP
powder. Yield: 177 mg (85%, 97% Cꢀenriched). NMR shifts 8.3 Hz, Ru), 221.5 (d, JCP = 77.3 Hz, CNHC), 152.0 (d, JCH
are in good agreement with those reported for GI in C D
barring those due to the alkylidene proton/deuteron.
coupling adds complexity to the splitting patterns observed.
3
6
6
1
3
31
1
2
1
6
6
1
H
Ph), 9.49 (br s,
ꢀC ; overlaps with
L, 1.28 mmol, 5.0 solvent C D H), 3.68ꢀ0.74 (m, 55H, Cy and CH2, CH3 of
5
6
6
1
3
o
H), 7.45ꢀ5.30 (m, 8H, Ph, Mes mꢀCH
1
3
α-
C (146
ꢀ
6
1
3
1
2
=
=
2
6
6
1
3
2
1
2
5
D
45.9 Hz, Ph
iꢀ
C
), 139.4 (br s), 138.3, 137.8, 137.6, 137.3 (br, s),
135.9, 130.3, 129.4, 52.2 (d, JCP = 3.3 Hz, NHC
JCP = 2.0 Hz, NHC
= 8.0 Hz, Cy), 28.2 (d, JCP = 10.0 Hz, Cy), 26.6 (s, Cy), 21.2 (s,
6
1
6,
3
4
C
C
H ), 51.2 (d,
2
4
CH ), 32.0 (d, JCP = 16.5 Hz, Cy), 29.7 (s,
2
1
1
2
P{ H} NMR (121.5 MHz, C D ): δ 36.9 (d,
J
p
ꢀ
CH3),
6
6
PC
1
1
P
Cy ). H NMR (300.1 MHz, C D ): δ 20.61 (d, JHC = 146.6 21.1 (s,
p
ꢀ
C
H ), 20.5 (s,
o
ꢀ
C
H ), 19.0 (br s,
o
ꢀ
CH ). Swivelling
3
3
6
6
3
3
Hz, 1H, Ru=C
H
m
Ph), 8.72 (br s, 2H, Ph
ꢀC ; overlaps with solvent C D5
H, Cy), 2.10ꢀ1.85 (m, 12H, Cy), 1.83ꢀ1.41 (m, 30H, Cy), 1.38ꢀ
o
ꢀC
H
), 7.40ꢀ7.00 (m, about the Ru=CHPh bond prevents observation of all phenyl
3
6
H, Ph
p
ꢀCH
,
H
H
), 2.87 (m, carbons except the ipsoꢀcarbon, and broadens the corresponding
6
1
H NMR signals.
1
3
1
1
2
.05 (m, 18H, Cy). C{ H} NMR (C D , 75.5 MHz) δ 295.0 (t,
6 6
D
JCP = 8.0 Hz, Ru), 153.4 (d, JCC = 44.6 Hz, Ph
H) 129.4 (d, JCC = 4.0 Hz, Ph
H), 32.5 (t, JCP = 9.1 Hz, Cy), 30.2 (s, Cy), 28.2 (t, 0.367 mmol, 1.1 equiv), and Amberlyst 15 resin (284 mg, 1.34
iꢀC) 131.5 (d, RuCl (H IMes)(PCy )(=CDPh), GII: Prepared as for *GII
2 2 3
D
JCC = 2.2 Hz, Ph
29.3 (
o
ꢀ
C
mꢀCH), above, but using GI (275 mg, 0.334 mmol), H IMes (113 mg,
2
1
pꢀC
2
JCP = 5.0 Hz, Cy), 27.0 (s, Cy).
mmol, 4 equiv). Yield: 244 mg (86%, 96% Hꢀenriched). NMR
chemical shifts are in excellent agreement with the values
D
41
RuCl (PCy ) (=CDPh), GI: Prepared as for *GI above, but reported for nonꢀlabelled GII, barring those due to the
2
3 2
2
using styreneꢀ
α-d1 (247 ꢀL, 2.37 mmol, 5 equiv) and GI (390 alkylidene proton/deuteron. H NMR (46.1 MHz, C H ): δ
6 6
2
mg, 0.474 mmol). Yield: 330 mg (85%, 96% Hꢀenriched). 19.64 ppm (br s, Ru=C
D
Ph).
2
5
NMR data agree with those reported; they are reproduced
here for convenience. Resolution is slightly improved relative RuCl (PCy ) (= CH ), *GIm. In the glovebox, a 50 mL
1
3
2
3 2
2
3
1
1
to *GI above. P{ H} NMR (121.5 MHz, C D ): δ 36.7 roundꢀbottom flask equipped with a Kontes valve was charged
6
6
1
3
(
2
(
P
Cy ). H NMR (300.1 MHz, C D ): 8.77 (d, JHH = 7.8 Hz, with purple GI (403 mg, 0.490 mmol) and C H (20 mL). The
3
6
6
6
6
3
H, Ph
m, 2H, Ph
o
ꢀC
H
m
), 7.31 (t, JHH = 7.4 Hz, 1H, Ph
ꢀC ; overlaps with solvent C D5
Cy), 2.10ꢀ1.93 (m, 12H, Cy), 1.86ꢀ1.50 (m, 30H, Cy), 1.44ꢀ1.12 valve to the C H lecture bottle and a Schlenk line. Ethylene
p
ꢀC
H ), 7.18ꢀ7.12 flask was removed to a Schlenk line, degassed by five
H
H), 2.91 (m, 6H, consecutive freeze/pump/thaw cycles, and connected via a Tꢀ
6
1
3
2
4
2
(
m, 18H, Cy). H NMR (46.1 MHz, C H ): δ 20.61 ppm (br s, was introduced from a lecture bottle (for details, see SI). Once a
6 6
Ru=CD2).
positive pressure was achieved, the reaction vessel was sealed
and allowed to stir at RT. A colour change from deep purple to
1
3
RuCl (H IMes)(PCy )(= CHPh), *GII: In the glovebox, a 50 red, then brown, was evident within 10 min. The flask was then
2
2
3
mL roundꢀbottomed flask was charged with pink *GI (174 mg, briefly opened to reꢀestablish positive pressure, and resealed.
.211 mmol) and THF (4.5 mL). To the stirred solution was The reaction was stirred for 45 min, after which the flask was
0
added free H IMes (71 mg, 0.233 mmol, 1.1 equiv). The returned to the glovebox and solvent was removed under
2
reaction was stirred at ambient temperature (27 °C) for 1 h, at vacuum. Styrene and ruthenium decomposition products were
1
which point an aliquot removed for H NMR analysis revealed extracted with cold pentane (5 x 1.5 mL; –35 °C) to afford a
ca. 1% *GI remaining, owing to hydrolysis of H IMes by trace pink solid consisting of *GIm and GI in 95:5 ratio (310 mg).
2
water. A further 7.0 mg H IMes (0.023 mmol, 0.1 equiv) was Following a second pass of reaction with ethylene, clean *GIm
2
1
3
added, and stirring was continued for 30 min, at which point was isolated as a pink solid. Yield 259 mg (71%, 99.5% Cꢀ
conversion was complete ( H NMR analysis). Offꢀtheꢀshelf enriched). NMR data agree with those reported for GIm
Amberlyst 15 exchange resin (180 mg, 4.0 equiv) was added the addition of C splitting. P{ H} NMR (121.5 MHz, C D ):
1
34
,
with
1
3
31
1
6
6
2
1
and the suspension was stirred vigorously for 1 h to sequester δ 43.4 ppm (d, JPC = 8.4 Hz,
PCy ). H NMR (300.1 MHz,
3
3
1
1
free PCy (confirmed by P NMR analysis). The resin was C D ): δ 19.41 (d, JHC = 156.7 Hz, 2H, Ru=CH2), 2.80ꢀ2.55
3
6
6
filtered off and rinsed with THF (3 x 1 mL). The filtrate was (m, 6H, Cy), 2.10ꢀ1.88 (m, 12H, Cy), 1.85ꢀ1.44 (m, 30H, Cy),
1
3
1
stripped to dryness to yield *GII as a pink powder. Yield: 155 1.38ꢀ1.10 (m, 18H, Cy). C{ H} NMR (C D , 75.5 MHz) δ
6
6
6
| J. Name., 2012, 00, 1-3
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DOI: 10.1039/C4CY01118J
2
1
2
2
94.7 (t, JCP = 8.4 Hz, Ru=
C
H ), 31.1 (t, JCP = 9.6 Hz, Cy), and H NMR chemical shifts are in excellent agreement with
2
3
4
9.7 (s, Cy), 28.1 (t, JCP = 5.3 Hz, Cy), 26.9 (s, Cy).
the values reported for the nonꢀlabelled isotopologue, barring
those due to the alkylidene proton/deuteron. H NMR (46.1
2
D
RuCl (PCy ) (=CD ), GIm. Prepared as for *GIm, but using MHz, C H ): δ 18.43 ppm (br s, Ru=CD2).
2
3 2
2
6
6
C D and GI (400 mg, 0.486 mmol). Yield: 272 mg (75%,
2
4
2
Representative procedure for C H solubility measurements
2 4
>
99% Hꢀenriched). NMR chemical shifts are in excellent
3
4
agreement with the values reported for nonꢀlabelled GIm
,
A sample of TMB (11.2 mg, 0.066 mmol) was weighed out
barring those due to the alkylidene proton/deuteron. H NMR using an analytical balance inside the glovebox, transferred to a
46.1 MHz, C H ): δ 19.44 ppm (br s, Ru=CD2). J. Young NMR tube, and dissolved in C D (750 L). The
solution was degassed via five consecutive freeze/pump/thaw
RuCl (H IMes)(PCy )(= CH ), *GIIm. In the glovebox, light cycles, then opened to an atmosphere of C H4 (oilꢀbubbler
2
(
ꢀ
6
6
6
6
1
3
2
2
3
2
2
pink *GIm (202 mg, 0.270 mmol) was dissolved in 12 mL pressure) for ca. 0.5 min. The concentration of dissolved C H
2
4
1
C H in a 100 mL Schlenk tube. White crystalline H IMes (91 was established by H NMR analysis by comparing the
6
6
2
mg, 0.297 mmol, 1.1 equiv) was added. The flask was removed integration of the C H singlet at 5.25 ppm (4H) against the
2
4
to a Schlenk line and immersed in a 60 °C oil bath. A colour TMB aromatic singlet at 6.25 ppm (3H). A recycle delay (D1
)
change from pink to yellowꢀbrown was observed within 15 of 20.0 s was used to ensure accurate integration and the
min, and heating was continued for a total of 45 min. The reported numbers are the average of three trials. The same
solvent was then removed under vacuum at room temperature procedure was used to measure the solubility of ethylene in
to yield a brown residue. This brown tar was transformed into a CD Cl .
2
2
wellꢀbehaved yellow powder by suspending in pentane in the
glovebox, scratching with a spatula, and stripping off the
Representative procedure for half-life measurements
3
1
pentane (3x). Yield 179 mg (86%) of a crude yellow solid;
P
In the glovebox, a J. Young NMR tube was charged with GIm
NMR analysis indicated contamination with [MePCy ]Cl. (10 mg, 0.013 mmol), TMB (ca. 1 mg), and THFꢀd (0.75 mL).
3
8
1
Dissolving 161 mg of crude product in 8 mL benzene and The initial ratio of GIm to TMB was measured by H NMR
1
washing with water (2 x 1.5 mL) removed the [MePCy ]Cl analysis. The NMR probe was heated to 35 °C and H NMR
3
impurity. The benzene was then removed under vacuum and the spectra were collected to 95% consumption of the starting
yellow solid was washed with cold pentane (3 x 1.5 mL) to give methylidene. The halfꢀlife of GIm in CD Cl , CDCl , and C D
6
2
2
3
6
*
GIIm as a fine yellow powder. Yield: 127 mg (68%, 99.5% was determined similarly.
1
3
Cꢀenriched). NMR chemical shifts are in excellent agreement
3
4
with the values reported for the nonꢀlabelled isotopologue,
although C coupling adds further complexity. P{ H} NMR
13
31
1
Representative procedure for amine-induced deactivation of
GIIm
2
1
(
121.5 MHz, C D ): δ 38.3 ppm (d, JPC = 8.5 Hz, PCy ). H
6 6 3
1
NMR (300.1 MHz, C D ): δ 18.42 (d, JHC = 158.6 Hz, 2H, In the glovebox, *GIIm (9.8 mg, 0.013 mmol) was dissolved in
6
6
Ru=CH2), 6.92 (s, 2H, Mes
m
ꢀC
.35ꢀ3.15 (m, 4H, NHC CH2), 2.78 (s, 6H,
ꢀCH3), 2.44ꢀ2.25 (m, 3H, Cy), 2.18 (s, 3H,
H, ꢀCH3), 1.70ꢀ1.45 (m, 15H, Cy), 1.30ꢀ0.95 (m, 15H, Cy). were collected. Loss of the methylidene signal was
H
), 6.75 (s, 2H, Mes
m
ꢀC
H
), C D (633 ꢁL) in a J Young NMR tube, and treated with
6
6
n
3
o
3
o
ꢀCH3), 2.55 (s, 6H H N Bu (12.5 ꢁL, 0.13 mmol; 10 equiv). The NMR tube was
2
1
3
p
ꢀCH3), 2.11 (s, shaken vigorously for 10 minutes, after which C NMR spectra
p
1
1
3
2
C{ H} NMR (C D , 75.5 MHz) δ 294.4 (d, JCP = 8.5 Hz, accompanied by the emergence of new peaks for [*MePCy ]Cl
6
6
2
3
1
n
Ru=
C
H ), 222.2 (d, JCP = 79.8 Hz, CNHC) 139.3 (s, MesꢀA
2
o
ꢀ
(1.5 ppm; d, JCP = 47.9 Hz) and NH Bu*Me (36.8 ppm; s),
), 137.8 (s, Mesꢀ with an integration ratio of 69 : 31.
), 135.0 (s, MesꢀA, ), 130.2 (s,
C
B
), 138.6 (s, MesꢀA
), 137.4 (s, MesꢀB
H), 129.7(s, MesꢀB,
pꢀC), 138.1 (s, MesꢀB pꢀC
o
ꢀ
C
iꢀ
C
iꢀC
4
MesꢀA,
NHC
7.8 Hz, Cy), 29.2 (s, Cy), 28.0 (d, JCP = 10.4 Hz, Cy), 26.7 (s,
Cy), 21.22 (s, Mes H ), 21.20 (s, Mes H ), 20.1 (s, Mesꢀ
H ), 19.1 (s, MesꢀB oꢀCH3). Note: MesꢀA and MesꢀB
m
ꢀ
C
m
ꢀ
C
H), 51.6 (d, JCP = 3.5 Hz,
4
C
H ), 50.0 (d, JCP = 1.7 Hz, NHC H ), 30.7 (d, JCP
2
C
=
Acknowledgements
2
1
Supported by the Natural Sciences and Engineering Research
Council (NSERC) of Canada.
p
ꢀ
C
pꢀC
3
3
A
o
ꢀ
C
3
denote the two unique mesityl groups.
Notes and references
D
a
RuCl (H IMes)(PCy )(=CD ), GIIm. Prepared as for *GIIm
Center for Catalysis Research & Innovation, Chemistry Department,
2
2
3
2
D
University of Ottawa, Ottawa, ON, Canada, K1N 6N5
above, but using GIm (210 mg, 0.280 mmol) and free H2IMes
94 mg, 0.308 mmol). Instead of dissolving the crude product in
(
Electronic Supplementary Information (ESI) available: details for
handling labelled ethylene; improved synthesis of GIIm, and spectra for
all eight complexes of Figure 1. See DOI: 10.1039/b000000x/
benzene and extracting with water (an improved workꢀup
developed with *GIIm), the crude product was washed with
H O (1 x 2 mL), then washed with acetone to remove residual
2
water (1 x 1 mL), and finally pentane (3 x 1 mL), yielding a
2
31
1
yellow solid. Yield: 131 mg (63%, >99% Hꢀenriched). P{ H}
This journal is © The Royal Society of Chemistry 2012
J. Name., 2012, 00, 1-3 | 7

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Page 8 of 9
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ARTICLE
DOI: 10.1039/C4CY01118J
Journal Name
1
.
A recent book contains comprehensive updates on ringꢀclosing 23. Z. Wu, S. T. Nguyen, R. H. Grubbs and J. W. Ziller, J. Am. Chem.
metathesis (RCM) and crossꢀmetathesis, RCM in pharma, and Soc., 1995, 117, 5503–5511.
metathesis of renewable resources. (a) B. J. van Lierop, J. A. M. 24. W. J. van Rensburg, P. J. Steynberg, W. H. Meyer, M. M. Kirk and G.
Lummiss and D. E. Fogg, in Olefin Metathesis-Theory and Practice, S. Forman, J. Am. Chem. Soc., 2004, 126, 14332–14333.
ed. K. Grela, Wiley, Weinheim, 2014, ch. 3, pp. 85ꢀ152. (b) K. 25. M. B. Dinger and J. C. Mol, Organometallics, 2003, 22, 1089–1095.
Zukowska and K. Grela, in Olefin Metathesis-Theory and Practice, ed. 26. M. Oliván and K. G. Caulton, J. Chem. Soc., Chem. Commun., 1997,
K. Grela, Wiley, Weinheim, 2014, ch. 2, pp. 39ꢀ84. (c) K. R. Fandrick,
J. Savoie, N. Y. Jinhua, , J. J. Song, C. H. Senanayake, ch. 12, pp. 349ꢀ 27. C. Pietraszuk and H. Fischer, Organometallics, 2001, 20, 4641–4646.
66. (d) A. Nickel and R. L. Pederson, in Olefin Metathesis-Theory 28. A. Fürstner, O. R. Thiel, L. Ackermann, H.ꢀJ. Schanz and S. P. Nolan,
1733.
3
and Practice, ed. K. Grela, Wiley, Weinheim, 2014, ch. 11, pp. 335ꢀ
48.
S. Kress and S. Blechert, Chem. Soc. Rev., 2012, 41, 4389ꢀ4408
J. Org. Chem., 2000, 65, 2204–2207.
29. A prior synthesis reported the [Ru]=CD(C
albeit in 26% yield. See Ref. 27.
D
3
6 5
D ) isotopologue of GI,
2
3
.
.
U. Biermann, U. Bornscheuer, M. A. R. Meier, J. O. Metzger and H. J. 30. Workup in the Mol route involved washing with pentane (in which GI
Schafer, Angew. Chem. Int. Ed., 2011, 50, 3854–3871.
A. H. Hoveyda, S. J. Malcolmson, S. J. Meek and A. R. Zhugralin,
Angew. Chem. Int. Ed., 2010, 49, 34–44.
is more soluble) and methanol. Reaction was also carried out in
dichloromethane rather than benzene. The faster rate of metathesis in
aromatic media (see Ref. 28) was noted above.
4
5
.
.
G. C. LloydꢀJones and M. P. Munoz, J. Labelled Compd. 31. B. J. van Lierop, A. M. Reckling, J. A. M. Lummiss and D. E. Fogg,
Radiopharm., 2007, 50, 1072–1087.
ChemCatChem, 2012, 4, 2020–2025.
6
7
.
.
D. Schroder, Acc. Chem. Res., 2012, 45, 1521ꢀ1532.
C. Adlhart, C. Hinderling, H. Baumann and P. Chen, J. Am. Chem.
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32. S. H. Hong, A. G. Wenzel, T. T. Salguero, M. W. Day and R. H.
Grubbs, J. Am. Chem. Soc., 2007, 129, 7961–7968.
33. M. Ulman and R. H. Grubbs, J. Org. Chem., 1999, 64, 7202–7207.
8
9
1
1
1
1
.
R. H. Grubbs, D. D. Carr, C. Hoppin and P. L. Burk, J. Am. Chem. 34. J. A. M. Lummiss, N. J. Beach, J. C. Smith and D. E. Fogg, Catal. Sci.
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C. Pietraszuk, H. Fischer, S. Rogalski and B. Marciniec, J. 35. P. Schwab, R. H. Grubbs and J. W. Ziller, J. Am. Chem. Soc., 1996,
Organomet. Chem., 2005, 690, 5912–5921. 118, 100–110.
0. R. H. Grubbs, P. L. Burk and D. D. Carr, J. Am. Chem. Soc., 1975, 97, 36. A single entry for benzene in the IUPACꢀNIST Solubility Data Series
.
3
265ꢀ3267.
1. C. P. Casey and H. E. Tuinstra, J. Am. Chem. Soc., 1978, 100, 2270ꢀ
272.
2. I. C. Stewart, B. K. Keitz, K. M. Kuhn, R. M. Thomas and R. H.
Grubbs, J. Am. Chem. Soc., 2010, 132, 8534–8535.
database corresponds to the temperature and pressure regime used in
our experiments, while no relevant entries exist for dichloromethane.
Krauss and Gestrich reported a solubility in benzene of 140 mM at
298K, and 150 mM at 293K (see: V. W. Krauss, W. Gestrich, Khemie
ꢀ Technik, 1977, 6, 513–516). A solubility of 32 mM was reported by
2
3. A. Fürstner, L. Ackermann, K. Beck, H. Hori, D. Koch, K.
Langemann, M. Liebl, C. Six and W. Leitner, J. Am. Chem. Soc.,
2 2
the Diver group in CD Cl at room temperature and balloon pressure
(see: J. A. Smulik and S. T. Diver, J. Org. Chem., 2000, 65, 1788–
2
001, 123, 9000–9006.
4. J. McGinnis, T. J. Katz and S. Hurwitz, J. Am. Chem. Soc., 1976, 98,
05ꢀ606.
1792). Our study, carried out at 296 ±1.5 K and 1 atm (101.0 ±0.8
1
1
1
1
1
1
kPa), yielded values of 89 ±1 mM in C
To rule out potential integration errors arising from differences in the
relaxation of the ethylene protons, relative to TMB, we measured
6 6 2 2
D , and 54 ±3 mM in CD Cl .
6
5. K. Tanaka, K.ꢀI. Tanaka, H. Takeo and C. Matsumura, J. Am. Chem.
Soc., 1987, 109, 2422ꢀ2425.
6. E. M. Leitao, S. R. Dubberley, W. E. Piers, Q. Wu and R. McDonald,
Chem. Eur. J., 2008, 14, 11565–11572.
T
1
1
the H NMR spectra at different delay times. Minimal differences in
relative integration (<3%) were apparent for singleꢀpulse experiments,
1
versus 16ꢀscan experiments with an arbitrarily long D relaxation
7. F. C. Courchay, J. C. Sworen, I. Ghiviriga, K. A. Abboud and K. B.
Wagener, Organometallics, 2006, 25, 6074–6086.
8. J. S. Kingsbury and A. H. Hoveyda, J. Am. Chem. Soc., 2005, 127,
delay.
37. M. S. Sanford, J. A. Love and R. H. Grubbs, J. Am. Chem. Soc., 2001,
123, 6543–6554.
4
510–4517.
9. For a review describing NHCꢀmediated decomposition pathways, see:
a) G. C. Vougioukalakis and R. H. Grubbs, Chem. Rev., 2010, 110,
746–1787. Theoretical studies of such intrinsic deactivation pathways
38. Sterically accessible amines are most damaging, while αꢀsubstituted
amines are relatively innocuous. For a lucid review, see: (a) P.
Compain, Adv. Synth. Catal., 2007, 349, 1829–1846. For studies of
the decomposition of the Grubbs catalysts by primary amines, see (b)
G. O. Wilson, K. A. Porter, H. Weissman, S. R. White, N. R. Sottos
and J. S. Moore, Adv. Synth. Catal., 2009, 351, 1817–1825, and Ref.
39.
(
1
have been reviewed: (b) R. Credendino, A. Poater, F. Ragone and L.
Cavallo, Catal. Sci. Technol., 2011, 1, 1287ꢀ1297. Decomposition can
also be mediated by unintended contaminants. Alkoxide salts are
particularly aggressive, even at RT. See: (c) N. J. Beach, J. A. M. 39. J. A. M. Lummiss, B. J. Ireland, J. M. Sommers and D. E. Fogg,
Lummiss, J. M. Bates and D. E. Fogg, Organometallics, 2012, 31, ChemCatChem, 2014, 6, 459–463.
349–2356. Alcohols in the presence of NEt also promote 40. A. J. Arduengo, R. Krafczyk, R. Schmutzler, H. A. Craig, J. R.
2
3
decomposition, albeit under more forcing conditions. For leading
references, see: (d) N. J. Beach, K. D. Camm and D. E. Fogg,
Goerlich, W. J. Marshall and M. Unverzagt, Tetrahedron, 1999, 55,
14523–14534.
Organometallics, 2010, 29, 5450–5455, and references therein; (e) M. 41. L. Jafarpour, A. C. Hillier and S. P. Nolan, Organometallics, 2002, 21,
B. Dinger and J. C. Mol, Organometallics, 2003, 22, 1089–1095; (f) S.
Manzini, A. Poater, D. J. Nelson, L. Cavallo, A. M. Z. Slawin and S.
P. Nolan, Angew. Chem. Int. Ed., 2014, 53, 8995ꢀ8999. In the absence
of base, reaction with methanol is slow, even for GI: see Ref. (e). For
decomposition by primary and secondary amines, see discussion
below.
442–444.
13
2
0. The molar receptivity of C is 4.4 times higher than that of deuterium
at comparable levels of enrichment. Furthermore, spinꢀspin relaxation
times (T
relaxation, resulting in much broader signals, as lineꢀwidths at halfꢀ
height are determined by 1/πT . See NMR properties of selected
2
) for deuterium nuclei are accelerated by quadrupolar
2
isotopes in: Bruker Almanac 2013, p. T8.
2
2
1. B. Marciniec, S. Rogalski, M. J. Potrzebowski and C. Pietraszuk,
ChemCatChem, 2011, 3, 904–910.
2. J. M. Bates, J. A. M. Lummiss, G. A. Bailey and D. E. Fogg, ACS
Catal., 2014, 4, 2387−2394.
8
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Journal Name
Catalysis Science & Technology
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ARTICLE
DOI: 10.1039/C4CY01118J
Table of Contents entry
1
3
13
CꢀLabelled Grubbs catalysts, RuCl (L)(PCy )(= CHR) (R =
2
3
H, Ph), pinpoint the fate of the methylidene (benzylidene)
moiety during metathesis and deactivation.
This journal is © The Royal Society of Chemistry 2012
J. Name., 2012, 00, 1-3 | 9