Decomposition of a Phosphine-Free Metathesis Catalyst by Amines and Other Bronsted Bases: Metallacyclobutane Deprotonation as a Major Deactivation Pathway

Article abstract of DOI:10.1021/acscatal.5b00813

Reactions are described of the second-generation Hoveyda catalyst HII with amines, pyridine, and DBU (1,8-diazabicyclo[5.4.0]undec-7-ene), in the presence and absence of olefin substrates. These nitrogen bases have a profoundly negative impact on metathesis yields, but in most cases, they are innocuous toward the precatalyst. HII adducts were formed by primary and secondary amines (n-butylamine, sec-butylamine, benzylamine, pyrrolidine, morpholine), pyridine, and DBU at room temperature. No reaction was evident for NEt₃, even at 60 °C. On longer reaction at RT, unencumbered primary amines abstract the benzylidene ligand from HII. With 10 equiv of NH₂ⁿBu, this process was complete in 12 h, affording NHⁿBu(CH₂Ar) (Ar = o-C₆H₄-OⁱPr) and [RuCl(H₂IMes)(NH₂ⁿBu)₄]Cl. For benzylamine, benzylidene abstraction occurred over days at RT. No such reaction was observed for sec-butylamine, secondary amines, NEt₃, pyridine, or DBU. All of these bases, however, strongly inhibited metathesis of styrene by HII, with a general trend toward more deleterious effects with higher Bronsted basicity. Studies at 10 mol % of HII and 10 equiv of DBU, NEt₃, and pyrrolidine (60 °C, C₆D₆) indicated that the primary mechanism for decomposition involved base-induced deprotonation of the metallacyclobutane intermediate, rather than the Lewis base-mediated decomposition pathways previously established for the Grubbs catalysts. In the corresponding metathesis of ethylene, this decomposition process is rapid even at RT, highlighting the vulnerability of the less substituted metallacyclobutane.

Full text of DOI:10.1021/acscatal.5b00813

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Article
Decomposition of a Phosphine-Free Metathesis Catalyst
by Amines and Other Bronsted Bases: Metallacyclobutane
Deprotonation as a Major Deactivation Pathway
Benjamin J. Ireland, Bernadette Dobigny, and Deryn Elizabeth Fogg
ACS Catal., Just Accepted Manuscript • DOI: 10.1021/acscatal.5b00813 • Publication Date (Web): 30 Jun 2015
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ACS Catalysis
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Decomposition of a Phosphine-Free Metathesis Catalyst by
Amines and Other Bronsted Bases: Metallacyclobutane
Deprotonation as a Major Deactivation Pathway
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Benjamin J. Ireland, Bernadette T. Dobigny, and Deryn E. Fogg*
Department of Chemistry and Centre for Catalysis Research & Innovation, University of Ottawa, Ottawa, Ontario,
Canada K1N 6N5
<Supporting information placeholder>
ABSTRACT: Reactions are described of the second-generation Hoveyda catalyst HII with amines, pyridine, and DBU (1,8-
diazabicyclo[5.4.0]undec-7-ene), in the presence and absence of olefin substrates. These nitrogen bases have a profoundly
negative impact on metathesis yields, but in most cases are innocuous toward the pre-catalyst. HII adducts were formed
by primary and secondary amines (n-butylamine, sec-butylamine, benzylamine, pyrrolidine, morpholine), pyridine, and
DBU at room temperature. No reaction was evident for NEt3, even at 60 °C. On longer reaction at RT, unencumbered
n
primary amines abstract the benzylidene ligand from HII. With 10 equiv NH2 Bu, this process was complete in 12 h, af-
fording NHnBu(CH2Ar) (Ar = o-C6H4-OiPr) and [RuCl(H2IMes)(NH2nBu)4]Cl. For benzylamine, benzylidene abstraction
occurred over days at RT. No such reaction was observed for sec-butylamine, secondary amines, NEt3, pyridine, or DBU.
All of these bases, however, strongly inhibited metathesis of styrene by HII, with a general trend toward more deleterious
effects with higher Bronsted basicity. Studies at 10 mol% HII and 10 equiv DBU, NEt3, and pyrrolidine (60 °C, C6D6) indi-
cated that the primary mechanism for decomposition involved base-induced deprotonation of the metallacyclobutane
intermediate, rather than the Lewis base-mediated decomposition pathways previously established for the Grubbs cata-
lysts. In the corresponding metathesis of ethylene, this decomposition process is rapid even at RT, highlighting the vul-
nerability of the monosubstituted metallacyclobutane.
Keywords. homogeneous catalysis, olefin metathesis, amine, metallacyclobutane, decomposition, Hoveyda catalyst,
Hoveyda-Grubbs catalyst
Chart 1. Metathesis Catalysts Discussed, and the
Resting-State Methylidene Complex for GII
Introduction
Olefin metathesis offers exceptional power and efficiency
in the assembly of carbon-carbon bonds.1 The
development of readily-handled, highly active ruthenium
catalysts (preeminently the second-generation Grubbs
and Hoveyda catalysts GII and HII; Chart 1)2,3 led to
widespread uptake of these methodologies in organic
synthesis. Notwithstanding the importance of metathesis
in the synthesis of alkaloids and other nitrogen
heterocycles,4 however, compounds bearing sterically
accessible nitrogen sites challenge the functional-group
tolerance of these catalysts.5-7
Reports from pharma highlight the destructive effect on
metathesis of even traces of morpholine, DBU (1,8-
diazabicyclo[5.4.0]-undec-7-ene), and other nitrogen
bases.8-10 Likewise, metathesis of amine-bearing
substrates has long been known to require either N-
protection,11 or an adjacent substituent to block access to
and/or withdraw electron density from the nitrogen site.5-
7
The Cossy group recently extended the latter strategy
to metathesis of N-heteroaromatic compounds.12 For
protected amines,
a
survey of recent examples13-21
illustrates moderate to excellent metathesis yields.
Reaction is relatively slow even at high catalyst loadings,
however, suggesting competing catalyst deactivation.
A clear understanding of the processes by which catalysts
decompose is key to designing solutions.22-24 The delete-
rious effect of sterically accessible amine and pyridine
donors on metathesis is widely presumed to be due to
their excellent Lewis basicity,6,7,12 owing in large part to
studies of the Grubbs catalysts.25-28 Particularly damaging,
even toward the robust precatalyst GII, are sterically ac-
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cessible primary amines. We recently demonstrated that Chart 2. Nitrogen Bases Studied, with Binding Site
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n-butylamine abstracts the benzylidene ligand from GII
over several hours at room temperature (Scheme 1,
top).26,27,29 In contrast, secondary amines,26 DBU,26 and
pyridine30 form stable adducts with GII.
Shown in Blue.
Results and Discussion
Prior to examining the impact of a–f on HII during
catalysis, we established the reaction chemistry in the
absence of substrate. These experiments are important to
dissect out the respective roles of the metallacyclobutane
or other intermediates, relative to HII itself. They carry
further weight given that HII functions as not only the
Much more vulnerable is the resting-state methylidene
complex GIIm. Amines greatly accelerate decomposition
of this species.26,27 Such donors cause complete loss of the
methylidene ligand over hours at RT, a process that
requires days for GIIm at 55 °C in the absence of amine.28
In both cases, decomposition occurs via dissociation of
the PCy3 ligand, which then abstracts the methylidene
ligand. Consistent with the general pathway depicted in
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pre-catalyst, but also
a key resting state during
metathesis.33 Despite the presence of the oxygen donor in
the styrenyl ether ligand, the chemistry of HII itself was
found to parallel that previously communicated26 for
reaction of GII with a subset of these donors.
Scheme
crystallographically characterized the σ-alkyl species Ru-
for the first-generation Grubbs catalyst
RuCl2(PCy3)2(=CHPh) GI.31
1 (bottom), we recently intercepted and
Adduct formation on reaction of HII with N-donors.
In a series of NMR experiments, HII was treated with a
tenfold excess of a–h in C6D6, in the presence of an
internal integration standard (TMB, trimethoxybenzene)
to enable quantification of non-alkylidene Ru products.
As shown in Scheme 2 and described below, stable
adducts were observed for the secondary amines,
pyridine, and DBU (a–d), while no reaction was evident
for NEt3 e, even at 60 °C.
1
For the adducts of a–d, a new singlet for the alkylidene
proton was observed in the region 20.0–20.7 ppm (Table
1). Diagnostic for release of the chelated ether oxygen is
the downfield location of this signal relative to that for
HII at 16.72 ppm.34 Release of the chelate is further
supported by the upfield location of the CHMe2 septet,
for which the midpoint appears between 4.2-4.0 ppm,
near that of the free styrenyl ether (4.15 ppm). In
comparison, a midpoint of 4.48 ppm is found for this
signal in HII itself. A through-space interaction between
the isopropoxy CHMe2 methine and the alkylidene
proton was confirmed by NOE experiments with the
pyrrolidine adduct HIIb. Control experiment showed no
such NOE effect for HII itself, in which the position of
the isopropoxy group is locked by chelation.
Scheme 1. Amine-Induced Deactivation of the
Grubbs Catalysts.
While free PCy3 plays a central role in this decomposition
chemistry, a related pathway can be envisaged for
phosphine-free catalysts: that is, attack on the
methylidene ligand by nitrogen nucleophiles, in place of
PCy3. Despite the growing importance of HII and its
congeners, the decomposition behavior of such
phosphine-free catalysts has seen little attention.32 In the
present study, we examined the reactions of nitrogen
bases with HII in the presence and absence of metathesis
substrates. The bases selected for study (Chart 2) include
examples highlighted in the literature as particularly
deleterious, with the addition of others (NEt3, NH2CH2Ph,
NH2secBu) designed to gauge the effect of amine bulk and
basicity. Here we report that Bronsted basicity
specifically, proton abstraction from
metallacyclobutane intermediate
–
the
–
is the primary
contributor to deactivation of HII during metathesis.
Lewis basicity is found to play a significant role only for
the smallest, most accessible primary amines.
a L = H2IMes. For primary amines f–h, see below.
Scheme 2. Reaction of HII with Di- or Trisubstituted
N-Donors.a
Table 1. Key 1H NMR Data and Equilibrium Yields for
N-Adducts of HII and GII.a
N-donor
HII adducts
δH (yield)
GII adducts26
δH (yield)
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none
16.72
19.65
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a: morpholine
b: pyrrolidine
c: pyridine
d: DBU
20.39 (71)
19.73 (65)
20.25 (100)
19.97 (100)b,c 19.83 (55)b
19.67 (93)
20.71 (74)
no reaction
19.81 (95),b
18.58 (5)
19.93 (75)
e: NEt3
no reaction
19.56 (90)b,d
n
f: NH2 Bu
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g: NH2CH2Ph
h: NH2secBu
19.74 (78),b
18.84 (22)
20.00 (100)c
not reported
not reported
aChemical shift of [Ru]=CHAr (C6D6, 500 MHz). Equilibrium
yields in brackets, exclusive of decomposition. Assigned as
b
c
bis(amine) adduct; see text. Value at –20 °C in C7D8 (br s at
RT). dCf. value of 18.96 reported25 for GIId2 at –30 °C in
CD2Cl2.
Scheme 3. Reaction of HII with Primary Amines.
The resulting adducts were thermally stable at 60 °C,
showing no detectable decomposition after heating for 24
h. A dynamic equilibrium between the adducts and HII is
In situ quantification of the ruthenium co-product is
hampered by the excess amine present. We isolated the
n-butylamine derivative Ru-2 from both HII and GII, by
addition of 10 equiv f at RT in benzene (Scheme 4). The
yellow product precipitated over 24 h, and was purified
by extracting with hexanes (81% isolated yield for GII; or
69% for the smaller-scale reaction with HII). This
cationic complex is unstable in solution in the absence of
excess amine, presumably because of competing
coordination of the chloride counter-ion and
1
operative, as indicated by H EXSY experiments with
HIIb, which exhibited a correlation cross-peak between
the alkylidene signals for HII and HIIb (see S.I.) Partial
reversion to HII was induced on exposure to vacuum,
consistent with an equilibrium reaction.
In comparison, treating HII with n-butylamine f (Scheme
3) resulted in immediate formation of mono- and bis-
amine adducts: no HII was visible, but 9% loss of
alkylidene was evident at the time of the first NMR
measurement (4 min), increasing to 15% at 15 min. The
dominant product ([Ru]=CHAr δH 19.81 ppm) is assigned
as bis-amine adduct HIIf2, by analogy to the structure
crystallographically established for GIIf2.25 Mono-amine
derivative HIIf was present in minor amounts (δH 18.58
ppm, <5%). The analogous mono-amine complex was not
observed for GII, but reportedly formed via loss of amine
on drying GIIf2 under vacuum.25,26
n
displacement of bound NH2 Bu. Similar behavior,
including a cascade of ensuing reactions associated with
solvent-induced chlorination, was previously reported for
nitrile derivatives of Ru(II).37 The structure shown is
supported by combustion analysis, and by NMR analysis
in the presence of a small amount of added amine (1%
v/v).38
Ensuing benzylidene abstraction by f was slightly faster
than in the GII system.26 Loss of alkylidene was complete
after 12 h at RT (vs. 95% for GII), and the diagnostic
methylene
singlet
for
the
amine
product
NH(nBu)(CH2Ar) 1 (Ar = C6H4-o-OiPr) was evident at 3.93
ppm (0.8 equiv vs. starting HII).35
The corresponding reactions with benzylamine
g
proceeded similarly, affording mono- and bis-amine
derivatives HIIg and HIIg2 (Scheme 3; Table 1).
Decomposition was much slower, however, presumably
reflecting the greater bulk and lower basicity36 of the
amine. Thus, after 96 h, the alkylidene signal for the
HIIg2 adduct was still observable at 19.74 ppm (ca. 6%; cf.
zero remaining HIIf2 after 12 h). A similar proportion of
the amine derivative NH(CH2Ph)(CH2Ar) 1’ was observed.
a
Amine
co-products
(NH(nBu)(CH2Ar)
1
or
NH(nBu)(CH2Ph) not shown.
Scheme 4. Isolation of Ru-2 from the Reaction of HII
or GII with n-Butylamine.a
Notably, no benzylidene abstraction occurred in the
corresponding reaction of HII with sec-butylamine h.
Instead, mono-amine adduct HIIh was formed as the sole
product, and this species resisted decomposition even
after heating for 24
h at 60 °C. We infer that
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accessible primary amine to abstract the alkylidene
ligand from HII, as described above.
disubstitution at the carbon α to the nitrogen atom is
sufficient to block approach to the benzylidene ligand.
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The negligible proportion of stilbene (<5%) formed with
the stronger bases attests to the efficiency of
decomposition. Perhaps most unexpected is the low CM
yield observed in the presence of a tenfold excess of NEt3
e. This is particularly important given the steric
protection presumed for tertiary amine centers, as noted
in the Introduction. A role for proton abstraction in
catalyst deactivation is proposed below. N-binding (i.e.
sequestration of amine by binding to the metal, as in
Scheme 1) is presumed to compete with this pathway.
Consistent with this steric sensitivity is a mechanism
involving benzylidene abstraction via nucleophilic attack
at the [Ru]=CHAr carbon (Scheme 5).39 Precedent for the
σ-alkyl moiety in intermediate
A is provided by
structurally characterized Ru-1 (Scheme 1) in the Grubbs
system.31 Elimination of the alkyl ligand – whether by a
concerted pathway, as shown, or via a Ru-hydride
intermediate – would liberate the secondary amine 1.
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Scheme 5. Proposed Mechanism for Benzylidene Ab-
straction by Sterically Accessible Primary Amines.
The overall pattern of decomposition by primary amines
Figure 1. Impact of N–base on metathesis yields.36
outlines above indicates that
a sharp decline in
n
aggressiveness in the order NH2 Bu >> NH2CH2Ph, while
attack by α-substituted NH2secBu is completely inhibited.
HII is thus relatively tolerant toward amines or related
nucleophiles for which benzylidene abstraction is curbed
by bulk or limited basicity. Because ligation of these
Lewis donors is readily reversible, their negative impact
on the precatalyst (that is, HII itself) is better described
as deactivation than decomposition. Very different results
are found in the presence of olefin, as described in the
next section.
Decomposition Pathway. To gain insight into the
mechanism by which bases decompose the active
catalyst, NMR experiments were carried out under the
conditions above, but using 10 equiv each of styrene and
amine. In this portion of the study, we focused on the
three most deleterious bases, pyrrolidine b, DBU d, and
NEt3 e. (We omitted primary amine f in order to
highlight decomposition that originates in the active
species, as opposed to the precatalyst). For DBU and
NEt3, loss of all alkylidene species was complete within 30
min at 60 °C (Table 2); cf. 18 h for pyrrolidine b.
Base-Induced Decomposition of HII and Its Active
Species During Metathesis. We next examined the
impact of base on the longevity and productivity of HII
during metathesis. As a probe reaction, we chose the self-
metathesis of styrene by HII (1 mol%) at 60 °C in
benzene. The homodimerization of styrene to form
stilbene is known to proceed in high yield, but at
relatively slow rates even using 3-5 mol% Ru.40-42 It thus
Unexpectedly, experiments directed at assessing
temperature effects indicated that decomposition by NEt3
e is fast even at RT, with complete loss of alkylidene by
1h. In comparison, ca. 90% loss is found with DBU after 10
h at RT. In all cases, the sole or principal organic
decomposition product is (E)–PhCH=CHCH2Ph 3,
irrrespective of temperature. The identity of 3 was
confirmed by MS and NMR analysis. The olefinic signals
offer characteristic NMR values, in terms of both
chemical shift and multiplicity: a doublet at 6.31 ppm
(3JHH = 16 Hz) for the PhHC proton, and a doublet of
provides
a
convenient model for assessing the
detrimental effect of base.
In control reactions without added a–f, yields of stilbene
reached ca. 80% after 2 h, and 94% after 24 h. In the
presence of a–f, the maximum yield decreased in all cases
(Figure 1). The impact of just one equivalent of amine per
HII is offset by adduct formation. With 10 equiv a–f,
however, metathesis activity is dramatically reduced, and
a general trend toward lower CM yields with increasing
Bronsted basicity is evident.36 A minor anomaly with
NH2nBu f is attributed to the capacity of this sterically
3
triplets at 6.19 ppm (3JHH = 16 Hz, JHH = 7 Hz) for the
=CHCH2Ph proton, in excellent agreement with literature
values,43 and with DEPT-135 and COSY data. Trans-
3
selectivity is indicated by the magnitude of the JHH
coupling constant (16 Hz). A minor co-product, observed
in the control reaction without base, and in the presence
of NEt3, is the related species (E)-PhCH=CHCH3 3’.44 The
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origin of these products, and the mechanistic
implications thereof, are discussed below.
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3
4
Table 2. Decomposition Rates and Products on Reac-
tion of HII with Styrene in the Presence of Amines.a
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9
100
HII
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GIIb
3
%
0
N-base
T
time % loss of
% 3
% 3’
(°C) (h)
[Ru]=CHR
none
60
60
24
91
–
17
Time (h)
pyrrolidine
b
10
90
72
81
–
–
–
18
quant
quant
Scheme 6. Reaction of HII with Styrene and Pyrroli-
dine, and Rate Plot for Loss of Alkylidene.
DBU d
NEt3 e
DBU d
NEt3 e
60
60
21
0.5
88
0.5
18
1
quant
quant
quant
70
90
74
13
–
The three-carbon backbone present in 3 is an important
marker
implicating
attack
of
base
on
the
metallacyclobutane intermediate (e.g. Ru-4; Scheme 7).
Proton abstraction from the Cβ site is proposed to
generate an anionic σ-alkyl complex such as Ru-5, the
basicity of which enables E–H bond activation and
ensuing elimination, as earlier established for σ-alkyl
complex Ru-1.46 Key to this pathway is poor steric
protection of the kite-shaped32b metallacyclobutane ring,
which permits approach of amine. Notably absent is the
o-isopropoxyphenyl analog of 3 (i.e. PhCH=CHCH2Ar).
We infer that the increased bulk of the aryl substituent in
Ru-4” impedes approach of base to Cβ, and hence
inhibits deprotonation of this species.
21
9
aConditions: 200 mM styrene, C6D6, J. Young tube. H NMR
integration vs. TMB; ±2.5% in replicate runs. Yields of 3 are
based on starting HII. Yields of stilbene vs. starting styrene
<4%.
1
These reactions proceed via initial cross-metathesis of
HII with styrene, liberating isopropoxystyrene 2 in near-
quantitative amounts (95% based on starting HII).45
Complete, efficient uptake of the entire HII charge is
indicated, notwithstanding the relatively small
proportion of substrate present. This point is worth
emphasis, as it contradicts the widespread view that HII
initiates slowly: it is fully consistent, however, with the
rapid turnon established for this catalyst in recent 13C-
labelling studies.33
In the slower reaction with pyrrolidine b, we were able to
observe the known adduct GIIb26 (70% yield at 2 h, based
on starting HII). This complex is formed by trapping of
the four-coordinate benzylidene intermediate Ru-3
(Scheme 6). While GIIb disappears relatively slowly, it
does
not
successfully
engage
in
metathesis.
Decomposition accounts for the failure to observe GIIb
and HIIb in the expected equilibrium ratio. Instead, the
organic
PhCH=CHCH2Ph 3, accounts for 80-90% of the “missing”
HII at any time (see conversion plot of Scheme 6).
product
of
catalyst
decomposition,
Scheme 7. Proposed Mechanism for Base-Induced
Catalyst Decomposition During Metathesis.
Interestingly, on replacing pyrrolidine b with the bulkier,
less basic amine NEt3 e, 10–15% PhCH=CHMe 3’ is
observed, depending on temperature. Formation of 3’
indicates
that
metathesis
proceeds
to
the
monosubstituted metallacyclobutane (MCB) Ru-4’, a
reflection of the inability of NEt3 to trap out the four-
coordinate intermediate (see Ru-3, etc.) via adduct
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formation. More extensive metathesis is inhibited by Ru-4. This heightened vulnerability to base in the
1
2
3
4
5
6
7
8
decomposition. The rapidity of decomposition even at
RT, indicates that the transition state for β-elimination
(i.e. transformation of Ru-4 to Ru-5) is rather low in
energy. The barrier appears to decline as MCB
substitution decreases, as indicated by the very rapid
degradation of HII in the presence of ethylene and base
at RT; see below.
presence of ethylene is of particular interest from the
perspective of “ethenolysis” reactions used to generate α-
olefins from internal olefins, a subject of considerable
interest in multiple contexts, including metathesis of
renewable feedstocks.48 More generally, it underscores
the importance of efficiently sweeping ethylene out of
metathesis reactions where amines or other Bronsted
bases are present, as a means of minimizing catalyst
In the absence of base, catalyst decomposition during
styrene metathesis was much slower, with 9% HII still
present after 24 h at 60 °C. Stilbene was observed in ca.
70% yield. Of note, small amounts of PhCH=CHCH3 3’
and propylene (0.2 equiv vs. starting HII) were also
9
decomposition.
Decomposition
via
base-induced
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deprotonation of the unsubstituted MCB is thus expected
to be particularly problematic during industrial processes
involving HII and related catalysts, where mass transfer
limitations apply; during synthetic reactions with limited
headspace; and during NMR-tube or other sealed-tube
experiments.
evident,
indicating
decomposition
via
the
monosubstituted MCB intermediate. MCB deprotonation
can thus occur even without assistance by base. The Sasol
group earlier reported evidence for β-hydride transfer
from MCB intermediates as a key deactivation pathway
for GIIm in the presence of ethylene.47 Bespalova and co-
workers subsequently invoked such a pathway to account
for decomposition of HII and formation of propylene
under ethylene.32a
Conclusions
The foregoing represents the first study of the effect of
additives on decomposition of the important Hoveyda
catalyst HII. The precatalyst itself proved tolerant toward
all but the most sterically accessible, unbranched primary
amines. While the ether ligand is readily displaced by N-
donors, in most cases this merely generates stable
adducts, which exist in equilibrium with HII. Sterically
unencumbered amines, however, attack the precatalyst
and abstract the benzylidene moiety as NHR(CH2Ar) (R =
nBu, CH2Ph).
Decomposition was much faster under ethylene
atmosphere, even at RT. Exposing HII to ethylene in the
presence of pyrrolidine b (Scheme 8) resulted in >90%
loss of all alkylidene signals within 2 h. This should be
compared with just 8% loss at 2 h under these conditions
in the absence of base. Major products were
In the presence of substrate, the impact of base is much
more dramatic. Metathesis yields are highly sensitive to
the basicity of the amine, and even 1 equivalent of DBU
causes almost complete loss of activity. In all cases,
ArCH2CH=CH2
4
and its β-methylstyrene isomer
ArCH=CHMe 4’, formed in nearly 80% total yield relative
to starting HII. Both originate in MCB Ru-6, consistent
with the pathway shown for the analogous intermediate
Ru-4 in Scheme 7. Somewhat unexpectedly, no propylene
was observed, in contrast to the pyrrolidine-free control
reaction. This is certainly due in part to the efficiency of
decomposition, which hampers the ensuing formation of
the unsubstituted MCB Ru-6. We do not rule out,
however, the possibility that the balance of
decomposition (20%) occurs via this pathway, and that
the propylene gas is lost in the headspace.
however, metathesis is sharply reduced by
a
stoichiometric excess of amine. Closer examination of the
reactions with pyrrolidine, NEt3 and DBU revealed attack
on the key metallacyclobutane (MCB) intermediate, and
indicated that decomposition was complete within ca.
two cycles of metathesis. The organic products of
decomposition were consistent with deprotonation of the
metallacyclobutane by the Bronsted base to form a Ru-
alkyl intermediate, and elimination via E–H activation
pathways. The rapid deactivation by NEt3 is particularly
noteworthy, given the steric protection widely presumed
for tertiary nitrogen centers.
Also of note is the dramatically higher vulnerability of the
MCB intermediate formed in the presence of ethylene,
which was rapidly decomposed in the presence of base
even at ambient temperatures. These data suggest that,
where basic substrates or contaminants are present,
catalyst productivity will be highly sensitive to removal of
ethylene, the usual coproduct of metathesis.
Scheme 8. Organic Products from Base-Induced De-
composition of HII During Ethylene Metathesis.
Experimental
General Procedures. Reactions were carried out using
standard glovebox or Schenk techniques at ambient
temperature, unless otherwise indicated. Dry, oxygen-
free C6H6, CH2Cl2, and hexanes were obtained using a
Glass Contour solvent purification system. C6D6, C7D8,
and CD2Cl2 (Cambridge Isotopes) were degassed by five
Accelerated catalyst decomposition during metathesis of
ethylene, as compared with styrene, is consistent with the
greater
accessibility
of
the
monosubstituted
metallacyclobutane ring in Ru-6, relative to disubstituted
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ACS Catalysis
showed no change after 24 h at RT, or after heating to 60
consecutive freeze/pump/thaw cycles. All solvents were
1
2
3
4
5
6
7
8
stored over 4Å molecular sieves under N2 for at least 12 h
prior to use. Decane and styrene (>99%, Sigma-Aldrich)
were degassed as above and stored over 4 Å molecular
sieves. DBU (98%, Acros), pyridine (>99%, Fisher) and
NEt3 (99%, Alfa Aesar) were distilled over CaH2;
morpholine (Sigma-Aldrich, >99.5%, packed under N2)
was used as received. All other amines (Sigma-Aldrich or
Alfa Aesar; maximum grade, 99% or higher) were
degassed immediately on receipt and stored under N2.
°C for an additional 24 h.
Confirmation of HII–HIIb Equilibrium. A sample was
prepared as above, with collection of an 1H NMR
spectrum after 1 h. The sample was then dried under
vacuum (ca. 50 mTorr) for 20 min, and re-dissolved for
1
analysis. H NMR (C6D6, 500.1 MHz): δ 20.25 (Ru=CHAr
for HIIb, 53%), 16.72 (Ru=CHAr for HII, 47%).
n
Synthesis of [RuCl(H2IMes)(NH2 Bu)4]Cl (Ru-2). To a
9
pink solution of GII (175 mg, 0.206 mmol) in 13 mL C6H6
1
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
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42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
Amine purity was verified by H NMR analysis prior to
use. Ethylene (Linde grade 3.0), 1,3,5-trimethoxybenzene
n
was added NH2 Bu (0.200 mL, 2.02 mmol, 10 equiv). The
solution turned green immediately, and yellow over 24 h.
A pale yellow precipitate deposited over this time. The
solvent was stripped off, and the residue was washed with
hexanes (3 x 5 mL). Yield after drying under vacuum: 128
mg (81%). The corresponding reaction of HII likewise
(>99%,
Sigma-Aldrich)
and
potassium
tris(pyrazolyl)borate (>97%, TCI) were used as received.
Literature methods were used to prepare GII,49 HII,49 and
2-isopropoxybenzaldehyde.50
1
NMR spectra were recorded on Bruker Avance 300 and
500 spectrometers at 296 K, unless otherwise noted, and
referenced to the residual proton or carbon signals of the
deuterated solvent (1H, 13C). Signals are reported relative
to TMS at 0 ppm. Metathesis conversions and yields were
measured on a GC (Agilent 7890A) equipped with a flame
ionization detector (FID) and polysiloxane column
(Agilent HP-5) at an inlet split ratio of 10:1 and inlet
temperature of 250 °C. Retention times were confirmed
by comparison to pure samples. Styrene and stilbene
were quantified from integrated peak areas vs. decane
internal standard, corrected for response factors of
decane and analyte. Calibration curves (peak areas vs.
concentration) were constructed in the relevant
concentration regime to account for the dependence on
detector response for all analytes. GC-MS analysis was
perfomed using an Agilent 5975B inert XL EI/Cl
instrument equipped with a polysiloxane column.
afforded Ru-2, in 69% isolated yield. H NMR (CD2Cl2 +
1% NH2nBu, 500.1 MHz): δ 7.00 (s, 4H, m-CH of Mes), 3.96
(s, 4H, CH2 of H2IMes), 2.69–2.59 (m, 8H, NH2), 2.56 (s,
12H, o-CH3 of Mes), 2.29 (s, 6H, p-CH3 of Mes), 1.99–1.88
(m, 8H, α-CH2 of nBu), 1.33 (t of t, 3JHH = 7 Hz, 8H, β-CH2
of nBu), 1.14 (q of t, 3JHH = 7 Hz, 8H, γ-CH2 of nBu), 0.86 (t,
3JHH = 7 Hz, 12H, CH3 of Bu). 13C{1H} NMR (CD2Cl2 + 1%
n
NH2nBu, 125.8 MHz): δ 224.6 (CNHC of H2IMes), 139.9,
138.5, 137.7, 130.7 (m-CH of Mes), 53.6 (CH2 of H2IMes),
n
n
45.2 (α-CH2 of Bu), 35.8 (β-CH2 of Bu), 20.9 (p-CH3 of
Mes), 20.4 (γ-CH2 of nBu, detected from HMQC
n
correlation with γ-CH2 of Bu), 20.3 (o-CH3 of Mes), 14.0
(CH3 of nBu). IR (ATR, cm-1): ν(N-H) 3361–3134. Anal.
Calc'd. for C37H70N6Cl2Ru: C, 57.64; H, 9.15; N, 10.90.
Found: C, 57.52; H, 9.00; N, 10.79. Note: The NH, β-CH2,
n
and CH3 signals are obscured by added NH2 Bu. The
integration values and multiplicities for these signals
were confirmed from the spectrum for the dominant
species Ru-2 in CD2Cl2 (see SI). The chemical shifts for β-
CH2, and CH3 signals were confirmed by COSY
correlation with γ-CH2.
Preparation of NH(R)(CH2Ar); Ar = o-C6H4-OiPr.
Isopropoxy-substituted benzylamines were prepared by
Stoichiometric Reactions of HII with Nitrogen Bases.
To a solution of HII (15 mg, 0.024 mmol) in 1.00 mL C6D6
was added TMB (ca. 1 mg) as an internal integration
standard. This solution was divided into two portions
(0.012 mmol HII), half being treated with amine or
pyridine, and the other half being used as a control
reaction. In a screw-cap Rotoflo NMR tube, the initial
modification of
a
reported reductive amination
procedure.51 These reactions were carried out in air with
non-dried solvents.
1
ratio of HII : TMB was measured by integrating the H
NMR signals for the [Ru]=CH and TMB sp2-CH protons.
A solution of 12 ꢀL NH2nBu f (8.9 mg, 0.12 mmol, 10 equiv)
in 80 ꢀL C6D6 was injected using a gas-tight syringe. The
pierced septum was immediately protected with Parafilm,
a stopwatch was started, and the mixture was shaken
n
R = n-Bu (1). NH2 Bu (1.1 mL, 0.80 g, 11 mmol) and excess
Na2SO4 (ca. 4 g) were added to a stirred, colorless
solution of o-isopropoxybenzaldehyde (1.2 g, 7.1 mmol) in
30 mL THF. After 2 h, the mixture was filtered to remove
excess Na2SO4. The filtrate was treated with sodium
borohydride (1.1 g, 29 mmol) and 15 mL CH3OH, and
stirring was continued for 2 h. The reaction was then
quenched with 20 mL saturated aq. NH4Cl, extracted with
CH2Cl2, washed with brine, dried with Na2SO4, and
stripped of solvent. Chromatography on silica. gel (3%
MeOH + 0.5% NH4OH in CH2Cl2) afforded 1 as a colorless
1
vigorously for 30 s. The first H NMR spectrum was
collected within 4 min. Loss of the alkylidene signals was
monitored at 20 min intervals over 12 h.
For the corresponding reaction of benzylamine g, the first
spectrum was measured at 15 min and 24 h (ca. 50% loss
in total alkylidene at 24 h). Spectra were measured at 24
h intervals for a further 72 h. For all other amines
(morpholine a, pyrrolidine b, pyridine c, DBU d, NEt3 e,
sec-butylamine h), spectra were measured at 1 h and
again at 24 h. For pyridine c and sec-butylamine h,
spectra were recorded at –20 °C (C7D8) to reduce the
breadth of the alkylidene signal. Reactions of a–e and h
liquid. Yield 1.37
g (88%). Note: for compound
numbering, see SI. 1H NMR (C6D6, 300.3 MHz): δ 7.45 (dd,
4
3
3JHH = 7 Hz, JHH = 1 Hz, 1H, C3H of Ar), 7.11 (ddd, JHH = 8
Hz, 4JHH = 1 Hz, 1H, C5H of Ar), 6.90 (ddd, 3JHH = 7 Hz, 4JHH
= 1 Hz, 1H, C4H of Ar), 6.65 (d, 3JHH = 8 Hz, 1H, C6H of Ar),
ACS Paragon Plus Environment

ACS Catalysis
Page 8 of 12
3
i
4.20 (septet, JHH = 6 Hz, 1H, CH of Pr), 3.93 (s, 2H, remaining solution was likewise treated with styrene, and
3
n
1
2
3
4
5
6
7
8
used as a control reaction. Both reactions were heated to
60 °C, and monitored at 2 h intervals. At 10 h: 90% loss of
alkylidene; 99% at 18 h. Additional experiments utilized
10 equiv DBU d or NEt3 e. No alkylidene signals were
evident for either of these bases after 30 min. For
additional experiments at 21 °C: complete loss of
alkylidene after 1h for NEt3 e. With DBU d: 88% loss at 10
h, complete decomposition by 18 h. With pyrrolidine b:
78% loss of alkylidene at 7 d (NMR data collected at 24 h
intervals). Under all conditions, <4% stilbene was formed
(GC-FID analysis). The organic decomposition products
ArCH2N), 2.59 (t, JHH = 7 Hz, α-CH2 of Bu), 2.46 (br s,
1H, NH), 1.57–1.39 (m, 2H, β-CH2 of nBu), 1.37–1.20 (m, 2H,
γ-CH2 of nBu), 1.10 (d, 3JHH = 6 Hz, 6H, CH3 of iPr), 0.85 (t,
3JHH = 7 Hz, CH3 of nBu). 13C{1H} NMR (C6D6, 75.53 MHz): δ
156.5 (C1 of Ar), 130.4 (C3H of Ar), 130.0 (C2 of Ar), 128.1
(C5H of Ar, by HMQC correlation with C5H), 120.6 (C4H
of Ar), 112.9 (C6H of Ar), 69.7 (CH of iPr), 49.2 (ArCH2N),
n
n
i
49.1 (α-CH2 of Bu), 32.5 (β-CH2 of Bu), 22.1 (CH3 of Pr),
9
n
n
20.8 (γ-CH2 of Bu), 14.2 (CH3 of Bu). GC-MS m/z: [M+]
calc’d for C14H23NO, 221.2; found, 221.2. IR (ATR, cm-1):
ν(N-H) 3365. Anal. Calc'd. for C14H23NO: C, 75.97; H,
10.47, 6.33. Found: C, 75.63; H, 10.20; N, 6.56.
10
11
12
13
14
15
16
17
18
19
20
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23
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59
60
were (E)–PhCH=CHCH2Ph
3
(major) and (E)–
PhCH=CHCH3 3’ (minor): proportions are given in Table
2. Alkylidene signal for GIIb intermediate): δ 19.6 7 ppm.
R = CH2Ph (1’). Synthesis as for 1, using NH2CH2Ph in
n
1
place of NH2 Bu. Yield: 61%. H NMR (C6D6, 300.3 MHz):
1
δ 7.37 (d, 3JHH = 8 Hz, 2H, o-Ph), 7.31 (dd, 3JHH = 8 Hz, 4JHH
Characterization data for (E)–PhCH=CHCH2Ph 3. H
3
3
NMR (C6D6, 500.1 MHz): δ 6.31 (d, JHH = 16 Hz, 1H,
= 2 Hz, 1H, C3H of Ar), 7.20 (t, JHH = 8 Hz, 2H, m-Ph),
PhHC=), 6.19 (dt, 3JHH = 16 Hz, 3JHH 7 Hz, 1H, =CHCH2Ph),
7.14–7.07 (overlapping m, 2H, p-Ph + C5H of Ar), 6.89
(ddd, 3JHH = 7 Hz, 4JHH = 1 Hz, 1 H, C4H of Ar), 6.64 (d, 3JHH
= 8 Hz, 1H, C6H of Ar), 4.16 (septet, 3JHH = 6 Hz, 1H, CH of
iPr), 3.89 (s, 2H, NCH2Ar), 3.71 (s, 2H, NCH2Ph), 1.50 (br s,
1H, NH), 1.04 (d, 3JHH = 6 Hz, 6H, CH3 of iPr). 13C{1H} NMR
(C6D6, 75.53 MHz): δ 156.4 (C1 of Ar), 141.6 (ipso-Ph), 130.4
(C3H of Ar), 130.3 (C2 of Ar), 128.53, 128.52, 128.4, 127.0 (p-
Ph), 120.6 (C4H of Ar), 112.9 (C6H of Ar), 69.7 (CH of iPr),
3
1
13
3.25 (d, JHH = 7 Hz, 2H, =CHCH2Ph). H and C{1H} NMR
signals for the Ph group of 3 were incompletely resolved
from those for styrene and styrenyl ether 2. Key 13C{1H}
NMR data (C6D6, 125.8 MHz): δ 131.5 (PhHC=), 129.4
(=CHCH2Ph), 39.6 (=CHCH2Ph). DEPT-135 experiments
support assignment of the key olefin and methylene
1
signals; H-COSY experiments confirm connectivity (for
i
spectra, see SI). GC-MS m/z: [M+] calc’d for C15H14, 194.1;
found, 194.1. NMR43 and EI-MS52 data agree with
literature values for 3.
53.4 (NCH2Ph), 49.1 (NCH2Ar), 22.1 (CH3 of Pr). GC-MS
m/z: [M+] calc’d for C17H21NO, 255.2; found, 255.2. IR
(ATR, cm-1): ν(N-H) 3337. Anal. Calc'd. for C17H21NO: C,
79.96; H, 8.29, 5.49. Found: C, 79.77; H, 8.09; N, 5.36.
1
Characterization data for (E)–PhCH=CHCH3 3’. H
3
NMR (C6D6, 500.1 MHz): δ 6.29 (d, JHH = 16 Hz, 1H,
Assessing Impact of Base on Maximum Turnover
Numbers (TON) in Self-Metathesis of Styrene. A
stock solution of styrene and decane was prepared (0.275
M and 0.215 M, respectively) and an aliquot (ca. 50 µL)
was taken to measure the initial ratio of substrate to
internal standard. A Schlenk tube equipped with a stir-
bar was charged with 2.0 mL of this stock solution (0.55
mmol styrene, 0.43 mmol decane) and diluted to 4.9 mL
with C6H6. Pyrrolidine b was then added (0.10 mL of a
0.55 M stock solution in C6H6; 0.055 mmol; 10 equiv vs.
HII). Finally, HII (0.50 mL of a 0.011 M stock solution, 5.5
µmol) was added. Final volume: 5.5 mL C6H6, [styrene] =
100 mM, [base] = 10 mM, [HII] = 1 mM). The reaction
vessel was transferred to a Schlenk line and heated to 60
°C within 10 min. After stirring for 24 h and 48 h, aliquots
were removed against a flow of N2, quenched with excess
KTp (ca. 1 mg, >10 equiv vs. Ru) in 1 mL CH2Cl2, and
analyzed by GC-FID. Values are averages of two
independent trials (± 2.5%).
3
3
PhHC=C), 6.03 (d of q, JHH = 16 Hz, JHH = 7 Hz, 1H,
C=CHCH3), 1.64 (d, 3JHH = 7 Hz, 3JHH = 3H, C=CHCH3).
(b) During Degenerate Metathesis of Ethylene. A
solution of HII (15 mg, 0.024 mmol) and TMB (ca. 2 mg,
0.012 mmol) was prepared in 1.20 mL C6D6. An aliquot
(0.60 mL, 0.012 mmol HII) was transferred to a J-Young
NMR tube, and pyrrolidine (10 ꢀL, 0.12 mmol, 10 equiv)
was added. The remaining solution was used as a control
reaction. A 1H NMR spectrum was collected to determine
the integration ratio of HII relative to TMB. To saturate
the solutions in ethylene, each sample was freeze-pump-
thaw degassed (5 x), then thawed under static vacuum. 1
atm of C2H4 was introduced at RT, samples were shaken
vigorously, and a timer was started. 1H NMR spectra were
collected after 2 h and 16 h (when full decomposition was
evident). In situ yields of styrenyl ether 2, ArCH2CH=CH2
4, and ArCH=CHCH3 4’ were quantified by integration of
well-isolated olefinic signals relative to starting HII
(normalized against TMB). Specific values: 6.10–6.00 (m,
1H, 4), 6.21–6.13 (m, 1H, 4’), 5.74 (dd, 3JHH = 10 Hz, 2JHH = 2
Hz, 1H, 2). Values for 4 and 4’ agree with data previously
Identifying Catalyst Decomposition Products
Formed by Metathesis in the Presence of Base.
(a) During Self-Metathesis of Styrene. A solution of
HII (15 mg, 0.024 mmol) and TMB (ca. 1 mg, 0.006 mmol)
was prepared in 1.20 mL C6D6. An aliquot (0.60 mL, 0.012
mmol HII) was transferred to a J-Young NMR tube.
Pyrrolidine b (10 ꢀL, 0.12 mmol, 10 equiv) was added, and
a 1H NMR spectrum was collected to determine the initial
integration ratio of HII relative to TMB. Styrene (14 ꢀL,
0.12 mmol, 200 mM, 10 equiv) was then added. The
reported.53
decomposition.
GC-MS
data
collected
after
full
1
Characterization data for ArCH2CH=CH2 4. H NMR
(C6D6, 500.1 MHz): δ 6.09–5.97 (m, 1H, CH=CH2), 5.12–
i
5.00 (m, 2H, CH=CH2), 4.24–4.13 (m, 1H, CH3 of Pr,
3
overlaps with 4’), 3.48 (d, JHH
=
6
Hz, 2H,
3
i
ArCH2CH=CH2), 1.09 (d, JHH = 6 Hz, 6H, CH3 of Pr).
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ACS Catalysis
Chem. 2005, 9, 1535–1549. (f) Gaich, T.; Mulzer, J. Curr. Top.
Med. Chem. 2005, 5, 1473–1494. (g) Deiters, A.; Martin, S. F.
Chem. Rev. 2004, 104, 2199–2238.
Aromatic signals not assigned due to overlap with signals
from Ru species present. ESI-MS, [M+]: m/z calc’d for
1
2
3
4
5
6
7
8
C12H16O, 176.1. Found: 176.1.
(5)
Compain, P.; Hazelard, D. Top. Heterocyclic Chem.
Characterization data for (E)-ArCH=CHCH3 4’. 1H
2015, 1–43.
NMR (C6D6, 500.1 MHz): δ 6.17 (d of q, 3JHH = 16 Hz, 3JHH
=
(6)
van Lierop, B. J.; Lummiss, J. A. M.; Fogg, D. E., Ring-
6 Hz, 1H, =CHCH3), 4.24–4.13 (m, 1H, CH3 of iPr, overlaps
Closing Metathesis. In Olefin Metathesis-Theory and Practice,
Grela, K., Ed. Wiley: Hoboken, NJ, 2014; pp 85–152.
3
4
4
with 4), 1.75 (dd, JHH = 7 Hz, JHH = 3 Hz, JHH = 3H,
C=CHCH3), 1.10 (d, 3JHH = 6 Hz, 6H, CH3 of iPr). Aromatic
signals not assigned due to overlap with signals from Ru
species present. ESI-MS, [M+]: m/z calc’d for C12H16O,
176.1. Found: 176.1.
(7)
(8)
Compain, P. Adv. Synth. Catal. 2007, 349, 1829–1846.
Nicola, T.; Brenner, M.; Donsbach, K.; Kreye, P. Org.
9
Process Res. Dev. 2005, 9, 513–515.
(9)
Yee, N. K.; Farina, V.; Houpis, I. N.; Haddad, N.;
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Frutos, R. P.; Gallou, F.; Wang, X.-J.; Wei, X.; Simpson, R. D.;
Feng, X.; Fuchs, V.; Xu, Y.; Tan, J.; Zhang, L.; Xu, J.; Smith-
Keenan, L. L.; Vitous, J.; Ridges, M. D.; Spinelli, E. M.; Johnson,
M.; Donsbach, K.; Nicola, T.; Brenner, M.; Winter, E.; Kreye, P.;
Samstag, W. J. Org. Chem. 2006, 71, 7133–7145.
ASSOCIATED CONTENT
Supporting Information. NMR spectra for isolated
Ru-1, amine derivatives 1 and 1’, in situ-generated
HIIb, and NMR spectra and GC traces for base-
induced decomposition of HII. This material is availa-
(10)
Clark, W. M. Org. Process Res. Dev. 2008, 12, 226–234.
(11) For an early report noting the importance of
Wang, H.; Goodman, S. N.; Dai, Q.; Stockdale, G. W.;
protecting groups in RCM of amine-containing substrates, see:
(a) Fu, G. C.; Nguyen, S. T.; Grubbs, R. H. J. Am. Chem. Soc. 1993,
115, 9856–9857. For an excellent overview of effective and
undesirable protecting-group strategies, and the inhibiting
effect of carbonyl chelation, see Ref. 7; for updates, see Refs. 5–6.
Robinson and co-workers have reported the efficacy of simple
ammonium salts, where solubility permits. See: (b) Woodward,
C. P.; Spiccia, N. D.; Jackson, W. R.; Robinson, A. J. Chem.
Commun. 2011, 47, 779–781.
ble free of
http://pubs.acs.org.
charge via the Internet at
AUTHOR INFORMATION
Corresponding Author
* Email dfogg@uottawa.ca
Notes
(12)
Lafaye, K.; Nicolas, L.; Guérinot, A.; Reymond, S. b.;
The authors declare no competing financial interest.
Cossy, J. Org. Lett. 2014, 16, 4972−4975.
(13)
Saha, N.; Chatterjee, B.; Chattopadhyay, S. K. J. Org.
ACKNOWLEDGMENT
Chem. 2015, 80, 1896–1904.
(14)
Curto, J. M.; Kozlowski, M. C. J. Org. Chem. 2014, 79,
This work was funded by NSERC of Canada. NSERC is
thanked for a CGSD scholarship to BJI, and Lycée P.-G.
de Gennes-ENCPB and DAREIC (France) for support to
BTD under the BTS Chemistry exchange program.
5359–5364.
(15)
Garzon, C.; Attolini, M.; Maffei, M. Eur. J. Org. Chem.
2013, 2013, 3653–3657.
(16)
Komatsu, Y.; Yoshida, K.; Ueda, H.; Tokuyama, H.
Tetrahedron Lett. 2013, 54, 377–380.
(17)
Cochet, T.; Roche, D.; Bellosta, V.; Cossy, J. Eur. J. Org.
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generation Grubbs catalyst is immediately decomposed to non-
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18 Hz, 2JHH = 2 Hz); the other at 5.21 ppm (3JHH(cis) = 11 Hz, 2JHH
=
2 Hz).
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(where Ar is the non-chelated aryl group o-iPrO-C6H4). This
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supported by GC-MS analysis of a reaction aliquot, and by
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1
comparison of the H NMR spectrum with that of an authentic
sample prepared by reductive amination of the parent aldehyde:
see S.I.
(36) Reported pKa values for the conjugate acids in
acetonitrile: morpholine, a: 16.6; pyrrolidine b: 19.6; pyridine c:
12.6; DBU d: 24.1; triethylamine e: 18.5; n-butylamine f: 18.3;
benzylamine g: 16.9. See: Cox, B. G., Acids and Bases: Solvent
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(38) The structure depicted for Ru-2, in which the chloride
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proposed on the basis of the high symmetry evident by 1H NMR
analysis. Consistent with the presence of four equivalent
butylamine ligands, one singlet is seen for the H2IMes backbone
protons, and for the mesityl CH protons, integrating 4:4:8
relative to the multiplet for the n-butylamine NCH2 protons.
(39) Nucleophilic attack of phosphines on Ru-benzylidene
species has likewise been reported, although the occurrence is
relatively rare, presumably owing to steric restrictions.
Exceptions include Hofmann’s RuCl2(tBu2PCH2PtBu2)(=CHPh)
system, in which the ring strain of the four-membered κ2-PP
chelate is relieved by attack at the benzylidene carbon. See: (a)
Hansen, S. M.; Rominger, F.; Metz, M.; Hofmann, P. Chem. Eur.
J. 1999, 5, 557–566. In a second example, reaction of GI with
CO triggered migration of a PCy3 ligand to the alkylidene
carbon: the presence of the π-acceptor CO ligands renders the
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