Donor-induced decomposition of the Grubbs catalysts: An intercepted intermediate

Article abstract of DOI:10.1021/om501011y

The σ-alkyl species RuCl₂(CH₂PCy₃)(py)₃ (3a) is intercepted on adding pyridine to the first-generation Grubbs catalyst 1a during RCM or to the isolated resting-state species RuCl₂(PCy₃)₂(=CH₂) (2a). Complex 3a is formed by pyridine-induced displacement of PCy₃ and nucleophilic attack of the liberated PCy₃ on the methylidene carbon. The rapid, near-quantitative conversion of 2a into 3a indicates that nucleophilic attack by PCy₃ is the primary deactivating event. Once formed, 3a decomposes more slowly via several competing pathways. One such pathway involves elimination of the σ-alkyl ligand as [CH₃PCy₃]Cl (A), following proton and chloride abstraction. Observation of nearly 80% 3a during RCM by 1a in the presence of pyridine confirms the relevance of this behavior to metathesis and implicates the resting-state methylidene 2a as the vulnerable species, rather than the metallacyclobutane intermediate. Any donor capable of displacing PCy₃ and stabilizing a five-coordinate methylidene adduct is predicted to trigger the same deactivation sequence, steric factors permitting.

Full text of DOI:10.1021/om501011y

Communication
pubs.acs.org/Organometallics
Donor-Induced Decomposition of the Grubbs Catalysts:
An Intercepted Intermediate
Justin A. M. Lummiss,† William L. McClennan,† Robert McDonald,‡ and Deryn E. Fogg*,†
†Center for Catalysis Research & Innovation and Department of Chemistry, University of Ottawa, Ottawa, Ontario, Canada K1N
6N5
‡Department of Chemistry, University of Alberta, Edmonton, Alberta, Canada T6G 2G2
S
* Supporting Information
ABSTRACT: The σ-alkyl species RuCl2(CH2PCy3)(py)3 (3a) is intercepted on
adding pyridine to the first-generation Grubbs catalyst 1a during RCM or to the
isolated resting-state species RuCl2(PCy3)2(CH2) (2a). Complex 3a is formed by
pyridine-induced displacement of PCy3 and nucleophilic attack of the liberated PCy3
on the methylidene carbon. The rapid, near-quantitative conversion of 2a into 3a
indicates that nucleophilic attack by PCy3 is the primary deactivating event. Once
formed, 3a decomposes more slowly via several competing pathways. One such
pathway involves elimination of the σ-alkyl ligand as [CH3PCy3]Cl (A), following
proton and chloride abstraction. Observation of nearly 80% 3a during RCM by 1a in
the presence of pyridine confirms the relevance of this behavior to metathesis and
implicates the resting-state methylidene 2a as the vulnerable species, rather than the
metallacyclobutane intermediate. Any donor capable of displacing PCy3 and stabilizing
a five-coordinate methylidene adduct is predicted to trigger the same deactivation
sequence, steric factors permitting.
lefin metathesis is now a core tool in organic synthesis.1,2
With industrial applications of the molecular metathesis
catalysts now emerging, an improved understanding of their
deactivation pathways3,4 is becoming increasingly important.5
The Grubbs benzylidene precatalysts (1; Chart 1) were shown
Scheme 1. Proposed Pathway for Decomposition of 2b via
Zwitterionic 3b
O
Chart 1. Grubbs Metathesis Catalysts and Their Resting-
State Methylidene Derivatives
Attack of the liberated PCy3 on the methylidene ligand is
proposed on the basis of prior work with isolated 2b discussed
below. The ensuing elimination of the alkylphosphine ligand in
3b as phosphonium salt A is facilitated by the presence of the
NH group. Such proton-shuttling pathways are well established
in Ru-amine chemistry.18,19 In prior examples in which A or
related species were observed in the absence of an N−H
moiety,20−24 proton abstraction most probably involves C−H
activation.
in early work to be significantly more robust than the
methylidene derivatives (e.g., 2) that represent the catalyst
resting state.6,7 High-yield routes to the latter species,8,9
including 13C-labeled isotopologues 1* and 2*,10 facilitate
investigation of decomposition pathways relevant to catalysis.
Reports from pharma highlight NH-amine contaminants,
among others,1c as detrimental to RCM.11,12 A deeper
understanding of amine-mediated deactivation is thus of keen
interest.13−15 Adding 1 equiv of primary or secondary amine to
RCM reactions promoted by the second-generation catalyst 1b
was recently shown to effect complete loss of the catalyst
charge within 90 min at 60 °C.15 A plausible mechanism is
shown in Scheme 1. The initial displacement of phosphine has
ample precedents in the reactions of 1b with amines.14−17
The σ-alkyl moiety in putative intermediate 3b is modeled on
the proposed structure of the key intermediate in decom-
position of isolated 2b, suggested in a seminal study by Hong
Received: October 4, 2014
© XXXX American Chemical Society
A
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Organometallics
Communication
and Grubbs.23 Such species have been invoked in other
deactivation studies,20−22,25 while related structures were
reported in early work by the Roper26 and Hofmann27 groups.
The relevance of the Hong−Grubbs study to deactivation
during catalysis is clouded, however, by the much slower rate of
decomposition of 2b (days at 55 °C), as well as the observation
of multiple products,23 suggesting the operation of several
competing pathways. Here we describe the successful
interception of the first-generation σ-alkyl complex 3a; we
show that formation of 3a is the primary deactivation event,
irrespective of ensuing decomposition pathways, and we
demonstrate that this behavior is relevant not merely to
methylidene complex 2a but also to RCM reactions promoted
by 1a.
With the intention of inhibiting E−H activation pathways
that promote elimination of the alkylphosphine ligand, we
turned to reactions with pyridine, in place of a secondary
amine. From prior work, however, we suspected that use of
pyridine would be insufficient to retard proton abstraction from
electron-rich 2b. Stirring 2b in 1/5 pyridine/toluene was
reported to yield RuCl2(H2IMes)(py)3 (29%; isolated) and
unspecified amounts of A.23,28 Indeed, we found that the
corresponding in situ reaction of labeled 2b* with 10 equiv of
py (Scheme 2a) liberated ca. 90% A* within <5 min at ambient
temperature, without observable intermediates.
Figure 1. Crystal structure of RuCl2(σ-CH2PCy3)(py)3 (3a). Non-
hydrogen atoms are represented by Gaussian ellipsoids at the 30%
probability level. Hydrogen atoms attached to C1 are shown with
arbitrarily small thermal parameters; other hydrogen atoms are
omitted.
Instead, bis-pyridine adducts RuCl2(L)(py)2(CHPh) were
reported for both first- and second-generation systems (L =
PCy3,30 H2IMes16).
Complete decomposition of isolated 3a in solution at room
temperature occurred over days in C6D6 or hours in CD2Cl2. At
60 °C in C6D6, no 3a remained after 18 h. Free PCy3 was
observed by 31P{1H} NMR analysis, accompanied by significant
amounts of A (Scheme 3). Crystals of the known31 complex
Scheme 2. Speciation on Treating 13C-Labeled 2* with
Pyridine (Percent of Total 31P{1H} NMR Integration): (a)
Decomposition of 2b*; (b) Formation of σ-Alkyl Species 3a*
via Displacement of PCy3 from 2a* and Attack of Liberated
PCy3 at the Methylidene Carbon
Scheme 3. Thermally Promoted Decomposition of Isolated
3a: Products Observed by 31P{1H} NMR Analysis (Percent
vs Total Integration) or Precipitation
RuCl2(py)4 also deposited. The phosphonium salt A is
presumably formed via C−H activation pathways, as noted
above. Multiple decomposition reactions are operative,
however, as indicated by the observation of three further,
unidentified 31P{1H} NMR signals (B−D). To determine
whether any of these are due to the proposed ylide Cy3P
CH2,23 we monitored the decomposition of labeled 3a*. The
singlet multiplicity of B−D was retained, however (see the
Supporting Information; Figure S7). This rules out assignment
To retard proton abstraction, we therefore employed the less
electron rich first-generation complex. Addition of pyridine to
13C-labeled 2a* at room temperature resulted in immediate loss
of the methylidene signal (Scheme 2b). Only ca. 5% A* was
apparent, however. The 31P{1H} NMR spectrum was instead
dominated by a doublet at 55.7 ppm (1JPC = 9.8 Hz),29 which
accounted for 95% of the 13C-labeled methylidene moiety. The
corresponding 13C{1H} NMR doublet appeared unusually far
13
of any of these compounds as Cy3P CH2 and indeed
indicates that none retain the 13C−P moiety. Elimination of A
via intramolecular proton abstraction may be a valid alternative
to the proposed ylide-extrusion pathway.
1
upfield (−12.3 ppm; JPC = 9.8 Hz), implying considerable
shielding. Assignment as 3a was confirmed by X-ray analysis of
crystals that deposited from pentane/pyridine, following a
preparative-scale reaction of 2a (150 mg; 90% crude yield).
The ORTEP plot of 3a is depicted in Figure 1. Of note, three
pyridine ligands are present, and no Ru-bound PCy3 remains.
In contrast, reaction of the Grubbs catalysts 1a,b with pyridine
showed no evidence for attack on the benzylidene ligand.
While the data above indicate that the fate of the σ-alkyl
moiety is not limited to A,32 all of the products observed
originate in 3a. Nucleophilic attack of free PCy3 can thus be
identified as the key vector for decomposition of 2a in the
presence of pyridine. Importantly, 3a is also observed during
metathesis by the first-generation Grubbs catalyst 1a, where
pyridine is present (Scheme 4). Thus, in the RCM of 4, the
B
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Organometallics
Communication
Scheme 4. Donor-Induced Decomposition during RCM
ASSOCIATED CONTENT
* Supporting Information
■
S
Text, figures, a table, and a CIF file giving experimental and
crystallographic data for 3a and NMR spectra. This material is
available free of charge via the Internet at http://pubs.acs.org.
AUTHOR INFORMATION
Corresponding Author
*E-mail for D.E.F.: dfogg@uottawa.ca.
■
proportion of 3a reached ca. 80% of the theoretical maximum
at 1 h. We infer that py-induced decomposition during catalysis
results from attack on the methylidene resting state 2a, rather
on than the metallacyclobutane intermediate.33
This behavior holds potentially general implications. Of keen
interest is the possibility illustrated in Scheme 5a: that is, that
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
The NSERC of Canada is thanked for financial support.
■
REFERENCES
■
Scheme 5. (a) Donor-Induced Decomposition of the Grubbs
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1
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D
dx.doi.org/10.1021/om501011y | Organometallics XXXX, XXX, XXX−XXX