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.
O
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
Chart 1. Grubbs Metathesis Catalysts and Their RestingState 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. The σ-alkyl moiety in putative intermediate 3b is modeled on the proposed structure of the key intermediate in decomposition of isolated 2b, suggested in a seminal study by Hong
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 © XXXX American Chemical Society
Received: October 4, 2014
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dx.doi.org/10.1021/om501011y | Organometallics XXXX, XXX, XXX−XXX
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
