Ireland, B. J.; Dobigny, B. T.; Fogg, D. E. “Decomposition of a Phosphine-Free Metathesis Catalyst by Amines and Other Bronsted Bases: Metallacyclobutane Deprotonation as a Major Deactivation Pathway” ACS Catal. 2015 5 (8) 4690-4698 [DOI: 10.1021/acscatal.5b00813]
Rationally expanding the functional group tolerance of an organometallic catalyst requires a detailed understanding of the mechanism(s) contributing to its decomposition. While the implementation of ruthenium catalyzed olefin metathesis has benefitted from a broad functional group tolerance, nitrogen bases have remained challenging often requiring N-protection to achieve good yields with reasonable catalyst loadings. Beyond their ability to function as Lewis bases and occupy open coordination sites necessary for catalysis, the Fogg group has recently demonstrated the abstraction of benzylidene ligand from Grubbs Catalyst® C848 upon reaction with n-butylamine and the decomposition of a related methylidene complex in the presence of a variety of amines (Figure 1). Aside from the reaction with n-butylamine, PCy3 plays a critical role in these mechanisms. In the title publication, Fogg extends these studies to phosphine-free catalysts (ex: Grubbs Catalyst C627).
Figure 1: Adduct formation and decomposition of 1st and 2nd generation Grubb’s catalysts
Studies were initiated by examining the interaction of an excess of nitrogen base with Grubbs Catalyst C627 and Grubbs Catalyst C848 (Table 1). Secondary, heterocyclic, and bulky primary amines were observed to form stable adducts with both catalyst precursors while no reaction was observed with the tertiary amine. Sterically uncongested primary amines afforded adducts rapidly and were additionally observed to afford non-alkylidene containing ruthenium species (decomposition). The rate of this decomposition tracked with substrate basicity [H2NnBu > H2NBn] and a proposed mechanism involves nucleophilic attack of the primary amine at the [Ru]=CHR carbon.
Table 1: Reactions of Grubbs Catalyst C627 and Grubbs Catalyst C848 with various amines
Though adduct formation affords a reasonable explanation for reduced rates of catalysis, the Fogg group continued their investigation by examining the effect of these bases on the homocoupling of styrene (Figure 2). While 1 mol% of amine additive was offset by adduct formation, reactions conducted in the presence of 10 mol% amine show a strong correlation between Brønsted basicity and reduced yields. To further understand these results, NMR experiments were conducted with 10 equivalents each of styrene and amine. In each of the reactions examined, o-isopropoxystyrene was quantitatively liberated and within 18 h decomposition resulted affording the organic byproduct trans-1,3-diphenylpropene. The structure of the byproduct implicates attack of base on the metallacyclobutane intermediate as the key mode of decomposition. Additional experiments were conducted under an ethylene atmosphere affording an increased rate of catalyst decomposition (presumably through reduced steric protection of the metallacyclobutane) and the appropriate byproducts (Figure 3).
Figure 2: Self-metathesis of styrene in the presence of amines
Figure 3: Catalyst decomposition in the presence of amine
While this is only the first study of additives on the decomposition of Grubbs Catalyst C627 (or similar Hoveyda-Grubbs type precatalysts), the Fogg group has already elucidated two catalyst vulnerabilities:
- decomposition of precatalysts by sterically unencumbered primary amines – though most amines form adducts with precatalysts resulting in deactivation
- decomposition of base sensitive metallacyclobutane intermediates by deprotonation
Unfortunately a general solution for increasing amine tolerance is not disclosed, however, the importance of efficient ethylene removal is underscored. Future work will hopefully focus on new catalyst structures that are electronically or sterically predisposed to greater amine tolerance.