Challenging Metathesis Catalysts with Nucleophiles and Brønsted Base: Examining the Stability of State-of-the-Art Ruthenium Carbene Catalysts to Attack by Amines

Abstract

Critical to advancing the uptake of olefin metathesis in leadingcontexts, including pharmaceutical manufacturing, is identification of highlyactive catalysts that resist decomposition. Amines constitute an aggressivechallenge to ruthenium metathesis catalysts. Examined here is the impact of1,8-diazabicyclo[5.4.0]undec-7-ene (DBU), morpholine,n-butylamine, andtriethylamine on Ru metathesis catalysts that represent the current state ofthe art, including cyclic alkyl amino carbene (CAAC) and N-heterocycliccarbene (NHC) complexes. Accordingly, the amine-tolerance of the nitro-Grela catalyst RuCl2(H2IMes)(CHAr) (nG;Ar=C6H4-2-OiPr-5-NO2)iscompared with that of its CAAC analoguesnGC1andnGC2, and theHoveyda-class catalyst RuCl2(C2)(CHAr′)HC2(Ar′=C6H4-2-OiPr). InC1, the carbene carbon isflanked by anN-2,6-Et2C6H3group and a CMePhquaternary carbon; inC2,byanN-2-iPr-6-MeC6H3group and a CMe2quaternary carbon. The impact of 1 equiv amine per Ru onturnover numbers (TONs) in ring-closing metathesis of diethyl diallylmalonate was assessed at 9 ppm Ru, at RT and 70°C. Thedeleterious impact of amines followed the trend NEt3∼NH2nBu≪DBU∼morpholine. Morpholine is shown to decomposenGC1by nucleophilic abstraction of the methylidene ligand; DBU, by proton abstraction from the metallacyclobutane. Decomposition wasminimized at 70°C, at whichnGC1enabled TONs of ca. 60 000 even in the presence of morpholine or DBU, vs ca. 80 000 in theabsence of base. Unexpectedly, H2IMes catalystnGdelivered 70−90% of the performance ofnGC1at high temperatures, andunderwent decomposition by Brønsted base at a similar rate. Density functional theory (DFT) analysis shows that this similarity isdue to comparable net electron donation by the H2IMes andC1ligands. Catalysts bearing the smallerC2ligand were comparativelyinsensitive to amines, owing to rapid, preferential bimolecular decomposition.