Competitive Isomerization and Catalyst Decomposition During Ring-Closing Metathesis



Ring-closing metathesis (RCM) is an elegant means of forming cyclic structural elements in both simple and complex molecules. Mechanistically, the reaction cycle is well understood, though subtle details concerning the fate of the catalyst and the appearance of yield-reducing by-products remain to be fully deciphered. We applied real-time analysis using electrospray ionization mass spectrometry (ESI-MS) to probe the RCM reaction, including studying the dynamics of all charged species in the reaction mixture and investigating the nature of the by-products formed. The catalyst of choice was Grubbs’ second-generation catalyst. The principal findings included the fact that for slower reactions, by-products appeared that differed in mass from the starting material and product by increments of CH2; that isomerization reactions were responsible for these by-products; and that the catalyst decomposes to form charged products including [ClPCy3]+, [HPCy3]+, and the imidazolinium salt of the N-heterocyclic carbene (NHC) ligand. In cases where RCM is slow, isomerization reactions play a disproportionate part in affecting yield of the desired product.


Supplementary material

Supporting Information
Page 2: Experimental procedures Pages 3-5: Substrate synthesis and tabulated 1H and 13C NMR data Pages 6-15: 1H and 13C NMR spectra for substrates Page 16: Tabulated competition experiment rate data Pages 17-21: Plotted kinetic data from competition experiments Page 22: Plotted kinetic data for the R7 vs. R7’ rate comparison experiment Page 23: Expanded mechanistic plot for all R9 side reactions and byproducts Page 24: Substrate-free GII speciation experiment data Pages 25-36: X-ray crystallographic data for R5 and R7 Page 37: Supporting information references