Real-time analysis of ring closing metathesis reactions




Liu, Jie

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Ring closing metathesis (RCM) is a chemical transformation that converts a bisalkene compound into a cycloalkene. It is catalyzed by transition metal complexes containing carbene ligands (that feature metal-carbon double bonds). The mechanism is well-understood, however, there are numerous details of the reaction that are less well understood, especially concerning catalyst activation and decomposition and formation of byproducts. This thesis takes a new approach to the study of RCM: analysis of the reaction using real-time mass spectrometric techniques. Electrospray ionization (ESI) mass spectrometry was employed in this study, and the real-time aspect was enabled by using pressurized sample infusion (PSI). Observation of the reactants and products was enabled using charge-tagged bis-alkenes of the general formula [Bu2N{(CH2)nCH=CH2}2]+ [PF6]–. These were synthesized in two steps using a generally applicable methodology to generate a wide range of ring sizes of the product, from 5- to 15-membered rings. Examination of their behavior under carefully optimized RCM conditions using Grubbs’ second-generation catalyst showed a wide variation in reaction rates and amount of byproducts, largely due to ring-strain effects (especially high for 5- and 9-membered rings). Byproducts always exhibited a 14 Da mass unit difference from starting materials or products, and Orbitrap MS analysis confirmed it was CH2. Isomerization was suspected to lead to byproducts. A pathway for byproducts via isomerization and cross metathesis was proposed. The source of actual isomerization catalyst was believed to be from the precatalyst itself as the evidence of precatalyst decomposition was observed. Finally, to prove our isomerization hypothesis, an authentic isomerization catalyst was deliberately added into a fast and clean reaction along with Grubbs’ second-generation catalyst, and it produced the expected byproducts. Only small amounts of oligomeric intermediates were observed, probably because of the low concentrations used. [ClPCy3]+ was a new short-lived decomposition product stemming from catalyst breakdown, along with already-known imidazolium and protonated phosphine decomposition products. Overall, the thesis provides deep new insights into the nature of RCM reactions, in particular revealing the importance of isomerization in RCM reactions that are slow due to ring strain effects and in uncovering a new decomposition pathway for important RCM catalysts.



Ring Closing metathesis, Grubbs II catalyst, ESI-MS, isomerization, real-time monitoring, charged tag