Olefin Metathesis under Spatial Confinement and Continuous Flow: Investigation of Isomeric Side Reactions with a Grubbs-Hoveyda Type Catalyst

A 2(nd)-generation Grubbs-Hoveyda type catalyst was immobilized inside mesoporous silica and used in the ring-closing metathesis (RCM) of an alpha,omega-diene to a large macro(mono)cycle. The goal was to investigate the relationship between substrate concentration, reaction time, and overall experiment time on the rate of isomerization under spatial (mesopore space) confinement with continuous-flow microreactors. RCM reactions are commonly monitored by H-1 NMR analysis, however, elucidation of reaction mixtures yielding large rings with a difference of only a single carbon atom remains difficult, because NMR signals are sometimes indistinguishable. In this work, an analytical platform with on-line separation and detection of UV-active substrate as well as (side) products by high-performance liquid chromatography and a UV/Vis-diode array detector (DAD) plus mass spectrometry served as enabling technology to quantify yield and selectivity under the respective reaction conditions. Using this setup, competitive reaction equilibria and isomerization reactions, in particular, could be resolved. Identification and quantification of relevant compounds of the reaction scheme under spatial confinement became possible despite chemical similarity. Kinetic data revealed that isomerization increases with higher substrate concentrations (up to 250 mM) and longer reaction times (from 1.2 to 18.6 min), but shows a distinct decline for prolonged overall experiment times (up to similar to 250 min).

Automated summary

In this study, a 2(nd)-generation Grubbs-Hoveyda type catalyst was immobilized in mesoporous silica and used in the ring-closing metathesis (RCM) of an alpha,omega-diene to a large macro(mono)cycle. The relationship between substrate concentration, reaction time, and overall experiment time on the rate of isomerization under spatial confinement with continuous-flow microreactors was investigated. The results showed that higher substrate concentrations and longer reaction times increased the isomerization rate, while prolonged overall experiment times led to a decline in the isomerization rate.