Org. Process Res.Dev. 2018, 22, 918−946. DOI:10.1021/acs.oprd.8b00093
◆Ethylene, the byproduct of RCM reactions, is the least sterically hindered and most reactive alkene in olefin metathesis reactions. The removal of ethylene from the reaction mixture therefore accelerates the conversion of the starting diene, although in a nonselective fashion, as the rates of both intramolecular and intermolecular reactions are increased by the removal of ethylene.
◆To reduce the cumulative effect of ethylene, which decreases metathesis productivity, RCM reactions are often carried out at elevated temperatures and under an inert atmosphere. The removal of ethylene is often effective because the solubility of ethylene in organic solvents is generally low at elevated temperatures. A more efficient way to remove ethylene completely during RCM is by sparging the reaction mixture with a stream of inert gas.
Note
◆In the example of the synthesis of ciluprevir, low-level (<20 ppm) morpholine was observed in the technical-grade toluene, which caused the inhibition of the catalysis and led to epimerization derived from isomerization of the vinylcyclopropane moiety, requiring an acid wash of the solvent prior to use.