Semiheterogeneous Purification Protocol for the Removal of Ruthenium Impurities from Olefin Metathesis Reaction Products Using an Isocyanide Scavenger

A low-waste, time-economical and scalable semi-heterogeneous purification protocol for the removal of ruthenium residues from olefin metath-esis (OM) reactions has been developed. It is based on the noncovalent immobilization of commercially available isocyanide QA (QA = 1,4-Bis(3-isocyanopropyl)piperazine) on unmodified silica gel. The use of heterogeneous scavenger QA@SiO2 synthesized in situ during the puri-fication process, is shown to yield OM products with metal contamination usually below 5 ppm. Furthermore, the new purification protocol was effective on a gram scale in the ring-closing OM of an intermediate in the synthesis of cathepsin K inhibitors, leading to a product with only 0.29 ppm of Ru. Finally, isocyanide QA was used in an aqueous medium reducing the metal contamination from 9977 to 21 ppm.