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

• Published in: Organic process research & development Vol. 23; no. 5; pp. 836 - 844
• Main Authors: Szczepaniak, Grzegorz, Nogaś, Wojciech, Piątkowski, Jakub, Ruszczyńska, Anna, Bulska, Ewa, Grela, Karol
• Format: Journal Article
• Language: English
• Published: American Chemical Society 17-05-2019
• Subjects: olefin metathesis; ruthenium; isocyanide; metal scavenger
• ISSN: 1083-6160; 1520-586X
• DOI: 10.1021/acs.oprd.8b00392

A low-waste, time-economical, and scalable semiheterogeneous purification protocol for the removal of ruthenium residues from olefin metathesis (OM) reactions has been developed. It is based on the non-covalent immobilization of the commercially available isocyanide 1,4-bis­(3-isocyanopropyl)­piperazine (QA) on unmodified silica gel. The use of the heterogeneous scavenger QA@SiO 2 synthesized in situ during the purification process was 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 containing only 0.29 ppm Ru. Finally, QA was used in an aqueous medium and reduced the metal contamination from 9977 to 21 ppm.