Year: 2025
Type: editorial
Abstract: Nitrogen insertion has emerged as a powerful strategy for converting five-membered rings into six-membered nitrogencontaining heterocycles.Morandi and co-workers from Switzerland reported a continuous-flow adaptation of their previously developed nitrogen insertion methodology, addressing the safety and scalability limitations associated with the batch process (Chem.Commun., DOI: 10.1039/d5cc03194j).A key factor for success is the in situ formation of ammonium carbonate by combining methanolic ammonia with gaseous carbon dioxide, along with the establishment of a Taylor flow regime that prevents clogging caused by solid accumulation.To enable rapid fine-tuning of conditions for each substrate, the authors designed a modular six-feed flow setup, including two feeds dedicated to in-line quenching (dibutyl sulfide and nitrogen).A broad range of five-membered heterocycles, such as TBS-protected indoles and pyrroles as well as indenes and cyclopentadienes, were successfully converted into the corresponding azaarenes in modest to high yields.The method also tolerates various functional groups such as halogens, amides, and alcohols, and its scalability was demonstrated by a gram-scale synthesis example.
Authors: James A. Schwindeman, Alex Kosanovich, Timothy Kwok, Annabel Q. Ansel, James M. MacDougall, Sylvain Guizzetti, Jimmy Lauberteaux, Alexandra Bodnar, Elizabeth M. Dauncey, John Knight
Language: English
Subfield: Biomedical Engineering
Field: Engineering
Domain: Physical Sciences
Open Access status: bronze
OpenAlex ID: W4417166013