Spirocyclizations Involving Oxonium Ylides Derived from Cyclic α‑Diazocarbonyl Compounds: An Entry into 6‑Oxa-2-azaspiro[4.5]decane Scaffold

• Published in: Journal of organic chemistry 2020-12, Vol.85 (23), p.15586-15599
• Main Authors: Dar’in, Dmitry, Kantin, Grigory, Bakulina, Olga, Inyutina, Anna, Chupakhin, Evgeny, Krasavin, Mikhail
• Format: Article
• Language: English
• ISSN: 0022-3263; 1520-6904
• DOI: 10.1021/acs.joc.0c02356

New types of cyclic diazo compounds capable of Rh­(II)-catalyzed spirocyclizations with tetrahydrofuran have been discovered. The formation of the spirocyclic framework is thought to proceed via the formation of Rh­(II) carbene species followed by interaction with the Lewis basic oxygen atom of tetrahydrofuran to give oxonium ylide species. The latter evolves predominantly via the Stevens type rearrangement leading to an [n + 1] ring expansion of the tetrahydrofuran moiety, which results in the formation of a medicinally relevant 6-oxa-2-azaspiro[4.5]­decane scaffold. The spirocyclization process was often observed in competition with mechanistically distinct C–H insertion into a tetrahydrofuran molecule. This competing process gave compounds based on the 3-(tetrahydrofur-2-yl)­pyrrolidine scaffold, which are also relevant from the medicinal chemistry standpoint. These findings enrich the available arsenal of metal-catalyzed spirocyclization methods based on the use of cyclic diazo compounds.