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Published on: November 9, 2019
Single-carbon insertion enables conversion of cyclopropenes into cyclobutenes: access to oxaspiro[2.3]hexenes
Maria Chiara Cabua1,2, Iktedar Mahdi1, Ernesto Mesto3
1Department of Pharmacy-Drug Sciences, University of Bari Aldo Moro Via E. Orabona 4 70125 Bari Italy Renzo.Luisi@uniba.it.
Abstract:
We report 1-oxaspiro[2.3]hex-4-enes as a novel strained spiro heterocycle. This motif was accessed via a formal C1 insertion into cyclopropenes. The method employs dihalocarbenes to trigger a skeletal editing process involving in situ bicyclo[1.1.0]butane formation and strain-release-driven ring expansion, delivering halogenated cyclobutenes under simple conditions. A broad substrate scope is demonstrated, enabling access to chloro-, bromo-, and fluoro-substituted spirocycles, including derivatives of bioactive molecules. Mechanistic studies supported by in silico calculations demonstrate an asynchronous, concerted carbene addition followed by intramolecular epoxidation and ring expansion as the rate-determining step.
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