Single-carbon-atom transfer to para-quinone methides from TMSCF2Br

Single-carbon-atom transfer reactions offer a powerful strategy for constructing complex molecular architectures by sequential assembly of substituents around the atomic carbon core. However, the limited availability of atomic carbon sources has significantly hindered progress in this field. Herein, we demonstrate a single-carbon atom transfer reaction utilizing commercially available TMSCF2Br as an atomic carbon equivalent. Through a cascade of 1,6-addition and TBAF-catalyzed intramolecular cyclization with para-quinone methides (p-QMs), gem-difluorinated spiro[2.5]octa-4,7-dien-6-ones were efficiently formed. These spirocyclic intermediates exhibit remarkable electrophilicity, enabling stereoselective capture of diverse nucleophiles to access fluorinated alkenes with excellent stereocontrol. The resulting fluoroalkenes serve as versatile platforms for constructing tetrasubstituted alkenes via nucleophilic vinylic substitution (SNV), achieving excellent stereoselectivities. In the presence of a 1,3-bisnucleophile, for example a C2-substituted acetoacetate ester, cyclic 2-methylene-2,3-dihydrofuran was generated via a sequential SNV reaction with excellent stereoselectivities. Moreover, a computational study and a control experiment provide insight into the mechanism of the reaction.

• Publication year

  2025

• Venue

  Chemical Science

• Publication date

  2025-06-04

• Fields of study

  Medicine, Chemistry

• Identifiers
  DOI 10.1039/d5sc03234bPMID 40510325PMCID 12152741
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

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