Dearomative Intramolecular (4+3) Cycloadditions of Thiophenes

Yufen Zheng; Yueyao Chen; Yuxuan He; Antonio Rizzo; Yuchen Zhou; Kam-Hung Low; Elizabeth H Krenske; Pauline Chiu

doi:10.1002/anie.202407059

Dearomative Intramolecular (4+3) Cycloadditions of Thiophenes

Angew Chem Int Ed Engl. 2024 May 17:e202407059. doi: 10.1002/anie.202407059. Online ahead of print.

Authors

Yufen Zheng¹, Yueyao Chen², Yuxuan He¹, Antonio Rizzo³, Yuchen Zhou⁴, Kam-Hung Low¹, Elizabeth H Krenske⁵, Pauline Chiu⁶

Affiliations

¹ The University of Hong Kong, Chemistry, HONG KONG.
² The University of Hong Kong, Laboratory for Synthetic Chemistry and Chemical Biology, HONG KONG.
³ The University of Hong Kong, Department of Chemistry, HONG KONG.
⁴ The University of Queensland, School of Chemistry and Molecular Biosciences, AUSTRALIA.
⁵ The University of Queensland, School of Chemistry and Molecular Biosciences, 4072, St. Lucia, AUSTRALIA.
⁶ The University of Hong Kong, Department of Chemistry and State Key Laboratory of Synthetic Chemistry, Pokfulam Road, 00000, Hong Kong, HONG KONG.

PMID: 38758985
DOI: 10.1002/anie.202407059

Abstract

Unexpectedly facile dearomative intramolecular (4+3) cycloadditions of thiophenes with epoxy enolsilanes, providing sulfur-bridged cycloadducts, are reported. A total of fifteen thiophene substrates have been found to undergo (4+3) cycloaddition smoothly to produce endo and exo (4+3) adducts in yields of up to 83% with moderate to good diastereoselectivity. Complete conservation of enantiomeric purity was observed when the optically enriched epoxide was used. The desulfurizing transformations of the sulfur-bridged skeleton of the cycloadducts provide functionalized 6,7-fused bicyclic frameworks consisting of 1,3-cycloheptadiene subunits. Density functional theory calculations reveal the origins of the facile dearomatization of thiophenes in these (4+3) cycloadditions.

Keywords: DFT calculations; Dearomatization; cycloadditions; heterocycles; stereochemistry.