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Synthesis of Bicyclo[1.1.1]Pentane Z‐Substituted Enamides, Enol Ethers, and Vinyl Sulfides Using Iodine (III) Reagents

2025/05/28 by Najung Lee, Jonas Dechent, Elija Grinhagena +1 · 1 voice · 1 citation
Chemistry · #Catalytic C–H Functionalization Methods #Oxidative Organic Chemistry Reactions #Synthesis and Catalytic Reactions

paper · doi:10.1002/anie.202508404

openalex publication_date 2025/05/28 · openalex created_date 2025/10/10 · openalex updated_date 2026/07/02

Abstract

Bicyclo[1.1.1]pentanes (BCPs) are well-studied bioisosteres for para-substituted benzene rings, and numerous methods for synthesizing 1,3-difunctionalized BCPs have been developed. However, synthetic approaches to access vinyl BCP motifs remain limited, with only few reports on the synthesis of BCP-olefins bearing heteroatom substituents. Herein, we present the synthesis of BCP-substituted enamides, enol ethers, and vinyl sulfides through the sequential functionalization of ethynylbenziodoxolone (EBX) reagents containing a BCP scaffold. Stereoselective addition of a nucleophile generates heteroatomic Z-vinylbenziodoxolone (VBX) reagents. The hypervalent iodine substituent of the VBX reagents serves then as a versatile platform for further arylation, vinylation, and trifluoromethylation. This method provides a modular synthesis of previously inaccessible heteroatom-substituted vinyl BCPs.

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