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◆ Organic Letters2025-12-12· Chemistry

Strain-Release-Driven 1,3-Halo-hydroxylamination of Bicyclo[1.1.0]butanes Enabled by Anomeric Amide Reagents

Xiujuan He, Wei Li, Ting Zhang, Shengchao Yang, Zhihua Cai, Lin He

原始摘要(英文原文)· Original abstract
A catalyst-free, strain-release-driven 1,3-halo-hydroxylamination of bicyclo[1.1.0]butanes (BCBs) is reported. This strategy employs anomeric amide reagents (N-protected N-halo-O-activated hydroxylamines) as difunctionalization reagents, yielding highly regioselective 1,1,3-trisubstituted cyclobutanes bearing both a hydroxylamine moiety and a halogen in a one-step manner. Preliminary mechanistic studies suggest this transformation may be involved in a radical chain pathway, and it is proposed that BCBs substituted with electron-withdrawing groups, such as esters or amides, are key to overcoming the challenge of radical polarity mismatch. Moreover, the synthetic utilities of these products are illustrated in the conversion into pyrrole derivatives and serve as nitrene precursors for metal-catalyzed aziridination of olefins.
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Strain-Release-Driven 1,3-Halo-hydroxylamination of Bicyclo[1.1.0]butanes Enabled by Anomeric Amide Reagents — 科研速览 Science Skim