Divergent and consecutive skeletal editing of saturated primary amines

• 成果类型: Article
• 署名作者: Li, Long-Hai; Su, Shiwei; Zheng, Xian; Zhang, Lumin
• 署名单位: Chinese Academy of Sciences; University of Chinese Academy of Sciences, CAS; Shanghai Institute of Organic Chemistry, CAS
• 刊物名称: SCIENCE
• ISSN/ISSBN: 0036-8075; 1095-9203
• DOI: 10.1126/science.aee5416
• 发表日期: 2026-04-30
• 页码: 528-535
• 关键词: OXIDATIVE REARRANGEMENT; potent; hydrogenation; inhibitors; conversion; DISCOVERY; route

摘要

Given the prevalence of nitrogen heterocycles in pharmaceuticals, divergent skeletal editing techniques that enable rapid access to a diverse library of azacycles from a single substrate are highly desirable. Herein, we report a skeletal editing approach that converts abundant saturated primary amines into N-heterocycles, with exceptional functional-group compatibility, broad skeletal diversity, superior regioselectivity, and diastereospecificity (both >20:1). By harnessing the reactivity of hypervalent iodines, an imino ether intermediate is generated through mild iodane-mediated oxidation, facile N-internalization, and methoxy anion addition. This pivotal intermediate serves as a versatile platform capable of interception by a wide spectrum of nucleophiles, thereby enabling the generation of structurally diverse nitrogen heterocycles (>15 classes). Furthermore, this strategy enables challenging site-controlled carbon-to-nitrogen transmutation and ring contraction of natural products through a one-pot, consecutive skeletal editing sequence.