Divergent and consecutive skeletal editing of saturated primary amines
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.
Authors
- Longhai Li (ORCID: https://orcid.org/0000-0002-3072-2499)
- Lumin Zhang
- Shiwei Su
- Xian Zheng
Institutions
- Shanghai Advanced Research Institute (CN)
- Shanghai Institute of Organic Chemistry (CN)
Publication Details
- Journal
- Science
- Published
- 2026-04-30
- DOI
- https://doi.org/10.1126/science.aee5416
- Citations
- 1
- Primary Topic
- Oxidative Organic Chemistry Reactions
- Type
- article
- Field-Weighted Citation Impact
- 10.35
Funders
- Chinese Academy of Sciences