Divergent and consecutive skeletal editing of saturated primary amines
Abstract
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.
Fields of Study & Subjects
Oxidative Organic Chemistry Reactions
Radical Photochemical Reactions
Catalytic C–H Functionalization Methods
Publication details
- Journal / source
- Science
- Publisher
- American Association for the Advancement of Science (AAAS)
- Volume
- 392
- Issue
- 6797
- Pages
- 528–535
- Publication date
- 30 April 2026
- Language
- EN