Divergent and consecutive skeletal editing of saturated primary amines

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Authors: Longhai Li, Shiwei Su, Xian Zheng, Lumin Zhang
Cited by: 8
References: 69

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