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.

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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

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article

Divergent and consecutive skeletal editing of saturated primary amines

Longhai Li, Lumin Zhang, Shiwei Su, Xian Zheng
1 citations
Science
Oxidative Organic Chemistry Reactions
10.35
article

Divergent and consecutive skeletal editing of saturated primary amines

Longhai Li, Lumin Zhang, Shiwei Su, Xian Zheng
article en
1 citations

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.

ScienceVol. 392(6797)
Shanghai Advanced Research Institute (CN), Shanghai Institute of Organic Chemistry (CN)
Chinese Academy of Sciences
Openalex Percentile: Top 2%
Oxidative Organic Chemistry Reactions
10.35
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