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Synlett
DOI: 10.1055/a-2782-2936
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Unlocking Tertiary Halides from Primary Alkylamines through Deamination

Authors

  • Hongjian Lu 

    1   School of Chemistry and Chemical Engineering, Nanjing University, Nanjing, China (Ringgold ID: RIN12581)

  • Zhangkai Cui 

    1   School of Chemistry and Chemical Engineering, Nanjing University, Nanjing, China (Ringgold ID: RIN12581)

Funding Information Financial support for this work was provided by the National Natural Science Foundation of China (22271148).
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Graphical Abstract

Abstract

Selective halogenation at sterically congested alkyl centers remains a long-standing challenge due to limited steric accessibility and the lack of general approaches. Deaminative strategies offer a powerful solution, leveraging the abundance of primary alkylamines in synthetic and bioactive molecules. In this context, O-diphenylphosphinylhydroxylamine enables transient amine-to-radical conversion, allowing efficient installation of Cl, Br, and I at otherwise inaccessible tertiary carbon centers. The method operates across highly hindered scaffolds—including bicyclo[1.1.1]pentane, cubane, and aza-bicyclo[2.1.1]hexane frameworks—demonstrating that native alkylamines can serve as programmable entry points for functionalizing saturated, sterically encumbered sites. This advance establishes deaminative logic as a versatile blueprint for accessing halogenated, saturated architectures beyond the reach of conventional approaches.

Keywords

Magic chloro effect - Deaminative halogenation - Nitrogen deletion - α-Tertiary amines - 3D bioisosteres


Publication History

Received: 26 November 2025

Accepted: 07 January 2026

Accepted Manuscript online:
08 January 2026

Article published online:
23 January 2026

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