Development of an Organoautocatalyzed Double σ-Bond C(sp2)-N Transamination Metathesis Reaction

Klein V, Schuster F, Amthor J, Maid H, Bijalwan P, Himo F, Santoro S, Tsogoeva S (2025)

Publication Type: Journal article

Publication year: 2025

Journal

Angewandte Chemie International Edition Wiley

DOI: 10.1002/anie.202505275

Abstract

The transamination reaction, which involves the conversion of one amine to another, traditionally relies on biological enzyme catalysts. Although chemists have recently developed a few transition metal-catalyzed methods, mimicking these enzymes to interconvert amine groups in acyclic substrates via transamination metathesis of a single C(sp2)─N bond, transamination of cyclic tertiary amines has remained a challenge in synthetic chemistry. Here, we present the development of organoautocatalyzed transamination metathesis of two C(sp2)─N bonds in a cyclic substrate that allows for the challenging transformation to take place with up to 95% yield under exceptionally mild reaction conditions at room temperature without external catalysts and/or additives. The reaction mechanism has been studied in detail through time-resolved 1H-NMR, 2D NMR, and computational methods. Remarkably, in situ-formed pyrrolidinium salt acts as a hydrogen bond donor (HBD) organoautocatalyst in this multi-step domino process. The new organoautocatalyzed methodology gives environmentally friendly, atom-economical, straightforward, and rapid access to N-substituted 3,5-dinitro-1,4-dihydropyridines (DNDHPs), thus offering facile entry to privileged bioactive compounds.

Authors with CRIS profile

Volker Klein Lehrstuhl für Organische Chemie I Florian Schuster Interdisziplinäres Zentrum für Molekulare Materialien (ICMM) Jonas Amthor Lehrstuhl für Organische Chemie I Harald Maid Lehrstuhl für Organische Chemie II Svetlana Tsogoeva Professur für Organische Chemie

Involved external institutions

Stockholm University / Stockholms universitet SE Sweden (SE) Università degli Studi di Perugia IT Italy (IT)

How to cite

APA:

Klein, V., Schuster, F., Amthor, J., Maid, H., Bijalwan, P., Himo, F.,... Tsogoeva, S. (2025). Development of an Organoautocatalyzed Double σ-Bond C(sp2)-N Transamination Metathesis Reaction. Angewandte Chemie International Edition. https://doi.org/10.1002/anie.202505275

MLA:

Klein, Volker, et al. "Development of an Organoautocatalyzed Double σ-Bond C(sp2)-N Transamination Metathesis Reaction." Angewandte Chemie International Edition (2025).

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