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

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.