Development of an Organoautocatalyzed Double σ‐Bond C(sp ² )‐N Transamination Metathesis Reaction

Abstract

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(sp 2 )─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(sp 2 )─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 1 H‐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.