Electrochemically Tunable Ring-Contracting Cyanation and Imination of Saturated Cyclic Amines

The green and facile protocol for the tunable transformation of alicyclic amines is meaningful due to the immense importance of the functionalized azaheterocycles in pharmaceuticals. In this work, electrochemically selective synthesis of α-cyano amines and cyclic amidines from the reaction of saturated cyclic amines with TMSN₃ is developed. Using thiomorpholines as amine substrates, the regioselective cleavage of C(sp³)─S bond, followed by recombination and cyanation, enables the construction of α-cyano thiazolidines via a ring contraction process. In the presence of sodium sulfinate, alicyclic amines undergo cycloaddition, N₂ extrusion, hydride transfer, and sulfonylation to give sulfonyl amidines. Notable features of the methods developed herein include simple and broad tertiary/secondary cyclic amine substrates, diverse novel transformations, catalyst-free and external oxidant-free conditions. Importantly, these reaction systems are amenable to the late-stage functionalization of complex targets containing basic N-heterocyclic moieties that are prevalent in medicinally active agents. In addition, electrolysis of the N-aryl sulfonyl amidine triggers further cleavage of the N─S bond and coupling of C(sp²)─N bond to provide fused amines.