Electrochemical Generation of N‐Centered Radicals and Their Reactivity Toward Cyclization and Subsequent C─C Bond Cleavage

ABSTRACT N‐containing heterocycles are widely used in medicinal chemistry, and they can be synthesized efficiently by the intramolecular cyclization of N‐centered radicals. Furthermore, N‐centered radicals also act as excellent hydrogen atom transfer (HAT) reagents. On the other hand, nitrogen atoms in the nitrogen‐containing heterocycles are used as a handle to cleave stable five and six‐membered rings. However, the electrochemical generation of N‐centered radicals and their application in forming heterocycles have been extensively studied. Study beyond cyclization remains largely unexplored; in this manuscript, we summarize our new findings as follows. Under electrochemical conditions, the N─H bond is cleaved, forming an N‐centered radical that adds to the double bond in a 6‐endo‐trig cyclization fashion. The newly formed C‐centered radical reacts with oxygen and undergoes C─C bond cleavage to form the corresponding carbonyl compounds. The reactivity is dependent on the substituents present on nitrogen. In the case of aromatic amine‐derived amide, the TEMPO trapping cyclization product was isolated. A mechanism has been proposed to explain the formation of the products.