Regioselective Radical Alkylation Of Nitrogen-containing Heterocycles

The heteroarenes,especially N-heteroarenes,are important and ubiquitous structural motifs in pharmaceuticals,natural products,and materials.Minisci reaction is an important and effective method for the synthesis of azaarene.However,the harsh conditions of classical Minisci reaction limit its scope of application.So far,most of the results in the field of visible light-mediated photoredox are carried out by light-excited single-electron transfer mode,while the Minisci reaction of the energy transfer type mediated by visible light is rarely reported.Deconstructive functionalization of cyclic amines is an effective method to realize the diversity of molecular frameworks.Few examples are silver-catalyzed ring-opening chlorination,bromination or fluorination and ring-opening of cyclic amines to afford distal aminoalkyl-substituted quinones.However,the method of combining it with Minisci reaction to functionalize azaarene has not been developed.In this paper,unactivated carboxylic acid,inert C(sp~3)–H and cyclic amine are used as radicals to realize the alkylation process of N-heteroarenes,and two goals are achieved:(1)For the first time,using(4-CzIPN)as energy transfer agent to activate N-heteroarenes through visible light mediation,a new activation mode of Minisci reaction without using acid additives was developed.(2)For the first time,the combination of deconstruction and functionalization of cyclic amines and Minisci reaction was realized,avoiding using equivalent silver.The results of this paper not only realize the innovation of Minisci reaction model,but also expand the application scope of Minisci reaction and enhance the practicality of Minisci reaction.