Copper-catalyzed Aerobic Oxidative Synthesis Of N-heterocyclic Compounds

Many natural products, drugs and biologically active molecules were synthesizedvia the transition metal-catalyzed C-H activation. During the past few years, there hasbeen great progress in copper-catalyzed C-H activation. Obviously, molecular oxygen isthe ideal oxidant because of its abundance, low cost and lack of toxic by-products.Recently, advances have been made in copper-catalyzed aerobic oxidative formation ofbonds, and some heterocycles have been synthesized through this strategy. Compared toexpensive palladium-, rhodium-, ruthenium-catalyzed organic synthesis,copper-catalyzed aerobic oxidative reactions are more attractive and competitive inlaboratory and industrial field. In this dissertation, copper-catalyzed aerobic oxidativesynthesis of acridin-9-(10H)-one and imidazo[1,2-a]pyridine derivatives wereinvestigated, and the results were as follows:A novel and efficient copper-catalyzed aerobic oxidative method has beendeveloped for the synthesis of acridin-9-(10H)-one. The reaction involves readilyavailable substituted1-(2-(arylamino)aryl)ethanone as the starting materials,Cu(O2CCF3)2as the catalyst, O2as the oxidant, DMF as the solvent and pyridine as thebase. The synthesized acridin-9-(10H)-ones derivatives with various functional groupsincluding bromine and cyano. The present method provides opportunity for constructionof diverse molecules in medicinal chemistry.A practical and highly efficient copper-catalyzed aerobic oxidative method hasbeen developed for synthesis of imidazo[1,2-a]pyridine derivatives. The protocol usedreadily available substituted N-(alkylinene)-4H-1,2,4-triazol-4-amine and pyridines asthe starting materials, CuI as the catalyst, O2as the oxidant and DMF as the solvent.The reaction underwent cleavage of N-N bond, two C-H activation including pyridinylC-H bond and methyl sp3C-H bond leading to formation of two C-N bonds. Thereactions provided the imidazo[1,2-a]pyridines in moderate to excellent yields.Importantly, this method was effective for the synthesis of Zolimidin on a gram-scale.The novel method provides diverse and useful N-fused heterocyclic compounds formedicinal chemistry.