Transition Metal-Catalyzed Sp~3C-H Bonds Activation And N-Methylation Of Amides And O-Methylation Of Carboxylic Acids

Transition metal-catalyzed C-H bonds activation methods have been widely developed for the functionalization of arenes and heteroarenes in the past two decades. Compared to sp2C-H activation, much less research has been devoted to the activation of more inert sp3C-H bonds. The sp3C-H bonds have no empty lowenergy orbitals or filled high-energy orbitals that could readily interact with orbitals of the metal center, as is the case with unsaturated hydrocarbons. Therefore, catalytic sp3C-H bonds activation seems to represent a significantly bigger challenge.In this paper,we report N-Alkylation of azoles via oxidative activation of C-H bonds and N-methylation of amides and O-methylation of carboxylic acids.1. Iron-catalyzed direct C-N bond formation between imidazoles and benzylic hydrocarbons is described. The inexpensive and readily available catalyst oxidant system is of practical interest for N-alkylation of imidazoles. Compared to traditional N-alkylation of imidazoles, benzylic hydrocarbons are more easily available and environmentally friendly than alkyl halides.2. Iron-catalyzed direct C-N bond formation between azoles and amides is described. The oxidative coupling reactions of sp3C-H bonds adjacent to a nitrogen atom in amides and sulfonamides with the N-H bond in azoles proceeded smoothly in the presence of FeCl2and di-tert-butyl peroxide (DTBP). A wide range of amides and sulfonamides can be used as substrate for N-alkylation of azoles.3. The copper-catalyzed N-methylation of amides and O-methylation of carboxylic acids by using peroxides as the methylating reagent are described. Various amides and carboxylic acids were methylated affording N-substituted amides and esters. Tentative mechanistic studies suggest that this reaction is likely to involve a radical process.