Copper-Catalyzed Oxidative Amination of Benzoxazoles via C−H and C−N Bond Activation: A New Strategy for Using Tertiary Amines as Nitrogen Group Sources

Abstract

An efficient and conceptually new method for oxidative amination of azoles with tertiary amines via copper-catalyzed C-H and C-N bond activation has been developed. This protocol can be performed in the absence of external base and only requires atmospheric oxygen as oxidant. The catalyst system is very simple and efficient, which opens a new way for using tertiary amines as nitrogen group sources for C-N bond formation reactions.

Aerobic Copper-Catalyzed Organic Reactions

“…For example, Guo and co-workers demonstrated that an imminium ion, derived from oxidation of a tertiary amine, can undergo C–N bond cleavage via hydrolysis to afford a copper amide species (LnCu–NR 1 R 2 ) which can react further with benzoxazole via a copper mediated C–H insertion to afford the desired aminated product. 1121 Alkyl tertiary amines bearing α–hydrogens reacted efficiently while amines without an α–H failed to react. An increase in yield was observed when a phenyl substituent was installed at the α–position of the amine.…”

Transition-Metal-Catalyzed Cleavage of C–N Single Bonds

“…140 This approach could be performed in the absence of an external base with molecular oxygen as the oxidant. This reaction combines the cleavage of the C−N bond and amination of the C−H bond, presenting the utility of tertiary amines as the nitrogen source in the C−H bond activation process.…”

Oxidation and Reduction

“…276 The CuBr 2 -catalysed oxidative C−H amination of azoles by atmospheric O 2 in the presence of acetic acid and tertiary amines (acting as base and nitrogen source) forms corresponding amines in good yields thereby providing a powerful method for new C−H amination reactions involving a new strategy for C−N bond activation. 277 Benzylic C−H oxygenation was achieved using 2-benzyl benzonitrile derivatives and p-tolylmagnesium bromide (Grignard reagent) in DMF under O 2 atmosphere with Cu(OAc) 2 catalyst in the presence of K 3 PO 4 . The reaction is proposed to proceed via O 2 oxidation of an iminyl copper intermediate to give a peroxycopper(III) compound, which undergoes intra-molecular 1,5-H-shift with formation of a benzylic radical that proceeds to give a ketoimine via a peroxy copper species.…”