Tertiary amine-directed and involved carbonylative cyclizations through Pd/Cu-cocatalyzed multiple C–X (X = H or N) bond cleavage

Abstract

A novel Pd/Cu-cocatalyzed carbonylative cyclization by C–H activation and N-dealkylative C–N bond activation has been developed for the chemoselective construction of synthetically useful heterocycles. The N,N-dimethylamine group on o-indolyl-N,N-dimethylarylamines was found to act as both the directing group and reactive component in this C–H carbonylative cyclization reaction. Furthermore, a unique C–H oxidation/carbonylative lactonization of diarylmethylamines is firstly demonstrated under modified reaction conditions, which could be easily applicable to the one-step synthesis of multi-substituted phthalides bearing an N,O-ketal skeleton that is difficult to access by previously reported methods. Mechanistic studies implicate that Pd/Cu-cocatalyzed C–H oxidation/carbonylative lactonization is a sequential reaction system via Cu-catalyzed C(sp³)–H oxidation and Pd-catalyzed oxidative carbonylation of the C(sp²)–H bond. It was found that trace amounts of water are essential to promote the Cu-catalyzed C(sp³)–H oxidation of diarylmethylamine for the formation of the hydroxyl group, which could act as an in situ-formed directing group in the intramolecular carbonylative lactonization step.