Palladium-catalyzed picolinamide-directed iodination of remote ortho-C-H bonds of arenes: Synthesis of tetrahydroquinolines

Abstract

A new palladium-catalyzed picolinamide (PA)-directed ortho-iodination reaction of ϵ-C(sp2 )-H bonds of γ -arylpropylamine substrates is reported. This reaction proceeds selectively with a variety of γ-arylpropylamines bearing strongly electron-donating or withdrawing substituents, complementing our previously reported PA-directed electrophilic aromatic substitution approach to this transformation. As demonstrated herein, a three step sequence of Pd-catalyzed γ-C(sp3)-H arylation, Pd-catalyzed ϵ -C(sp2 )-H iodination, and Cu-catalyzed C-N cyclization enables a streamlined synthesis of tetrahydroquinolines bearing diverse substitution patterns.