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

A new palladium-catalyzed picolinamide (PA)-directed ortho-iodination reaction of ε-C(sp(2))−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(sp(3))−H arylation, Pd-catalyzed ε-C(sp(2))−H iodination, and Cu-catalyzed C−N cyclization enables a streamlined synthesis of tetrahydroquinolines bearing diverse substitution patterns.