Iodination of Remote Ortho-C-H Bonds of Arenes via Directed SEAr: A Streamlined Synthesis of Tetrahydroquinolines

A new strategy for the synthesis of tetrahydroquinolines (THQs) via the sequential functionalizations of remote C-H bonds is reported. This method uses a single picolinamide directing/protecting group to effect Pd-catalyzed gamma-C(sp(3))-H arylation, metal-free epsilon-C(sp(2)) H iodination, and Cu-catalyzed intramolecular C-N cross-coupling. The overall sequence is efficient and versatile, and offers a streamlined synthesis of THQs with complex substitution patterns from readily available aryl iodide and aliphatic amine precursors.