Monodentate Transient Directing Group-Assisted Palladium-Catalyzed Direct ortho-C-H Iodination of Benzaldehydes for Total Synthesis of Hernandial

Abstract

The first palladium-catalyzed direct o-C-H iodination of benzaldehydes was successfully developed with the assistance of commercially available 2,5-bis(trifluoromethyl)aniline as the optimal monodentate transient directing group (MonoTDG). Moderate to excellent yields and good selectivity were achieved for a broad substrate scope under mild conditions. More importantly, the synthetic application was demonstrated by a concise two-step total synthesis of the natural product hernandial, which was accomplished by merging this new MonoTDG-assisted C-H iodination and subsequent copper-catalyzed cross-coupling.