Enantioselective Construction of Inherently Chiral Saddle-Shaped Azepines via Palladium-Catalyzed Intramolecular C-H Arylation.

Saddle-shaped seven-membered rings with inherent chirality remain challenging targets due to their high conformational mobility and low inversion barriers. Herein, we report a palladium-catalyzed enantioselective intramolecular C-H arylation of azepine precursors enabled by 2,2,3,3-tetramethylcyclopropylcarboxylic acid (TMCPA) as a sterically hindered carboxylic acid additive. This protocol provides efficient access to a range of inherently chiral saddle-shaped azepines in up to 96% yield and 95% ee. Thermal racemization studies further show that representative products possess useful configurational stability. We further demonstrate the synthetic applicability of this protocol and report an initial chiroptical evaluation, highlighting its potential for functional material development.