Chiral Phosphoric Acid-Catalyzed Kinetic Resolution of Tertiary Alcohol-Tethered Ynamides via Controllable Hydroalkoxylation

Catalytic kinetic resolution has proven to be a powerful and practical method for the preparation of enantioenriched tertiary alcohols since their racemates are easy to access. However, this strategy is highly challenging and generally relies on transition-metal catalysis and is mostly limited to the construction of five- and six-membered O-heterocycles. Herein, we disclose an efficient and controllable kinetic resolution of tertiary alcohol-tethered ynamides enabled by chiral phosphoric acid catalysis, which represents a unique chiral Brønsted acid-catalyzed alkyne functionalization via kinetic resolution of tertiary alcohols. This metal-free protocol allows the practical and atom-economic formation of chiral medium-sized N-heterocycles such as nine-membered lactams and benzoxazepines with high enantioselectivities.