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.