Enantioselective Synthesis of Pyrano[3,2‐ <i>c</i> ]coumarin Bearing Aza‐Quaternary Stereocenter via [3 + 3] Annulation Reaction with <i>α</i> ‐CF ₃ Alkynyl Ketimines and 4‐Hydroxycoumarins

An efficient regio‐ and enantioselective synthesis of pyrano[3,2‐ c ]coumarins has been developed via a [3 + 3] annulation reaction between α ‐CF 3 alkynyl ketimines and 4‐hydroxycoumarins. The reaction proceeds via a squaramide‐catalyzed stereospecific Mannich reaction followed by a Lewis acid‐mediated annulation, enabling excellent control of both regio‐ and enantioselectivity. Notably, this represents the first enantioselective synthesis of pyrano[3,2‐ c ]coumarin derivatives bearing an aza‐quaternary stereocenter. The methodology exhibits broad substrate compatibility with both steric and electronic variations. Practicality of the protocol is demonstrated by scale‐up reaction as well as diverse downstream functionalizations.