Switchable Annulation Pathways of Ynamides: Dual Catalytic Routes to 2H‐1,6‐Benzoxazocines vs. TBSOTf‐Catalyzed Selective 4‐Aminoquinoline Formation

Comprehensive Summary We report a substrate‐dependent annulation system where 6‐substituents of 2 H ‐1,4‐benzoxazines dictate divergent pathways with ynamides. Non‐methoxy substrates undergo TBSOTf/Zn(OTf)₂‐catalyzed [2 + 2] annulation/ring expansion to form 2 H ‐1,6‐benzoxazocines, while 6‐methoxy derivatives preferentially yield 4‐aminoquinolines via a TBSOTf‐catalyzed [4 + 2] annulation/deformylation pathway. This electronic effect‐driven selectivity operates under mild conditions with high fidelity. The method provides orthogonal access to two medicinally important heterocycle classes from identical precursors, features broad functional group tolerance, demonstrates scalability (up to 1 mmol scale), and eliminates the need for transition metals. The selectivity may originate from the differential stabilization of intermediates by the 6‐substituent.