Switchable Annulation Pathways of Ynamides: Dual Catalytic Routes to 2H-1,6-Benzoxazocines vs. TBSOTf-Catalyzed Selective 4-Aminoquinoline Formation
Wozheng Fang , Longyu Xiao , Yijie Wang , Junbiao Chang , Xiao-Na Wang
Chinese Journal of Chemistry ›› 2025, Vol. 43 ›› Issue (22) : 2971 -2978.
Switchable Annulation Pathways of Ynamides: Dual Catalytic Routes to 2H-1,6-Benzoxazocines vs. TBSOTf-Catalyzed Selective 4-Aminoquinoline Formation
We report a substrate-dependent annulation system where 6-substituents of 2H-1,4-benzoxazines dictate divergent pathways with ynamides. Non-methoxy substrates undergo TBSOTf/Zn(OTf)₂-catalyzed [2 + 2] annulation/ring expansion to form 2H-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.
Ynamides / 2H-1,4-Benzoxazines / 2H-1,6-Benzoxazocines / 4-Aminoquinolines / Annulation / Dual catalytic / Ring expansion / Deformylation
2025 SIOC, CAS, Shanghai, & WILEY-VCH GmbH
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