A concise and unexpected one-pot methodology for the synthesis of pyrazinone-fused pyridones

• Published in: ORGANIC CHEMISTRY FRONTIERS Vol. 7; no. 18; pp. 2657 - 2663
• Main Authors: Lei, Jie, Xu, Jia, Tang, Dian-Yong, Shao, Jing-Wei, Li, Hong-yu, Chen, Zhong-Zhu, Xu, Zhi-Gang
• Format: Journal Article
• Language: English
• Published: CAMBRIDGE Royal Soc Chemistry 21.09.2020; Royal Society of Chemistry
• Subjects: Adducts; Alkynes; Cascade chemical reactions; Catalysts; Chemical synthesis; Chemistry; Chemistry, Organic; Crystallography; Michael reaction; NMR; Nuclear magnetic resonance; Organic chemistry; Physical Sciences; Protonation; Science & Technology; PRAZIQUANTEL; GAMMA-SECRETASE MODULATORS; DESIGN; ACID-CATALYZED HYDRATION; KINASE; RECEPTOR; HYDROAMINATION; CYCLOISOMERIZATIONS; ACCESS; PDE5 INHIBITORS EVALUATION
• ISSN: 2052-4129; 2052-4110; 2052-4110
• DOI: 10.1039/d0qo00590h

A facile one-pot cascade reaction for the synthesis of pyrazinone-fused pyridones has been developed without a metal catalyst. Hydroamination of the Ugi propargyl adducts arising from aromatic isocyanides would be promoted by the intramolecular protonation of the alkyne with the amide NH to form an unstable oxazolopyridinium. The cascade reaction was applied to alkyl isocyanide to synthesize pyrazinone-fused pyridones under strongly acidic conditions. This novel cascade reaction proceeds through an Ugi/Michael/Retro-Michael reaction, aromatization, and 5-exo-digcyclization cascade sequence. The reaction features a simple operation procedure, one purification step, and good yields, which could be applicable to a broad scope of Ugi starting materials. This is the first report on the intramolecular hydroamination occurring between an amide and an alkyne under conditions with an organic base.