PdCl₂‐Catalyzed Oxidative Cyclization of N‐(2’‐Alkynylaryl)‐1,3‐ketoamides: Synthesis of 3,4‐Diacyl‐2‐Quinolones

Abstract

Diacyl-2-quinolone derivatives were prepared in a rapid manner starting from N-(2'-alkynylaryl)-1,3-ketoamide substrates. The reaction showcased a mild radical process mediated by ceric ammonium nitrate (CAN) in the presence of 5 mol% PdCl 2 under basic conditions and was applicable to a wide range of substrates, giving 3,4-diacyl-2-quinolone products in up to 91% yield in over 40 examples. The reaction proceeded via the generation of a radical intermediate which could be trapped as a TEMPO-adduct that was isolated and fully characterized. The reported method provided a practical and scalable synthetic access to densely functionalized 3,4diacyl-2-quinolone derivatives which would be suitable for further applications including medicinal and bioactivity evaluations as well as synthetic transformations.

An Efficient Approach Towards the Synthesis of Nintedanib

“…Therefore, another attempt was made to convert amine 3 to β‐keto amide 5 via coupling with benzoyl acetic acid 4 [16] in presence of N,N′‐dicyclohexylcarbodiimide (DCC), catalytic DMAP in anhydrous DCM at 25 °C for 10 hours(Table 1, Entry 1). However, the yield of the desired product was also very low and multiple spot formation on TLC was observed.…”

Ceric Ammonium Nitrate Promoted Oxidative Coupling of Terminal Alkynes and 1,3-Keto Esters: A Synthesis of Unsymmetrical 1,1,2-Triacylalkenes

“…Finally, dienol H is oxidized in the presence of CAN to yield the final triacylalkene product 3 . Evidence for the radical process was provided by the isolation of compound 6 in 54% yield 8 when the reaction was conducted in the presence of (2,2,6,6-tetramethylpiperidin-1-yl)oxyl (TEMPO) under the standard conditions, while only 10% of product 3a was obtained (Scheme 5b ).…”