Facile synthesis of iodopyridines from N-propargylic β-enaminones via iodine-mediated electrophilic cyclization

Zinc Chloride Mediated Synthesis of 1,4‐Oxazepines from N‐Propargylic β‐Enaminones

“…First, we synthesized the requisite N ‐propargylic β‐enaminones according to a recent report . Conjugate addition of propargylamine to α,β‐alkynic ketones provided N ‐propargylic β‐enaminones in good to excellent yields (61–98 %).…”

“…Our continued interest in the synthesis of new heterocyclic compounds as potential pharmaceuticals and scaffolds has prompted us to investigate new reactivity patterns of N ‐propargylic β‐enaminones. In this regard, we have recently shown that when treated with molecular iodine in the presence of sodium hydrogen carbonate, N ‐propargylic β‐enaminones undergo electrophilic cyclization to afford iodo‐substituted pyridines in good to high yields with a broad range of functional group tolerance . Iodopyridines have been further elaborated to more complex structures by metal‐catalyzed coupling reactions such as Suzuki–Miyaura and Sonogashira reactions .…”

Facile synthesis of aryl-substituted pyridines via Suzuki–Miyaura approach

“…42 First, conjugate addition of propargylamine to α,β-alkynic ketones 1 in refluxing methanol produced N-propargylic β-enaminones 2 in 94-99% yields. Then palladium-catalyzed cross-coupling of β-enaminones 2 with aryl iodides was carried out at room temperature to provide the arylated β-enaminones 3 in 77-88% yields.…”

“…41 We have recently synthesized N-propargylic β-enaminones 3 from α,β-alkynic ketones 1 and investigated their regioselective cyclization to 5-iodo-substituted pyridines 4 (Scheme 1). 42 We have found that when reacted with molecular iodine in the presence of sodium bicarbonate, N-propargylic β-enaminones 3 experiences electrophilic cyclization to furnish 5-iodopyridines 4 in good to high yields. Iodocyclization has been found to be general for a range of N-propargylic β-enaminones and allowed the presence of a variety of aromatic, heteroaromatic and aliphatic groups with electron-withdrawing and electron-donating substituents.…”

“…Iodocyclization has been found to be general for a range of N-propargylic β-enaminones and allowed the presence of a variety of aromatic, heteroaromatic and aliphatic groups with electron-withdrawing and electron-donating substituents. 42 Admittedly, iodine-containing pyridines are very attractive building blocks for the synthesis of diverse natural products and pharmaceuticals since they present a platform for the metal-catalyzed cross-coupling strategies that can elaborate the corresponding molecules to more complex structures. 43 In this regard, the coupling of 5-iodopyridines with boronic acids, classified as a Suzuki-Miyaura reaction, 38 may offer a rapid entry to a diverse range of 5-arylpyridines.…”