An annulation method for the synthesis of alkyl-substituted 6-carbomethoxy-2-pyridones

Exploration of an epoxidation–ring-opening strategy for the synthesis of lyconadin A and discovery of an unexpected Payne rearrangement

“…Based on the aforementioned model study [11], 7- exo –6- exo tandem radical cyclization of phenyl selenoester 4 was expected to produce ketone 3 . Disassembly of the pyridone moiety of 4 according to our annulation protocol [14] revealed thioester 5 as a suitable precursor. We believed that this compound could be prepared from alkene 6 in two consecutive epoxidation–ring-opening sequences involving vinyl nucleophiles.…”

“…Subsequent to this observation, we performed model studies that demonstrated the viability of highly stereoselective 7- exo - trig acyl radical–6- exo - trig alkyl radical cyclizations as a means of preparing bicyclo[5.4.0]undecanes fused to aromatic rings [11]. Then, we devised an annulation protocol inspired by the work of Donohoe and co-workers [12–13] that provided access to substituted pyridones of the type found in 1 from thioester precursors [14]. Based on these encouraging results, we decided to target lyconadin A for synthesis.…”

Synthesis and reduction reactions of pyridones and 5-acyl-2-methoxypyridines

“…26 A mixture of benzyl bromide (4.40 mL, 6.34 g, 37.05 mmol), methyl 6-methoxynicotinate 2b (3.00 g, 17.96 mmol) and potassium carbonate (4.96 g, 35.89 mmol) in dry acetonitrile (72 mL) was stirred at 80 °C for 48 h. The mixture was filtered and concentrated under reduced pressure and purified by column chromatography (ethyl acetate -hexane 1:1) to give product 3b (1.25 g, 5.14 mmol, 29 % yield) as a yellow oil; δH (300 MHz, CDCl3 (6-Methoxypyridin-3-yl)methanol, 2c. 27 Under nitrogen, a suspension of lithium aluminum hydride solution in THF (1M, 6.58 mL, 6.58 mmol) in THF (3.39 mL) was stirred at 0 °C for 5 min.…”

One‐Pot Synthesis of 3‐Cyano‐2‐pyridones

“…Development of methods to prepare substituted 2‐pyridones has been a significant area of research in organic synthesis, and a multitude of cyclization strategies based on various bond forming processes have been reported .…”