Et₃N-Induced Demethylation−Annulation of 3-Alkynyl-4-methoxy-2-pyridones and Structurally Related Compounds in the Synthesis of Furan-Fused Heterocycles

Abstract

Various 3-iodo-4-methoxypyridin-2-ones and related pyrone and coumarin derivatives have been demonstrated as readily available precursors of 2-substituted furan-fused heterocycles by means of in situ sequential Sonogashira-acetylide coupling, dealkylation, and regioselective furan annulation reactions. A Et3N-induced S(N)2 process has been established that accounts for the dealkylation process.

A convenient access to furo[3,2-c]pyridin-6(5H)-ones by the reaction of 5-iodo-4-methoxy-2-pyridones with terminal alkynes under microwave-enhanced Sonogashira conditions

“…1). 3 We envisioned this methodology to be applicable to the synthesis of the regioisomeric arylfuropyridones 4 (Scheme 1, Eq. 2).…”

Coumarin heterocyclic derivatives: chemical synthesis and biological activity

“…50 The initial dealkylation steps can be achieved via a Et 3 N-induced S N 2 reaction as demonstrated by Monteiro and Balme, who described the synthesis of 2-substituted furan-fused coumarin 48 from 3-iodo-4-methoxycoumarin 46 by means of an in situ sequential Sonogashira-acetylide coupling and demethylation step induced by Et 3 N, followed by an intramolecular attack of the enolate onto the cuprohalide p-complex of the triple bond (Scheme 15). 51 When the reaction was carried out in MeCN at 60 C, the furocoumarin system 48 was obtained directly. More recently, Xu has described the elaboration of furocoumarins 50 via a similar palladium/copper-catalyzed coupling/cyclization reaction cascade from 3-bromo-4-acetoxycoumarins 49 with in situ prepared dialkynylzincs (Scheme 16).…”

Access to trifluoromethylated 4-alkoxy-2-pyrones, pyridones and quinolones

“…19 F NMR (282 MHz) spectra and 19 F NMR (470 MHz) were recorded on Bruker Avance 300 NMR and Bruker Avance 600 NMR spectrometers respectively in proton decoupled mode. 13 C NMR (125 MHz) spectra and 13 C NMR (75.5 MHz) spectra were recorded on Bruker Avance 500 and Bruker Avance 300 NMR spectrometers respectively in proton decoupled mode. All spectra were recorded at University College Cork.…”

“…Numerous protocols have been designed for the synthesis and decoration of 2-pyrones. [4][5][6][7][8][9] More specifically, functionalisation of the 3-position of 4-alkoxy-2-pyrones has been accomplished under Suzuki-Miyaura [10][11][12] and Sonogashira 13 conditions. The 2-pyrone moiety is also present in bioactive polyketides such as Nigerapyrone E 1 (Figure 1), 14 which possesses a methyl group at C-3.…”

“…2H, s),5.88 (1H, s), 7.14-7.16 (2H, m), 7.23-7.32 (3H, m) ppm;13 C NMR (75.5 MHz, CDCl 3 ): δ 21.1, 48.7, 56.7, 72.1, 95.3, 126.7, 127.5, 128.8, 136.3, 147.9, 162.2, 166.7 ppm; HRMS (ESI) m/z calcd for C 14 H 15 O 2 NI [(M + H) + ]: 356.0148, found 356.0141.1-(4-Fluorophenyl)-3-iodo-4-methoxy-6-methylpyridin-2(1H)-one, 30 2 equiv. N-iodosuccinimide required.…”