Cascade Reactions Assisted by Microwave Irradiation: Ultrafast Construction of 2-Quinolinone-Fused γ-Lactones from N-(o-Ethynylaryl)acrylamides and Formamide

Abstract

An ultrafast (10 s) methodology to construct novel highly functionalized 2-quinolinones from N-(o-ethynylaryl)acrylamides (1,7-enynes) is described for the first time. Microwave irradiation enabled the ultrafast synthesis of 2-quinolinone-fused γlactones from Fenton's reagents in formamide. After six key consecutive reactions, including a diastereoselective step, 2quinolinone-fused γ-lactones were obtained in good overall yield (up to 46%; 10 s).

Molecular Construction Using Formamide as a C1 Feedstock

“…After that, the methodology was improved by combining photocatalysis and flow chemistry, and oxindoles were obtained after only 10 minutes [33b] . Other starting materials were used, such as hydroxymethyl‐ N ‐alkylphenylacrylamides, [33c,d] α,β‐unsaturated esters [33d] and 1,7‐enynes [33e] to generate new oxindoles and 2‐quinazolinones (Scheme 26).…”

“…This process demanded an excess of hydrogen peroxide (4 equiv.) to afford hydroxyl radicals needed for the six‐step process as suggested in the reaction mechanism [33e] . Sanabria et al [26f] .…”

Radical Cascade Cyclization of Alkene‐Tethered Compounds: Versatile Approach towards Ring‐Fused Polycyclic Structures

“…[46] In 2021, Andrades' group disclosed an unprecedented microwave-assisted ultrafast methodology to synthesize 2quinolinone-fused γ-lactones from 1,7-enynes and Fenton's reagents (H 2 O 2 , FeSO 4 , and H 2 SO 4 ) in the formamide (Scheme 21). [47] Mechanistically, Fenton's reaction generates the hydroxyl radical, which reacts with formamide to give the carbamoyl radical 21-A. The addition of 21-A to the CÀ C double bond and subsequent 6-exo cyclization, hydroxylation, epoxidation and lactonization give product 21-F.…”

Difunctionalization of Dienes, Enynes and Related Compounds via Sequential Radical Addition and Cyclization Reactions

“…The Andrade group reported an ultrafast Fe-promoted reaction for the synthesis of 2-quinolinone-fused γ -lactones in 2021. The reaction of benzene-tethered 1,7-enynyl amides and formamide and Fenton’s reagent under microwave irradiation for 10 s gave product 50 in a good overall yield ( Scheme 51 ) [ 63 ]. The reaction mechanism suggests that the hydroxyl radical generated from Fenton’s reaction adds to the C=C double bond of amide followed by 6- exo cyclization, coupling with hydroxyl radical, epoxidation, and lactonization to give product 50a .…”