Iron-Promoted Oxidative Alkylation/Cyclization of Ynones with 4-Alkyl-1,4-dihydropyridines: Access to 2-Alkylated Indenones

Abstract

An iron-promoted oxidative tandem alkylation/cyclization of ynones with 4-alkyl-substituted 1,4-dihydropyridines for the efficient synthesis of 2-alkylated indenones is described. The process occurs via oxidative homolysis of a C–C σ-bond in 1,4-dihydropyridines to generate an alkyl radical followed by the addition of C–C triple bonds in ynones and intramolecular cyclization. A wide range of alkyl radicals could be efficiently transferred to generate a series of synthetically useful 2-alkylated indenones with excellent selectivity under mild conditions.

Strategies and Mechanisms of First-Row Transition Metal-Regulated Radical C–H Functionalization

“…In 2022, Fan et al developed a process for the Fe-catalyzed oxidative alkylation/cyclization of ynones with 4-alkyl-1,4-dihydropyridines (30-20) (Scheme 30d). 290 This protocol permitted C(sp 2 )−H alkenylation for the synthesis of 2alkylated indenones via a SET between an cyclohexadienyl radical and an Fe complex. Trials employing TEMPO, BHT or 1,1-stilbene as a radical scavenger generated none of the cyclization product but rather gave the adduct resulting from the addition of an alkyl radical to the radical scavenger, suggesting that the reaction proceeded through a radical mechanism.…”

Iron-Catalyzed Synthesis of Benzosultams from N-Phenyl-N-(prop-2-yn-1-yl)benzenesulfonamide and Benzenesulfonyl Hydrazine

“…Based on the above-mentioned results and the related reports, 10,11 a possible reaction mechanism for the sulfonylation and C(sp 2 )−H activation/cyclization was illustrated in Scheme 6. Initially, in the presence of Fe(II) and S 2 O 8 2− , radical A was formed through the sequential single-electron transfer and deprotonation.…”