The carbomethylation of arylacrylamides leading to 3-ethyl-3-substituted indolin-2-one by cascade radical addition/cyclization

Abstract

An FeCl2-promoted carbomethylation of arylacrylamides by di-tert-butyl peroxide (DTBP) is achieved, leading to 3-ethyl-3-substituted indolin-2-one in high yield. The reaction tolerates a series of functional groups, such as cyano, nitro, ethyloxy carbonyl, bromo, chloro, and trifluoromethyl groups. The radical methylation and arylation of the alkenyl group are involved in this reaction.

tert-Butyl Peroxybenzoate-Promoted α-Methylation of 1,3-Dicarbonyl Compounds

“…First, thermally promoted homolytic cleavage of the radical initiator TBPB produces the tert-butoxy radical t BuO·, which converts to the methyl radical by releasing 1 equiv of acetone. 26 Then the copper(II) reacts with the 1,3-dicarbonyl compound to generate copper enolate intermediate 4.…”

Progress in Synthesis of Oxindoles by Radical Addition-Cyclization

“…2). 一年后, Jiao [6] 和 Cheng [7] 课题组又分别报道了 通过 Fe 催化的类似过程, 反应机理均通过自由基加成/ 关环过程, 可以在吲哚-2-酮的 3 位的甲基上再引入一个 甲基或砜的基团, 极大的丰富了该方法的研究内容, 扩 展了研究的底物的选择(Eqs. 3～4).…”

Iron‐Catalyzed Radical Cleavage/C−C Bond Formation of Acetal‐Derived Alkylsilyl Peroxides

“…The reaction of 1 a with 2 a could be conducted on a gram scale, although the product 3 aa was obtained in slightly lower yield (entry 1). The reaction of other carbon electrophiles, such as acrylamide 2 b , isocyanide 2 c with 1 a successfully afforded the oxindole derivative 3 ab and phenanthridine derivative 3 ac , respectively (entries 2 and 3). In addition, the reaction with pharmaceutically important quinoxaline derivative 2 d was also possible (entry 4).…”

“…[9] The reaction of 1 a and 1,1-diphenylethene (2 a, 2.0 equiv) in the presence of FeCl 3 (10 mol%) was carried out in DMSO at 80°C for 1 h to furnish 6,6-diphenylhex-5-en-1-yl formate (3 aa) as the ring-opened product in 77 % yield (Table 1, entry 1). [10] Increasing the catalyst loading from 10 mol% to 20 and 40 mol% under otherwise identical conditions afforded 3 aa in 81 % and 70 % yield, respectively (entries 2 and 3). The reaction did not proceed in the absence of FeCl 3 .…”

“…Based on these results, a plausible reaction mechanism is proposed in Scheme 5. First, the iron catalyst cleaves the OÀ O bond of 1 a via a single-electron transfer (SET) process, [10,12] that yields oxy-radical 7 and a silanoxide. Oxy-radical 7 then undergoes a β-scission to furnish alkyl radical 8, which subsequently reacts with 2 a to afford intermediate carbon radical 9.…”