3,3-二烷基-2-吲哚酮骨架是广泛存在于天然产物和生物活性分子中的关键结构单元. 然而, 其传统合成方法通常依赖于卤代苯基丙烯酰胺的反应, 且需要使用贵金属或化学计量的有毒自由基引发剂. 本工作报道了一种无金属光化学合成3,3-二取代-2-吲哚酮的策略. 该方法以2-碘-N-甲基甲基丙烯酰胺为底物, 在可见光照射下, 利用廉价易得的汉斯酯同时作为化学计量的光还原剂和氢原子供体, 经分子内自由基环化反应高效构建目标产物. 该反应条件温和, 底物适用性广, 共合成了25个2-吲哚酮衍生物, 产率高达98%. 机理研究表明, 反应经由光诱导电子转移生成芳基自由基中间体, 随后发生5-exo-trig环化及氢原子转移, 最终得到3,3-二取代-2-吲哚酮.

The 3,3-dialkyl-2-oxindole scaffold is a privileged structure found in numerous bioactive compounds, yet its synthesis often relies on precious metal catalysts or toxic radical initiators. Addressing these limitations, we report a sustainable, metal-free photochemical strategy for constructing 3,3-disubstituted oxindoles via visible-light-induced radical cyclization. This method employs an economical Hantzsch ester (HEH) as a dual-function reagent, serving simultaneously as a stoichiometric photoreductant and a hydrogen atom donor, eliminating the need for external photocatalysts or transition metals. The reaction proceeded with 2-iodo-N-methylmethacrylamides using HEH (2.0 equiv) and tetramethylguanidine (TMG, 1.0 equiv.) in acetonitrile under argon atmosphere. Irradiation with a 20 W blue LED at room temperature for 21 h afforded the target oxindoles in excellent yields (up to 98%). Control experiments confirmed the essential roles of HEH, TMG, light, and inert conditions. The protocol showed strong preference for aryl iodides, with bromo- and chloro-analogs giving significantly lower yields. Substrate scope investigation demonstrated broad functional group tolerance. Various substituents on the aryl ring, including electron-donating (-OMe, -Me) and electron-withdrawing groups (-F, -Cl, -Br, -COOMe), were well accommodated. Modifications on the acrylamide moiety, such as different N-alkyl groups (ethyl, cyclopropyl, benzyl) and variations at the α- and β-positions of the acryloyl group, also proceeded successfully, though efficiency depended on the alkene's electronic properties. A gram-scale reaction delivered the product in 87% yield, demonstrating practical scalability. Post-synthetic derivatizations, including reduction, thionation, and N-deprotection, highlighted the method's synthetic utility. Mechanistic studies revealed a photoinduced electron transfer pathway. Radical trapping experiments confirmed aryl radical intermediate, while deuterium labeling identified HEH as the hydrogen source. Fluorescence quenching studies supported PET from photoexcited HEH to the substrate. Based on this evidence, we propose a mechanism involving photoexcitation of HEH/TMG complex to generate a potent reductant, single electron transfer (SET) to cleave the C—I bond, forming an aryl radical, 5-exo-trig cyclization, and hydrogen atom transfer (HAT) from HEH-derived species to furnish the product.