Trifluoromethyl radical triggered radical cyclization of N-benzoyl ynamides leading to isoindolinones

Synthesis of Polysubstituted Isoindolinones via Radical Cyclization of 1,3-Dicarbonyl Ugi-4CR Adducts Using Tetrabutylammonium Persulfate and TEMPO

“…The authors confirmed through electronic structure calculations by density functional theory (DFT) that the cyclization of the vinyl radical species generated after the intermolecular radical attack of CF 3 • onto the ynamide functional group always takes place in the electron-deficient N -benzoyl moiety via a barrier of 6.3 kcal/mol instead of the benzyl group present in the molecule, which requires 16.1 kcal/mol. This behavior can be attributed to the weaker lowest unoccupied molecular orbital (LUMO)–singly occupied molecular orbital (SOMO) gap between the radical species and the N -benzoyl moiety …”

“…These radicals subsequently participate in two process: (a) the generation of species I via the SET process from adduct 19 and (b) the oxidation of TEMPO 21 to species A [TEMPO + ]­SO 4 2– ( n -Bu 4 N + ) . After intramolecular 5- endo -trig radical cyclization onto the N -benzoyl moiety, transient cyclohexanedienyl radical species II is oxidized to cation III by the effect of the strong oxidant oxoammonium salt A . Finally, this species suffers a subsequent rearomatization process followed by an acid–base reaction to lead to product 20 (Scheme ).…”

Recent Advances in the Ring-Forming Reactions of Ynamides

“…此种方法还被应用于串联的自由基环合反应高效地合 成了一种新型的原小檗碱类似物 6. 图式 3 炔酰胺的自由基环化反应合成 4-硫代芳基吡咯 Scheme 3 Synthesis of 4-thioarylpyrroles by radical cyclization of ynamides 同年, Ollivier 和 Fensterbank 等 [8] 通过三氟甲基自由 基引发炔酰胺发生环化构建了一系列异吲哚啉酮类化 合物 21 (Scheme 4). 在光催化条件下, 三氟甲基自由基 首先对炔酰胺进行三氟甲基化生成自由基 18, 然后 18 进行分子内环合得到了一系列异吲哚酮类化合物 21, 该环化主要得到 E-构型为主的产物.…”

Ynamides in Free Radical Reactions

“…In 2019, the group of Ollivier and Fensterbank developed a photocatalyzed trifluoromethylation of benzoyl ynamides ( 73 ), which led to the formation of various isoindolinones 74 after cyclization on the benzoyl fragment (Scheme 28). [35] The reaction proceeds under blue light irradiation with an iridium(III) photocatalyst using Togni II trifluoromethylation reagent.…”