Iron-Catalyzed Oxidative Coupling of Indoline-2-ones with Aminobenzamides via Dual C–H Functionalization

Abstract

We describe an unprecedented dual C–H functionalization of indolin-2-one via an oxidative C­(sp3)–H/N–H/X–H (X = N, C, S) cross-coupling protocol, which is catalyzed by a simple iron salt under mild and ligand-free conditions and employs air (molecular oxygen) as the terminal oxidant. This method is readily applicable for the construction of tetrasubstituted carbon centers from methylenes and provides a wide variety of spiro N-heterocyclic oxindoles.

Gold‐Catalyzed Formal [4+2] Cycloaddition as Access to Antitumor‐Active Spirocyclic Oxindoles from Alkynes and Isatin‐Derived Ketimines

“…Interestingly, this excellent yield was maintained using reduced catalyst loadings (1 mol % and 0.1 mol %) at room temperature (entries 16 and 17). Several acids, including para-toluenesulfonic acid (p-TSA), HNTf 2 , ZnCl 2 , CF 3 COOH and SnCl 4 , were evaluated as well, but all resulted in lower yields (entries [18][19][20][21][22].…”

“…[20] Then, Xu's group reported an iron-catalyzed oxidative dual CÀ H functionalization of indolin-2-ones with aminobenzamides to provide spiro N-heterocyclic oxindoles under mild conditions. [21] In 2022, Guo's group described a palladium-catalyzed domino Heck/decarboxylative alkynylation sequence towards spiro N-heterocyclic oxindoles. [22] Nevertheless, there is still a high demand for effective protocols to rapidly synthesize six-membered spiro N/Oheterocyclic oxindoles, especially spirocarbamate oxindoles.…”

Advances in the Iron-Catalyzed Direct Functionalizations of ­Heterocycles

“…The Xu group demonstrated the ligand-free iron-catalyzed C-H functionalization of oxindole for the facile synthesis of spiro Nheterocyclic oxindole derivatives using oxindole with aminobenzamide in the presence of p-TSA (Scheme 21). 40 Without p-TSA, the transformation was ineffective, resulting in a lower yield, which indicates that acid might act as a co-catalyst for intramolecular cyclization/dehydration. This novel strategy was applied to various amides, sulfonamides, anilines, and aliphatic amines to construct spiro N-heterocyclic oxindole.…”

5,5’-Indigodisulfonic acid as an efficient catalyst for the synthesis of 2,3-dihydroquinazolinone derivatives

“…White solid, TLC Rf = 0.33 (PE/EA = 1:3), m.p. = 268-270 °C (literature [38] 267-268 °C). 1 H NMR (400 MHz, DMSO) δ 10.29 (brs, 1H), 8.33 (brs, 1H), 7.60 (dd, J = 7.7, 1.2 Hz, 1H), 7.47 (d, J = 7.3 Hz, 1H), 7.33 (td, J = 7.7, 1.0 Hz, 1H), 7.27 (brs, 1H), 7.25 -7.19 (m, 1H), 7.05 (t, J = 7.5 Hz, 1H), 6.84 (d, J = 7.7 Hz, 1H), 6.68 (t, J = 7.5 Hz, 1H), 6.61 (d, J = 8.0 Hz, 1H).…”