Unified and Benign Synthesis of Spirooxindoles via Bifunctional and Recyclable Iodide‐Salt‐Catalyzed Oxidative Coupling in Water

Abstract

Herein we develop a novel micellar catalytic system based on amphiphilic bifunctional iodide salts for oxidative intramolecular α‐oxygenation and α‐amination of carbonyl substrates in water, thus enabling a unified and benign synthesis of various 2‐oxindoles containing spirotetrahydrobenzofurans, spiroisochromanones, spiroindolines and spirolactones. Notably, the terminal oxidant H2O2 produced water as the only by‐product. The excellent recyclability of the aqueous medium containing the catalyst further highlights the synthetic utility of this system.

Cinchona Alkaloid Derived Iodide Catalyzed Enantioselective Oxidative α-Amination of Carbonyl Compounds toward the Construction of Spiroindolyloxindole

“…9 They are small yet have considerable complexity, and of particular structural interest are their inherent multiple stereogenic centers, rigid and nucleophilic tertiary amine, and Along the line of our interest in sustainable oxidative coupling reactions, 12 we recently described an amphiphilic ammonium iodide tethering a long and hydrophobic alkyl chain that could form a micellar microreactor for oxidative intramolecular αoxygenation and amination of oxindoles in water. 13 The selection of these substrates was motivated by the prevalence of the resulting spirotetrahydrobenzofurans and spiroindolines in many biologically important molecules. 14 Herein, we report our study on the cinchona alkaloid based iodide catalyzed oxidative α-amination of 3-substituted oxindoles, which provides a powerful and practical tool for the straightforward synthesis of optically active spiroindolyloxindoles (Scheme 1d).…”

“…For example, by simple alkylation, many chiral quaternary ammonium halides can be obtained as robust chiral phase transfer catalysts . Along the line of our interest in sustainable oxidative coupling reactions, we recently described an amphiphilic ammonium iodide tethering a long and hydrophobic alkyl chain that could form a micellar microreactor for oxidative intramolecular α-oxygenation and amination of oxindoles in water . The selection of these substrates was motivated by the prevalence of the resulting spirotetrahydrobenzofurans and spiroindolines in many biologically important molecules .…”

Efficient Synthesis of 2,3′-Spirobi (Indolin)-2′-Ones and Preliminary Evaluation of Their Damage to Mitochondria in HeLa Cells

“…( Cao and Zhou, 2015 ; He et al, 2020 ; Liu X. et al, 2020 ; Nakamura et al, 2020 ; Reddy et al, 2020 ; Bortolami et al, 2021 ; Nasri et al, 2021 ; Saranya et al, 2021 ) Nevertheless, the construction of the structurally similar spirobi (indolin) frameworks (Skeleton B, Figure 1 bottom left) has been less studied, and until now, only two synthetic methods have been reported for the synthesis of 2,3′-spirobi (indolin)-2′-ones. ( Gui et al, 2019 ; Wang et al, 2019 ) In 2019, Shi and co-workers pioneered the (4 + 1) annulation of 3-isothiocyanato oxindoles and aza- o -quinone methides, affording the corresponding condensed products in two steps. Meanwhile, Zhong’s group reported an ioide salts catalyzed functionalization of carbonyl compounds with sulfonamides.…”

Electrochemical Umpolung C–H Functionalization of Oxindoles

“…Relevant transformations of the C-3 position, invariably employing the oxindole fragment as a nucleophile, include arylation, 7 alkynylation, 8 alkylation, 9 fluorination, 10 trifluoromethylation, 11 nitration, 12 azidation, 13 amination, 14 and thiolation. 15 When it comes to its use as an electrophilic synthon, Kotagiri has described the stoichiometric use of an hypervalent iodine reagent [PhI(OCOCF 3 ) 2 ] for the oxidative alkoxylation of oxindoles ( Scheme 1 B, eq 2), 16 and more recently, the oxidative intramolecular α-oxygenation and α-amination of oxindoles was reported by Zhong, employing a micellar catalytic system based on amphiphilic bifunctional iodide salts in water ( Scheme 1 B, eq 3), 17 featuring H 2 O 2 as the terminal oxidant. Few methods were also reported for the direct CH-functionalization of oxindoles using electrochemistry.…”