Direct organocatalytic transfer hydrogenation and C–H oxidation: high-yielding synthesis of 3-hydroxy-3-alkyloxindoles

Abstract

A two-step, high-yielding transfer hydrogenation/C–H oxidation protocol has been developed for the synthesis of 3-alkyl-3-hydroxyoxindoles and medicinally important 3-cyanomethyl-3-hydroxyoxindole, and formal total synthesis of (±)-alline and (±)-CPC-I.

Photoredox-Neutral Radical–Radical Cross-Coupling of Isatins and Benzyl Carboxylic Acids

“…For example, 3-alkylindoles can be oxidized to 3-hydroxy-3-alkyloxindoles with IBX in the presence of CeCl 3 ·7H 2 O (Scheme a) . 3-Hydroxy-3-alkyloxindoles can be obtained from 3-substituted-2-oxindoles in the presence of extra additives (such as t BuOK, TEMPO, dodecyl sulfate SDS, 1,1,3,3-tetramethylguanidine TMG) with air/O 2 /peroxides as the hydroxylation reagent (Scheme b). − 2-Oxindoles can react with alcohols to provide 3-hydroxy-3-alkyloxindole derivatives under heating conditions (110–140 °C) with or without transition-metal catalysis (such as Ru complex; Scheme c). − Transition-metal-mediated Barbier-type reaction using isatins and organic halides as substrates can also construct 3-hydroxy-3-alkyloxindoles successfully (Scheme d). , Although these methods have successfully constructed 3-hydroxy-3-alkyloxindoles, they still face issues, such as the demand for transition metals, substrate preparation, stringent reaction conditions, and limited substrate range. Therefore, it is still necessary to develop effective and transition-metal-free methods to build such valuable skeletons.…”