Metal‐Free Hypervalent‐Iodine‐Promoted C3 Difluorination and C2 Oxidation of N‐Substituted Indoles

Abstract

Am etal-free, highly regioselectiveC 3d ifluorination and C2 oxidation of N-substituted indoles, with the aid of in situ generated PhIF 2 in the presenceo ft wo types of fluorinating agents, was reported. This reaction provided 3,3-difluoro-2-oxindoles with yields up to 64 %u nder mild reaction conditions. Am echanism for this reaction was proposed.

Synthetic strategies for the construction of C3-fluorinated oxindoles

“…Difluorination at C-3 was performed with PhI(OAc) 2 and PhIF 2 as a fluorinating agent (Scheme 10). 20 Substrate scope was well explored with different substituents at different positions on the indole ring that afforded the desired products 28 in good yield. Further different substitutions on the N -benzyl ring gave products in moderate yields.…”

Environmentally Friendly Protocol for 2,3-Difunctionlization of Indole Derivatives

“…1 H NMR spectra were recorded at 500 and 600 MHz in CDCl 3 and dimethyl sulfoxide (DMSO)-d 6 . 13 C NMR spectra were recorded at 150 MHz in CDCl 3 and DMSO-d 6 using tetramethylsilane (TMS) or residual solvent signals as an internal standard. J values are given in hertz.…”

“…We recently demonstrated an efficient route to 3,3-dichloro-2-oxindoles from N-substituted indoles using PhICl 2 as an oxidation reagent and a chlorine source . In 2017, our group employed aryliodide, selectfluor, and amine (HF) x to in situ generate PhIF 2 to synthesize 3,3-difluoro-2-oxindoles . With our continuous interest in the synthesis of 3,3-dihalo-2-oxindoles, we herein report 4-iodotoluene-promoted water-phase C-3 dichlorination and C-2 oxidation of N-substituted indoles at room temperature.…”

Highly efficient synthesis of C3-heteroaryl 3-fluorooxindoles via a one-pot stepwise Ce(iii)/photoassisted cross-dehydrogenative coupling/fluorooxidation process

“…Over the past few years, some leading approaches for the synthesis of these scaffolds have been well-established. Among them, fluoro-oxidation 3 or nucleophilic fluorination 4 of specifically functionalized indole or oxindole motifs has been well studied (Scheme 1a). In 2016, Jiang and co-workers reported fluorination-oxidation of 2-hydroxymethylindoles using selectfluor as the electrophilic fluorinating reagent.…”