Difluorocarbene-Enabled Synthesis of 3-Alkenyl-2-oxindoles from ortho-Aminophenylacetylenes

Abstract

Herein, we report a transition-metal-free [4 + 1] cyclization pathway from difluorocarbene and ortho-amino aryl alkynone, rendering an effective and universal strategy for the construction of 3-alkenyl-2-oxindoles. Our strategy starts from cheap and accessible ortho-amino aryl alkynone instead of the direct indole skeleton; moreover, in situ generated difluorocarbene from commercially available halogenated difluoroalkylative reagents enables the cleavage of a C–N bond and formation of new C–N bonds and C–C bonds.

Regio- and diastereoselective synthesis of thioxothiazolidin- indolin-2-ones, oxoindolin-carbamodithioate hybrids, and their base-catalyzed conversion into dispirocyclopentanebisoxindoles

“…Moreover, the reaction gave satisfactory answers with different aromatic and aliphatic amines. 1 H and 13 C NMR, FT-IR, and elemental analysis determined the structure of the nal products. Compound 3c and 5g were also crystallized from EtOAc by slow evaporation at room temperature and the structure was con rmed by Xray crystallographic analysis (Figure 1).…”

“…Analytical TLC was carried out using Merck 0.2 mm silica gel 60 F-254 Al-plates. 1 H NMR and 13 C NMR spectra were recorded on a Bruker Avance DRX-500 machine using DMSO-d 6 as solvent and TMS as an internal standard at room temperature (DMSO-d 6 1 H NMR: δ (ppm) =2.50 ppm; 13 C NMR: δ (ppm) =39.9 ppm; CDCl 3 1 HNMR: δ (ppm) = 7.26 and 13 C-NMR: δ (ppm) = 77.00 ppm). Chemical shifts were reported in ppm scale.…”

“…12 In 2023, Song and coworkers described the synthesis of 3-alkenyl-2-oxindoles via a transition-metal-free [4 + 1] cyclization pathway. 13 Again in 2023, Stephan et al developed a metal-free, B(C 6 F 5 ( 3 catalyzed cyclopropanation of 3-alkenyl-oxindoles with diazomethanes. 14 Copper-catalyzed hydroboration of these compounds was also reported by Moro and coworkers.…”

C–F bond functionalizations via fluorinated carbenes

“…77 In 2023, the same group reported that o-aminoarynyne and difluorocarbene precursors followed a [4 + 1] cycloaddition pathway to construct 3-alkenyl-2-oxindole under transition metal-free conditions (Scheme 25a). 78 Difluorocarbene not only promotes breaking of the C-N bond, but also undergoes C-F bond cleavage as a carbonyl source. Various drug candidates could be synthesized through this strategy in moderate to good yields.…”

Difluorocarbene as a C–F source for the construction of fluorinated benzothiazoles

“…8 b ,10 In all of the above reactions, difluorocarbene functions as a CF 2 source without the loss of any fluorine atom. Recent studies have shown that difluorocarbene can also act as a nonfluorinated C 1 precursor of various functional groups, such as carbonyl, 8 b ,11 cyanide 12 and isocyanide 13 groups (Scheme 1b). The complete loss of the two fluorine atoms is mainly ascribed to the participation of neighboring groups.…”