Hypervalent Iodine(III)-Promoted C3–H Regioselective Halogenation of 4-Quinolones under Mild Conditions

Abstract

A simple and practical protocol for the C3–H regioselective halogenation of 4-quinolones by the action of potassium halide salt and PIFA/PIDA in good to excellent yields was developed. The current approach provides feasible access to the diversity of C3-halgenated 4-quinolones at room temperature with high regioselectivity and good functional group tolerance, from which bioactive compounds can be easily constructed. Moreover, the current method featured eco-friendly, operational convenience and is suitable for halogenation in a gram scale of 4-quinolones in water without sacrificing yields.

Aqueous Mediated Reactions Involving Hypervalent Iodine Reagents

“…(2021) in aqueous media using PIFA as an oxidant and potassium bromide salt as a bromine source at room temperature (Scheme 51). [97] Halogenated quinolones have medical importance and can be used further for the synthesis of bioactive compounds. The reaction proceeds through ligand exchange mechanism via formation of hypervalent iodine intermediate (Scheme 52).…”

“…(2021) in aqueous media using PIDA and KI as an oxidant and iodine source respectively (Scheme 62). [97] …”

“…Regioselective bromination of 2-phenylquinolin-4(1H)-one at C-3 position in 83% yield was reported by Yang et al (2021) in aqueous media using PIFA as an oxidant and potassium bromide salt as a bromine source at room temperature (Scheme 51). [97] Halogenated quinolones have medical importance and can be used further for the synthesis of bioactive compounds. The reaction proceeds through ligand exchange mechanism via formation of hypervalent iodine intermediate (Scheme 52).…”

“…[99] Yang et al in 2021 disclosed a simple and green methodology for the regioselctive C-3 chlorination of 2-(4-methoxyphenyl)quinolin-4(1H)-one in good yield using PIFA as an oxidant and KCl salt as a chlorine source at room temperature in aqueous media (Scheme 57). [97]…”

“…[103] Iodination of 2-phenylquinolin-4(1H)-one at room temperature to afford 3-iodo-2-phenylquinolin-4(1H)-one in 86 percent yield was carried out by Yang et al (2021) in aqueous media using PIDA and KI as an oxidant and iodine source respectively (Scheme 62). [97] 9. Carbonylation Reaction Grushin et al in 1993 reported the carbonylation of a number of aromatic ring substituted iodoxyarenes in water to give corresponding carboxylic acids in good to modest yields in gentle reaction conditions, in absence of any organic solvents (Scheme 63).…”