Synthesis of 3,3-dichloroindolin-2-ones from isatin-3-hydrazones and (dichloroiodo)benzene

Abstract

Aryl- and N-substituted isatins were converted to isatin-3-hydrazones and subjected to a dichlorination reaction with PhICl2. Lewis base-catalysis was key to the reaction occurring rapidly and chemoselectively, providing 3,3-dichloroindolin-2-ones in 49-99% yield, and offering a new approach to the deoxygenative dihalogenation reaction.

Designs and Strategies for the Halo‐Functionalization of Diazo Compounds

“…A series of diversely substituted isatin‐derived diazo compounds 128 treated with (dichloroiodo)benzene ( 125 ) in the presence of a Lewis base and pyridine as the iodane‐activator, afforded biologically relevant 3,3‐dichloro‐2‐oxindole scaffolds 129 (Scheme ). An alternative route to 129 was also demonstrated by the same group in another report via the reactions of isatin‐3‐hydrazones with 125 using pyridine as the activator …”

Synthesis of 3,3-dichloro-2-oxindoles from isatin-3-p-tosylhydrazones and (dichloroiodo)benzene

“…22 This process gave the dichloride products of aryl-and N-functionalized substrates in good to excellent yield, and was compatible with a broad range of different steric and electronic substituents including halogens, ethers, alkyl, allyl, propargyl and aryl groups. We were unable to test N-acetyl, -benzoyl, -sulfonyl and N-carbamate derivatives in the reaction as these groups were incompatible with the aqueous hydrazine used for hydrazone formation.…”

“…Inspiration for a solution to the functional group incompatibility problem came from analyzing both our 22 and Barton's 21a mechanistic proposals for the oxidation of hydrazones with iodanes ( Figure 2). Reaction of the activated iodane (PhICl 2 py) with hydrazone 12 would give intermediate A, which, in the presence of chloride anions, would react to lose iodobenzene and give azo compound B.…”

Hypervalent iodine reagents for heterocycle synthesis and functionalization

“…The common feature of these reactions is the transfer of the two chlorine ligands from PhICl 2 in a germinal fashion rather than vicinal. 37,38 In 2014, He et al 39…”