An efficient route to synthesize isatins by metal-free, iodine-catalyzed sequential C(sp³)–H oxidation and intramolecular C–N bond formation of 2′-aminoacetophenones

Abstract

A novel molecular I2-catalyzed synthesis of isatins through C(sp(3))-H oxidation and intramolecular C-N bond formation of 2'-aminoacetophenones with excellent yields up to 97% under transition metal, base, additive, peroxide and ligand free conditions is described. The present protocol is suitable for gram scale synthesis of isatins and retained its high yield. Further, the synthetic utility of this present reaction towards synthesis of bioactive 3-hydroxy-2-oxindoles and oxindoles is demonstrated.

Titania‐Supported Gold Nanoparticles as Efficient Catalysts for the Oxidation of Cellobiose to Organic Acids in Aqueous Medium

“…Subsequently, a series of methods for transition‐metal‐catalyzed C–H oxidation were documented,9 including the copper‐catalyzed intramolecular oxidative C(sp 3 )–H amidation of 2‐aminoacetophenones,9a the copper‐mediated C–H oxidation and C–N cross‐coupling of 2′‐aminoacetophenones,9b as well as oxidative palladium‐catalyzed CH/NH double carbonylation 9c. Furthermore, several other protocols have been established, including ylide‐mediated carbonyl homologations,10 selenium‐mediated oxidations,11 modified Sandmeyer reactions,12 I 2 ‐catalyzed synthesis of isatins from 2′‐aminoacetophenones,13a and I 2 ‐mediated oxidative amidation of sp, sp 2 , and sp 3 C–H bonds 13b…”

The Applications of Dimethyl Sulfoxide as Reagent in Organic Synthesis

“…The isatins were formed via intramolecular CN bond formation of 2′‐aminophenylacetylene ( sp carbon) or 2′‐aminostyrene ( sp 2 carbon) as well as 2′‐amino‐β‐keto ester ( sp 3 ‐C) (Scheme ) 63. The same transformation could also be achieved with I 2 as the catalysis as reported by Sekar, Rajeshkumar and co‐workers (Scheme ) 64…”

Metal‐Free Cross‐Dehydrogenative Coupling (CDC): Molecular Iodine as a Versatile Catalyst/Reagent for CDC Reactions

“…The synthesis of as eries of isatins throught he oxidative intramolecular cyclization of 2-aminoacetophenone has been accomplished in good to excellent yields (Scheme28). [40] The reaction can be performed with different substituents on the phenylring and amine nitrogen atom, and in general,the reaction works well for the synthesis of isatins.T he a-iodination of methylk etone 121 gives 122;t his is followed by Kornblumo xidation to give 123 and subsequenta nnulation to provide intermediate 124,w hich eliminates HI to form isatin 125.D MSO oxidizesliberated HI to regenerate I 2 .…”

“…The synthesis of a series of isatins through the oxidative intramolecular cyclization of 2‐aminoacetophenone has been accomplished in good to excellent yields (Scheme ) . The reaction can be performed with different substituents on the phenyl ring and amine nitrogen atom, and in general, the reaction works well for the synthesis of isatins.…”