Access to Phenothiazine Derivatives via Iodide-Mediated Oxidative Three-Component Annulation Reaction

Abstract

Herein, a new iodide-mediated three-component annulation reaction of secondary anilines, cyclohexanones, and elemental sulfur is demonstrated, which allows access to various phenothiazines with the merits of formation of multiple chemical bonds in one single operation, high step and atom efficiency, readily available feedstocks and catalyst system, and good substrate and functional group compatibility. The developed chemistry capable of constructing novel phenothiazines with structural diversity offers a significant basis for further applications.

Recent Advances in the Synthesis of Heterocycles via Reactions Involving Elemental Sulfur

“…[127] 1,2,3,4-Tetrahydroquinolines and N-substituted anilines 282 were found to react with cyclohexanones 283 and sulfur under similar aerobic conditions (KI or I 2 catalyst, DMSO additive, PhCl solvent) to provide phenothiazines 284 (Scheme 99). [128] While the I 2 -catalyzed reaction of N,N-diarylanilines with sulfur leading to phenothiazines was known for more than one century, [129] there is an obvious possibility for the involvement of phenothiazines in the transformation, which could be generated from oxidative condensation of 1,2,3,4-tetrahydroquinolines or Nsubstituted anilines 282 with cyclohexanones.…”

Recent Advances in Sulfur-Containing Heterocycle Formation via Direct C–H Sulfuration with Elemental Sulfur

“…To enable access to unsymmetrical phenothiazines, 9b the Zhang group developed a new iodide-mediated threecomponent annulation reaction (Scheme 56). 91 Various secondary anilines, including tetrahydroquinolines, benzocyclic amines, N-alkylanilines, and diarylamines, were efficiently transformed in combination with cyclohexanones and elemental sulfur, delivering a diverse range of phenothiazine derivatives. Salient features of this method include transition-metal-free conditions, broad substrate scope, and environmentally benign oxygen as the final oxidant.…”

A Mild Two-Step Synthesis of Structurally Valuable Indole-Fused Derivatives

“…Wang and co-workers developed efficient syntheses of acridines from cyclohexanones and aminobenzophenones under metal-free conditions . In 2020, Zhang and co-workers reported a iodide-mediated synthesis of phenothiazines from secondary anilines, cyclohexanones, and elemental sulfur . Our group is devoted to the dehydroaromatization of cyclohexanones and has developed a series of methods for the preparation of various aromatic heterocycles .…”