Transition Metal‐Free Synthesis of Substituted Isothiazoles via Three‐Component Annulation of Alkynones, Xanthate and NH₄I

Abstract

A protocol was described to access diverse isothiazoles with functionalization potential via transition metal‐free three‐component annulation of alkynones, potassium ethylxanthate (EtOCS2K) and ammonium iodide (NH4I). A sequential regioselective hydroamination/thiocarbonylation/intramolecular cyclization cascade achieved the efficient formation of consecutive C−N, C−S and N−S bonds in a one‐pot process.

Selective Synthesis of Substituted Pyridines and Pyrimidines through Cascade Annulation of Isopropene Derivatives

“…In addition to being an iodine source for promoting reactions, NH 4 I is a promising nitrogen source for the synthesis of nitriles and nitrogen-containing heterocycles. Recently, our group realized a metal-free cascade annulation of isopropene derivatives, NH 4 I, and EtOCS 2 K for the synthesis of 4-substituted isothiazoles, where the isopropene derivatives were used as C3 synthons and NH 4 I was the “N” source (Scheme , a) . To further explore novel methods for the construction of nitrogen-containing heterocycles, we propose a metal-free cascade annulation of isopropene derivatives that selectively synthesizes substituted pyridines and pyrimidines (Scheme , b).…”

KI/K2S2O8 Mediated Cascade C(sp3)−H/C(sp2)−H Thiolation for the Synthesis of Multi‐Substituted Thiazoles

“…Then, mercaptoeneamine (Ia-3) could be formed after the removal of a molecule of EtOC(= S)OH from Ia-2 according to the previous research. [17] Finally, C(sp 3 )À H dehydroiodination, intramolecular ring closure, aromatization, and oxidation to thiazole c1 under the action of iodine and DMSO.…”

“…This active intermediate would immediately react with potassium ethyl xanthate giving crucial Ia‐2 via nucleophilic substitution. Then, mercaptoeneamine ( Ia‐3 ) could be formed after the removal of a molecule of EtOC(=S)OH from Ia‐2 according to the previous research [17] . Finally, C( sp 3 )−H dehydroiodination, intramolecular ring closure, aromatization, and oxidation to thiazole c1 under the action of iodine and DMSO.…”

Transition‐Metal‐Free Synthesis of N‐Heterocyclic Compounds via Multi‐Component Reactions

“…A Metal-free MCR for the synthesis of these important substituted isothiazoles 250 was reported by Li et al (Scheme 45). [61] This reaction was carried out by three-component annulations of alkynones 249, xanthateandammonium iodide.…”