Copper‐Catalyzed Thioannulation of Propynamides with Sodium Sulfide for the Synthesis of Isothiazol‐3‐ones

Abstract

A method for the copper-catalyzed thioannulation of propynamides with sodium sulfide was developed for the synthesis of isothiazol-3ones. The reaction involves a nucleophilic addition and an intramolecular cross-dehydrogenative coupling reaction. The thioannulation features the use of an inexpensive and odorless sulfur source and easily prepared propynamides with excellent functional group tolerance.

Genetic validation of Aspergillus fumigatus phosphoglucomutase as a viable therapeutic target in invasive aspergillosis

“…This article contains supporting information ( 71 , 95 , 108 , 138 , 139 , 140 , 142 , 143 , 144 , 167 , 169 , 170 , 171 , 172 , 173 , 174 , 175 , 176 , 177 , 178 , 179 , 180 , 181 , 182 , 183 , 184 , 185 , 186 , 187 , 188 ).…”

Selectfluor-Promoted Intramolecular N–S Bond Formation of α-Carbamoyl Ketene Dithioacetals in the Presence of Water: Synthesis of Multifunctionalized Isothiazolones

“…13 C{ 1 H} NMR (CDCl 3 , 100 MHz): δ 16. 8,163.9,136.4,129.6 (2C),128.3,124.5 (2C),73.2,48.0,5.5. HRMS (ESI) (d,2H,J = 8.4 Hz),7.48 (t,2H,J = 7.8 Hz),7.38 (t,1H,J = 7.4 Hz),7.26 (d,2H,J = 8.0 Hz),1H),1H), 2.41 (s, 3H), 1.52 (t, 3H, J = 7.6 Hz).…”

“…7 Later, the thiocyclization reaction of propynamides and sodium sulfide in the presence of a copper catalyst also provided access to Nsubstituted-5-arylisothiazolones, which was reported by Zhang and co-workers (Scheme 1c). 8 Very recently, an array of Nquinolyl-4-aryl-isothiazolones was synthesized using Pd-catalyzed C−H bond functionalization of acrylamides using an SCN agent as the sulfur source (Scheme 1d). 9 Although considerable progress has been achieved in this field, the exploration of simple and efficient methods for producing diversified isothiazolones with various structural variations at the nitrogen atom as well as in the C4 and C5 positions is still highly desirable, which can meet different requirements of stability, solubility, and modulation of bioactivity.…”

“…In 2017, Reddy’s group reported cascade thiocyanation followed by intramolecular decyanative S -amidation cyclization of ynamides to give N -substituted-5-phenylisothiazolones . Later, the thiocyclization reaction of propynamides and sodium sulfide in the presence of a copper catalyst also provided access to N -substituted-5-arylisothiazolones, which was reported by Zhang and co-workers (Scheme c) . Very recently, an array of N -quinolyl-4-aryl-isothiazolones was synthesized using Pd-catalyzed C–H bond functionalization of acrylamides using an SCN agent as the sulfur source (Scheme d) .…”

1,10‐Phenanthroline: A versatile ligand to promote copper‐catalyzed cascade reactions

“…In 2019, Zhang's group reported Cu(OTf) 2 ‐catalyzed thioannulation of propynamide 42 and sodium sulfide 43 (Scheme 10). [ 45 ] This transformation involved a nucleophilic addition and an intramolecular cross‐dehydrogenative coupling reaction as tandem steps. This method featured the advantages of a low‐cost and odorless sulfur source and easily prepared propynamides, and excellent functional group tolerance, while aliphatic propynamides could not be smoothly converted.…”