Highly mild approach towards synthesis of tetrasubstituted thiophenes by an organic salt afforded by cyclic thioureas and ketene dithioacetals

Abstract

An organic salt generated by cyclic thioureas and 2-di(methylsulfanyl)methylene malononitrile in reaction with primary and secondary a-haloketones leads to tetrasubstituted thiophenes without using additional base or catalyst at room temperature. The S-methylisothiourea moiety of this salt as an organocatalyst performs a hybrid function of thiourea and imidazole to activate electrophiles via H-bonding and trigger cyclization via Lewis basicity character, respectively. Interestingly, a green solvent (in two step mode), short reaction time, easy purification, high yield and selectivity accompany this protocol. The structures of the intermediate and afforded adducts are fully characterized by analytical investigations and X-ray crystallography.

Palladium‐Catalyzed Migratory Insertion of Isocyanides into C(thiophene)–SMe Bonds: Access to Atom‐Transfer Reactions

“…Initially, the reaction between imidazoline‐2‐thione ( 1 ), 2‐[bis(methylsulfanyl)methylene]malononitrile ( 2 ), 2‐bromoacetophenone ( 3 ), and tert ‐butyl isocyanide ( 4 ) was performed as the model input for the optimization of the reaction conditions (Table ). According to our previous report, the best solvent system for the synthesis of the thiophene as a starting material is the combination of DMF and EtOH, and so the optimization was performed in this. The reaction was evaluated in the presence of various Pd sources (5 mol‐%) at 80 °C (Table ).…”

“… Reaction conditions: one‐pot, 1 (0.25 mmol), 2 (0.25 mmol), DMF (1 mL), 120 °C, 3 h; next, 3 (0.14 mmol), EtOH (1 mL), room temp., 10 min (see ref); next, 4 (0.15 mmol, 1.1 equiv. ), 80 °C, 8 h.…”

Recent Advances in Palladium-Catalyzed Isocyanide Insertions

“…An early example (2017) of such an imidoylative Liebeskind-Srogl coupling was performed in a one-pot fashion as depicted in Scheme 43 [81]. The thiophene 156 is formed via an S-demethylation/Thorpe-Ziegler cyclization [82], and is directly subjected to the imidoylative reaction conditions. The reaction reliably affords the thioimidate 155 in 62-74% yield.…”