A Thioannulation Approach to Substituted Thiophenes from Morita–Baylis–Hillman Acetates of Acetylenic Aldehydes

Abstract

A new protocol has been developed for the synthesis of substituted thiophenes under mild and metal-free reaction conditions via the base-promoted thioannulation of Morita-Baylis-Hillman acetates of acetylenic aldehydes with potassium thioacetate involving a tandem allylic substitution/deacetylative 5-exo-dig-thiocycloisomerization. The obtained products provide an entry to 4H-thieno[3,2-c]chromene and thieno[3,2-c]dihydroquinoline.

Recent Advances in the Synthesis of Thiophene Derivatives by Cyclization of Functionalized Alkynes

“…More recently, a strictly related method has been published, regarding the metal-free cyclization of 4-en-1-yn-3-yl acetates 3 to give 2,4-disubstituted thiophenes 5 through the intermediate formation of ( Z )-2-en-4-yne-1-thiolate derivatives 4 , formed in situ by allylic nucleophilic substitution with KSAc followed by base-promoted deacylation (Scheme 3) [59]. Intermediates 4 were then converted into thiophenes 5 by 5- exo - dig cyclization and aromatization.…”

“…Intermediates 4 were then converted into thiophenes 5 by 5- exo - dig cyclization and aromatization. The reaction has been applied to the synthesis of several 2,4-disubstitued thiophenes, but presented limitations due to the strong basic conditions employed (for example, the reaction could not be applied to substrates bearing a terminal triple bond) and to the need for the presence of an electron-withdrawing group (EWG) at the C-4 of the starting material (Scheme 3) [59].…”

“…Synthesis of 2,4-disubstitued thiophenes 5 from 4-en-1-yn-3-yl acetates 3 by sequential allylic nucleophilic substitution with KSAc followed by base-promoted deacylation, to give ( Z )-2-en-4-yne-1-thiolate derivatives 4 , and base-promoted thiocyclization [59]. …”

Efficient Thiophene Synthesis Mediated by 1,3‐Bis(carboxymethyl)imidazolium Chloride: C‐C and C‐S Bond Formation

“…11 An efficient and simple copper catalyzed route for the synthesis of di-, tri-and tetrasubstituted thiophenes, with excellent yields, has been reported starting from 1,4-diiodo-1,3dienes and potassium sulfide. 12 Some methodologies use different sulfur reagents (such as K2S, 13 KSCN 14 or KSAc) 15 that decrease the atomic economy of the process. Therefore, the use of elemental sulfur (S8) is a more sustainable alternative for preparing sulfur-containing compounds, being considered a cheap and environmentally friendly reagent.…”

One‐pot, Multicomponent Cascade Reaction for the Synthesis of Various Aralkyl/alkylthio‐3,5‐dimethyl‐1H‐pyrazolyl‐4H‐1,2,4‐triazol‐4‐amine and Their Docking Studies

“…Organosulfur chemistry is one of the most useful and important branch in organic synthesis. Compounds possessing C─S bonds are important in organic chemistry . Thioethers are beneficial and important compounds in different branches such as materials, agriculture, industry, pharmaceutical, medicine, heterocyclic chemistry, and biological processes .…”