Synthesis of Substituted Thiophenes through Dehydration and Heterocyclization of Alkynols

Abstract

A protocol was described for obtaining a variety of substituted thiophenes with functional potential via metal-free dehydration and sulfur cyclization of alkynols with elemental sulfur (S8) or EtOCS2K in moderate-to-good yields. The method provides the base-free generation of a trisulfur radical anion (S3 •–) and its addition to alkynes as an initiator. This research broadens the applications of S3 •– in the synthesis of sulfur-containing heterocycles.

Applications of trisulfide radical anion S3˙− in organic synthesis

“…27 The authors propose that this transformation occurs via a multi-step pathway involving initial attack of S base-free dehydration and sulfur cyclization of alkynols 27 with elemental sulfur (S 8 ). 28 Actually, 1,3-enynes 28 can be easily in situ generated from alkynols 27 under the reaction conditions. Various substituted thiophenes such as 2-substituted thiophene 29a, 2,4-disubstituted thiophene 29d, 2,5-disubstituted thiophenes 29b, 29c, 2,3-disubstituted thiophene 29e, 2,3,5-trisubstituted thiophene 29f were obtaine in good to excellent yields by using iodine in N-methyl-2-pyrolidone (NMP) (Scheme 9).…”

From Conventional to Sustainable Catalytic Approaches for Heterocycles Synthesis

“…This approach provides the base-free generation of a trisulfur radical anion and its addition to alkynes as an initiator, broadening the applications of this radical in the synthesis of sulfur-containing heterocycles. [93]…”

“…Then, trisulfur radical anion (S 3 ⋅ − ) adds to the C−C triple bond of II to generate the alkenyl radical III , which then undergoes intramolecular 1,3‐hydrogen migration to obtain another intermediate that after intramolecular radical coupling gives the product and release S 2 ⋅ − species. This approach provides the base‐free generation of a trisulfur radical anion and its addition to alkynes as an initiator, broadening the applications of this radical in the synthesis of sulfur‐containing heterocycles [93] …”

One‐Pot Access to Tetrasubstituted 2‐Aminothiophenes via Regio‐ and Chemoselective Domino Reactions of Dithioesters with Fumaronitrile at Room Temperature

“…2‐Aminothiophenes unobtainable via the Gewald reaction were synthesized by three‐component reaction of α ‐cyanoacetates with chalcones and elemental sulfur (Scheme 1c) [15c] . Synthesis of substituted thiophenes through dehydration and heterocyclization of alkynols have been reported [15d] (Scheme 1d). Along with the above reported method, there are several synthetic strategies for the synthesis of 2‐aminothiophene derivaties [16] .…”