p-TSA/Base-Promoted Propargylation/Cyclization of β-Ketothioamides for the Regioselective Synthesis of Highly Substituted (Hydro)thiophenes

Abstract

Metal-free, p-toluenesulfonic acid (p-TSA)-mediated, straightforward propargylation of β-ketothioamides with aryl propargyl alcohol has been achieved at room temperature. In addition, the reaction also provided thiazole rings as byproducts. Furthermore, the propargylated thioamides undergo intramolecular 1,5-cyclization to afford fully substituted (hydro)thiophenes in the presence of base. Notably, the approach is pot, atom, and step economical (PASE).

One‐Pot Synthesis of 2,3,5‐Trisubstituted Thiophenes through Three‐Component Assembly of Arylacetaldehydes, Elemental Sulfur, and 1,3‐Dicarbonyls

“…Recently, the transition‐metal‐catalyzed direct C−H arylation of thiophenes has found to be an efficient tool for the thiophene diversification ,. With respect to annulation reactions, non‐readily available starting materials such as functional mercaptans,thioamides,, dialkynes,– and 1,2,3‐thiadiazoles, were frequently employed to generate substituted thiophenes through intermolecular or intramolecular cyclization. Also, few examples of multicomponent reactions led to the construction of thiophene rings from readily available chemicals ,.…”

Electrochemical Synthesis of 1,2,3-Thiadiazoles from α-Phenylhydrazones

“…However, the challenging electrochemical method leading to heterocycles with intramolecular N–S bond formation is still limited . In particular, because of our ongoing interest in metal-free bond formation reactions and our curiosity in electro-organic synthesis, we planned to develop an electrochemical N–S bond formation reaction and to apply it to the synthesis of N,S-heterocycles.…”

Chemoselective Ullmann Reaction of α-Trisubstituted Thioamides: Synthesis of Novel 2-Iminobenzothiolanes

“…They are also precursors for the synthesis of the well-known drug raloxifene and its analogues . Therefore, several elegant synthetic methods have been developed for the construction of 2-aminobenzothiophene derivatives, whereas those for the 2-iminobenzothiophene core remain elusive in the literature. , Recently, a 2-iminothiophene-fused polyaromatic compound A were synthesized from thioamides (Figure ). The photophysical studies show emission in the range of 500–606 nm with quantum yields up to 0.64 .…”