Regioselective Metal-Free One-Pot Synthesis of Functionalized 2-Aminothiophene Derivatives

Abstract

A facile metal-free synthesis of 2-aminothiophene derivatives by the reaction of 2-ynals with thioamides in alcohols has been developed. This transformation allows the assembly of 2-aminothienyl ether derivatives via a well-designed aldol condensation/regioselective intramolecular cyclization/conjugate addition cascade reaction and provides a straightforward synthetic protocol for constructing 2,3,5-trisubstituted 2-aminothiophenes.

C–H Imidation and Dual C–H Bond Aminobromination of Five-Membered Heterocycles

“…Five-membered heterocycles bearing an amine group are commonly found in natural products, bioactive compounds, and pharmaceuticals . For example, 2-aminothiophenes are widely used as inhibitors of APE 1 and tubulin polymerization . Zyprexa (Olanzapine), which contains a 2-aminothiophene core, is ranked as one of the world’s top 200 drugs in terms of sales.…”

Chemo-, Regio-, and Stereoselective Construction of Core Skeleton of Furo[2,3-b]pyrrole via Multicomponent Bicyclization Reaction

“…Reactions of KTAs with a variety of biselectrophilic groups have so far been applied to make five- and six-membered and fused heterocycles during the past years . Recently, the groups of Singh and Deng reported two methods for the synthesis of pyrroles and thiophenes, respectively. Nandi also developed a tandem reaction for synthesis of pyrrole and furan derivatives using the KTAs as synthons.…”

Copper-Catalyzed N-Arylation of Azoles and Mannich-Type Coupling of Ketones and Azoles under Metal-Free Conditions

“…Five-membered heterocycles bearing an amine substituent are commonly used in medicinal chemistry. For example, several 2-aminothiophene derivatives are currently used as inhibitors of APE 1 and tubulin polymerization . Furthermore, Zyprexa (Olanzapine), which is based on a 2-aminothiophene core, is ranked as one of the world’s top 200 drugs in terms of its sales.…”