Studies Of One-pot Synthesis Polysubstituted Thiophenes From 1, 3-Dicarbonyl Compounds

Thiophene derivatives represent a class of important and well-studied heterocycles. Gewald and co-workers developed the synthesis of 2-aminothiophenes from the multicomponent condensation of ketones or aldehydes, cyanoacetate and elemental sulfur. Later on, there are several reviews and papers reported on the variations and improvements on the originally published Gewald synthesis of polysubstituted thiophenes. Some of recent novel synthetic pathways involve the cyclisation ofα-oxo ketene-(S,S)-acetals, obtained from active methylene compounds and carbon disulfide, in basic media. However, Gewald method requires long reaction time and suffers from harsh conditions such as strong base, high cost of catalyst, and difficult purification, whereas the cyclisation ofα?oxo ketene-(S,S)-acetals is a two-step and low yielding reaction.α?Oxoketene dithioacetals are a kind of versatile intermediates used in organic synthesis. This work mainly based on the following two aspects:1. A facile and convenient one-pot synthesis of polysubstituted thiophenes and polysubstituted thieno [2,3-b] thiophenes based on the reactions ofβ-dicarbonyl compounds in the presence of K2CO3 in water is developed. The simple procedure, mild conditions, high yields, and especially the relation to the current environmental concerns, make this protocol much attractive for academic research and practical application.2. We developed a facile and convenient one-pot synthesis of highly substituted thiophenes. A series of polysubstituted thiophenes was synthesized by reacting 1,3-dicarbonyl compounds with CS2, and stepwise added alkyl bromides and methylene active bromides via an intramolecular cyclization reaction in high yields. A mechanism involved in the one-pot synthesis of thiophenes of type was proposed.In summary, a facile and convenient one-pot synthesis of polysubstituted thiophenes was developed. The simplicity of execution, mild conditions, high yields, ready availability of substrates, flexible substituted patterns, and broad range of potential synthetic utility of the products, make the protocol attractive for academic research and practical applications.