Recent Advances in the Synthesis of Thiophenes and Benzothiophenes

Abstract

The use of thiophenes in medicinal chemistry and materials sciences has grown enormously during the past several years. For example, thiophene is the backbone of several important pharmaceuticals such as Reloxifen, duloxetine (Cymbalta), tiotropium (Spiriva), Cosopt (dorzolamide), etc. Importantly, the syntheses the aforementioned drugs use simple thiophenes as starting materials. The quest for these exotic small molecules has been brought forth by either modification of classical methods and, more importantly, novel synthesis by highly creative synthetic chemists. Likewise attention has been drawn to the efficient synthesis of thiophenes-containing organic materials due to the importance of atom-economics and green chemistry. Due to the facile synthesis of thiophene derivatives much progress has been made in thiophenes containing organic materials with respect to light-emitting diodes, firld-effect transistors, solar cells, etc. This report details the major synthetic methods for the synthesis of thiophenes and benzo[b]thiophenes including Gewald reaction, Wilgerodt-Kindler reaction, Paul-Knorr reaction, fluorous synthetic protocol, sulfur-assisted reactions, electrophilic cylization and direct arylation methods. Where possible, the reactions will be categorized. However, in several cases major overlapping of two or more synthetic methods have prevented such categorizations.