Synthesis of 2-(Substituted-silyl)thiophene-3-carboxylates via a Facile [3+2] Cycloaddition Reaction Catalyzed by Potassium tert-Butoxide

Background: Substituted-silyl thiophene carboxylates are important intermediates for the synthesis of substituted-silyl thiophene carboxamides which have been found to show high biological activities. Methods: Using α-mercapto ketones and 3-(substituted-silyl)propiolates as raw materials, 2-(substituted-silyl)thiophene-3-carboxylates could be synthesized smoothly via cycloaddition reaction catalyzed by potassium tert-butoxide. Results: A small library of target compounds was prepared under optimized reaction conditions in moderate to good yields. The reaction mechanism has been proposed. Conclusion: Potassium tert-butoxide is an environmentally friendly and efficient catalyst for the cycloaddition reaction of α -mercapto ketones and 3-(substituted-silyl)propiolates. This methodology provides ready access to 2-(substituted-silyl)thiophene-3-carboxylic acids which can be serve as the raw materials of 2-(substituted-silyl)thiophene-3-carboxamide and other pharmaceutically intriguing compounds.