A novel approach towards 2,3,5-trisubstituted thiophenes via tandem Michael addition/intramolecular Knoevenagel condensation

Article abstract of DOI:10.1002/hlca.19970800217

Starting from the easily available, highly functionalized acetylenic ketones 4a-i, novel 2,3,5-trisubstituted thiophenes 1a-i were synthesized in good yields using a tandem Michael-addition/intramolecular Knoevenagel-condensation strategy, featuring Cs₂CO₃/MgSO₄ (1:2) as an efficient base to effect the cyclization. Subsequent simple one-step transformations yielded 2,3-disubstituted thiophene-5-carbaldehydes 7a-c, carboxylic-acid derivatives 8, 9, and 11, and alcohol 10. These molecules constitute interesting novel thiophene-containing building blocks, useful for the preparation of low-molecular-weight compound libraries by combinatorial and parallel-chemistry techniques.