A NOVEL-APPROACH TOWARDS 2,3,5-TRISUBSTITUTED THIOPHENES VIA TANDEM MICHAEL ADDITION INTRAMOLECULAR KNOEVENAGEL CONDENSATION

Starting from the easily available, highly functionalized acetylenic k etones 4a-i (Scheme 1), novel 2,3,5-trisubstituted thiophenes 1a-i (Sc heme 2) were synthesized in good yields using a tandem Michael-additio n/intramolecular Knoevenagel-condensation strategy, featuring Cs2CO3/M gSO4 (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 alco hol 10 (Scheme 3). These molecules constitute interesting novel thioph ene-containing building blocks, useful for the preparation of low-mole cular-weight compound libraries by combinatorial and parallel-chemistr y techniques.