Solid-Phase Synthesis of Thiophenes

Significance

A variety of substituted thiophenes was prepared on polymer supports via Knoevenagel condensation and Wittig olefination. A chloro­trityl chloride polystyrene resin reacted with thioacids to give polymeric ester-acid 1a, ester-amide 1b, and disulfide acid 2. Polymeric ester-isopropyl ester 1c and polymeric phosphonium salt 1d were derived from 1a and 2 (via thiol 3), respectively. Condensation reactions of the polymers 1b and 1c with various 1,2-diketones 4 were conducted under basic conditions using KOt-Bu, and the resulting polymer resins were treated with TFA to release the desired thiophenes 5a and 5b bearing a CONEt₂ group (from 1b) and COOH (from 1c), respectively. A phosphonium precursor 1d reacted with 4 under similar conditions to give thiophenes 5c. The Wittig olefination is more likely to initiate the thiophene formation with 1d to give 5-nonsubstituted 5c (X = H).