Stereoselektive Synthesen von ( Z )‐(10‐Methoxy‐4 H ‐benzo[4,5]cyclohepta[1,2‐ b ]thiophen‐4‐yliden)essigsäure

Stereoselective Syntheses of ( Z )‐(10‐Methoxy‐4 H ‐benzo[4,5]cyclohepta[1,2‐ b ]thiophen‐4‐ylidene)acetic Acid Two stereoselective syntheses for the antiinflammatory compound 1 (( Z )‐isomer) are described. In the first approach ( Strategy A, Scheme 1 ) the stereoselective synthesis of 1 was realized via the bicyclic compound 11 under thermodynamic conditions, followed by a thiophene annelation with retention of the double‐bond geometry ( Schemes 2–4 ). Optimized conditions were necessary to avoid ( E / Z )‐isomerization during annelation. In the second approach ( Strategy B, Scheme 1 ), diastereoisomer 17b was obtained selectively from a mixture of the diastereoisomers 17b and 18b by combining thermodynamic epimerization and solubility differences ( Scheme 5 ). Diastereoisomer 17b was converted into the tricyclic compound 23 using a novel thiophene annelation method which we described recently ( Scheme 6 ). In a final step, a stereospecific ‘ syn ’‐elimination transformed the sulfoxide 24 into the target compound 1 ( Scheme 7 ). To avoid ( E / Z )‐isomerization, it was necessary to trap the sulfenic acid liberated during the reaction. The key reactions of both approaches are highly stereoselective (> 97:3).