Synthetic Uses of Ring-Opening and Cycloaddition Reactions of Thiophene-1,1-Dioxides

The reaction of 3-bromo-2,5-thiophene-1,1-dioxides with various nucleophiles has been studied. Organolithium derivatives gave hexenynes by a 1,6-Michael addition followed by ring-opening and elimination of sulfur dioxide and lithium bromide. In a competing reaction lithium enyne sulphinates were formed. Grignard reagents gave cage compounds through a series of Michael type additions, while organocopper reagents gave 3-alkyl or 3-aryl substituted derivatives. Reaction with secondary cyclic amines in refluxing benzene resulted in a 1,4-Michael type addition to the exomethylene tautomer providing 3-bromo-6-amino-(2Z,4E)-2,4-hexadienes as main products and dialkylaminomethyl substituted cis 2,3-dihydrothiophene-1,1-dioxides. Reactions in aqueous piperidine on the other hand resulted in a normal 1,4-Michael addition producing 3-bromo-2,5-dimethyl-4-piperidino-4,5-trans-dihydrothiophene-1,1-dioxide. The reaction of the thiophene-1,1-dioxides with thiolates and alkoxides under various conditions were also studied. New high yielding methods for the preparation of pentasubstituted and 1,2,3-trisubstituted benzenes were discovered in a tandem dimerization ring-opening reaction of 3-halo-2,5-dialkylthiophene-1,1-dioxides and 2-alkyl- and 2-aryl-3-bromothiophene-1,1-dioxides, respectively. From 3,5-dibromo-2-methyland 3,5-dibromo-2-phenylthiophene-1,1-dioxide as well as 4-bromo-2-methylthiophene-1,1-dioxide, benzo[b]thiophene-1,1-dioxides were obtained