Preparation of Congested Thiophenes Carrying Bulky Substituents on the 3- and 4-Positions and Their Conversion to the Benzene Derivatives

Highly congested thiophenes, 3,4-di- tert -butyl-, 3,4-di(1-adamantyl)-, 3,4-dineopentyl-, and 3-(1-adamantyl)-4- tert -butylthiophenes ( 4a − d), were prepared in satisfactory overall yields by intramolecular reductive coupling of 3-thiapentane-1,5-diones ( 1a − d ) followed by acid-catalyzed dehydration of the resulting thiolane-3,4-diols ( 2a − d ). Experimental procedures of this thiophene synthesis are fully described. Oxidation of the thiophenes 4a − d with m -CPBA gave the corresponding thiophene 1,1-dioxides 13a − d in good yields. The Diels−Alder reactions of 13a − d with phenyl vinyl sulfone gave o -di- tert -butyl-, o -di(1-adamantyl)-, o -dineopentyl-, and o -(1-adamantyl)- tert -butylbenzenes ( 17a − d ) directly in high yields with loss of benzenesulfinic acid and sulfur dioxide. The dioxides 13a − d also underwent Diels−Alder reactions with alkynic dienophiles to give the corresponding benzene derivatives carrying two bulky substituents on adjacent positions. Pyridazines 25b, c, carrying bulky substituents on the 4- and 5-positions, were also synthesized through Diels−Alder reaction of 13b, c with PTAD. Dimethylation of the 2- and 5-positions of 13a − d was attained by treatment with strong bases followed by reactions with methyl iodide. The resulting tetrasubstituted thiophene 1,1-dioxides 14a − d reacted with DMAD to give highly congested hexasubstituted benzene derivatives 15a − d in good yields. Finally, structural features of the congested molecules are discussed on the basis of NMR analyses. Typically, the barriers to rotation (Δ H ⧧ ) about the benzene to the bulky substituents of 15a, c, d were determined to be 8.59, 15.3, and 7.40 kcal/mol, respectively, by NMR total line-shape analysis.