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 (ΔH⧧) 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.
Read full abstract