| Abstrakt: |
The dienediyne models 23 and 28 of the pharmacophore of the antitumor natural product neocarzinostatin were prepared. Each synthesis requires only six steps from α-formylcyclohexanone. Our approach uses two key steps. The first consists of one-pot biscoupling reactions between propargyl alcohol, 2,2-dimethyl-3-butyn-1-ol and the bis(enoltrifluoromethanesulfonate) 17. The second key step corresponds to ring-closing pinacol coupling reactions of the dialdehydes 20 and 25. The dienediyne models 23 and 28 cycloaromatized efficiently when treated with methyl thioglycolate and 1,4-cyclohexadiene at 25°C via a Saito–Myers cyclizatio (to give the octahydroanthracenones 29, iso-29 and octahydrophenanthrenones 34, 35, respectively); in addition, we isolated compounds tentatively assigned as the octahydrobenzazulenones 30 and iso-30, which would stem from a competing Schmittel cyclization. According to density functional theory (B3LYP/6-31G*) and abinitio calculations [CASMP2(2.2)/6-31G//CAS(2.2)/6-31G], the core structures of the octahydroanthracenones and octahydrophenanthrenones obtained here and elsewhere form via the Saito–Myers cyclization of enyneallenyl ketones 53 to toluene-α,meta biradicals 55 and not via neocarzinostatin-like cycloaromatizations of the tautomeric enyne[3]cumulenols 54 to styrene α,meta-biradicals 56. This is so because, on the one hand, the two cyclization modes are predicted to have similar activation barriers (Saito–Myers: 16.0 kcal mol-1; neocarzinostatin type: 18.3 kcal mol-1) but, on the other hand, the enyneallenyl ketone 53 is a much more stable (21.1 kcal mol-1) cycloaromatization substrate than the enynecumulenol 54. In addition, the Saito–Myers cyclization product 55 is calculated to be considerably more stable (35.3 kcal mol-1) than the neocarzinostatin-type cycloaromatization product 56. |
