000K  utf8
1100  $c1998
1500  eng
2050  urn:nbn:de:gbv:8-publ-569
2051  10.1039/a709205i
3000  Ferri, Fabiola
3010  Brückner, Reinhard
3010  Herges, Rainer
4000  Straightforward syntheses of biradical-producing bicyclic dienediynes—dienediyne ketones cycloaromatize ia the Saito–Myers and not ia the neocarzinostatin pathway  [Ferri, Fabiola]
4209  The dienediyne models 23 and 28 of the pharmacophore of the antitumor natural product neocarzinostatin were prepared. Each synthesis requires only six steps from a-formylcyclohexanone. Our approach uses two key steps. The Ðrst consists of one-pot biscoupling reactions between propargyl alcohol, 2,2-dimethyl-3-butyn-1-ol and the bis(enoltriÑuoromethanesulfonate) 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 SaitoÈMyers cyclization4 (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 ab initio 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 SaitoÈMyers cyclization of enyneallenyl ketones 53 to toluene-a,meta biradicals 55 and not via neocarzinostatin-like cycloaromatizations of the tautomeric enyne[3]cumulenols 54 to styrene a,meta-biradicals 56. This is so because, on the one hand, the two cyclization modes are predicted to have similar activation barriers (SaitoÈMyers: 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 SaitoÈMyers cyclization product 55 is calculated to be considerably more stable (35.3 kcal mol~1) than the neocarzinostatin-type cycloaromatization product 56.
4950  https://doi.org/10.1039/a709205i$xR$3Volltext$534
4950  https://nbn-resolving.org/urn:nbn:de:gbv:8-publ-569$xR$3Volltext$534
4961  https://macau.uni-kiel.de/receive/publ_mods_00000056
5051  540
5550  Neocarzinostatin