PT Journal
AU Ferri, F
   Brückner, R
   Herges, R
TI Straightforward syntheses of biradical-producing bicyclic dienediynes—dienediyne ketones cycloaromatize ia the Saito–Myers and not ia the neocarzinostatin pathway
SO New Journal of Chemistry
PY 1998
BP 531
EP 545
VL 22
IS 5
PU Royal Society of Chemistry
DI 10.1039/a709205i
WP https://macau.uni-kiel.de/receive/publ_mods_00000056
LA en
DE Neocarzinostatin
SN 1144-0546
AB 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.
PI London
ER