Synthesis of 6‐/10‐Membered Ring Analogs of the Dienediyne Core of the Neocarzinostatin Chromophore by Palladium(0)‐Mediated Ring‐Closure Reactions

A strategy for the synthesis of the benzo‐annulated bicyclic dienediyne analogs 46 and 48 of the DNA‐cleaving natural product neocarzinostatin chromophore was developed. 2‐Formylcyclohexanone ( 9 ) was converted stereoselectively first into the mono(enol triflate) Z‐ 11 and thereafter into the bis(enol triflate) Z‐ 2 . The isomeric triflates E ‐ 11 and E ‐ 2 were prepared to facilitate correct E , Z assignments. The C≡C bonds of the target dienediynes 46 and 48 were introduced with the aid of the unsymmetrical bisalkynes 17 and 16 , respectively. However, the latters furnished the formers not by reactions with the monotriflate Z‐ 11 (Schemes 4, 7, 10) but only by reactions with the bistriflate Z‐ 2 . The success of this approach is due to a regioselective C sp 2/C sp monocoupling which unites the reaction partners and to another Pd‐catalyzed C sp 2/C sp coupling which furnished the 6‐/10‐membered ring dienediyne 46 (Scheme 13) and its isomer 48 (Scheme 14). Starting from ortho ‐bromobenzaldehyde and cyclohexanone these syntheses required a total of 9 and 10 steps, respectively, the longest linear sequence comprising 6 steps.