The First Syntheses of 6‐/10‐Membered Ring Analogs and of a 6‐/11‐Membered Ring Analog of the Dienediyne Core of the Neocarzinostatin Chromophore by Ring‐Closure According to the Nozaki‐Hiyama Reaction

The Z‐configurated dienediyne aldehydes 11, 13, 19, and 20 were prepared as pure isomers by Pd(0)‐catalyzed C,C couplings between appropriate terminal alkynes and the bis‐(enol trifluoromethanesulfonate) 5 or its mono(enol trifluoro‐methanesulfonate) derivative 18. Irrespective whether these aldehydes contained a C≡CH or a C≡CSiMe3 moiety, they cyclized with low efficiency (11, 13, 19) or not at all (20) to the corresponding 6‐/10‐membered ring dienediynes (compounds 10, 8, 21, and 22, respectively). However, the C≡CI analogs 6 and 26 of these aldehydes furnished the desired 6‐/10‐membered ring dienediynes 8 and 22 by Nozaki‐Hiyama reactions; these cyclizations were complete and essentially clean conversions, provided an excess of CrCl2 and a stoichiometric amount of NiCl2 were used. However, since dienediynes 8 and 22 decompose very readily they were isolated only in 26 and 53% yield. Similar ring‐closure reactions of the iodinated alkinyl aldehydes 36a and b — which were obtained from the same mono(enol trifluoromethanesulfonate) 18 and the alkynes 32a and b, respectively, in four steps (Scheme 7) — furnished the 6‐/10‐membered ring dienediyne 38 (51% yield) and the 6‐/11‐membered ring dienediyne 39 (54% yield). They are the most stable dienediyne analogs of the neocarzinostatin chromophore which we have so far synthesized. They were oxidized to the corresponding dienediyne ketones 40 and 41 (Scheme 8). The latter compounds cycloaromatized in the presence of methyl thioglycolate and 1,4‐cyclohexadiene at 35–37°C to give the tetrasubstituted benzenes 47 and 48 as the only and as the main product, respectively (Scheme 9).