beta-alkoxycarbonyl enol triflates as precursors of stereopure 3-ene-1,5-diyne building blocks for the chromophores of neocarzinostatin, C-1027, kedarcidin, maduropeptin, and N1999A2

A 5-step synthesis of alpha-alkoxymethyl-, alpha-siloxymethyl and alpha-(ca rbamoyloxy)methyl-substituted enediynes 7 from type 23 beta-oxo esters was developed following the strategy of Scheme 2. Specifically, the beta-oxo es ters 33, 36 and 38 (prepared as shown in Scheme 4) and NaH (or t-BuLi) gave Z-enolates in THF and E-enolates in DMF which were scavenged as enol trifl ates Z-27a-c and E-27a-c, respectively, upon treatment with triflimides 40 or 41 (Scheme 5). The Z-configurated enol triflates underwent Cacchi coupli ngs with (trimethylsilyl)acetylene to give the pent-2-en-4-yne-1-carboxylat es E-42a-c (Scheme 5). These were reduced to the corresponding aldehydes E- 44a-c (Scheme 6) which were homologated with lithio(trimethylsilyl)diazomet hane to furnish the desired enediynes 45a-c as pure E-isomers.