Synthetic approach to potential precursors of sclerophytin A

A direct approach to simple bicyclic analogues of the antitumor natural diterpene, sclerophytin A, is described. The readily available bicyclic ketone (prepared from furan and trichloroacetone) was enantioselectively methylated to give the optically active ketone . Regioselective allylation using Negishiʹs method afforded the α,α-dialkyl ketone , which was converted to the chloroacetate by hydroboration–oxidation and protection. Regioselective Baeyer–Villiger oxidation afforded the lactone which could be transformed into the silyl ether . Tebbe olefination furnished a mixture of two enol ethers in which the desired product was the minor isomer. Several attempts to use the major endocyclic enol ether to give the tricyclic analogues of sclerophytin proved unsuccessful. Opening of the lactone of and selective protection of the diol afforded the primary alcohol which was oxidized to the keto aldehyde . Unfortunately pinacol coupling of did not give any cyclic product. The diene was also prepared from but all attempts at ring-closing metathesis of met with the same fate. The failure of these various cyclization methods underscores the difficulty in forming medium-sized ring systems, especially those cis-fused at the 2- and 5-positions of a tetrahydrofuran ring.