Triply Convergent Synthesis of 15-(Phenoxymethyl) and 4,5-Allenyl Prostaglandins. Preparation of an Individual Isomer of Enprostil

Article abstract of DOI:10.1021/jo00066a020

A triply convergent synthesis of the PGE₂ derivatives 1, 3, 4, and 5, containing either the 15-(phenoxymethyl) or the 15-amyl ω side chain and the 5,6-didehydro or the 4,5-allenyl α side chain, is described.This two-pot method employs organocopper reagents of the type Li2R_ωCuCNMe to selectively introduce the ω side chain to enantiopure enone 6 followed by in situ trapping of the so-formed enolates as silyl enol ethers 22a and 22b.The key step is the alkylation of regiochemically defined lithium enolates, generated from the corresponding silyl enol ethers 22a and 22b, with the unsaturated α side chain triflates 8b and 9c.The method was found to be general for propargylic and allenic α side chains but unsuccessful for the cis allylic and saturated α side chains found in PGE₂ and PGE₁, respectively.