A total synthesis of zoapatanol

Abstract

A key step in a new synthesis of zoapatanol involves stannic chloride catalysed isomerisation of the epoxy diol (21) to the oxepane (22) with inversion of configuration of the tertiary carbon atom. Differential protection of the hydroxy groups allows oxidation to the acid (28) followed by addition of the prenyl group to complete the side-chain. An important step in construction of the intermediate epoxy diol (21) was the zirconium catalysed cis-addition of trimethylaluminium to the acetylene according to Negishi and reaction of the ‘ate’ complex with butyl-lithium with ethylene oxide to form the E-alcohol (18). The derived iodide (13) was used to alkylate the adduct of triphenylphosphine and diethyl maleate and the product reduced to the diol (20). Epoxidation of the diacetate occurred at the 6- double bond to give, after hydrolysis, the key epoxy diol (21).