CuLi 2 Cl 4 catalysed cross-coupling strategy for the formal synthesis of the diterpenoid (+)-subersic acid from (–)-sclareol

Abstract

A CuLi₂Cl₄-catalysed regioselective cross-coupling is used in a key step leading to the concise synthesis of (+)-subersic acid with an overall yield of 25.7% from commercially available (–)-sclareol. The coupled product 15-(2-methoxy-5-carbomethoxy)phenyl-labda-8(9),13E-diene was obtained in 62% yield under CuLi₂Cl₄ conditions starting from 2-iodo-4-carbomethoxyanisole and 15-acetoxy-labda-8(9),13E-diene. These were derived from 4-hydroxybenzoic acid and (–)-sclareol respectively. The 15-(2-methoxy-5-carbomethoxy)phenyl-labda-8(9),13E-diene was easily transformed into (+)-subersic acid by demethylation of the phenol ether and ester. This cross-coupling strategy showed a good functional group tolerance and various (+)-subersic acid derivatives were obtained in moderate yields.