Synthesis of intramolecular cross-coupling analogues of forskolin

Abstract

A ring distortion strategy was applied to the synthesis of a series of intramolecular cross-coupled analogues of forskolin 1. Treatment with palladium acetate, forskolin underwent an intramolecular cross-coupling reaction to generate a novel cycloalkene ether 2 in 85% yield. Under the same conditions, a series of forskolin ester analogues 4a-4d were prepared from 1-OH ester derivatives of forskolin 3a-3d in 85–93% yields. Treating cycloalkene ether 2 with aryl iodides in the presence of a palladium catalyst afforded Z-isomers arylation products 5a-5e in a stereoselective manner in 70–85% yields.