Oxidation of ent-cleistanthanes through C-H bond functionalization

This study aims to investigate the synthesis of ent-cleistanthanes, using acanthoic acid (1) as the starting material, a natural product isolated from Annona amazonica, an endemic species from South America. The first step is a rearrangement under oxidative conditions, affording intermediate 2, which can be hydrogenated to give the ent-cleistantha-8,11,13-trien-19-oic acid (3). This compound will be used as a platform for C—H bond oxidations, leading to the natural products 4 and 5. In the first case, we aim to employ an electrochemical oxidation to selectively functionalize the endocyclic benzylic position, as has been reported for other aromatic diterpenes. For the synthesis of 5, we will investigate iridium-catalyzed benzylic borylation reactions, followed by exhaustive oxidation to the corresponding carboxylic acid.