Total Synthesis of ent-Kaurenoic Acid Diterpenoids Enabled by Distal Conformational Control in Photoredox Radical Polyene Cyclization.

Abstract

We report a divergent synthesis of ent-kaurenoic acid-derived diterpenoids enabled by a stereoselective photoredox radical polyene cyclization directed by distal conformational control. A chiral bicyclo[3.2.1]octane unit biases the reactive polyene conformation and controls stereochemical outcome remotely during cascade cyclization. This substrate-encoded process enables highly diastereoselective construction of the 6/6/6/5 ent-kaurenoic acid framework under visible-light conditions. A convergent nickel-catalyzed reductive cross-electrophile coupling rapidly assembles the cyclization precursor. Late-stage oxidation-state and stereochemical editing from a common intermediate provide access to seven structurally distinct diterpenoids, including the first total synthesis of noueinsiancin D.