Total Synthesis of <i>ent</i> ‐Kaurenoic Acid Diterpenoids Enabled by Distal Conformational Control in Photoredox Radical Polyene Cyclization

Abstract

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.