Enantioselective Oxidative Spirocyclization of Biaryl Hydroxy Carboxylic Acids: Enantioselective Synthesis of (–)‐Arnottin II

The first metal‐free, catalytic, and highly enantioselective total synthesis of the natural product (–)‐arnottin II is described. The central challenge of this synthesis lies in the oxidative spirolactonization of a conformationally rigid biaryl hydroxy carboxylic acid (BHCA), an intrinsically unstable intermediate that is prone to an unwanted intramolecular dehydrative condensation that regenerates the thermodynamically stable aromatic lactone arnottin I. To overcome this issue, we have developed a one‐pot strategy in which BHCA is generated in situ from arnottin I and immediately subjected to an enantioselective oxidative spirolactonization, catalyzed by a chiral hypervalent iodine. The use of a phosphate buffer (pH = 6.3) proved essential to suppress re‐lactonization and competing side reactions. Under the optimized conditions, (–)‐arnottin II was obtained in up to 83% isolated yield with 91% enantiomeric excess, establishing a practical and sustainable solution to a long‐standing synthetic challenge.