Comprehensive Summary Isochromanone is the core structure of many bioactive compounds. Direct oxidation of isochromans is one of leading methods for the construction of isochromanones, while most established processes remain suffering from the use of environmentally unfriendly metal oxidants, harsh reaction conditions, and the difficulty in catalyst recycling and product separation. Herein, we report a convenient, cost‐effective, and green method for the synthesis of high‐value added isochromanones via isochroman oxidations with O2 by a novel heterogeneous vanadium cluster catalyst (Cat.1) under mild conditions. This reaction protocol demonstrates high catalytic activity with good catalyst recyclability and reusability for a wide scope of substrates.

Isochromanone is the core structure of many bioactive compounds. Direct oxidation of isochromans is one of leading methods for the construction of isochromanones, while most established processes remain suffering from the use of environmental unfriendly metal oxidants, harsh reaction conditions, and the difficulty in catalyst recycling and production separation. Herein, we report a convenient, cost-effective, and green method for the synthesis of high-value added isochromanones via isochroman oxidations with O2 by a novel heterogeneous vanadium cluster catalyst (Cat.1) under mild conditions. This reaction protocol demonstrates high catalytic activity with good catalyst recyclability and reusability for a wide scope of substrates.