Hypervalent Iodine Phenol Dearomatization Mediated by Mechanochemistry

Oxidative phenol dearomatization using hypervalent iodine(III) reagents is a powerful tool for developing efficient synthetic routes to complex natural products and pharmaceuticals. This process enables the rapid formation of a functionalized dienone, a key intermediate derived from simple and inexpensive aromatic systems, thereby increasing structural complexity in a single step. Current methods, however, often require the use of perfluorinated alcohols as protic, non-nucleophilic solvents, which environmentally harmful nature deteriorates the green metrics of the reaction. This paper presents a solvent-free, mechanochemical methodology using a planetary ball mill to achieve the intramolecular oxidative dearomatization of several phenols that contain a heteronucleophile on a side chain. This process yields various spiranic systems within 5 min, with decent to good yields, and eliminates the need for expensive, environmentally harmful solvents. This approach has also been extended to a tandem Diels-Alder process and the first application of a bimolecular example. This paper thus introduces a greener strategy for dearomatizing phenols using hypervalent iodines, offering a more sustainable path for this widely used synthetic transformation.