Biocatalytic Aromaticity-Breaking Epoxidation of Naphthalene

Aromatic hydroxylation reactions catalyzed by heme-thiolate enzymes proceed via an epoxide intermediate. These aromatic epoxides could be valuable building blocks for organic synthesis giving access to a range of chiral transdisubstituted cyclohexadiene synthons. Here we show that naphthalene epoxides generated by fungal peroxygenases can be subjected to nucleophilic ring opening yielding non-racemic trans-disubstituted cyclohexadiene derivates, which in turn can be used for further chemical transformations. Following the ring-opening reactions, the synthetic possibility of cyclohexadiene derivates also demonstrated by four examples yielding functional compounds. This novel approach may represent a promising shortcut for the synthesis of natural products and APIs.