Chemical Equivalent of Arene Monooxygenases: Dearomative Synthesis of Arene Oxides and Oxepines

Direct
epoxidation of aromatic nuclei by cytochrome P450 monooxygenases
is one of the major metabolic pathways of arenes in eukaryotes. The
resulting arene oxides serve as versatile precursors to phenols, oxepines,
or trans-dihydrodiol-based metabolites. Although
such compounds have an important biological and chemical relevance,
the lack of methods for their production has hampered access to their
utility. Herein, we report a general arenophile-based strategy for
the dearomative synthesis of arene oxides. The mildness of this method
permits access to sensitive monocyclic arene oxides without any noticeable
decomposition to phenols. Moreover, this method enables direct conversion
of polycyclic arenes and heteroarenes into the corresponding oxepines.
Finally, these studies provided direct connection between simple aromatic
precursors and complex small organic molecules via arene oxides and
oxepines.