Dearomative 1,4-Difunctionalization of Non-Activated Arenes Enabled by Boryl Radical-Mediated Halogen-Atom Transfer

Given
the widespread presence of spirocyclic scaffolds in natural
products and pharmacologically relevant synthetic compounds, the development
of efficient methodologies for their construction holds great importance
in medicinal chemistry and pharmaceutical research. In this study,
a general photochemical dearomative spirocyclization of nonactivated
arenes has been established. The key to this method lies in the ability
of amine-borane radicals to activate aryl bromides and iodides via
halogen-atom transfer, thereby allowing for the conversion of aryl
halides into the corresponding aryl radicals for subsequent chemodivergent
transformations. The remarkable compatibility and versatility of this
dearomative 1,4-difunctionalization is showed by the rapid assembly
of structurally diverse 1,4-cyclohexadiene-based spirocycles incorporating
oxindole, indoline, or dihydrobenzofuran subunits. Moreover, the potential
utility of this protocol is exemplified by a formal total synthesis
of the vasopressin V2 receptor antagonist Satavaptan.