The Fluorinative Skeletal Rearrangement of Lumisantonin: An Unanticipated Dual Role of Selectfluor

Synthetic chemists have been intrigued by the rearrangement reactions of α-santonin and santonin-derived natural products for over 150 years. Herein, we report an unprecedented fluorinative skeletal rearrangement of lumisantonin in the presence of Selectfluor. To our surprise, mechanistic studies suggest that the rearrangement proceeds through a thermal two-electron process, rather than a photochemical radical fluorination mechanism as initially conceived. A series of synthetic experiments and transition state studies reveal that the reaction is governed by an unusual, concerted strain-release electrophilic fluorination, followed by rearrangement of the carbon skeleton to generate a key tertiary carbocation intermediate. This intermediate is then readily trapped by either the tetrafluoroborate counteranion (Balz-Schiemann-type fluorination) or acetonitrile (Ritter-type amination), affording novel fluorinated derivatives of isophotosantonic lactone, as confirmed by single crystal X-ray crystallography.