Palladium-Based Dyotropic Rearrangement Enables A Triple Functionalization of Gem-Disubstituted Alkenes: An Unusual Fluorolactonization Reaction

We report in this paper a Pd(II)-catalyzed migratory gem-fluorolactonization of ene-carboxylic acids. Reaction of 4-methylenealkanoic acid derivatives with Selectfluor in the presence of Pd(OAc)(2) (1.0 mol %) at room temperature affords fluorolactones in good to excellent yields. 2-(2-Methylenecycloalkanyl)acetic acids are transformed to bridged fluorolactones under identical conditions. One C-C, one C-O and one tertiary C-F bond were generated along the gem-disubstituted carbon-carbon double bond in this operationally simple transformation. Trapping experiments indicates that the reaction is initiated by a 5-exo-trig oxypalladation followed by Pd oxidation, regioselective ring-enlarging 1,2-alkyl/Pd(IV) dyotropic rearrangement and C-F bond forming reductive elimination cascade. Post-transformations of these fluorolactones taking advantage of the electrophilicity of the 1-fluoroalkylcarboxylate function are also documented.