Radical 1,4/5-Amino Shift Enables Access to Fluoroalkyl-Containing Primary β(γ)-Aminoketones under Metal-Free Conditions

Abstract

A novel radical 1,4/5-amino shift from the oxygen center of alkene-tethered diphenyl ketoxime ethers to the carbon center to achieve high value-added fluoroalkyl-containing primary β(γ)-amino-ketones is reported. Mechanism studies reveal that the migration is triggered by the alkene addition of fluoroalkyl radical derived from the electron donor-acceptor (EDA) complex of Togni's reagent II or fluoroalkyl iodides and quinuclidine, and involves a unique 5(6)-exo-trig cyclization of the carbon-centered radical onto the N-atom of ketoxime ethers followed by a cascade sequence of N-O bond cleavage and dehydrogenation. Notably, besides Togni's reagent II and fluoroalkyl iodides, this protocol is also compatible with other radical precursors to provide various functionalized primary aminoketones.

Keywords: amino migration; fluoroalkylamination; ketoxime ethers; radical rearrangement; synthetic methods.