Regioselective Rearrangement of Nitrogen- and Carbon-Centered Radical Intermediates in the Hofmann-Löffler-Freytag
Gabrijel Zubčić1, Jiangyang You2, Fabian L Zott3
1Faculty of Pharmacy and Biochemistry, University of Zagreb, Ante Kovačića 1, 10000 Zagreb, Croatia.
Abstract:
The Hofmann-Löffler-Freytag (HLF) reaction serves as a late-stage functionalization technique for generating pyrrolidine heterocyclic ring systems. Contemporary HLF protocols utilize in situ halogenated sulfonamides as precursors in the radical-mediated rearrangement cycle. Despite its well-established reaction mechanism, experiments toward the detection of radical intermediates using EPR techniques have only recently been attempted. However, the obtained spectra lack the distinct features of the N-centered radicals expected for the employed reactants. This paper presents phenylbutylnitrone spin-trapped C-centered and N-centered radicals, generated via light irradiation from N-halogen-tosyl-sulfonamide derivatives and detected using EPR spectroscopy. NMR spectroscopy and DFT calculations are used to explain the observed regioselectivity of the HLF reaction.
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