Regioselective Rearrangement of Nitrogen- and Carbon-Centered Radical Intermediates in the Hofmann–Löffler–Freytag Reaction

Zubčić, Gabrijel; You, Jiangyang; Zott, Fabian L.; Ashirbaev, Salavat S.; Kolympadi Marković, Maria; Bešić, Erim; Vrček, Valerije; Zipse, Hendrik; Šakić, Davor (2024) Regioselective Rearrangement of Nitrogen- and Carbon-Centered Radical Intermediates in the Hofmann–Löffler–Freytag Reaction. The Journal of Physical Chemistry A, 128 (13). pp. 2574-2583. ISSN 1089-5639

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Abstract

The Hofmann-L & ouml;ffler-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.

Item Type:	Article
Uncontrolled Keywords:	radical rearrangement ; photoinitiation ; remote functionalization ; spin trap ; EPR and NMR ; DFT
Subjects:	NATURAL SCIENCES > Chemistry
Divisions:	Division of Physical Chemistry
Projects:	Project title Project leader Project code Project type Svjetlošću pogonjena funkcionalizacija nereaktivnih pozicija korištenjem oksidacijske aminacije-LIGHT-N-RING Davor Šakić; Mirsada Ćehić UIP-2020-02-4857 HRZZ Kemijska sudbina zabrinjavajućih farmaceutika u okolišu: eksperimentalno i računalno istraživanje produkata razgradnje i njihovih ekotoksikoloških svojstava Valerije Vrček IP-2022-10-2634 HRZZ Jačanje znanstveno-istraživačkih i inovacijskih kapaciteta Farmaceutsko-biokemijskog fakulteta Sveučilišta u Zagrebu-FarmInova Jasmina Lovrić KK.01.1.1.02.0021 EK
Depositing User:	Ema Buhin Šaler
Date Deposited:	13 Apr 2026 07:25
URI:	http://fulir.irb.hr/id/eprint/11659
DOI:	10.1021/acs.jpca.3c07892

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