Naslov
From aminyl radicals to cations. Mechanism switch in Hofmann-Löffler-Freytag-like reactions

Autori
Zubčić, Gabrijel ; Shkunnikova, Sofia ; Šakić, Davor

Vrsta, podvrsta i kategorija rada
Sažeci sa skupova, sažetak, ostalo

Izvornik
27th Croatian Meeting of Chemists and Chemical Engineers. Book of Abstracts / Marković, Dean - Zagreb : Hrvatsko knjižničarsko društvo, 2021

Skup
27. hrvatski skup kemičara i kemijskih inženjera (27HSKIKI)

Mjesto i datum
Veli Lošinj, Hrvatska, 05.10.2021. - 08.10.2021

Vrsta sudjelovanja
Poster

Vrsta recenzije
Recenziran

Ključne riječi
N-centered cations, N-centered radicals, rearrangement

Sažetak
C-H functionalization methods are often used in late-stage functionalization synthesis in the pharmaceutical industry. Inside the “reaction toolbox of C-H functionalization” are amination reactions that combine remote C(sp3)-H bond activation at otherwise unfunctionalized positions with C-N bond formation in a synthetically attractive fashion.1 A traditional reaction in this class is the Hofmann-Löffler-Freytag (HLF) reaction.2 This reaction utilizes N-centered radicals, generated via heat or light from N- halogen homolytical bond breaking. After intramolecular 1, 5-HAT step, a δ-C-centered radical is formed, which is then subsequently functionalized. In this process stereo-information is not conserved. Recently, an ionic mechanism is proposed involving nitrenium cations.3 Heterolytically cleaved N-halogen bond produces nitrenium cation, that rearranges to carbocation with concerted nucleophilic attack that prevents loss of stereo- information. Substrates carrying a chiral benzylic position and a halogen activated nitrogen atom were transformed with full retention of configuration, which makes a radical mechanism less likely. Also, unlike many radical reactions, this transformation is promoted neither by light nor heat. In this work comparison between relative stabilities of radical species involved in typical HLF type of reactions, with relative stabilities of cationic species involved in this alternative ionic pathway will be discussed. Differentiation between pathways may suggest conditions needed to steer reactions through mechanisms that may (or may not) retain stereochemical information.

Izvorni jezik
Engleski

Znanstvena područja
Kemija, Farmacija

POVEZANOST RADA