Aminoalkyl radicals as halogen-atom transfer agents for activation of alkyl and aryl halides

Abstract

Organic halides are important building blocks in synthesis, but their use in (photo)redox chemistry is limited by their low reduction potentials. Halogen-atom transfer remains the most reliable approach to exploit these substrates in radical processes despite its requirement for hazardous reagents and initiators such as tributyltin hydride. In this study, we demonstrate that α-aminoalkyl radicals, easily accessible from simple amines, promote the homolytic activation of carbon-halogen bonds with a reactivity profile mirroring that of classical tin radicals. This strategy conveniently engages alkyl and aryl halides in a wide range of redox transformations to construct sp3-sp3, sp3-sp2, and sp2-sp2 carbon-carbon bonds under mild conditions with high chemoselectivity.

Photocatalytic methods for amino acid modification

“…Dha was also recently used as a substrate to demonstrate work from Leonori and co-workers on a-amino-radicalpromoted halogen atom transfer (XAT). 46 The process, involving 4CzIPN as the photocatalyst, generates the a-radical of a tertiary amine through SET and deprotonation. This radical demonstrates efficient XAT from alkyl and aryl halides, producing the corresponding alkyl and aryl radicals.…”

Visible-light mediated carbonyl trifluoromethylative amination as a practical method for the synthesis of β-trifluoromethyl tertiary alkylamines

“…This species can undergo a reversible halogen atom transfer (XAT) event with triuoroiodomethane to produce an a-iodoamine as well as generate another CF 3 radicalwhich then propagates a chain reaction. 8,10,12 Due to the instability of the a-iodoamine intermediate, a fast a-iodoelimination will form a b-triuoromethylated iminium iodide species. It is also possible that the a-amino radical can engage triuoroiodomethane through single electron transfer (SET) to form the iminium ion product and generate the CF 3 radical.…”

Polysulfide Anions as Visible Light Photoredox Catalysts for Aryl Cross-Couplings

“…The protocol could successfully engage five-membered ring heteroaryl halides based on furan (16), thiophene (17,18), and thiazole (19). The chemistry was also extended to functionalize six-membered ring heteroaryl halides such as pyridine (20,21), quinoline (22) and pyrazine (23). We also found that non-activated aryl halides having a highly negative reduction potential (Ered > -2.4 V vs SCE) are suitable substrates (24)(25)(26)(27).…”

“…In particular, consecutive photoelectron-transfer processes shown by König (17,18) and electrophotocatalytic strategies detailed by Lambert and Lin (19) and Wickens (20) have successfully generated excited radical anions. Leveraging of readily accessible aminoalkyl radicals for halogen-atom transfer agents was recently proven useful to promote aryl cross-coupling by Leonori (21), while the inherent net-oxidative nature of the process necessitates use of a stoichiometric amount of the oxidant. Our optimization of the reaction conditions revealed that irradiation of blue light (lmax = 440 nm) to the mixture of 1 and 2 in the presence of K2Sx (12.5 mol% per S atom), potassium carbonate (K2CO3, 1.5 equiv.)…”