Pyridyl Radical Cation for C−H Amination of Arenes

Abstract

Electron‐transfer photocatalysis provides access to the elusive and unprecedented N‐pyridyl radical cation from selected N‐substituted pyridinium reagents. The resulting C(sp2)−H functionalization of (hetero)arenes furnishes versatile intermediates for the development of valuable aminated aryl scaffolds. Mechanistic studies that include the first spectroscopic evidence of a spin‐trapped N‐pyridyl radical adduct implicate SET‐triggered, pseudo‐mesolytic cleavage of the N−X pyridinium reagents mediated by visible light.

C–H Pyridonation of (Hetero-)Arenes by Pyridinium Radical Cations

“…Earlier this year, Carreira and Togni as well as our laboratory have independently demonstrated the ability of pyridinium radical cations to react with arenes to afford N-arylpyridinium salts. 34,35 Here we show that 2-or 4chloropyridinium radical cations can function as surrogates for the installation of 2-and 4-pyridones on (hetero-)arenes, respectively. Although we anticipated that chlorine-substituted pyridinium radical cations would display different spin density distributions when compared to the parent counterparts, 36 we identified novel reaction chemistry to access aryl chloropyridiniums, from which the corresponding N-aryl-2-or 4-pyridone compounds can be accessed upon hydrolysis (Scheme 1).…”

“…The proposed mechanism for the C−H pyridonation is outlined in Scheme 4. 34,35,64 Excitation of the photocatalyst Ru(bpy) 3 (PF 6 ) 2 under visible-light irradiation produces a longlived (1100 ns) photoexcited state, [Ru II ]*. 65 Single-electron reduction of reagent A (onset reduction potential = 0.23 V vs saturated calomel electrode) is hypothesized to generate the pyridinium σ-radical cation (I) and [Ru III ].…”

I(III)-Mediated Arene C-H Amination using (Hetero)Aryl Nucleophiles

“…The N-heterocycles would act as "oxidatively masked" nucleophilic amines and the product would be shielded from over oxidation as a cationic pyridinium salt (3). 8,22 Pioneering work by Yoshida, 8 as well as recent reports by Carreira, 23 Ritter, 24 and Sanford 25,26 have achieved oxidative arene amination via (hetero)aryl nucleophiles through the use of electrochemistry, photoredox catalysis, or EDA-complexes, and we demonstrated a complementary benzylic-selective C-H collidination, 27 demonstrating the utility of such an approach.…”

Recent Advances in Pyridinium Salts as Radical Reservoirs in Organic Synthesis

“…Recently, the group of Togni and Carreira documented that N-sulfonyloxypyridinium reagent 46 could serve as pyridinyl radical cation precursor for the C−H amination of (hetero)arenes, furnishing the corresponding pyridinium salts 47 bearing different functional groups (Scheme 36). 35 On the basis of the EPR studies and DFT calculations, it was suggested that the direct C−H amination process involved pyridinyl radical cation as the key intermediate. Additionally, the Narylpyridinium products 47 could be further transformed into anilines 48 with piperidine at room temperature for 14 h. Moreover, the N-arylated piperidines 49 were obtained from the direct hydrogenation of N-arylpyridinium products in the presence of PtO 2 .…”