Metal-Free, Redox-Neutral, Site-Selective Access to Heteroarylamine via Direct Radical–Radical Cross-Coupling Powered by Visible Light Photocatalysis

Abstract

Transition-metal-catalyzed C–N bond-forming reactions have emerged as fundamental and powerful tools to construct arylamines, a common structure found in drug agents, natural products, and fine chemicals. Reported herein is an alternative access to heteroarylamine via radical–radical cross-coupling pathway, powered by visible light catalysis without any aid of external oxidant and reductant. Only by visible light irradiation of a photocatalyst, such as a metal-free photocatalyst, does the cascade single-electron transfer event for amines and heteroaryl nitriles occur, demonstrated by steady-state and transient spectroscopic studies, resulting in an amine radical cation and aryl radical anion in situ for C–N bond formation. The metal-free and redox economic nature, high efficiency, and site-selectivity of C–N cross-coupling of a range of available amines, hydroxylamines, and hydrazines with heteroaryl nitriles make this protocol promising in both academic and industrial settings.

Pyridylphosphonium salts as alternatives to cyanopyridines in radical–radical coupling reactions

“…In addition, Wu recently reported a method for photoredox catalyzed amination using cyanopyridines as coupling partners, and we attempted to replicate this transformation using pyridylphosphonium salts ( Scheme 2C ). 15 Applying salt 1a to the reaction protocol with N -methyl aniline resulted in diaryl amine 4 . 16 Similarly, using N , O -dimethylhydroxylamine as a coupling partner, followed by in situ cleavage of the N–O bond, formed aniline 5 in reasonable yield.…”

Organic thermally activated delayed fluorescence (TADF) compounds used in photocatalysis

“…152c). 342 High throughput experimentation was used to determine the optimal conditions when using oximes as the coupling partner, with 4CzIPN and 4DPAIPN being the TADF PCs under investigation. The best photocatalyst was identified as [Ir(dF(Me)ppy) 2 (dtbbpy)]PF 6 giving a 71% yield with DIPA, while 4CzIPN and 4DPAIPN managed only 2% and 4%, respectively.…”

“…151 in that the PC is reductively quenched by the amine reagent and the reduced PC is used to reduce the cyanoarene. 342 These two radicals then couple together, releasing HCN, to form the final product. A range of spectroscopic techniques were used to support these mechanistic studies, including flash vacuum photolysis and transient absorption spectroscopy.…”

Applications of Proton-Coupled Electron Transfer in Organic Synthesis

“…However, despite their versatility, traditional methods commonly require metal catalysts, which indicates the unavoidable toxicity, and the high cost of metal reagents may prevent them from further development. In order to find out a methodology without the requirement of metal catalysts, also in 2020, Wu and co-workers [80] developed an access to afford heteroarylamine via radical-radical cross-coupling pathway as an alternative method for traditional transition-metal-catalyzed C -N bond-forming reactions (Scheme 28). With a mild reaction conditions including 3DPAFIPN as photocatalyst, DABCO as base, this method leads to the photochemical, metal-free, and site-selective synthesis of a diverse range of heteroarylamine and pharmaceutical arylamines in both good to excellent yields, with no requirements of external oxidant or reductant.…”