Synthesis of 2-Arylpyridines and 2-Arylbipyridines via Photoredox-Induced Meerwein Arylation with in Situ Diazotization of Anilines

Abstract

We report herein a sustainable method for the preparation of 2-arylpyridines through C−H arylation of pyridines using in-situ formed diazonium salts (from commercially available aromatic amines) in the presence of a photoredox catalyst under blue LEDs irradiation. The reaction is tolerant to a wide range of functional groups (e.g., halogen, nitrile, formyl, acetyl, ester). Applications to the C-H bond arylation of bipyridine ligands is also presented.A c c e p t e d m a n u s c r i p t or from metalated pyridines and aryl pseudo-halides. 4 Among these protocols, the use of 2-(tributylstannyl)pyridine remains the most employed starting materials, albeit it is a hazardous and harmful reagent (Figure 2a). More sustainable approaches based on transition-metal catalyzed C-H bond arylation of pyridines were often carried out under harsh reaction conditions and displayed a poor substrate scope, or required the prior oxidation of pyridines to N-oxide pyridines. 6 Recently, photoredox catalysis has emerged as an eco-friendly alternative to build C-C bond from C(sp 2 )-H bond under mild reaction conditions. 7 In 2014, Xue and coworkers reported the photoredox-catalyzed C-H bond arylation of pyridine derivatives at C2 or/and C4 positions with aryldiazonium salts using Ru(bpy) 3 2+ (Figure 2b). 8 This Merweintype arylation of pyridines was also developed using different photosensitizers. 9 In 2017, Heinrich and co-workers demonstrated that the arylation of heteroarenes with aryldiazonium salts could also proceed in the absence of an external photosensitizer. 10 The reaction involves the formation of charge-transfer complexes 11 between the electron-poor aryl diazonium salts with electron-rich (hetero)aromatics. In the case of pyridine, only 3-hydroxypyridine has been arylated owing to its specific electronic nature, which allows the formation of charge-transfer complexes with aryl diazonium and is a good aryl radical acceptor. Besides the regioselectivity issue due to the low control of the radical additions, an additional challenge is the handling of the potentially unstable aryldiazonium precursors. In 2014, to avoid the use of such hazardous chemicals and employed commercially available chemicals, Martín, Carrillo, and co-workers have developed C-H bond arylation of (hetero) arenes using in-situ diazotization from anilines with tert-butyl that is promoted by catalytic amounts of L-ascorbic acid, with no heating or irradiation. 12 However, these protocols were limited to the direct arylation of 5-membered ring heteroarenes, electron-rich arenes and N-oxide pyridines (Figure 2c). The reaction can be also promoted by a mild base (Na 2 CO 3 ), 13 or polyamine. 14 Later, Horan's group showed that the reaction can also proceed at 40 ºC in the absence of L-ascorbic acid. 15 In 2015, Frutos, Kappe, and co-workers also demonstrated that the C-H bond arylation of (hetero) arenes using in-situ diazotization from anilines with tert-butyl could proceeded at room temperate under visiblelight irradiation. 16 Again, the scope of the re...

Recent Development of Aryl Diazonium Chemistry for the Derivatization of Aromatic Compounds

“…Moreover, the ruthenium­(II) complex has emerged as efficient photosensitizers for catalyzing C–H arylations of aryl diazonium salts. − In 2014, the direct arylation of N -heteroarenes with aryl diazonium salts was successfully implemented in water, using Ru­(bpy) 3 Cl 2 ·6H 2 O as a photosensitizer and a commercial household light bulb as a light source (Scheme ). This water-phase arylation reaction provides a variety of arylated heterocycle scaffolds including xanthene, thiazole, pyrazine, pyridazine, and pyridine with good regioselectivity.…”

“…Recently, from the substrates of arylamines as safe aryl radical precursors, the selective C−H arylation of pyridines was realized upon visible-light irradiation, allowing the synthesis of 2-aryl pyridines and 2-aryl bipyridines with moderate to good yields (Scheme 43). 109 Apart from utilizing homogeneous photosensitizers, a series of metal oxides have demonstrated promise as efficient heterogeneous catalysts for visible-light-induced radical-type arylation reactions, opening up the green protocol of a costeffective, sustainable operation through catalyst recycling. In 2015, a photoredox direct arylation of electron-rich heteroarenes had been disclosed with an easily accessible and recyclable, heterogeneous TiO 2 catalyst (Scheme 44).…”

Synthesis of 2,2’‐Bipyridines through Catalytic C−C Bond Formations from C−H Bonds

“…The first step is the C−H bond arylation of 4,4′‐disubstituted 2,2′‐bipyridines using in‐situ formed diazonium salts (from commercially available aromatic amines) in the presence of a photoredox catalyst under blue LEDs irradiation (Scheme 20). [42] Besides safety concerns avoiding the manipulation of explosive aryl diazonium salts, the other main advantage to employ in‐situ diazotization of anilines is a slower generation of the aryl radical than reactions from aryl diazonium salts favorizing the monoarylation. The coupling reaction between 4,4′‐di‐tert‐butyl‐2,2′‐bipyridine (4 equivalents) or 4,4′‐dimethyl‐2,2′‐bipyridine and diversely substituted aniline (1 equivalent) – in a mixture of CH 3 CN/TFA (8 : 1) solvent containing 1 mol % (Ir[dF(CF 3 )ppy] 2 (dtbpy))PF 6 and 1.2 equivalents of t ‐BuONO under blue LEDs irradiation – afforded the monoarylation of 2,2’‐bipyridines in good yields.…”

Front Cover: Synthesis of 2,2’‐Bipyridines through Catalytic C−C Bond Formations from C−H Bonds (Eur. J. Org. Chem. 39/2021)

“…The first step is the C-H bond arylation of 4,4'-disubstituted 2,2'-bipyridines using in-situ formed diazonium salts (from commercially available aromatic amines) in the presence of a photoredox catalyst under blue LEDs irradiation (Scheme 20). [42] Besides safety concerns avoiding the manipulation of explosive aryl diazonium salts, the other main advantage to employ in-situ diazotization of anilines is a slower generation of the aryl radical than reactions from aryl diazonium salts favorizing the monoarylation. The coupling reaction between 4,4'-di-tert-butyl-2,2'-bipyridine (4 equivalents) or 4,4'-dimethyl-2,2'bipyridine and diversely substituted aniline (1 equivalent) -in a mixture of CH3CN/TFA (8:1) solvent containing 1 mol% (Ir[dF(CF3)ppy]2(dtbpy))PF6and 1.2 equivalents of t-BuONO under blue LEDs irradiation-afforded the monoarylation of 2,2'-bipyridines in good yields.…”