Room-Temperature Direct Arylation of Anilides under External Oxidant-Free Conditions Using CO₂-Derived Dimethyl Carbonate (DMC) as a ′Green′ Solvent

Abstract

Here, an efficient catalytic protocol for direct C−H bond arylation of anilides under base‐ and external oxidant‐free conditions is reported. This reaction proceeds readily at room temperature using CO2‐derived dimethyl carbonate (DMC) as a ′green′ solvent under visible‐light dual catalysis. Later, application of our strategy for the gram‐scale synthesis of Boscalid has been successfully shown. An unprecedented unsymmetrical bis‐arylation of anilides is also demonstrated under mild, redox‐neutral conditions.

Palladium-Catalyzed Ortho C–H Arylation of Aniline Carbamates with Diazonium Salts under Mild Conditions: Expedient Synthesis of Carbazole Alkaloids

“…From control experiments and previous literature, 11,12,13a,17 we speculate that the present C–H arylation at ambient condition initiates through the formation of arylpalladium(II) palladacycle. Subsequently, oxidative addition to the aryldiazonium salt may lead to the formation of cationic palladium(III) (via 1e – process with aryl radical from the diazonium salts) or palladium(IV) (via 2e – process) intermediate.…”

“…Whereas, Sanford and others have demonstrated that a distinct single-electron process is evoke merging of palladium(II) and photoredox catalysts. 11,12 When we performed the standard reaction in the presence of stoichiometric amount of radical scavengers such as TEMPO or BHT, the reaction was completely suppressed. We have also detected the TEMPO-adduct of the corresponding diazonium salt from gas chromatography mass spectrometry.…”

“…11 Several other groups have also extended this concept to other molecular systems. 12 Although palladium and photoredox dual catalysis has been explored, only palladium-catalyzed C–H arylation of aniline carbamates with aryldiazonium salt is not known. Previously, ortho C–H arylation of aniline derivatives was reported by the Lipshutz and the Jeganmohan group with arylboronic acids where stoichiometric metal or nonmetal oxidants were necessary.…”

Sustainable protocols for direct C–H bond arylation of (hetero)arenes

“…In 2017, Balaraman et al described the photocatalytic direct ortho-arylation of anilides with aryldiazonium salts as arylating agents, performed under visible light irradiation in dimethyl carbonate, in the presence of Pd(OAc) 2 as the main catalyst and [Ru(bpy) 3 ]Cl 2 as the photocatalyst. 240 The use of a highly sustainable solvent, in combination with arylating agents characterized by high atom economy and waste prevention, as well as the application of a photocatalytic process, made this procedure of significant interest from a sustainability point of view. Scheme 79 First application of DEC as the solvent in direct C-H arylation of (hetero)arenes: ortho-arylation of 2-phenylpyridine 202 with (hetero)aryl chlorides reported by Dixneuf et al 239 In 2018, the ortho-diarylation of the benzene ring of 1-phenylpyrazoles with aryl triflates, catalyzed by [RuCl 2 ( p-cymene)] 2 and in the presence of KOAc as the base, was performed in DEC. 241 From a synthetic point of view this reaction is definitely interesting since it allowed access to highly functionalized compounds.…”

“…In 2017, Balaraman and co-workers proposed the combination of Pd(OAc) 2 catalyst (5 mol%) with Ru(bpy) 3 Cl 2 photocatalyst (2.5 mol%) for the direct ortho-arylation of anilides 250 with aryldiazonium salts, performed at room temperature in 8-14 h under visible light irradiation with a 32 W compact fluorescent light lamp, using dimethyl carbonate (DMC) as the solvent, affording the corresponding ortho-arylated anilides 251 in 67-97% yields (Scheme 95). 240 The protocol is in our opinion appealing in the framework of Green Chemistry: reactions proceeded under very mild experimental conditions, thanks to the combination of a photochemical approach as non-conventional energy source with the use of an environmentally benign medium and the choice of aryl diazonium as arylating agents, characterized by high atom economy and waste prevention.…”