Ascorbic Acid as an Aryl Radical Inducer in the Gold‐Mediated Arylation of Indoles with Aryldiazonium Chlorides

Abstract

In recent years interestint he development of protocols that facilitate the oxidativea ddition of gold to access mild cross-coupling processes mediated by this metal hasincreased. In this context, we report herein that ascorbic acid, an atural and readily accessible antioxidant, can be used to accelerate the oxidative addition of aryldiazonium chlorides onto Au I .T he aryl-Au III speciesg enerated in this way,h as been used to prepare 3-arylindoles in ao ne-pot protocol startingf rom anilines and para-, meta-, and ortho-s ubstituted aryldiazonium chlorides. The mechanism underlying the oxidative addition has been examined in detail based on EPR analyses, cyclic voltammetry,a nd DFT calculations. Interestingly, we have found that in this protocol, the chloride atom induces the Au II /Au III oxidation step.

Recent Advances in Gold(III) Chemistry: Structure, Bonding, Reactivity, and Role in Homogeneous Catalysis

“…319 Indeed, para-nitro and para-benzoyl benzene diazonium chlorides afford the corresponding Au (III) A follow-up study revealed that oxidative addition of aryldiazonium chloride salts to Me 2 SAuCl or Ph 3 PAuCl can be catalyzed by substoichiometric amounts of ascorbic acid as a radical initiator. 320 This strategy was used to develop a stoichiometric arylation of indoles under mild conditions, with a good tolerance of functional groups on both indole and diazonium salt. EPR, DFT and electrochemical studies supported a mechanistic scenario where the oxidative addition occurs through a double one-electron oxidation pathway, where initially the Au(I) precursor is oxidized by an aryl radical to an Au II −aryl species, which then reacts with further diazonium salt to generate the Au III aryl dichloride.…”

“…A follow-up study revealed that oxidative addition of aryldiazonium chloride salts to Me 2 SAuCl or Ph 3 PAuCl can be catalyzed by substoichiometric amounts of ascorbic acid as a radical initiator . This strategy was used to develop a stoichiometric arylation of indoles under mild conditions, with a good tolerance of functional groups on both indole and diazonium salt.…”

Gold-Catalyzed Ascorbic Acid-Induced Arylative Carbocyclization of Alkynes with Aryldiazonium Tetrafluoroborates

“…Our group has been focused on the development of gold redox processes with aryldiazonium salts. In particular, we have been interested in processes where the diazonium salt is thermally or chemically activated . Initial reports on catalytic redox processes of Au­(I) with aryldiazonium salts required the use of a cocatalyst and light irradiation to promote the formation of Au­(III) species, but later studies manifested that, in some cases, just light, heat, or certain ligands and bases are enough to promote this process. , Recently, we evidenced that ascorbic acid, a natural reducing agent, is able to promote the oxidative addition of Au­(I) with aryldiazonium chlorides, and used this protocol for the arylation of N -methyl indoles .…”

Insights into the Mechanism of Gold(I) Oxidation with Aryldiazonium Salts

“…In an effort to expand our oxidation protocolw ith aryldiazonium chlorides to other transformations of synthetic interest, we decidedt oe xplore the arylationo fN-methylindoles. [59] This time, to accelerate the oxidation step, we examined the effect of adding ascorbic acid or gallic acid, as both compounds have been shown to be able to reduce aryldiazonium salts to aryl radicals. [60] Satisfactorily,w eo bservedt hat ascorbic acid had a notable acceleration effect,r educing the oxidative addition times.…”