On the Barton Copper‐Catalyzed C3‐Arylation of Indoles using Triarylbismuth bis(trifluoroacetate) Reagents

The C3-arylation of C2-substituted indoles using Barton's protocol is investigated. The reaction is performed using triarylbismuth bis(trifluoroacetates) and is catalyzed by copper bis(trifluoroacetate). The reaction operates under mild conditions, shows excellent substrate scope, and demonstrates good function group tolerance. Electron neutral or poor aryl groups substituted at any position are efficiently transferred. Computational studies point towards a mechanism involving a carboxylate-assisted C−H activation step.

Abstract

We disclose herein our detailed investigation into the Barton copper-promoted C3-arylation of indoles using triarylbismuth bis(trifluoroacetates). The arylation of unsubstituted 1H-indole using Barton's conditions gave a low yield of the C3-arylated indole, along with small amounts of the product of double C2/C3-arylation and traces of the product of C2 arylation. On the contrary, the arylation of indoles blocked at the C2 position is highly efficient, affording the desired products of C3-arylation in good to excellent yields. The reaction operates under simple conditions, shows good substrate scope, excellent functional group compatibility, and allows the transfer of electron-neutral or deficient aryl groups. Computational studies propose a mechanism involving a trifluoroacetate-assisted C−H activation step.

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