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

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.

Automated summary

In this study, we investigated the C3-arylation of indoles using triarylbismuth bis(trifluoroacetates) promoted by Barton's copper. The arylation of unsubstituted 1H-indole under Barton's conditions yielded a low yield of C3-arylated indole, along with some double C2/C3-arylation product and traces of C2 arylation product. On the other hand, the arylation of C2-blocked indoles showed high efficiency and good to excellent yields of the desired C3-arylation products. The reaction demonstrated simple conditions, broad substrate scope, excellent functional group compatibility, and the ability to transfer electron-neutral or deficient aryl groups. Computational studies proposed a mechanism involving trifluoroacetate-assisted C-H activation.