Late-Stage C-H Arylation of Azepinoindole via Pd/Cu Catalysis: A Step Efficient and Convergent Synthesis of Rucaparib

The C-H arylation of indoles holds the promise to shorten synthetic routes in the production of pharmaceuticals. However, late-stage C-H activation reactions often rely on the presence of protecting groups or stoichiometric metal additives. The regiospecific C-H arylation of a highly functionalized azepino[5,3,4-cd]indole scaffold lacking directing groups via Pd(II) and Cu(II) co-catalysis is reported. The direct C-H coupling was demonstrated in the convergent synthesis of rucaparib, an FDA approved anticancer drug.

Automated summary

This study reports a regiospecific C-H arylation of a highly functionalized azepino[5,3,4-cd]indole scaffold lacking directing groups via Pd(II) and Cu(II) co-catalysis, which offers a promising method to surpass the limitations of traditional protecting groups or metal additives in late-stage C-H activation reactions. The direct C-H coupling was demonstrated in the convergent synthesis of the FDA approved anticancer drug rucaparib.