Synthesis of α- and β-Carbolines by a Metalation/Negishi Cross-Coupling/SNAr Reaction Sequence

A methodology for the synthesis of alpha- and beta-carbolines from fluoropyridines and 2-haloanilines is reported. This procedure consists of a four-step directed ortho-lithiation, zincation, Negishi cross-coupling, and intramolecular nucleophilic aromatic substitution, providing access to a diverse set of functionalized carbolines. While the procedure is applicable to batch conditions, the generation of arylzinc intermediates in continuous flow has been demonstrated.

Automated summary

A methodology for the synthesis of alpha- and beta-carbolines from fluoropyridines and 2-haloanilines is described. The procedure involves a four-step directed ortho-lithiation, zincation, Negishi cross-coupling, and intramolecular nucleophilic aromatic substitution, enabling the synthesis of a diverse set of functionalized carbolines. The generation of arylzinc intermediates in continuous flow has also been demonstrated.