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

Abstract

Carbolines are privileged scaffolds in medicinal chemistry, and therefore, novel and efficient approaches to their synthesis are in high demand. An efficient method for the synthesis of α- and β-carbolines from fluoropyridines and 2-haloanilines is reported. This streamlined 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 functionalised carbolines. While the procedure is applicable to batch conditions, the generation of arylzinc intermediates in continuous flow has been demonstrated .