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

17 December 2021, Version 2
This content is a preprint and has not undergone peer review at the time of posting.


Carbolines are considered to be privileged scaffolds in medicinal chemistry. 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 functionalized carbolines. While the procedure is applicable to batch conditions, the generation of arylzinc intermediates in continuous flow has been demonstrated.


Directed lithiation
Negishi cross-coupling
Continuous flow

Supplementary materials

Supporting Information
The Supporting Information for this article contain experimental procedures and characterisation data for all new compounds as well as copies of 1H, 13C and 19F NMR spectra.


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