Selective Halogenation of Pyridines Using Designed Phosphine Reagents

26 August 2019, Version 1
This content is a preprint and has not undergone peer review at the time of posting.

Abstract

Halopyridines are key building blocks for synthesizing pharmaceuticals, agrochemicals, and ligands for metal complexes, but strategies to selectively halogenate pyridine C–H precursors are lacking. We designed a set of heterocyclic phosphines that are selectively installed at the 4-position of pyridines as phosphonium salts and then displaced with halide nucleophiles. A broad range of unactivated pyridines can be halogenated, and the method is viable for late-stage halogenation of complex pharmaceuticals. The study concludes that both tuning the phosphonium electrophilicity and pyridine substitution patterns influence the efficiency of the carbon-halogen bond-forming step.

Keywords

Pyridines
Halogenation
Phosphonium Salts
4-Selective
Late-stage functionalization

Supplementary materials

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Description
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Title
Halogenation SI ChemRxiv
Description
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