4-Selective Pyridine Functionalization Reactions via Heterocyclic Phosphonium Salts

Abstract

Pyridines are widely used across the chemical sciences in applications ranging from pharmaceuticals, ligands for metal complex and battery technologies. Direct functionalization of pyridine C–H bonds is an important strategy to make useful pyridine derivatives, but there are few ways to selectively transform the 4-position of the scaffold. We recently reported that pyridines can be converted into heterocyclic phosphonium salts that can serve as generic handles for multiple subsequent bond-forming processes. Reactions with nucleophiles and transition-metal cross-couplings will be described to make C–O, C–S, C–N, and C–C bonds in a diverse range of pyridines including those embedded in complex pharmaceuticals.

1 Introduction

2 Direct, Regioselective Functionalization of Pyridines

3 4-Position Selectivity via Metal Catalysis

4 Versatile Functional Groups versus Specific Bond Constructions

5 Phosphonium Salts as Reagents for Pyridine Functionalization

6 Conclusions

Key words

pyridines - C–H functionalization - phosphonium salts - late-stage functionalization - pharmaceuticals

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