Willis Pyridinates for Palladium-Catalyzed Cross-Coupling Reactions

Introduction

The Suzuki-Miyaura cross-coupling reaction is one of the most used transformations in the pharmaceutical industry to form carbon-carbon bonds.1,2 However, limitations to the application of this reaction in discovery chemistry persist, including the notorious low reaction efficiency, poor stability, and difficulty in preparing pyridine-2-boronates and boronic acids for cross-coupling.

Professor Willis and industrial partners at Pfizer have shown that by replacing boronates with pyridine-2-sulfinates as nucleophilic coupling partners, a palladium-catalyzed desulfinylative cross-coupling process of exceptional scope can be realized.3 Both aryl bromides and aryl chlorides can be employed as coupling partners to access challenging and medicinally relevant linked pyridine-heterocycle building blocks.

Professor Willis and industrial partners

 

Representative Scheme and Examples

Representative Scheme and Examples

 

Advantages

  • Bench-stable, solid reagents
  • Efficient nucleophilic cross-coupling partners
  • Convenient removal during aqueous work-up

Special thanks to Tim Markovic and Prof. Michael Willis for contributing this Technology Spotlight!

 

Materials