Desulfinative Cross-Coupling as a Method to Overcome Problematic Suzuki–Miyaura Reactions of Pharmaceutically Relevant Heteroaromatic Boronates

The well documented difficulties associated with direct (hetero)-arylation of aza-aromatics (e.g., azines) at the α-position to nitrogen led to a collaborative project between the Willis group at Oxford and the Medicine Design department at Pfizer with the aim of addressing this challenge. The result of this collaboration has been a series of reports detailing the development of 2-aza-aryl sulfinates, as well as related 2-aza-aryl sulfone derivatives, as efficient nucleophilic reagents in palladium-catalyzed coupling reactions with (hetero)-aryl halides. The developed chemistry is routinely used in the medicinal chemistry laboratories at Pfizer, and the patent literature now contains many examples of these methods being embraced across the pharmaceutical industry. Hundreds of pyridyl (and related heterocyclic) sulfinates are now commercially available from multiple vendors. In this microperspective we discuss the development and evolution of these methods and highlight subsequent applications.