The 2-Pyridyl Problem: Challenging Nucleophiles in Cross-Coupling Arylations.

Azine-containing biaryls are ubiquitous scaffolds in many areas of chemistry, and efficient methods for their synthesis are continually desired. Pyridine rings are prominent amongst these motifs. Transition-metal-catalysed cross-coupling reactions have been widely used for their synthesis and functionalisation as they often provide a swift and tuneable route to related biaryl scaffolds. However, 2-pyridine organometallics are capricious coupling partners and 2-pyridyl boron reagents in particular are notorious for their instability and poor reactivity in Suzuki-Miyaura cross-coupling reactions. The synthesis of pyridine-containing biaryls is therefore limited, and methods for the formation of unsymmetrical 2,2'-bis-pyridines are scarce. This Review focuses on the methods developed for the challenging coupling of 2-pyridine nucleophiles with (hetero)aryl electrophiles, and ranges from traditional cross-coupling processes to alternative nucleophilic reagents and novel main group approaches.