Abstract
2-Pyridyl tosylate derivatives have proved to be highly reactive electrophiles in palladium-catalyzed Mizoroki-Heck reactions with electron-rich olefins. These results suggest that the tosylate anion is able to dissociate from the catalyst's metal center subsequent to the oxidative addition step, providing a tricoordinated cationic complex mandatory for a high degree of alpha-regioselectivity. Further development of the 2-pyridyl electrophiles as counterparts in palladium catalysis led to the development of several efficient protocols including amidation, amination, aminocarbonylations, Suzuki-Miyaura, and a fast iron-catalyzed Kumada-Tamao-Curriu cross coupling. Interestingly, in all but one of the palladium-catalyzed reactions, the optimized conditions employed the ligand DPPF (1,1'-bis(diphenylphosphino)ferrocene) or the diisopropyl analog DiPrPF (1,1'-bis(diisopropylphosphino)ferrocene) in dioxane. As with the Mizoroki Heck couplings, the existence of the cationic tricoordinated complex in dioxane was speculated to play an important role, facilitating steps such as transmetallation and CO incorporation. The mild conditions developed in all of the catalytic reactions described in this overview can be applied to the pyridine/pyrimidine core, providing highly functionalized heteroaromatic compounds in a few steps.