The Rational Development of Precatalysts for Cross-Coupling and Cross-Electrophile Coupling Reactions

Transition metal catalyzed cross-coupling has found applications in diverse areas of chemistry and is widely considered to be one of the most powerful and general synthetic methods. Both Ni and Pd complexes are now commonly used to facilitate cross-coupling reactions. The mechanism for both Ni and Pd catalysts is typically proposed to involve a series of complexes in the M(0) and M(II) oxidation states. In this presentation we will describe results that indicate that state-of-the-art Ni and Pd precatalysts form a significant quantity of species in the M(I) oxidation state during catalytic reactions. We will describe the mechanistic pathways through which these M(I) complexes are formed. The M(I) complexes are catalytically inactive and by understanding how they are formed it is possible to stop their generation during catalysis. We have used this information to design improved catalytic systems, which are now commercially available. The implications of our results to cross-electrophile coupling will also be explored.