In 2010, Richard Heck, Ei-ichi Negishi, and Akira Suzuki joined the prestigious circle of Nobel Laureate chemists for their roles in discovering and developing highly practical methodologies for C-C bond construction. From their original contributions in the early 1970s the landscape of the strategies and methods of organic synthesis irreversibly changed for the modern chemist, both in academia and in industry. In this Review, we attempt to trace the historical origin of these powerful reactions, and outline the developments from the seminal discoveries leading to their eminent position as appreciated and applied today.

Strategies for the development of Pd catalysts based on utilization of L2Pd and LPd species, beyond the contributions of the 2010 Nobel Laureates Richard Heck, Ei-ichi Negishi, and Akira Suzuki, along with their contemporaries, are reviewed. These well-defined, preformed Pd catalysts improve the selectivity and activity of selected cross-coupling reactions by reducing the metal loading and the ligand-to-metal ratios. This review describes predominantly the development of Pd precatalysts over the last 10 years and highlights the benefits often observed when using well-defined preformed catalysts relative to those generated in situ.

Alpha-arylated carbonyl compounds are commonly occurring motifs in biologically interesting molecules and are therefore of high interest to the pharmaceutical industry. Conventional procedures for their synthesis often result in complications in scale-up, such as the use of stoichiometric amounts of toxic reagents and harsh reaction conditions. Over the last decade, significant efforts have been directed towards the development of metal-catalyzed alpha-arylations of carbonyl compounds as an alternative synthetic approach that operates under milder conditions. This Review summarizes the developments in this area to date, with a focus on how the substrate scope has been expanded through selection of the most appropriate synthetic method, such as the careful choice of ligands, precatalysts, bases, and reaction conditions.

Two new classes of highly active yet air- and moisture-stable π-R-allylpalladium complexes containing bulky biaryl- and bipyrazolylphosphines with extremely broad ligand scope have been developed. Neutral π-allylpalladium complexes incorporated a range of biaryl/bipyrazolylphosphine ligands, while extremely bulky ligands were accommodated by a cationic scaffold. These complexes are easily activated under mild conditions and are efficient for a wide array of challenging C-C and C-X (X = heteroatom) cross-coupling reactions. Their high activity is correlated to their facile activation to a 12-electron-based "L-Pd(0)" catalyst under commonly employed conditions for cross-coupling reactions, noninhibitory byproduct release upon activation, and suppression of the off-cycle pathway to form dinuclear (μ-allyl)(μ-Cl)Pd2(L)2 species, supported by structural (single crystal X-ray) and kinetic studies. A broad scope of C-C and C-X coupling reactions with low catalyst loadings and short reaction times highlight the versatility and practicality of these catalysts in organic synthesis.