A Catalytic Collaboration: Pairing Transition Metals and Lewis Acids for Applications in Organic Synthesis

The use of metal catalysts to accelerate an organic transformation has proven indispensable for access to structural motifs having applications across medicinal, polymer, materials chemistry, and more. Most catalytic approaches have cast transition metals as the “leading role”; these players mediate important reactions such as C-C cross coupling and the hydrogenation of unsaturated bonds. These catalysts may require collaboration, featuring Lewis acidic or basic additives to promote a desired reaction outcome. Lewis acids can serve to accelerate reactions by way of substrate stabilization and/or activation, and as such, are valuable in optimizing catalytic transformations. A burgeoning area of chemical research which unifies these concepts has thus sought to develop transition metal complexes having ambiphilic (containing a Lewis basic and acidic unit) ligands. This approach takes advantage of metal-ligand cooperativity to increase the efficiency of a given chemical transformation, leveraging intramolecular interactions between a transition metal and an adjacent secondary ligand site. While this has shown significant potential to facilitate challenging and important transformations, there remains unexplored depth for creativity and future advancement. This Frontier highlights inter- and intramolecular combinations of transition metals and Lewis acids that together, provide a collaborative platform for chemical synthesis.