First-row transition metal catalysts have become essential tools in organic synthesis, exhibiting unique reactivity and selectivity profiles in reductions, oxidations, and cross coupling chemistry. While catalysts based on Fe and Ni have been touted as sustainable alternatives to precious metal catalysts, their application is limited in high-throughput discovery campaigns due to the dearth of precedented pre-catalysts, reported commercial ligands, and the risk of deleterious speciation events.

Nickel-catalyzed cross-coupling reactions have emerged as sustainable and cost-effective synthetic methods. While nickel operates via classical closed-shell pathways to catalyze biaryl coupling reactions, its ability to mediate radical pathways has significantly broadened the scope of cross-coupling to include a diverse range of alkyl motifs. Building on mechanistic insights, we developed the ProPhos ligand, which enhances the reactivity of nickel-catalyzed Suzuki-Miyaura couplings.

Alkenes serve as a key handle for further functionalization, thus methods of activation that provide both selectivity, and tolerance to substitution and functional groups are highly sought after. Metal hydride atom transfer (MHAT) has seen a high level of interest for this reason. It avoids issues that occur in other common alkene functionalization methods like hydrometallation and Bronsted acid conditions.

Cytochrome P450 (P450, CYP) enzymes are very versatile catalysts and, in the current literature, involved in more oxidations than any other family of enzymes. They oxidize drugs, steroids, vitamins, carcinogens, natural products, and industrial chemicals. Several of the 57 human P450s are critical for life, but others have been therapeutic targets.

Our laboratory has long focused on the development of especially concise strategies for the synthesis of structurally complex natural products with compelling biological activities. These exploits are usually destined to provide opportunities for deeper studies of their mechanism of action or aspects of their biosynthesis. To aid in these goals, we often design strategies that are amenable to the procurement of multiple members of a family of secondary metabolites.