Research

Our research program uses fundamental principles of molecular design to address some of the grand challenges in the fields of small molecule activation and catalysis. We are interested in developing strategies to reversibly store energy in the form of chemical bonds, and also to rapidly convert abundant chemical (bio)feedstocks into value-added chemicals and fuels.

The overarching themes of our research program are to (a) understand how to exploit carefully positioned secondary-sphere sites to control reactivity, and (b) develop transition metal compounds to promote otherwise difficult transformations of small molecule chemical feedstocks such as N₂, CO₂, O₂, and CO.

We are working to establish new ways by which molecular catalysts can be tuned by the incorporation of pendent functional groups within a metal’s secondary coordination sphere environment. We are using these appended functional groups (hydrogen bond donor/acceptors, or Lewis acid/bases) to augment reactivity of the central transition metal in order to promote the activation/delivery of small molecules to appropriate substrates. Overall, our approach aims to move the emphasis away from the transition metal, and instead, place high importance on secondary-coordination sphere interactions (not directly bound to the metal) to develop new metal complexes and catalysts that synergistically engage substrates for binding/reduction, regulate activity, and ultimately incorporate earth-abundant metals.

Hydrogen Transfer and Related Catalysis for Selective Oxidation and Fuel-Forming Reactions:

We developed a dehydrogenation catalyst (now commercially available through Sigma-Aldrich^®; 794414 and 794406) that efficiently removes hydrogen from alcohols and amines under mild conditions, which represents an alternative strategy for hydrogen recovery/transfer from available chemical feedstocks. In the absence of any base or hydrogen acceptor additives, alcohols are chemoselectively oxidized to ketones in the presence of primary alcohols. Amines are dehydrogenatively oxidized to nitriles, with liberation valuable H₂. These catalysts also are highly active for upgrading ethanol to 1-butanol. Ethanol can be produced from renewable feedstocks (bio-ethanol) and is currently used as a gasoline additive. Compared to ethanol, 1-butanol has a much higher energy density and is immiscible with water, mitigating corrosion and storage issues. We are continuing to develop strategies to convert biorenewable feedstocks, such as ethanol into useful fuels or platform chemicals. Another reaction enabled by our suite of catalysts is the stereoretentive α-C deuteration of chiral amines. Deuteration of pharmaceuticals has recently been recognized as a highly attractive strategy to improve pharmacokinetic properties of drug candidates when incorporated at sites relevant to metabolism. Our catalyst uses D₂O as the deuterium source and is tolerant to a variety of functional groups found in many pharmaceutical drugs (e.g. thiophenes, pyridines, esters, and amides).

Second-Sphere Modifications for Catalyst Redesign

One of the guiding hypotheses for the ligand (re)design efforts in hydrogen transfer catalysis is that carefully selected and positioned secondary sphere groups participate in the activation and transfer processes. We have modified a series of pincer-based ligands that contain distinct spatial positioning of sites closest to the metal. By modifying the donor and acceptor properties of these groups, we found that the reactivity toward alcohols, H₂ and H-E bonds is perturbed in important ways.

The placement of ortho-appended groups changes the favored mechanism of E-H activation/transfer from a classical inner-sphere to a bifunctional outer-sphere type pathway. As a result, the chemoselectivity for the reduction reactions is distinct and reduction favors polar double bonds over nonpolar olefinic bonds due to a charged transition state. The appended groups serve at least three roles: they (1) promote a bifunctional activation pathway of H-H and related bonds, (2) regulate the charge, and thus the hydricity of intermediate ruthenium hydrides, (3) function as a tethering group for a Lewis acid (alkali metal or borane) to coordinate to a substrate and direct hydride transfer, and (4) significantly improve reaction rates and product selectivities.

Second-Sphere Modifications for Small Molecule Reduction

Reduction of commonly inert substrates such as CO₂, CO, and N₂ is one of the grand challenges within the chemistry community, yet is readily accomplished by metalloenzymes. Biology has provided a type of “instruction manual” for the synthetic community, and for efficient small molecule activation, precise control over substrate binding, interconversion between redox states, and delivery of H⁺/e^- equivalents is required. We have found that secondary sphere interactions can play a key role to regulate the primary coordination geometry of a transition metal, as well as to enable reversible and rapid redox transformations. Ligand/substrate interactions with appropriately positioned hydrogen bond donors and/or acceptors can outcompete a metal’s coordination preference and enhance the stability of otherwise weakly interacting substrates. These interactions can facilitate binding, electron transfer, proton/electron transfer, or redox tuning. Our studies clearly show that completely different reactivity can be enabled by very simple targeted modifications to a ligand’s secondary coordination sphere.