Over the course of the past greater decade, our research here at the Rovis group has covered a broad range of topics in asymmetric catalysis, organocatalysis, and organometallic chemistry. Since its inception, our group has disclosed findings ranging from the stereoselective rearrangements of vinyl acetals and ethers, to Ni-catalyzed desymmetrizations of various cyclic meso-anhydrides, and even disclosing the synthesis of several natural products using various technologies developed within the lab. We also have a rich and prominent history within the field of N-heterocyclic carbenes (NHCs) as organocatalysts, pioneering studies in acyl-anion, azolium-enolate, and homoenolate reactivities as catalyzed by triazolylidene-based carbenes. We use the methodology developed within our group to provide easier access to nitrogen and oxygen containing heterocycles, those of which are of significant interest to the fields of medicinal chemistry and pharmaceutical development. Though various opportunities still exist in the aforementioned research areas, our more contemporary foci include some of the following:
Photoredox catalysis has allowed chemists to activate inert functionalities using visible-light energy as the main driving force. The ubiquity and tunability of photons makes them an ideal external stimulus for enabling catalysis of traditionally non-reactive functionalities. As such, metal poly-pyridyl complexes, upon absorbing visible-light radiation, may function as either oxidants or reductants of stable Co(II) pre-catalysts. One of our research aims is to combine photoredox and cobalt catalysis to generate catalytically active species capable of unprecedented reactivity and unforeseen applications in materials science.
Another one of our research aims in this domain is to provide a unified strategy for the functionalization of aliphatic amines via sp3-hybridized C-H bond activation. In this regard, we can generate alkyl radicals via a photo-chemically enabled oxidation of an N-H bond and subsequent intramolecular hydrogen atom transfer (HAT). We can trap these alkyl radicals with a variety of radical acceptors to then generate a wide breadth of functionalized amines. By varying the directing group on nitrogen, we are able to dictate the site-selectivity of the alkyl-radical intermediate to thus functionalize positions α, β, γ, and δ from a nitrogen moiety. Further exploration into in situ transient directing groups is currently ongoing for the functionalization of both nitrogen and oxygen containing aliphatic chains.
Our group is also interested in studying new transformations promoted by Rh(III)-cyclopentadienyl complexes. One domain of research involves directed metalation of sp2-hybridized carbon centers, leading to the formation of rhodacyclic intermediates. These species then undergo insertion with unsaturated coupling partners such as alkenes, alkynes, or diazo compounds, leading to the formation of nitrogen heterocycles of varying ring sizes. Alternatively, by clever design of the directing group, an intriguing carboamination reaction was recently discovered. In this reaction, the initial C-H activation is followed by cleavage of the directing group, which is then followed by reductive elimination to construct the carbon-nitrogen bond, leading to acyclic products. Also, our group is equally interested in systematic studies on the effect that perturbed steric and electronic parameters of the Cp-ligands has on the overall reactivity of Rh(III) complexes. We have found that regioselectivity, diastereoselectivity, chemoselectivity, and reactivity are all influenced by the nature of the Cp-ligands employed. Finally, enantioselective variants of some Rh(III)-promoted transformations have been previously disclosed and are also currently under development. The strategy employed relies on artificial metallozenymes and has led to a diverse research topic within our group.
Enzymes that are found in nature enable a plethora of powerful chemical transformations. We have a marked interest in utilizing what nature has done best for eons and applying it in a laboratory setting, with a particular focus toward organometallic-enabled chemical transformations. In recent years, artificial metalloenzymes, which are simply enzymes that are resultant from the incorporation of an organometallic cofactor within a host protein, has proven to be an effective alternative to traditional modes of catalysis. As such, we are interested in using biotin-streptavidin technology as a means of incorporating Rh(III)-cofactors en route to generating metalloenzymes that enable C-H activation chemistry in aqueous environments. Site-directed mutagenesis has allowed us to generate a library of streptavidin (SAV) metalloenzymes that are ultimately responsible for enhancements in reactivity as well as improved selectivity. More specifically, our current interest in this field involves utilizing these metalloenzymes as macro-catalysts for increased reactivity and selectivity in Rh(III) catalyzed C-H activation reaction systems.
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(Photo Credits: Melissa Ashley, Benjamin Ravetz)