Our lab has developed a class of copper(II)-catalyzed reactions that operate via polar-radical cascades. The polar alkene additions, aminocupration and oxycupration, are rendered enantioselective via hetero-cuprations using chiral copper catalysts. The resulting alkyl copper(II) species can generate alkyl radicals that can undergo additions to double bonds, atom abstractions and group transfers or copper-facilitated heteroatom bond formations. We study these reaction mechanisms using stereochemistry, reaction kinetics, various spectroscopic methods and density functional theory calculations. In some of these mechanistic studies we have collaborated with Profs. Jerry Keister, Travis Dudding and Eva Zurek. We have developed a broad range of alkene addition reactions including catalytic enantioselective aminooxygenation, carboamination, diamination, aminohalogenation, aminosulfenylation, hydroamination, carboetherification, hydroetherification, dioxygenation and oxysulfenylation. Formation of 5- and 6-membered rings is most common. In most of these reactions, inexpensive MnO2 has served as the stoichiometric oxidant, [O].
Application of molecular oxygen as a green oxidant to turn over the catalyst (oxidase activity) as well as an oxygen source for C-O bond formations (oxygenase activity) is a current major thrust in our research efforts to develop new transformations as well as refine existing transformations to be more atom economical and generate less waste.
We are also investigating reaction sequences that initiate with copper-catalyzed alkyl radical formation and alkene addition. Depending on the reaction components, net alkyl Heck, carboetherification or carboamination results. Development of enantioselective approaches to these reactions are under investigation.
Finally, we collaborate with more biologically-oriented scientists, e.g. Profs. Ekin Atilla-Gokcumen and Xinjiang Wang, by synthesizing reactive (photoactive, clickable) probes for their use in chemical biology studies. We are also in the process of expanding our efforts to apply our copper-catalyzed reactions in medicinal chemistry endeavors.