Research

The selective modification of complex biological molecules holds great promise for the develoment of new, potent therapies for a wide range of diseases. Our lab is currently exploring new methods for rapid, efficient, and selective modification for an array of complex, biologically important molecules.

Amines, aryl ethers, and other nitrogen or oxygen containing functional groups are prevalent and essential constituents of many pharmaceuticals and other biologically active compounds. We are currently pursuing the development of new, highly active catalyst systems for both carbon-nitrogen (C–N) bond formation and carbon-oxygen (C–O) bond formation.

Transition metal-catalyzed systems offer a straightforward route for the formation of carbon−carbon bonds. Suzuki−Miyaura, Heck, and Negishi cross coupling are all classical methods for introducing molecular complexity and for simplifying the synthesis of desired targets. Our lab is interested in the continued development of systems for carbon−carbon bond formation. Much of this work relies on the practicality and robustness of the approach, which is often achieved through mechanistic understanding, ligand design and catalyst development.

The development of methods for the construction of organofluorine compounds is of great importance due to the broad presence of fluorine in pharmaceuticals and agrochemicals. Fluorine substitution markedly changes the properties and behavior of the molecule (i.e. lipophilicity, cell membrane permeability, drug potency, and half-life time in the body). Thus, significant efforts have been made towards the development of new fluorination systems. Our research group has worked on methods for introducing fluorine atoms with the use of a palladium catalyst under mild conditions for late-stage functionalization of advanced synthetic intermediates. Mechanistic understanding and ligand development have been crucial for the success of a broadly applicable and efficient system. Fluorination is a vibrant area of research within our lab, and future efforts will be extended towards the development of radiochemical PET applications.

Catalysts that are derived from earth-abundant materials and display unique reactivity are of interest to the synthetic and the chemistry community as a whole. Although copper(I) hydride (CuH) was discovered in the 1840s and widely applied in organic synthesis since the 1980s, the potential of a catalytic system has not been fully realized. We have recently discovered that copper(I) hydride (CuH) complexes can undergo migratory insertion (hydrocupration) with relatively unactivated olefins. By intercepting the catalytically generated alkylcopper intermediates, a variety of useful bonds can be formed. A major focus has been the development of mild, enantioselective hydroamination of many types of olefins using N-electrophiles. We have also studied the use of CuH catalysts for C–C and C–X coupling, including in stereoselective addition to carbonyl derivatives. Our group is interested in the development and understanding of new catalysts and reagents that can broaden the scope and improve the efficiency of CuH-catalyzed asymmetric hydrofunctionalization reactions.