Paul Vadola

Vadola's research focuses on the development of new methods for the synthesis of organic molecules with a particular emphasis C­–H bond functionalization. C–H bonds are ubiquitous in organic molecules but classically have been viewed as fairly unreactive, thus causing them to be overlooked as potential functional handles in organic synthesis. The field of C–H bond functionalization is focused on exploring new methods to directly convert these unreactive bonds into more desirable functionalities, such as C–C, C–N, and C–O bonds, through the formation of reactive intermediates (Figure 1, intermediates highlighted in blue). By this approach, valuable organic molecules with significant structural complexity may be accessed in a concise manner from simple C–H-bond-containing precursors. This ability to selectively functionalize a targeted C–H bond can provide new routes to chemical structures previously inaccessible by classical organic chemistry.

His group's approach to reaction design is target driven with the goal of developing new methods that grant access to chemical structures found in pharmaceuticals and naturally occurring medicinally active molecules. They are particularly interested in new approaches to the synthesis of spirocycles. Spirocyclic scaffolds of varying complexity are prevalent in a variety of organic molecules, ranging from biologically active natural products and pharmaceuticals to organic materials (Figure 2). The fully substituted carbon center that defines this broad class of compounds makes them a particularly attractive target to synthetic organic chemists. The group is currently investigating new catalytic methods of generating complex spirocyclic structures within the setting of natural product synthesis.

In addition to the development of new chemical reactions, he is interested in using synthetic organic chemistry as a means to develop chemical tools for the study of biological systems. The balance of various chemical processes within the cell is responsible for maintaining proper cellular function, and disruption of this balance can lead to a disease state. One area of research in his group will focus on developing fluorescent molecules that will enable in vivo imaging of the cellular environment as a means to study the physiochemical changes that occur in diseased tissue.

Selected Publications

• Paul A. Vadola and Dalibor Sames “Intramolecular Coupling of sp2 C–H Bonds and Alkynes for the Synthesis of Coumarins: Exploring the Scope and Application to the Development of Neuroimaging Agents.” J. Org. Chem., 2012,77, 7804-7814.

• Paul A. Vadola, Ignacio Carrera, and Dalibor Sames “C–H Bond Functionalization via Hydride Transfer: Formation of a-Arylated Piperidines and 1,2,3,4-Tetrahydroisoquinolines via Stereoselective Intramolecular Amination of Benzylic C-H Bonds.” J. Org. Chem., 2012, 77, 6689-6702. Published as a Featured Article and Featured on the Cover of volume 77, issue 18.

• Rebecca M. Wilson, Jennifer L. Stockdill, Xiangyang Wu, Xuechen Li, Paul A. Vadola, Peter K. Park, Ping Wang, and Samuel J. Danishefsky “A Fascinating Journey into History: Exploration of the World of Isonitriles En Route to Complex Amides.” Angew. Chem. Int. Ed., 2012, 51, 2834-2848.

• Paul A. Vadola and Dalibor Sames “C–H Bond Functionalization via Hydride Transfer: Direct Coupling of Unactivated Alkynes and sp3 C–H Bonds Catalyzed by Platinum Tetraiodide” J. Am. Chem. Soc., 2009, 131, 16525-16528.

• Niko G. Gubernator, Hui Zhang, Ronald G. W. Staal, Eugene V. Mosharov, Daniela Pereira, Minerva Yue, Vojtech Balsanek, Paul A. Vadola, Bipasha Mukherjee, Robert H. Edwards, David Sulzer, and Dalibor Sames “Fluorescent False Neurotransmitters Visualize Dopamine Release from Individual Presynaptic Terminals” Science, 2009, 324, 1441-1444.

 Professional Society Memberships

• American Chemical Society