The NSF Chemical Catalysis Program supports the efforts of Professor Steven E. Wheeler of Texas A&M University Main Campus to rationally design highly stereoselective catalysts for the propargylation of aromatic aldehydes. These design efforts are facilitated by the development of a set of computational tools for the rapid and reliable prediction of the stereoselectivities of these reactions. The team seeks to accurately predict the stereoselectivity provided by a given catalyst within a 24-hour time frame, which allows for the relatively rapid screening of potential new catalysts. Propargylation catalysts are designed based on the concept that the stereoselectivities of bipyridine N-oxide catalyzed alkylation reactions are dictated primarily by the chiral arrangement of ligands around a hexacoordinate silicon transition state. Notably, only certain ligand arrangements are stereoselective, and catalysts are designed to adopt these inherently stereoselective configurations. To maximize the impact of these studies and to validate the computational predictions, propargylation catalysts predicted to be highly stereoselective are synthesized and tested by an experimental collaborator, Professor Martin Kotara of Charles University in Prague, Czech Republic. This collaboration provides valuable feedback while also ensuring that new catalysts developed are immediately applied in natural product syntheses. These metal-free catalysts for asymmetric organic reactions promise new, more environmentally friendly routes to important chiral molecules, including natural products and pharmaceuticals and thus, represent important efforts in sustainable chemistry. An additional outcome of this research is the development of a computational toolkit for the prediction of stereoselectivities of N-oxide alkylation catalysts. This project lays the foundation for a general toolkit for computational catalyst design, which is distributed freely under an open-source license.
The NSF Chemical Catalysis Program supports the efforts of Professor Steven E. Wheeler of Texas A&M University Main Campus to develop new catalysts and improve existing metal-free catalysts for valuable and sustainable chemical syntheses used in producing natural products and pharmaceuticals. The development of new catalysts requires a detailed understanding of the underlying reaction mechanisms and the myriad of factors that control stereoselectivity. Computational chemistry, by providing structural and energetic information about not only the operative reaction pathway but also higher-lying transition states, provides key insights into the origin of stereoselectivity of such organocatalyzed reactions. This effort focuses on the use of computational resources for the preparation of metal-free catalysts thereby making the materials more environmentally friendly than previous routes. Undergraduate and graduate students receive extensive hands-on training in computational organic chemistry as well as more formal training in quantum chemistry and electronic structure theory. Close collaborations with a synthetic organic collaborator exposes the students to a broad range of topics in modern organic chemistry and teaches them to clearly communicate their results to a non-computational audience. The computational methods that are developed are freely distributed under an open-source license so that others in the scientific community may benefit.
