The Catalyst Controlled Regioselective C-H Functionalization of Arenes and Heterocycles

San Diego State University Foundation, San Diego CA

Investigators

Abstract

With this award, the Chemical Synthesis Program of the NSF Division of Chemistry is supporting the research of Professor Jeffrey Gustafson of San Diego State University (SDSU) to develop reactions that can selectively modify biologically relevant molecules. Most biologically active molecules where occurring naturally or developed as unnatural therapeutic agents are structurally quite complex and have multiple positions that can be modified in a given reaction. A mixture of several different compounds is often obtained, resulting in the need for costly and time-consuming purification steps. The ability to develop a set of reactions that selectively modify different positions of a molecule is highly desirable. Such strategies have the potential to transform how complex molecules are made in a manner that is both more economical and environmentally friendly. Professor Gustafson and his team of students are addressing this need through the development of a set of small molecule catalysts that can direct a reaction to a specific location of a molecule. Educational impacts of this project include improving the SDSU student experience in organic chemistry through the incorporation of virtual reality experiences to aid students in the 3-dimensional visualization of organic molecules. Virtual reality is also to be used in outreach programs aimed at SDSU’s general population, as well as local high schools and community colleges. Additional societal benefits include the recruitment and participation of underrepresented students (high school, undergraduate, and graduate) in research projects and volunteer work as part of the aforementioned outreach projects. Professor Gustafson and his team of students develop ‘organocatalysts’ that effect the regioselective C-H functionalization of simple and complex aromatics. They design bifunctional catalysts that possess one moiety that interacts with the substrate and another moiety that interacts with a reactant, directing it to a specific C-H bond in the substrate. They study diverse transformations that traditionally yield poor regioselectivities including electrophilic aromatic substitution, vicarious nucleophilic substitution and the addition of radicals into aromatics. For the addition of electrophiles into aromatics they utilize bifunctional Lewis basic catalysts that intercept and direct the electrophile to a specific position. For the regioselective addition of nucleophiles into aromatics, they utilize a broad array of organocatalytic strategies such as cation-directed catalysis, hydrogen bonding catalysis and Lewis acid catalysis. Professor Gustafson and his lab focus on incorporating functionalities that add value to the molecular systems being targeted. The ability to site-selectively modify simple and complex aromatic systems can greatly simplify synthetic strategy and lessens the need for lengthy and costly purification steps. The site-selective modification of complex intermediates has the potential to transform how the late-stage structural optimization process, in natural product-inspired synthesis, the development of designed therapeutic agent and in the development of functional molecular scaffolds, in general. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.