New Catalytic Stereoselective Strategies for Hydrocarbon Functionalization Via Ionic Intermediates

项目总结

Project Summary Chemical methodologies for the predictable transformation of hydrocarbons to functional synthetic intermediates have revolutionized the preparation of small-molecule therapeutics. Nonetheless, the continued development of new chemical tools that compliment current existing technologies and address gaps in synthetic strategy offer the potential to further accelerate drug innovation and imaging techniques. The goal of this proposed research program is to develop new areas of asymmetric catalysis by means of chiral ionic intermediates. More specifically, the two research areas proposed here are centered on the study of catalysts that promote the stereoselective trapping of cationic intermediates to address longstanding challenges in synthesis. The first research area will focus on the development of novel strategies for catalytic enantioselective halogenation via chiral Lewis base catalysis. This work draws upon our initial findings in this area regarding the Lewis base activation of latent halide sources for the catalytic generation of chiral halogenating reagents. The second research area details a conceptually novel approach for the generation of chiral molecules via hydride abstraction processes. Specifically, we aim to exploit the reactivity and selectivity of superacid catalysts to enable the regio- and stereoselective functionalization of saturated hydrocarbons. This strategy represents the starting point for a broader research program aimed at developing a new mode of asymmetric Csp3–H functionalization. Taken together, these research programs will expand the available chemical space and streamline chemical synthesis for drug discovery and development.