New Catalytic Stereoselective Strategies for Hydrocarbon Functionalization Via Ionic Intermediates - 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.
