UC San Diego

The functionalization of arenes and heterocycles via direct C-H activation is a valuable tool in medicinal chemistry as it allows for the manipulation of a diversity of complex structures without the need for de novo methodologies. It can be utilized as a late-stage strategy to address pharmacological problems such as pharmacokinetic profile, metabolism and on-off target activity of a lead compound. One of the drawbacks to current methodologies is the lack of regioselectivity, wherein a scaffold possesses multiple sites of reactivity, leading to multiple constitutional isomers. Our lab has developed a regioselective catalyst-controlled Lewis base halogenation of phenols and anilines, which is discussed in two manuscripts in Chapter 1 and 2. We also explore photoredox catalysis to explore the intramolecular synthesis of benzothiazoles and intermolecular sulfenylation of indoles, which is presented in Chapter 3. Last, Chapter 4 discusses an enantioselective functionalization of a diaryl ether naphthoquinone scaffold to access enantioenriched atropisomeric molecules. We believe these works can be utilized to obtain a diversity of highly regioselective and enantioselective heterocycle and arene motifs that are relevant towards drug discovery efforts.