(Graduate Students Initiated)
IMPACT Lecture Series
"Replacing Atoms"
Abstract: Medicinal chemists frequently conduct "nitrogen scans" as part of their optimization processes, wherein a nitrogen atom is systematically walked across aromatic CH positions of the lead compound to identify which isomeric azine possess the best mix of biochemical and physicochemical properties. This intellectual exercise has until recently not been matched by an analogous chemical process, necessitating de novo synthesis of each new candidate, despite the availability of the immediate arene precursor. This presentation will cover work from the Levin laboratory which addresses this longstanding synthetic challenge, offering several new methods for replacement of aromatic carbons for nitrogen. This work has revealed important guiding principles regarding the regiochemical selectivity of the underlying steps as well as strategic lessons that help to guide the development of further members of this reaction family. Applications to questions of regiochemical selectivity in azoles will also be presented alongside mechanistic findings.