Atropisomerism is a type of chirality that is ubiquitous in drugs scaffold in medicinal chemistry. With our interest in pyrrolopyrimidines (PPYs) scaffold that is known to possess bioactivity as kinase inhibitors, we developed a method to obtain atropisomerically pure PPYs via dynamic kinetic resolution. The activation of fluorinated PPYs containing chiral axis at C3 position was accomplished using chincona alkaloid catalyst with a bulky C9-thiourea substitution. The following atroposelective thiophenol addition to a variety of PPY analogs was successfully achieved via nucleophilic aromatic substitution (S<sub>N</sub>Ar) in excellent yields with good to moderate enantioselectivities. These results enabled us to obtain larger amount of enantiomerically rich PPYs that we previously could not achieve via kinetic resolution.

Atroposelective nucleophilic aromatic substitution of fluorinated pyrrolopyrimidines

2019 Fall National Meeting

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.