Enantiodivergent Prenylation via Deconjugative Isomerization

Enantioselective platforms to facilitate prenylation are potentially expansive for translational research due to the importance of this motif as a key regulatory of biological function. Motivated by the conspicuous dearth of methods to generate chiral prenyl fragments for contemporary drug discovery, a light-enabled deconjugative isomerization of activated alkenes containing an aryl ketone antenna is disclosed through sequential geometric isomerization/hydrogen atom transfer (HAT)/protonation. Detailed mechanistic analyses have guided the development of an enantioselective variant of this atom economical process (up to 99% and 95:5 e.r.). Importantly, the chiral pool quasi-enantiomers quinine and quinidine serve as effective catalysts, thereby rendering this addition to the chiral drug discovery module portfolio enantiodivergent.