Enantiodivergent Prenylation via Deconjugative Isomerization
Tobias Morack, Carina Onneken, Hiroshi Nakakohara, Christian Mück‐Lichtenfeld, Ryan Gilmour
Abstract
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.