Hatice G. Yayla

The synthesis of imidazole fused spirocyclic ketones as templates for acetyl-CoA carboxylase (ACC) inhibitors is reported. By completing the spirocyclic ring closure via divergent pathways, the synthesis of these regioisomers from common intermediates was developed. Through an aldehyde homologation/transmetalation strategy, one isomer was formed selectively. The second desired isomer was obtained via an intramolecular aromatic homolytic substitution reaction.

We report a new photocatalytic protocol for the redox-neutral isomerization of cyclic alcohols to linear ketones via C–C bond scission. Mechanistic studies demonstrate that key alkoxy radical intermediates in this reaction are generated via the direct homolytic activation of alcohol O–H bonds in an unusual intramolecular PCET process, wherein the electron travels to a proximal radical cation in concert with proton transfer to a weak Brønsted base.

Elbasvir is a potent NS5A antagonist for the treatment of chronic hepatitis C. A seemingly trivial indoline oxidation en route to the target compound was complicated by epimerization of a stereogenic hemiaminal center under most standard oxidation conditions. To address this issue, a novel visible light photoredox process for indoline oxidation was developed involving an iridium photosensitizer and environmentally-benign perester oxidant.