Asymmetric Catalytic Epoxidation of Terminal Enones for the Synthesis of Triazole Antifungal Agents

An enantioselective epoxidation of a-substituted vinyl ketones was realized to construct the key epoxide intermediates for the synthesis of various triazole antifungal agents. The reaction proceeded efficiently in high yields with good enantioselectivities by employing a chiral N,N'-dioxide/Sc-III complex as the chiral catalyst and 35% aq. H2O2 as the oxidant. It enabled the facile transformation for optically active isavuconazole, efinaconazole, and other potential antifungal agents.

Automated summary

An enantioselective epoxidation of a-substituted vinyl ketones was successfully achieved using a chiral N,N'-dioxide/Sc-III complex as the catalyst and 35% aq. H2O2 as the oxidant. This method greatly improved the efficiency and yield of the synthesis of various triazole antifungal agents, including isavuconazole and efinaconazole.