Asymmetric Synthesis of Triazole Antifungal Agents Enabled by an Upgraded Strategy for the Key Epoxide Intermediate.

A streamlined and efficient approach to the key epoxide intermediate for the asymmetric synthesis of triazole antifungal agents is presented. This synthesis highlights a P(NMe 2 ) 3 -mediated nonylidic olefination of α-keto ester, ensuring the exclusive formation of the requisite ( Z )-alkene, followed by a highly enantioselective Jacobsen epoxidation to establish the two vicinal stereocenters in a single step. The versatility of this strategy is exemplified through the efficient synthesis of efinaconazole and ravuconazole.