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(NMe2)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.