Concise Synthesis of Optically Active Oxirane Precursors for the Preparation of Triazole Antifungals Using the Friedel-Crafts Reaction of (S)-2-Tosyloxypropionyl Chloride

Article abstract of DOI:10.1016/0040-4039(91)80530-J

Optically active epoxide (2R,3S)-4, a key intermediate for the preparation of triazole antifungal agents (4R,5R)-1 and (2R,3R)-2 (X = 2,4-F2), was synthesized.The Friedel-Crafts reaction between the (S)-lactic acid derivative (S)-10 and m-difluorobenzene gave the (R)-2-chloropropiophenone derivative (R)-11, which was converted into (2R,3R)-18 via Peterson olefination, stereoselective osmium(VIII) oxide oxidation, and mesylation.Treatment of (2R,3R)-18 with sodium triazolide gave (2R,3S)-4.Similarly, the 4-chlorophenyl analog (2R,3S)-4' was prepared.