Taxol Total Synthesis: Preparation of a Chiral Ring A Moiety via Biomimetic Cyclization and Evaluation of a Tandem Nitrile Oxide Strategy for Rings B/C

Article abstract of DOI:10.1021/jo00127a028

A fully functionalized taxol ring A moiety 7 was efficiently prepared via biomimetic cation-olefin cyclization of chiral geraniol epoxide 2b using SnCl4 in toluene.Fractional crystallization provided endo-3 (50percent yield from 2b) that was converted to aldehyde 5 by stereospecific epoxidation, secondary alcohol protection, and PCC oxidation.NaOMe-mediated ring opening secured enal 6.Addition of lithium dithianne to 6 at low temperature provided 7 as the sole product in good yield.A tandem nitrile oxide cycloaddition strategy for creating the remaining B/C carbocycles as well as key functionality present in both rings was validated, in part, by cyclization of 14 to tricyclic isoxazoline 15.