Asymmetric Synthesis of Chiral Organofluorine Compounds: Use of Nonracemic Fluoroiodoacetic Acid as a Practical Electrophile and Its Application to the Synthesis of Monofluoro Hydroxyethylene Dipeptide Isosteres within a Novel Series of HIV Protease

摘要

Two strategies are developed for the construction of monofluorinated stereogenic center. In the first, the enolate of a chiral fluoroacetamide is used as a nucleophile towards a nitroolefin Michael acceptor. By choosing the chirality of teh starting material and separating syn, anti diastereomers, all four optical antipodes can potentially be accessed (Scheme 1). In the second approach, fluoroiodoacetic acid is prepared that resolved. The individual enantiomers were found to undergo reaction with chiral carbon nucleophiles with inversion of configuration to produce adducts with both high enantioselectivity and diastereoselectivity (Scheme 2).