Fluorination of Organic Compounds Using Molecular Fluorine and Application to Synthesis of Fluorine Containing Biologically Active Compounds

Abstract

In order to perform selective fluorination using molecular fluorine, mechanistic studies using ab initio MO calculation were carried out. As a result, it was confirmed that both fluorine addition to ethylene and fluorine substitution of methane are electrophilic reactions. These studies suggested that bicyclo [2.2.1] hept-2-ene derivatives would be suitable fluorinating substrates because they have tertiary hydrogens with somewhat lower p-character than sp³ and a more activated double bond. As expected, addition of molecular fluorine to the bicyclo [2.2.1] hept-2-ene derivatives having electronegative substituents on the ethano bridge was found to give exo, exo-difluoro adducts selectively. The difluoro adducts derived from 2-azabicyclo [2.2. 1] kept-5-en-3-one or 7-oxabicyclo [2.2. 1] hept-2-ene derivatives were converted to the difluorinated carbocyclic nucleosides or ribofuranosides. Novel α-fluorination of alkyl phenyl sulfoxides by molecular fluorine was also developed and applied to the synthesis of cis-2-fluorocyclopropane-1-carboxylic acid and fluorine substituted 1-aminocyclopropane-l-carboxylic acid derivatives.