Lithiated Fluorinated Styrene Oxides: Configurational Stability, Synthetic Applications, and Mechanistic Insight

The configurational stability of some lithiated fluorinated styrene oxides has been investigated Chemical studies have shown that in ethereal solvents alpha-lithiated ortho-. meta-. and para-fluorostyrene oxides (2-Li. alpha-5-Li. and alpha-6-Li) are all configurationally stable in the reaction time scale, whereas alpha-lithiated ortho-. meta-. and para-trifluoromethylstyrene oxides (9-Li. 13-Li. and 14-Li) are configurationally unstable Optically active oxiranyllithiums 2-Li and 9-Li. could be stereospecifically generated and quenched with electrophiles The corresponding derivatives were then successfully subjected to regiospecific ring-opening reactions with amines to give fluorinated beta-amino alcohols with a stereodefined quaternary carbinol center. which are useful synthons in medicinal chemistry The barriers of inversion have been calculated (Eyring equation) for oxiranyllithiums 9-Li. 13-Li, and 14-Li by determining the enantiomeric ratios after electrophilic quenching on aging the enantioenriched organolithium fen different times in THF. in the case of 9-Li. activation parameters have also been determined Mechanisms that may be responsible of the racemization oxiranyllithiums 9-Li. 13-Li. and 14-Li undergo once generated are also discussed