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 α‐lithiated ortho ‐, meta ‐, and para ‐fluorostyrene oxides ( 2‐Li , α‐ 5‐Li , and α‐ 6‐Li ) are all configurationally stable in the reaction time scale, whereas α‐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 β‐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 for 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.