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 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.
Capriati
Vito
V
Dipartimento Farmaco-Chimico, Università di Bari A. Moro, Consorzio Interuniversitario Nazionale Metodologie e Processi Innovativi di Sintesi C.I.N.M.P.I.S. Via E. Orabona 4, 70125 Bari, Italy. capriati@farmchim.uniba.it
Florio
Saverio
S
Perna
Filippo Maria
FM
Salomone
Antonio
A
D000605:Amino Alcohols / Q000737:chemistry*; D004852:Epoxy Compounds / Q000737:chemistry*; D054879:Halogenation; D007700:Kinetics; D008094:Lithium / Q000737:chemistry*; D015394:Molecular Structure; D009942:Organometallic Compounds / Q000737:chemistry*; D013237:Stereoisomerism; D013343:Styrenes / Q000737:chemistry*
D000605:Amino Alcohols; D004852:Epoxy Compounds; D009942:Organometallic Compounds; D013343:Styrenes; D008094:Lithium; C013690:styrene oxide