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.
Chemistry. 2010 Aug 23;16(32):9778-88. doi: 10.1002/chem.201000897.
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.
已经研究了一些氟化苯乙烯氧化物锂化的构型稳定性。化学研究表明，在醚类溶剂中，α-锂化邻位、间位和对位氟代苯乙烯氧化物（2-Li、α-5-Li 和 α-6-Li）在反应时间尺度内均具有构型稳定性，而α-锂化邻位、间位和对位三氟甲基苯乙烯氧化物（9-Li、13-Li 和 14-Li）则具有构型不稳定性。旋光活性的氧杂环戊烷基锂 2-Li 和 9-Li 可以立体特异性地生成，并与亲电试剂进行立体特异性淬灭。然后，相应的衍生物成功地与胺进行区域特异性开环反应，得到具有立体定义的季碳醇中心的氟化β-氨基醇，这是药物化学中的有用合成子。通过确定在 THF 中不同时间老化手性富集的有机锂后，亲电猝灭后的对映体比率，通过 Eyring 方程计算了氧杂环戊烷基锂 9-Li、13-Li 和 14-Li 的反转势垒；在 9-Li 的情况下，还确定了活化参数。还讨论了一旦生成，可能导致氧杂环戊烷基锂 9-Li、13-Li 和 14-Li 外消旋化的机制。
