Optimisation of a lithium magnesiate for use in the non-cryogenic asymmetric deprotonation of prochiral ketones.
Optimisation of a lithium magnesiate for use in the non-cryogenic asymmetric deprotonation of prochiral ketones.
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DOI：
10.1039/c3dt52577e
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发表时间：
2014-01
影响因子：
4
通讯作者：
J. Francos;Silvia Zaragoza-Calero;C. T. O’Hara
中科院分区：
文献类型：
--
作者：
J. Francos;Silvia Zaragoza-Calero;C. T. O’Hara
研究了镁酸锂是否是4-烷基环己酮对映选择性去质子化的可行候选物。利用市售手性胺(+)-双[(R)-1-苯乙基]胺（2-H）诱导对映体选择。将其转化为锂盐并与(n)Bu2Mg结合，在20℃下观察到4-叔丁基环己酮（相对于单金属锂酰胺）的对映选择性去质子化。为了进一步优化反应，在锂酰胺中加入了不同的添加剂。在0℃条件下，加入（Me3SiCH2）2Mg （er pro-S 74: 26）和（Me3SiCH2）2Mn （er pro-S 72: 28）的脱质子反应效果最好，因此在剩余的研究中使用了镁酸锂“LiMg(2)(CH2SiMe3)2”。该反应的最佳溶剂为四氢呋喃。对D8-THF溶液“LiMg(2)(CH2SiMe3)2”的核磁共振光谱研究表明，这种单酰胺双烷基物种与双酰胺单烷基化合物（和三烷基镁酸锂）处于平衡状态。当使用真正的二酰胺镁酸锂溶液时，脱质子结果与“LiMg(2)(CH2SiMe3)2”的脱质子结果基本相同。将LiCl加入到“LiMg(2)(CH2SiMe3)2”中，在0°C时的er提高到81:19。在-78℃时，产率高，比为93:7。该含锂碱成功地使其它4-烷基环己酮去质子化。
A study has been conducted to determine whether lithium magnesiates are feasible candidates for the enantioselective deprotonation of 4-alkylcyclohexanones. The commercially available chiral amine (+)-bis[(R)-1-phenylethyl]amine (2-H) was utilised to induce enantioselection. When transformed to its lithium salt and combined with (n)Bu2Mg, improved enantioselective deprotonation of 4-tert-butylcyclohexanone (with respect to the monometallic lithium amide) at 20 °C was observed. In an attempt to optimise the reaction further, different additives were added to the lithium amide. The best performing deprotonations at 0 °C were those in which (Me3SiCH2)2Mg (er pro-S 74 : 26) and (Me3SiCH2)2Mn (er pro-S 72 : 28) were added, hence the lithium magnesiate "LiMg(2)(CH2SiMe3)2" was used in the remainder of the study. The optimum solvent for the reaction was found to be THF. NMR spectroscopic studies of a D8-THF solution of "LiMg(2)(CH2SiMe3)2" appear to show that this mono-amide bis-alkyl species is in equilibrium with a bis-amide mono-alkyl compound (and a tris-alkyl lithium magnesiate). When a genuine bis-amide lithium magnesiate solution is used, the deprotonation results were essentially identical to those obtained for "LiMg(2)(CH2SiMe3)2". By adding LiCl to "LiMg(2)(CH2SiMe3)2" the er at 0 °C improved to 81 : 19. At -78 °C good yields and an er of 93 : 7 were obtained. This LiCl-containing base was used to successfully deprotonate other 4-alkylcyclohexanones.