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Nature:形成非对称C-C键的一个新路径

摘要 : 这篇论文报告了用于C-C键的催化非对称合成的一个新的、广泛适用的方法,该方法填补了合成有机化学家“武器库”中一个长期存在的空白。

 这篇论文报告了用于C-C键的催化非对称合成的一个新的、广泛适用的方法,该方法填补了合成有机化学家“武器库”中一个长期存在的空白。

非对称C-C键的形成,会在分子框架构建的同时产生手性分子单一对映异构体,从而为合成设计提供一个战略性的强大选择。

该方法采用外消旋基质和烷基亲核试剂,利用一个由铜催化的动态非对称转变实现C-C键的形成。通过氢金属化从烯烃原位产生了有机金属试剂,并在温和的反应条件下生成了对映异构体浓度很高的产物。

原文链接:Non-stabilized nucleophiles in Cu-catalysed dynamic kinetic asymmetric allylic alkylation

The development of new reactions forming asymmetric carbon–carbon bonds has enabled chemists to synthesize a broad range of important carbon-containing molecules, including pharmaceutical agents, fragrances and polymers1. Most strategies to obtain enantiomerically enriched molecules rely on either generating new stereogenic centres from prochiral substrates or resolving racemic mixtures of enantiomers. An alternative strategy—dynamic kinetic asymmetric transformation—involves the transformation of a racemic starting material into a single enantiomer product, with greater than 50 per cent maximum yield2, 3. The use of stabilized nucleophiles (pKa < 25, wher Ka is the acid dissociation constant) in palladium-catalysed asymmetric allylic alkylation reactions has proved to be extremely versatile in these processes4, 5. Conversely, the use of non-stabilized nucleophiles in such reactions is difficult and remains a key challenge6, 7, 8, 9. Here we report a copper-catalysed dynamic kinetic asymmetric transformation using racemic substrates and alkyl nucleophiles. These nucleophiles have a pKa of ≥50, more than 25 orders of magnitude more basic than the nucleophiles that are typically used in such transformations. Organometallic reagents are generated in situ from alkenes by hydrometallation and give highly enantioenriched products under mild reaction conditions. The method is used to synthesize natural products that possess activity against tuberculosis and leprosy, and an inhibitor of para-aminobenzoate biosynthesis. Mechanistic studies indicate that the reaction proceeds through a rapidly isomerizing intermediate. We anticipate that this approach will be a valuable complement to existing asymmetric catalytic methods.

对应Nature杂志: 2015年01月15日Nature杂志精选

来源: Nature 浏览次数:179

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