A unique approach to aldol products for the creation of all-carbon quaternary stereocentres
A unique approach to aldol products for the creation of all-carbon quaternary stereocentres
复制标题
DOI：
10.1038/nchem.131
复制
发表时间：
2009-05-01
期刊：
影响因子：
21.8
通讯作者：
Marek, Ilan
中科院分区：
文献类型：
--
作者：
Das, Jaya Prakash;Chechik, Helena;Marek, Ilan
在不对称合成所面临的挑战中，选择性构建四元立体中心，特别是那些带有全碳取代基的中心，显得尤为突出。醛醇反应有可能产生这样的立体中心，但是，尽管在这一领域取得了许多进展，一个高度选择性和高效的过程仍然是难以捉摸的。在这里，我们表明，通过选择一种替代的反合成方法，这种产品可以以高度选择性的方式制备。通过连续加成几种有机金属衍生物，制备了烯丙基锌试剂，并在醛的基础上加成醛型产品。一锅操作包括三个新的碳-碳键的构建和全碳季立体中心的形成。该反应的产物可以进行下游改性，并且该过程应该在天然产物合成和药物发现领域找到应用。
Among the challenges facing asymmetric synthesis the selective construction of quaternary stereogenic centres, particularly those bearing all-carbon substituents, stands out. The aldol reaction has the potential to create such stereocentres, but, despite the many advances in this field, a highly selective and efficient procedure has remained elusive. Here we show that, by choosing an alternative retrosynthetic approach, such products can be prepared in a highly selective fashion. Through the consecutive addition of several organometallic derivatives, an allylzinc reagent is prepared and, on addition to an aldehyde, an aldol-type product is created. The one-pot operation involves the construction of three new carbon-carbon bonds and the formation of an all-carbon quaternary stereocentre. The products of the reaction are amenable to downstream modification, and the procedure should find applications in the fields of natural product synthesis and drug discovery.