英国爱丁堡大学教授Lawrence, Andrew L.团队报道了立体保留对映收敛反应。相关研究成果于2024年4月17日发表在国际顶尖学术期刊《自然—化学》。

对映体会聚反应在当代不对称合成中是突出的，因为它们将外消旋起始材料的两种对映体转化为单一的对映体富集产物，从而避免了与拆分相关的最大50%产率。所有目前已知的对映转化过程都需要，外消旋底物的立体化学信息的损失或部分损失，从而将潜在的底物范围限制在含有不稳定立体生成单元的分子上。

该文中，研究人员提出了一种对映转化反应的替代方法，该方法可以完全保留外消旋底物的构型。如果外消旋起始材料的两种对映体连接在一起，形成一种非内消旋产物的对映体，这种独特的立体经济方法是可能的。使用两种不同的策略对这一概念进行了实验验证：（1）直接不对称耦合方法和（2）多组分方法，其表现出对映纯度的统计放大。因此，对映转化反应需要含有不稳定立体生成单元的底物的既定教条，被证明是不正确的。

附：英文原文

Title: Stereoretentive enantioconvergent reactions

Author: Bennett, Steven H., Bestwick, Jacob S., Demertzidou, Vera P., Jones, David J., Jones, Helen E., Richard, Franois, Homer, Joshua A., Street-Jeakings, Rosie, Tiberia, Andrew F., Lawrence, Andrew L.

Issue&Volume: 2024-04-17

Abstract: Enantioconvergent reactions are pre-eminent in contemporary asymmetric synthesis as they convert both enantiomers of a racemic starting material into a single enantioenriched product, thus avoiding the maximum 50% yield associated with resolutions. All currently known enantioconvergent processes necessitate the loss or partial loss of the racemic substrate’s stereochemical information, thus limiting the potential substrate scope to molecules that contain labile stereogenic units. Here we present an alternative approach to enantioconvergent reactions that can proceed with full retention of the racemic substrate’s configuration. This uniquely stereo-economic approach is possible if the two enantiomers of a racemic starting material are joined together to form one enantiomer of a non-meso product. Experimental validation of this concept is presented using two distinct strategies: (1) a direct asymmetric coupling approach, and (2) a multicomponent approach, which exhibits statistical amplification of enantiopurity. Thus, the established dogma that enantioconvergent reactions require substrates that contain labile stereogenic units is shown to be incorrect.

DOI: 10.1038/s41557-024-01504-1

Source: https://www.nature.com/articles/s41557-024-01504-1