Department of Chemistry, Brown University, Providence, Rhode Island 02912, USA.
J Org Chem. 2011 Dec 16;76(24):10279-85. doi: 10.1021/jo201817k. Epub 2011 Nov 10.
Isocyanoacetates are uniquely reactive compounds characterized by an ambivalent isocyano functional group and an enolizable α-carbon. It is widely believed that chiral α-substituted isocyanoacetates are configurationally unstable in some synthetically useful isocyanide-based multicomponent reactions. Herein, we demonstrate that chiral isocyanoacetates can be used with minimal to negligible epimerization in a variety of canonical Ugi four-component condensations as well as Joullié-Ugi three-component condensations, reactions that are particularly useful for constructing complex peptide structures in a single synthetic operation.
异氰基乙酸酯是一类具有独特反应活性的化合物，其特征为一个双官能团的异氰基和一个可烯醇化的α-碳。人们普遍认为，手性α-取代的异氰基乙酸酯在一些合成上有用的基于异氰化物的多组分反应中，构型是不稳定的。在此，我们证明手性异氰基乙酸酯可以在多种典型的 Ugi 四组分缩合反应以及 Joullié-Ugi 三组分缩合反应中，以最小至可忽略不计的外消旋化来使用，这些反应特别适用于在单个合成操作中构建复杂的肽结构。
