Alcaide Benito, Almendros Pedro, Quirós M Teresa, Lázaro Carlos, Torres M Rosario
Grupo de Lactamas y Heterociclos Bioactivos, Departamento de Química Orgánica I, Unidad Asociada al CSIC, Facultad de Química, Universidad Complutense de Madrid , 28040-Madrid, Spain.
J Org Chem. 2014 Jul 3;79(13):6244-55. doi: 10.1021/jo500993x. Epub 2014 Jun 16.
A straightforward metal-mediated method for the synthesis of bis(dihydrofuryl) cyclophane scaffolds from carbonyl compounds has been developed. The combination of the dihydrofuran moiety with different heterocycles such as β-lactams and sugars allows high levels of skeletal diversity. The process comprises indium-promoted one-pot carbonyl bis(allenylation) and gold- or palladium-catalyzed double cyclization in the resulting bis(allenols), followed by selective ruthenium-catalyzed macrocyclization. In some cases, the method has been successfully applied to the synthesis of the challenging Z-isomers. The E- versus Z-stereochemistry of the metathesis-formed double bonds could not be assigned taking into consideration the usual coupling constants criteria, but a diagnostic based on the chemical shifts of the two olefinic protons located at the macrocyclic double bond was established.
已开发出一种直接的金属介导方法，用于从羰基化合物合成双（二氢呋喃基）环芳骨架。二氢呋喃部分与不同杂环（如β-内酰胺和糖类）的结合可实现高水平的骨架多样性。该过程包括铟促进的一锅法羰基双（烯丙基化）以及所得双（烯丙醇）中金或钯催化的双环化反应，随后是选择性钌催化的大环化反应。在某些情况下，该方法已成功应用于具有挑战性的Z-异构体的合成。考虑到通常的耦合常数标准，无法确定复分解形成的双键的E-与Z-立体化学，但基于位于大环双键处的两个烯属质子的化学位移建立了一种诊断方法。
