Sierra Miguel A, Pellico Daniel, Gómez-Gallego Mar, Mancheño María José, Torres Rosario
Departamento de Química Organica and Laboratorio de Difracción de Rayos X, Facultad de Química, Universidad Complutense, 28040 Madrid, Spain.
J Org Chem. 2006 Nov 10;71(23):8787-93. doi: 10.1021/jo0614689.
The easily available macrocyclic diimines 4-7 can be stereoselectively transformed to macrocyclic bis-beta-amino acids 13-17, macrocyclic bisazetidines 18-20, and macrocyclic bisamides 21 and 22 by means of the corresponding bis-beta-lactam scaffolds 8-12. These key intermediates are available through standard Staudinger reaction and obtained as the cis-cis diastereomers, exclusively. An interesting relation between the proximity of the reactive C=N bonds and the selectivity in the formation of the bis-beta-lactams 8-12 is observed. Thus, diimine 4 leads to low selectivities, producing a 1:1 mixture of cis-syn-cis and cis-anti-cis diastereomers, while diimines 5-7 having the diimine sites more separated lead almost exclusively to the cis-anti-cis diastereomers. The stereochemistry of all the products was unambiguously assigned by X-ray diffraction analysis of compounds cis-syn-cis 8 and cis-anti-cis 12-Co2CO6 complex.
易于获得的大环二亚胺4 - 7可以通过相应的双β-内酰胺支架8 - 12立体选择性地转化为大环双β-氨基酸13 - 17、大环双氮杂环丁烷18 - 20以及大环双酰胺21和22。这些关键中间体可通过标准施陶丁格反应获得，并且仅以顺式 - 顺式非对映异构体形式得到。观察到反应性C=N键的接近程度与双β-内酰胺8 - 12形成过程中的选择性之间存在有趣的关系。因此，二亚胺4导致选择性较低，生成顺式 - 顺式 - 顺式和顺式 - 反式 - 顺式非对映异构体的1:1混合物，而二亚胺位点间隔更远的二亚胺5 - 7几乎 exclusively生成顺式 - 反式 - 顺式非对映异构体。通过对顺式 - 顺式 - 顺式8和顺式 - 反式 - 顺式12 - Co₂(CO)₆配合物进行X射线衍射分析，明确确定了所有产物的立体化学结构。
