Claeys Diederica D, Moonen Kristof, Roman Bart I, Nemykin Victor N, Zhdankin Viktor V, Waroquier Michel, Van Speybroeck Veronique, Stevens Christian V
Research Group SynBioC, Department of Organic Chemistry, Faculty of Bioscience Engineering, Ghent University, Coupure links 653, B-9000 Ghent, Belgium.
J Org Chem. 2008 Oct 17;73(20):7921-7. doi: 10.1021/jo801138s. Epub 2008 Sep 12.
During the synthesis of tricyclic phosphonopyrrolidines via intramolecular Diels-Alder reactions of 1-acylamino(furan-2-yl)methyl phosphonates, two isomers are formed in most cases. The presence of a short three-atom tether together with spectroscopic data, including difference NOE, revealed that the cycloaddition occurred exo, but the phosphonate substituent on the tether had an exo or endo orientation. This was confirmed via X-ray analysis. A thermodynamic preference for the product with the phosphonate function in the endo position was observed experimentally and was confirmed theoretically. Density functional theory methods and several high-level post Hartree-Fock procedures were used to rationalize the observed isomer ratio of the IMDAF-reactions. This was done for two different types of reagents: with the activating carbonyl group in the tether or as a substituent on the tether. For the first type of molecules there is a large steric hindrance of the bulky tether substituents that disfavors the exo-isomer. In the latter case, there was a very small energy difference between the transition states causing a mixture of epimers being formed.
在通过1-酰氨基（呋喃-2-基）甲基膦酸酯的分子内狄尔斯-阿尔德反应合成三环膦酰基吡咯烷的过程中，大多数情况下会形成两种异构体。短的三原子连接链的存在以及包括差异核Overhauser效应（difference NOE）在内的光谱数据表明，环加成反应是外型发生的，但连接链上的膦酸酯取代基具有外型或内型取向。这通过X射线分析得到了证实。实验观察到并从理论上证实了内型位置具有膦酸酯官能团的产物具有热力学优势。采用密度泛函理论方法和几种高级后哈特里-福克程序来解释分子内狄尔斯-阿尔德反应（IMDAF）中观察到的异构体比例。针对两种不同类型的试剂进行了此项工作：连接链上带有活化羰基或作为连接链上的取代基。对于第一种类型的分子，庞大的连接链取代基存在较大的空间位阻，不利于外型异构体的形成。在后一种情况下，过渡态之间的能量差非常小，导致形成了差向异构体的混合物。
