García Rosa, Seco José M, Vázquez Saulo A, Quiñoá Emilio, Riguera Ricardo
Departamento de Química Orgánica, Facultad de Química, and Unidad de RMN de Biomoléculas Asociada al CSIC, Universidad de Santiago de Compostela, E-15782 Santiago de Compostela, Spain.
J Org Chem. 2006 Feb 3;71(3):1119-30. doi: 10.1021/jo0522207.
The assignment of the absolute configuration of alpha-chiral primary amines by complexation of their MPA derivatives with Ba2+ and NMR analysis of the changes generated is presented. All that is required is (a) the derivatization of the amine of unknown configuration with one enantiomer of the auxiliary reagent (MPA), either (R) or (S)-alpha-methoxyphenylacetic acid, (b) the recording of the 1H NMR spectrum of the resulting amide in MeCN-d3, (c) the addition of Ba(ClO4)2 to the NMR tube, and (d) the recording of a second spectrum after a few minutes of shaking. The above steps take a few minutes and are followed by an analysis of the shifts (measured as Deltadelta(Ba)) produced on the L1 and L2 substituents of the amine by the addition of Ba2+ and their comparison with those expected from the conformational changes produced by the complexation. The conformational changes initiated by complexation have been subjected to NMR and CD studies, which showed that the formation of the complex shifts the equilibrium from an antiperiplanar (AP) to a synperiplanar (SP) form, leading to an increase of the shielding by the phenyl group of MPA of the substituent of the amine located on the same side. In addition, theoretical calculations [density functional theory (DFT)] provide further support for the formation, structure, and stability of the complexes. The general applicability of this method and the trustworthiness of the resulting configurational assignment were guaranteed with a series of amines of known absolute configuration and varied structures, used as test compounds. The method proposed is simple, fast, and inexpensive, and it requires a very small amount of sample, only one derivatization, and the recording of just two 1H NMR spectra at room temperature. A graphical guide to simplify the application of this method is included.
介绍了通过α-手性伯胺的MPA衍生物与Ba²⁺络合以及对所产生变化进行核磁共振（NMR）分析来确定其绝对构型的方法。所需的全部操作是：（a）用辅助试剂（MPA）的一种对映体，即（R）或（S）-α-甲氧基苯乙酸，对构型未知的胺进行衍生化；（b）记录所得酰胺在MeCN-d₃中的¹H NMR谱；（c）向NMR管中加入Ba(ClO₄)₂；（d）摇晃几分钟后记录第二个谱。上述步骤只需几分钟，随后分析加入Ba²⁺后胺的L1和L2取代基上产生的位移（以Δδ(Ba)表示），并将其与络合产生的构象变化所预期的位移进行比较。通过NMR和圆二色性（CD）研究对络合引发的构象变化进行了研究，结果表明络合物的形成使平衡从反式共平面（AP）形式转变为顺式共平面（SP）形式，导致位于同一侧的胺取代基上的MPA苯基屏蔽增加。此外，理论计算[密度泛函理论（DFT）]为络合物的形成、结构和稳定性提供了进一步支持。使用一系列已知绝对构型且结构各异的胺作为测试化合物，保证了该方法的普遍适用性以及所得构型归属的可信度。所提出的方法简单、快速且成本低廉，仅需极少量样品，只需一次衍生化，且在室温下只需记录两个¹H NMR谱。文中还包含一个简化该方法应用的图形指南。
