Beijing National Laboratory for Molecular Sciences (BNLMS), CAS Key of Molecular Recognition and Function Institute of Chemistry, Chinese Academy of Sciences, Beijing 100190, China.
Chem Asian J. 2012 Nov;7(11):2569-76. doi: 10.1002/asia.201200674. Epub 2012 Sep 10.
A mechanistic study of the tert-aminocyclization reaction was performed by using DFT calculations and labeling experiments. The results showed that the reaction proceeded through a rate-limiting-, stereospecific-, and suprafacial 1,5-H-transfer pathway, followed by a barrier-less C-C bond formation. The mode of stereocontrol for facial selection could be ruled out owing to the high activation energy of C-N bond rotation. The intrinsic feature of this Lewis acid activation was found to be the activation of the LUMO, as well as an intermediate-stabilization effect. The catalytically active species was believed to be a 1:1 complex of phosphoric acid and MgCl(2), which was stabilized by a H⋅⋅⋅Cl hydrogen bond. The chiral catalytic complex selectively recognizes and activates one of the two helical conformations of substrate A, required for 1,5-suprafacial H-transfer, which dictates the stereoselectivity of the forming products.
通过 DFT 计算和标记实验对叔-氨基环化反应进行了机理研究。结果表明，该反应经过一个限速、立体专一性和超面 1,5-H 转移途径，然后是无势垒的 C-C 键形成。由于 C-N 键旋转的活化能很高，因此可以排除立体选择性的面选择模式。这种路易斯酸活化的固有特征被发现是对 LUMO 的活化，以及中间稳定效应。催化活性物种被认为是磷酸和 MgCl(2)的 1:1 配合物，它通过 H⋅⋅⋅Cl 氢键稳定。手性催化配合物选择性地识别和激活底物 A 的两种螺旋构象之一，这对于 1,5-超面 H 转移是必需的，这决定了形成产物的立体选择性。
