Department of Chemistry, University of Minnesota-Twin Cities , 207 Pleasant Street SE, Minneapolis, Minnesota 55455, United States.
J Org Chem. 2017 Apr 7;82(7):3721-3726. doi: 10.1021/acs.joc.7b00196. Epub 2017 Mar 15.
We studied key aspects of the mechanism of Pd-catalyzed C-CN bond activation and intramolecular enantioselective alkene cyanoamidation. An Abboud-Abraham-Kamlet-Taft (AAKT) linear solvation energy relationship (LSER) model for enantioselectivity was established. We investigated the impact of Lewis acid (BPh), Lewis base (DMPU), and no additives. BPh additive led to diminished enantioselectivity and differing results in CN crossover experiments, initial rate kinetics, and natural abundance C/C kinetic isotope effect measurements. We propose two catalytic mechanisms to account for our experimental results. We propose that the DMPU/nonadditive pathway passes through a κ-phosphoramidite-stabilized Pd intermediate, resulting in high enantioselectivity. BPh prevents the dissociation of CN, leading to a less rigid κ-phosphoramidite-neutral Pd intermediate.
我们研究了 Pd 催化的 C-CN 键活化和分子内对映选择性烯烃氰基酰胺化反应的关键方面。建立了 Abboud-Abraham-Kamlet-Taft (AAKT) 线性溶剂化能关系 (LSER) 模型来预测对映选择性。我们研究了路易斯酸 (BPh)、路易斯碱 (DMPU) 和无添加剂的影响。BPh 添加剂导致对映选择性降低，并且在 CN 交叉实验、初始速率动力学和自然丰度 C/C 动力学同位素效应测量中得到不同的结果。我们提出了两种催化机制来解释我们的实验结果。我们提出 DMPU/非添加剂途径通过 κ-膦酰胺稳定的 Pd 中间体进行，从而导致高对映选择性。BPh 阻止了 CN 的解离，导致更不稳定的 κ-膦酰胺中性 Pd 中间体。
