Enantioselective Conjugate Addition Catalyzed by a Copper Phosphoramidite Complex: Computational and Experimental Exploration of Asymmetric Induction
Enantioselective Conjugate Addition Catalyzed by a Copper Phosphoramidite Complex: Computational and Experimental Exploration of Asymmetric Induction
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DOI：
10.1021/acscatal.7b01453
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发表时间：
2017-10-01
期刊：
影响因子：
12.9
通讯作者：
Fletcher, Stephen P.
中科院分区：
文献类型：
--
作者：
Ardkhean, Ruchuta;Roth, Philippe M. C.;Fletcher, Stephen P.
通过实验和计算研究，确定了亚磷酰胺配体在烷基锆物种与环烯酮不对称共轭加成反应中的立体化学作用。模块配体的系统的合成变化确定了联苯酚主链的构型负责绝对的立体控制，而氨基取代基的调制导致不对称诱导水平的显著变化。手性氨基取代基不需要对映体选择性，这导致了一类新的基于非手性胺的容易合成的亚磷酰胺的发现，它们提供了与Feringa配体同等水平的选择性。对于这类配体，芳香酰胺基团的长度与实验确定的对映选择性之间存在线性关系，经过优化后，这类配体的选择性高(高达94%的ee)，带有萘基而不是苯基。通过核磁共振和密度泛函理论研究了空间相似芳香族取代基的电子效应，结果表明富含电子的芳基具有较好的铜配位能力。金属中心和芳香族基团之间的相互作用导致了这种增强的亲和力，并导致了更紧密的配位过渡结构，从而产生了主要的对映体。这些研究说明了使用参数定量结构选择性关系来生成不对称诱导和催化剂结构的机理模型，这些模型可以通过实验和计算来进一步探索。这种综合的方法导致了手性配体的合理修饰，以实现更高水平的选择性。
The stereochemical role of the phosphoramidite ligand in the asymmetric conjugate addition of alkylzirconium species to cyclic enones has been established through experimental and computational studies. Systematic, synthetic variation of the modular ligand established that the configuration of the binaphthol backbone is responsible for absolute stereo control, whereas modulation of the amido substituents leads to dramatic variations in the level of asymmetric induction. Chiral amido substituents are not required for enantioselectivity, leading to the discovery of a new family of easily synthesized phosphoramidites based on achiral amines that deliver equal levels of selectivity to Feringa's ligand. A linear correlation between the length of the aromatic amido groups and experimentally determined enantioselectivity was uncovered for this class of ligand, which, following an optimization, led to highly selective ligands (up to 94% ee) with naphthyl rather than phenyl groups. An electronic effect of sterically similar aromatic substituents was investigated through NMR and DFT studies, showing that electron-rich aryl groups allow better Cu coordination. An interaction between the metal center and an aromatic group is responsible for this enhanced affinity and leads to a more tightly coordinated transition structure, leading to the major enantiomer. These studies illustrate the use of parametric quantitative structure selectivity relationships to generate mechanistic models for asymmetric induction and catalyst structures that may be further probed by experiment and computation. This integrated approach leads to the rational modification of chiral ligands to achieve enhanced levels of selectivity.