From Inorganic/Organic Hybrid Catalysis to Non-Innocent Ligand Catalysis: New Concepts for (Enantioselective) Group 2 Metal Catalysis

人们对更多富含地球的无毒、廉价和价格稳定的金属催化剂的兴趣日益浓厚。我们的团队是有机钙催化的先驱之一，这是一个快速增长的领域，已扩展到一般的第二族金属催化(镁、钙、锶、钡)。与过渡金属不同，第2族金属不容易在氧化态之间切换，也不具有底物活化的d-轨道。这类金属的催化作用纯粹是基于极性反应机理和Lewis酸活化。我们最近发现Lewis酸的活化对未活化底物的转化是至关重要的，并开发了由金属盐(CaI2)和强中性有机碱(Schwesinger碱P4)组成的无机/有机杂化催化剂，用于分子内烯烃氢胺化。用CaI_2取代LCA(L为非反应性螯合二阴离子配体)催化剂体系的初步研究表明，在某些情况下不需要P_4。配体L如预期的那样表现出较高的反应活性，可能作为非无辜配体积极参与催化循环。虽然协同催化的概念在过渡金属催化中已广为人知，但它对第二族金属催化是新的。本研究项目将由两名博士生紧密合作进行，旨在解决第二族催化的两个主要缺点：(I)有限的官能团耐受性(Ii)由于Schlenk平衡L*MR&lt；=&gt；L*2M+MR2(L*=手性配体)而导致的有限的对映选择性控制。我们建议对无机/有机杂化催化剂在烯烃分子内氢胺化反应(金属盐、有机中性碱、底物的变化)中进行广泛的研究，并通过实验方法(中间体分离、核磁共振、动力学)以及从头计算理论对其机理进行深入的研究。我们还对LM/P4(L=未反应的双阴离子旁观配体，M=第2族金属，锌)等催化剂混合物感兴趣。增加L的布朗斯特碱度将导致从杂化催化向协同催化的转变。这些不同催化剂类型之间的边界将通过增加布伦斯特德碱度的体系来探索。由于这两种催化剂都不符合Schlenk平衡，所以对映体选择性催化是一个有趣的应用。我们合成了大量的手性催化剂(L*M和L*M/P4)。这两个概念，无机/有机杂化催化和协同催化，也将在其他转化(烯烃氢磷化和硅氢化)和官能团耐受性方面进行测试。通过从头计算来研究反应机理，这些新的催化体系可能在第二族金属催化方面取得重大突破。

There is an increasing interest in catalysts of more earth-abundant metals that are non-poisonous, cheap and price-stable. Our group is among the pioneers in organocalcium catalysis, a fast-growing area that has been extended to general group 2 metal catalysis (Mg, Ca, Sr, Ba). In contrast to transition metals, the group 2 metals cannot easily switch between oxidation states and do not posses d-orbitals for substrate activation. Catalysis with such metals is purely based on polar reaction mechanisms and Lewis-acid activation. We recently discovered that Lewis-acid activation is crucial for conversion of unactivated substrates and developed inorganic/organic hybrid catalysts that consist of a metal salt (CaI2) and a strong neutral organic base (Schwesinger-base P4) for intramolecular alkene hydroamination. Preliminary investigations on catalyst systems in which CaI2 is replaced for LCa (L = unreactive chelating dianionic ligand) showed that in some cases P4 is not needed. The ligand L showed a higher reactivity as expected and likely takes actively part in the catalytic cycle as a non-innocent ligand. Although the concept of cooperative catalysis is well-known in transition metal catalysis, it is new to group 2 metal catalysis.The research project will be carried out by two PhD students that work closely together and aims to tackle the two main shortcomings of group 2 catalysis: (i) limited functional group tolerance (ii) limited enantioselectivity control due to Schlenk equilibria L*MR <=> L*2M + MR2 (L* = chiral ligand). We propose extensive investigations on inorganic/organic hybrid catalysts in the intramolecular hydroamination of alkenes (variation of the metal salt, the organic neutral base, substrates) and an in-depth study towards the mechanism by experimental methods (isolation of intermediates, NMR, kinetics) as well as by ab initio theory. We are also interested in catalyst mixtures like LM/P4 (L = unreactive, dianionic spectator ligand, M = group 2 metal, Zn). Increasing the Brönsted basicity of L will result in a switch from hybrid catalysis to cooperative catalysis. The border between these different catalyst types will be probed by making systems of increasing Brönsted basicity. As both types of catalysts are not subject to Schlenk equilibria, enantioselective catalysis is an interesting application. We propose syntheses of a large number of chiral catalysts (L*M and L*M/P4). Both concepts, inorganic/organic hybrid catalysis and cooperative catalysis, will also be tested for their scope in other transformations (alkene hydrophosphination and hydrosilylation) and for functional group tolerance. Mechanisms will be studied by ab initio calculations.These new catalytic systems may result in important breakthroughs in group 2 metal catalysis.