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

人们对无毒、廉价和价格稳定的地球上更丰富的金属催化剂越来越感兴趣。我们的团队是有机钙催化领域的先驱之一，这是一个快速发展的领域，已扩展到一般的第2族金属催化（Mg，Ca，Sr，Ba）。与过渡金属相反，第2族金属不能容易地在氧化态之间切换，并且不具有用于衬底活化的双轨道。用这样的金属催化纯粹基于极性反应机理和路易斯酸活化。我们最近发现路易斯酸活化对于未活化底物的转化是至关重要的，并开发了由金属盐（CaI 2）和强中性有机碱（Schwesinger碱P4）组成的无机/有机混合催化剂用于分子内烯烃加氢胺化。对其中CaI 2被LCa（L =非反应性螯合双阴离子配体）取代的催化剂体系的初步研究表明，在某些情况下不需要P4。配体L表现出更高的反应活性，并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是众所周知的，但对于第2族金属催化来说却是新的。该研究项目将由两名博士生密切合作进行，旨在解决第2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 <=> L* 2 M + MR 2（L* =手性配体），有限的对映选择性控制。我们提出了广泛的调查无机/有机杂化催化剂在分子内氢胺化的烯烃（金属盐，有机中性碱，底物的变化）和深入的研究机制，通过实验方法（分离的中间体，NMR，动力学）以及从头算理论。我们还对催化剂混合物如LM/P4（L =非反应性的双阴离子旁观配体，M =第2族金属，Zn）感兴趣。增加L的布朗斯台德碱度将导致从混合催化到协同催化的转变。这些不同类型的催化剂之间的边界将通过制造增加布朗斯台德碱度的系统来探索。由于这两种类型的催化剂不受Schlenk平衡，对映选择性催化是一个有趣的应用。我们提出了大量的手性催化剂（L*M和L*M/P4）的合成。这两个概念，无机/有机混合催化和协同催化，也将测试其在其他转化（烯烃氢化膦化和氢化硅烷化）和官能团的耐受性的范围。这些新的催化体系可能会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.