手性双氮氧-金属配合物结构、性质及催化Roskamp-Feng反应机理研究

Chiral N,N’-dioxide-metal complexes are efficient and versatile catalysts, which have been successfully applied in a variety of asymmetric reactions. The key of this work is to investigate the structures and electronic properties of metal catalysts formed by coordinating the typical C2-symmetric N,N’-dioxides with different subunits and substitutes to the group IIIB metal ions (e.g. Sc3+,Y3+ and La3+), and explore the relationship between geometrical factor and their activity of N,N’-dioxide-metal complexes. Meanwhile, the key for chirality transfer process by N,N’-dioxide-metal catalysts will be understood. The universal rules involving in the interaction between N,N’-dioxides and substrates (carbonyl and diazoester) as well as essence and features of catalysis are studied. The matching relationship between reactants’ structures as well electronic properties and catalysts are explored by investigating mechanism of Roskamp-Feng reaction. The influence of catalysts on group shift order, chemselectivity and enantioselectivity of products will also be explored. Additionally, effect of solvent and additives on the interaction between ligand, metal ions centre and substrate will be considered. Furthermore, new chiral ligands and N,N’-dioxide-metal catalysts for Roskamp-Feng reaction will be designed and synthesized to provide useful hints for developing high efficiency chiral catalysts for asymmetric synthesis.

手性双氮氧－金属配合物是一类高效、应用范围很广的金属配合物催化剂，已在多类不对称催化反应中获得优异结果。本项目拟采用量子化学计算方法，研究含不同取代基及分子骨架的典型手性C2对称双氮氧配体与第IIIB族金属离子(Sc3+、Y3+、La3+)形成的配合物的空间结构和电子性质，揭示双氮氧－金属配合物结构与活性之间的关系及手性传递的关键。通过Roskamp-Feng反应机理研究，探明反应底物（羰基化合物及重氮酯等）与配合物的相互作用规律及该类催化剂作用本质和特点，揭示反应底物的电子效应和空间结构与催化剂之间的匹配关系，总结出催化剂对基团迁移、产物选择性控制及反应对映选择性影响的规律。进一步考察溶剂及添加剂对氮氧偶极、反应底物与金属中心的配位作用的影响。在此基础上进行新型双氮氧配体及金属配合物的设计及合成，并将其用于不对称Roskamp反应实验研究，为进一步研制高效不对称合成催化剂提供知识积累。

手性双氮氧－金属配合物是一类高效、应用范围很广的金属配合物催化剂，已在多类不对称催化反应中获得优异结果。本项目采用量子化学计算方法，研究了Roskamp-Feng反应机理，揭示了手性双氮氧-Sc(III)催化剂在该反应中对立体选择性及基团迁移的影响；研究了含Zn2+, Sc3+, Mg2+, Ni2+等金属中心催化剂作用下羰基-烯、Diels-Alder (杂Diels-Alder)、[2+2]环化、靛红的直接Aldol 反应、Friedel-Crafts烷基化、Michael加成及环丙烷化等反应的机理，从分子水平上探明了上述反应中关键中间物种 (即：过渡态和中间体) 的结构及其在势能面上的演变规律；确定了可能的反应路径并获得了相应的能量曲线；揭示了反应的手性控制步骤及速率控制步骤，获得了催化循环中催化剂转化频率(TOF)；初步明确了催化剂对底物的活化及手性传递的关键结构单元；阐明了底物-底物、底物-配体之间弱相互作用(如：pai-pai 堆积)对反应选择性的影响；初步明确了抗衡离子在催化反应中稳定关键中间体、参与质子转移、调变金属中心Lewis酸性等作用。在此基础上对配合物进行结构修饰及新的设计，并预测了选择性结果。通过理论模拟，从分子水平上探明了手性双氮氧-金属配合物结在不对称反应中催化作用的本质及特点，获得配合物催化剂电子效应和空间结构与其反应活性及对映选择性关系的规律，为进一步研制高效不对称合成催化剂提供知识积累。