金属镁催化高张力三元环系的不对称开环反应

Magnesium catalyzed asymmetric ring-opening reactions of high-strained three membered cyclic systems

利用储量丰富、廉价易得、低污染元素作为催化资源构筑重要立体化学结构具有重要研究意义.含杂原子的手性化合物,例如手性氨基醇类、手性酰胺类、取代四唑类,吲哚衍生物、吡咯烷衍生物等结构单元广泛存在于天然产物中,并且在药物研发过程中具有重要的价值.高效构建以上结构单元一直以来都是化学、生命科学、药学科研工作者重点关注的问题.三元环系结构具有较大的环张力,导致其稳定性低,因此具有较高的反应活性.重要三元环系化合物主要包括:环氧乙烷(oxirane)、氮杂环丙烷(aziridine)以及供体-受体环丙烷(donor-acceptor,D-A cyclopropane),这些结构的不对称开环反应成为构建上述重要结构骨架的合成砌块.值得注意的是,近些年在金属催化剂催化策略下,经三元环类化合物的不对称开环反应高效构建高对映选择性的含杂原子结构片段及杂环骨架受到了广泛的研究关注.同时,伴随了多种催化策略的发展.本文主要综述了近年基于金属镁催化策略的三元环类化合物不对称开环反应研究进展,讨论了基于不同类型亲核试剂及催化条件下的开环反应途径和方法,阐述了反应的相关应用,探讨了部分机理过程.最后,对三元环类化合物不对称开环反应当前的发展状况进行了总结,并在此基础上进行了相关展望.

It is of great research significance to construct important three-dimensional skeletons by employing abundant, inexpensive,and easily accessible elements as catalytic resources. Magnesium (Mg) is a usual, non-toxic, readily available andrecyclable alkaline earth metal, which is highly stored in the earth’s crust. So the investigation of the catalytic strategy byusing magnesium element is highly attractive and with highly practical value, on consideration of the problem ofincreasingly prominent shortage of metal resources and the intrinsic demand of sustainable chemistry. In recent years,tremendous endeavors and advances have been made on the development of effective catalysts with abundant metalresources such as magnesium for construction of important three-dimensional skeletons with high level ofenantioselectivities. In the context of organic synthesis, chiral compounds containing heteroatoms, such as chiral aminoalcohols, chiral amides, substituted tetrazoles, indole derivatives, pyrrolidine derivatives and relative structural units, arewidely found in natural products or pharmaceutical compounds, have drawn intense research interest in organic synthesis,life sciences and the discovery of drugs. The three-membered ring structure featured in strong ring tension and alwaysresulted in low stability, so it has higher reactivity compared with other common cyclic ring systems. Important ternarycyclic compounds mainly include: Oxiranes, aziridines, and donor-acceptor cyclopropanes. The desymmetrization orasymmetric ring-opening reaction of these ring systems becomes a powerful synthetic tool for effective construction of theabove important chiral skeletons. Meanwhile, it is worth noting that in recent years, the efficient construction ofheteroatom-containing structural fragments and heterocyclic skeletons with high enantioselectivity through asymmetricring-opening reactions of ternary cyclic compounds under metal-catalyzed strategies has received extensive researchattention. A variety of attractive catalytic strategies were rapidly developed during the research progress. In this reviewpaper, on the basis of our recent years work, the research progress of asymmetric ring-opening reactions of three-memberedring systems based on magnesium catalysis strategy are briefly introduced.This review includes three part: (1) The ring-opening reaction of oxiranes, which mainly include the desymmetrizationreaction of oxiranes with amine compounds under in situ generated magnesium catalyst. (2) The ring-opening reaction ofaziridines, several heteroatom and carbon based nucleophiles are well developed in the reaction under typical magnesiumcatalytic strategies. (3) The ring-opening reaction as well as asymmetric cyclization reaction of donor-acceptorcyclopropanes by employing magnesium catalysis are also discussed. These high tension compounds with different typesof nucleophiles and relative magnesium catalytic methods are applied for building types of highly important chiralskeletons. Moreover, the possible catalytic mechanism is also shown in some cases, which might be useful forunderstanding the relative magnesium catalytic strategies. Finally, we have summarized the current stage of theseasymmetric ring-opening reactions, and provided brief outlook of this research field. Novel developments are expected toarise from designing of new ligands and assembly strategies for developing novel magnesium catalysts, and thus newactivation models can be established to conquer more catalytic ring-opening reactions of these high tension compounds.Furthermore, we foresee the combinational or synergistic use of magnesium catalysts with other catalytic strategies,including organocatalysts or transition metals, as well as merging with photo- or electro-catalytic protocols will arise tounlock novel methods for achieving new ring-opening reactions of oxiranes, aziridines, and donor-acceptor cyclopropanes.These endeavors will be also helpful for development of innovative and structure-creative magnesium catalysts and greatlyexpanding the synthetic toolbox of modern chemists.