新型 ate-络合物的设计、合成与反应研究

Ate-complex is a class of unique metal reagents derived from the classic metal reagents through their combination with Lewis acid. The manners of their preparation, the ratios of metal reagent to Lewis acid, their functions and reactions were rather limited in literature reports. This project aims to enrich the chemistry of ate-complexes regarding their species, preparation, the ratios of metal reagent to Lewis, their functions and reactions. A variety of new ate-complexes will be designed and prepared by varying the central atoms and ligands of Lewis acids with the use of sub-stoichiometric or catalytic amount of Lewis acid, and thus the reactions such as Negishi, Stille, Suzuki coupling reactions using sub-stoichiometric or catalytic amount of Zr, Al, In, Zn, Sn, B, etc. compounds as well as other highly selective reactions will be established. Besides, the new types of mixed ate-complexes containing two different alkyl groups or one alkyl group with one dialkylamino group will be designed and prepared, and their multi-functions and reactions will be also explored. Furthermore, taking advantage of the functions and reactions of these new ate-complexes, the novel syntheses of heterocycles and highly stereoselective reactions will be developed as well. Finally, these achievements will be applied to the new total syntheses of pharmaceutically active compounds or natural products..This project will diversify the types of ate-complexes and greatly expand their preparations and the related reaction scopes. It will also help in further understanding the structures and reactivity of ate-complexes. Obviously, it will be of important significance to the development of the organometallic reagents and their reactions as well as the mechanism of synergic effect.

ate-络合物是由经典金属试剂衍生出的一类独具特色的金属试剂。文献中它们的种类、制备及配比、用途与反应等均较单一，仍有很大探索的空间。本项目旨在种类、制备与配料比、反应等多方面对ate-络合物进行拓展和革新。通过调整Lewis酸的中心原子与配体种类，采用亚化学计量或催化量的Lewis酸，设计合成出新型ate-络合物，建立只需亚化学计量或催化量 Zr、Al、In、Zn、Sn、B等元素参与的Negishi、Stille、Suzuki等偶联反应或其他高选择性反应。设计和研究双烃基或烃基、胺基混合型ate-络合物，开发出具有双功能的新型ate-络合物及反应。利用这些反应建立新的杂环合成法和高选择性不对称反应；最终进行药物、天然产物等新法合成。课题将较大程度上拓展ate-络合物种类、制备与相关反应，加深对ate-络合物结构与性能的理解，对丰富有机金属试剂及相关反应，深入了解协同效应机制等有重要的意义

直到目前为止，文献中金属试剂的ate-络合物的制备与形成基本上是以等摩尔的路易斯酸与金属试剂作用而成，例如比较典型的有RLi•R3B （又写作R4BLi）或BuLi•Bu2Mg（又写作Bu3MgLi）等。对钛试剂而言，已见文献报道的ate-络合物型钛试剂基本形式为RM•Ti(OR’)4（又写做RTi(OR’)4M）。本项目拟使用亚化学计量的路易斯酸与金属试剂形成ate-络合物，并在此基础上进一步发展出只需亚化学计量路易斯酸参与的新型ate-络合物及相关反应。.本项目的研究很好地实现了以上目标，探索了以亚化学计量（40-50%）和催化计量（20%）的不同钛试剂形成的新型ate-络合物；并建立了以下这些钛ate-络合物参与的钴钛和铁钛共催化偶联反应：（1）钛ate-络合物参与的钴钛共催化C-F活化反应，在无需膦或NHC配体以及底物活化基的条件下，C-F强键被活化并发生偶联，为强化学键的活化提供了指导；（2）酚盐参与的新型钛ate-络合物的铁钛共催化联芳偶联反应，很大程度上拓展了铁催化偶联反应的范围；（3）N-甲基二乙醇胺形成的新型钛ate-络合物参与的铁催化下N-甲基芳基甲酰胺的邻位C-H芳基化反应，很大程度地拓展了铁催化和邻位C-H芳基化反应的范围；（4）酚盐参与的新型钛ate-络合物的铁钛共催化立体专一性芳基化反应，为立体专一性合成三取代或四取代丙烯酸酯衍生物的合成提供了首个铁催化方法。此外，本项目还意外地建立两个游离基型去芳构化反应：（5）硝基为离去基的去芳构化反应；（6）C-H活化型去芳构化反应，两种方法为建立新型螺稠环体系提供了重要的方法。.本项目的部分成果已在国际重要期刊 Org. Lett.、Chem. Commun.、Adv. Synth. Catal.、J. Org. Chem.期刊上发表，共计6篇；另两个发明专利已进入公开实审。文章引起同行的关注，有2篇文章被 Synfacts 期刊和 Org. Process Res. Dev. 作为亮点文章评述，其中一篇被J. Org. Chem.刊登为封面文章。此外，还有不少工作正在整理。