【作者】 蒋波；

【导师】 陈应春；

【作者基本信息】 四川大学 ， 药物化学， 2023， 博士

【摘要】 过渡金属催化广泛应用于化工、制药、材料等领域。过渡金属可以通过经典的π-Lewis酸途径活化不饱和体系,并已被大量报道。最近我们课题组发展了零价钯作为π-Lewis碱的催化策略:零价钯与不饱和体系形成η~2-配合物,进而通过d电子对π*键轨道的反馈作用提高共轭不饱和体系的电子云密度,从而与亲电试剂发生不对称反应。相比于发展成熟的π-Lewis酸催化体系,过渡金属作为π-Lewis碱的催化模式仍处于初步的探索阶段,但已经显示出重要的应用潜力。因此,我们开展了系列探索,进一步拓展了π-Lewis碱的应用范围和反应类型。本论文主要由五个部分组成:第一部分总结了近年来过渡金属活化不同底物构建烯丙基醚的研究进展。第二部分工作中,我们采用零价钯作为π-Lewis碱催化剂,实现了1,3-丁二烯与靛红、醇的三组分不对称羟甲基醚化反应,高效构建了一系列手性烯丙基醚衍生物。另外,该催化模式还能扩展应用至其他活性醛、酮、亚胺等亲电试剂,但立体选择性有待进一步优化。第三部分和第四部分工作中,我们通过零价钯与芳杂基不饱和化合物的双键或三键络合,提高芳杂环的电子云密度,从而实现了其与亚胺、Michael受体的不对称傅-克烷基化、甚至串联环化反应,合成了多类手性芳杂环化合物。详细的机理研究实验表明该类反应是通过零价钯作为π-Lewis碱活化实现的。该工作进一步拓展了零价钯作为π-Lewis碱的底物应用范围(从1,3-二烯拓展至芳杂环化合物),为构建具有潜在生物活性的手性芳杂环化合物提供了新途径。最后,我们对上述研究工作的核心内容进行了简要总结。更多还原

【Abstract】 Transition metals have been widely applied in various fields,such as chemical manufacturing,pharmaceuticals,materials science,and so on.Classically,transition metals can activate unsaturated compounds asπ-Lewis acids,which have been extensively explored.On the other hand,a novel Pd~0-π-Lewis base catalytic mode has been uncovered by our group recently.Pd~0 can formη~2-complexes with unsaturated systems,and enhance their electron density upon back bonding toπ*-orbitals,thus enabling the attack towards electrophilic reagents stereoselectively.Compared to well-establishedπ-Lewis acid catalysis,π-Lewis base catalysis is still in its early exploration stage but has already demonstrated significant application potential.Therefore,we conducted a series of studies to further expand the scope and reaction types ofπ-Lewis base catalysis.The thesis consists of five parts.The first part summarized the progress of the construction of allylic ethers from different substrates catalyzed by transition metals in recent years.In the second part,we developed a Pd~0-π-Lewis base catalyzed asymmetric hydroxymethylative etherification reaction of 1,3-dienes with isatins and aliphatic alcohols,proceeding through a sequential vinylogous addition and O-allylic alkylation process.A series of chiral allylic ether products were efficiently and concisely constructed in good yields and stereoselectivity.In addition,this catalytic protocol can be extended to activated benzaldehydes,paraformaldehyde and aldimines,albeit with fair stereoselectivity.In the third and fourth parts,we developed asymmetric Friedel-Crafts reactions of heteroarenes tethered to an unsaturated system via Pd~0-π-Lewis base activation,resulting in the construction of diverse enantioenriched heteroaromatic compounds.Through various mechanistic studies,it was demonstrated that Pd~0coordinated to the double(or triple)bond conjugated to the heteroarenes,thus increasing the electron density of heteroaromatic rings and facilitating the Friedel-Crafts addition.This work further expanded the substrates scope of Pd~0-π-Lewis base catalysis from 1,3-dienes to heteroaromatic compounds,thereby offering a new pathway for the construction of biologically relavent chiral heteroaromatic compounds.The fifth part is a brief summary of the key contents of the research work described above.更多还原