【作者】 李苗苗；

【导师】 陆良秋； 肖文精；

【作者基本信息】 华中师范大学 ， 有机化学， 2021， 博士

【摘要】 烯酮是有机合成化学中一类十分重要的活性中间体,被广泛用于有机催化或路易斯酸催化的环加成反应。然而,过渡金属催化的烯酮环加成反应研究较少,这主要是因为烯酮作为高度缺电子的物种,在过渡金属存在的条件下容易发生脱羰、聚合等副反应。因此,通过合理地设计反应、选用合适的催化体系,特别是手性的催化体系,发展过渡金属催化的烯酮环加成反应对发展新的烯酮环加成化学、合成结构新颖的环状化合物具有十分重要的意义。本论文利用可见光促进Wolff重排反应,通过原位产生烯酮中间体的方式,发展了钯催化的不对称[5+2]、[4+2]以及[3+2]环加成反应,高效构建手性5-7元氧杂环化合物。具体而言:首先,我们使用α-重氮酮和1,3-茚酮衍生的烯基环丙烷为起始原料,在可见光照射下实现了钯催化的串联Wolff重排/不对称[5+2]环加成反应。通过使用我们课题组发展手性膦硫配体,高效、高立体选择性地构建了一系列手性的七元环内酯(52-92%yields,87:13-99:1 er,up to 12.5:1 dr)。同时,我们还通过DFT理论计算和ESI-MS分析对反应的的机理和选择性(包括化学选择性和环系选择性)做了合理的解释。随后,我们使用α-重氮酮和亚2-丙烯基三亚甲基碳酸酯为起始原料,在可见光照射下实现了钯催化的串联Wolff重排/不对称[4+2]环加成反应。通过使用Carreira类型的手性膦烯配体,高对映选择性地构建了含有手性季碳中心的氧杂六元环内酯骨架(53-95%yields,71:29-98:2 er,up to>95:5 Z/E)。同时,我们也对该类产物进行了双官能团化以及还原氢化等进一步合成转化,产物的对映选择性几乎不受影响。最后,我们使用α-重氮酮和2-氰基羧酸酯衍生的烯基环丙烷及其类似物为起始原料,在可见光照射下实现了钯催化的串联Wolff重排/不对称[3+2]环加成反应。通过使用Trost类型的手性双膦配体,成功合成了手性的多取代四氢呋喃类化合物(56-99%yields,80-99%ee,up to>95:5 dr)。上述三类反应的产物都经过核磁和质谱表征确认,代表性产物还通过X-射线单晶衍射进一步确认。更多还原

【Abstract】 Ketenes are a class of versitatle synthons in organic chemistry,which are widely used in the organocatalytic and Lewis acid catalyzed cycloaddition reactions leading to a wide range of significant hetereocycles.However,the ketene cycloaddition through transition metal catalysis are still under-developed due to the unfavored decarbonylation,polymerization and other competitive processes in the presence of transition metal catalyts.Therefore,the development of such cycloadditions is of great significance from the perspective of enriching the ketene cycloaddition chemistry and contructing new cyclic skeletons by rationally designing the new reactions and exploiting the appropriate catalytic systems,especially the chiral ones.For this purpose,in this PhD thesis we developed palladium-catalyzed asymmetric[5+2],[4+2]and[3+2]cycloaddition reactions with ketones by introducing visible-light-induced Wolff rearrangements.By doing so,a wide range of chiral 5-7 oxyheterocyclic motifs were constructed in high reaction efficiency and selectivity.To be more specific:Firstly,we accomplished a palladium-catalyzed Wolff rearrangement/asymmetric[5+2]cycloaddition sequential reaction of α-diazo ketones and indane-1,3-dione-2-spirovinylcyclopropanes under visible light irradiation.By using chiral P,S ligand developed by our group,a series of chiral seven-membered lactones were produced with high efficiency and enantioselectivity(52-92%yields,87:13-99:1 er,up to 12.5:1 dr).Moreover,DFT theory calculation and ESI-MS experiments were performed to illustrate the reaction mechanism and explain the peri-and chemo-selectivity.Secondly,we further developed a palladium-catalyzed Wolff rearrangement/asymmetric[4+2]cycloaddition sequential reaction of α-diazo ketones and 2-alkylidenetrimethylene carbonates under visible light irradiation.By using chiral phosphoene ligand developed by Carreira,a variety of chiral six-membered lactones bearing chiral all-carbon stereocenters were obtained with high efficiency and enantioselectivity(53-95%yields,71:29-98:2 er,up to>95:5 Z/E).Meanwhile,in order to demonstrate the synthetic practicability,the bifunctional reaction and reductive hydrogenation of the product were realized,and the enantioselectivity of the product was almost not affected.Finally,we explored a palladium-catalyzed Wolff rearrangement/asymmetric[3+2]cycloaddition sequential reaction of α-diazo ketones with 2-cyanocarboxylate substituted vinylcyclopropanes under visible light irradiation.By using chiral biphosphine ligand developed by Trost,a range of chiral highly substituted tetrahydrofurans were successfully synthesized with high efficiency and enantioselectivity(52-99%yields,80-98%ee,up to>95:5 dr).All the products were confirmed by NMR and MS characterization,and the representative products were further confirmed through X-ray single crystal analysis.更多还原