【作者】 李翔；

【导师】 周永贵；

【作者基本信息】 大连理工大学 ， 有机化学， 2024， 博士

【摘要】 氢解是指在催化剂作用下,发生碳碳键或碳杂键断裂,由氢(氢气及其等价体)取代离去基团生成烃的一类反应。氢解是有机合成化学中重要的基本转化之一。目前,采用过渡金属负载催化剂的多相催化氢解反应在有机合成中已经取得广泛应用,但是通过均相催化不对称氢解反应来合成手性化合物一直是该领域的挑战。主要原因如下:(1)氢解反应途径较多且副反应严重;(2)底物中σ-键同催化剂金属中心之间相互作用较弱;(3)反应的化学选择性和对映选择性难以控制。针对上述难点,本论文利用底物设计以及发展高活性和高对映选择性手性催化氢解体系策略,开展了钯催化碳氧键不对称氢解的研究工作,分别实现了芳基三氟甲磺酸酯和环氧化合物的不对称氢解,合成一系列轴手性以及中心手性化合物。其详细的研究内容和实验结果如下:首先,使用醋酸钯/(R)-DTBM-Seg Phos/硼氢化钠手性催化体系,成功实现了芳基双三氟甲磺酸酯的氢解去对称化,以良好收率和优异对映选择性合成各种轴手性联芳基化合物。随后,氘代实验和克级规模实验证明了该方法的实用性。此外,从光学纯的轴手性化合物出发,经两步转化合成了手性单膦配体,并成功应用于钯催化不对称烯丙基烷基化反应中,以优异的区域及对映选择性获得烷基化产物。其次,使用醋酸钯/(R)-DTBM-Seg Phos/硼氢化钠手性催化体系,通过动力学拆分策略,顺利实现芳基三氟甲磺酸酯的不对称氢解,其选择性因子最高可达70.0。随后,在钯催化下进行了轴手性芳基三氟甲磺酸酯的Kumada偶联反应,能够以良好收率和优异对映选择性获得偶联产物。该反应也可以在克级规模下进行,其选择性因子能达到19.8。最后,醋酸钯/(R)-DTBM-Seg Phos/硼氢化钠手性催化体系还可以应用于内消旋环氧化合物的氢解去对称化,高效合成了一系列手性醇(最高达87%收率和95%ee)。当反应中使用硼氘化钠作为氘源时,以优异的收率和对映选择性合成各种手性含氘化合物。该方法也可以实现外消旋环氧化合物的氢解动力学拆分,其选择性因子最高可以达到23.5。机理研究表明,该反应可能经过Pd(0)/Pd(II)催化循环过程。总之,基于合理的底物设计和高效手性催化氢解体系的发展,成功实现了具有sp~2碳-氧键化合物和sp~3碳-氧键化合物的不对称氢解,构建了结构多样的手性化合物。另外,本论文的研究也为均相催化不对称氢解的发展提供新思路。更多还原

【Abstract】 The hydrogenolysis refers to the cleavage of C-C bond or C-X bond in the presence of catalyst and the leaving group is replaced by hydrogen atom(hydrogen and its equivalents),which is one of important fundamental transformations in organic synthetic chemistry.At present,the heterogeneous catalytic hydrogenolysis reaction with transition-metal-supported catalyst has been widely applied.However,the homogeneous catalytic asymmetric hydrogenolysis to construct chiral compounds is still a long-standing challenge.The main problems are as follows:(1)multiple ways of hydrogenolysis and serious side reaction;(2)weak interact between theσ-bond in the substrate and the central metal of the catalyst;(3)the difficulty in controlling chemo-and enantioselectivity.In view of the above challenges,palladium-catalyzed asymmetric hydrogenolysis of C-O bonds was carried out through the strategies of rational substrate design and the development of chiral catalytic hydrogenolysis systems in this paper.The asymmetric hydrogenolysis of aryl triflates and epoxides was realized,respectively,and a series of axial and central chirality compounds were synthesized.The detailed research contents and experimental results are as follows:Firstly,the desymmetrization of aryl bistriflates was successfully achieved by hydrogeno-lysis with the palladium/(R)-DTBM-Seg Phos/sodium borohydride system,and the biaryl compounds with axial chirality were synthesized with good yields and excellent enantio-selectivities.The deuteration and gram-scale experiments proved the practicability of this methodology.In addition,chiral monophosphine ligands could be synthesized from the above optically pure products through two-step transformation and successfully applied to palladium-catalyzed asymmetric allylic alkylation,affording the alkylation products with excellent regio-and enantioselectivities.Secondly,the asymmetric hydrogenolysis of aryl triflates was realized with the palladium/(R)-DTBM-Seg Phos/sodium borohydride system through kinetic resolution with a selectivity factor of up to 70.0.Subsequently,the Kumada coupling reaction of axially chiral aryl triflate was carried out by the palladium catalysis,and the coupling product was obtained with good yield without loss of optical purity.The hydrogenolysis could also be performed on the gram scale with a selectivity factor of 19.8.Finally,the catalytic system palladium/(R)-DTBM-Seg Phos/sodium borohydride could also be applied to hydrogenolysis desymmetrization of the meso-epoxides,and a series of chiral alcohols were efficiently synthesized(up to 87%yield and 95%ee).When the sodium borodeuteride was used as deuterium source,various chiral deuterium-containing compounds were obtained with excellent yields and enantioselectivities.The kinetic resolution of racemic epoxides could also be accomplished by hydrogenolysis,and the selectivity factor could reach up to 23.5.The mechanism studies indicated that the hydrogenolysis reaction may undergo the Pd(0)/Pd(II)catalytic cycle.In conclusion,the asymmetric hydrogenolysis of compounds containing C(sp~2)-O and C(sp~3)-O bonds has been successfully realized through rational substrate design and the development of efficient chiral catalytic hydrogenolysis systems,affording a myriad of chiral compounds with axial and central chirality.In addition,this research provides a new hint for the development of homogeneous catalytic asymmetric hydrogenolysis.更多还原