【作者】 刘玉峰；

【导师】 张绪穆；

【作者基本信息】 哈尔滨工业大学 ， 化学， 2020， 硕士

【摘要】 化学选择性氢化是氢化领域的重大挑战之一。实现多种不饱和键的化学选择性氢化,能大幅度简化合成路线,降低生产成本,具有重要意义。本文发展了一种钴催化体系,实现了极性双键的化学选择性氢化。手性醇、手性胺结构在药物分子、生物活性分子和功能材料中扮演着十分重要的角色。在众多合成手性醇、手性胺的策略中,不对称氢化有诸多的好处:原子利用率高,副反应少,符合绿色化学的要求和可持续发展的理念。本文发展了手性羟基膦和手性胺基膦片段的高效和高立体选择性合成方法。具体研究内容如下:本文发展了一种Co-P₄N₂催化体系,在不饱和键的选择性氢化方面取得了成功。该催化体系能对碳氧双键、碳氮双键的选择性氢化,而对共轭或非共轭碳碳双键都不会氢化,这是的钴催化体系具有该种化学选择性的首例报道。值得提及的是该催化剂相对稳定,对水和氧不敏感,而且可以最大15克级规模制备,具有良好的应用前景。并且该催化体系底物范围广,转化数高达24000。本文使用课题组之前发展的O-Spiro PAP螺环配体的铱络合物,实现了2-（二苯基磷酰基）-1-苯基乙酮的不对称氢化。虽然含磷底物具有较强的配位作用,但该催化体系能实现该类底物的高效不对称氢化,说明了Ir-O-Spiro PAP催化剂的稳定性。经过条件优化,成功实现了对该类底物的高效高对映选择性的氢化,在甲醇作溶剂,碳酸钾作添加剂的条件下,可以取得99%的转化率和99%ee。基于课题组之前报道的简单酮的还原胺化策略,本文使用醋酸铵做氨源,使用Ru[（R）-DTBM-Segphos]（OAc）₂做催化剂,实现了2-（二苯基磷酰基）-1-苯基乙酮的不对称还原胺化。首次用还原胺化策略实现了氨基膦类手性片段的不对称合成,与传统方法相比,该方法反应效率和原子经济性高,更加符合绿色化学的要求。更多还原

【Abstract】 Chemical selective hydrogenation is one of the major challenges in the field of hydrogenation.The chemical selective hydrogenation of various unsaturated bonds is of great significance,which can greatly simplify the synthetic route and reduce the costs.In this paper,a cobalt catalyst system has been developed,which can achieve the chemical selective hydrogenation of polar double bonds.Chiral alcohols and chiral amine structures usually play an important role in drug molecules,bioactive molecules and functional materials.Among the methods for the synthesis of chiral alcohols and chiral amines,asymmetric hydrogenation has many advantages: high atom utilization,few side reactions and more in line with the concepts of green chemistry and sustainable development.In this paper,the efficient and highly stereoselective synthesis methods of chiral hydroxyphosphine and chiral aminophosphine fragments were developed.The contents of researches in this article are as follows:In this paper,a Co-P4N2 catalytic system has been developed,which was successful in the selective hydrogenation of unsaturated bonds.The catalytic system can selectively hydrogenate carbon-oxygen double bonds and carbon-nitrogen double bonds,but it will not hydrogenate conjugated or non-conjugated carbon-carbon double bonds.This is the first report that the cobalt catalyst system has this kind of chemical selectivity.It is worth mentioning that the catalyst is relatively stable,insensitive to water and oxygen,and can be prepared on a scale of 15 grams,which has good application prospects.In addition,the catalytic system achieved excellent results among wide range of substrates,with the turnover number up to 24,000.In this paper,the asymmetric hydrogenation of 2-(diphenylphosphoryl)-1-phenylethanone was achieved using the iridium complex of the O-Spiro PAP ligand previously developed by our group.Although the phosphorus-containing substrate has a strong coordination effect,the catalytic system can achieve highly efficient asymmetric hydrogenation of this type of substrate,indicating the stability of the Ir-O-Spiro PAP catalyst.After the optimization of the conditions,the highly efficient and high enantioselective hydrogenation of this type of substrate was successfully achieved.When using methanol as the solvent and potassium carbonate as the additive,99% conversion and 99% ee can be obtained.Based on the reductive amination strategy for ketones previously reported by our research group,asymmetric reductive amination of 2-(diphenylphosphoryl)-1-phenylethyl ketones was achieved,using Ru[(R)-DTBM-Segphos](OAc)2 as the catalyst and ammonium acetate as the ammonia source.For the first time,reductive amination strategy was used to synthesis of chiral fragments of aminophosphines.Compared to traditional methods,primary amines are constructed in one pot,with higher efficiency and atomic economy,which is in line with green chemical requirements.更多还原