鸡钠碱衍生物催化的不对称Michael加成-缩酮环化反应中文摘要本论文以手性的金鸡纳碱衍生物为催化剂，研究了不同的亲核试剂对水杨醛衍生的β,γ-不饱和α-酮酸酯的不对称Michael加成-缩酮化串联环化反应，构建了一系列具有潜在生物活性的手性缩酮骨架化合物。论文的第一部分工作，我们研究了手性有机小分子催化的不对称Michael加成-缩酮化反应。我们以水杨醛衍生的β,γ-不饱和α-酮酸酯与吡唑啉酮为反应底物，通过手性金鸡纳碱衍生物催化的不对称Micheal加成以及连续的有机催化剂催化的分子内缩酮化反应，最终构建了杂环缩酮化合物。论文的第二部分工作，我们针对第一部分的反应优化了实验条件，主要是对催化剂进行了筛选，使反应达到了优秀的产率及对映体选择性。论文的第三部分工作，我们从第二部分催化剂筛选的结果出发，分析并优化出了一种可以提高反应对映选择性的催化剂。关键词：不对称Micheal加成，对映选择性，缩酮骨架，有机催化，金鸡纳碱衍生催化剂CinchonaAlkaloidDerivatives-CatalyzedAsymmetricMichaelAddition-KetalizationCyclizationAbstractInthisthesis,chiralcinchonaalkaloidderivativeswereusedascatalyststoinvestigatetheasymmetricMichaeladdition-ketalizationannulationofsalicylaldehyde-derivedβ,γ-unsaturatedα-ketoesterswithdifferentnucleophiles.Inthereaction,aseriesofchiralketalskeletoncompoundswithpotentialbiologicalactivitywereconstructed.Inthefirstpartofthethesis,westudiedtheasymmetricMichaeladdition-ketalizationcatalyzedbychiralorganicsmallmolecules.Weusedasalicylaldehyde-derivedβ,γ-unsaturatedα-ketoesterandpyrazoloneasthereactionsubstrates,asymmetricMichealadditioncatalyzedbychiralcinchonaalkaloidderivativesandcontinuousorganiccatalystcatalysisIntramolecularketalizationreaction,andeventuallyaheterocyclicketalcompoundwasconstructed.Inthesecondpartofthethesis,weoptimizedtheexperimentalconditionsforthefirstpartofthereaction,whichwasmainlytoscreenthecatalystandachieveexcellentyieldandenantioselectivity.Inthethirdpartofthethesis,weproceededfromtheresultsofthesecondpartofthecatalystscreeningandanalyzedandoptimizedacatalystthatcanimprovetheenantioselectivityofthereaction.Keywords:asymmetricMichealaddition,enantioselectivity,ketalskeleton,organicCatalysis,cinchonaalkaloidderivativeCatalysts目录第一章引言..................................................................................................................41.1金鸡纳碱催化剂..................................................................................................41.2杂环缩酮[3.3.1]骨架化合物................................................................................7第二章立题思想........................................................................................................11第三章实验部分........................................................................................................113.1不对称Michael加成-缩酮化反应....................................................................113.2实验条件的筛选................................................................................................133.3催化剂的合成....................................................................................................15第四章结论与展望....................................................................................................17部分化合物谱图..........................................................................................................18参考文献..........................................................................................
