有机催化论文：手性伯胺催化不对称Michael反应研究.docVIP

有机催化论文：手性伯胺催化不对称Michael反应研究 【中文摘要】用有机催化的不对称Michael反应以形成新的C-C键,从而高效地从简单的前体分子构建复杂的分子结构,近年来得到广泛发展,也大大拓展了有机催化在不对称催化领域的应用。本论文首先较全面地综述了手性伯胺催化不对称反应的研究现状,特别是不对称Michael反应的研究进展。在此基础上,对手性伯胺分别催化2-羟基-1, 4-萘醌和β-二酮酯与α,β-不饱和酮的不对称Michael反应进行了较深入的研究。通过手性伯胺催化2-羟基-1, 4-萘醌和α,β-不饱和酮的不对称Michael反应实现了Lapachol类似物的手性合成。由天然金鸡纳碱作为手性源,合成的一系列金鸡纳碱手性伯胺催化剂,在以三氟乙酸为助催化剂的条件下,对各种α,β-不饱和酮都有较好的催化活性(高达93%收率)和对映选择性(高达98% ee)。通过圆二色CD光谱与计算相结合的方法确定了产物的绝对构型,并通过ESI-MS确证了反应关键中间体的存在,证实了亚胺离子的活化机理。通过手性伯胺催化剂实现了β-二酮酯和α,β-不饱和酮的不对称Michael反应。金鸡纳碱型手性伯胺催化剂对各种α,β-不饱和酮和β-二酮酯底物都有较好的催化活性,取得了较高的收率(高达93%)和对映体选择性(最高大于99.5% ee)。通过ESI-MS发现伯胺与不饱和酮形成亚胺活化的关键中间体,证实了手性伯胺催化剂与反应底物通过亚胺离子与氢键协同催化活化的反应过渡态模型。 【英文摘要】The strategy of organocatalytic asymmetric Michael addition reaction to form new C-C bond for complex molecular structures from simple precursors has been widely developed in the recent years and also greatly expand the field of organocatalytic applications in asymmetric synthesis. In this dissertation, recent advances in the chiral primary amines catalyzed asymmetric reactions were summarized and reviewed, particularly the asymmetric Michael reactions. On this basis of above, the primary amine catalyzed Michael reactions ofα,β-unsaturated ketones with 2-hydroxy-1,4-naphthoquinone andβ-ketoesters were made in-depth study respectively.An enantioselective Michael reaction of substitutedα,β-unsaturated ketones with 2-hydroxy-1,4-naphthoquinone has been developed by using a chiral primary amine organocatalyst derivated from cinchona combined with a co-catalyst TFA for the asymmetric synthesis of lapachol analogues. The corresponding products were obtained in moderate to good yields (up to 93% yield) with up to 98% ee under mild conditions. To determine the absolute configurations of the final adducts, a useful technique by comparing the electronic circular dichroism (ECD) spectra of the chiral product with calculated time-dependent density functional theory (TDDFT) results was adopted. Based on the experimental results and ESI-MS of sev