【作者】 王晓琴；

【导师】 马成；

【作者基本信息】 浙江大学 ， 化学， 2012， 硕士

【摘要】 3,4-二氢吡喃结构单元大量存在于具有生物活性的天然产物和药物分子中,同时也是非常重要的有机合成前体。因此,快速和立体选择性构建二氢吡喃衍生物显得尤为必要。本论文研究了α-取代-β-羰基醛与β}γ-烯基-a-酮酸酯的不对称环合反应,在双官能团四方胺催化剂作用下,利用环状β-羰基醛底物,高立体选择性地构建了具有3个连续手性碳原子的螺-3,4-二氢吡喃衍生物。在此基础上,探索了此类化合物的分子内Oxo-Micheal反应。全文共分三个部分：第一章对3,4-二氢毗喃衍生物的合成方法和研究进展作了概述。介绍了目前常见合成螺环中心的方法。同时,总结了一种以四方胺为核心结构的氢键催化剂的研究进展与应用。第二章研究了手性四方胺催化的Michael/半缩醛化串联反应,由β-羰基醛与β,γ-烯基-a-酮酸酯高度立体选择性构建了具有三个连续手性中心的螺-3,4-二氢吡喃衍生物,其中螺环中心碳原子为全碳取代。我们观察到各种底物均能以中等到优秀的产率和高度的立体选择性得到目标产物,催化剂用量可低至3mol%。第三章在之前的研究基础上,发展了底物诱导的非对映体选择性的分子内Oxo-Micheal加成反应,在温和条件下成功构建出碳-氧键,并以优秀的收率和一定的非对映体选择性得到环化产物。更多还原

【Abstract】 3,4-Dihydropyransare important structural motifs in a myriad of biologically interesting natural products and pharmaceutical targets; they also serve as versatile building blocks in organic synthesis. Accordingly, asymmetric transformations enabling expeditious and stereoselective construction of dihydropyran derivatives are of particular importance in organic synthesis. This dissertation demonstrates the cyclization ofβ-oxo aldehydes withβ,γ-unsaturated a-keto ester which was carried by utilizing squaramide organocatalyst. This procedure provided a promising approach to a variety of spiro-3,4-dihydropyrans bearing three continues quateranery and tertiary stereocenters in moderate to good yield with high stereoselectivities. On that basis, we have developed an intramolecular Oxo-Michael reaction using phase transfer catalyst. The dissertation is consisted of three chapters.In the first chapter, we summarized the synthetic methods of3,4-dihydropyrans as well as their current research and trends, respectively. Then we discuss various general methods that involve the generation of spirocyclic centers. Moreover, we describe here the development and successful demonstration of a new family of H-bonding catalysts based on the squaramide catalophore.In the second chapter, we investigated the domino Michael/hemiacetalization reaction of cyclic β-oxo aldehydes withβ,γ-unsaturated a-keto ester in the presence of squaramide, obtained the complex of spiro-dihydropyran architectures, which containing three continuous chiral centers. To our delight, good yields as well as high diastereo-and enatioselectivities was observed, even the catalyst loading was reduced to3mol%.In the third chapter, we explored an intramolecular Oxo-Michael reaction using phase transfer catalyst, to afford spirocyclic compound in excellent yield, based on previous experimental results.更多还原