Diversified Synthesis of Chiral Chromane-Containing Polyheterocyclic Compounds via Asymmetric Organocatalytic Cascade Reactions

Two different organocatalytic cascade reaction pathways have been developed toward the diversified synthesis of chromane-containing polyheterocyclic compounds from the readily available starting materials. The application of Hantzsch ester is proposed to be the key to achieve the switch between these two different cascade reaction pathways, and then the electron-deficient 1-aza-1,3-butadienes could be used as the four-atom and two-carbon unit, respectively, to react with 2-hydroxy cinnamaldehydes in a highly regio- and stereocontrolled manner. On the basis of larger-scale synthesis, further transformations of the obtained products have also been realized, leading to cycloadducts with high structural and stereogenic complexity bearing five stereogenic centers, and one is a tetrasubstituted stereocenter.本研究开发了两条不同的有机催化级联反应路径，可从易得起始原料出发，实现含色满（chromane）的多杂环化合物的多样化合成。研究提出，汉斯酯（Hantzsch ester）的应用是实现这两条级联反应路径切换的关键；借此，缺电子1-氮杂-1,3-丁二烯可分别作为四原子单元与两碳单元，以高度区域和立体选择性可控的方式与2-羟基肉桂醛发生反应。基于放大合成的需求，本研究还实现了所得产物的进一步转化，得到了兼具高度结构复杂性与立体复杂性的环加成产物，该产物包含五个手性中心，其中一个为四取代手性中心。