Study on Addition Reaction of 3,4-Dihydroisoquinolines with γ-Hydroxy-α,β-unsaturated Phenyl Ketone at Room Temperature

[[abstract]]有機催化劑應用在不對稱aza-Michael加成反應為碳-氮鍵生成中重要的一環，常見其應用於天然物或藥物分子的合成，利用有機催化劑進行不對稱aza-Michael加成反應，是一符合經濟效益與環保的不對稱合成方法。而1,3-oxazolidine的結構是有機藥物分子內重要架構。例如具有1,3- oxazolidine 環的quinocarcin和 terazomine已被證實具有抗癌效果。 因此我們利用本實驗室已開發出的樟腦擴環衍生物為起始物合成一些含硫尿素官能基的有機催化劑(59、60)，並且將其應用於3,4-二氫異喹?與羥基不飽和苯酮類化合物的不對稱合環反應，生成含有1,3-oxazolidine環的化合物。此合環反應即包含aza-Michael加成反應，但是我們發現反應速率太快導致催化劑無法作用。我們更進一步發現合環反應在室溫下反應十五分鐘便可快速得到產物並且不需加入任何添加劑。於是改變3,4-二氫異喹?苯環上不同的取代基，且合成一系列的3,4-二氫異喹?-1,3-oxazolidine的衍生化合物，並且得到良好的產率(82-98%)。[[abstract]]The application of asymmetric aza-Michael addition reactions by utilizing organic catalyst is one of the important synthesis methods to create a carbon-nitrogen bond. And it is useful for nature product and medicine synthesis. It has economic benefits and is environmentaly friendly in asymmetric synthesis. In this thesis, aza-Michael addition reaction’s product is 1,3-oxazolidine. 1,3-Oxazolidines are important structural moieties that exist in many biologically active compound. For example, quinocarcin and its analogue terazomine are polycyclic tetrahydroisoquinoline alkaloids with remarkable activities against several tumor cell lines. Therefore, we synthesised the new type of organocatalysts 59、60 containing camphor derived [3.2.1] bicyclic thiourea has also been designed and prepared. It shows low [α]D values to cyclize 3,4-dihydroisoquinolines and γ-hydroxy-α,β-unsaturated phenyl ketone. But, the cyclization took only 15 min at room temperature without any catalyst and addition agent. Then, we examined a wide variety of 3,4-dihydroisoquinolines substates. The results showed that the reaction tolerated both electron-donating and –withdrawing groups at the various positions on the phenyl ring of 3,4-dihydroisoquinolines. The reaction provides the various products in good to excellent yields (82-98%).[[note]]碩