利用雙官能基硫脲為有機催化劑及1,5-雙氟基-2,4-二硝基苯合成掌性異噁唑類衍生物的研究

Abstract

本論文是延續本實驗室先前已畢業的研究生之研究，利用兩個分開的步驟來合成掌性的雙環異噁唑類化合物，首先，以β-硝基苯乙烯與丙二酸酯類衍生物作為起始物並以雙官能基硫脲有機催化劑提供不對稱環境進行1,4-共軛加成反應時引進一個立體化學中心，之後以此具光學活性之硝基烷化物進行分子內氧化腈經1,3-偶極環加成反應來合成具掌性的異噁唑類衍生物。This thesis deals with the synthesis of biologically active chiral bicyclic isoxazole and isoxazoline derivatives. The synthetic methodology involves two steps. In the first step, β-nitrostyrene derivatives were treated with allyl or propargyl malonates in the presence of chiral bifunctional thiourea catalyst to obtain the corresponding optically active Michael adducts. The resultant chiral Michael adducts were treated with DBU and 1,5-difluoro-2,4-dinitrobenzene (DFDNB) to generate nitrile oxides in situ. The nitrile oxide intermediates underwent intramolecular 1,3-dipolar cycloaddition with the neighboring dienophile to form chiral isoxazole and isoxazoline derivatives. In terms of yield and enatiomeric excess, this approach represents a highly efficient method for constructing the important class of molecules.