新型手性双金属络合物催化的不对称Kinugasa反应研究

许多手性β-内酰胺化合物具有优良抗菌活性或其他生物活性，同时作为关键中间体也广泛应用于有机合成中。末端炔烃与硝酮的不对称Kinugasa反应合成β-内酰胺因反应物简单易得、反应条件温和且反应不受多种官能团影响等优点而在近些年备受关注。虽然已有了几个高对映选择性反应，但是在收率和选择性上仍有改善的空间；在底物的广谱性上，针对很多含β-内酰胺或衍生结构的手性药物、先导化合物的合成存在不足。申请者拟设计合成多个含N、O的多齿配体，并与金属试剂络合，构建新型双金属催化剂，用于不对称Kinugasa反应。拟研究不同的炔烃、硝酮、催化剂及其他反应条件对不对称Kinugasa反应的影响。通过各种实验手段和理论知识，探究催化反应中的各种相互作用，进而研究反应的催化循环机理和过渡态，寻找手性识别和控制产物立体选择性的规律，从而实现高产率、高对映选择性地合成β-内酰胺类化合物，同时发展新型手性双金属催化体系。

Many chiral β-lactams have excellent antibacterial activity or other biological activity. They are also used as key intermediates in organic synthesis. The synthesis of chiral β-lactams by the asymmetric Kinugasa reaction between terminal alkynes and nitrones is attractive for the readily available reagents, mild conditions and the variety of functional groups in recent years. Although high enantioselectivity has been achieved with certain type of substrates, the development of a highly efficient and enantioselective catalytic Kinugasa reaction is still a challenging task especially for many chiral drugs and lead compounds containing the structure of β-lactams. Series of polyfunctional ligands containing N and O would be designed and synthesized to complex with various metal reagents so as to construct novel bimetallic catalysts. Thus the bimetallic catalysts will be applied in the asymmetric Kinugasa reaction. The Kinugasa reaction will be studied to achieve high yields and enantioselectivities by investigating different alkynes, nitrones, catalysts and other reaction conditions. The interaction laws of the catalytic reaction, the binding sites of the catalysts as well as the role of the two metals in bimetallic catalysts will be explored through a variety of experimental methods and theoretical knowledge. And then the catalytic mechanism and the transition state will be studied which will indicate the chiral recognition and the control of the stereoselectivity. At the same time a novel catalytic system based on bimetallic catalysts will be developed.