【作者】 李俊；

【导师】 王春江；

【作者基本信息】 武汉大学 ， 化学、有机化学， 2017， 博士

【摘要】 含氮杂环化合物普遍存在于各种天然产物和具有生理活性的手性药物分子中。利用催化不对称环化反应构建手性含氮杂环骨架也是常用的高效方法之一。以探索高效构建手性六元含氮杂环化合物方法学为目标,我们主要完成了以下两个方面的工作:1)发展了以Cu(Ⅱ)/tBu-Box为手性路易斯酸催化剂,首次实现了2-硅氧基呋喃与原位生成的1,2-二氮杂二烯的催化不对称串联1,6-Michael/1,4-Michael加成反应,以很高的收率、优秀的非对映选择性和对映选择性获得了含有四氢哒嗪并γ-丁内酯结构单元的杂环化合物。通过对反应的13C同位素效应的研究,我们验证了该反应的分步机理;2)以本课题组发展的新型手性配体TF-Biphamphos与金属Cu(I)形成手性络合物作为催化剂,实现了芳基取代亚硝基化合物与各类环状双烯或者非环状双烯的Nitroso Diels-Alder反应,高效高立体选择性地合成了一系列多取代二氢1,2-噁嗪化合物。结合反应产物的绝对构型,我们提出了可能的反应过渡态。更多还原

【Abstract】 Enantioenriched nitrogen heterocycles exist widely in numerous natural products and chiral bioactive pharmaceutical molecules.Catalytic asymmetric annulation reaction is one of the commonly used and effective methods for the synthesis of chiral nitrogen heterocycles.For the purpose of developing efficient methodologies for the constructing of chiral six-membered nitrogenous heterocycles,we have accomplished two following research works:1)An unprecedented Cu(Ⅱ)/tBu-BOX catalyzed cascade 1,6-Michael addition/1,4-Michael addition reaction of 2-silloxyl furan with in situ generated aza-alkene was developed successfully for the first time.An array of optically active tetrahydrofuro[3,2-c]pyridazine containing multiple stereocenters was generally obtained in high yields with excellent diastereo-and enantioselectivities.Studies on the Carbon isotope effects of 2-silloxyl furan in the reaction revealed a stepwise mechanism for this annulation process;2)A highly efficient enantioselective Nitroso Diels-Alder reaction of aryl-nitroso compounds with various 1,3-dienes was successfully developed under the catalysis of Cu(Ⅰ)and chiral ligand TF-BiphamPhos which was designed and synthezed by our laboratory recently.A series of multi-substituted dihydro 1,2-oxazines derivatives was obtained in good yields with excellent enantioselectivities and diastereoselectivities.Based on the absolute configuration of the cycloaddition products,a possible transition state was proposed to rationalize the stereoselectivity of this Nitroso Diels-Alder reaction.更多还原