Asymmetric Synthesis Of Dihydropyridinones Via Chiral Phosphoric Acid Catalyzed [4+2] Cycloadditions Of 3-Amdio Allylic Alcohols

Chiral dihydropyridinone structures are important motifs of many natural products and biologically active drugs.Therefore,the asymmetric catalytic synthesis of these compounds has drawn a lot of research interest.The asymmetric cycloaddition reaction represent as the most powerful methods for asymmetric synthesis of chiral dihydropyridinones,which include asymmetric[4+2] cycloadditions and [3+3] cycloadditions.Among these methods,the asymmetric [4+2] cycloaddition(Aza-Diels-Alder reaction)between enolate equivalent and ?,?-unsaturated imines have been well developed,in which a large number of asymmetric catalysis strategies have find their applications.However,the utilization of ?,?-disubstituted ?,?-unsaturated imines as substrate in asymmetric synthesis of dihydropyridinones with C-4 quaternary stereocenters has never been achieved.In this dissertation,we proposed activation of 3-amido allylic alcohol by chiral phosphoric acid catalyst would generate highly active ?,?-disubstituted?,?-unsaturated imines intermediate,which would undergo asymmetric [4+2]cycloadditions with oxazolones to give dihydropyridinones possessing vicinal quaternary stereocenters.We optimized the reaction conditions via modification of catalysts structures,solvents,reaction temperature and reaction time,and finally achieved the asymmetric synthesis of dihydropyridinones with good yields,high diastereo-and enantioselectivities.A series of substituents at the C-1 and C-3positions of 3-amido allylic alcohols and substituents at the C-4 position of oxazolones were well tolerated in these reactions,especially the dialkyl substituents at the C-1 position of 3-amido allylic alcohols.The control experiment demonstrate the uniqueness of these reactions,whose product were not available by [4+2] cycloadditions of common ?,?-unsaturated imines.The mechanistic studies indicated that these reaction went through the rare?,?-unsaturated N-H imine intermediates.The facile transformations of chiral products into pyridinones and tetrapyridines well proved the potential of these methods.