Highly Efficient Catalytic Asymmetric Synthesis Of Chiral Amines

Nitrogen containing compounds are widely found in drug molecules and natural products,and have important applications in the synthesis of drugs and natural products with biological activity.Enantioenriched N-containing heterocycles are core structures of pharmaceuticals and natural alkaloids,and useful building blocks in organic synthesis.As?-trifluoromethylamine compounds can be easily modified and transformed,they are important building blocks in organic synthesis.In view of the importance of these two kinds of chiral amines and the previous research work of our group,this Ph D dissertation aims at exploring efficient synthetic methods of these two chiral amines,and completes the following two aspects:1.Kinetic resolution of alkylidene norcamphors via a ligand-controlled umpolung-type1,3-dipolar cycloadditionTransition metal-catalyzed asymmetric 1,3-dipolar cycloaddition of azomethine ylides offers the diversity-oriented synthesis(DOS)for the convergent construction of numerous enantioenriched N-containing heterocycles in stereocontrolled fashion,but the opposite regioselective 1,3-dipolar cycloaddition was only sporadically reported in limited examples.We have developed an expedient kinetic resolution of synthetically important racemic alkylidene norcamphors by Cu(I)-catalyzed umpolung-type 1,3-dipolar cycloaddition of azomethine ylide with the DOS of natural-product-inspired spiro[norbornane-pyrrolidines]containing multiple stereogenic centers.The success of this methodology relies heavily on the rational design,which led to implement the strategy of kinetic resolution,and serendipity,which led to the discovery of a unique ligand-controlled regiospecific cycloaddition,which is especially notable and provides direct experimental evidence for the existence of two zwitterionic resonance forms in metallated azomethine ylide.The chiral alkylidene norcamphor could be applied to the facile synthesis of the key intermediate of(Z)and(E)-?-santalol.Through pyrolytic retro-1,3-dipolar cycloaddition we obtained the other entiomer in one kinetic resolution.2.Catalytic Asymmetric Synthesis of?-Tetrasubstituted?-Trifluoromethyl Homoallylic Amines via Ir-Catalyzed Umpolung Allylation/2-aza-Cope RearrangementWe developed a general protocol for the catalytic asymmetric cascade umpolung allylation/2-aza-Cope rearrangement of trifluoromethylated fluorenone imines with allylic carbonates.Despite the low propensity of formation of the highly reactive nucleophilic 2-azaallyl anion and significant challenge in stereoselective control associated the chirality transfer,the cascade allylation/rearrangement of a wide range of trifluoromethylated fluorenone imines has been realized with excellent efficiency and remarkable stereoselectivity,enabled by the suitable protective imino moiety and reaction conditions.Both?-tetrasubstituted and?-trisubstituted?-trifluoromethyl homoallylic amines can be generated in good yields with excellent enantioselectivity.Those amines could easily be produced in gram scale and could be transformed to active three stereogenic centers contaning pyrrolidine by I₂-promoted cyclization.