Study On Copper-Catalyzed Asymmetric Unpolung Hydroamination Of ?,?-Unsaturated Amides

Chiral nitrogen-containing are a class of important organic compounds,which widely exist in natural products and biologically active drug molecules,and play an indispensable role inproduction and life.For example,natural alkaloid monomorine is a key component of many medicinal plants,crispine A can inhibit the growth of some human cancer cells,etc.Therefore,Therefore,the synthesis of chiral nitrogen compounds has become an important research topic in synthetic chemistry.Asymmetric construction of the C-N bonds is one of the important missions for organic synthetic chemists.The asymmetric aza-Michael additions of alpha,?-unsaturated carboxylic acid and its derivatives?e.g.unsaturated esters,unsaturated amides?with lower reactivity are less studied than those of high reactivity alpha,?-unsaturated aldehydes and ketones,owing to their low reactiviting.It mainly depends on the introduction of an additional active group to improve its reactivity,so for.Therefore,it is very important to develop a simple and direct method to construct C-N bond.In recent years,the asymmetric hydroamination of unsaturated hydrocarbons has attracted much attention of some chemists.Hydroamination is a kind of reaction that adds nitrogen-hydrogen bond to carbon-carbon unsaturated bond.Compared with the common methods,such as nucleophilic substitution,reductive amination and allyl substitution,hydroamination is one of the most efficient methods to construct chiral C-N bond.The traditional precious metals?Ru,Rh,Pd,Ir,Au?as well as the cheap transition metals?Cu?and the rare earth metals?Y,Yb,Sm?can catalyze this type of reaction to produce chiral amino substituted amide compounds.Literature research shows that the asymmetric amination of a,?-unsaturated amides to synthesize chiral amino substituted amides in Michael system,especially those with low reactivity,has not been reported.Owing to the importance of chiral amino substituted amides,we speculated that?,?unsaturated amides can be used as the substrates for asymmetric hydroamination under CuH catalysis.In this thesis,the asymmetric umpolung hydrogenation of?,?unsaturated amides with nitrogen sources to sythesize chiral?-amin amides has been finished.Under in situ generation of CuH catalysis,which drired from Ph-BPE ligated Cu?OAc?₂ in the presence of silanes.using and rac-Ph-BPE as catalysts.The amides substituted by?-amines were obtained with high yields and regioselectivities.On the basis of racemic tramsformation the asymemetric rersion has also been realized,providing chiray?-amin amino in good yields withmoderate to high enantioselectivities.The umpolung strategy regulated by the ligand provides a new method for the synthesis of chiral?-amino substituted amides,and also offer new opportunities for the asymmetric transformation of other Michael systems..