Studies On The Reductive Vinylation Of Secondary Amides And Asymmetric Hydrogenation Of Annular Enamide

Development of efficient organic synthetic methodology is one of the central goal in organic synthesis,which promotes the development of total synthesis and other relative academic subjects.Allylic amines play an important role in organic chemistry.Allylic amines have received significant attention because they represent a common scaffold natural products,alkaloids and diverse biologically relevant compounds.In addition,allylic amines play an important role as intermediates in organic synthesis,which have been used for the synthesis of numerous heterocycles and bioactive amines,such as a-andβ-amino acids.Therefore,it is necessary and important to develop efficient method for synthesis of allylic amines and derivatives.Chiral amines are an important class of organic compounds,which present in many natural product,pharmaceutical drugs and biologically active compounds.Transition metal catalyzed enantioselective hydrogenation of enamides is one of the most important methods for the preparation of a-chiral amides.Recent years,our group have focused on the decelopment of synthetic methods for construction of C-C bond based on amide activation.Combining enantioselective hydrogenation of annular enamides and amide activation,it is meaningful to develop a new method for the transformation of annular enamides into annular chiral amines.However,catalytic enantioselective hydrogenation of annular enamides still be a challenge.This dissertation contains the following two parts:(1)Based on amide activation,we have developed a reductive vinylation method for transformation of secondary amides into allylic amines with enamine as nucleophiles.This method shows a good chemoselectivity and tolerance of functional groups.Allylic amines were obtained in moderate to good yield.This method can be used in the synthesis of a wide range of allyl amines including β-monosubstituented,y-monosubstituented and P,y-substituented ones.(2)We hope to find a suitable catalytic system for enantioselective hydrogenation of annular enamides to preparae a-chiral amides,then construct chiral amines based on amide activation.We have made some attempts with several chiral rhodium complexes,chiral iridium complexes and chiral ruthenium complexes.It is a pity that we have not got satisfied results.