Active Alkyne-Mediated Rearrangement Reactions Of Tertiary 2,3-Allenylamines And Propargylamines

Tertiary amines are widely present in many natural products and drug molecules,and their rearrangement reactions provide a unique and efficient method for the synthesis of nitrogen-containing molecules with specific skeletons.Generally,rearrangement reactions of tertiary amines require high temperature,strong acids,strong bases or transition metals,which limit the application of tertiary amines in synthetic chemistry.In this dissertation,we utilized active alkynes,such as arynes and acetylenic esters,to activate the C-N bond of tertiary amines,and realized the[2,3]-sigmatropic rearrangement of tertiary 2,3-allenylamines and the aza-Claisen rearrangement of tertiary propargylamines.This dissertation is divided into four chapters.Chapter one:Research progress on in situ activation and rearrangement reactions of tertiary amines.We summarized the methods of in situ activation of tertiary amines and their participation in rearrangement reactions.Including:(1)the rearrangement reactions of tertiary amlines activated by acids or bases;(2)the rearrangement reactions of tertiary amines triggered by diazo compounds which catalyzed by transition metals;(3)the rearrangement reactions of tertiary amines triggered by allylcarbonates which catalyzed by palladium catalysts;(4)the rearrangement reactions of tertiary amines triggered by electrophiles,such as arynes,epoxides/aziridine,acetylenic esters,acetylenic sulfones,ketenes,allenoates,allenones,ketenimines,carbodiimides,isocyanates and isothiocyanates.The[1,2]-,[2,3]-,[3,3]-sigmatropic rearrangement and Smiles rearrangement were realized by various methods of in situ activation of tertiary amines.Chapter two:Aryne-mediated[2,3]-sigmatropic rearrangement of tertiary 2,3-allenylamines.Using 2-(trimethylsilyl)aryl triflates as aryne precursors,a[2,3]-sigmatropic rearrangement of 2,3-allenylammonium ylides,generated in suit from the nucleophilic addition of tertiary 2,3-allenylamines to arynes,has been established,delivering structurally diverse 2-vinylallyamines or 1-amino-1,3-dienes in moderate to excellent yields.The reaction was carried out under mild conditions and proceeded in the absence of strong bases and transition metals which required in traditional rearrangement reactions,is compatible with moisture and air,and tolerates a wide variety of functional groups.Chapter three:Aromatic aza-Claisen rearrangement of arylpropargylammonium salts generated in situ.An aromatic aza-Claisen rearrangement of arylpropargylammonium salts which generated in situ from the nucleophilic addition of tertiary propargylamines to arynes,has been established,delivering structurally diverse 2-propargylanilines in moderate to good yields with high regioselectivity.The reaction was carried out under mild conditions and proceeded in the absence of high temperature,strong acids and transition metals which are required by traditional aromatic aza-Claisen rearrangement reactions,and tolerates a wide variety of functional groups.Moreover,the 2-propargylaniline products were treated with aluminum chloride in ethanol to afford multisubstituted indoles in moderate to excellent yields.A series of deuterium-labelling experiments support that the reaction proceeds by aromatic aza-Claisen rearrangement of the arylpropargylammonium salts generated in situ followed by allenyl-to-propargyl isomerization.Chapter four:Acetylenic ester-mediated aza-Claisen rearrangement of tertiary propargylamines.An aza-Claisen rearrangement and cyclization of propypargylvinylammonium salts,which are generated in suit from the conjugated addition of tertiary propargylamines to acetylenic esters in the presence of zinc chloride,has been established,delivering structurally diverse multisubstituted pyrroles in moderate to good yields with high regioselectivity.The reaction was carried out under mild conditions,is compatible with moisture and air,and tolerates a wide variety of functional groups.