| Amides are of great significance in many fields,including organic synthesis,chemical biology,and biochemistry.Enamides,tryptanthrins,and tertiary alkyl amides exist in many natural products,pharmaceuticals,and agrochemicals.This dissertation mainly focuses on the chemical transformations and derivatization of three types of amide compounds: enamides,tryptanthrin,and tertiary alkyl amides.We have mainly studied the asymmetric Mannich reaction involving enamides,asymmetric Aldol reaction of tryptanthrin,and the transamidation of tertiary alkyl amides.The thesis includes the following three parts:Firstly,the asymmetric Mannich reaction of enamides with cyclic N-acylimines has been developed by using chiral phosphoric acids as the catalyst.This method provides facile access to the construction of chiral 3,3’-disubstituted isoindolin-1-one compounds with high yields and enantioselectivities.The Mannich products can be readily converted into corresponding esters and alcohols without the loss of enantiopurity;A chiral phosphoric acid-catalyzed enantioselective addition of enamides with C-alkynyl N-Boc N,O-acetals has also been developed.This method directly affords chiral β-keto propargyl amines in high yields and enantioselectivity.Meanwhile,the products can be further converted to alkenyl amines,alkyl amines,β-amino ketones,β-amino esters and other compounds without the loss of enantioselectivity.In the second section,a copper-catalyzed enantioselective decarboxylative aldol reaction of tryptanthrins with aryl-substituted β-keto acids has been developed,providing a series of phaitanthrin A analogues in good to high yields with excellent enantioselectivity.In the presence of the identical chiral bisoxazoline ligand,two enantiomers can be obtained by simply changing the copper salts.Based on the X-ray crystal analysis of chiral Cu(II)-bisoxazoline complexes,a preliminary stereochemical model is proposed to explain the enantioselective reversal induced by the counteranion.Finally,a new transamidation reaction of intrinsically robust tertiary alkyl amides is reported.The transamidation reaction of tertiary alkyl amides and amines is successfully carried out with cheap and readily available tungsten(VI)-phenanthroline complexes as catalyst and chlorotrimethylsilane as additive.At the same time,sensitive groups such as ketone,carboxylic acid and ester groups in the substrates are tolerated.In addition,the method can be applied to the synthesis of amide drugs and agrochemical molecules,and provides a simple and convenient method for the further derivatization of tertiary amide drugs.Furthermore,we proposed a possible reaction mechanism based on independent experiements.In the reaction mechanism,tungsten(VI)-phenanthroline complex catalyst activates the amide bonds of tertiary amines to form W–O bonded imine species intermediates.TMSCl can be used as Lewis acid to promote the above process and the elimination of the more basic dialkyl amine.The synergistic effect of tungsten complex catalyst and additive can significantly induce the nucleophilic acyl substitution of tertiary alkyl amide by amine to enable the transamidation reaction. |
