Studies On The Direct Transformation Methodologies Of Secondary Amides Based On Amide Activation And Ni-Catalyzed Alcoholysis Of N-Acyloxazolidinones

Amides,an important class of compounds with the carbonyl founctional group,are the starting materials,important intermediates for organic and medicinal synthesis.They are also the key structural units of proteins and natural/synthetic compounds.However,the low reactivity of the amide has limited their broad synthetic applications due to the weak electrophilicity of the carbonyl groups in amides.Although amides can be readily transformed into other functional groups by related enzymes in biosynthesis,it is difficult to realize the selective transformations of the amides in organic synthetic chemistry.Therefore,it is of great significance to develop efficient and step-economical methods for the direct transformations of amides.A chiral auxiliary is a stereogenic group or unit that is temporarily incorporated into the substrate to control the stereochemical outcome of the synthesis.It usually needs to be converted into a more reactive functional group after the reaction to undergo the further transformations.However,the methods for achieving this conversion usually need stoichiometric activating agens,and the catalytic version is rarely.The catalytic methods by transition metal with good chemoselectivity and reaction economy have attracted the attention of many organic chemists.It is of great significance to develop new strategies for the effective transformations of chiral N-acyloxazolidinone compounds with inexpensive metal catalysts and the recycling of chiral auxiliaries.Our group have developed a series of methodological studies for the direct transformations of amides by the Tf2O-activation strategy and the construction of C-C bonds by metal catalyzed amides activation.In this thesis,we have further developed several efficient and general transformation strategies for the amide activation and the direct alcoholysis reaction of chiral N-acyloxazolidinone compounds using inexpensive metal catalysts.The main results of these studies are listed as follows.Part 1.Based on the strategy of secondary amide activation,we have developed a series of methods for the direct transformations of secondary amides:1)A general method for the direct reduction of secondary amides to amines under mild conditions(Chapter 2);2)A versatile and chemoselective method for the transformation of secondary amides into nitriles(Chapter 3);3)A general method for the direct transformation of secondary amides into functionalized ?-lactams(Chapter 4);4)A general deaminative alkylation for the direct access to ketones from secondary amides and alkenes(Chapter 5).Part 2.A versatile and chemoselective method for the transformation of N-acyloxazolidinones to esters has been developed.An effective alcoholysis reaction has been developed for the direct access to esters from N-acyloxazolidinone compounds.The reaction features mild reaction condition,broad substrate scope and economical operation for the recycling of chiral auxiliaries.This method provides a new strategy for the late-stage transformations of chiral auxiliaries induced asymmetric synthesis and the construction of chiral ?-lactone units in natural products and drug molecules(Chapter 6).