Asymmetric Cascade Reaction Catalyzed By Chiral Secondary Amines

In this thesis,based on reviewing the recent advances in asymmetric organocatalytic cascade reactions,we designed and developed four novel asymmetric domino reactions catalysted by chiral proline thioether or J(?)gensen-Hayashi catalysts.These studies further expanded the application of organocatalytic asymmetric cascade reaction.Several series chiral complex compounds,which are polycyclic and include three or more chiral centers,were synthsized in one-pot process.This dissertation includes the following five parts.(1)The introduction simply generalized the background of asymmetric oraganocatalysis and its domino reactions as well as the activation model of chiral amine catalysts.Some general examples of asymmetric cascade reactions catalysted by chiral secondary amines were reviewed.Especially,those initiated by asymmetric Michael reaction were introduced in detials.For example,Michael-Michael,Michael-aldol,Michael-Henry,Michael-intramolecular heterocyclization and so on;(2)The efficient simultaneous activation of cyclohexenones and 2-hydroxynitrostyrenes was realized in presence of a chiral proline thioether catalyst for the first time.An environmentally friendly oxa-Michael-Michael cascade reaction was developed by using saturated NaCl as the solvent.Thus,a series of functionalized tetrahydroxanthenones including three continued chiral centres were afforded in good to high yields(up to 99%),with good to excellent diastereoselectivities(dr up to>99:1)and excellent enantioselectivities(up to>99%ee).Furthermore,the“iminium-enamine" catalytic cycle was proposed and indentified by ESI-MS as well as HRMS method.(3)An unprecedented oxa-Michael-Michael cascade reaction of simple alkyl acyclic enones with 2-hydroxynitrostyrenes was firstly developed by using a chiral proline thioether catalyst.This simultaneous activation could provide an effective strategy for stereoselectively activating the alkyl acyclic enones.The study demonstrated that the reaction could effeciently proceed at 60 ? for 24 h when p-cymene was used as the solvent,a series of functionalized chromanes with three continued chiral centers were obtained in good to high yields(up to 85%)with good to excellent diastereoselectivities(dr up to 54:1)and excellent enantioselectivities(up to 99%ee).(4)A diastereochemical switch was successfully realized for the first time by simply controlling reaction temperature using the same chiral catalyst,substrates and solvents.A series of enantiomerically enriched bicyclic lactams with inverse configuration were provided by an unprecedented Michael-hemiaminalization-hemiacetalization cascade reaction between a-ketoamide and ?,?-unsaturated aldehydes at 0 ? and 50 ?,respectively.Abroad substrate scope has been sueeessfully employed in this process,including alkyl and aromatic a,P-unsaturated aldehydes.(5)We designed and studied a novel enantioselective organocatalytic domino Michael-Michael-Henry-hemiacetalization reaction of a-ketoamides,?,?-unsaturated aldehydes with nitroolefins.Catalyzed by Jorgensen-Hayashi catalyst,this domino process could provide a series of bicyclic cyclohexanes which are synthetically important structural units and found in many natural products.In this catalytic system,the initiated step of the domino reaction almost entirely started from the Michael reaction between ?-ketoamides and ?,?-unsaturated aldehydes,high chemoselectivity determined good to high yields(43%-92%)and excellent diastereoselectivities(>20:1 dr)as well as enantioselectivities(>99%ee).