Research On The Aza-Michael Addition-Involved Domino Reactions

Asymmetric organocatalytic reactions are considered to be the third asymmetric catalytic method relative to transition-metal catalysis and enzyme catalysis reactions.Because of its stability,cheapness,et al,asymmetric organocatalysis has become an important tool to construct complex molecular skeletons and has broad application in the fields of medicine,biology and materials science.Using chiral catalysts,organocatalytic asymmetric aza-Michael reaction can form C-N bond with stereoselectivity and build nitrogen-containing heterocycles with chiral center.Therefore,it is highly valuable in organic synthesis.Highly enantioselective or diastereoselective synthesis three kinds of nitrogen-containing heterocyclics using aza-Michael addition-involved domino reactions were reported in this thesis which can be divided into three parts.In the first part,domino reactions and asymmetric organocatalytic aza-Michael additions and their application in the synthesis of biologically active compounds research progress are summarized.In the second part,firstly,an efficient and enantioselective strategy to synthesize benzoindolizidines from amino a,p-unsaturated ketones via intramolecular domino aza-Michael addition/alkylation has been described.A variety of benzoindolizidines with different functionalities were prepared in good yields(up to 93%)and enantioselectivities(up to 92.8/7.2 er)as one diastereomer catalyzed by a chiral phase transfer catalyst.Secondly,an efficient and diastereoselective strategy to synthesis expoxide-fused benzoquinolizidine has been described.This strategy is relied on intramolecular domino aza-Michael/Darzens reaction.Three bonds,three rings and three chiral centres can be constructed in single pot under very mild condition.All the products were isolated in only one diastereomer.In the third part,an efficient and stereoselective strategy to synthesize enantio-enriched substituted pyrrolidines bearing an all-carbon quaternary stereocenter via domino cross metathesis/desymmetric intramolecular aza-Michael addition has been described.A variety of pyrrolidines with different functionalities were prepared in good yields(up to 98%yield)and excellent stereoselectivity(up to 24.3/1 dr,up to 99.6/0.4 er).