Asymmetric 1,3-Dipolar Cycloadditions Of Azomethine Ylides With Dipolarophiles

The modern organic chemistry tries to mimic the nature by creating enantiomerically pure substances through several sophisticated methodologies developed exponentially during the last decades.Despite all the recent advances in catalytic asymmetric synthesis,this branch of chemistry is trying to figure out how to create the most complicated chemical structures via straightforward,simple and cheap under mild conditions without harming the environment.The nature always inspired the scientists by its fabulous capacity to combine several small organic entities into one macromolecule in such chemo-,regio-and stereoselective manner.And among the other virtue of nature is that many of its own bio-synthetic products have biological or therapeutic activities.Based on this approach,we fixed as objective to imitate the nature and we take this challenge to synthesis enantiopure heterocyclic products through well-designed chiral complexes or by simply using natural catalysts.On the other hand,we aim to synthesize a wide range of complex molecular structure similar to ones existing in the nature such as heterocyclic rings containing nitrogen or spirocyclic compounds containing heterocyclic moieties.To achieve those objectives,our approach focuses on the catalytic asymmetric 1,3-dipolar cycloaddition reaction.Thanks to this well-developed synthetic strategy,we believe that it is possible to imitate the nature by producing infinite organic structures straightforwardly and efficiently.In this thesis,we emphasized our research on three themes:-The asymmetric synthesis of pyrrolidines derivatives through one step reaction under mild conditions:We reported a highly stereo-and regioselective asymmetric catalytic 1,3-dipolar cycloaddition of azomethine ylides generated in situ from?-amino esters with maleate and fumarate ester derivatives in the presence of copper-ferrocenic chiral complex.The later allowed the formation of exo-tricarboxylated pyrroldine derivatives in high yield,diastereo-and enantioselectivities?up to 95%yield,>99:<1 dr and>99 ee?.-Asymmetric construction of spirocyclic compounds containing azaspiro[4.5]decane moiety:We have reported the first 1,3-dipolar cycloadditions of azomethine ylides generated in situ from?-amino esters with bis-arylidenecyclohexanone in the presence of the natural chiral catalyst“Cinchonine”.Under optimized condition,the cycloadducts containing unique spiro quaternary center were obtained in excellent yields and good stereoselectivities.-Catalytic synthesis of 5/5 spiro fused ring system at C2 position via novel metal/amino acid chiral complex:We have reported the first 1,3-dipolar cycloadditions of azomethine ylides generated in situ from?-amino esters with arylidenindane-1,3-diones affording 5/5 spiro fused ring system.This asymmetric reaction was undertaken by a cobalt^II?L-Phenylalanine?₂ and we are the first one who have reported a successful catalytic asymmetric reaction in the presence of such chiral complex.