Application Of Chiral Oxazoline Ligands In The Asymmetric Kinugasa Reaction

Chiral β-lactams is the core structure of many biologically active molecules andalso a type of useful and extensively employed synthetic intermediates in modernorganic synthesis. Much attention has been paid to their highly stereoselective synthesisin recent years. This thesis mainly focused on the development of new oxazoline ligandsby introducing an additional sidearm at the bridging carbon atoms of traditionalbisoxazolines and their applications in asymmetric Kinugasa reaction.In the first chapter, the synthesis of β-lactams and the development of asymmetricKinugasa reaction is summarized.In the second chapter, we detail the investigation on the application ofaforementioned ligands in asymmetric Kinugasa reaction. TOX30/CuOTf·Tol complexproved to be a good catalyst in the coupling reaction of nitrones and terminal aromaticalkyne. Under optimized conditions, cis-or trans-β-lactams were obtained in moderateto good yields (up to98%) and with excellent diastereoselectivities (up to97/3) andenantioselectivities (up to99%). Moreover, the enantiomeric purity of product C1canbe readily increased to>99%ee through a single of recrystallization.In the third chapter, the asymmetric Kinugasa reaction between various nitronesand propargyl ester was investigated. By optimizing the reaction conditions andchanging the chiral ligands, a series of β-lactams were synthesized with the highest89%enantioselectivity,8/1diastereoselectivity and80%yield.