Synthesis And Application Of Novel Chiral P/N/N Ligands In Asymmetric Decarboxylative Propargylic Amination

The carbon-carbon triple bond of propargyl compounds are widely used as key intermediates in the synthesis of drugs and many natural products. Therefore, the development of the methods to construct such structures is one of the most important topics in organic chemistry. Among many of the synthetic methods, the copper -catalyzed propargylic substituted is an important method, which obtain propargyl substituted product in high chemoselectivity and regioselectivity. But the scope of nucleophiles and electrophiles is still relatively narrow, the development of new methods of asymmetric catalytic synthesis of propargyl compound remains a very important and challenging task. In this thesis, we have developed a series of new chiral tridentate P, N, N ligands, and apply it to the asymmetric copper-catalyzed decarboxylation propargyl amine reaction.A new fmily of chiral tridentate P, N, N ligands (L3.10) have been designed and synthesized. After a literature survey and experimental attempts, further modifications to the ligand(L3.9) scaffold have been made and get a new chiral tridentate P, N, N ligands L3.10. We have explored an mature method to prepare this ligand:toluene as solvent, (S)-DPPNH2 and benzoyl pyridine at the catalytic of the alumina, water-absorbing agent (anhydrous magnesium sulfate) was added,then heat to reflux, give the ligand (L3.10) in high yield.The new tridentate P, N, N ligands has been successfully applied to the asymmetric copper-catalyzed decarboxylation amination of propargyl carbamate, of the ligands screened and the reaction conditions optimized the new tridentate P, N, N ligands(L3-10) provide the highest enantioselectivities and yields(96% yield,94% ee). Under the optimized reaction conditions we investigated the effect of the propargyl and amino moieties of propargyl carbamates on the reaction.to the propargyl part:all phenyl substituted propargyl can well adapt to the reaction,but aliphatic propargyl group has low activity in the reaction. To Amino part, open-chain, cyclic (five-, six-membered ring), quaternary ammonium carbamate and secondary carbamates can achieve good results.