The Application Of Chiral Semi-aza-crown Ether Ligand In The Catalytic Asymmetric Minnich Reaction

The Mannich reaction is one of the most widely used chemical transformationsfor the construction of β-amino carbonyl molecules and β-amino alcohol derivatives,valuable synthetic intermediates to synthesize drugs and biologically activecompounds. Among the methods available for their catalytic asymmetric syntheses,catalytic enantioselective Mannich-type reactions of α-alkoxy enolate are of particularinterest, for two adjacent stereocenters are constructed simultaneously with aconcomitant carbon-carbon bond formation.This thesis mainly studied the asymmetric Mannich reaction of3-hydroxy-1-methylindolin-2-one with Boc-imine and hydroxyacetophenone with aryl-imine underthe catalysis of the chiral semi-aza-crown ether ligand.1. Direct catalytic asymmetric Mannich-type reaction of3-hydroxy-1-methylindolin-2-one and Boc-imine using the chiral semi-aza-crown etherligand(Scheme1)We developed the asymmetric Mannich reaction of3-hydroxy-1-methylindolin-2-one to Boc-imine, which is catalyzed by chiral semi-aza-crown ether ligand. It wasfound that at the optimized conditions, toluene as solvent,5mol%of1and10mol%of Et2Zn as catalyst, at room temperature, we got excellent result with81%yield, up to90%ee and d.r.1/1.6.2. Direct catalytic asymmetric Mannich-type reaction of Aryl-imine and hyroxy-acetophenone using the chiral semi-aza-crown ether ligand(Scheme2)We use the ligand L1for the direct Mannich reaction of aromatic hydroxyketones and imine that derived from aromatic aldehydes, the corresponding β-aminoalcohols was obtained in92%yield,98%ee, with syn/anti>27/1.