Studies On The Enantioselective Desymetrization Of Triacylamines

Enantioselective desymmetrization of prochiral or meso compounds consists of one of versatile powerful tools for synthesizing enantioenriched compounds,and its related research has become an important topic in asymmetric catalysis.This thesis mainly concerns about the enantioselective desymmetrization of structurally unique prochiral and meso triacylamines,and the following four chapters in this dissertation are as follows:Chapter 1:Studies on the enantioselective reductive desymmetrization of prochiral triacylamines.Based on the optimization of Na BH₄/Cu Cl as reducing agent and proline-derived amino alcohol as chiral ligand,we have investigated the enantioselective reduction reaction of prochiral triacylamines via desymmetrization,giving a series of structurally novel,chiralδ-lactam-hemiacetals in moderate yields（30%～50%）with high enantioselectivities（up to 97%ee）.The current studies on this reduction reaction offer an alternative route to the desymmetrization of prochiral triacylamines.Chapter 2:Studies on the enantioselective alcoholytic desymmetrization of prochiral triacylamines by using chiral Lewis acids and Br?nsted acids.Based on the catalysis of chiral Lewis acid and Br?nsted acid,we have examined the enantioselective nucleophilic ring opening reaction of prochiral triacylamines via desymmetrization,affording a series of functionalized chiral 1,5-dicarbonyl compounds in high yields（up to 99%）with moderate enantioselectivities（up to 55%ee）.The related investigations of this alcoholysis reaction enrich the development of asymmetric methodology associated with the enantioselective desymmetrization of prochiral triacylamines.Chapter 3:Studies on the enantioselective alcoholytic desymmetrization of prochiral triacylamines by using chiral bifunctional guanidine-guanidinium catalysts.Based on the organocatalysis of chiral guanidine-guanidinium salt,we have explored the enantioselective nucleophilic ring opening reaction of prochiral triacylamines via desymmetrization,delivering various synthetically useful,functionalized1,5-dicarbonyls in high yields（up to 99%）with high enantioselectivities（up to 95%ee）.Notably,this reaction has been applied to the enantioselective synthesis ofγ-aminobutyric acid（GABA）-related drugs,（R）-Baclofen·HCl and（S）-Pregabalin,and the current methodology provides new routes to structurally relevant chiral drugs.Chapter 4:Studies on the enantioselective alcoholytic desymmetrization of meso triacylamines by using chiral squaramide catalysts.Based on the organocatalysis of chiral squaramide,we have studied the enantioselective nucleophilic ring opening reaction of meso triacylamines via desymmetrization,achieving a series of structurally interesting 1,4-dicarbonyls containing multiple chiral stereocenters in excellent yields（up to 99%）with high enantioselectives（up to 95%ee）in most cases.The corresponding investigations of this alcoholysis reaction provide a new perspective on the development of the enantioselective desymmetrization of meso triacylamines.