Studies On The Amine Catalyzed Asymmetric Conjugate Addition And Epoxidation

With this paper, new methods for amine catalyzed asymmetric conjugate addition base on base-base bifunctional catalytic system and asymmetric phase-transfer catalytic accessed toα,β-epoxyketones had been developed.Base-base bifunctional catalysis is a novel and efficient system for the asymmetric conjugate addition. In this system, a weak basic chiral amine was used as catalyst to active the enal and induces the chirality of the reaction; another weak basic lithium salt was used as additive to active the weak nucleophilic reagent, malonate. The effect of various conditions, such as catalyst, additive base, solvent, temperature and the amount of reactant, was under investigation. Under the optimum condition, the addition of a series of enals and malonates could take place using 1-5 mol% of (S)-2-(diphenyl(trimethyl- silyloxy)methyl)pyrrolidine as catalyst and 5-30 mol% of lithium 4-fluoro- benzonate as additive base with up to >99% ee.The base-base bifunctional catalytic asymmetric conjugate addition of enals and nitroalkanes has been developed. The effect of various conditions, such as additive base, solvent and the amount of reactant, was under investigation. Under the optimum condition, the addition of a series of enals and nitroalkanes could take place using 2-5 mol% of (S)-2-(diphenyl(trimethylsilyloxy)methyl) pyrrolidine as catalyst and 10 mol% of lithium acetate as additive base with up to 97% ee.The Clasisen-Schmidt condensation-epoxidation sequence was developed for the synthesis ofα,β-epoxyketones. The method allow to affordα,β-epoxyketones efficiently and conveniently from simple aldehydes and ketones by a two step sequence, firstly the condensation in potassium hydroxide aqueous and then the epoxidation under asymmetric phase-transfer catalytic condition. The effect of various conditions, such as the concentration of potassium hydroxide aqueous, temperature, solvent and the amount of reactant, was under investigation. Under the optimum condition, 5 mol% of O-benzyl-N-(9-anthracenylmethyl)dihydro- cinchonidium bromide was used as catalyst with up to 96% ee.The tandem oxidation-epoxidation reaction was developed for the synthesis ofα,β-epoxyketones. The method allows affordingα,β-epoxyketones directly from allylic alcohols under liquid-solid bi-phase conditions using trichloro- isocyanuric acid as a mild and efficient oxidant. The effect of various conditions, such as the concentration of potassium hydroxide aqueous, temperature, solvent and the amount of reactant, was under investigation. Under the optimum condition, 5 mol% of O-benzyl-N-(9-anthracenylmethyl)dihydrocinchonidium bromide was used as catalyst with up to 91% ee.