Research On Nucleophilic Addtion Reactions Of Phosphonyl And Phosphinyl Imines

Constant interests of nucleophilic addition of phosphinyl imines always exist in both methodology and total synthesis. In this thesis, we have developed a series of multi-functionalized phosphonyl and phosphinyl imines and nucleophilic addition reactions of them; besides, we also prepared α,β-diamino esters by one-pot synthesis.1. Mannich reaction between (E)-4-phenylbut-3-en-2-one and phosphonyl aldiminesThrough asymmetric Mannich reaction induced by chiral phosphonyl auxiliary, we have developed a fecile method to synthesize β’-amino-α,β-enones. Reaction was carried out between (E)-4-phenylbut-3-en-2-one derived enolates and phosphonyl aldimines under-78℃in THF. Good yields (68%-96%) and diastereoselectivities (89:11-982dr) were available. The product was transformed into a known sample by cleavage of its auxiliary. After comparision of the optical rotation between these two compounds, the new chiral center was assigned as S. At the same time, determination of diastereoselectivities by chiral HPLC was identical with that by31P NMR, thus confirming31P NMR measurement.2.Grignard reaction between allylmagnesium bromide and α,β-unsaturated phosphonyl iminesThrough asymmetric Grignard reaction induced by chiral phosphonyl auxiliary, we have developed a facile method to synthesize α-alkenyl homoallylic primary amines. Reaction was carried out between allylmagnesium bromide and α,β-unsaturated phosphonyl aldimines under-78℃in THF. Good yields (66%-87%) and diastereoselectivities (87:13-99:1dr) were available. The product was transformed into a known sample by cleavage of its auxiliary. After comparision of the optical rotation between these two compounds, the new chiral center was assigned as S.3. Reduction between L-Selectride and phosphinyl imino estersThrough asymmetric reduction by chiral phosphinyl auxiliary, we have developed a facile method to synthesize a-amino esters. Reaction was carried out between L-Selectride and chiral phosphinyl imino esters under-78℃in THF. Excellent yields (88%-98%) and diastereoselectivities (96:4-99:1dr) were available. Some products could be purified by GAP (Group-assisted-purification) method, without column or recrystallization. The product was transformed into a known sample by cleavage of its auxiliary. After comparision of the optical rotation between these two compounds, the new chiral center was assigned as S.4. One-pot synthesis of α,β-diamino estersThrough one-pot diamination of cinnamic esters, we have developed a facile method to synthesize α,β-diamino esters. Reaction experienced Copper (Ⅱ) trifluoromethanesulfonate catalyzed aminohalogenation of cinnamic esters and amination of benzylamine without purification in the process. Good yields (53%-83%) and stereoselectivities (syn:anti>99:1)were available. The absolute configuration of products was confirmed by XRD.