Synthesis Of Phosphine-bisamide Catalyst Based On Chiral Sulfenamide And Its Application In Asymmetric Michael Addition Reaction

Since 21^st century,the use of chiral tertiary phosphines as organic catalysts,for the asymmetric catalysis of functionalized chiral molecules and building blocks has developed into an extremely important organic synthesis strategy.Among the chiral tertiary phosphine catalysts,chiral β-aminophosphine is a versatile and highly efficient catalyst with excellent performance in a wide range of asymmetric catalysis.However,there are some shortcomings in the traditional route of synthetic β-amino chiral tertiary phosphine catalysts,such as long route,difficult to modify the structure and harsh reaction conditions.The development of new strategies and new routes for synthesizing β-amino chiral tertiary phosphine catalysts is particularly significant important and necessary.In this paper,we use the addition of Ph₂PCH₂Li to chiral sulfoximine to obtain Xiao-Phos with high yield and high diastereoselectivity,and proceed from Xiao-Phos through a series of structural modifications.A large number of mono-or poly-hydrogen bonded β-amino chiral tertiary phosphine catalysts were also investigated for their applications in asymmetric Michael addition and chiral alkene production.The main contents include the following three aspects:1.Synthesis of Chiral Tertiary Phosphine-Bisamide Multifunctional Catalysts Based On Chiral SulfonamideStarting from the cheap and readily available chiral tert-butylsulfinamides,dehydration condensation with commercially available aldehydes yields chiral sulfinylimides.It can react with LiCH₂PPh₂ to gain Xiao-Phos in high yields.The phosphine on Xiao-Phos was protected by BH₃,then the t-butylsulfinyl group was removed under the condition of HCl/MeOH=1/2,then BH₃ was removed by diethylamine,the corresponding chiral β-amino phosphine can be obtained.The resulting chiral β-amino phosphine,on the one hand,can be directly reacted with an acid chloride to give a mono-hydrogenated chiral tertiary phosphine catalyst.On the other hand,dehydration acylation can be carried out with the NBoc amino acid to give a dipeptide backbone of the chiral tertiary phosphine.In addition,it is also possible to remove the Boc group by treatment with TFA,and then react with various acid chlorides to obtain various chiral tertiary phosphine catalysts having dipeptide skeletons.2.Michael addition reaction of β-dicarbonyl compound to trifluoromethyl ketene catalyzed by β-amino chiral tertiary phosphineThe results showed that the double hydrogen bond tertiary phosphine catalyst obtained after the modification of Xiao-Phos showed excellent catalytic activity in the asymmetric Michael addition reaction between β-dicarbonyl compound and trifluoromethyl ketene molecule and substantially universal:on the one hand,malonates and trifluoromethyl ketenes can smoothly undergo asymmetric Michael addition under the influence of 5 mol%of catalyst,the highest 99%yield and 99%ee to get a series of chiral trifluoromethyl compounds;on the other hand,under the effect of 5 mol%of the catalyst,asymmetric Michael addition reaction of β-ketoester trifluoro ketene can smoothly occur,the highest 99%yield,98%ee and 13:1 dr to get a series of compounds containing chiral trifluoromethyl centers and quaternary carbon chiral centers.3.Preparation of chiral organolenes by the reaction of malonic esters catalyzed by β-amino chiral tertiary phosphines with enoxynonesBased on the double-hydrogen bond tertiary phosphine catalyst obtained after the modification of Xiao-Phos,it can be applied to the reaction of malonate with ethynyne:the malonates and ethynylesters can smoothly occur under the influence of10 mol%of catalyst addition gave the highest chiral alkene compound in 99%yield,99%ee and 93:7 dr.