Development Of A Novel Chiral Superstrong Br(?)nsted Carbonic Acid And Its Catalytic Asymmetric Three-component Imino-Ene Reaction

Chiral Br(?)nsted acids are a class of small-molecule hydrogen-bond donors with superior ability to activate substrates,which have great advantages in the efficient construction of asymmetric carbon-carbon and carbon-heteroatom bonds.As one of the earliest chiral Br(?)nsted acids,chiral phosphate BPA has shown excellent activity and enantioselectivity in catalyzing numerous asymmetric reactions.However,the low acidity of chiral phosphoric acid BPA limits its application to a certain extent.Although chiral Br(?)nsted acid catalysts with higher acidities were subsequently developed,their performance was still unsatisfactory when catalyzing some weakly basic or low activity substrates.Therefore,there is an urgent need to develop more novel chiral Br(?)nsted acid catalysts with higher acidity in the field of chiral Br(?)nsted acid catalysis to solve the asymmetric catalytic transformations of challenging low-activity substrates.Chiral homoallylamines are an important class of amine compounds and play an important role in the field of organic synthesis.The three-component asymmetric Imino-Ene reaction is an efficient and simple synthetic method for the asymmetric synthesis of chiral homoallylamines.Meanwhile,the Imino-Ene reaction is also a classic reaction for the construction of carbon-carbon bonds and carbon-heteroatom bonds.However,the insufficient acidities of the currently developed chiral Br(?)nsted acid catalysts resulted in the low reactivity of the reaction.Therefore,it is a challenge to develop novel chiral Br(?)nsted acids with stronger acidity to solve the low activity of chiral acid catalysts in the three-component asymmetric Imino-Ene reaction.Based on the study of the acidity development rule of known achiral Br(?)nsted acids,we designed and synthesized a new type of chiral Br(?)nsted C-H acids,i.e.BINOL-derived phosphoryl bis((trifluoromethyl)sulfonyl)methane(BPTM).Consistent with our expectation,the calculation study revealed that the p K_a of BPTM in acetonitrile can be as low as 1.3.Subsequently,we applied the developed chiral super Br(?)nsted C-H acid catalyst BPTM in the asymmetric three-component Imino-Ene reaction,and achieved good results.In the presence of 2.5 mol%of chiral superacid BPTM,aromatic aldehydes,fluorene methoxycarbonamide(Fmoc NH₂)and trimethylallyl silicon reagents can react smoothly under mild reaction conditions,to generate a series of chiral homoallylamine compounds in good yields(up to 99%yield)with excellent enantioselectivities(up to 95%ee).In addition,catalyst comparison experiments of three different types of chiral Br(?)nsted acids(BPA,NTPA,IDPi)with BPTM have also been carried out.The results demonstrated that our newly developed chiral super Br(?)nsted C-H acid BPTM possess significantly enhanced reactivity and excellent stereoselectivity in this reaction.