Double Axially Chiral Bisphosphorylimides In Asymmetric C=N Addition Reaction

Chiral molecules containing asymmetric carbon centers bonded withnitrogen are ubiquitous in nature and also form important structuralfragments in both natural and man-made biologically activemolecules.Therefore, much attention has been paid on the asymmetricaddition of C=N. This easy works on two types of asymmetric addition toC=N: asymmetric three-component Mannich reaction and asymmetricPictet-Spengler reaction, details are as follows:Firstly, we introduce the significances and difficulties in the researchof asymmetric addition to C=N. Combining with the developments inthis field in the last decades, great progress has been made incontrolling stereoselectivity by using chiral organometallic-andorganocatalysts in asymmetric addition of C=N reactions, here we willfocus on the asymmetric Mannich reaction.Secondly, we designed and synthesized the double axially chiralbisphosphorylimides and used these catalysts for asymmetricthree-component Mannich reaction. The catalytic asymmetric Mannich reaction is one of the most efficient methods for preparingenantioenriched β-amino carbonyl compounds, which are highly usefulchiral building blocks and intermediates in organic synthesis. Comparedto indirect asymmetric two-component Mannich reactions, directthree-component Mannich reactions do not need the tedious preparationof enolates or imines; as a result they have received increasing interest.The effect of many factors, such as catalysts, the catalyst loading,molecular sieves, on reactivities and stereoselectivities of products wereinvestigated. In the optimal catalytic conditions (25℃,2mol%of1d asa catalyst, toluene as solvents,5molecular sieve as additive), weexamined electron withdrawing substituents and electron donatingsubstituents aldehydes, both gained excellent results. The correspondingcompounds were obtained in83%-99%yields with highdiastereoselective(99:1)and enantioselectivity(90%-99%ee). There aretwo points should be mentioned: a. optically active syn-β-amino ketoneswere obtained in high yields (up to99%) with excellentdiastereoselectivity (99:1) and enantioselectivity (up to99%ee); b. Agram-scale reaction was also performed to prove the synthetic applicationvalue of this reaction. The optical rotation,1H NMR,13C NMR,IR,HMRSof these compounds were all characterized.Thirdly, we used double axially chiral bisphosphorylimides inasymmetric Pictet-Spengler reaction. the reaction has become one of the most successful synthetic strategies particularly directed towards thesynthesis of the isoquinoline and indole alkaloid frameworks. Wesynthesized eight amines used in the Pictet-Spengler reaction, afterscreening of the aldehydes and ketoesters, we selected compound i andethyl pyruvate as the reactants. The effect of many factors such ascatalysts, catalyst loading, solvents and reaction temperature onreactivities and stereoselectivities of products were investigated.Fortunately the reaction achieved80%ee, related work is in furtherexploration.In this esay, we got excellent asymmetric C=N adducts and alsoprovided some experimental data for the research in this field. Furtherapplications of double axially chiral bisphosphorylimides in otherenantioselective reactions are currently in progress.