Asymmetric Kabachnik-Fields/Cyclization Cascade Reaction Catalyzed By Chiral Silver Spirocyclic Phosphate

Heterocyclic compounds form an important branch of organic chemistry.Due to their structural diversity and effective biological activities,organic chemists are greatly interested in them.The construction of carbon-hetero bonds is the simplest and most effective method for the synthesis of heterocyclic compounds.Organic compounds containing nitrogen and phosphorus are closely related to life chemistry and are involved in almost all life activities such as energy conversion,substance metabolism,and expression of genetic information in the body.Therefore,the construction of carbon-nitrogen?C-N?and carbon-phosphorus?C-P?bonds plays a very important role in the formation of carbon-hetero bonds.1,2-dihydroisoquinoline heterocyclic compound,?-aminophosphonic acid and its derivatives are a kind of important organic matter,nitrogen,phosphorus and has extensive biological activities,especially the chiral compounds are widespread in the drug molecules and natural products,hence C1-phosphate-substituted the dihydrogenisoquinoline and its derivatives of asymmetric synthesis has important research value and application value.In this paper,an asymmetric three-component Kabachnik-Fields/cyclization cascade reaction involving o-alkynylbenzaldehyde,primary amine and dialkyl phosphite was designed.By chiral silver spirocyclic phosphate catalysis,a variety of chiral?-aminophosphonates with 1,2-dihydroisoquinoline structure can be synthesized rapidly and efficiently,which greatly develops the asymmetrical synthesis method of such heterocyclic compounds.Through the screening and optimization of Lewis acid,chiral Bronsted acid and reaction conditions,it was finally determined that Ag₂CO₃ was used as the Lewis acid and the 3,3'position was 4-?4-^tBuC₆H₄?-3-CH₃C₆H₃ substituted chiral spirocyclic phosphate was used as the Bronsted acid,using MTBE as a solvent,was added to 5?MS,and a higher yield?99%?and enantioselectivity?94%?were obtained at-10?.