Study On Kinetic Resolution Of 1,2-Diamine Catalyzed By Chiral Phosphoric Acid

Chiral quaternary carbon 1,2-diamine not only has important physiological activities,but also can be used as a key intermediate for the synthesis of complex natural products and drug molecules.It is also an important chiral structural unit for chiral catalysts and ligands in organic synthesis.Therefore,the synthesis of chiral quaternary 1,2-diamines,especially asymmetric synthesis,has become a topic of common concern for organic chemists and medicinal chemists.We have introduced the synthesis methods of chiral 1,2-diamine derivatives in recent years.Various methods have enriched the synthesis methods of 1,2-diamine derivatives.Quaternary 1,2-diamines are rarely reported because of the challenges in their chiral synthesis.Therefore,the development of a simple and efficient method for synthesizing chiral quaternary carbon 1,2-diamine has important theoretical significance and practical application value.In this chapter,the newly developed（S）-BINOL-9-（10-Ph）-An phosphoric acid catalyst has successfully realized the high-efficiency kinetic resolution reaction of racemicα-tertiary amine,and efficiently synthesized chiral o-diamine products.The reaction uses 10 mol%（S）-BINOL-9-（10-Ph）-An as a catalyst,ultra-dry toluene as a solvent,5（?）molecular sieve as an additive,and reacts for ten hours at-25 ^oC.Successfully realized the high-efficiency kinetic resolution of racemicα-tertiary amines substituted with different substituents.It is worth noting that the tetra-substituted chiral o-diamine derivatives obtained by this method containα-tertiary amine quaternary carbon chiral centers,which is different from the previously reported methods and most of them can only achieveα-secondary amine products.The asymmetric catalytic synthesis.At the same time,the reaction has a high catalytic efficiency,generally only 10 mol%catalyst is needed,and after a few hours of reaction,anα-tertiary amine product with a quaternary carbon chiral center can be obtained with an excellent enantioselectivity coefficient.The chiralα-tertiary amine derivatives obtained by this method are not only important organic ligands,but also key intermediates for the synthesis of certain drugs and natural products,which proves the potential applicability of this method.At the same time,this method is different from the traditional asymmetric Mannich reaction,the diamination reaction of olefins,and the asymmetric ring-opening reaction of aziridine.This reaction synthesizes racemic 1,2-diamine raw materials through a simple three-step reaction,and the kinetic resolution of racemic 1,2-diamine substrates can almost quantitatively recover enantioselective raw materials and obtain chirality.Quaternary 1,2-diamine product.High atom utilization rate,in line with green,environmentally friendly and economical reactions.At the same time,we are looking forward to the report of the new o-diamine derivative method.