Synthesis Of A New BINOL Axial Chiral Thiourea And Its Application In Asymmetric Reactions

Thiourea has been proven to be a new high-efficiency and universal hydrogen-bonded bifunctional organic catalyst,which can promote many reactions in a highly stereoselective manner.Among the various organic catalysts that have been developed,bifunctional thiourea catalysts show With high efficiency and versatility,it has become the most prominent hydrogen bond donor catalyst in various organic reactions.In this paper,3-hydroxy-2-naphthoic acid was used as raw material to prepare R-type BINOL axial chiral framework intermediates through simple four-step reaction,and then 8 new BINOL axial chiral thiourea catalysts were successfully synthesized from the intermediates（7a～7h）,its structure was characterized by H¹ NMR,C¹³ NMR,IR,HR-MS melting point and other data.Pyrazolinone is a five-membered heterocyclic compound as well as an extremely important intermediate.It has huge application development potential in the development of medicinal chemistry,coordination chemistry and functional materials.We synthesized 8 new BINOL axial chiral thiourea catalysts successfully catalyzed the asymmetric Michael addition reaction of pyrazolones（8a～8c）and nitroolefin compounds（9a～9i）.By optimizing the reaction conditions,experiments show that at35℃,10 mmol%7a is used as a catalyst,the substrate molar ratio is 1:1.5,and the reaction is refluxed in 10ml CH₂Cl₂ solvent for 24 hours,and the target product has a good yield of 89%And ee value is 91%,the range of substrates is wide,and it has good universality.The thiopyran heterocyclic compounds are widely used in clinical medicines and are extremely important in the synthesis of medicines.At present,thiopyran compounds are indispensable intermediates in medicinal chemistry research,and they are also one of the valuable structural unit synthesizers in organic synthesis.They can be made into organic conductors,and can also be used as herbicides,inhibitors,and Antibacterial,antimalarial agents,etc.The thiopyran compounds have potential medicinal value,so it is very important to synthesize high-efficiency and green organic small molecule catalysts for the synthesis of thiopyran compounds.Then,we applied 8 synthetic BINOL axial chiral thiourea catalysts to the asymmetric Aldol reaction of thiopyranone and aromatic aldehyde.Under the optimal reaction conditions,the product yield and ee value of the reaction were as high as 85% And 90%.