Synthesis Of Bifunctional Axial Chiral Dithiourea And Its Application In Pictet-Spengler Asymmetric Reaction

Many notable catalytic systems in the past were organic catalytic systems derived from metals and relied on chiral Lewis acid and organometallic reducing group catalysis,which provided a wealth of ways for the development and optimization of catalytic asymmetric reactions.However,the asymmetric transformation using organic molecules as reaction catalysts has gradually been developed after Lewis-acid metals and many chiral ligands combined catalysts,in order to develop enantioselective catalytic processes with high optical efficiency and stereo control.Provides more potential.Organic amine catalysts include proline,guanidines,urea and thiourea,etc.Chiral thiourea catalysts use an ionic catalytic process to promote the formation of key C-C bonds.The adduct formed by the catalyst and the substrate activates the electrophilicity of the substrate,thereby promoting the reaction.In recent years,chiral thiourea catalysts have been widely used in organic asymmetric synthesis,and are also widely used in many natural science and technology fields such as food processing,medicine,and agriculture.Based on the research of the research group,3-hydroxy-2-naphthoic acid was used as the starting material to synthesize BINOL acid with axial chirality through multiple steps,and then it was combined with pyrrolidinamine,benzylamine,phenoxyethylamine,etc.A series of thiourea catalysts containing multiple hydrogen bonds and multiple active centers were synthesized by the reaction,and the synthesized thiourea was involved in the asymmetric P-S condensation reaction of tryptamine or 6-methoxytryptamine and aromatic aldehyde as the substrate.Satisfatory conditions are obtained: 20 mmol of catalyst(9c)is added at room temperature and dissolved in 10 m L of toluene,benzoic acid is used as an additive to react for 66 h,and finally tetrahydro-1H–pyridine[3,4-b]indole compounds are obtained.The yield(82%)and ee(88%)were characterized by NMR.At the same time,the reaction adaptability is revealed by expanding the reaction substrate.The results show that the synthesized chiral thiourea catalyst can effectively catalyze the P-S condensation reaction and obtain tetrahydro-1H-pyridine with up to 88% enantiomeric excess [3,4-b] Indole.All products were characterized by NMR and MS.