Design And Synthesis Of A Novel C₂ Axial Chiral Dithiourea Catalyst And Its Application In Asymmetric Tandem Reaction

Chiral thiourea catalysts have the ability to activate substrates by hydrogen bonding,which can effectively promote the occurrence of asymmetric reactions.At present,many types of chiral thiourea catalysts have been synthesized,for example:chiral thiourea catalyst with cyclohexanediamine as skeleton,chiral thiourea catalyst prepared with 1,2-diphenylethy lenediamine as skeleton,thiurarea catalyst with proline amide as skeleton etc.Since thiourea organic catalysts are alsowidely used in many natural science and technology fields such as food processing,medicine,agriculture etc,the design and synthesis of thiourea catalysts have important application value.In this paper,a series of novel C₂-axis chiral dithiourea catalysts with multiple hydrogen bonds and multiple active centers are designed and prepared to catalyze asymmetric series reactions.First,we prepared a compound containing a chiral BINOL skeleton using a simple and easily available natural chiral source 2-naphthol-3-carboxylic acid as a raw material,and after a multi-step reaction,finally synthesized a shaft-chiral binapholic acid skeleton catalyst.The synthesized catalyst was then applied to the asymmetric Knoevenagel-Michael tandem reaction with 1,3-carbonyl compounds,malononitrile and aromatic aldehydes as substrates and 1,3-dipolar cycloaddition and intramolecular tandem reaction with ohydroxybenzaldehyde ylide and unsaturated azlactone as reactants.The catalytic conditions were optimized.At room temperature,using only 5 mol% of the catalyst in 10 m L of CH₂Cl₂ for 8 h,2-amino-4H-pyran derivatives were obtained.The reaction substrate was extended,the substrate was well adapted,and the aromatic aldehyde wasattached to the electron withdrawing group to obtain higher yields?up to 97%?and enantioselectivity?up to 93%?;At room temperature,the amount of catalyst was 10 mol%,and the reaction was performed in 10 m L of CH₂Cl₂ for 12 h.Benzopyran compounds were synthesized with good yield and enantio seletivity,with a maximum yield of 88% and 86% ee,diastereoselectivity is > 20:1 dr.In this paper,atotal of 14 4H-pyran derivatives and 11 benzopyran derivatives have been synthesized.The resulting product is characterized by NMR,IR,MS etc,These two types of chiral compounds have wide application research value in the fields of pharmacology,materials science and agrochemistry.