Synthesis Of C₂-Axis Chiral Binaphthamide And Its Application In Asymmetric Series Reactions

C₂-axis chiral binaphthoic acid is a typical skeleton in axial chirality,which is combined with amine through condensation reaction to form C₂-axis chiral binaphthyl amide-type catalysts with symmetrical upper and lower structures and multiple chiral centers.These catalysts contain hydrogen bonds,which catalyze asymmetric reactions by hydrogen bonding,and can both activate the reaction substrate well and detach easily from the target product at the end of the reaction.Not only can the reaction be made with high enantioselectivity,but also the catalyst itself can be recycled many times.Moreover,the synthesis method is simple,the raw materials are cheap and easy to obtain,and it is friendly to the environment,which fully satisfies the theory of green chemistry and atomic economy.Based on this paper,six C₂-axis chiral binaphthylamides catalysts（1a-1f）were synthesized and the experimental results were characterized by ~1H NMR,¹³C NMR,IR,HR-MS and melting point.Tandem reactions are multi-component,multi-step reactions converted into one-step reactions by a one-pot method,which saves reaction time and reduces the difficulty of the reaction,while one-step synthesis eliminates the need for post-processing purification of intermediate compounds,which saves drugs and solvents.In this paper,the six C₂-axis chiral binaphthylamido catalysts（1a-1f）synthesized were applied to catalyze the Sulfa-Michael/Aldol tandem reaction and the Knoevenagel-Michael tandem reaction,respectively.The Sulfa-Michael/Aldol tandem reaction can synthesize chiral sulfur-containing heterocyclic compounds,and the Knoevenagel-Michael tandem reaction can synthesize chiral nitrogen-containing heterocyclic compounds.The results showed that both of the above tandem reactions could be well catalyzed by C₂-axis chiral binaphthylamides catalysts,and the reaction conditions of the two tandem reactions were optimized by the single variable method.For the Sulfa-Michael/Aldol tandem reaction 25°C,THF（3m L）as solvent,10mmol%1d as catalyst and 10h were the optimal reaction conditions,which were applied for the extension of the substrates to obtain 10 chiral thiophene compounds（4a-4j）.For the Knoevenagel-Michael tandem reaction using catalyst1d（2mmol%）as the catalyst and CH₂Cl₂ as the reaction solvent at room temperature for 9h is the optimal reaction condition.The substrates were extended using this condition to obtain12 chiral pyran compounds（8a-8l）.Both of the above reactions gave goodyields and ee values.