Design And Synthesis Of Chiral 3-Substituted Aminopyridine Catalysts And Their Application In Asymmetric Allyl Amination And Acylation Reactions

Chiral aminopyridine（DMAP）,as a kind of classical basic catalyst,is widely used in organic synthesis.Most of the traditional chiral DMAP catalysts have some disadvantages such as long synthesis steps,low yield and single structure.In this paper,a series of chiral aminopyridine catalysts with a variety of structures were efficiently constructed using 4-diaminopyridine and L-proline as the framework and the chiral source.Based on the research of chiral DMAP-N-oxides by our group,the two kinds of chiral DMAP catalysts were designed and synthesized.（1）A series of chiral 3-（L-prolinamide）-4-aminopyridine catalysts was synthesized,and the different amine substituents at the C4 position of the pyridine ring and large steric hindrance chiral amide groups at the C3 position were introduced to control the stereoselectivity.（2）A series of chiral amine pyridine catalysts was synthesized by using the interaction of nitrogen atoms on the pyridine ring with the aromatic ring with large steric hindrance through π bonds to control the stereoselectivity.The synthesized catalyst was applied to the asymmetric allyl amination reaction with MBH adducts,and a series of chiral allyl amination products were obtained with medium enantioselectivity（84:16 ER）and high yield（95%）.At the same time,the substrate of the reaction can be applied widely in phthalimide with different substituents,benzotriazole,indole and other nitrogenous heterocycles.In addition,the catalytic activities of the synthetic DMAP catalyst were investigated in the asymmetric Morita-Baylis-Hillman（MBH）reaction between indigo and acrylic ester,the asymmetric [3+2] cyclozation reaction of indigo derivatives and the acyl transfer reaction.The target products were obtained with medium yield and lower enantioselectivity.Finally,the synthesized catalyst and the product were characterized by high resolution mass spectrometry and nuclear magnetic resonance,and the final structure was determined.In summary,the three kinds of chiral 3-substituted aminopyridine catalysts were designed and synthesized and they have been successfully applied to asymmetric allyl amination reactions to construct a series of optically active allylamine compounds.In addition,this type of catalyst has also been used to catalyze asymmetric Morita-Baylis-Hillman（MBH）reactions,cycloaddition and acylation reactions,respectively,to synthesize optically active cyclopentenone-substituted alcohols,bisoxyspirindole Derivatives and products such as phenylalanine methyl ester.