Asymmetric Organocatalytic Mannich Addition Reaction Of α,β-unsaturated Ketones And Mechanism Study

Optically active β-aminocarbonyl derivatives are important intermediates in organic synthesis.They have many functional groups and can be easily converted into biologically active drugs.β-Aminocarbonyl derivatives play an important role in the fields of medicine,pesticides and fragrances.Therefore,it is very interesting to synthesize a series of β-aminocarbonyl derivatives.In this thesis,the asymmetric Mannich addition reaction of N-sulfonylaldimines with α,β-unsaturated ketones co-catalyzed by chiral primary amine-tertiaryamine-thiourea catalysts and acids was studied to synthesize optically active β-aminocarbonyl derivatives.1.Asymmetric organocatalytic Mannich addition reaction of α,β-unsaturated ketones.Chiral primary-tertiary amine-thiourea trifunctional catalysts and acids co-catalyzed asymmetric Mannich addition reactions of N-sulfonyl aldimines with α,β-unsaturated ketones are reported.Through optimization of the reaction conditions,we identified the best reaction conditions to synthesize optically active β-aminocarbonyl derivatives in moderate yields and enantioselectivities(up to 89% yield,>99% ee).Gram-scale experiments also proceeded smoothly with essentially unchanged yields and enantioselectivities.Derivatization experiments were carried out on the obtained products.A method for the direct synthesis of optically active β-aminocarbonyl derivatives is provided.2.Reaction-based mechanistic investigations of asymmetric organocatalysis Mannich addition ofα,β-unsaturated ketones.Two products were obtained by the reaction of N-sulfonyl aldehydes with α,β-unsaturated ketones,the main product is the Mannich addition product and the secondary product is the [4+2]cycloaddition product.Theoretically,the [4+2] cycloaddition product is obtained by the intramolecular aza-Michael reaction of the Mannich addition product.But this is not the case,we initially reacted the Mannich addition product under the best conditions,and the [4+2] cycloaddition product could not be detected.The cyclic product can generate Mannich addition product under optimal conditions.Through a series of mechanistic experiments,it can be determined that this reaction produces a cyclic product that is not a Mannich/aza-Michael tandem reaction but rather a [4+2] cycloaddition via an enamine intermediate.The conversion of the [4+2] cycloaddition product to the Mannich product was experimentally demonstrated to be a retro-Michael reaction via an iminium intermediate,and there was kinetic splitting during the conversion.