Chiral Amine-Catalyzed Asymmetric Carbocyclization Of Ynamides For The Preparation Of Morphans And Normorphans

For nearly two decades,organocatalysis has been a hot research area in the field of asymmetric catalysis.The relative advantages,including metal free,insensitive to air and water,easily prepared and recovered of the catalysts,render the organocatalytic reactions to meet the requirements of green chemistry.In the organocatalysis,enamine catalysis is the most classical and significant reaction type,which involves the generation of the enamine intermediate from the condensation of the substrate and chiral amine catalyst,then the nucleophilic addition of this intermediate to electrophilic reagent forms new bond and chiral product.In this paper,a chiral amine-catalyzed desymmetric carbocyclization of ynamides have been developed for the synthesis of morphans and normorphans.Initially,starting from ynamide-cyclohexanones,an intramolecular organocatalytic desymmetrizing carbocyclization is achieved under the catalysis of proline-derived secondary amine.This protocol allows the efficient preparation of various valuable morphans with excellent yields and enantioselectivities.Importantly,an unusual addition at the β position is detected.Furthermore,the substitution of the protecting group on the nitrogen atom of ynamides can lead to regiodivergent synthesis of normorphans.The present strategy offers new opportunities for the development of asymmetric organocatalysis based on ynamides.